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Sample records for acute alcohol administration

  1. The effects of acute alcohol administration on the human brain: insights from neuroimaging.

    PubMed

    Bjork, James M; Gilman, Jodi M

    2014-09-01

    Over the last quarter century, researchers have peered into the living human brain to develop and refine mechanistic accounts of alcohol-induced behavior, as well as neurobiological mechanisms for development and maintenance of addiction. These in vivo neuroimaging studies generally show that acute alcohol administration affects brain structures implicated in motivation and behavior control, and that chronic intoxication is correlated with structural and functional abnormalities in these same structures, where some elements of these decrements normalize with extended sobriety. In this review, we will summarize recent findings about acute human brain responses to alcohol using neuroimaging techniques, and how they might explain behavioral effects of alcohol intoxication. We then briefly address how chronic alcohol intoxication (as inferred from cross-sectional differences between various drinking populations and controls) may yield individual brain differences between drinking subjects that may confound interpretation of acute alcohol administration effects. This article is part of the Special Issue Section entitled 'Neuroimaging in Neuropharmacology'.

  2. Chronic and acute alcohol administration induced neurochemical changes in the brain: comparison of distinct zebrafish populations.

    PubMed

    Chatterjee, Diptendu; Shams, Soaleha; Gerlai, Robert

    2014-04-01

    The zebrafish is increasingly utilized in the analysis of the effects of ethanol (alcohol) on brain function and behavior. We have shown significant population-dependent alcohol-induced changes in zebrafish behavior and have started to analyze alterations in dopaminergic and serotoninergic responses. Here, we analyze the effects of alcohol on levels of selected neurochemicals using a 2 × 3 (chronic × acute) between-subject alcohol exposure paradigm randomized for two zebrafish populations, AB and SF. Each fish first received the particular chronic treatment (0 or 0.5 vol/vol% alcohol) and subsequently the acute exposure (0, 0.5 or 1.0% alcohol). We report changes in levels of dopamine, DOPAC, serotonin, 5HIAA, glutamate, GABA, aspartate, glycine and taurine as quantified from whole brain extracts using HPLC. We also analyze monoamine oxidase and tyrosine hydroxylase enzymatic activity. The results demonstrate that compared to SF, AB is more responsive to both acute alcohol exposure and acute alcohol withdrawal at the level of neurochemistry, a finding that correlates well with prior behavioral observations and one which suggests the involvement of genes in the observed alcohol effects. We discuss correlations between the current results and prior behavioral findings, and stress the importance of characterization of zebrafish strains for future behavior genetic and psychopharmacology studies.

  3. Acute and chronic alcohol administration: effects on performance of zebrafish in a latent learning task.

    PubMed

    Luchiari, Ana C; Salajan, Diana C; Gerlai, Robert

    2015-04-01

    Alcohol abuse is a major medical problem. Zebrafish have been proposed to model alcohol related human disorders. Alcohol impairs learning and memory. Here, we analyze the effects of alcohol on performance of zebrafish in a recently developed latent learning paradigm. We employ a 2×3×2 experimental design (chronic×acute alcohol treatment×path blocked). The latent learning task had two phases: one, 30min long exploration trials (16 days, 1 trial/day) with left or right path of a complex maze blocked, and two, a subsequent probe trial with all paths open leading to a goal box that now contained stimulus fish. During the 16 days each fish received one of two chronic treatments: freshwater or 0.50% (v/v%) alcohol. Subsequently, fish were immersed for 1h in one of the following solutions: 0.00 (freshwater), 0.50% or 1.00% alcohol, the acute challenge. Behavior of fish was recorded during the probe trial that commenced immediately after the acute treatment. Path choices, latency to leave the start box and to enter the goal box, time spent in the goal box, distance traveled, and duration of freezing were quantified. We found that acute exposure to 1.00% alcohol after chronic freshwater disrupted learning performance, so did exposure to freshwater after chronic alcohol treatment (withdrawal). We also found exposure to chronic alcohol to diminish the effect of subsequent acute alcohol suggesting development of tolerance. Our results demonstrate that analysis of learning performance of zebrafish allows detection of alcohol-induced functional changes. The simplicity and scalability of the employed task also imply the utility of the zebrafish in high throughput drug screens. PMID:25557800

  4. Acute and Chronic Alcohol Administration: Effects on Performance of Zebrafish in a Latent Learning Task

    PubMed Central

    Luchiari, Ana C; Salajan, Diana C; Gerlai, Robert

    2015-01-01

    Alcohol abuse is a major medical problem. Zebrafish have been proposed to model alcohol related human disorders. Alcohol impairs learning and memory. Here, we analyze the effects of alcohol on performance of zebrafish in a recently developed latent learning paradigm. We employ a 2 × 3 × 2 experimental design (chronic × acute alcohol treatment × path blocked). The latent learning task had two phases: one, 30 min long exploration trials (16 days, 1 trial/day) with left or right path of a complex maze blocked, and two, a subsequent probe trial with all paths open leading to a goal box that now contained stimulus fish. During the 16 days each fish received one of two chronic treatments: freshwater or 0.50% (vol/vol%) alcohol. Subsequently, fish were immersed for 1h in one of the following solutions: 0.00 (freshwater), 0.50 or 1.00% alcohol, the acute challange. Behavior of fish was recorded during the probe trial that commenced immediately after the acute treatment. Path choices, latency to leave the start box and to enter the goal box, time spent in the goal box, distance travelled, and duration of freezing were quantified. We found that acute exposure to 1.00% alcohol after chronic freshwater disrupted learning performance, so did exposure to freshwater after chronic alcohol treatment (withdrawal). We also found exposure to chronic alcohol to diminish the effect of subsequent acute alcohol suggesting development of tolerance. Our results demonstrate that analysis of learning performance of zebrafish allows detection of alcohol-induced functional changes. The simplicity and scalability of the employed task also imply the utility of the zebrafish in high throughput drug screens. PMID:25557800

  5. Acute alcohol exposure, acidemia or glutamine administration impacts amino acid homeostasis in ovine maternal and fetal plasma.

    PubMed

    Washburn, Shannon E; Sawant, Onkar B; Lunde, Emilie R; Wu, Guoyao; Cudd, Timothy A

    2013-09-01

    Fetal alcohol syndrome (FAS) is a significant problem in human reproductive medicine. Maternal alcohol administration alters maternal amino acid homeostasis and results in acidemia in both mother and fetus, causing fetal growth restriction. We hypothesized that administration of glutamine, which increases renal ammoniagenesis to regulate acid-base balance, may provide an intervention strategy. This hypothesis was tested using sheep as an animal model. On day 115 of gestation, ewes were anesthetized and aseptic surgery was performed to insert catheters into the fetal abdominal aorta as well as the maternal abdominal aorta and vena cava. On day 128 of gestation, ewes received intravenous administration of saline, alcohol [1.75 g/kg body weight (BW)/h], a bolus of 30 mg glutamine/kg BW, alcohol + a bolus of 30 mg glutamine/kg BW, a bolus of 100 mg glutamine/kg BW, alcohol + a bolus of 100 mg glutamine/kg BW, or received CO2 administration to induce acidemia independent of alcohol. Blood samples were obtained simultaneously from the mother and the fetus at times 0 and 60 min (the time of peak blood alcohol concentration) of the study. Administration of alcohol to pregnant ewes led to a reduction in concentrations of glutamine and related amino acids in plasma by 21-30%. An acute administration of glutamine to ewes, concurrent with alcohol administration, improved the profile of most amino acids (including citrulline and arginine) in maternal and fetal plasma. We suggest that glutamine may have a protective effect against alcohol-induced metabolic disorders and FAS in the ovine model.

  6. Neuroprotective effect of small heat shock protein, Hsp27, after acute and chronic alcohol administration.

    PubMed

    Toth, Melinda Erzsebet; Gonda, Szilvia; Vigh, Laszlo; Santha, Miklos

    2010-11-01

    Alcohol induces degeneration of neurons and inhibits neurogenesis in the brain. Small heat shock proteins are able to protect neurons in cerebral ischemia and oxidative stress. In this study, we investigated the neuroprotective effect of small heat shock protein, Hsp27, after acute and chronic ethanol administrations using transgenic mice overexpressing the human Hsp27 protein. Transgenic mice and wild-type littermates were injected with 2 g/kg ethanol intraperitoneally, and then motor coordination and muscle strength were analyzed using different behavioral tests, such as footprint analysis, balance beam, and inverted screen tests. Ethanol-injected transgenic mice showed similar footprints to control saline-injected mice, did not fall of the beam, and were able to climb to the top of the inverted screen, while wild-type mice showed ataxia and incoordination after ethanol injection. The effect of Hsp27 on chronic ethanol consumption was also investigated. Drinking water of mice was replaced by a 20% ethanol solution for 5 weeks, and then brain sections were stained with Fluoro Jade C staining. We found significantly lesser amount of degenerating neurons in the brain of ethanol-drinking transgenic mice compared to wild-type mice. We conclude that Hsp27 can protect neurons against the acute and chronic toxic effects of ethanol.

  7. Neuroprotective effect of small heat shock protein, Hsp27, after acute and chronic alcohol administration

    PubMed Central

    Toth, Melinda Erzsebet; Gonda, Szilvia; Vigh, Laszlo

    2010-01-01

    Alcohol induces degeneration of neurons and inhibits neurogenesis in the brain. Small heat shock proteins are able to protect neurons in cerebral ischemia and oxidative stress. In this study, we investigated the neuroprotective effect of small heat shock protein, Hsp27, after acute and chronic ethanol administrations using transgenic mice overexpressing the human Hsp27 protein. Transgenic mice and wild-type littermates were injected with 2 g/kg ethanol intraperitoneally, and then motor coordination and muscle strength were analyzed using different behavioral tests, such as footprint analysis, balance beam, and inverted screen tests. Ethanol-injected transgenic mice showed similar footprints to control saline-injected mice, did not fall of the beam, and were able to climb to the top of the inverted screen, while wild-type mice showed ataxia and incoordination after ethanol injection. The effect of Hsp27 on chronic ethanol consumption was also investigated. Drinking water of mice was replaced by a 20% ethanol solution for 5 weeks, and then brain sections were stained with Fluoro Jade C staining. We found significantly lesser amount of degenerating neurons in the brain of ethanol-drinking transgenic mice compared to wild-type mice. We conclude that Hsp27 can protect neurons against the acute and chronic toxic effects of ethanol. PMID:20461564

  8. Effects of acute administration of ethanol on cerebral glucose utilization in adult alcohol-preferring and alcohol-nonpreferring rats.

    PubMed

    Strother, Wendy N; McBride, William J; Lumeng, Lawrence; Li, Ting-Kai

    2005-02-01

    Local cerebral glucose utilization (LCGU) rates, as determined by the [(14)C]-2-deoxyglucose (2-DG) technique, were examined after acute ethanol administration within selected brain regions of alcohol-preferring (P) and alcohol-nonpreferring (NP) rats. Adult male P and NP rats were injected with saline, 0.25 g/kg, or 1.0 g/kg ethanol, intraperitoneally (ip), 10 min before an intravenous bolus of [(14)C]2-DG (125 microCi/kg). Timed arterial blood samples were collected over 45 min and assayed for plasma glucose, ethanol, and [(14)C]2-DG levels. Image densities were determined using quantitative autoradiography and LCGU values calculated. Data were collected from several key limbic, basal ganglionic, cortical, and subcortical structures. Low-dose ethanol (0.25 g/kg) significantly decreased LCGU rates in several brain regions including the medial prefrontal cortex, olfactory tubercles, and the CA1 subregion of the hippocampus of P rats. Low-dose ethanol had no significant effects on LCGU rates in the NP rats. Moderate-dose ethanol (1.0 g/kg) also significantly lowered LCGU rates in many brain regions of P rats, including key limbic structures, such as the medial prefrontal cortex, olfactory tubercles, ventral tegmental area, basolateral nucleus of the amygdala, lateral septum, and ventral pallidum. Moderate-dose ethanol also significantly lowered LCGU rates in the medial prefrontal cortex as well as in the habenula of NP rats. All other regions were unaffected in the NP rats. These findings support the suggestion that certain central nervous system regions of P rats may be more sensitive than those of NP rats to the effects of low to intermediate doses of ethanol.

  9. Acute Alcohol Consumption, Alcohol Outlets, and Gun Suicide

    PubMed Central

    Branas, Charles C.; Richmond, Therese S.; Ten Have, Thomas R.; Wiebe, Douglas J.

    2014-01-01

    A case–control study of 149 intentionally self-inflicted gun injury cases (including completed gun suicides) and 302 population-based controls was conducted from 2003 to 2006 in a major US city. Two focal independent variables, acute alcohol consumption and alcohol outlet availability, were measured. Conditional logistic regression was adjusted for confounding variables. Gun suicide risk to individuals in areas of high alcohol outlet availability was less than the gun suicide risk they incurred from acute alcohol consumption, especially to excess. This corroborates prior work but also uncovers new information about the relationships between acute alcohol consumption, alcohol outlets, and gun suicide. Study limitations and implications are discussed. PMID:21929327

  10. Acute Alcohol-Induced Liver Injury

    PubMed Central

    Massey, Veronica L.; Arteel, Gavin E.

    2012-01-01

    Alcohol consumption is customary in most cultures and alcohol abuse is common worldwide. For example, more than 50% of Americans consume alcohol, with an estimated 23.1% of Americans participating in heavy and/or binge drinking at least once a month. A safe and effective therapy for alcoholic liver disease (ALD) in humans is still elusive, despite significant advances in our understanding of how the disease is initiated and progresses. It is now clear that acute alcohol binges not only can be acutely toxic to the liver, but also can contribute to the chronicity of ALD. Potential mechanisms by which acute alcohol causes damage include steatosis, dysregulated immunity and inflammation, and altered gut permeability. Recent interest in modeling acute alcohol exposure has yielded new insights into potential mechanisms of acute injury, which also may well be relevant for chronic ALD. Recent work by this group on the role of PAI-1 and fibrin metabolism in mediating acute alcohol-induced liver damage serve as an example of possible new targets that may be useful for alcohol abuse, be it acute or chronic. PMID:22701432

  11. Operant alcohol self-administration in dependent rats: focus on the vapor model.

    PubMed

    Vendruscolo, Leandro F; Roberts, Amanda J

    2014-05-01

    Alcoholism (alcohol dependence) is characterized by a compulsion to seek and ingest alcohol (ethanol), loss of control over intake, and the emergence of a negative emotional state during withdrawal. Animal models are critical in promoting our knowledge of the neurobiological mechanisms underlying alcohol dependence. Here, we review the studies involving operant alcohol self-administration in rat models of alcohol dependence and withdrawal with the focus on the alcohol vapor model. In 1996, the first articles were published reporting that rats made dependent on alcohol by exposure to alcohol vapors displayed increased operant alcohol self-administration during acute withdrawal compared with nondependent rats (i.e., not exposed to alcohol vapors). Since then, it has been repeatedly demonstrated that this model reliably produces physical and motivational symptoms of alcohol dependence. The functional roles of various systems implicated in stress and reward, including opioids, dopamine, corticotropin-releasing factor (CRF), glucocorticoids, neuropeptide Y (NPY), γ-aminobutyric acid (GABA), norepinephrine, and cannabinoids, have been investigated in the context of alcohol dependence. The combination of models of alcohol withdrawal and dependence with operant self-administration constitutes an excellent tool to investigate the neurobiology of alcoholism. In fact, this work has helped lay the groundwork for several ongoing clinical trials for alcohol dependence. Advantages and limitations of this model are discussed, with an emphasis on what future directions of great importance could be. PMID:24290310

  12. Acute Alcohol Intoxication-Induced Microvascular Leakage

    PubMed Central

    Doggett, Travis M.; Breslin, Jerome W.

    2014-01-01

    Background Alcohol intoxication can increase inflammation and worsen injury, yet the mechanisms involved are not clear. We investigated whether acute alcohol intoxication elevates microvascular permeability, and investigated potential signaling mechanisms in endothelial cells that may be involved. Methods Conscious rats received a 2.5 g/kg alcohol bolus via gastric catheters to produce acute intoxication. Microvascular leakage of intravenously administered FITC-albumin from the mesenteric microcirculation was assessed by intravital microscopy. Endothelial-specific mechanisms were studied using cultured endothelial cell monolayers. Transendothelial electrical resistance (TER) served as an index of barrier function, before and after treatment with alcohol or its metabolite acetaldehyde. Pharmacologic agents were used to test the roles of alcohol metabolism, oxidative stress, p38 mitogen-activated protein (MAP) kinase, myosin light chain kinase (MLCK), rho kinase (ROCK), and exchange protein activated by cAMP (Epac). VE-cadherin localization was investigated to assess junctional integrity. Rac1 and RhoA activation were assessed by ELISA assays. Results Alcohol significantly increased FITC-albumin extravasation from the mesenteric microcirculation. Alcohol also significantly decreased TER and disrupted VE-cadherin organization at junctions. Acetaldehyde significantly decreased TER, but inhibition of ADH or application of a superoxide dismutase mimetic failed to prevent alcohol-induced decreases in TER. Inhibition of p38 MAP kinase, but not MLCK or ROCK, significantly attenuated the alcohol-induced barrier dysfunction. Alcohol rapidly decreased GTP-bound Rac1 but not RhoA during the drop in TER. Activation of Epac increased TER, but did not prevent alcohol from decreasing TER. However, activation of Epac after initiation of alcohol-induced barrier dysfunction quickly resolved TER to baseline levels. Conclusions Our results suggest that alcohol intoxication increases

  13. Progression of alcoholic acute to chronic pancreatitis.

    PubMed Central

    Ammann, R W; Muellhaupt, B

    1994-01-01

    Alcoholic chronic pancreatitis usually progresses from acute attacks to chronic pancreatitis within one to 19 years. The factors responsible for the appreciable variability in progression are unclear. In this study the relation between progression and the incidence and severity of acute episodes in a large cohort of patients with alcoholic chronic pancreatitis was analysed. All patients with at least one documented episode of acute pancreatitis have been studied prospectively over the past 30 years according to our protocol. Patients were classified according to their long term course into (a) calcific (n = 185), (b) non-calcific (n = 30), and (c) non-progressive (n = 39) chronic pancreatitis groups. The yearly incidence of acute attacks of pancreatitis was significantly higher in groups (a) and (b) than in group (c). Furthermore, the progression rate to advanced chronic pancreatitis (groups (a) and (b)) correlated with the incidence of severe pancreatitis (associated with pseudocysts in more than 55%). Pseudocysts were located primarily in the cephalic pancreas in groups (a) and (b) (58-71%) and in the pancreatic tail in group (c) (61%). In conclusion, these data suggest that the progression of acute to chronic pancreatitis is closely related to the incidence and severity of acute attacks. This finding and the primary location of pseudocysts in the cephalic pancreas (groups (a) plus (b)) are compatible with the 'necrosis-fibrosis' pathogenetic hypothesis. PMID:8174996

  14. Acute effects of nicotine on alcohol cue-reactivity in nondependent and dependent smokers.

    PubMed

    McGrath, Daniel S; Peloquin, Marcel P; Ferdinand, Justin C; Barrett, Sean P

    2015-02-01

    Evidence from alcohol self-administration studies suggests that nicotine replacement therapy may influence subjective and behavioral responses to alcohol. However, its effect on alcohol cue-reactivity is unknown. The present study examined the impact of acutely administered nicotine on subjective responses to alcohol-focused pictorial stimuli. In a mixed within/between-subjects design, nondependent smokers (n = 51) and dependent smokers (n = 45) who socially drink were assigned to either a nicotine (4 mg) or placebo lozenge condition following overnight tobacco abstinence. Following lozenge absorption, participants viewed neutral images followed by alcohol-focused pictures. Craving measures for alcohol and tobacco were completed at baseline, following lozenge absorption, following neutral cues, and following alcohol cues. The presentation of alcohol cues increased alcohol-related craving relative to neutral cues, especially among men, but the administration of nicotine did not influence the magnitude of these effects. Nicotine lozenges were found to decrease intentions to smoke and withdrawal-related craving in dependent but not in nondependent smokers. Finally, the presentation of alcohol cues was found to increase intentions to smoke relative to neutral cues across participants regardless of lozenge condition. Findings suggest that although the presentation of alcohol cues can increase alcohol- and tobacco-related cravings in smokers, such effects do not appear to be affected by acute nicotine administration. PMID:25643027

  15. 27 CFR 27.55 - Federal Alcohol Administration Act permit.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... thereto (27 CFR part 1), any person except an agency of a State or political subdivision thereof, or any... 27 Alcohol, Tobacco Products and Firearms 1 2014-04-01 2014-04-01 false Federal Alcohol Administration Act permit. 27.55 Section 27.55 Alcohol, Tobacco Products and Firearms ALCOHOL AND TOBACCO TAX...

  16. 27 CFR 27.55 - Federal Alcohol Administration Act permit.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... thereto (27 CFR part 1), any person except an agency of a State or political subdivision thereof, or any... 27 Alcohol, Tobacco Products and Firearms 1 2013-04-01 2013-04-01 false Federal Alcohol Administration Act permit. 27.55 Section 27.55 Alcohol, Tobacco Products and Firearms ALCOHOL AND TOBACCO TAX...

  17. 27 CFR 27.55 - Federal Alcohol Administration Act permit.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... thereto (27 CFR part 1), any person except an agency of a State or political subdivision thereof, or any... 27 Alcohol, Tobacco Products and Firearms 1 2012-04-01 2012-04-01 false Federal Alcohol Administration Act permit. 27.55 Section 27.55 Alcohol, Tobacco Products and Firearms ALCOHOL AND TOBACCO TAX...

  18. 27 CFR 27.55 - Federal Alcohol Administration Act permit.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... thereto (27 CFR part 1), any person except an agency of a State or political subdivision thereof, or any... 27 Alcohol, Tobacco Products and Firearms 1 2010-04-01 2010-04-01 false Federal Alcohol Administration Act permit. 27.55 Section 27.55 Alcohol, Tobacco Products and Firearms ALCOHOL AND TOBACCO TAX...

  19. 27 CFR 27.55 - Federal Alcohol Administration Act permit.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... thereto (27 CFR part 1), any person except an agency of a State or political subdivision thereof, or any... 27 Alcohol, Tobacco Products and Firearms 1 2011-04-01 2011-04-01 false Federal Alcohol Administration Act permit. 27.55 Section 27.55 Alcohol, Tobacco Products and Firearms ALCOHOL AND TOBACCO TAX...

  20. Inhibitory effects of pretreatment with radon on acute alcohol-induced hepatopathy in mice.

    PubMed

    Toyota, Teruaki; Kataoka, Takahiro; Nishiyama, Yuichi; Taguchi, Takehito; Yamaoka, Kiyonori

    2012-01-01

    We previously reported that radon inhalation activates antioxidative functions in the liver and inhibits carbon tetrachloride-induced hepatopathy in mice. In addition, it has been reported that reactive oxygen species contribute to alcohol-induced hepatopathy. In this study, we examined the inhibitory effects of radon inhalation on acute alcohol-induced hepatopathy in mice. C57BL/6J mice were subjected to intraperitoneal injection of 50% alcohol (5 g/kg bodyweight) after inhaling approximately 4000 Bq/m(3) radon for 24 h. Alcohol administration significantly increased the activities of glutamic oxaloacetic transaminase (GOT), glutamic pyruvic transaminase (GPT) in serum, and the levels of triglyceride and lipid peroxide in the liver, suggesting acute alcohol-induced hepatopathy. Radon inhalation activated antioxidative functions in the liver. Furthermore, pretreatment with radon inhibited the depression of hepatic functions and antioxidative functions. These findings suggested that radon inhalation activated antioxidative functions in the liver and inhibited acute alcohol-induced hepatopathy in mice.

  1. Immune dysfunction in acute alcoholic hepatitis

    PubMed Central

    Dhanda, Ashwin D; Collins, Peter L

    2015-01-01

    Acute alcoholic hepatitis (AAH) is a serious complication of alcohol misuse and has high short term mortality. It is a clinical syndrome characterised by jaundice and coagulopathy in a patient with a history of recent heavy alcohol use and is associated with profound immune dysfunction with a primed but ineffective immune response against pathogens. Here, we review the current knowledge of the pathogenesis and immune defects of AAH and identify areas requiring further study. Alcohol activates the immune system primarily through the disruption of gut tight junction integrity allowing the escape of pathogen-associated molecular particles (PAMPs) into the portal venous system. PAMPs stimulate cells expressing toll-like receptors (mainly myeloid derived cells) and initiate a network of intercellular signalling by secretion of many soluble mediators including cytokines and chemokines. The latter coordinates the infiltration of neutrophils, monocytes and T cells and results in hepatic stellate cell activation, cellular damage and hepatocyte death by necrosis or apoptosis. On the converse of this immune activation is the growing evidence of impaired microbial defence. Neutrophils have reduced phagocytic capacity and oxidative burst and there is recent evidence that T cell exhaustion plays a role in this. PMID:26576079

  2. Functional biomarkers for the acute effects of alcohol on the central nervous system in healthy volunteers

    PubMed Central

    Zoethout, Remco W M; Delgado, Wilson L; Ippel, Annelies E; Dahan, Albert; van Gerven, Joop M A

    2011-01-01

    The central nervous system (CNS) effects of acute alcohol administration have been frequently assessed. Such studies often use a wide range of methods to study each of these effects. Unfortunately, the sensitivity of these tests has not completely been ascertained. A literature search was performed to recognize the most useful tests (or biomarkers) for identifying the acute CNS effects of alcohol in healthy volunteers. All tests were grouped in clusters and functional domains. Afterwards, the effect of alcohol administration on these tests was scored as improvement, impairment or as no effect. Furthermore, dose–response relationships were established. A total number of 218 studies, describing 342 different tests (or test variants) were evaluated. Alcohol affected a wide range of CNS domains. Divided attention, focused attention, visuo-motor control and scales of feeling high and of subjective drug effects were identified as the most sensitive functional biomarkers for the acute CNS effects of alcohol. The large number of CNS tests that are used to determine the effects of alcohol interferes with the identification of the most sensitive ones and of drug–response relationships. Our results may be helpful in selecting rational biomarkers for studies investigating the acute CNS effects of alcohol or for future alcohol- interaction studies. PMID:21284693

  3. Adaptation of Mesenteric Collecting Lymphatic Pump Function Following Acute Alcohol Intoxication

    PubMed Central

    Souza-Smith, Flavia M.; Kurtz, Kristine M.; Molina, Patricia E.; Breslin, Jerome W.

    2010-01-01

    Objective Acute alcohol intoxication increases intestinal lymph flow by unknown mechanisms, potentially impacting mucosal immunity. We tested the hypothesis that enhanced intrinsic pump function of mesenteric lymphatics contributes to increased intestinal lymph flow during alcohol intoxication. Methods Acute alcohol intoxication was produced by intragastric administration of 30% alcohol to concious, unrestrained rats through surgically-implanted catheters. Time-matched controls received either no bolus, vehicle, or isocaloric dextrose. Thirty minutes after alcohol administration, rats were anesthetized and mesenteric collecting lymphatics were isolated and cannulated to study intrinsic pumping parameters. In separate experiments, mesenteric lymphatics were isolated to examine direct effects of alcohol on intrinsic pump activity. Results Lymphatics isolated from alcohol-intoxicated animals displayed slgnificantly decreased contraction frequency (CF) than the dextrose group, elevated stroke volume index (SVI) versus all other groups, and decreased myogenic responsiveness compared to sham. Elevating pressure from 2 to 4 cm H2O increased the volume flow index 2.4-fold in the alcohol group versus 1.4-fold for shams. Isolated lymphatics exposed to 20 mM alcohol had reduced myogenic tone, without changes in CF or SVI. Conclusions Alcohol intoxication enhances intrinsic pumping by mesenteric collecting lymphatics. Alcohol directly decreases lymphatic myogenic tone, but effects on phasic contractions occur by an unidentified mechanism. PMID:21040117

  4. After-effects of acute alcohol intoxication.

    PubMed

    York, J L; Regan, S G

    1988-01-01

    Female, Long-Evans hooded rats (N = 10, 4 months of age) were given ethanol via intragastric intubation in doses of 2.0, 3.0 or 4.0 g/kg (repeated measures design). After-effects (hypothermia, free operant activity, motor performance) were measured at six, twelve and sixteen hours, respectively, for the above doses and were compared to the effects observed after the intubation of equivolume amounts of tap water. The after-effects of ethanol on rectal temperature were varied. Both rotarod performance and free operant activity were impaired after each of the above doses of ethanol. Blood ethanol analyses revealed low blood levels of ethanol (range 6.6 +/- 1.5 to 24.6 +/- 3.4 mg/100 ml) at the time behavioral tests were performed. Thus, quantifiable behavioral impairment was observed after blood ethanol values had declined following acute intoxication episodes. These changes may be related to "hangover" symptomatology in man and may serve as a model for investigating the influence of a variety of factors related to drug dosage, rate of ethanol ingestion, type of alcoholic beverage, and prophylactic or acute intervention therapeutics.

  5. Immediate and Complex Cardiovascular Adaptation to an Acute Alcohol Dose

    PubMed Central

    Buckman, Jennifer F.; Eddie, David; Vaschillo, Evgeny G.; Vaschillo, Bronya; Garcia, Aaron; Bates, Marsha E.

    2016-01-01

    Background The detrimental effects of chronic heavy alcohol use on the cardiovascular system are well established and broadly appreciated. Integrated cardiovascular response to an acute dose of alcohol has been less studied. This study examined the early effects of an acute dose of alcohol on the cardiovascular system, with particular emphasis on system variability and sensitivity. The goal was to begin to understand how acute alcohol disrupts dynamic cardiovascular regulatory processes prior to the development of cardiovascular disease. Methods Healthy participants (N = 72, age 21 to 29) were randomly assigned to an alcohol, placebo, or no-alcohol control beverage condition. Beat-to-beat heart rate (HR) and blood pressure (BP) were assessed during a low-demand cognitive task prior to and following beverage consumption. Between-group differences in neurocardiac response to an alcohol challenge (blood alcohol concentration ~ 0.06 mg/dl) were tested. Results The alcohol beverage group showed higher average HR, lower average stroke volume, lower HR variability and BP variability, and increased vascular tone baroreflex sensitivity after alcohol consumption. No changes were observed in the placebo group, but the control group showed slightly elevated average HR and BP after beverage consumption, possibly due to juice content. At the level of the individual, an active alcohol dose appeared to disrupt the typically tight coupling between cardiovascular processes. Conclusions A dose of alcohol quickly invoked multiple cardiovascular responses, possibly as an adaptive reaction to the acute pharmacological challenge. Future studies should assess how exposure to alcohol acutely disrupts or dissociates typically integrated neurocardiac functions. PMID:26614647

  6. [Alcohol and acute respiratory distress syndrome: casuality or causality?].

    PubMed

    Sarmiento, Xavier; Guardiola, Juan J; Soler, Manuel

    2013-06-18

    Alcohol has been considered an important risk factor for the development of pneumonia since the last century. Nevertheless, it was not thought that it had relevant effects on lung structure and functions until recently. Recent studies have shown that the risk for acute respiratory distress syndrome (ARDS) is 2-4 times higher among alcoholic patients with sepsis or trauma, and that alcoholism can play a roll in more than 50% of cases in the pathogenesis of this syndrome. Although alcoholism per se does not cause acute lung injury it predisposes to pulmonary dysfunction after inflammatory stress, that is present in clinical situations that cause ARDS leading to its development and complicating its outcome. Recent investigations in animals and humans with alcohol abuse have uncovered several alterations currently known as the "alcoholic lung". This revision discusses the association between alcohol abuse and lung injury/ARDS and tries to explain the physiopathology along with possible treatments.

  7. Leptin levels are reduced by intravenous ghrelin administration and correlated with cue-induced alcohol craving.

    PubMed

    Haass-Koffler, C L; Aoun, E G; Swift, R M; de la Monte, S M; Kenna, G A; Leggio, L

    2015-01-01

    Increasing evidence supports the role of appetite-regulating pathways, including ghrelin and leptin, in alcoholism. This study tested the hypothesis that intravenous exogenous ghrelin administration acutely decreases endogenous serum leptin levels, and that changes in leptin levels negatively correlate with alcohol craving. This was a double-blind, placebo-controlled human laboratory study. Non-treatment-seeking, alcohol-dependent, heavy drinkers (n=45) were randomized to receive intravenous ghrelin or placebo, followed by a cue-reactivity procedure, during which participants were exposed to neutral (juice) and alcohol trial cues. There was a main effect for intravenous ghrelin administration, compared with placebo, in reducing serum leptin levels (P<0.01). Post hoc analysis showed significant differences in serum leptin levels at the alcohol trial (P<0.05) that persisted at the end of the experiment (P<0.05). By contrast, there were no significant differences in serum leptin levels at the juice trial (P=not significant (NS)). The change of serum leptin level at the alcohol trial correlated with the increase in alcohol urge (P<0.05), whereas urge to drink juice was not correlated with the leptin change at the juice trial (P=NS). These findings provide preliminary evidence of ghrelin-leptin cross-talk in alcoholic individuals and suggest that their relationship may have a role in alcohol craving.

  8. Dose-dependent effects of alcohol administration on behavioral profiles in the MCSF test.

    PubMed

    Karlsson, Oskar; Roman, Erika

    2016-02-01

    The acute effects of alcohol administration are age-, dose-, time- and task-dependent. Although generally considered to be a sedative drug, alcohol has both stimulatory and depressant effects on behavior, depending on dose and time. Alcohol-induced motor activating effects are consistently shown in mice but rarely demonstrated in adult, outbred rats using conventional behavioral tests. The aim of the present experiment was to study acute alcohol-induced effects on behavioral profiles in a more complex environment using the novel multivariate concentric square field™ (MCSF) test, designed for assessing different behaviors in the same trial including locomotor activity. Adult male Wistar rats (Sca:WI) were administered one intraperitoneal (i.p.) injection of alcohol (0.0 g/kg, 0.5 g/kg, 1.0 g/kg, or 1.5 g/kg) 5 min prior to the 30-min MCSF test. The two highest doses induced marked motor-suppressing effects. A significant interaction between group and time was found in general activity when comparing rats exposed to alcohol at 0.0 g/kg and 0.5 g/kg. In contrast to the 0.0 g/kg dose that increased the activity over time, animals administered the low dose (0.5 g/kg) demonstrated an initial high activity followed by a decline over time. No indications for acute alcohol-induced anxiolytic-like effects were found. The multivariate setting in the MCSF test appears to be sensitive for detecting motor-activating effects of low doses of alcohol as well as reduced locomotion at doses lower than in other behavioral tasks. The detection of subtle changes in behavior across time and dose is important for understanding alcohol-induced effects. This approach may be useful in evaluating alcohol doses that correspond to different degrees of intoxication in humans. PMID:26695588

  9. Effects of acute caffeine administration on adolescents.

    PubMed

    Temple, Jennifer L; Dewey, Amber M; Briatico, Laura N

    2010-12-01

    Acute caffeine administration has physiological, behavioral, and subjective effects. Despite its widespread use, few studies have described the impact of caffeine consumption in children and adolescents. The purpose of this study was to investigate the effects of acute caffeine administration in adolescents. We measured cardiovascular responses and snack food intake after acute administration of 0 mg, 50 mg, 100 mg, and 200 mg of caffeine. We also compared usual food intake and subjective effects of caffeine between high- and low-caffeine consumers. Finally, we conducted a detailed analysis of caffeine sources and consumption levels. We found main effects of caffeine dose on heart rate (HR) and diastolic blood pressure (DBP), with HR decreasing and DBP increasing with increasing caffeine dose. There were significant interactions among gender, caffeine use, and time on DBP. High caffeine consumers (>50 mg/day) reported using caffeine to stay awake and drinking coffee, tea, soda, and energy drinks more than low consumers (<50 mg/day). Boys were more likely than girls to report using getting a rush, more energy, or improved athletic performance from caffeine. Finally, when we examined energy and macronutrient intake, we found that caffeine consumption was positively associated with laboratory energy intake, specifically from high-sugar, low-fat foods and also positively associated with protein and fat consumption outside of the laboratory. When taken together, these data suggest that acute caffeine administration has a broad range of effects in adolescents and that the magnitude of these effects is moderated by gender and chronic caffeine consumption. PMID:21186925

  10. Protective effect of calpain inhibitor N-acetyl-L-leucyl-L-leucyl-L-norleucinal on acute alcohol consumption related cardiomyopathy.

    PubMed

    Kartkaya, Kazim; Kanbak, Güngör; Oğlakçı, Ayşegül; Burukoğlu, Dilek; Ozer, Mehmet Caner

    2014-10-01

    Excessive alcohol consumption and alcoholism cause medical problems with high mortality and morbidity rates. In this study we aimed to decrease the alcohol related tissue damage by inhibiting calpain activation which plays an important role in apoptosis and necrosis, in rats with cardiomyopathy induced by acute alcohol consumption. Male Sprague-Dawley rats were separated into four groups (control, vehicle, alcohol and alcohol + inhibitor) with 10 rats in each. Control group received isocaloric maltose while vehicle group received isocaloric maltose with DMSO, and alcohol group received 8 g/kg absolute ethanol by gavage. Inhibitor group received 20 mg/kg calpain inhibitor 1 intraperitonally prior to alcohol administration. Calpain activities, cathepsin L levels and cytochrome c release rates were significantly increased in alcohol group compared to control group (p < 0.05). Serum CK MB and BNP levels of alcohol group were excessively increased compared to control group (respectively p < 0.001 and p < 0.01). Serum BNP levels of alcohol + inhibitor group were significantly (p < 0.05) decreased compared to alcohol group. In addition to these, histological evaluation of light microscope images and the results of DNA fragmentation and immunohistochemical caspase-3 activity results showed significant improvement of these parameters in alcohol + inhibitor group compared to alcohol group. Results of our biochemical and histological evaluation results revealed that the calpain inhibitor N-acetyl-leu-leu-norleucinal may have an ameliorating effect on acute alcohol consumption related cardiac tissue damage due to its effects on cell death pathways. PMID:24996291

  11. Differential Effects of Acute Alcohol on EEG and Sedative Responses in Adolescent and Adult Wistar Rats

    PubMed Central

    Pian, Jerry P.; Criado, Jose R.; Walker, Brendan M.; Ehlers, Cindy L.

    2008-01-01

    Age-related developmental differences in sensitivity to the acute effects of alcohol may play an important role in the development of alcoholism. The present study was designed to evaluate the acute effects of alcohol on cortical electroencephalogram (EEG) in adolescent (P36) and adult (P78) Wistar rats. Five minutes of EEG was recorded after administration of 0, 0.75 or 1.5 g/kg alcohol. The righting reflex was performed to measure the sedative effects of alcohol (3.5 g/kg) and total sleeping time for each rat. Our results showed that alcohol (1.5 g/kg) increased power in the 1–2 Hz band and decreased the power in the 32–50 Hz band in the parietal cortical region of adolescent rats. Alcohol (1.5 g/kg) also increased stability of the EEG power in the slow-wave frequency bands (2–4 Hz, 4–6 Hz, and 6–8 Hz) of adolescent rats. In the frontal cortex of adult rats, but not in adolescent rats, alcohol (1.5 or 0.75 g/kg) decreased the power in the 16–32 Hz frequency band. Alcohol (1.5 g/kg) differentially increased power in a multiple of slow-wave frequency bands (2–4 Hz and 4–6 Hz) in the parietal cortex of adult rats as compared to adolescent rats. Adolescent rats were shown significantly shorter sleeping time and higher blood alcohol levels after regaining reflex than adult rats. Our results provide additional evidence of age-related differences in the effects of acute alcohol on cortical EEG, sedation and tolerance. PMID:18191821

  12. The Protective Effects of Buzui on Acute Alcoholism in Mice

    PubMed Central

    Wen, Da-Chao; Gao, Shu-di; Hu, Xiao-yu; Yi, Cheng

    2016-01-01

    This study was designed to investigate the role of a traditional buzui recipe in anti-inebriation treatment. Buzui consists of Fructus Schisandrae Chinensis, Fructus Chebulae, Fructus Mume, Fructus Crataegi, Endothelium Corneum Gigeriae Galli, and Excrementum Bombycis. The buzui mixture was delivered by gavage, and ethanol was delivered subsequent to the final treatment. The effects of buzui on the righting reflex, inebriation rates, and the survival curve are depicted. Blood alcohol concentrations, alanine aminotransferase (ALT) levels, aspartate aminotransferase (AST) levels, and alkaline phosphatase (ALP) levels were recorded. The activities of alcohol dehydrogenase (ADH), aldehyde dehydrogenase (ALDH), and superoxide dismutase (SOD), as well as malonaldehyde (MDA) levels, were also measured. Our results demonstrated that a traditional buzui recipe showed significant effects on promoting wakefulness and the prevention of acute alcohol intoxication, accelerating the metabolism of alcohol in the liver and reducing the oxidative damage caused by acute alcoholism. PMID:26884793

  13. Acute alcohol intoxication in a child following ingestion of an ethyl-alcohol-based hand sanitizer.

    PubMed

    Hertzog, James H; Radwick, Allison

    2015-07-01

    While uncommon, ingestion of ethanol-based hand sanitizers by children may be associated with significant intoxication. We report the case of a 7-year-old with acute alcohol intoxication following hand sanitizer ingestion. Alcohol elimination in this patient followed zero-order kinetics with a clearance rate of 22.5 mg/kg/h, consistent with the limited pharmacokinetic information available for children who experience alcohol intoxication from more traditional sources. PMID:25943177

  14. Acute alcohol effects on narrative recall and contextual memory: an examination of fragmentary blackouts.

    PubMed

    Wetherill, Reagan R; Fromme, Kim

    2011-08-01

    The present study examined the effects of alcohol consumption on narrative recall and contextual memory among individuals with and without a history of fragmentary blackouts in an attempt to better understand why some individuals experience alcohol-induced memory impairments whereas others do not, even at comparable blood alcohol concentrations (BACs). Standardized beverage (alcohol and no alcohol) administration procedures and neuropsychological assessments measured narrative recall and context memory performance before and after alcohol consumption in individuals with (n=44) and without (n=44) a history of fragmentary blackouts. Findings indicate that acute alcohol intoxication led to impairments in free recall, but not next-day cued recall. Further, participants showed similar memory performance when sober, but individuals who consumed alcohol and had a positive history of fragmentary blackouts showed greater contextual memory impairments than those who had not previously experienced a fragmentary blackout. Thus, it appears that some individuals may have an inherent vulnerability to alcohol-induced memory impairments due to alcohol's effects on contextual memory processes. PMID:21497445

  15. Length of smoking deprivation moderates the effects of alcohol administration on urge to smoke.

    PubMed

    Day, Anne M; Kahler, Christopher W; Spillane, Nichea S; Metrik, Jane; Rohsenow, Damaris J

    2014-05-01

    Although smoking deprivation is often used in laboratory studies to induce urges to smoke cigarettes, the optimal length of deprivation has not been established. Previous research showed that overnight abstinence from cigarettes led to high baseline urge to smoke that potentially masked alcohol's acute effects on urge to smoke (Kahler et al., 2012). The current study examined whether alcohol's effects on smoking urge were more pronounced when a shorter length of smoking deprivation was used (i.e., 3h instead of overnight abstinence). Using a balanced placebo design for alcohol administration, we found that participants experienced a significant increase in self-reported urge to smoke when administered alcohol after a 3-h smoking deprivation (n=32), whereas this effect was smaller and nonsignificant when smokers were required to be abstinent overnight (n=96). Research on factors that heighten smoking urges may find stronger effects if a 3-h deprivation is used compared to using overnight abstinence.

  16. [The mode of differential diagnostic of and acute alcoholic gastroenteritis].

    PubMed

    Makarov, V K; Makarov, P V

    2014-12-01

    The study was carried out to develop mode of differential diagnostic of salmonella and acute alcoholic gastroenteritis on the basis of phospholipid specter of blood serum. The indicators of phospholipid fractions of blood serum were analyzed in 50 healthy persons, 50 patients with acute alcoholic gastroenteritis and 50 patients with salmonella gastroenteritis were analyzed. The relative content of following fractions of whole phospholipids were analyzed--total lysophospholipids, sphyngomiyelin, phosphatidcholine, phosphatidyletanolamin. The phospholipid spectrum of blood serum can be applied in differential diagnostic of salmonella gastroenteritis and acute alcoholic gastroenteritis. The disorders of metabolism of lipids under given pathological conditions have a multidirectional character. The salmonella gastroenteritis is characterized by decreasing of relative content of total lysophospholipids and increasing of phosphatidcholine as compared with standard conditions. The acute alcoholic gastroenteritis is characterized by increasing of relative content of total lysophospholipids and phosphatidcholine and decreasing of level of phosphatidcholine. The content of total Iysophospholipids in blood serum is lower on 35% or 30.0 mg% permits diagnosing acute alcoholic gastroenteritis. The content of phosphaltidcholine in blood serum higher than 40% or 50 mg% permits diagnosing salmonella gastroenteritis.

  17. Pharmacotherapy of acute alcoholic hepatitis in clinical practice

    PubMed Central

    Abenavoli, Ludovico; Milic, Natasa; Rouabhia, Samir; Addolorato, Giovanni

    2014-01-01

    Severe alcoholic hepatitis (AH) is an acute form of alcohol induced liver disease with a poor prognosis that is seen in the patients who consume large quantities of alcohol. The diagnosis of AH is based on the appropriate alcohol intake history and is supported with clinical and histological features, and several scoring systems. Glucocorticoids are the mainstay for treating severe AH with pentoxifylline used as an alternative to steroids in addition to total alcohol abstinence. Liver transplantation is a possible therapeutic option for severe AH. Among the anti-craving medications able to improve abstinence rate, baclofen seems to be effective and safe in the alcoholic patients affected by severe liver damage. PMID:24605014

  18. Circadian modulation of acute alcohol sensitivity but not acute tolerance in Drosophila.

    PubMed

    van der Linde, Kim; Lyons, Lisa C

    2011-05-01

    An increased understanding of the factors affecting behavioral and neurological responses to alcohol and alcohol physiology is necessary given the tremendous toll alcohol abuse and alcoholism exert on individuals and society. At the behavioral and molecular levels, the response to alcohol appears remarkably conserved from Drosophila to humans, suggesting that investigations across model species can provide insight into the identification of common modulatory factors. We investigated the interaction between the circadian clock and alcohol sensitivity, alcohol tolerance, and alcohol absorbance in Drosophila melanogaster. Using a loss-of-righting reflex (LoRR) assay, we found that flies exhibit a circadian rhythm in the LoRR, with the greatest sensitivity to alcohol occurring from mid to late night, corresponding to the flies' inactive phase. As predicted, a circadian rhythm in the LoRR was absent in circadian mutant flies and under conditions in which the circadian clock was nonfunctional. Circadian modulation of the response to alcohol was not due to circadian regulation of alcohol absorbance. Similar to other animals, Drosophila develop acute and chronic tolerance to alcohol upon repeat exposures. We found that the circadian clock did not modulate the development of acute alcohol tolerance measured as the difference in sensitivity to alcohol between naïve and pre-exposed flies. Thus, the circadian clock modulates some, but not all, of the behavioral responses to alcohol exposure, suggesting that specific mechanisms underlie the observed circadian modulation of LoRR rather than global cellular circadian regulation. This study provides valuable new insights in our understanding of the circadian modulation of alcohol-induced behaviors that ultimately could facilitate preventative measures in combating alcohol abuse and alcoholism.

  19. Alcohol administration attenuates hypothalamic-pituitary-adrenal (HPA) activity in healthy men at low genetic risk for alcoholism, but not in high-risk subjects.

    PubMed

    Mick, Inge; Spring, Konstanze; Uhr, Manfred; Zimmermann, Ulrich S

    2013-09-01

    Acute alcohol challenge studies in rodents and naturalistic observations in drinking alcoholics suggest that alcohol stimulates the hypothalamic-pituitary-adrenal (HPA) system. The literature on respective studies in healthy volunteers is more inconsistent, suggesting differential alcohol effects depending on dosage, recent drinking history, family history of alcoholism and alcohol-induced side effects. These papers and the putative pharmacologic mechanisms underlying alcohol effects on the HPA system are reviewed here and compared with a new study, in which we investigated how secretion of adrenocorticotrophin (ACTH) and cortisol is affected by ingestion of 0.6 g/kg ethanol in 33 young healthy socially drinking males with a paternal history of alcoholism (PHP) versus 30 family history negative (FHN) males. Alcohol and placebo were administered in a 2-day, double-blind, placebo controlled crossover design with randomized administration sequence. After administration of placebo, ACTH and cortisol decreased steadily over 130 minutes. In FHN subjects, secretion of both hormones was even more attenuated after alcohol, resulting in significantly lower levels compared with placebo. In PHP subjects, no alcohol effect on hormone secretion could be detected. The ratio of cortisol to ACTH secretion, each expressed as area under the secretion curve, was significantly increased by alcohol in FHN and PHP participants. These results argue against HPA stimulation being a mechanism that promotes the transition from moderate to dependent drinking. The fact that alcohol-induced HPA suppression was not detected in PHP males is consistent with the general concept that subjects at high risk for alcoholism exhibit less-pronounced alcohol effects.

  20. Symptoms and signs of acute alcoholic hepatitis

    PubMed Central

    Basra, Gurjot; Basra, Sarpreet; Parupudi, Sreeram

    2011-01-01

    Although there is not one specific sign or symptom related to alcoholic hepatitis (AH), a constellation of symptoms and signs can help make the diagnosis of AH with reasonable accuracy. Documentation of chronic and active alcohol abuse is paramount in making a diagnosis of AH. Clinical presentation after abstinence for more than 3 m should raise doubts about the diagnosis of AH and dictate the need for considering other causes of liver disease, decompensation of alcoholic cirrhosis, sepsis and malignancy as the cause of patient’s clinical profile. PMID:21731904

  1. Animated bird silhouette above the tank: Acute alcohol diminishes fear responses in zebrafish

    PubMed Central

    Luca, Ruxandra M.; Gerlai, Robert

    2012-01-01

    Alcohol dependence and alcohol abuse represent major unmet medical needs. The zebrafish is considered to be a promising vertebrate species with which the effects of alcohol on brain function and behavior and the mechanisms underlying these effects may be studied. Alcohol is known to induce alterations in motor function as well as fear and anxiety. Here we present a recently developed fear paradigm in which we employ an animated (moving) image of a bird silhouette. We measure the effect of acute alcohol administration (dose range employed: 0.00 – 0.75 vol/vol percentage, bath exposure for 60 minutes) on the behavioral responses of zebrafish. We test these responses during a pre-stimulus, stimulus and post-stimulus period of the task using both a video-tracking and an observation based quantification method. The fear inducing stimulus was found to decrease the distance of the zebrafish from the bottom of the tank, to increase number of erratic movements, and to increase the number of jumps in alcohol exposed fish (versus control fish). Alcohol attenuated these fear responses in a dose dependent manner. In addition, alcohol decreased general activity at the highest dose, an effect that was independent of the presentation of the stimulus. We discuss the similarities and differences between observation and video-tracking based results and conclude that fear paradigms will be useful in revealing alcohol induced functional changes in the brain of zebrafish. PMID:22266470

  2. Electroencephalographic study of naloxone effects in the recovery of an acute alcoholic intoxication.

    PubMed

    Dawid-Milner, M S; Díaz-Calavia, E J; Lara, J P; Fernández del Moral, R; Jiménez-Vargas, J

    1989-06-01

    Experimental assays analysing EEG changes during the recovery of an acute alcoholic intoxication were carried out in three groups of cats: 1) Recovery of acute alcoholic intoxication produced by continuous intravenous perfusion of ethanol, 0.06 g/kg/min, during 20 minutes. 2) Recovery of acute alcoholic intoxication by injecting naloxone (400 micrograms/kg), just after finishing alcohol perfusion. 3) Recovery of acute alcoholic intoxication by injecting naloxone (400 micrograms/kg), 15 min after finishing perfusion. Naloxone administered after an acute alcoholic intoxication worsens the recovery of EEG parameters; 1-2 (p less than 0.05), 1-3 (p less than 0.05).

  3. Influences of Situational Factors and Alcohol Expectancies on Sexual Desire and Arousal Among Heavy-Episodic Drinking Women: Acute Alcohol Intoxication and Condom Availability

    PubMed Central

    George, William H.; Nguyen, Hong V.; Heiman, Julia R.; Davis, Kelly Cue; Norris, Jeanette

    2013-01-01

    Although studies suggest that alcohol increases women’s sexual desire, no studies to our knowledge have examined the effects of acute alcohol intoxication on women’s sexual desire. The majority of research examining alcohol’s effects on sexual arousal in women suggests that alcohol increases self-reported arousal. In an alcohol administration study in which women projected themselves into an eroticized scenario depicting a consensual sexual encounter with a new male partner, we examined the effects of alcohol and condom condition on women’s sexual desire and arousal. The moderating effects of sex-related alcohol expectancies were also examined. Results revealed that alcohol intoxication was related to less desire to engage in sex with a new partner and condom presence was related to more desire. Alcohol interacted with sexual disinhibition alcohol expectancies, indicating that more expectancy endorsement was associated with greater sexual desire and self-reported arousal in the alcohol condition, but not the control condition. Condom condition had no effect on self-reported sexual arousal. The present research suggests that sexual desire merits research attention in non-clinical samples, and experimental methodology can provide valuable information about alcohol’s influence on women’s sexual desire, thus advancing our understanding of this relationship beyond cross-sectional correlations. The current findings also provide evidence that sex-related alcohol expectancies may play an important role in alcohol-involved sexual experiences including desire and arousal. PMID:23661324

  4. Inpatient management of acute alcohol withdrawal syndrome.

    PubMed

    Perry, Elizabeth C

    2014-05-01

    Alcohol withdrawal is a common condition encountered in the hospital setting after abrupt discontinuation of alcohol in an alcohol-dependent individual. Patients may present with mild symptoms of tremulousness and agitation or more severe symptoms including withdrawal seizures and delirium tremens. Management revolves around early identification of at-risk individuals and symptom assessment using a validated tool such as the revised Clinical Institute Withdrawal Assessment for Alcohol score. Benzodiazepines remain the mainstay of treatment and can be administered using a front-loading, fixed-dose, or symptom-triggered approach. Long-acting benzodiazepines such as chlordiazepoxide or diazepam are commonly used and may provide a smoother withdrawal than shorter-acting benzodiazepines, but there are no data to support superiority of one benzodiazepine over another. Elderly patients or those with significant liver disease may have increased accumulation and decreased clearance of the long-acting benzodiazepines, and lorazepam or oxazepam may be preferred in these patients. Patients with symptoms refractory to high doses of benzodiazepines may require addition of a rescue medication such as phenobarbital, propofol or dexmedetomidine. Anticonvulsants (carbamazepine, valproate, gabapentin) may have a role in the management of mild to moderate withdrawal. Other medications such as β-antagonists or neuroleptics may offer additional benefit in select patients but should not be used a monotherapy.

  5. An acute psychosocial stressor does not potentiate alcohol cue reactivity in non-treatment-seeking alcoholics

    PubMed Central

    Thomas, Suzanne E.; Randall, Patrick K.; Brady, Kathleen; See, Ronald E.; Drobes, David J.

    2010-01-01

    Background Relapse risk factors, such as psychological stress and alcohol cues, are often encountered together. Understanding how they interact has the potential to improve alcoholism treatments. The present study was conducted to examine whether an acute psychosocial stressor enhanced alcohol cue reactivity in non-treatment-seeking alcoholics. Methods Seventy-nine alcohol dependent individuals (39 women) randomly received either the Trier Social Stress Test or a no-stress control condition. Stress reactivity was measured with serum ACTH and cortisol, mean arterial blood pressure, and subjective distress. Immediately following the stress manipulation, participants held and sniffed a neutral cue then their preferred alcoholic beverage. Cue reactivity was measured by two subjective measures of craving following each cue. Additionally, general craving was assessed with the Alcohol Urge Questionnaire (AUQ) at the beginning and end of the laboratory procedure. Results The stress manipulation showed internal validity on all measures of stress reactivity. There was not a main effect of stress nor a stress x cue interaction on either cue reactivity measure. As expected, there was a main effect of cue (alcohol > neutral cue) on both measures of cue reactivity. General craving increased during the challenge, but not differently by stress group. Magnitude of stress reactivity was not associated with magnitude of cue reactivity, and all results were independent of gender. Conclusion In this well-controlled clinical laboratory study of non-treatment-seeking alcoholics, an acute psychological stressor did not make an alcohol cue a more potent urge-inducing stimulus, and stress had no effect on general alcohol craving. PMID:21143244

  6. Purtscher-like retinopathy in acute alcoholic pancreatitis.

    PubMed

    Nema, Nitin; Ishrat, Saba; Verma, Abha; Kela, Manoj

    2016-01-01

    A 23-year-old man with a history of alcoholism presented with vomiting, fever, and sharp epigastric pain radiating to the back and flanks. He was diagnosed as a case of acute alcoholic pancreatitis on the basis of clinical findings and investigations. On the next day of presentation, he developed sudden bilateral visual loss. His best-corrected visual acuity was finger counting at one-foot distance in both eyes. He had diffuse whitening in the circumpapillary area, haloes around the retinal vessels (Purtscher flecken) and intra-retinal hemorrhages on ophthalmoscopic examination. Optical coherence tomography revealed bilateral macular edema. These findings were characteristic of Purtscher-like retinopathy. The patient showed systemic and visual improvement at 8 weeks follow-up after receiving the conventional treatment for acute alcoholic pancreatitis. This case emphasizes the importance of fundus examination by an ophthalmologist in the diagnosis of this rare under-diagnosed entity. PMID:27433040

  7. Purtscher-like retinopathy in acute alcoholic pancreatitis

    PubMed Central

    Nema, Nitin; Ishrat, Saba; Verma, Abha; Kela, Manoj

    2016-01-01

    A 23-year-old man with a history of alcoholism presented with vomiting, fever, and sharp epigastric pain radiating to the back and flanks. He was diagnosed as a case of acute alcoholic pancreatitis on the basis of clinical findings and investigations. On the next day of presentation, he developed sudden bilateral visual loss. His best-corrected visual acuity was finger counting at one-foot distance in both eyes. He had diffuse whitening in the circumpapillary area, haloes around the retinal vessels (Purtscher flecken) and intra-retinal hemorrhages on ophthalmoscopic examination. Optical coherence tomography revealed bilateral macular edema. These findings were characteristic of Purtscher-like retinopathy. The patient showed systemic and visual improvement at 8 weeks follow-up after receiving the conventional treatment for acute alcoholic pancreatitis. This case emphasizes the importance of fundus examination by an ophthalmologist in the diagnosis of this rare under-diagnosed entity. PMID:27433040

  8. [State and local administration, alcoholism and narcotic addiction].

    PubMed

    Lach, U; Wiernikowski, A

    1997-01-01

    An important social and medical problem of alcoholism and drug addiction in Poland is presented. Alcoholism is a serious danger for individuals, families and society because it is so common and due to its consequences. Described is a three stage system of preventing measures being undertaken by state and local administration together with local community institutions. By the example of the activities performed by the plenipotentiary of the voivode of Krakow a duties of such institutions are presented. The special role is played by the high medical personnel according to the prevention and early detection of potential threats.

  9. [Biochemical markers for acute and chronic alcohol consumption].

    PubMed

    Geppert, Bogna; Tezyk, Artur; Zaba, Czesław

    2012-01-01

    In spite of the fact, that ethyl alcohol is a legal and socially accepted recreational drug its abuse may cause numerous problems for the individual and society. Casualties of car accidents caused by drunk drivers, aggressive behavior, family problems and effective less work are the main problems connected with alcohol abuse. The easiest and most effective way of proving recent alcohol consumption is confirming its presence in biological samples taken from the individual. However, the main disadvantage of this method is a short window detection for ethanol, because of its high speed of elimination process. Nowadays, in order to prevent and have a better control of alcohol abuse, markers that could provide a better view of short and long term ethanol consumption are in frequent use. Ethyl alcohol present in the body cause many qualitative and quantitative disturbances in biochemical metabolites that could be used as markers of its consumption. In practice markers of ethanol consumption are usually divided into acute (tests confirm single alcohol intake) and chronic (confirm long term alcohol consumption or lack of teetotalism). Markers of ethanol consumption are valuable alternative and complementation to customary examinations performed in medical practice and forensic medicine.

  10. The effects of acute alcohol on motor impairments in adolescent, adult, and aged rats.

    PubMed

    Ornelas, Laura C; Novier, Adelle; Van Skike, Candice E; Diaz-Granados, Jaime L; Matthews, Douglas B

    2015-03-01

    Acute alcohol exposure has been shown to produce differential motor impairments between aged and adult rats and between adolescent and adult rats. However, the effects of acute alcohol exposure among adolescent, adult, and aged rats have yet to be systematically investigated within the same project using a dose-dependent analysis. We sought to determine the age- and dose-dependent effects of acute alcohol exposure on gross and coordinated motor performance across the rodent lifespan. Adolescent (PD 30), adult (PD 70), and aged (approximately 18 months) male Sprague-Dawley rats were tested on 3 separate motor tasks: aerial righting reflex (ARR), accelerating rotarod (RR), and loss of righting reflex (LORR). In a separate group of animals, blood ethanol concentrations (BEC) were determined at multiple time points following a 3.0 g/kg ethanol injection. Behavioral tests were conducted with a Latin square repeated-measures design in which all animals received the following doses: 1.0 g/kg or 2.0 g/kg alcohol or saline over 3 separate sessions via intraperitoneal (i.p.) injection. During testing, motor impairments were assessed on the RR 10 min post-injection and on ARR 20 min post-injection. Aged animals spent significantly less time on the RR when administered 1.0 g/kg alcohol compared to adult rats. In addition, motor performance impairments significantly increased with age after 2.0 g/kg alcohol administration. On the ARR test, aged rats were more sensitive to the effects of 1.0 g/kg and 2.0 g/kg alcohol compared to adolescents and adults. Seven days after the last testing session, animals were given 3.0 g/kg alcohol and LORR was examined. During LORR, aged animals slept longer compared to adult and adolescent rats. This effect cannot be explained solely by BEC levels in aged rats. The present study suggests that acute alcohol exposure produces greater motor impairments in older rats when compared to adolescent and adult rats and begins to establish a

  11. [Features of acute alcoholic psychoses in the Far North].

    PubMed

    Korolenko, Ts P; Bochkareva, N L

    1977-01-01

    An analysis of the clinical picture and development of acute alcoholic psychosis in 300 inhabitants of the North Region permitted to distinguish some traits of these conditions. Psychoses were characterized by an expressed atypicity of the psychopathological picture, somato-vegetative disorders, a complication of the development of the psychoses in comparison with the inhabitants of the middle latitudes. The authors also distinguished some differences in the predilectiveness of some syndromes or symptoms, the character and content of them in alcoholic psychoses in natives and newcomers. It was also possible to establish disorders of psychophysiological adaptation to conditions of the North Regions in the newcomers and first of all in the clinical picture and development of alcoholic delirium.

  12. Low dose acute alcohol effects on GABAA receptor subtypes

    PubMed Central

    Wallner, Martin; Hanchar, H. Jacob; Olsen, Richard W.

    2010-01-01

    GABAA receptors (GABAARs) are the main inhibitory neurotransmitter receptors and have long been implicated in mediating at least part of the acute actions of ethanol. For example, ethanol and GABAergic drugs including barbiturates and benzodiazepines share many pharmacological properties. Besides the prototypical synaptic GABAAR subtypes, nonsynaptic GABAARs have recently emerged as important regulators of neuronal excitability. While high doses (≥100 mM) of ethanol have been reported to enhance activity of most GABAAR subtypes, most abundant synaptic GABAARs are essentially insensitive to ethanol concentrations that occur during social ethanol consumption (<30 mM). However, extrasynaptic δ and β3 subunit-containing GABAARs, associated in the brain with α4or α6 subunits, are sensitive to low millimolar ethanol concentrations, as produced by drinking half a glass of wine. Additionally, we found that a mutation in the cerebellar α6 subunit (α6R100Q), initially reported in rats selectively bred for increased alcohol sensitivity, is sufficient to produce increased alcohol-induced motor impairment and further increases of alcohol sensitivity in recombinant α6β3δ receptors. Furthermore, the behavioral alcohol antagonist Ro15-4513 blocks the low dose alcohol enhancement on α4/6/β3δ receptors, without reducing GABA-induced currents. In binding assays α4β3δ GABAARs bind [3H] Ro15-4513 with high affinity, and this binding is inhibited, in an apparently competitive fashion, by low ethanol concentrations, as well as analogs of Ro15-4513 that are active to antagonize ethanol or Ro15-4513’s block of ethanol. We conclude that most low to moderate dose alcohol effects are mediated by alcohol actions on alcohol/Ro15-4513 binding sites on GABAAR subtypes. PMID:16814864

  13. Kudzu Extract Treatment Does Not Increase the Intoxicating Effects of Acute Alcohol in Human Volunteers

    PubMed Central

    Penetar, David M.; MacLean, Robert R.; McNeil, Jane F.; Lukas, Scott E.

    2010-01-01

    Background Isoflavone administration in the form of a purified extract from the herbal medication kudzu root has been shown to reduce, but not eliminate, alcohol consumption in alcohol-abusing and alcohol-dependent men. The precise mechanism of this action is unknown, but one possible explanation for these results is that the isoflavones in kudzu might actually increase the intensity or duration of alcohol’s effects and thus delay the desire for subsequent drinks. The present study was designed to test this hypothesis. Methods Twelve (12) healthy adult men and women (27.5±1.89 yrs old) who consumed moderate amounts of alcohol (7.8±0.63 drinks/week) participated in a double-blind, placebo-controlled crossover study in which they were treated with either kudzu extract (total isoflavone dose of 750 mg/day) or matched placebo for nine days. On days 8 and 9, participants received an acute challenge of ethyl alcohol (either 0.35 or 0.7 g/kg alcohol). During the challenges the following measures were collected: subjective effects, psychomotor (body sway), cognitive performance (vigilance/reaction time), physiological measures (heart rate and skin temperature), and plasma ethanol concentration. Results Alcohol resulted in a dose-related alteration in subjective measures of intoxication, impairment of stance stability, and vigilance/reaction time. Kudzu extract did not alter participants’ subjective responses to the alcohol challenge or to alcohol’s effects on stance stability or vigilance/reaction time. However, individuals treated with kudzu extract experienced a slightly more rapid rise in plasma ethanol levels, but only after the 0.7 g/kg dose. This transient effect during the first 30 minutes of the ascending plasma alcohol curve lasted only 10-15 minutes; there were no differences in peak plasma alcohol levels or alcohol elimination kinetics. Additionally, kudzu pretreatment enhanced the effects of the 0.7 g/kg dose of alcohol on heart rate and skin

  14. 27 CFR 26.202 - Requirements of the Federal Alcohol Administration Act.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 1 2010-04-01 2010-04-01 false Requirements of the Federal Alcohol Administration Act. 26.202 Section 26.202 Alcohol, Tobacco Products and Firearms ALCOHOL... RICO AND THE VIRGIN ISLANDS Products Coming Into the United States From the Virgin Islands §...

  15. Gabapentin potentiates sensitivity to the interoceptive effects of alcohol and increases alcohol self-administration in rats.

    PubMed

    Besheer, Joyce; Frisbee, Suzanne; Randall, Patrick A; Jaramillo, Anel A; Masciello, Maria

    2016-02-01

    Gabapentin, a drug used in the treatment of epileptic seizures and neuropathic pain, has shown efficacy in the treatment of alcohol dependence. Moreover, given that gabapentin is used in the general population (e.g., non-dependent individuals, social drinkers), we sought to utilize preclinical assessments to examine the effects of gabapentin on sensitivity to moderate alcohol doses and alcohol self-administration in rats with a history of moderate drinking. To this end, we assessed whether gabapentin (0, 10, 30, 120 mg/kg, IG) pretreatment alters sensitivity to experimenter- and self-administered alcohol, and whether gabapentin alone has alcohol-like discriminative stimulus effects in rats trained to discriminate alcohol dose (1 g/kg, IG) vs. water. Second, we assessed whether gabapentin (0, 10, 30, 60 mg/kg, IG) would alter alcohol self-administration. Gabapentin pretreatment potentiated the interoceptive effects of both experimenter-administered and self-administered alcohol in discrimination-trained rats. Additionally, the highest gabapentin doses tested (30 and 120 mg/kg) were found to have partial alcohol-like discriminative stimulus effects when administered alone (e.g., without alcohol). In the self-administration trained rats, gabapentin pretreatment (60 mg/kg) resulted in an escalation in alcohol self-administration. Given the importance of interoceptive drug cues in priming and maintaining self-administration, these data define a specific behavioral mechanism (i.e., potentiation of alcohol effects) by which gabapentin may increase alcohol self-administration in non-dependent populations.

  16. Intravenous alcohol self-administration in the P rat.

    PubMed

    Windisch, Kyle A; Kosobud, Ann E K; Czachowski, Cristine L

    2014-08-01

    Alcohol consumption produces a complex array of effects that can be divided into two types: the explicit pharmacological effects of ethanol (which can be temporally separate from time of intake) and the more temporally "relevant" effects (primarily olfactory and taste) that bridge the time from intake to onset of the pharmacological effects. Intravenous (IV) self-administration of ethanol limits the confounding "non-pharmacological" effects associated with oral consumption, allows for controlled and precise dosing, and bypasses first order absorption kinetics, allowing for more direct and better-controlled assessment of alcohol's effect on the brain. IV ethanol self-administration has been reliably demonstrated in mouse and human experimental models; however, models of IV self-administration have been historically problematic in the rat. An operant multiple-schedule study design was used to elucidate the role of each component of a compound IV-ethanol plus oral-sucrose reinforcer. Male alcohol-preferring P rats had free access to both food and water during all IV self-administration sessions. Animals were trained to press a lever for orally delivered 1% sucrose (1S) on a fixed ratio 4 schedule, and then surgically implanted with an indwelling jugular catheter. Animals were then trained to respond on a multiple FR4-FR4 schedule composed of alternating 2.5-min components across 30-min sessions. For the multiple schedule, two components were used: an oral 1S only and an oral 1S plus IV 20% ethanol (25 mg/kg/injection). Average total ethanol intake was 0.47 ± 0.04 g/kg. We found significantly higher earning of sucrose-only reinforcers and greater sucrose-lever error responding relative to the compound oral-sucrose plus IV-ethanol reinforcer. These response patterns suggest that sucrose, not ethanol, was responsible for driving overall responding. The work with a compound IV ethanol-oral sucrose reinforcer presented here suggests that the existing intravenous ethanol

  17. The sap of Acer okamotoanum decreases serum alcohol levels after acute ethanol ingestion in rats.

    PubMed

    Yoo, Yeong-Min; Jung, Eui-Man; Kang, Ha-Young; Choi, In-Gyu; Choi, Kyung-Chul; Jeung, Eui-Bae

    2011-10-01

    In the present study, we examined whether Acer okamotoanum (A. okamotoanum) sap decreased the serum alcohol and acetaldehyde levels after acute ethanol treatment in a rat model. Male rats were orally administered 25, 50 or 100% A. okamotoanum sap 30 min prior to oral challenge with 3 ml of ethanol (15 ml/kg of a 20% ethanol solution in water), and the blood concentrations of alcohol and acetaldehyde were analyzed up to 7 h after the treatment. Pre-treatment with the sap significantly decreased the blood ethanol and acetaldehyde concentrations after 5 h when compared with ethanol treatment alone (a negative control). The expression levels of liver alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH) mRNA were increased significantly in animals pre-treated with A. okamotoanum sap when compared with negative and positive controls. The data suggest that sap pre-treatment enhanced the alcohol metabolism rate in the rat liver. To investigate the involvement of mitochondrial regulation in the ethanol-induced hepatocyte apoptosis, we carried out an immunohistochemical analysis of Bax and Bcl-2. Pre-treatment with sap significantly decreased Bax expression and increased Bcl-2 expression 7 h after ethanol administration when compared with the negative control. The data suggest that A. okamotoanum sap pre-treatment may reduce the alcohol-induced oxidative stress in the rat liver.

  18. Acute alcoholic hepatitis, end stage alcoholic liver disease and liver transplantation: an Italian position statement.

    PubMed

    Testino, Gianni; Burra, Patrizia; Bonino, Ferruccio; Piani, Francesco; Sumberaz, Alessandro; Peressutti, Roberto; Giannelli Castiglione, Andrea; Patussi, Valentino; Fanucchi, Tiziana; Ancarani, Ornella; De Cerce, Giovanna; Iannini, Anna Teresa; Greco, Giovanni; Mosti, Antonio; Durante, Marilena; Babocci, Paola; Quartini, Mariano; Mioni, Davide; Aricò, Sarino; Baselice, Aniello; Leone, Silvia; Lozer, Fabiola; Scafato, Emanuele; Borro, Paolo

    2014-10-28

    Alcoholic liver disease encompasses a broad spectrum of diseases ranging from steatosis steatohepatitis, fibrosis, and cirrhosis to hepatocellular carcinoma. Forty-four per cent of all deaths from cirrhosis are attributed to alcohol. Alcoholic liver disease is the second most common diagnosis among patients undergoing liver transplantation (LT). The vast majority of transplant programmes (85%) require 6 mo of abstinence prior to transplantation; commonly referred to as the "6-mo rule". Both in the case of progressive end-stage liver disease (ESLD) and in the case of severe acute alcoholic hepatitis (AAH), not responding to medical therapy, there is a lack of evidence to support a 6-mo sobriety period. It is necessary to identify other risk factors that could be associated with the resumption of alcohol drinking. The "Group of Italian Regions" suggests that: in a case of ESLD with model for end-stage liver disease < 19 a 6-mo abstinence period is required; in a case of ESLD, a 3-mo sober period before LT may be more ideal than a 6-mo period, in selected patients; and in a case of severe AAH, not responding to medical therapies (up to 70% of patients die within 6 mo), LT is mandatory, even without achieving abstinence. The multidisciplinary transplant team must include an addiction specialist/hepato-alcohologist. Patients have to participate in self-help groups.

  19. Acute alcoholic hepatitis, end stage alcoholic liver disease and liver transplantation: An Italian position statement

    PubMed Central

    Testino, Gianni; Burra, Patrizia; Bonino, Ferruccio; Piani, Francesco; Sumberaz, Alessandro; Peressutti, Roberto; Giannelli Castiglione, Andrea; Patussi, Valentino; Fanucchi, Tiziana; Ancarani, Ornella; De Cerce, Giovanna; Iannini, Anna Teresa; Greco, Giovanni; Mosti, Antonio; Durante, Marilena; Babocci, Paola; Quartini, Mariano; Mioni, Davide; Aricò, Sarino; Baselice, Aniello; Leone, Silvia; Lozer, Fabiola; Scafato, Emanuele; Borro, Paolo

    2014-01-01

    Alcoholic liver disease encompasses a broad spectrum of diseases ranging from steatosis steatohepatitis, fibrosis, and cirrhosis to hepatocellular carcinoma. Forty-four per cent of all deaths from cirrhosis are attributed to alcohol. Alcoholic liver disease is the second most common diagnosis among patients undergoing liver transplantation (LT). The vast majority of transplant programmes (85%) require 6 mo of abstinence prior to transplantation; commonly referred to as the “6-mo rule”. Both in the case of progressive end-stage liver disease (ESLD) and in the case of severe acute alcoholic hepatitis (AAH), not responding to medical therapy, there is a lack of evidence to support a 6-mo sobriety period. It is necessary to identify other risk factors that could be associated with the resumption of alcohol drinking. The “Group of Italian Regions” suggests that: in a case of ESLD with model for end-stage liver disease < 19 a 6-mo abstinence period is required; in a case of ESLD, a 3-mo sober period before LT may be more ideal than a 6-mo period, in selected patients; and in a case of severe AAH, not responding to medical therapies (up to 70% of patients die within 6 mo), LT is mandatory, even without achieving abstinence. The multidisciplinary transplant team must include an addiction specialist/hepato-alcohologist. Patients have to participate in self-help groups. PMID:25356027

  20. Acute alcoholic hepatitis, end stage alcoholic liver disease and liver transplantation: an Italian position statement.

    PubMed

    Testino, Gianni; Burra, Patrizia; Bonino, Ferruccio; Piani, Francesco; Sumberaz, Alessandro; Peressutti, Roberto; Giannelli Castiglione, Andrea; Patussi, Valentino; Fanucchi, Tiziana; Ancarani, Ornella; De Cerce, Giovanna; Iannini, Anna Teresa; Greco, Giovanni; Mosti, Antonio; Durante, Marilena; Babocci, Paola; Quartini, Mariano; Mioni, Davide; Aricò, Sarino; Baselice, Aniello; Leone, Silvia; Lozer, Fabiola; Scafato, Emanuele; Borro, Paolo

    2014-10-28

    Alcoholic liver disease encompasses a broad spectrum of diseases ranging from steatosis steatohepatitis, fibrosis, and cirrhosis to hepatocellular carcinoma. Forty-four per cent of all deaths from cirrhosis are attributed to alcohol. Alcoholic liver disease is the second most common diagnosis among patients undergoing liver transplantation (LT). The vast majority of transplant programmes (85%) require 6 mo of abstinence prior to transplantation; commonly referred to as the "6-mo rule". Both in the case of progressive end-stage liver disease (ESLD) and in the case of severe acute alcoholic hepatitis (AAH), not responding to medical therapy, there is a lack of evidence to support a 6-mo sobriety period. It is necessary to identify other risk factors that could be associated with the resumption of alcohol drinking. The "Group of Italian Regions" suggests that: in a case of ESLD with model for end-stage liver disease < 19 a 6-mo abstinence period is required; in a case of ESLD, a 3-mo sober period before LT may be more ideal than a 6-mo period, in selected patients; and in a case of severe AAH, not responding to medical therapies (up to 70% of patients die within 6 mo), LT is mandatory, even without achieving abstinence. The multidisciplinary transplant team must include an addiction specialist/hepato-alcohologist. Patients have to participate in self-help groups. PMID:25356027

  1. Phosphodiesterase 10A regulates alcohol and saccharin self-administration in rats.

    PubMed

    Logrip, Marian L; Vendruscolo, Leandro F; Schlosburg, Joel E; Koob, George F; Zorrilla, Eric P

    2014-06-01

    A history of stress produces increases in rodent relapse-like alcohol self-administration behavior and regional brain gene expression of phosphodiesterase 10A (PDE10A), a dual-specificity cyclic adenosine monophosphate/cyclic guanosine monophosphate-inhibiting enzyme. Here, we tested the hypothesis that administration of TP-10, a specific PDE10A inhibitor, would reduce alcohol self-administration in conditions predisposing to elevated self-administration. TP-10 administration dose-dependently (0.562, 1.0 mg/kg; subcutaneously) reduced relapse-like alcohol self-administration regardless of stress history enhancement of relapse-like behavior. TP-10 also reduced alcohol self-administration in genetically alcohol-preferring rats, as well as in alcohol-non-dependent and -dependent rats. Effective systemic TP-10 doses did not alter alcohol pharmacokinetics, significantly reduce motor activity or intrabout operant response speed, or promote a conditioned place aversion. TP-10 also reduced saccharin self-administration, suggesting a general role for PDE10A in the self-administration of reinforcing substances. PDE10A inhibition in the dorsolateral striatum, but not the nucleus accumbens, reduced alcohol self-administration. Taken together, the results implicate dorsolateral striatum PDE10A in facilitating alcohol intake and support further investigation of PDE10A systems in the pathophysiology and potential treatment of substance use disorders.

  2. Exercise capacity is not impaired after acute alcohol ingestion: a pilot study.

    PubMed

    Popovic, Dejana; Damjanovic, Svetozar S; Plecas-Solarovic, Bosiljka; Pešić, Vesna; Stojiljkovic, Stanimir; Banovic, Marko; Ristic, Arsen; Mantegazza, Valentina; Agostoni, Piergiuseppe

    2014-08-01

    The usage of alcohol is widespread, but the effects of acute alcohol ingestion on exercise performance and the stress hormone axis are not fully elucidated.We studied 10 healthy white men, nonhabitual drinkers, by Doppler echocardiography at rest, spirometry, and maximal cardiopulmonary exercise test (CPET) in two visits (2-4 days in between), one after administration of 1.5 g/kg ethanol (whisky) diluted at 15% in water, and the other after administration of an equivalent volume of water. Plasma levels of NT-pro-BNP, cortisol, and adrenocorticotropic hormone (ACTH) were also measured 10 min before the test, at maximal effort and at the third minute of recovery. Ethanol concentration was measured from resting blood samples by gas chromatography and it increased from 0.00 ± 0.00 to 1.25 ± 0.54‰ (P < 0.001). Basal echocardiographic and spirometric parameters were normal and remained so after acute alcohol intake, whereas ACTH, cortisol, and NT-pro-BNP nonsignificantly increased in all phases of the test. CPET data suggested a trend toward a slight reduction of exercise performance (peak VO2 = 3008 ± 638 vs. 2900 ± 543 ml/min, ns; peak workload = 269 ± 53 vs. 249 ± 40 W, ns; test duration 13.7 ± 2.2 vs. 13.3 ± 1.7 min, ns; VE/VCO2 22.1 ± 1.4 vs. 23.3 ± 2.9, ns). Ventilatory equivalent for carbon dioxide at rest was higher after alcohol intake (28 ± 2.5 vs. 30.4 ± 3.2, P = 0.039) and maximal respiratory exchange ratio was lower after alcohol intake (1.17 ± 0.02 vs. 1.14 ± 0.04, P = 0.04). In conclusion, we showed that acute alcohol intake in healthy white men is associated with a nonsignificant exercise performance reduction and stress hormone stimulation, with an unchanged exercise metabolism. PMID:25083719

  3. R(+)-Baclofen, but Not S(−)-Baclofen, Alters Alcohol Self-Administration in Alcohol-Preferring Rats

    PubMed Central

    Lorrai, Irene; Maccioni, Paola; Gessa, Gian Luigi; Colombo, Giancarlo

    2016-01-01

    Racemic baclofen [(±)-baclofen] has repeatedly been reported to suppress several ­alcohol-motivated behaviors, including alcohol drinking and alcohol ­self-administration, in rats and mice. Recent data suggested that baclofen may have bidirectional, stereospecific effects, with the more active enantiomer, R(+)-baclofen, suppressing alcohol intake and the less active enantiomer, S(−)-baclofen, stimulating alcohol intake in mice. The present study was designed to investigate whether this enantioselectivity of baclofen effects may also extend to the reinforcing properties of alcohol in rats. To this end, selectively bred Sardinian alcohol-preferring (sP) rats were initially trained to lever respond on a fixed ratio 4 (FR4) schedule of reinforcement for alcohol (15%, v/v) in daily 30-min sessions. Once responding had stabilized, rats were tested with vehicle, (±)-baclofen (3 mg/kg), R(+)-baclofen (0.75, 1.5, and 3 mg/kg), and S(−)-baclofen (6, 12, and 24 mg/kg) under the FR4 schedule of reinforcement. Treatment with 3 mg/kg (±)-baclofen reduced the number of lever responses for alcohol and estimated amount of self-administered alcohol by approximately 60% in comparison to vehicle treatment. R(+)-baclofen was approximately twice as active as (±)-baclofen: treatment with 1.5 mg/kg R(+)-baclofen decreased both variables to an extent similar to that of the decreasing effect of 3 mg/kg (±)-baclofen. Conversely, treatment with all doses of S(−)-baclofen failed to affect alcohol self administration. These results (a) confirm that non-sedative doses of (±)-baclofen effectively suppressed the reinforcing properties of alcohol in sP rats and (b) apparently do not extend to operant alcohol self-administration in sP rats the capability of S(−)-baclofen to stimulate alcohol drinking in mice. PMID:27148096

  4. Effect of acute alcohol use on the lethality of suicide attempts in patients with mood disorders.

    PubMed

    Sher, Leo; Oquendo, Maria A; Richardson-Vejlgaard, Randall; Makhija, Nita M; Posner, Kelly; Mann, J John; Stanley, Barbara H

    2009-07-01

    Acute alcohol use is an important risk factor for attempted and completed suicide. We evaluated the effect of acute alcohol intake on the lethality of suicide attempts to test the hypothesis that acute alcohol intoxication is associated with more lethal suicide attempts. This retrospective study included 317 suicide attempters enrolled in mood disorders protocols. Demographic and clinical parameters were assessed. The use of alcohol at the time of the most lethal suicide attempt was determined. On the basis of their responses participants were classified into three groups: participants who reported "Enough alcohol intake to impair judgment, reality testing and diminish responsibility" or "Intentional intake of alcohol in order to facilitate implementation of attempt" were included in the group "Alcohol" (A); participants who reported "Some alcohol intake prior to but not related to attempt, reportedly not enough to impair judgment, reality testing" were included in the group "Some Alcohol" (SA); and participants who reported "No alcohol intake immediately prior to attempt" were included in the group "No Alcohol" (NA). Lethality of the most lethal suicide attempts was higher in the A group compared to the SA and NA groups. Prevalence of patients with alcohol use disorders was higher in the A group compared to the SA and NA groups. SA participants reported more reasons for living and lower suicide intent scores at the time of their most lethal suicide attempt compared to the A and NA groups. Acute alcohol use increases the lethality of suicide attempts in individuals with mood disorders.

  5. Alcohol administration increases cocaine craving but not cocaine cue attentional bias

    PubMed Central

    Marks, Katherine R.; Pike, Erika; Stoops, William W.; Rush, Craig R.

    2015-01-01

    Background Alcohol consumption is a known antecedent to cocaine relapse. Through associative conditioning, it is hypothesized that alcohol increases incentive motivation for cocaine and thus the salience of cocaine-related cues, which are important in maintaining drug-taking behavior. Cocaine-using individuals display a robust cocaine cue attentional bias as measured by fixation time during the visual probe task. The purpose of the present study was to evaluate the influence of alcohol administration on cocaine cue attentional bias using eye-tracking technology to directly measure attentional allocation. Methods Twenty current cocaine users completed a double-blind, placebo-controlled, within-subjects study that tested the effect of three doses of alcohol (0.00, 0.325, 0.65 g/kg alcohol) on cocaine cue attentional bias using the visual probe task with eye-tracking technology. The participant-rated and physiological effects of alcohol were also assessed. Results Participants displayed a robust cocaine cue attentional bias following both placebo and alcohol administration as measured by fixation time, but not response time. Alcohol administration did not influence cocaine cue attentional bias, but increased craving for cocaine in a dose dependent manner. Alcohol produced prototypic psychomotor and participant-rated effects. Conclusions Alcohol administration increases cocaine craving but not cocaine cue attentional bias. Alcohol-induced cocaine craving suggests that alcohol increases incentive motivation for cocaine but not the salience of cocaine-related cues. PMID:26331880

  6. Quantifying alcohol-related emergency admissions in a UK tertiary referral hospital: a cross-sectional study of chronic alcohol dependency and acute alcohol intoxication

    PubMed Central

    Vardy, J; Keliher, T; Fisher, J; Ritchie, F; Bell, C; Chekroud, M; Clarey, F; Blackwood, L; Barry, L; Paton, E; Clark, A; Connelly, R

    2016-01-01

    Objectives Alcohol is responsible for a proportion of emergency admissions to hospital, with acute alcohol intoxication and chronic alcohol dependency (CAD) implicated. This study aims to quantify the proportion of hospital admissions through our emergency department (ED) which were thought by the admitting doctor to be (largely or partially) a result of alcohol consumption. Setting ED of a UK tertiary referral hospital. Participants All ED admissions occurring over 14 weeks from 1 September to 8 December 2012. Data obtained for 5497 of 5746 admissions (95.67%). Primary outcome measures Proportion of emergency admissions related to alcohol as defined by the admitting ED clinician. Secondary outcome measures Proportion of emergency admissions due to alcohol diagnosed with acute alcohol intoxication or CAD according to ICD-10 criteria. Results 1152 (21.0%, 95% CI 19.9% to 22.0%) of emergency admissions were thought to be due to alcohol. 74.6% of patients admitted due to alcohol had CAD, and significantly greater than the 26.4% with ‘Severe’ or ‘Very Severe’ acute alcohol intoxication (p<0.001). Admissions due to alcohol differed to admissions not due to alcohol being on average younger (45 vs 56 years, p<0.001) more often male (73.4% vs 45.1% males, p<0.001) and more likely to have a diagnosis synonymous with alcohol or related to recreational drug use, pancreatitis, deliberate self-harm, head injury, gastritis, suicidal ideation, upper gastrointestinal bleeds or seizures (p<0.001). An increase in admissions due to alcohol on Saturdays reflects a surge in admissions with acute alcohol intoxication above the weekly average (p=0.003). Conclusions Alcohol was thought to be implicated in 21% of emergency admissions in this cohort. CAD is responsible for a significantly greater proportion of admissions due to alcohol than acute intoxication. Interventions designed to reduce alcohol-related admissions must incorporate measures to tackle CAD. PMID:27324707

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

    SciTech Connect

    Chen Bo; Xia Jing; Li Guangxing; Zhou Yifeng

    2010-03-15

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

  8. Altered prefrontal connectivity after acute heroin administration during cognitive control.

    PubMed

    Schmidt, André; Borgwardt, Stefan; Gerber, Hana; Schmid, Otto; Wiesbeck, Gerhard A; Riecher-Rössler, Anita; Bendfeldt, Kerstin; Smieskova, Renata; Lang, Undine E; Rubia, Katya; Walter, Marc

    2014-09-01

    Neuroimaging studies have reported reduced activity in a broad network of brain regions during response inhibition in heroin-dependent patients. However, how heroin in an acute dose modulates the neural correlates of response inhibition and the underlying brain connectivity has not yet been investigated. In this double-blind placebo-controlled study, we used functional magnetic resonance imaging to examine whether acute heroin administration changed whole brain activity during response inhibition in 26 heroin-dependent patients. We then applied dynamic causal modelling to investigate the effect of an acute dose of heroin on the functional interactions between the dorsal anterior cingulate cortex (dACC) and the bilateral inferior frontal gyri (IFG). Heroin acutely reduced dACC activity, as well as the inhibition-induced modulation of connectivity from the dACC to the right IFG compared with placebo. Furthermore, dACC activity was positively related to false alarm rates after placebo but not heroin administration. These results suggest that acute heroin administration impairs cognitive control in dependent patients by reducing the activity in the dACC activity and the functional connectivity from the dACC to the right IFG.

  9. Purtscher's-like retinopathy in acute alcoholic pancreatitis.

    PubMed

    Subudhi, Praveen; Kanungo, Sanghamitra; Rao Subudhi, Nageswar

    2016-01-01

    A 28-year-old man presented with a sudden onset of visual loss in both eyes (OU). He had a known history of acute pancreatitis and hepatitis following alcohol abuse. Examination of the anterior segment of the eye revealed non-sustained pupillary light reaction. The fundus showed typical Purtscher's flecken over the posterior pole with multiple cotton wool spots and retinal superficial haemorrhages in OU. Fundus fluorescein angiogram revealed abnormal hypofluorescence in both the posterior poles. Optical coherence tomography (OCT) for Purtscher's flecken showed abnormal retinal thickening with hyper-reflective areas in the inner neurosensory layers. The patient responded favourably to high-dose corticosteroid therapy (1.5 mg/kilogram per body weight) with a tapering dose. There was a mild reduction of the ischaemic areas with a corresponding improvement in visual acuity. This case has been presented owing to its rarity and under-reporting. Treatment with corticosteroids yielded favourable results. PMID:27628016

  10. Alcohol-induced vascular damage of brain can be ameliorated by administration of magnesium

    SciTech Connect

    Altura, B.M.; Altura, B.T.; Gebrewold, A.

    1986-03-01

    Long-term as well as short-term administration of alcohol can cause neuronal and vascular damage in the brain. The authors have reported that acute administration of ethyl alcohol (ALC), either directly into the rat brain, IV or locally, can produce concentration-dependent spasms of cerebral arterioles, venules, arteries and veins followed by irreversible rupture of capillaries and veins followed by irreversible rupture of capillaries and venules. Several experiments have suggested that administration of magnesium ions (Mg/sup 2 +/) can modify vascular tone. Whether Mg/sup 2 +/ can exert direct actions on the intact cerebral microcirculation is not known. Using the above intact rat brain model, and TV-image intensification, the authors determine whether administration of Mg/sup 2 +/ : 1) exerts actions on cerebral (coritical) arterioles (A) and venules (V) (12-40..mu..m); 2) directly into the brain alters arterial blood pressure (BP); and 3) could ameliorate or prevent some of the detrimental cerebral-vascular actions ALC exerts in the brain. The data show that infusion of Mg/sup 7 +/ : 1) into the rat brain result in a rapid dose-dependent lowering of systolic and diastolic and BP; 2) IV or intra-arterially (IA) produces dose-dependent vaso-dilation of A and V; 3) IV or IA prevents spasms and rupture of A and V induced by 10% ALC. The cerebral vascular actions of Mg/sup 2 +/ may prove to be useful in treatment and prevention of ALC-induced brain damage.

  11. 77 FR 14342 - Polyvinyl Alcohol From Taiwan: Correction to Notice of Opportunity To Request Administrative Review

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-03-09

    ... International Trade Administration Polyvinyl Alcohol From Taiwan: Correction to Notice of Opportunity To Request... antidumping duty order on polyvinyl alcohol from Taiwan. See Antidumping or Countervailing Duty Order, Finding, or Suspended Investigation; Opportunity To Request Administrative Review, 77 FR 12559 (March 1,...

  12. Brain-derived neurotrophic factor mediates the suppression of alcohol self-administration by memantine.

    PubMed

    Jeanblanc, Jérôme; Coune, Fabien; Botia, Béatrice; Naassila, Mickaël

    2014-09-01

    Brain-derived neurotrophic factor (BDNF) within the striatum is part of a homeostatic pathway regulating alcohol consumption. Memantine, a non-competitive antagonist of N-methyl-D-aspartate receptors, induces expression of BDNF in several brain regions including the striatum. We hypothesized that memantine could decrease ethanol (EtOH) consumption via activation of the BNDF signalling pathway. Effects of memantine were evaluated in Long-Evans rats self-administering moderate or high amounts of EtOH 6, 30 and 54 hours after an acute injection (12.5 and 25 mg/kg). Motivation to consume alcohol was investigated through a progressive ratio paradigm. The possible role for BDNF in the memantine effect was tested by blockade of the TrkB receptor using the pharmacological agent K252a and by the BDNF scavenger TrkB-Fc. Candidate genes expression was also assessed by polymerase chain reaction array 4 and 28 hours after memantine injection. We found that memantine decreased EtOH self-administration and motivation to consume EtOH 6 and 30 hours post-injection. In addition, we found that inhibition or blockade of the BDNF signalling pathway prevented the early, but not the delayed decrease in EtOH consumption induced by memantine. Finally, Bdnf expression was differentially regulated between the early and delayed timepoints. These results demonstrate that an acute injection of memantine specifically reduces EtOH self-administration and motivation to consume EtOH for at least 30 hours. Moreover, we showed that BDNF was responsible for the early effect, but that the delayed effect was BDNF-independent.

  13. Enhanced AMPA receptor activity increases operant alcohol self-administration and cue-induced reinstatement.

    PubMed

    Cannady, Reginald; Fisher, Kristen R; Durant, Brandon; Besheer, Joyce; Hodge, Clyde W

    2013-01-01

    Long-term alcohol exposure produces neuroadaptations that contribute to the progression of alcohol abuse disorders. Chronic alcohol consumption results in strengthened excitatory neurotransmission and increased α-amino-3-hydroxyl-5-methyl-4-isoxazole-propionate receptors (AMPA) receptor signaling in animal models. However, the mechanistic role of enhanced AMPA receptor activity in alcohol-reinforcement and alcohol-seeking behavior remains unclear. This study examined the role of enhanced AMPA receptor function using the selective positive allosteric modulator, aniracetam, in modulating operant alcohol self-administration and cue-induced reinstatement. Male alcohol-preferring (P-) rats, trained to self-administer alcohol (15%, v/v) versus water were pre-treated with aniracetam to assess effects on maintenance of alcohol self-administration. To determine reinforcer specificity, P-rats were trained to self-administer sucrose (0.8%, w/v) versus water, and effects of aniracetam were tested. The role of aniracetam in modulating relapse of alcohol-seeking was assessed using a response contingent cue-induced reinstatement procedure in P-rats trained to self-administer 15% alcohol. Aniracetam pre-treatment significantly increased alcohol-reinforced responses relative to vehicle treatment. This increase was not attributed to aniracetam-induced hyperactivity as aniracetam pre-treatment did not alter locomotor activity. AMPA receptor involvement was confirmed because 6,7-dinitroquinoxaline-2,3-dione (AMPA receptor antagonist) blocked the aniracetam-induced increase in alcohol self-administration. Aniracetam did not alter sucrose-reinforced responses in sucrose-trained P-rats, suggesting that enhanced AMPA receptor activity is selective in modulating the reinforcing function of alcohol. Finally, aniracetam pre-treatment potentiated cue-induced reinstatement of alcohol-seeking behavior versus vehicle-treated P-rats. These data suggest that enhanced glutamate activity at AMPA

  14. Acute alcohol intoxication increases atrogin-1 and MuRF1 mRNA without increasing proteolysis in skeletal muscle

    PubMed Central

    Vary, Thomas C.; Frost, Robert A.; Lang, Charles H.

    2008-01-01

    Acute alcohol intoxication decreases muscle protein synthesis, but there is a paucity of data on the ability of alcohol to regulate muscle protein degradation. Furthermore, various types of atrophic stimuli appear to regulate ubiquitin-proteasome-dependent proteolysis by increasing the muscle-specific E3 ligases atrogin-1 and MuRF1 (i.e., “atrogenes”). Therefore, the present study was designed to test the hypothesis that acute alcohol intoxication increases atrogene expression leading to an elevated rate of muscle protein breakdown. In male rats, the intraperitoneal injection of alcohol dose- and time-dependently increased atrogin-1 and MuRF1 mRNA in gastrocnemius, the latter of which was most pronounced. A comparable change was absent in the soleus and heart. The ability of in vivo-administered ethanol to increase atrogene expression was independent of the route of alcohol administration (intraperitoneal vs. oral), as well as of nutritional status (fed vs. fasted) and gender (male vs. female). The increase in atrogin-1 and MuRF1 was independent of alcohol metabolism, and the overproduction of endogenous glucocorticoids and could not be prevented by maintaining the circulating concentration of insulin-like growth factor-I. Despite marked changes in atrogene expression, acute alcohol in vivo did not alter the release of either 3-methylhistidine (MH) or tyrosine from the isolated perfused hindlimb, suggesting that the rate of muscle proteolysis remains unchanged. Moreover, alcohol did not increase the directly determined rate of protein degradation in isolated epitrochlearis muscles or cultured myocytes. Finally, no increase in atrogene expression or 3-MH release was detected in muscle from rats fed an alcohol-containing diet. Our results indicate that although acute alcohol intoxication increases atrogin-1 and MuRF1 mRNA preferentially in fast-twitch skeletal muscle, this change was not associated with increased rates of muscle proteolysis. Therefore, the loss

  15. Effect of acute ethanol administration on zebrafish tail-beat motion.

    PubMed

    Bartolini, Tiziana; Mwaffo, Violet; Butail, Sachit; Porfiri, Maurizio

    2015-11-01

    Zebrafish is becoming a species of choice in neurobiological and behavioral studies of alcohol-related disorders. In these efforts, the activity of adult zebrafish is typically quantified using indirect activity measures that are either scored manually or identified automatically from the fish trajectory. The analysis of such activity measures has produced important insight into the effect of acute ethanol exposure on individual and social behavior of this vertebrate species. Here, we leverage a recently developed tracking algorithm that reconstructs fish body shape to investigate the effect of acute ethanol administration on zebrafish tail-beat motion in terms of amplitude and frequency. Our results demonstrate a significant effect of ethanol on the tail-beat amplitude as well as the tail-beat frequency, both of which were found to robustly decrease for high ethanol concentrations. Such a direct measurement of zebrafish motor functions is in agreement with evidence based on indirect activity measures, offering a complementary perspective in behavioral screening.

  16. Personality and the effects of acute alcohol intake. A contingent negative variation study in healthy subjects.

    PubMed

    Fattapposta, Francesco; Venturi, Piero; Carella Prada, Ozrem; Costamagna, Luisa; D'Alessio, Carmelo; Mostarda, Mirella; Mina, Concetta; Parisi, Leoluca; Pirro, Cristina; Amabile, Giuseppe

    2004-01-01

    This study investigates the relationship between blood alcohol concentrations (BACs) and contingent negative variation (CNV). Fourteen healthy subjects were divided on the basis of their personality profiles--the Minnesota Multiphasic Personality Inventory (Hs+Hy+D/3)--into a high score (HS) and low score (LS) subgroup. The CNV was recorded using a choice-reaction time (RT) task. CNV recording was performed in two conditions: inter-stimulus intervals (ISIs) of 1500 ms and 2500 ms at three different BACs (0.3, 0.5 and 0.8 g/L) after acute alcohol administration. At the high BAC (0.8 g/L), both subgroups showed a reduced CNV amplitude area and a longer RT (p<.05) in both ISI conditions. No effects either on the CNV or on the RT were observed at the low BAC (0.3 g/L). At the intermediate BAC (0.5 g/L), the HS subgroup displayed an increased CNV amplitude (p<.05), not accompanied by a significantly longer RT (short ISI condition), and a reduced late CNV (p<.05) with a longer RT (p<.05) (long ISI condition). In the LS group, only a longer RT was observed in the long ISI condition. CNV modifications point to an individual, apparently personality-related, threshold of sensitivity to different alcohol levels. PMID:15212113

  17. Interactive effects of contextual cues and acute alcohol intoxication on the associations between alcohol expectancy activation and urge to drink.

    PubMed

    Wardell, Jeffrey D; Read, Jennifer P

    2014-10-01

    This study examined the joint effects of contextual cues and alcohol intoxication on the associations between activation of positive and negative alcohol expectancies in memory and self-reported urges to drink alcohol after a laboratory alcohol administration. Young adult heavy drinkers were randomly assigned to drink a moderate dose of alcohol or a placebo (alcohol manipulation), and then listened to positive or negative drinking scenarios (cue manipulation). Before and after these manipulations, participants completed an alcohol expectancy Stroop task assessing positive and negative expectancy activation, as well as self-report measures of urges to drink. Regression analyses revealed that the alcohol and cue manipulations had a joint, moderating impact on the associations between expectancy activation and postcue changes in urge to drink. Specifically, both increased activation of negative expectancies and decreased activation of positive expectancies predicted decreases in urges to drink, but only for intoxicated participants in the negative cue condition. There were no associations between expectancy activation and urges to drink for those in the positive cue condition regardless of beverage condition. Results suggest that whether memory activation of alcohol expectancies has an impact on urge to drink after alcohol is on board may depend on the relevance of the activated expectancies to the current drinking context. This process appears to be influenced by a complex interaction between contextual cues in the environment and the pharmacological effects of alcohol. PMID:25111186

  18. Effects of the benzodiazepine GABAA α1-preferring ligand, 3-propoxy-β-carboline hydrochloride (3-PBC), on alcohol seeking and self-administration in baboons

    PubMed Central

    Kaminski, Barbara J.; Van Linn, Michael L.; Cook, James M.; Yin, Wenyuan; Weerts, Elise M.

    2013-01-01

    Rationale The various α subtypes of GABAA receptors have been strongly implicated in alcohol reinforcement and consumption. Objectives The effects of the GABAA α1-preferring ligand, 3-propoxy-β-carboline hydrochloride (3-PBC), on seeking and self-administration responses were evaluated in two groups of baboons trained under a 3 component chained schedule of reinforcement (CSR). Methods Alcohol (4% w/v; n=5; alcohol group) or a preferred non-alcoholic beverage (n=4; control group) was available for self-administration only in component 3 of the CSR. Responses in component 2 provided indices of motivation to drink (seeking). 3-PBC (1.0 – 30.0 mg/kg) and saline were administered before drinking sessions under both acute and 5-day dosing conditions. Results Repeated, and not acute, doses of 3-PBC significantly decreased total self-administration responses (p<0.05), volume consumed (p<0.05) and g/kg of alcohol (p<0.05) in the alcohol group. In the control group, 5-day administration of 3-PBC significantly decreased total self-administration responses (p<0.05) but produced nonsignificant decreases in volume consumed. Within-session pattern of drinking was characterized by a high level of drinking in the first 20 min of the session for both groups, which was significantly (p<0.05) decreased by all doses of 3-PBC (1.0-18.0 mg/kg) only in the alcohol group. In contrast, the first drinking bout in the control group was only reduced at the highest doses of 3-PBC (10.0 and 18.0 mg/kg). Conclusions The results support the involvement of the GABAA α1 subtype receptor in alcohol reinforcement and consumption. PMID:23271191

  19. The Contribution of Postingestive Associations to Alcohol Self-Administration

    ERIC Educational Resources Information Center

    Roll, John M.; Mercado, Pedro; Chudzynski, Joy; Reilly, Mark P.

    2009-01-01

    Drugs, including alcohol, that are abused function as powerful reinforcers. Effective drug and alcohol addiction treatments decrease the reinforcing efficacy of the abused substance. Reinforcing efficacy arises from a variety of sources, documentation of which may aid in designing treatment and prevention interventions. Understanding the origin…

  20. Marchiafava-Bignami and Alcohol Related Acute Polyneuropathy: The Cooccurrence of Two Rare Entities

    PubMed Central

    Boloursaz, Samine; Nekooei, Sirous; Seilanian Toosi, Farrokh; Rezaei-Dalouei, Hossein; Davachi, Behrooz; Kazemi, Sahar

    2016-01-01

    Objectives. The aim of this article is to represent the first reported case with cooccurrence of two rare alcohol related complications. Case Report. We report a 38-year-old man with chronic alcoholism who presented with both cranial and peripheral nerve palsy. On MRI examination characteristic findings of Marchiafava-Bignami disease were recognized. Discussion. Marchiafava-Bignami disease (MBD) is a rare complication of long-term, heavy alcohol abuse that has characteristic MRI findings. Acute alcohol related polyneuropathy (AARP) is another rare and not-well-understood complication of chronic alcohol abuse. We could not find any previous report of the cooccurrence of these two complications in the literature.

  1. Alcohol self-administration by rats in the presence of a tangible object.

    PubMed

    Files, Forrest J; Meyer, Alexander; Cantz, Paul; Young, Melissa; Sierra, Gabriela; Berman, Dara; Stachelski, April; Cantz, Vanessa

    2006-04-01

    The authors used the sucrose-substitution procedure to train operant self-administration of a 10% alcohol solution in 8 Long-Evans rats. After they established stable responding, they began a 10-session baseline. A 10-session experimental phase followed the baseline phase. During the experimental phase, the authors placed a large glass marble in the center of the experimental chambers before self-administration sessions. The presence of the marble decreased the rats' responding and alcohol intake significantly. The authors discussed the results in terms of distraction and the effects of concurrently available reinforcers on alcohol self-administration.

  2. Resistance to change of alcohol self-administration: effects of alcohol-delivery rate on disruption by extinction and naltrexone.

    PubMed

    Jimenez-Gomez, Corina; Shahan, Timothy A

    2007-03-01

    A common finding in resistance to change research with food-maintained operant behavior is that the persistence of behavior depends on the rate of reinforcement delivered in the context in which the behavior occurs. The present experiment evaluated the effects of rate of response-dependent alcohol delivery on the resistance to change of rats' alcohol self-administration in the face of disruption produced by extinction and a range of doses of naltrexone (1.0, 3.0, 10.0 mg/kg, subcutaneous). Rats responded for a 10% alcohol solution in a multiple schedule of reinforcement arranging a higher rate of alcohol delivery (variable interval 15 s) in the presence of one stimulus and a lower rate of alcohol delivery (variable interval 45 s) in the presence of another stimulus. Baseline response rates and resistance to extinction were higher in the presence of the stimulus associated with higher rates of alcohol delivery. This finding is consistent with studies of the resistance to change of food-maintained behavior. The rate of alcohol delivered in the components, however, did not systematically affect resistance to disruption by naltrexone. One interpretation of this finding from the perspective of behavioral momentum theory is that naltrexone may decrease the impact of alcohol-associated stimuli on the persistence of drinking by reducing sensitivity to the relative reinforcement conditions arranged in the presence of different stimuli.

  3. [THE ROLE OF BIOLOGICAL MEMBRANES IN DIFFERENTIAL DIAGNOSTICS OF SALMONELLA AND ACUTE ALCOHOL GASTROENTERITIS].

    PubMed

    Makarov, V K; Makarov, P V

    2015-01-01

    We evaluated the influence of Salmonella infection and alcohol on biological membranes from the content of serum phospholipid fraction known to be a component ofenterocyte membranes. Any change of membrane phospholipid content leads to a change of their blood level. The study included 50 patients with acute alcohol gastroenteritis, 50 ones with salmonella gastroenteritis, and 50 healthy subjects. Both salmonellosis and alcohol caused differently directed changes in biological membranes. The mechanism of diarrhea in patients with salmonella and acute alcohol gastroenteritis is different. Diarrhea associated with alcohol gastroenteritis is due to enhanced viscosity of biomembranes that decreases in salmonella gastroenteritis. It suggests different approaches to the treatment of these conditions. The membrane destruction coefficient below 2 is an additional proof of alcoholic etiology of gastroenteritis whereas its value above 3 confirms the involvement of salmonellosis in pathogenesis of gastroenteritis.

  4. CB1 Receptors Regulate Alcohol-Seeking Behavior and Alcohol Self-administration of Female Alcohol-Preferring (P) Rats

    PubMed Central

    Getachew, Bruk; Hauser, Sheketha R.; Dhaher, Ronnie; Bell, Richard L.; Oster, Scott M.; McBride, William J.; Rodd, Zachary A.

    2015-01-01

    Rationale The endogenous cannabinoid (CB) system mediates a number of behaviors associated with drug-seeking and drug self-administration. In this study the effects of CB1 receptor manipulations on operant ethanol (EtOH) responding during EtOH-seeking, EtOH- relapse as well as on-going EtOH self-administration were determined. Methods Alcohol-preferring (P) rats were trained in 2-lever operant chambers to self-administer 15% EtOH (v/v) and water on a concurrent fixed-ratio 5 – fixed-ratio 1 (FR5-FR1) schedule of reinforcement in daily 1-hr sessions. After 10 weeks, rats underwent 7 extinction sessions, followed by 2 weeks in their home cages without access to EtOH or operant chambers. Rats were then returned to the operant chambers for testing of EtOH-seeking behavior (no EtOH present) for 4 sessions. After a week in their home cages following the EtOH-seeking test, rats were returned to the operant chambers with access to EtOH and water (relapse). Rats were then maintained in the operant chambers for daily 1-hr sessions with access to 15% EtOH and water for several weeks. Results The CB1 receptor antagonist (SR141716A), at doses of 1 and 2 mg/kg, i.p. reduced EtOH-seeking and transiently reduced EtOH self-administration during relapse and maintenance. Conversely, treatment with the CB1 receptor agonist CP, 55-940, at doses of 1 and 10 μg/kg i.p., increased EtOH-seeking and EtOH self-administration during relapse. Conclusions The results of this study demonstrate that activation of CB1 receptors are involved in regulating EtOH-seeking as well as the reinforcing effects of EtOH under relapse and on-going self-administration conditions. PMID:21110997

  5. Acute neuropsychological effects of MDMA and ethanol (co-)administration in healthy volunteers

    PubMed Central

    Wezenberg, E.; Valkenberg, M. M. G. J.; de Jong, C. A. J.; Buitelaar, J. K.; van Gerven, J. M. A.; Verkes, R. J.

    2008-01-01

    Rationale In Western societies, a considerable percentage of young people expose themselves to 3,4-methylenedioxymethamphetamine (MDMA or “ecstasy”). Commonly, ecstasy is used in combination with other substances, in particular alcohol (ethanol). MDMA induces both arousing as well as hallucinogenic effects, whereas ethanol is a general central nervous system depressant. Objective The aim of the present study is to assess the acute effects of single and co-administration of MDMA and ethanol on executive, memory, psychomotor, visuomotor, visuospatial and attention function, as well as on subjective experience. Materials and methods We performed a four-way, double-blind, randomised, crossover, placebo-controlled study in 16 healthy volunteers (nine male, seven female) between the ages of 18–29. MDMA was given orally (100 mg) and blood alcohol concentration was maintained at 0.6‰ by an ethanol infusion regime. Results Co-administration of MDMA and ethanol was well tolerated and did not show greater impairment of performance compared to the single-drug conditions. Impaired memory function was consistently observed after all drug conditions, whereas impairment of psychomotor function and attention was less consistent across drug conditions. Conclusions Co-administration of MDMA and ethanol did not exacerbate the effects of either drug alone. Although the impairment of performance by all drug conditions was relatively moderate, all induced significant impairment of cognitive function. PMID:18305926

  6. Acute effects of ethanol on sex hormones in non-alcoholic men and women.

    PubMed

    Ellingboe, J

    1987-01-01

    Chronic alcohol consumption has long been known to interfere with reproductive function and sexual behavior, but specific effects of acute alcohol ingestion on sex hormones have been studied only recently. An attempt is made in this review to summarize and explain conflicting results from studies of the acute effects of alcohol on the hypothalamic-pituitary-gonadal axis, with healthy non-alcoholic men and women as subjects. In men, moderate to high doses of ethanol have been reported to suppress plasma testosterone. Although some clinical studies have not supported this observation, considerable evidence documents direct alcohol inhibition of testosterone biosynthesis in the testis. After alcohol ingestion, plasma LH remains unchanged or increases, probably because of reduced androgen negative feedback. In analogous studies with women during the late follicular phase of the menstrual cycle, alcohol does not decrease plasma estradiol or alter LH levels. Furthermore, it has been reported that plasma levels of estradiol, progesterone and testosterone increase during alcohol treatment in the midluteal phase, while gonadotropins tend to decrease. Alcohol has no effect on LH secretion in post-menopausal women. Because reports on the acute effects of alcohol in men have not been consistent, it remains to be determined if acute alcohol effects in men and women are really different. In men, provocative tests of gonadotropin response to LHRH stimulation were normal during periods of intoxication and hangover, indicating that ethanol has no significant direct effect on LH secretion at the pituitary level. It seems more likely that alcohol changes plasma levels of sex steroids by altering hepatic, gonadal, and possibly adrenal metabolism.(ABSTRACT TRUNCATED AT 250 WORDS)

  7. Effect of L-ornithine L-aspartate on Liver Injury Due to Acute Ethyl Alcohol Intoxication in Rats

    PubMed Central

    Durgun, HM; Ozhasenekler, A; Dursun, R; Basarali, MK; Turkcu, G; Orak, M; Ustundag, M; Guloglu, C

    2015-01-01

    ABSTRACT Objective: Ethyl alcohol is a substance that is widely used worldwide and known to exert toxic effects on liver. In this study, we aimed to examine the effect of L-ornithine L-aspartate (LOLA) on the toxicity of a single dose of ethyl alcohol in rats. Subjects and Method: We used 32 randomly selected male Sprague-Dawley rats weighing 200–250 g. The rats were grouped into four groups with each group containing eight rats: Group 1: the control group, Group 2: the ethyl alcohol group, Group 3: the LOLA group and Group 4: the ethyl alcohol+LOLA group. Ethyl alcohol was administered orally through a nasogastric tube at a dose of 6 g/kg after diluting with distilled water. One hour after ethyl alcohol administration, LOLA was administered to pre-specified groups orally through a nasogastric tube at a dose of 200 mg/kg after diluting with distilled water. Liver tissue and blood samples were obtained from all rats 24 hours later to study total antioxidant capacity (TAC), total oxidant status (TOS) and oxidative stress index (OSI) levels in liver samples, and aspartate aminotransferase (AST), alanine transferase (ALT), TAC, TOS and OSI levels in blood samples. Results: Serum TAC, TOS and OSI levels were higher in the groups that were administered ethyl alcohol. In addition, tissue TAC level was higher and TOS and OSI levels were lower in groups that were given ethyl alcohol. No significant changes were observed in serum and tissue TAC, TOS, OSI, ALT and AST levels in the LOLA administered groups. Conclusion: This study showed that LOLA was not biochemically effective and exerts no oxidative stress reducing activity in liver injury due to acute ethyl alcohol toxicity. PMID:26426168

  8. The effects of acute alcohol on psychomotor, set-shifting, and working memory performance in older men and women.

    PubMed

    Hoffman, Lauren A; Sklar, Alfredo L; Nixon, Sara Jo

    2015-05-01

    A limited number of publications have documented the effects of acute alcohol administration among older adults. Among these, only a few have investigated sex differences within this population. The current project examined the behavioral effects of acute low- and moderate-dose alcohol on 62 older (ages 55-70) male and female, healthy, light to moderate drinkers. Participants were randomly assigned to one of three dose conditions: placebo (peak breath alcohol concentration [BrAC] of 0 mg/dL), low (peak BrAC of 40 mg/dL), and moderate (peak BrAC of 65 mg/dL). Tasks assessed psychomotor, set-shifting, and working memory performance. Better set-shifting abilities were observed among women, whereas men demonstrated more efficient working memory, regardless of dose. The moderate-dose group did not significantly differ from the placebo group on any task. However, the low-dose group performed better than the moderate-dose group across measures of set shifting and working memory. Relative to the placebo group, the low-dose group exhibited better working memory, specifically for faces. Interestingly, there were no sex by dose interactions. These data suggest that, at least for our study's task demands, low and moderate doses of alcohol do not significantly hinder psychomotor, set-shifting, or working memory performance among older adults. In fact, low-dose alcohol may facilitate certain cognitive abilities. Furthermore, although sex differences in cognitive abilities were observed, these alcohol doses did not differentially affect men and women. Further investigation is necessary to better characterize the effects of sex and alcohol dose on cognition in older adults.

  9. Effects of alcohol administration on the disinhibition of racial prejudice.

    PubMed

    Reeves, S B; Nagoshi, C T

    1993-10-01

    Eighty-two white male undergraduate social drinkers were selected from high and low scorers on the Modern Racism Scale. Subjects were randomly assigned to 1 of 3 balanced placebo design conditions. After consuming their beverages, subjects viewed a videotape interaction between a Black and a White confederate. The subjects were told to rate the behaviors of the confederates, including an ambiguous shove of the White confederate by the Black confederate. It was expected, according to attribution theory, that high racism subjects would label the shove as more aggressive when they believed they had consumed alcohol, because alcohol could be used as an excuse for the socially unacceptable behavior of racial discrimination. A mood measure was also administered. Significant main effects of racism group and alcohol dosing were found for seriousness of aggression ratings, with high racism subjects and those expecting alcohol reporting more serious aggression, but the racism group by dosing condition interaction was not significant. A significant racism group by dosing condition interaction was found for the tension/anxiety mood scale, with greater tension being reported by high racism subjects who received alcohol. The results were related to theories of alcohol's disinhibiting and attention-limiting properties.

  10. The incidence of acute pancreatitis: impact of social deprivation, alcohol consumption, seasonal and demographic factors1

    PubMed Central

    Roberts, SE; Akbari, A; Thorne, K; Atkinson, M; Evans, PA

    2013-01-01

    Background The incidence of acute pancreatitis has increased sharply in many European countries and the USA in recent years. Aim To establish trends in incidence and mortality for acute pancreatitis in Wales, UK, and to assess how incidence may be linked to factors including social deprivation, seasonal effects and alcohol consumption. Methods Use of record linked inpatient, mortality and primary care data for 10 589 hospitalised cases of acute pancreatitis between 1999 and 2010. Results The incidence of acute pancreatitis was 30.0 per 100 000 population overall, mortality was 6.4% at 60 days. Incidence increased significantly from 27.6 per 100 000 in 1999 to 36.4 in 2010 (average annual increase = 2.7% per year), there was little trend in mortality (0.2% average annual reduction). The largest increases in incidence were among women aged <35 years (7.9% per year) and men aged 35–44 (5.7%) and 45–54 (5.3%). Incidence was 1.9 times higher among the most deprived quintile of patients compared with the most affluent (3.9 times higher for alcoholic acute pancreatitis and 1.5 for gallstone acute pancreatitis). Acute pancreatitis was increased significantly during the Christmas and New Year weeks by 48% (95% CI = 24–77%) for alcoholic aetiology, but not for gallstone aetiology (9%). Alcoholic admissions were increased with higher consumption of spirits and beer, but not wine. Conclusions The study shows an elevated rate of alcoholic acute pancreatitis during the Christmas and New Year period. Acute pancreatitis continues to rise, most rapidly for young women, while alcoholic acute pancreatitis is linked strongly with social deprivation. PMID:23859492

  11. Acute Alcohol Use and Injury Patterns in Young Adult Prehospital Patients.

    PubMed

    Barton, David J; Tift, Frank W; Cournoyer, Lauren E; Vieth, Julie T; Hudson, Korin B

    2016-01-01

    The objective was to determine if acute alcohol consumption is associated with differences in injury pattern among young adult patients with traumatic injuries presenting to emergency medical services (EMS). A cross-sectional, retrospective review of prehospital patient care reports (PCRs) was conducted evaluating injured patients who presented to a collegiate EMS agency from January 1, 2011 to December 31, 2012. Included patients were age 18-24 y and sustained an injury within the previous 24 h. PCRs were reviewed independently by two abstractors to determine if the patient was documented to have acutely consumed alcohol proximate to his/her injury. Primary and secondary sites of regional body injury were recorded. Injury severity was recorded using the Revised Trauma Score (RTS). The association between primary injury site and acute alcohol use was assessed using a chi-square test. Multiple logistic regression was used to control for sex in predicting injury type. Of 440 injured patients, 135 (30.6%) had documented alcohol use prior to injury. Acute alcohol consumption altered the overall pattern of regional injury (p < 0.001). Alcohol users were more likely to present with injury secondary to assault, fall/trip, and unknown mechanism of injury (p < 0.001, all comparisons). RTS scores were statistically lower in the alcohol group (p < 0.001), although the clinical significance of this is unclear. Controlling for sex, acute alcohol consumption predicted increased risk of head/neck injury 5.59-fold (p < 0.001). Acute alcohol use in collegiate EMS patients appears to alter injury patterns in young adults and increases risk of head/neck injury. EMS providers in similar agencies should consider these trends when assessing and treating injured college-aged patients. PMID:27002348

  12. Transient increase in alcohol self-administration following a period of chronic exposure to corticosterone.

    PubMed

    Besheer, Joyce; Fisher, Kristen R; Lindsay, Tessa G; Cannady, Reginald

    2013-09-01

    Stressful life events and chronic stressors have been associated with escalations in alcohol drinking. Stress exposure leads to the secretion of glucocorticoids (cortisol in the human; corticosterone (CORT) in the rodent). To model a period of heightened elevations in CORT, the present work assessed the effects of chronic exposure to the stress hormone CORT on alcohol self-administration. Male Long Evans rats were trained to self-administer a sweetened alcohol solution (2% sucrose/15% alcohol) resulting in moderate levels of daily alcohol intake (0.5-0.7 g/kg). Following stable baseline operant self-administration, rats received CORT in the drinking water for 7 days. A transient increase in alcohol self-administration was observed on the first self-administration session following CORT exposure, and behavior returned to control levels by the second session. Control experiments determined that this increase in alcohol self-administration was specific to alcohol, unrelated to general motor activation, and functionally dissociated from decreased CORT levels at the time of testing. These results indicate that repeated exposure to heightened levels of stress hormone (e.g., as may be experienced during stressful episodes) has the potential to lead to exacerbated alcohol intake in low to moderate drinkers. Given that maladaptive drinking patterns, such as escalated alcohol drinking following stressful episodes, have the potential to put an individual at risk for future drinking disorders, utilization of this model will be important for examination of neuroadaptations that occur as a consequence of CORT exposure in order to better understand escalated drinking following stressful episodes in nondependent individuals. PMID:23643750

  13. The effects of varenicline on alcohol seeking and self-administration in baboons

    PubMed Central

    Kaminski, Barbara J.; Weerts, Elise M.

    2013-01-01

    Background Nicotinic acetylcholine receptors (nAChRs) may play a critical role in alcohol reinforcement and consumption. The effects of varenicline, a nAChR partial agonist, on alcohol seeking and self-administration responses were evaluated in 2 groups of baboons trained under a 3-component chained schedule of reinforcement (CSR). Methods Alcohol (4% w/v; n=4; alcohol group) or a preferred non-alcoholic beverage (n=4; control group) was available for self-administration only in component 3 of the CSR. Responses in component 2, required to gain access to alcohol, provided indices of seeking behavior. Varenicline (0.032 – 0.32 mg/kg; 0.32 mg/kg BID) and vehicle were administered before CSR sessions subchronically (5 consecutive days). Higher doses (0.56, 1.0 mg/kg) were attempted but discontinued due to adverse effects. Results Subchronic varenicline administration significantly (p<0.05) decreased the seeking response rate and increased the time to complete the response requirement to gain access to the daily supply of alcohol at the higher doses (0.32 mg/kg, 0.32 mg/kg BID dosing) in the alcohol group compared to the control group. Mean number of drinks was significantly decreased (p<0.05), but effects did not differ between groups. The pattern of drinking was characterized by a high rate during an initial bout. Number of drinks during and duration of the initial bout were significantly decreased in the alcohol group, compared to the control group, at 0.32 mg/kg (p<0.05). Conclusions Varenicline may be clinically useful for reducing alcohol seeking behaviors prior to alcohol exposure. Given the modest effects on drinking itself, varenicline may be better suited as a treatment in combination with a pharmacotherapy that significantly reduces alcohol consumption. PMID:24033702

  14. Acute caffeine administration affects zebrafish response to a robotic stimulus.

    PubMed

    Ladu, Fabrizio; Mwaffo, Violet; Li, Jasmine; Macrì, Simone; Porfiri, Maurizio

    2015-08-01

    Zebrafish has been recently proposed as a valid animal model to investigate the fundamental mechanisms regulating emotional behavior and evaluate the modulatory effects exerted by psychoactive compounds. In this study, we propose a novel methodological framework based on robotics and information theory to investigate the behavioral response of zebrafish exposed to acute caffeine treatment. In a binary preference test, we studied the response of caffeine-treated zebrafish to a replica of a shoal of conspecifics moving in the tank. A purely data-driven information theoretic approach was used to infer the influence of the replica on zebrafish behavior as a function of caffeine concentration. Our results demonstrate that acute caffeine administration modulates both the average speed and the interaction with the replica. Specifically, zebrafish exposed to elevated doses of caffeine show reduced locomotion and increased sensitivity to the motion of the replica. The methodology developed in this study may complement traditional experimental paradigms developed in the field of behavioral pharmacology.

  15. Nurses' medication administration practices at two Singaporean acute care hospitals.

    PubMed

    Choo, Janet; Johnston, Linda; Manias, Elizabeth

    2013-03-01

    This study examined registered nurses' overall compliance with accepted medication administration procedures, and explored the distractions they faced during medication administration at two acute care hospitals in Singapore. A total of 140 registered nurses, 70 from each hospital, participated in the study. At both hospitals, nurses were distracted by personnel, such as physicians, radiographers, patients not under their care, and telephone calls, during medication rounds. Deviations from accepted medication procedures were observed. At one hospital, the use of a vest during medication administration alone was not effective in avoiding distractions during medication administration. Environmental factors and distractions can impact on the safe administration of medications, because they not only impair nurses' level of concentration, but also add to their work pressure. Attention should be placed on eliminating distractions through the use of appropriate strategies. Strategies that could be considered include the conduct of education sessions with health professionals and patients about the importance of not interrupting nurses while they are administering medications, and changes in work design.

  16. Enhanced AMPA receptor activity increases operant alcohol self-administration and cue-induced reinstatement.

    PubMed

    Cannady, Reginald; Fisher, Kristen R; Durant, Brandon; Besheer, Joyce; Hodge, Clyde W

    2013-01-01

    Long-term alcohol exposure produces neuroadaptations that contribute to the progression of alcohol abuse disorders. Chronic alcohol consumption results in strengthened excitatory neurotransmission and increased α-amino-3-hydroxyl-5-methyl-4-isoxazole-propionate receptors (AMPA) receptor signaling in animal models. However, the mechanistic role of enhanced AMPA receptor activity in alcohol-reinforcement and alcohol-seeking behavior remains unclear. This study examined the role of enhanced AMPA receptor function using the selective positive allosteric modulator, aniracetam, in modulating operant alcohol self-administration and cue-induced reinstatement. Male alcohol-preferring (P-) rats, trained to self-administer alcohol (15%, v/v) versus water were pre-treated with aniracetam to assess effects on maintenance of alcohol self-administration. To determine reinforcer specificity, P-rats were trained to self-administer sucrose (0.8%, w/v) versus water, and effects of aniracetam were tested. The role of aniracetam in modulating relapse of alcohol-seeking was assessed using a response contingent cue-induced reinstatement procedure in P-rats trained to self-administer 15% alcohol. Aniracetam pre-treatment significantly increased alcohol-reinforced responses relative to vehicle treatment. This increase was not attributed to aniracetam-induced hyperactivity as aniracetam pre-treatment did not alter locomotor activity. AMPA receptor involvement was confirmed because 6,7-dinitroquinoxaline-2,3-dione (AMPA receptor antagonist) blocked the aniracetam-induced increase in alcohol self-administration. Aniracetam did not alter sucrose-reinforced responses in sucrose-trained P-rats, suggesting that enhanced AMPA receptor activity is selective in modulating the reinforcing function of alcohol. Finally, aniracetam pre-treatment potentiated cue-induced reinstatement of alcohol-seeking behavior versus vehicle-treated P-rats. These data suggest that enhanced glutamate activity at AMPA

  17. Management Skills for Alcohol Program Administrators; Trainer Manual.

    ERIC Educational Resources Information Center

    National Center for Alcohol Education, Arlington, VA.

    This trainer's manual contains complete instructions and resource references for delivering the management skills program designed to upgrade the skills and performance of managerial personnel in the alcoholism field. It provides four areas of information: (1) course content and methodology, target audience, assumptions and suggestions; (2)…

  18. Nicotine administration in the wake-promoting basal forebrain attenuates sleep-promoting effects of alcohol.

    PubMed

    Sharma, Rishi; Lodhi, Shafi; Sahota, Pradeep; Thakkar, Mahesh M

    2015-10-01

    Nicotine and alcohol co-abuse is highly prevalent, although the underlying causes are unclear. It has been suggested that nicotine enhances pleasurable effects of alcohol while reducing aversive effects. Recently, we reported that nicotine acts via the basal forebrain (BF) to activate nucleus accumbens and increase alcohol consumption. Does nicotine suppress alcohol-induced aversive effects via the BF? We hypothesized that nicotine may act via the BF to suppress sleep-promoting effects of alcohol. To test this hypothesis, adult male Sprague-Dawley rats were implanted with sleep-recording electrodes and bilateral guides targeted toward the BF. Nicotine (75 pmol/500 nL/side) or artificial cerebrospinal fluid (ACSF; 500 nL/side) was microinjected into the BF followed by intragastric alcohol (ACSF + EtOH and NiC + EtOH groups; 3 g/kg) or water (NiC + W and ACSF + W groups; 10 mL/kg) administration. On completion, rats were killed and processed to localize injection sites in the BF. The statistical analysis revealed a significant effect of treatment on sleep-wakefulness. While rats exposed to alcohol (ACSF + EtOH) displayed strong sleep promotion, nicotine pre-treatment in the BF (NiC + EtOH) attenuated alcohol-induced sleep and normalized sleep-wakefulness. These results suggest that nicotine acts via the BF to suppress the aversive, sleep-promoting effects of alcohol, further supporting the role of BF in alcohol-nicotine co-use.

  19. The administration of atomoxetine during alcohol deprivation induces a time-limited increase in alcohol consumption after relapse.

    PubMed

    Alén, Francisco; Serrano, Antonia; Gorriti, Miguel Ángel; Pavón, Francisco Javier; Orio, Laura; de Heras, Raquel Gómez; Ramírez-López, María Teresa; Antón, María; Pozo, Miguel Ángel; Rodríguez de Fonseca, Fernando

    2014-11-01

    The administration of selective serotonin reuptake inhibitors (SSRIs) typically used as antidepressants increases alcohol consumption after an alcohol deprivation period in rats. However, the appearance of this effect after the treatment with selective noradrenaline reuptake inhibitors (SNRIs) has not been studied. In the present work we examined the effects of a 15-d treatment with the SNRI atomoxetine (1, 3 and 10 mg/kg, i.p.) in male rats trained to drink alcohol solutions in a 4-bottle choice test. The treatment with atomoxetine (10 mg/kg, i.p.) during an alcohol deprivation period increased alcohol consumption after relapse. This effect only lasted one week, disappearing thereafter. Treatment with atomoxetine did not cause a behavioral sensitized response to a challenge dose of amphetamine (1.5 mg/kg, i.p.), indicating the absence of a supersensitive dopaminergic transmission. This effect is markedly different from that of SSRI antidepressants that produced both long-lasting increases in alcohol consumption and behavioral sensitization. Clinical implications are discussed. PMID:25025529

  20. Gender Specific Effects of Mood on Alcohol Seeking Behaviors: Preliminary Findings Using Intravenous Alcohol Self-Administration

    PubMed Central

    Cyders, Melissa A.; VanderVeen, J. Davis; Plawecki, Martin; Millward, James B.; Hays, James; Kareken, David A.; O’Connor, Sean

    2016-01-01

    Background Although negative mood has long been implicated in differences in alcohol seeking by men and women, little research has used precise, well-controlled laboratory experiments to examine how negative mood affects alcohol seeking behaviors. Methods A total of 34 (19 Women) community-dwelling, alcohol using adults aged 21–32 (mean age=24.86, SD=3.40, 74.3% Caucasian; Alcohol Use Disorder Identification Test [AUDIT]= 10.1, SD= 3.4) completed two counter-balanced intravenous alcohol self-administration sessions: one under negative mood and one under neutral mood. Fourteen individuals (9 women; mean age=25.00, SD=2.77) participated in an alcohol “liking” experiment (i.e., free access drinking) and 20 individuals (10 women; mean age=24.77, SD=3.73) participated in an alcohol “wanting” experiment, in which gaining access to alcohol required progressively effortful work. There was no significant difference between men and women on the AUDIT (t(34)=−0.38, p=.71). Results Priming with negative mood induction caused a significant decrease in self-reported mood (mean change=−1.90, t(39)=−6.81, p<.001), as intended. In free access, negative mood was associated with a significantly increased peak breath alcohol concentration (BrAC; F=9.41, p=.01), with a trend toward a greater effect in men than in women (F=2.67, p=.13). Negative mood also had a significant effect on peak BrAC achieved in the progressive work paradigm (F=5.28, p=.04), with a significantly stronger effect in men (F=5.35, p=.03) than women; men also trended toward more consistent work for alcohol across both neutral and negative sessions. Conclusions These preliminary findings demonstrate a gender-specific response on how mood affects alcohol seeking and suggest gender-specific interventions to prevent mood-based alcohol consumption. PMID:26842258

  1. Acute and chronic tramadol administration impair spatial memory in rat

    PubMed Central

    Hosseini-Sharifabad, Ali; Rabbani, Mohammad; Sharifzadeh, Mohammad; Bagheri, Narges

    2016-01-01

    Tramadol hydrochloride, a synthetic opioid, acts via a multiple mechanism of action. Tramadol can potentially change the behavioral phenomena. The present study evaluates the effect of tramadol after single or multiple dose/s on the spatial memory of rat using object recognition task (ORT). Tramadol, 20 mg/kg, was injected intraperitoneally (i.p) as a single dose or once a day for 21 successive days considered as acute or chronic treatment respectively. After treatment, animals underwent two trials in the ORT. In the first trial (T1), animals encountered with two identical objects for exploration in a five-minute period. After 1 h, in the T2 trial, the animals were exposed to a familiar and a nonfamiliar object. The exploration times and frequency of the exploration for any objects were recorded. The results showed that tramadol decreased the exploration times for the nonfamiliar object in the T2 trial when administered either as a single dose (P<0.001) or as the multiple dose (P<0.05) compared to the respective control groups. Both acute and chronic tramadol administration eliminated the different frequency of exploration between the familiar and nonfamiliar objects. Our findings revealed that tramadol impaired memory when administered acutely or chronically. Single dose administration of tramadol showed more destructive effect than multiple doses of tramadol on the memory. The observed data can be explained by the inhibitory effects of tramadol on the wide range of neurotransmitters and receptors including muscarinic, N-methyl D-aspartate, AMPA as well as some second messenger like cAMP and cGMP or its stimulatory effect on the opioid, gama amino butyric acid, dopamine or serotonin in the brain. PMID:27051432

  2. Acute and chronic tramadol administration impair spatial memory in rat.

    PubMed

    Hosseini-Sharifabad, Ali; Rabbani, Mohammad; Sharifzadeh, Mohammad; Bagheri, Narges

    2016-01-01

    Tramadol hydrochloride, a synthetic opioid, acts via a multiple mechanism of action. Tramadol can potentially change the behavioral phenomena. The present study evaluates the effect of tramadol after single or multiple dose/s on the spatial memory of rat using object recognition task (ORT). Tramadol, 20 mg/kg, was injected intraperitoneally (i.p) as a single dose or once a day for 21 successive days considered as acute or chronic treatment respectively. After treatment, animals underwent two trials in the ORT. In the first trial (T1), animals encountered with two identical objects for exploration in a five-minute period. After 1 h, in the T2 trial, the animals were exposed to a familiar and a nonfamiliar object. The exploration times and frequency of the exploration for any objects were recorded. The results showed that tramadol decreased the exploration times for the nonfamiliar object in the T2 trial when administered either as a single dose (P<0.001) or as the multiple dose (P<0.05) compared to the respective control groups. Both acute and chronic tramadol administration eliminated the different frequency of exploration between the familiar and nonfamiliar objects. Our findings revealed that tramadol impaired memory when administered acutely or chronically. Single dose administration of tramadol showed more destructive effect than multiple doses of tramadol on the memory. The observed data can be explained by the inhibitory effects of tramadol on the wide range of neurotransmitters and receptors including muscarinic, N-methyl D-aspartate, AMPA as well as some second messenger like cAMP and cGMP or its stimulatory effect on the opioid, gama amino butyric acid, dopamine or serotonin in the brain. PMID:27051432

  3. Alternative substance paradigm: effectiveness of beverage blinding and effects on acute alcohol responses.

    PubMed

    Conrad, Megan; McNamara, Patrick; King, Andrea

    2012-10-01

    A fundamental goal of double-blind alcohol challenge studies is to reduce alcohol expectancies, though there is little research on the effectiveness of blinding procedures and their relationship to acute alcohol responses. This study examined social drinkers' perception of beverage content and related alcohol response during 3 separate double-blind experimental sessions with placebo, low-dose alcohol (0.4 g/kg), and high-dose alcohol (0.8 g/kg). Using the alternative substance paradigm, participants (N = 182) were informed that the beverage they consumed might contain alcohol, a stimulant, a sedative, or a placebo. At several time points, subjective and objective measures were obtained, and participants were asked to identify which substance they received. During both placebo and low-dose alcohol sessions, 33% and 50% of participants, respectively, did not correctly identify the beverage content; during the high-dose alcohol session, 20% did not correctly identify the beverage. Although correct and incorrect identifiers at any dose level did not differ on major background variables, drinking characteristics, or psychomotor performance during these sessions, they did differ on self-reported subjective responses, with greater sedation reported by incorrect identifiers in the placebo and high-dose conditions. In summary, results suggest that the alternative substance paradigm may be a viable option for alcohol laboratory studies, particularly for repeated sessions in within-subject designs and in cases in which the experimenter wants to reduce expectancy by not revealing a priori that alcohol is being administered.

  4. 78 FR 39256 - Polyvinyl Alcohol From Taiwan: Rescission of Antidumping Duty Administrative Review; 2012-2013

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-07-01

    ... FR 13858 (March 1, 2013). \\2\\ See Initiation of Antidumping and Countervailing Duty Administrative Reviews and Request for Revocation in Part, 78 FR 25418 (May 1, 2013). On May 24, 2013, CCPC withdrew its... International Trade Administration Polyvinyl Alcohol From Taiwan: Rescission of Antidumping Duty...

  5. Acute Alcohol Drinking Promotes Piecemeal Percepts during Binocular Rivalry.

    PubMed

    Cao, Dingcai; Zhuang, Xiaohua; Kang, Para; Hong, Sang W; King, Andrea C

    2016-01-01

    Binocular rivalry refers to perceptual alternation when two eyes view different images. One of the potential percepts during binocular rivalry is a spatial mosaic of left- and right-eye images, known as piecemeal percepts, which may result from localized rivalries between small regions in the left- and right-eye images. It is known that alcohol increases inhibitory neurotransmission, which may reduce the number of alternations during binocular rivalry. However, it is unclear whether alcohol affects rivalry dynamics in the same manner for both coherent percepts (i.e., percepts of complete left or right images) and piecemeal percepts. To address this question, the present study measured the dynamics of binocular rivalry before and after 15 moderate-to-heavy social drinkers consumed an intoxicating dose of alcohol versus a placebo beverage. Both simple rivalrous stimuli consisting of gratings with different orientations, and complex stimuli consisting of a face or a house were tested to examine alcohol effects on rivalry as a function of stimulus complexity. Results showed that for both simple and complex stimuli, alcohol affects coherent and piecemeal percepts differently. More specifically, alcohol reduced the number of coherent percepts but not the mean dominance duration of coherent percepts. In contrast, for piecemeal percepts, alcohol increased the mean dominance duration but not the number of piecemeal percepts. These results suggested that alcohol drinking may selectively affect the dynamics of transitional period of binocular rivalry by increasing the duration of piecemeal percepts, leading to a reduction in the number of coherent percepts. The differential effect of alcohol on the dynamics of coherent and piecemeal percepts cannot be accounted for by alcohol's effect on a common inhibitory mechanism. Other mechanisms, such as increasing neural noise, are needed to explain alcohol's effect on the dynamics of binocular rivalry. PMID:27092096

  6. [Alcohol consumption in administrative and service personnel in an Ecuadorian university].

    PubMed

    Bravo Ortiz, Carmita María; Marziale, Maria Helena Palucci

    2010-01-01

    The aim of this descriptive study was to characterize the consumption of alcohol among workers in the administrative and service sectors at an Ecuadorian university and to determine differences in consumption between the two groups of workers. The Alcohol Use Disorders Identification Test (AUDIT) was applied to 102 participants. The results showed that the service personnel consumed more alcohol than the administrative personnel with a mean total score of 7.26 against 1.84. The total prevalence of non-prejudicial consumption was 79.41%, prejudicial consumption 19.61% and dependency 0.98%. The total scores of 76.47% of the participants were within risk zone one; 18.63% risk zone two; 3.92% risk zone three; 0.98% risk zone four. In conclusion, due to the identification of hazardous consumption, it is necessary to implement a program of alcohol use prevention in the institution studied. PMID:20694416

  7. Acute Alcohol Drinking Promotes Piecemeal Percepts during Binocular Rivalry

    PubMed Central

    Cao, Dingcai; Zhuang, Xiaohua; Kang, Para; Hong, Sang W.; King, Andrea C.

    2016-01-01

    Binocular rivalry refers to perceptual alternation when two eyes view different images. One of the potential percepts during binocular rivalry is a spatial mosaic of left- and right-eye images, known as piecemeal percepts, which may result from localized rivalries between small regions in the left- and right-eye images. It is known that alcohol increases inhibitory neurotransmission, which may reduce the number of alternations during binocular rivalry. However, it is unclear whether alcohol affects rivalry dynamics in the same manner for both coherent percepts (i.e., percepts of complete left or right images) and piecemeal percepts. To address this question, the present study measured the dynamics of binocular rivalry before and after 15 moderate-to-heavy social drinkers consumed an intoxicating dose of alcohol versus a placebo beverage. Both simple rivalrous stimuli consisting of gratings with different orientations, and complex stimuli consisting of a face or a house were tested to examine alcohol effects on rivalry as a function of stimulus complexity. Results showed that for both simple and complex stimuli, alcohol affects coherent and piecemeal percepts differently. More specifically, alcohol reduced the number of coherent percepts but not the mean dominance duration of coherent percepts. In contrast, for piecemeal percepts, alcohol increased the mean dominance duration but not the number of piecemeal percepts. These results suggested that alcohol drinking may selectively affect the dynamics of transitional period of binocular rivalry by increasing the duration of piecemeal percepts, leading to a reduction in the number of coherent percepts. The differential effect of alcohol on the dynamics of coherent and piecemeal percepts cannot be accounted for by alcohol’s effect on a common inhibitory mechanism. Other mechanisms, such as increasing neural noise, are needed to explain alcohol’s effect on the dynamics of binocular rivalry. PMID:27092096

  8. [Psychopathology and various mechanisms contributing to the formation of the Kandinsky syndrome in acute alcoholic hallucinosis].

    PubMed

    Guliamova, N M

    1983-01-01

    Forty patients with acute alcoholic hallucinosis associated with the Kandinsky syndrome were examined clinicopsychopathologically. Manifestation of the Kandinsky syndrome was limited by associative automatism in patients with stage II alcoholism with transient hallucinosis lasting 2-4 days. In patients with stage III alcoholism with more prolonged (6-9 days) psychoses, the non-extensive Kandinsky syndrome manifested itself in integrity. Psychopathological phenomena of the syndrome in the picture of acute alcoholic hallucinosis were notable for their descriptiveness, concreteness, extreme simplicity, and instability. Senestopathic and kinesthetic automatisms were localized at the sites of real painful disorders. Therefore, apart from cerebral disorders, the peripheral sensory mechanisms are considered to be of importance in the genesis of the Kandinsky syndrome.

  9. The culture of science and the ethics of alcohol administration in research.

    PubMed

    Goldman, M S

    2000-12-01

    The failure of ethicists to develop an absolute ethical code has led to the consideration of ethics in particular contexts. In the alcohol field, such consideration has resulted in considerable controversy, because this field has been influenced by parallel cultural contexts: a scientific research culture and a layman's spiritual culture (represented by Alcoholics Anonymous). Both cultures can inform ethical decisions, but for scientific decisions to be made the influence of these cultures must be disentangled. This article reviews issues pertaining to this disentangling in connection with the use of alcohol administration in research.

  10. Adolescents and Alcohol: Acute Sensitivities, Enhanced Intake, and Later Consequences*

    PubMed Central

    Spear, Linda Patia

    2014-01-01

    Adolescence is an evolutionarily conserved developmental period characterized by notable maturational changes in brain along with various age-related behavioral characteristics, including the propensity to initiate alcohol and other drug use and consume more alcohol per occasion than adults. After a brief review of adolescent neurobehavioral function from an evolutionary perspective, the paper will turn to assessment of adolescent alcohol sensitivity and consequences, with a focus on work from our laboratory. After summarizing evidence showing that adolescents differ considerably from adults in their sensitivity to various effects of alcohol, potential contributors to these age-typical sensitivities will be discussed, and the degree to which these findings are generalizable to other drugs and to human adolescents will be considered. Recent studies are then reviewed to illustrate that repeated alcohol exposure during adolescence induces behavioral, cognitive, and neural alterations that are highly specific, replicable, persistent and dependent on the timing of the exposure. Research in this area is in its early stages, however, and more work will be necessary to characterize the extent of these neurobehavioral alterations and further determine the degree to which observed effects are specific to alcohol exposure during adolescence. PMID:24291291

  11. Cigarettes and alcohol: The influence of nicotine on operant alcohol self-administration and the mesolimbic dopamine system.

    PubMed

    Ostroumov, Alexey; Thomas, Alyse M; Dani, John A; Doyon, William M

    2015-10-15

    Studies in human populations consistently demonstrate an interaction between nicotine and ethanol use, each drug influencing the use of the other. Here we present data and review evidence from animal studies that nicotine influences operant self-administration of ethanol. The operant reinforcement paradigm has proven to be a behaviorally relevant and quantitative model for studying ethanol-seeking behavior. Exposure to nicotine can modify the reinforcing properties of ethanol during different phases of ethanol self-administration, including acquisition, maintenance, and reinstatement. Our data suggest that non-daily intermittent nicotine exposure can trigger a long-lasting increase in ethanol self-administration. The biological basis for interactions between nicotine and ethanol is not well understood but may involve the stress hormone systems and adaptations in the mesolimbic dopamine system. Future studies that combine operant self-administration with techniques for monitoring or manipulating in vivo neurophysiology may provide new insights into the neuronal mechanisms that link nicotine and alcohol use.

  12. Behavioral economic analysis of stress effects on acute motivation for alcohol.

    PubMed

    Owens, Max M; Ray, Lara A; MacKillop, James

    2015-01-01

    Due to issues of definition and measurement, the heavy emphasis on subjective craving in the measurement of acute motivation for alcohol and other drugs remains controversial. Behavioral economic approaches have increasingly been applied to better understand acute drug motivation, particularly using demand curve modeling via purchase tasks to characterize the perceived reinforcing value of the drug. This approach has focused on using putatively more objective indices of motivation, such as units of consumption, monetary expenditure, and price sensitivity. To extend this line of research, the current study used an alcohol purchase task to determine if, compared to a neutral induction, a personalized stress induction would increase alcohol demand in a sample of heavy drinkers. The stress induction significantly increased multiple measures of the reinforcing value of alcohol to the individual, including consumption at zero price (intensity), the maximum total amount of money spent on alcohol (Omax), the first price where consumption was reduced to zero (breakpoint), and the general responsiveness of consumption to increases in price (elasticity). These measures correlated only modestly with craving and mood. Self-reported income was largely unrelated to demand but moderated the influence of stress on Omax. Moderation based on CRH-BP genotype (rs10055255) was present for Omax, with T allele homozygotes exhibiting more pronounced increases in response to stress. These results provide further support for a behavioral economic approach to measuring acute drug motivation. The findings also highlight the potential relevance of income and genetic factors in understanding state effects on the perceived reinforcing value of alcohol.

  13. [Preventive administration of new UDCA derivatives in experimental alcoholic steatohepatitis].

    PubMed

    Belonovskaia, E B; Naruta, E E; Lukivskaia, O Ia; Abakumov, V Z; Buko, V U

    2013-01-01

    We have studied the prophylactic effect of new derivatives of ursodeoxycholic acid (UDCA), including UDCA-N-acetylcysteine, UDCA-L-acetylcysteine, and nor-UDCA (in doses equivalent to 40 mg/kg of UDCA) on the development of experimental alcoholic steatohepatitis induced by the Lieber-DeCarli liquid ethanol-containing diet. Results demonstrated that most of the investigated compounds produced a hepatoprotective effect, improving biochemical tests and liver morphology, as manifested by decreasing steatosis intensity, activity of alkaline phosphatase and gamma-glutamyltranspeptidase, triglyceride level in blood serum and liver, and TNF alpha content. However, nor-UDCA was most effective as compared to UDCA in preventing the accumulation of triglycerides in the liver.

  14. Marchiafava-Bignami and Alcohol Related Acute Polyneuropathy: The Cooccurrence of Two Rare Entities

    PubMed Central

    Boloursaz, Samine; Nekooei, Sirous; Seilanian Toosi, Farrokh; Rezaei-Dalouei, Hossein; Davachi, Behrooz; Kazemi, Sahar

    2016-01-01

    Objectives. The aim of this article is to represent the first reported case with cooccurrence of two rare alcohol related complications. Case Report. We report a 38-year-old man with chronic alcoholism who presented with both cranial and peripheral nerve palsy. On MRI examination characteristic findings of Marchiafava-Bignami disease were recognized. Discussion. Marchiafava-Bignami disease (MBD) is a rare complication of long-term, heavy alcohol abuse that has characteristic MRI findings. Acute alcohol related polyneuropathy (AARP) is another rare and not-well-understood complication of chronic alcohol abuse. We could not find any previous report of the cooccurrence of these two complications in the literature. PMID:27668107

  15. Marchiafava-Bignami and Alcohol Related Acute Polyneuropathy: The Cooccurrence of Two Rare Entities.

    PubMed

    Boloursaz, Samine; Nekooei, Sirous; Seilanian Toosi, Farrokh; Rezaei-Dalouei, Hossein; Davachi, Behrooz; Kazemi, Sahar; Abbasi, Bita

    2016-01-01

    Objectives. The aim of this article is to represent the first reported case with cooccurrence of two rare alcohol related complications. Case Report. We report a 38-year-old man with chronic alcoholism who presented with both cranial and peripheral nerve palsy. On MRI examination characteristic findings of Marchiafava-Bignami disease were recognized. Discussion. Marchiafava-Bignami disease (MBD) is a rare complication of long-term, heavy alcohol abuse that has characteristic MRI findings. Acute alcohol related polyneuropathy (AARP) is another rare and not-well-understood complication of chronic alcohol abuse. We could not find any previous report of the cooccurrence of these two complications in the literature. PMID:27668107

  16. Enhanced alcohol self-administration and reinstatement in a highly impulsive, inattentive recombinant inbred mouse strain.

    PubMed

    Loos, Maarten; Staal, Jorn; Smit, August B; De Vries, Taco J; Spijker, Sabine

    2013-01-01

    Deficits in executive control have frequently been associated with alcohol use disorder. Here we investigated to what extent pre-existing genetically encoded levels of impulsive/inattentive behavior associate with motivation to take alcohol and vulnerability to cue-induced reinstatement of alcohol seeking in an operant self-administration paradigm. We took advantage of BXD16, a recombinant inbred strain previously shown to have enhanced impulsivity and poor attentional control. We compared BXD16 with C57BL/6J mice in a simple choice reaction time task (SCRTT) and confirmed its impulsive/inattentive phenotype. BXD16 mice were less active in a novel open field (OF), and were equally active in an automated home cage environment, showing that increased impulsive responding of BXD16 mice could not be explained by enhanced general activity compared to C57BL/6J mice. After training in a sucrose/alcohol fading self-administration procedure, BXD16 showed increased motivation to earn 10% alcohol solution, both under fixed ratio (FR1) and progressive ratio (PR2) schedules of reinforcement. Responding on the active lever readily decreased during extinction training with no apparent differences between strains. However, upon re-exposure to alcohol-associated cues, alcohol seeking was reinstated to a larger extent in BXD16 than in C57BL/6J mice. Although further studies are needed to determine whether impulsivity/inattention and alcohol seeking depend on common or separate genetic loci, these data show that in mice enhanced impulsivity coincides with increased motivation to take alcohol, as well as relapse vulnerability. PMID:24198771

  17. Hepatic Steatosis in Response to Acute Alcohol Exposure in Zebrafish requires Srebp Activation

    PubMed Central

    Passeri, Michael J.; Cinaroglu, Ayca; Gao, Chuan; Sadler, Kirsten C.

    2008-01-01

    Steatosis is the most common consequence of acute alcohol abuse and may predispose to more severe hepatic disease. Increased lipogenesis driven by the sterol response element binding protein (SREBP) transcription factors is essential for steatosis associated with chronic alcohol ingestion, but the mechanisms underlying steatosis following acute alcohol exposure are unknown. Zebrafish larvae represent an attractive vertebrate model for studying alcoholic liver disease (ALD), because they possess the pathways to metabolize alcohol, the liver is mature by 4 days post-fertilization (dpf), and alcohol can be simply added to their water. Exposing 4 dpf zebrafish larvae to 2% ethanol (EtOH) for 32 hours achieves ∼80 mM intracellular EtOH and upregulation of hepatic cyp2e1, sod and bip, indicating that EtOH is metabolized and provokes oxidant stress. EtOH-treated larvae develop hepatomegaly and steatosis accompanied by changes in the expression of genes required for hepatic lipid metabolism. Based on the importance of SREPBs in chronic ALD, we explored the role of Srebps in this model of acute ALD. Srebp activation was prevented in gonzo larvae, which harbor a mutation in the membrane bound transcription factor protease 1 (mbtps1) gene, and in embryos injected with a morpholino to knock-down Srebp cleavage activating protein (scap). Both gonzo mutants and scap morphants were resistant to steatosis in response to 2% EtOH, and the expression of many Srebp target genes are down regulated in gonzo mutant livers. Conclusion Zebrafish larvae develop signs of acute ALD, including steatosis. Srebp activation is required for steatosis in this model. The tractability of zebrafish genetics provides a valuable tool for dissecting the molecular pathogenesis of acute ALD. PMID:19127516

  18. Cinnamon extract protects against acute alcohol-induced liver steatosis in mice.

    PubMed

    Kanuri, Giridhar; Weber, Synia; Volynets, Valentina; Spruss, Astrid; Bischoff, Stephan C; Bergheim, Ina

    2009-03-01

    Acute and chronic consumption of alcohol can cause increased intestinal permeability and bacterial overgrowth, thereby increasing portal endotoxin levels. This barrier impairment subsequently leads to an activation of hepatic Kupffer cells and increased release of reactive oxygen species as well as of tumor necrosis factor-alpha (TNFalpha). Recent studies have suggested that cinnamon extract may have antiinflammatory effects. In the present study, the protective effects of an alcoholic extract of cinnamon bark was assessed in a mouse model of acute alcohol-induced steatosis and in RAW 264.7 macrophages, used here as a model of Kupffer cells. Acute alcohol ingestion caused a >20-fold increase in hepatic lipid accumulation. Pretreatment with cinnamon extract significantly reduced the hepatic lipid accumulation. This protective effect of cinnamon extract was associated with an inhibition of the induction of the myeloid differentiation primary response gene (MyD) 88, inducible nitric oxide (NO) synthase (iNOS), and plasminogen activator inhibitor 1 mRNA expression found in livers of alcohol-treated animals. In vitro prechallenge with cinnamon extract suppressed lipopolysaccharide (LPS)-induced MyD88, iNOS, and TNFalpha expression as well as NO formation almost completely. Furthermore, LPS treatment of RAW 264.7 macrophages further resulted in degradation of inhibitor kappaB; this effect was almost completely blocked by cinnamon extract. Taken together, our data show that an alcohol extract of cinnamon bark may protect the liver from acute alcohol-induced steatosis through mechanisms involving the inhibition of MyD88 expression. PMID:19126670

  19. The pre-synaptic Munc13-1 binds alcohol and modulates alcohol self-administration in Drosophila.

    PubMed

    Das, Joydip; Xu, Shiyu; Pany, Satyabrata; Guillory, Ashley; Shah, Vrutant; Roman, Gregg W

    2013-09-01

    Munc13-1 is a pre-synaptic active-zone protein essential for neurotransmitter release and involved in pre-synaptic plasticity in brain. Ethanol, butanol, and octanol quenched the intrinsic fluorescence of the C1 domain of Munc13-1 with EC₅₀ s of 52 mM, 26 mM, and 0.7 mM, respectively. Photoactive azialcohols photolabeled Munc13-1 C1 exclusively at Glu-582, which was identified by mass spectrometry. Mutation of Glu-582 to alanine, leucine, and histidine reduced the alcohol binding two- to five-fold. Circular dichroism studies suggested that binding of alcohol increased the stability of the wild-type Munc13-1 compared with the mutants. If Munc13-1 plays some role in the neural effects of alcohol in vivo, changes in the activity of this protein should produce differences in the behavioral responses to ethanol. We tested this prediction with a loss-of-function mutation in the conserved Dunc-13 in Drosophila melanogaster. The Dunc-13(P84200) /+ heterozygotes have 50% wild-type levels of Dunc-13 mRNA and display a very robust increase in ethanol self-administration. This phenotype is reversed by the expression of the rat Munc13-1 protein within the Drosophila nervous system. The present studies indicate that Munc13-1 C1 has binding site(s) for alcohols and Munc13-1 activity is sufficient to restore normal self-administration to Drosophila mutants deficient in Dunc-13 activity. The pre-synaptic Mun13-1 protein is a critical regulator of synaptic vesicle fusion and may be involved in processes that lead to ethanol abuse and addiction. We studied its interaction with alcohol and identified Glu-582 as a critical residue for ethanol binding. Munc13-1 can functionally complement the Dunc13 haploinsufficient ethanol self-administration phenotype in Drosophila melanogaster, indicating that this protein participates in alcohol-induced behavioral plasticity.

  20. Acute Alcohol Consumption Elevates Serum Bilirubin, an Endogenous Antioxidant

    PubMed Central

    O’Malley, Stephanie S.; Gueorguieva, Ralitza; Wu, Ran; Jatlow, Peter I.

    2015-01-01

    Background Moderate alcohol consumption has been associated with both negative and favorable effects on health. The mechanisms responsible for reported favorable effects remain unclear. Higher (not necessarily elevated) concentrations of serum bilirubin, an antioxidant, have also been associated with reduced risk of cardiovascular disease and all-cause mortality. This study tests the hypothesis that single dose alcohol consumption elevates bilirubin providing a potential link between these observations. Methods 18 healthy individuals (8 cigarette smokers) were administered alcohol, calibrated to achieve blood concentrations of 20, 80 and 120 mg/dL, in random order in 3 laboratory sessions separated by a week. Each session was preceded by and followed by 5–7 days of alcohol abstinence. Serum bilirubin was measured at 7:45 am prior to drinking, at 2 pm, and at 7:45 the next morning. Mixed effects regression models compared baseline and 24 hr. post-drinking bilirubin concentrations. Results Total serum bilirubin (sum of indirect and direct) concentration increased significantly after drinking from baseline to 24 hours in non-smokers (from Mean=0.38, SD=0.24 to Mean=0.51 SD=0.30, F(1, 32.2) =24.24, p<.0001) but not in smokers (from Mean=0.25, SD=0.12 to Mean=0.26, SD=0.15, F(1, 31.1) =0.04, p=0.84). In nonsmokers the indirect bilirubin concentration and the ratio of indirect (unconjugated) to direct (conjugated) bilirubin also increased significantly. Conclusions Alcohol consumption leads to increases in serum bilirubin in nonsmokers. Considering the antioxidant properties of bilirubin, our findings suggest one possible mechanism for the reported association between alcohol consumption and reduced risk of some disorders that could be tested in future longitudinal studies. PMID:25707709

  1. Effect of acute ethanol administration on zebrafish tail-beat motion.

    PubMed

    Bartolini, Tiziana; Mwaffo, Violet; Butail, Sachit; Porfiri, Maurizio

    2015-11-01

    Zebrafish is becoming a species of choice in neurobiological and behavioral studies of alcohol-related disorders. In these efforts, the activity of adult zebrafish is typically quantified using indirect activity measures that are either scored manually or identified automatically from the fish trajectory. The analysis of such activity measures has produced important insight into the effect of acute ethanol exposure on individual and social behavior of this vertebrate species. Here, we leverage a recently developed tracking algorithm that reconstructs fish body shape to investigate the effect of acute ethanol administration on zebrafish tail-beat motion in terms of amplitude and frequency. Our results demonstrate a significant effect of ethanol on the tail-beat amplitude as well as the tail-beat frequency, both of which were found to robustly decrease for high ethanol concentrations. Such a direct measurement of zebrafish motor functions is in agreement with evidence based on indirect activity measures, offering a complementary perspective in behavioral screening. PMID:26314628

  2. Mechanics of the carotid artery wall and baroreflex sensitivity after acute ethanol administration in young healthy volunteers.

    PubMed

    Fazio, M; Bardelli, M; Macaluso, L; Fiammengo, F; Mattei, P L; Bossi, M; Fabris, B; Fischetti, F; Pascazio, L; Candido, R; Carretta, R

    2001-09-01

    The effects of ethanol administered orally (300 mg/kg in 250 ml of water) or intravenously (7.5 mg.min(-1).kg(-1) in 250 ml of saline over 40 min) on common carotid haemodynamics, wall mechanics and baroreflex sensitivity were compared with the effects of the intravenous infusion of 250 ml of saline. Ethanol or saline was administered to 10 healthy volunteers after 30 min of supine rest, and measurements were obtained 40 min (median; range 34-46 min) after administration. After ethanol administration, the plasma alcohol level rose from 0 to 0.3+/-0.07 g/l. Mean arterial blood pressure had risen slightly at 20 min, but was normalized by 40 min, the time at which the haemodynamic study was performed. Heart rate decreased after infusion of either saline or alcohol, but was unchanged after oral ethanol administration. Both oral and intravenous ethanol administration were associated with significant decreases in baroreflex sensitivity, carotid shear stress and blood velocity, compared with resting values, while the mean carotid artery diameter was increased, and blood viscosity and mean blood flow were unchanged. No changes were observed in these parameters after saline administration. Ethanol, administered either intravenously or orally, increased the stiffness of the carotid artery and decreased the pulsatility (systo-diastolic changes) of its diameter. A direct, statistically significant correlation was found between the decrease in shear stress and the decrease in baroreflex heart rate control sensitivity after both modes of alcohol administration, while no such correlation was found between the increase in the Peterson elastic modulus and the decrease in carotid diameter pulsatility on the one hand or the decrease in baroreflex sensitivity on the other. In conclusion, reduced shear stress associated with vasodilatation of the carotid artery wall may contribute to the decrease in baroreflex sensitivity observed after acute ethanol administration.

  3. Effect of acute and chronic alcohol treatment and their superimposition on lysosomal, cytoplasmic, and proteosomal protease activities in rat skeletal muscle in vivo.

    PubMed

    Koll, M; Ahmed, S; Mantle, D; Donohue, T M; Palmer, T N; Simanowski, U A; Seltz, H K; Peters, T J; Preedy, V R

    2002-01-01

    Alcohol can be considered as a nutritional toxin when ingested in excess amounts and leads to skeletal muscle myopathy. We hypothesized that altered protease activities contribute to this phenomenon, and that differential effects on protease activities may occur when: (1) rats at different stages in their development are administered alcohol in vivo; (2) acute ethanol treatment is superimposed on chronic alcohol-feeding in vivo; and (3) muscles are exposed to alcohol and acetaldehyde in vivo and in vitro. In acute studies, rats weighing approximately 0.1 kg (designated immature) or approximately 0.25 kg (designated mature) body weight (BW) were dosed acutely with alcohol (75 mmol/kg BW; intraperitoneal [IP], 2.5 hours prior to killing) or identically treated with 0.15 mol/L NaCl as controls. In chronic studies, rats (approximately 0.1 kg BW) were fed between 1 to 6 weeks, with 35% of dietary energy as ethanol, controls were identically treated with isocaloric glucose. Other studies included administration of cyanamide (aldehyde dehydrogenase inhibitor) in vivo or addition of alcohol and acetaldehyde to muscle preparations in vitro. At the end of the treatments, cytoplasmic (alanyl-, arginyl-, leucyl-, prolyl-, tripeptidyl-aminopeptidase and dipeptidyl aminopeptidase IV), lysosomal (cathepsins B, D, H, and L, dipeptidyl aminopeptidase I and II), proteasomal (chymotrypsin-, trypsin-like, and peptidylglutamyl peptide hydrolase activities) and Ca(2+)-activated (micro- and milli-calpain and calpastatin) activities were assayed. (1) Acute alcohol dosage in mature rats reduced the activities of alanyl-, arginyl- and leucyl aminopeptidase (cytoplasmic), dipeptidyl aminopeptidase II (lysosomal), and the chymotrypsin- and trypsin-like activities (proteosomal). No significant effects were observed in similarly treated immature rats. (2) Alcohol feeding in immature rats did not alter the activities of any of the enzymes assayed at 6 weeks. (3) In immature rats, activities of

  4. Acute Alcohol Effects on Repetition Priming and Word Recognition Memory with Equivalent Memory Cues

    ERIC Educational Resources Information Center

    Ray, Suchismita; Bates, Marsha E.

    2006-01-01

    Acute alcohol intoxication effects on memory were examined using a recollection-based word recognition memory task and a repetition priming task of memory for the same information without explicit reference to the study context. Memory cues were equivalent across tasks; encoding was manipulated by varying the frequency of occurrence (FOC) of words…

  5. Acute influence of alcohol, THC or central stimulants on violent suicide: A Swedish population study.

    PubMed

    Lundholm, Lena; Thiblin, Ingemar; Runeson, Bo; Leifman, Anders; Fugelstad, Anna

    2014-03-01

    Alcohol and substance abuse in general is a risk factor for suicide, but very little is known about the acute effect in relation to suicide method. Based on information from 18,894 medico-legal death investigations, including toxicological findings and manner of death, did the present study investigate whether acute influence of alcohol, tetrahydrocannabinol (THC), or central stimulants (amphetamine and cocaine) was related to the use of a violent suicide method, in comparison with the nonviolent method self-poisoning and alcohol-/illicit drug-negative suicide decedents. Multivariate analysis was conducted, and the results revealed that acute influence of THC was related to using the violent suicide method–– jumping from a height (RR 1.62; 95% CI 1.01–2.41). Alcohol intoxication was not related to any violent method, while the central stimulant-positive suicide decedent had a higher, albeit not significant, risk of several violent methods. The study contributes with elucidating suicide methods in relation to acute intoxication. PMID:24745078

  6. No Effects of Acute Alcohol Ingestion on Subjective Visual Horizontal Determination During Eccentric Rotation.

    PubMed

    Lindgren; Svenson; Olsson; Ödkvist; Ledin

    1998-01-01

    Evaluating the function of the vestibular part of the inner ear comprises more than the classic analysis of the lateral semicircular canal function. In healthy subjects, positional alcohol nystagmus may be seen after acute alcohol ingestion. Posturography has shown a deteriorated equilibrium after even moderate doses of alcohol, which speculatively could be an effect of otolith disturbance or a central integrative effect. We tested the possibility of an otolith effect by using linear acceleration in the lateral direction by means of eccentric rotation, stimulating mainly the outermost ear's otolith organ. The subject is seated eccentrically in a rotatory chair facing the direction of rotation. Thus, the otolith organs are stimulated in steady-state rotation. The subject experiences a lateral tilt and, in darkness, is instructed to put a short light bar in the position thought to be that of a water surface, which is identical to the perceived tilt. Twenty healthy subjects (10 men, 10 women) aged 20-29 years were tested before and approximately 1 hour after ingestion of alcohol, the amounts consumed corresponding to an approximate blood alcohol level of 0.05%, well above the maximum permissible level for driving in Sweden. No significant effects of alcohol were found. The otolith function probably is not affected by moderate alcohol intoxication levels. From this point of view, equilibrium deterioration due to alcohol ingestion in the erect position is caused by a central integrative deficit and not by an otolith effect.

  7. Effects of acute alcohol consumption on the perception of eye gaze direction.

    PubMed

    Penton-Voak, Ian S; Cooper, Robbie M; Roberts, Rachel E; Attwood, Angela S; Munafò, Marcus R

    2012-02-01

    Alcohol consumption is associated with increases in aggressive behaviour, but the mechanisms underlying this relationship are poorly understood. One mechanism by which alcohol consumption may influence behaviour is via alterations in the processing of social cues such as gaze. We investigated the effects of acute alcohol consumption on the perception of gaze, using a task in which participants determined whether a stimulus face was looking towards or away from them. Gaze direction varied across trials, allowing calculation of a threshold at which participants considered gaze to switch from direct to averted. Target faces varied in both sex and attractiveness. Thirty social drinkers attended three randomized experimental sessions. At each session, participants consumed 0.0, 0.2 or 0.4 g/kg alcohol, and completed the gaze perception task. A significant three-way interaction involving target sex, participant sex and alcohol dose indicated that alcohol increased the cone of gaze for females viewing male targets (i.e. females were biased towards making a direct gaze judgement), but decreased the cone of gaze for males viewing male targets. Our data indicate that alcohol consumption influences gaze perception, but that these effects vary across sex of both stimulus and rater. These effects may have important implications for alcohol-related violence.

  8. Effects of acute alcohol consumption on the perception of eye gaze direction.

    PubMed

    Penton-Voak, Ian S; Cooper, Robbie M; Roberts, Rachel E; Attwood, Angela S; Munafò, Marcus R

    2012-02-01

    Alcohol consumption is associated with increases in aggressive behaviour, but the mechanisms underlying this relationship are poorly understood. One mechanism by which alcohol consumption may influence behaviour is via alterations in the processing of social cues such as gaze. We investigated the effects of acute alcohol consumption on the perception of gaze, using a task in which participants determined whether a stimulus face was looking towards or away from them. Gaze direction varied across trials, allowing calculation of a threshold at which participants considered gaze to switch from direct to averted. Target faces varied in both sex and attractiveness. Thirty social drinkers attended three randomized experimental sessions. At each session, participants consumed 0.0, 0.2 or 0.4 g/kg alcohol, and completed the gaze perception task. A significant three-way interaction involving target sex, participant sex and alcohol dose indicated that alcohol increased the cone of gaze for females viewing male targets (i.e. females were biased towards making a direct gaze judgement), but decreased the cone of gaze for males viewing male targets. Our data indicate that alcohol consumption influences gaze perception, but that these effects vary across sex of both stimulus and rater. These effects may have important implications for alcohol-related violence. PMID:20937615

  9. Acute Ethanol Effects on Brain Activation in Low- and High-Level Responders to Alcohol

    PubMed Central

    Trim, Ryan S.; Simmons, Alan N.; Tolentino, Neil J.; Hall, Shana A.; Matthews, Scott C.; Robinson, Shannon K.; Smith, Tom L.; Padula, Claudia B.; Paulus, Martin P.; Tapert, Susan F.; Schuckit, Marc A.

    2013-01-01

    Background A low level of response (LR) to alcohol is an important endophenotype associated with an increased risk for alcoholism. However, little is known about how neural functioning may differ between individuals with low and high LRs to alcohol. This study examined whether LR group effects on neural activity varied as a function of acute alcohol consumption. Methods 30 matched high- and low-LR pairs (N=60 healthy young adults) were recruited from the University of California, San Diego and administered a structured diagnostic interview and laboratory alcohol challenge followed by two fMRI sessions under placebo and alcohol conditions, in randomized order. Task performance and BOLD response contrast to high relative to low working memory load in an event-related visual working memory (VWM) task was examined across 120 fMRI sessions. Results Both LR groups performed similarly on the VWM task across conditions. A significant LR group by condition interaction effect was observed in inferior frontal and cingulate regions, such that alcohol attenuated the LR group differences found under placebo (p<.05). The LR group by condition effect remained even after controlling for cerebral blood flow, age, and typical drinking quantity. Conclusions Alcohol had differential effects on brain activation for low and high LR individuals within frontal and cingulate regions. These findings represent an additional step in the search for physiological correlates of a low LR, and identify brain regions that may be associated with the low LR response. PMID:20477775

  10. The effect of nonrecurring alcohol administration on pain perception in humans: a systematic review

    PubMed Central

    Horn-Hofmann, Claudia; Büscher, Patricia; Lautenbacher, Stefan; Wolstein, Jörg

    2015-01-01

    Purpose Alcohol is believed to have pain-dampening effects and is often used as self-medication by persons with pain problems; however, experimental evidence confirming this effect is scarce. We conducted a systematic review of experimental studies on the effects of nonrecurring alcohol administration on pain perception in healthy human subjects and the underlying mechanisms. Method Three databases (PubMed, PsycINFO, and Web of Science) were searched for relevant studies using a predefined algorithm. In a next step, irrelevant articles were excluded by screening titles and abstracts. Finally, articles were checked regarding a set of methodological criteria; only publications meeting these criteria were selected for this review. A total of 14 experimental studies were identified. Results Overall, most of the studies were able to show a pain-dampening effect of alcohol. However, many of them had methodological shortcomings (eg, lack of placebo control, insufficient blinding, or very small sample sizes). In addition, comparability is limited due to considerable variations in alcohol administration and pain measurement. More importantly, potential mechanisms of action and moderating variables have scarcely been investigated. Conclusion Despite the frequent use of alcohol as self-medication by persons with pain problems, there are to date only a few experimental investigations of alcohol effects on pain perceptions. The results of these studies suggest that alcohol does in fact have pain-dampening effects. However, the mechanisms implicated in these effects are still unknown, and experimental research has been limited to pain-free subjects. Future research should provide more knowledge about alcohol effects on pain, especially in chronic pain patients. PMID:25960674

  11. Long-term alcohol self-administration and alcohol withdrawal differentially modulate microtubule-associated protein 2 (MAP2) gene expression in the rat brain.

    PubMed

    Putzke, J; De Beun, R; Schreiber, R; De Vry, J; Tölle, T R; Zieglgänsberger, W; Spanagel, R

    1998-11-20

    Chronic alcohol intoxication is known to produce neuronal degeneration in the central and peripheral nervous system of experimental animals and of humans. It is suggested that various components of the cytoskeleton undergo profound changes following chronic alcohol use and misuse. Here we studied the expression of the neuronal cytoskeletal microtubule-associated protein 2 (MAP2) following long-term alcohol consumption and subsequent alcohol withdrawal. Alcohol-preferring AA (Alko Alkohol) rats with a high voluntary alcohol consumption for a period of 16 months were compared with age-matched control rats without prior experience with alcohol. For comparison, in a second experiment, heterogeneous Wistar rats that also had voluntary access to alcohol for 8 months were examined following alcohol consumption and withdrawal. In situ hybridization and subsequent dot blot and Northern blot analysis for further quantification revealed that chronically alcoholized animals exhibit markedly decreased MAP2 mRNA levels in several parts of the extrapyramidal system (mainly in the caudate putamen, the substantia nigra pars compacta and the globus pallidus), the mesolimbic system, in several hypothalamic nuclei and in the nucleus inferior colliculus. Other areas such as the hippocampus, frontoparietal cortex and cerebellum were less affected by chronic alcohol intake, however, in these regions the MAP2 mRNA levels were increased during alcohol withdrawal. These results suggest that long-term alcohol self-administration affects central neurons involved in motor control via the influence on the integrity of the cytoskeleton and may thus induce motor dysfunction.

  12. 19 CFR 147.22 - Compliance with the internal revenue laws and Federal Alcohol Administration Act.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 19 Customs Duties 2 2010-04-01 2010-04-01 false Compliance with the internal revenue laws and Federal Alcohol Administration Act. 147.22 Section 147.22 Customs Duties U.S. CUSTOMS AND BORDER PROTECTION, DEPARTMENT OF HOMELAND SECURITY; DEPARTMENT OF THE TREASURY (CONTINUED) TRADE FAIRS Requirements of Other Laws § 147.22 Compliance with...

  13. Program Administrator's Handbook. Strategies for Preventing Alcohol and Other Drug Problems. The College Series.

    ERIC Educational Resources Information Center

    CSR, Inc., Washington, DC.

    This handbook is for administrators of programs in higher education settings which deal with alcohol and other drug (AOD) related problems. Chapter 1, "Defining the Problem, Issues, and Trends" examines the problem from various perspectives and presents the latest statistics on the extent of AOD use on campuses, specific problems affecting…

  14. Acute psychomotor effects of MDMA and ethanol (co-) administration over time in healthy volunteers.

    PubMed

    Dumont, G J H; Schoemaker, R C; Touw, D J; Sweep, F C G J; Buitelaar, J K; van Gerven, J M A; Verkes, R J

    2010-02-01

    In Western societies, a considerable percentage of young people use 3,4-methylenedioxymethamphetamine (MDMA or 'ecstasy'). The use of alcohol (ethanol) in combination with ecstasy is common. The aim of the present study was to assess the acute psychomotor and subjective effects of (co-) administration of MDMA and ethanol over time and in relation to the pharmacokinetics. We performed a four-way, double blind, randomized, crossover, placebo-controlled study in 16 healthy volunteers (nine men, seven women) between the ages of 18 and 29. MDMA (100 mg) was given orally while blood alcohol concentration was maintained at pseudo-steady state levels of approximately 0.6 per thousand for 3 h by a 10% intravenous ethanol clamp. MDMA significantly increased psychomotor speed but did not affect psychomotor accuracy and induced subjective arousal. Ethanol impaired both psychomotor speed and accuracy and induced sedation. Coadministration of ethanol and MDMA improved psychomotor speed but impaired psychomotor accuracy compared with placebo and reversed ethanol-induced sedation. Pharmacokinetics and pharmacodynamics showed maximal effects at 90-150 min after MDMA administration after which drug effects declined in spite of persisting MDMA plasma concentration, with the exception of ethanol-induced sedation, which manifested itself fully only after the infusion was stopped. In conclusion, results show that subjects were more aroused when intoxicated with both substances combined compared with placebo, but psychomotor accuracy was significantly impaired. These findings may have implications for general neuropsychological functioning as this may provide a sense of adequate performance that does not agree with a significant reduction in psychomotor accuracy.

  15. Acute withdrawal, protracted abstinence and negative affect in alcoholism: Are they linked?

    PubMed Central

    Heilig, M.; Egli, M.; Crabbe, J.C.; Becker, H.C.

    2012-01-01

    The role of withdrawal-related phenomena in development and maintenance of alcohol addiction remains under debate. A “self-medication” framework postulates that emotional changes are induced by a history of alcohol use, persist into abstinence, and are a major factor in maintaining alcoholism. This view initially focused on negative emotional states during early withdrawal: these are pronounced, occur in the vast majority of alcohol dependent patients, and are characterized by depressed mood and elevated anxiety. This concept lost popularity with the realization that, in most patients, these symptoms abate over 3 – 6 weeks of abstinence, while relapse risk persists long beyond this period. More recently, animal data have established that a prolonged history of alcohol dependence induces more subtle neuroadaptations. These confer altered emotional processing that persists long into protracted abstinence. The resulting behavioral phenotype is characterized by excessive voluntary alcohol intake and increased behavioral sensitivity to stress. Emerging human data support the clinical relevance of negative emotionality for protracted abstinence and relapse. These developments prompt a series of research questions: 1) Are processes observed during acute withdrawal, while transient in nature, mechanistically related to those that remain during protracted abstinence? 2) Is susceptibility to negative emotionality in acute withdrawal in part due to heritable factors, similar to what animal models have indicated for susceptibility to physical aspects of withdrawal? 3) To what extent is susceptibility to negative affect that persists into protracted abstinence heritable? PMID:20148778

  16. Changes in electrocortical arousal following acute trimethylbenzene administration in rats.

    PubMed

    Tomas, T; Lutz, P; Wiaderna, D

    2000-01-01

    The purpose of this investigation was to compare the neurotoxic potential of trimethylbenzene (TMB) isomers (the solvents) with that of benzene derivatives with a smaller number of methyl groups (toluene). The experiments were performed on WAG/Rij rats with EEG recording electrodes implanted in the fronto-parietal cortex. The solvents, toluene or TMB isomers: 1,3,5-TMB (mesitylene), 1,2,3-TMB (hemimellitene) or 1,2,4-TMB (pseudocumene), were diluted with olive oil and administered intragastrically via gavage at an acute dose of 0.002, 0.008, or 0.032 mol/kg. The electrocortical activity was recorded for 20 min before, and for 60 min after the solvent administration. The electrocorticograms were analysed with respect to the number and duration of the high-voltage spindles (HVS), a form of activity sensitive to the arousal level. In case of each solvent the observed effect--inhibition of the HVS activity--was dose-related. However, the effect produced by TMB isomers was in each case less pronounced than that of toluene. Among TMBs, pseudocumene displayed the least significant effect, and the efficacy of two other TMB isomers was similar. PMID:10846847

  17. Fluoxetine, Desipramine, and the Dual Antidepressant Milnacipran Reduce Alcohol Self-Administration and/or Relapse in Dependent Rats

    PubMed Central

    O'Brien, Emmanuelle Simon; Legastelois, Rémi; Houchi, Hakim; Vilpoux, Catherine; Alaux-Cantin, Stéphanie; Pierrefiche, Olivier; André, Etienne; Naassila, Mickaël

    2011-01-01

    A few clinical studies have shown that dual antidepressants (serotonergic (5-HT) and noradrenergic (NE) transporter inhibitors, SNRIs) may be effective in alcoholism treatment. We studied the effect of the dual antidepressant milnacipran on ethanol operant self-administration in acutely withdrawn ethanol-dependent and in -non-dependent Wistar rats, and used fluoxetine and desipramine to dissect both 5-HT and NE components, respectively, in the effect of milnacipran. Milnacipran was also tested for relapse after protracted abstinence and on ethanol-induced (1.0 g/kg) conditioned place preference in control rats and ethanol-induced locomotor sensitization in DBA/2J female mice. Milnacipran dose dependently (5–40 mg/kg) attenuated the increased ethanol self-administration observed during early withdrawal and was more potent in preventing reinstatement in dependent rats after protracted abstinence as compared with non-dependent rats. Desipramine and fluoxetine (10 mg/kg) blocked ethanol self-administration during early withdrawal, and recovery was delayed in dependent animals, indicating a potent effect. Ethanol self-administration was also reduced 1 day after treatment with desipramine and fluoxetine but not with milnacipran. Finally, milnacipran prevented ethanol-induced place preference in ethanol-naive rats and reduced the magnitude of ethanol-induced sensitization associated with a delayed induction in mice. Desipramine (20 mg/kg) countered sensitization development and reduced its expression at 1 week after treatment; fluoxetine (10 mg/kg) reduced sensitization expression. Thus, 5-HT and NE transmissions during sensitization expression may mediate the effect of milnacipran on sensitization induction. These results support that SNRIs may have a potential use in alcoholism treatment. PMID:21430652

  18. Management of Acute Alcohol Withdrawal Syndrome in Critically Ill Patients.

    PubMed

    Dixit, Deepali; Endicott, Jeffrey; Burry, Lisa; Ramos, Liz; Yeung, Siu Yan Amy; Devabhakthuni, Sandeep; Chan, Claire; Tobia, Anthony; Bulloch, Marilyn N

    2016-07-01

    Approximately 16-31% of patients in the intensive care unit (ICU) have an alcohol use disorder and are at risk for developing alcohol withdrawal syndrome (AWS). Patients admitted to the ICU with AWS have an increased hospital and ICU length of stay, longer duration of mechanical ventilation, higher costs, and increased mortality compared with those admitted without an alcohol-related disorder. Despite the high prevalence of AWS among ICU patients, no guidelines for the recognition or management of AWS or delirium tremens in the critically ill currently exist, leading to tremendous variability in clinical practice. Goals of care should include immediate management of dehydration, nutritional deficits, and electrolyte derangements; relief of withdrawal symptoms; prevention of progression of symptoms; and treatment of comorbid illnesses. Symptom-triggered treatment of AWS with γ-aminobutyric acid receptor agonists is the cornerstone of therapy. Benzodiazepines (BZDs) are most studied and are often the preferred first-line agents due to their efficacy and safety profile. However, controversy still exists as to who should receive treatment, how to administer BZDs, and which BZD to use. Although most patients with AWS respond to usual doses of BZDs, ICU clinicians are challenged with managing BZD-resistant patients. Recent literature has shown that using an early multimodal approach to managing BZD-resistant patients appears beneficial in rapidly improving symptoms. This review highlights the results of recent promising studies published between 2011 and 2015 evaluating adjunctive therapies for BZD-resistant alcohol withdrawal such as antiepileptics, baclofen, dexmedetomidine, ethanol, ketamine, phenobarbital, propofol, and ketamine. We provide guidance on the places in therapy for select agents for management of critically ill patients in the presence of AWS. PMID:27196747

  19. Regional Variation in Phasic Dopamine Release during Alcohol and Sucrose Self-Administration in Rats

    PubMed Central

    2015-01-01

    While dopamine input to the dorsal striatum is well-known to be critical for action selection, including alcohol-motivated behaviors, it is unknown whether changes in phasic dopamine accompany these behaviors. Long-term alcohol abuse is believed to promote alterations in the neurocircuitry of reward learning in both ventral and dorsal striatum, potentially through increasing dopamine release. Using fast-scan cyclic voltammetry, we measured phasic dopamine release in the dorsal and ventral striatum during alcoholic and nonalcoholic reward-seeking behavior and reward-related cues in rats trained on a variable-interval schedule of reinforcement. We observed robust phasic dopamine release in the dorsolateral striatum after reinforced lever presses and inconsistent dopamine release in the dorsomedial striatum. Contrary to our expectations, alcohol did not enhance dopamine release in rats drinking alcoholic rewards. Cue-induced dopamine release was also observed in the nucleus accumbens core of rats drinking the reward solutions. These data demonstrate that alcoholic and nonalcoholic reward self-administration on a variable-interval schedule of reinforcement in rats is accompanied by phasic dopamine release time-locked to reinforcement in the dorsolateral striatum and the nucleus accumbens, but not the dorsomedial striatum. PMID:25493956

  20. Acute effect of alcohol intake on sine-wave Cartesian and polar contrast sensitivity functions.

    PubMed

    Cavalcanti-Galdino, M K; Silva, J A da; Mendes, L C; Santos, N A da; Simas, M L B

    2014-04-01

    The aim of this study was to assess contrast sensitivity for angular frequency stimuli as well as for sine-wave gratings in adults under the effect of acute ingestion of alcohol. We measured the contrast sensitivity function (CSF) for gratings of 0.25, 1.25, 2.5, 4, 10, and 20 cycles per degree of visual angle (cpd) as well as for angular frequency stimuli of 1, 2, 4, 24, 48, and 96 cycles/360°. Twenty adults free of ocular diseases, with normal or corrected-to-normal visual acuity, and no history of alcoholism were enrolled in two experimental groups: 1) no alcohol intake (control group) and 2) alcohol ingestion (experimental group). The average concentration of alcohol in the experimental group was set to about 0.08%. We used a paradigm involving a forced-choice method. Maximum sensitivity to contrast for sine-wave gratings in the two groups occurred at 4 cpd sine-wave gratings and at 24 and 48 cycles/360° for angular frequency stimuli. Significant changes in contrast sensitivity were observed after alcohol intake compared with the control condition at spatial frequency of 4 cpd and 1, 24, and 48 cycles/360° for angular frequency stimuli. Alcohol intake seems to affect the processing of sine-wave gratings at maximum sensitivity and at the low and high frequency ends for angular frequency stimuli, both under photopic luminance conditions.

  1. Acute effects of alcohol on memory: impact of emotional context and serial position.

    PubMed

    Brown, Jennie; Brignell, Catherine M; Dhiman, Sharinjeet K; Curran, H Valerie; Kamboj, Sunjeev K

    2010-03-01

    Although the amnestic effects of alcohol in humans are well known, its effects on emotional memory are unclear. In this study, using a randomized double-blind placebo-controlled design, we examine narrative emotional episodic memory in healthy human female volunteers (n=32) who received either a single dose of alcohol (0.6g/kg), or a placebo and then viewed neutral story elements presented in either a neutral or emotional context. Memory was tested for gist and detail of the neutral elements 3days later in a surprise recognition test. Since alcohol modulates GABAergic neurotransmission and may exert its effects on emotion through the limbic system, we predicted that acute alcohol treatment would reduce the expected emotional memory-advantage for gist, leaving detail memory relatively unaffected. Furthermore, given previous findings showing that 'primacy' memory is enhanced by physiological arousal, we predicted that reduced arousal produced by alcohol would have the opposite effect and impair primacy memory relative to the middle or 'recency' sections of the narrative. Emotional arousal was expected to oppose this effect, so impaired primacy memory following alcohol was only expected in the neutral version of the narrative. Although there was a main effect of story phase (though not of story version), contrary to expectations, alcohol impaired primacy memory for emotionally encoded neutral material. The results suggest that under certain circumstances emotional context or physiological arousal make memories labile and susceptible to disruption through pharmacological manipulation during encoding.

  2. Acute effect of alcohol intake on sine-wave Cartesian and polar contrast sensitivity functions

    PubMed Central

    Cavalcanti-Galdino, M.K.; da Silva, J.A.; Mendes, L.C.; dos Santos, N.A.; Simas, M.L.B.

    2014-01-01

    The aim of this study was to assess contrast sensitivity for angular frequency stimuli as well as for sine-wave gratings in adults under the effect of acute ingestion of alcohol. We measured the contrast sensitivity function (CSF) for gratings of 0.25, 1.25, 2.5, 4, 10, and 20 cycles per degree of visual angle (cpd) as well as for angular frequency stimuli of 1, 2, 4, 24, 48, and 96 cycles/360°. Twenty adults free of ocular diseases, with normal or corrected-to-normal visual acuity, and no history of alcoholism were enrolled in two experimental groups: 1) no alcohol intake (control group) and 2) alcohol ingestion (experimental group). The average concentration of alcohol in the experimental group was set to about 0.08%. We used a paradigm involving a forced-choice method. Maximum sensitivity to contrast for sine-wave gratings in the two groups occurred at 4 cpd sine-wave gratings and at 24 and 48 cycles/360° for angular frequency stimuli. Significant changes in contrast sensitivity were observed after alcohol intake compared with the control condition at spatial frequency of 4 cpd and 1, 24, and 48 cycles/360° for angular frequency stimuli. Alcohol intake seems to affect the processing of sine-wave gratings at maximum sensitivity and at the low and high frequency ends for angular frequency stimuli, both under photopic luminance conditions. PMID:24676473

  3. Differences in extinction of cue-maintained conditioned responses associated with self-administration: alcohol versus a non-alcoholic reinforcer

    PubMed Central

    Holtyn, August F.; Kaminski, Barbara J.; Wand, Gary S.; Weerts, Elise M.

    2014-01-01

    Background Stimuli paired with alcohol may evoke conditioned responses that influence consumption and relapse. Understanding extinction of conditioned responses for both alcohol and non-alcoholic reinforcers, and their relation to subsequent consumption, may be useful in identifying methods to maintain abstinence. Methods Nine baboons self-administered alcohol (n=4) or a non-alcoholic reinforcer (orange-flavored Tang®, n=5) under a three-component chained schedule of reinforcement (CSR). Each component was associated with distinct stimuli and response requirements, which modeled periods of anticipation (Component 1), seeking (Component 2), and consumption (Component 3). No behavioral contingencies were in effect during Component 1. Responses in Component 2, required to gain access to Component 3, provided indices of seeking behavior. Alcohol or Tang was available only in Component 3. Initial conditions parametrically manipulated the concentration of alcohol (2–6% w/v) or Tang (25–100%) that was available for self-administration. The breaking point (BP) of alcohol- and Tang-seeking responses at each of the concentrations was determined by adding a progressive ratio schedule to Component 2. Extinction of responding under stimulus conditions identical to those during baseline, but with no access to alcohol or Tang, was examined using across- and within-session extinction procedures. Results The BP for 2% w/v alcohol was lower than that for 4% and 6%, which were closely similar. For Tang, BPs increased as the concentration increased. When concentrations of alcohol and Tang were adjusted to produce comparable BPs, self-administration of Tang was higher when compared to alcohol; however, alcohol-related cues maintained higher BPs than Tang-related cues when only water was available for self-administration. Alcohol seeking and self-administration responses were more resistant to extinction than those for Tang. Conclusions Stimuli paired with alcohol or non-alcoholic

  4. Influence of the acute alcoholism on the phagocytic function of the mononuclear phagocytic system

    PubMed Central

    Sabino, KR; Petroianu, A; Alberti, LR

    2011-01-01

    Rationale:Alcoholics are more likely to have infections, mainly in the respiratory system. Alcohol seems to inhibit the immune system. Despite the extensive literature related to alcoholism, data related to the immune system are still not conclusive. Objective: The purpose of this study was to verify the influence of acute alcohol intake on colloid distribution in the organs of the mononuclear phagocyte system. Methods and Results: Thirteen male Swiss mice were divided into two groups: Group 1 (n = 5) – control, and Group 2 (n = 8) – animals that received 0.5 ml ethanol 50%, 30 minutes before the experiment. Colloidal sulphur labeled with ⁸⁸mTc was used to evaluate colloid distribution in the liver, spleen and lungs. Colloid clearance was assessed as well. A gamma camera was used to measure the radioactivity of these organs and of a blood clot. No difference was found in the presence of colloid in the organs of both groups. The liver showed the highest phagocytic intake, followed by the spleen and lungs (p = 0.021 for Group 1 and p = 0.003 for Group 2). A minimum amount of radiation remained in the blood of both groups. Discussion: According to the experiential conditions of this work, acute ingestion of alcohol did not interfere with the phagocytic function of the mononuclear phagocyte system in mice. PMID:22514578

  5. Hyperhydrating effect of acute administration of angiotensin II in rats.

    PubMed

    Fregly, M J; Wilson, K M; Rowland, N E; Cade, J R

    1992-01-01

    Water intake, urine output, and fluid exchange (water intake less urine output) were measured in rats at hourly intervals for 7 hours and at 24 hours following acute administration of angiotensin II (AII, 200 micrograms/kg SC). AII induced the expected abrupt increase in water intake and a more gradual increase in urine output. The change in fluid exchange (fluid exchange of the AII-treated group less fluid exchange of controls) became positive within the first hour after treatment with AII, decreased linearly with time, and reached 0 at approximately 10 to 12 hours after treatment with AII. When AII was administered intracerebroventricularly (50 ng), similar results were observed. In this case, the change in fluid exchange (delta F) reached 0 in about 6 hours. Imposition of a water load (1% of body weight, IP) on the group receiving AII SC failed to affect the time required for delta F to reach 0 if the water load was disregarded. However, inclusion of the load as a part of intake extended the time the rats remained in positive fluid balance beyond that of the nonloaded, AII-treated control group. In the case of the larger water load (3% of body weight, IP), delta F returned to that of controls in about 4 to 5 hours if the water load was disregarded. However, inclusion of the load as part of intake extended the period of hyperhydration well beyond that of both the nonloaded, AII-treated group and the AII-treated group given the 1% load.(ABSTRACT TRUNCATED AT 250 WORDS)

  6. Behavioral economic analysis of stress effects on acute motivation for alcohol.

    PubMed

    Owens, Max M; Ray, Lara A; MacKillop, James

    2015-01-01

    Due to issues of definition and measurement, the heavy emphasis on subjective craving in the measurement of acute motivation for alcohol and other drugs remains controversial. Behavioral economic approaches have increasingly been applied to better understand acute drug motivation, particularly using demand curve modeling via purchase tasks to characterize the perceived reinforcing value of the drug. This approach has focused on using putatively more objective indices of motivation, such as units of consumption, monetary expenditure, and price sensitivity. To extend this line of research, the current study used an alcohol purchase task to determine if, compared to a neutral induction, a personalized stress induction would increase alcohol demand in a sample of heavy drinkers. The stress induction significantly increased multiple measures of the reinforcing value of alcohol to the individual, including consumption at zero price (intensity), the maximum total amount of money spent on alcohol (Omax), the first price where consumption was reduced to zero (breakpoint), and the general responsiveness of consumption to increases in price (elasticity). These measures correlated only modestly with craving and mood. Self-reported income was largely unrelated to demand but moderated the influence of stress on Omax. Moderation based on CRH-BP genotype (rs10055255) was present for Omax, with T allele homozygotes exhibiting more pronounced increases in response to stress. These results provide further support for a behavioral economic approach to measuring acute drug motivation. The findings also highlight the potential relevance of income and genetic factors in understanding state effects on the perceived reinforcing value of alcohol. PMID:25413719

  7. Multiday administration of ivermectin is effective in reducing alcohol intake in mice at doses shown to be safe in humans.

    PubMed

    Yardley, Megan M; Neely, Michael; Huynh, Nhat; Asatryan, Liana; Louie, Stan G; Alkana, Ronald L; Davies, Daryl L

    2014-09-10

    Ivermectin (IVM), an FDA approved anthelmintic agent, can significantly reduce ethanol intake in mice following acute administration. The current study evaluates the sustainability and safety of multiday IVM administration in reducing 10% v/v ethyl alcohol (10E) intake in mice at a dose shown to be safe in humans. We tested the effect of 10-day administration of IVM (3.0 mg/kg/day; intraperitoneally) on reducing 10E intake in C57BL/6J mice using a 24-h, two-bottle choice paradigm. On the 10th day of IVM administration, mice were sacrificed at 0, 0.5, 2, 8, 32, 48, and 72 h after injection. Brain tissue and plasma samples were collected and analyzed using liquid chromatography with tandem mass spectrometry (LC-MS/MS). Analysis of variance (ANOVA) was used to assess the effect of 10-day IVM administration on 10E intake, 10E preference, water intake, and total fluid intake with Dunnett's multiple comparison post-hoc test. Individual Student's t-tests were also used to further quantify changes in these dependent variables. IVM significantly decreased 10E intake over a 9-day period (P<0.01). Pre-IVM 10E intake was 9.1±3.2 g/kg/24 h. Following the 9th day of IVM injections, intake dropped by almost 30% (P<0.05). IVM had no effect on total water intake or mouse weight throughout the study; however, there was a significant decrease in both preference for 10E (P<0.01) and total fluid intake (P<0.05). Multiday administration of IVM significantly reduces 10E intake and preference in animals without causing any apparent adverse effects at a dose shown to be safe in humans.

  8. Multiday administration of ivermectin is effective in reducing alcohol intake in mice at doses shown to be safe in humans.

    PubMed

    Yardley, Megan M; Neely, Michael; Huynh, Nhat; Asatryan, Liana; Louie, Stan G; Alkana, Ronald L; Davies, Daryl L

    2014-09-10

    Ivermectin (IVM), an FDA approved anthelmintic agent, can significantly reduce ethanol intake in mice following acute administration. The current study evaluates the sustainability and safety of multiday IVM administration in reducing 10% v/v ethyl alcohol (10E) intake in mice at a dose shown to be safe in humans. We tested the effect of 10-day administration of IVM (3.0 mg/kg/day; intraperitoneally) on reducing 10E intake in C57BL/6J mice using a 24-h, two-bottle choice paradigm. On the 10th day of IVM administration, mice were sacrificed at 0, 0.5, 2, 8, 32, 48, and 72 h after injection. Brain tissue and plasma samples were collected and analyzed using liquid chromatography with tandem mass spectrometry (LC-MS/MS). Analysis of variance (ANOVA) was used to assess the effect of 10-day IVM administration on 10E intake, 10E preference, water intake, and total fluid intake with Dunnett's multiple comparison post-hoc test. Individual Student's t-tests were also used to further quantify changes in these dependent variables. IVM significantly decreased 10E intake over a 9-day period (P<0.01). Pre-IVM 10E intake was 9.1±3.2 g/kg/24 h. Following the 9th day of IVM injections, intake dropped by almost 30% (P<0.05). IVM had no effect on total water intake or mouse weight throughout the study; however, there was a significant decrease in both preference for 10E (P<0.01) and total fluid intake (P<0.05). Multiday administration of IVM significantly reduces 10E intake and preference in animals without causing any apparent adverse effects at a dose shown to be safe in humans. PMID:25004078

  9. [Comparative characteristics of glucose metabolism in the liver of rats under acute alcohol and morphine intoxication].

    PubMed

    Lelevich, S V

    2011-01-01

    The comparative analysis effect of acute alcohol and morphine intoxications on rats on hepatic glycolysis and pentose phosphate pathway was done. The dose-dependent inhibitory effect of ethanol on activity of limiting enzymes of these metabolic ways, as well as anaerobic reorientation of glucose metabolism was recognised with the increase of the dose of the intake alcohol. Morfine (10 mg/kg) activated enymes of glycolysis and pentose phosphate pathway, but in contrast to ethanol it did not influence these parameters at the dose 20 or 40 mg/kg.

  10. Alcohol

    MedlinePlus

    ... How Can I Help a Friend Who Cuts? Alcohol KidsHealth > For Teens > Alcohol Print A A A ... you can make an educated choice. What Is Alcohol? Alcohol is created when grains, fruits, or vegetables ...

  11. Geniposide protects against acute alcohol-induced liver injury in mice via up-regulating the expression of the main antioxidant enzymes.

    PubMed

    Wang, Junming; Zhang, Yueyue; Liu, Ruixin; Li, Xiaobing; Cui, Ying; Qu, Lingbo

    2015-04-01

    Geniposide (GP) is one of main compounds in Gardenia jasminoides Ellis, with both medicinal and nutritional value. This study was designed to determine, for the first time, how GP from G. jasminoides protects against acute alcohol-induced liver injury, and the underlying mechanisms. Mice were orally administered alcohol (6.0 g/kg body mass) 2 h after intragastric administration of GP and bifendate, every day for 7 continuous days. Six hours after the alcohol was administered, levels of serum alanine/aspartate transaminase (ALT/AST), hepatic lipid peroxidation (LPO), glutathione (GSH), glutathione-S-transferase (GST), glutathione peroxidase (GPx), copper- and zinc-containing superoxide dismutase (CuZn-SOD), and catalase (CAT), and mRNA expression of CuZn-SOD and CAT were assayed. The results demonstrated that GP (20.0, 40.0, or 80 mg/kg) significantly reversed the excessive, alcohol-induced elevation in both serum ALT/AST and hepatic LPO levels. Moreover, hepatic GSH, GST, GPx, CuZn-SOD, and CAT levels were all decreased in the alcohol-treated mice, whereas treatment with GP reversed these decreases. Further analysis indicated that hepatic mRNA expression of CuZn-SOD and CAT in the alcohol-treated mice was significantly down-regulated, whereas GP up-regulated such decreases. Taken together, this study shows that GP protects against acute alcohol-induced liver injury via up-regulating the expression of the main antioxidant enzymes, and thus ameliorates alcohol-induced oxidative stress injury in the liver. PMID:25730420

  12. Geniposide protects against acute alcohol-induced liver injury in mice via up-regulating the expression of the main antioxidant enzymes.

    PubMed

    Wang, Junming; Zhang, Yueyue; Liu, Ruixin; Li, Xiaobing; Cui, Ying; Qu, Lingbo

    2015-04-01

    Geniposide (GP) is one of main compounds in Gardenia jasminoides Ellis, with both medicinal and nutritional value. This study was designed to determine, for the first time, how GP from G. jasminoides protects against acute alcohol-induced liver injury, and the underlying mechanisms. Mice were orally administered alcohol (6.0 g/kg body mass) 2 h after intragastric administration of GP and bifendate, every day for 7 continuous days. Six hours after the alcohol was administered, levels of serum alanine/aspartate transaminase (ALT/AST), hepatic lipid peroxidation (LPO), glutathione (GSH), glutathione-S-transferase (GST), glutathione peroxidase (GPx), copper- and zinc-containing superoxide dismutase (CuZn-SOD), and catalase (CAT), and mRNA expression of CuZn-SOD and CAT were assayed. The results demonstrated that GP (20.0, 40.0, or 80 mg/kg) significantly reversed the excessive, alcohol-induced elevation in both serum ALT/AST and hepatic LPO levels. Moreover, hepatic GSH, GST, GPx, CuZn-SOD, and CAT levels were all decreased in the alcohol-treated mice, whereas treatment with GP reversed these decreases. Further analysis indicated that hepatic mRNA expression of CuZn-SOD and CAT in the alcohol-treated mice was significantly down-regulated, whereas GP up-regulated such decreases. Taken together, this study shows that GP protects against acute alcohol-induced liver injury via up-regulating the expression of the main antioxidant enzymes, and thus ameliorates alcohol-induced oxidative stress injury in the liver.

  13. Cigarettes and alcohol: The influence of nicotine on operant alcohol self-administration and the mesolimbic dopamine system

    PubMed Central

    Ostroumov, Alexey; Thomas, Alyse M.; Dani, John A.; Doyon, William M.

    2016-01-01

    Studies in human populations consistently demonstrate an interaction between nicotine and ethanol use, each drug influencing the use of the other. Here we present data and review evidence from animal studies that nicotine influences operant self-administration of ethanol. The operant reinforcement paradigm has proven to be a behaviorally relevant and quantitative model for studying ethanol-seeking behavior. Exposure to nicotine can modify the reinforcing properties of ethanol during different phases of ethanol self-administration, including acquisition, maintenance, and reinstatement. Our data suggest that non-daily intermittent nicotine exposure can trigger a long-lasting increase in ethanol self-administration. The biological basis for interactions between nicotine and ethanol is not well understood but may involve the stress hormone systems and adaptations in the mesolimbic dopamine system. Future studies that combine operant self-administration with techniques for monitoring or manipulating in vivo neurophysiology may provide new insights into the neuronal mechanisms that link nicotine and alcohol use. PMID:26253689

  14. A Heart too Drunk to Drive; AV Block following Acute Alcohol Intoxication.

    PubMed

    van Stigt, Arthur H; Overduin, Ruben J; Staats, Liza C; Loen, Vera; van der Heyden, Marcel A G

    2016-02-29

    Acute excessive alcohol consumption is associated with heart rhythm disorders like atrial fibrillation but also premature ventricular contractions, collectively known as the "holiday heart syndrome". More rarely but clinically significant are reports of atrioventricular (AV) conduction disturbances in binge drinkers with no underlying heart disease or chronic alcohol consumption. To obtain better insights into common denominators and the potential underlying mechanisms we collected and compared individual case reports of AV block following acute alcohol intoxication in otherwise healthy people. By screening PubMed, Google Scholar, Scopus and JSTOR, fifteen cases were found of which eight were sufficiently documented for full analysis. Blood alcohol levels ranged from 90 to 958 mg/dl (19 to 205 mM). Second and third degree AV block was observed most (6/8) albeit that in two of these patients a vagal stimulus led to deterioration from first into higher order AV block. In all cases, patients reverted to normal sinus rhythm upon becoming sober again. Mildly lowered body temperature (35.9 ± 0.5°C) was observed but can be excluded as a major cause of conduction blockade. We hypothesize that ethanol induced partial inhibition of calcium and potentially also sodium currents in conductive tissue structures may be one of the mechanisms of conduction slowing and block that may become exaggerated upon increased vagal tone. An impairment of gap junction function cannot be excluded as a contributing factor. In conclusion, cases of documented alcohol induced AV block are very rare but events can occur at relatively low serum alcohol levels which should prompt to awareness of this phenomenon in alcohol intoxicated patients. PMID:26875557

  15. A Heart too Drunk to Drive; AV Block following Acute Alcohol Intoxication.

    PubMed

    van Stigt, Arthur H; Overduin, Ruben J; Staats, Liza C; Loen, Vera; van der Heyden, Marcel A G

    2016-02-29

    Acute excessive alcohol consumption is associated with heart rhythm disorders like atrial fibrillation but also premature ventricular contractions, collectively known as the "holiday heart syndrome". More rarely but clinically significant are reports of atrioventricular (AV) conduction disturbances in binge drinkers with no underlying heart disease or chronic alcohol consumption. To obtain better insights into common denominators and the potential underlying mechanisms we collected and compared individual case reports of AV block following acute alcohol intoxication in otherwise healthy people. By screening PubMed, Google Scholar, Scopus and JSTOR, fifteen cases were found of which eight were sufficiently documented for full analysis. Blood alcohol levels ranged from 90 to 958 mg/dl (19 to 205 mM). Second and third degree AV block was observed most (6/8) albeit that in two of these patients a vagal stimulus led to deterioration from first into higher order AV block. In all cases, patients reverted to normal sinus rhythm upon becoming sober again. Mildly lowered body temperature (35.9 ± 0.5°C) was observed but can be excluded as a major cause of conduction blockade. We hypothesize that ethanol induced partial inhibition of calcium and potentially also sodium currents in conductive tissue structures may be one of the mechanisms of conduction slowing and block that may become exaggerated upon increased vagal tone. An impairment of gap junction function cannot be excluded as a contributing factor. In conclusion, cases of documented alcohol induced AV block are very rare but events can occur at relatively low serum alcohol levels which should prompt to awareness of this phenomenon in alcohol intoxicated patients.

  16. Effects of acute alcohol withdrawal on nest building in mice selectively bred for alcohol withdrawal severity.

    PubMed

    Greenberg, Gian D; Phillips, Tamara J; Crabbe, John C

    2016-10-15

    Nest building has been used to assess thermoregulatory behavior and positive motivational states in mice. There are known genetic influences on ethanol withdrawal severity as well as individual/thermoregulatory nest building. Withdrawal Seizure-Prone (WSP-1, WSP-2) and Withdrawal Seizure-Resistant (WSR-1, WSR-2) mice were selectively bred for high vs low handling-induced convulsion (HIC) severity, respectively, during withdrawal from chronic ethanol vapor inhalation. They also differ in HIC severity during withdrawal from an acute, 4g/kg ethanol injection. In our initial study, withdrawal from an acute dose of ethanol dose-dependently impaired nest building over the initial 24h of withdrawal in genetically segregating Withdrawal Seizure Control (WSC) mice. In two further studies, acute ethanol withdrawal suppressed nest building for up to two days in WSP-1 females. Deficits in nest building from ethanol were limited to the initial 10h of withdrawal in WSR-1 females and to the initial 24h of withdrawal in WSP-1 and WSR-1 males. Effects of ethanol on nest building for up to two days were found in WSP-2 and WSR-2 mice of both sexes. Nest building deficits in female mice from the first replicate could not be explained by a general decrease in locomotor behavior. These results suggest that nest building is a novel behavioral phenotype for indexing the severity of acute ethanol withdrawal, and that genes contributing to this trait differ from those affecting acute withdrawal HIC severity. PMID:27503811

  17. Evaluation of the antidepressant-like effects of acute and sub-acute administration of crocin and crocetin in mice

    PubMed Central

    Amin, Bahareh; Nakhsaz, Alireza; Hosseinzadeh, Hossein

    2015-01-01

    Objective: The present study was designed to investigate the putative antidepressant effects of crocin and crocetin, two major active ingredients of Crocus sativus L. (saffron) using mice in two different regimens of acute and sub-acute administration. Material and Methods: In acute treatment, antidepressant-like activities of crocin and crocetin (10, 20 and 40 mg/kg, i.p.) were evaluated using forced swim test (FST). In sub-acute study (21 times with 24-h intervals), antidepressant-like effects of oral administration of drugs were examined using FST and tail suspension test (TST). Locomotor activity and motor coordination were studied using open field and rotarod tests, respectively. Results: Acute treatment with crocin (40 mg/kg) and crocetin (20 and 40 mg/kg) produced antidepressant-like effect in FST without affecting the baseline locomotion in mice. Sub-acute oral administration of crocin significantly decreased immobility time only at the highest dose (100 mg/kg). Crocetin (12.5, 25 and 50 mg/kg) was able to decrease immobility time in FST and TST. Locomotor activity and coordination of mice were not affected by crocin or crocetin. Conclusion: Since higher doses of crocin was required to show antidepressant effects, more efficacy of crocetin may be concluded. This observation provides further support for metabolism of crocin to crocetin following oral administration. PMID:26468466

  18. Chronic alcohol self-administration in monkeys shows long-term quantity/frequency categorical stability

    PubMed Central

    Baker, Erich J.; Farro, Jonathan; Gonzales, Steven; Helms, Christa; Grant, Kathleen A.

    2014-01-01

    Background The current criteria for alcohol use disorders (AUD) do not include consumption (quantity/frequency) measures of alcohol intake, in part due to the difficulty of these measures in humans. Animal models of ethanol self-administration have been fundamental in advancing our understanding of the neurobiological basis of (AUD) and can address quantity/frequency measures with accurate measurements over prolonged periods of time. The non-human primate (NHP) model of voluntary oral alcohol self-administration has documented both binge drinking and drinking to dependence and can be used to test the stability of consumption measures over time. Methods and Results Here, an extensive set of alcohol intakes (g/kg/day) was analyzed from a large multi-cohort population of Rhesus (Macaca mulatta) monkeys (n=31). Daily ethanol intake was uniformly distributed over chronic (12 months) access for all animals. Underlying this distribution of intakes were subpopulations of monkeys that exhibited distinctive clustering of drinking patterns, allowing us to categorically define very heavy drinking (VHD), heavy drinking (HD), binge drinking (BD), and low drinking (LD). These categories were stable across the 12-month assessed by the protocol, but exhibited fluctuations when examined at shorter intervals. Conclusions The establishment of persistent drinking categories based on quantity/frequency suggests that consumption variables can be used to track long-term changes in behavioral, molecular or physiochemical mechanisms related to our understanding of diagnosis, prevention, intervention and treatment efficacies. PMID:25421519

  19. Long-term administration of tianeptine in depressed patients after alcohol withdrawal.

    PubMed

    Malka, R; Lôo, H; Ganry, H; Souche, A; Marey, C; Kamoun, A

    1992-02-01

    Alcohol interferes with the central metabolism of the catecholamines and especially with indolamines (5-HT). Thus, the use of an antidepressant such as tianeptine, whose main neurochemical effect is to increase the reuptake of 5-HT, seems to be particularly indicated for the continued treatment of depressed patients after alcohol withdrawal. This study evaluated the therapeutic efficacy and acceptability during long-term administration of tianeptine in depressed patients (major depressive episode or dysthymic disorder) in a multicentre trial, after withdrawal from alcohol abuse or dependence. The results relate to 130 depressed patients, who abstained from alcohol and received treatment for a year. Only one patient dropped-out because of side-effects, and medication was interrupted in 5% of subjects because of alcoholic relapses. Prescribed in the long term, tianeptine did not produce orthostatic hypotension, changes in bodyweight, or alterations in the ECG. All changes found in haematological and biochemical investigations suggested an improvement in patients' physical state. This, and other studies, indicate that tianeptine appears to have the potential to be a safe antidepressant, which might be particularly useful in those patients who are susceptible to the side-effects of psychotropic drugs.

  20. Plasma proteomic alterations in non-human primates and humans after chronic alcohol self-administration

    PubMed Central

    Freeman, Willard M.; VanGuilder, Heather D.; Guidone, Elizabeth; Krystal, John H.; Grant, Kathleen A.; Vrana, Kent E.

    2011-01-01

    Objective diagnostics of excessive alcohol use are valuable tools in the identification and monitoring of subjects with alcohol use disorders. A number of potential biomarkers of alcohol intake have been proposed, but none have reached widespread clinical usage, often due to limited diagnostic sensitivity and specificity. In order to identify novel potential biomarkers, we performed proteomic biomarker target discovery in plasma samples from non-human primates that chronically self-administer high levels of ethanol. 2-dimensional in-gel electrophoresis (2D-DIGE) was used to quantify plasma proteins from within subject samples collected before exposure to ethanol and after three months of excessive ethanol self-administration. Highly abundant plasma proteins were depleted from plasma samples to increase proteomic coverage. Altered plasma levels of SAA4, RBP, ITIH4, clusterin, and fibronectin, identified by 2D-DIGE analysis, were confirmed in unmanipulated, whole plasma from these animals by immunoblotting. Examination of these target plasma proteins in human subjects with excessive alcohol consumption (and control subjects) revealed increased levels of SAA4 and clusterin and decreased levels of fibronectin compared to controls. These proteins not only serve as targets for further development as biomarker candidates or components of biomarker panels, but also add to the growing understanding of dysregulated immune function and lipoprotein metabolism with chronic, excessive alcohol consumption. PMID:21303580

  1. Zn(II)-curcumin protects against hemorheological alterations, oxidative stress and liver injury in a rat model of acute alcoholism.

    PubMed

    Yu, Chuan; Mei, Xue-Ting; Zheng, Yan-Ping; Xu, Dong-Hui

    2014-03-01

    Curcumin can chelate metal ions, forming metallocomplexes. We compared the effects of Zn(II)-curcumin with curcumin against hemorheological alterations, oxidative stress and liver injury in a rat model of acute alcoholism. Oral administration of Zn(II)-curcumin dose-dependently prevented the ethanol-induced elevation of serum malondialdehyde (MDA) content and reductions in glutathione level and superoxide dismutase (SOD) activity. Zn(II)-curcumin also inhibited ethanol-induced liver injury. Additionally, Zn(II)-curcumin dose-dependently inhibited hemorheological abnormalities, including the ethanol-induced elevation of whole blood viscosity, plasma viscosity, blood viscosity at corrected hematocrit (45%), erythrocyte aggregation index, erythrocyte rigidity index and hematocrit. Compared to curcumin at the same dose, Zn(II)-curcumin more effectively elevated SOD activity, ameliorated liver injury and improved hemorheological variables. These results suggest that Zn(II)-curcumin protected the rats from ethanol-induced liver injury and hemorheological abnormalities via the synergistic effect of curcumin and zinc.

  2. Effects of Acute Alcohol Tolerance on Perceptions of Danger and Willingness to Drive after Drinking

    PubMed Central

    Amlung, Michael T.; Morris, David H.; McCarthy, Denis M.

    2014-01-01

    Rationale Drinking and driving is associated with elevated rates of motor vehicle accidents and fatalities. Previous research suggests that alcohol impairs judgments about the dangers of risky behaviors; however, how alcohol affects driving-related judgments is less clear. Impairments have also been shown to differ across limbs of the blood alcohol concentration (BAC) curve, which is known as acute tolerance. Objectives Examine whether perceptions about the dangerousness of driving after drinking and willingness to drive differed across ascending and descending limbs of the BAC curve. Test whether reductions in perceived danger were associated with willingness to drive on the descending limb. Methods Fifty-six participants were randomly assigned to receive either a moderate dose of alcohol (peak BAC = 0.10 g%) or placebo. We assessed perceived dangerousness and willingness to drive at matched BACs (~0.067-0.068 g%) on the ascending and descending limbs. Results Both perceived danger and willingness to drive showed acute tolerance in the alcohol group. Participants judged driving to be significantly less dangerous and were more willing to drive on the descending limb compared to the ascending limb. The magnitude of change in perceived danger significantly predicted willingness to drive on the descending limb. Conclusions Decreased impairment associated with acute tolerance may lead individuals to underestimate the dangerousness of driving after drinking and in turn make poor decisions regarding driving. This study further emphasizes the descending limb as a period of increased risk and offers support for enhancing prevention efforts by targeting drivers at declining BAC levels. PMID:24752657

  3. Differential Effects of Acute Alcohol on Prepulse Inhibition and Event-Related Potentials in Adolescent and Adult Wistar Rats

    PubMed Central

    Pian, Jerry P.; Criado, Jose R.; Ehlers, Cindy L.

    2009-01-01

    Background Previous studies have demonstrated that adolescent and adult rats show differential sensitivity to many of the acute effects of alcohol. We recently reported evidence of developmental differences in the effects of acute alcohol on the cortical electroencephalogram (EEG). However, it is unclear whether developmental differences are also observed in other neurophysiological and neurobehavioral measurements known to be sensitive to alcohol exposure. The present study determined the age-related effects of acute alcohol on behavioral and event-related potential (ERP) responses to acoustic startle (AS) and prepulse inhibition (PPI). Methods Male adolescent and adult Wistar rats were implanted with cortical recording electrodes. The effects of acute alcohol (0.0, 0.75, and 1.5 g/kg) on behavioral and ERP responses to AS and PPI were assessed. Results Acute alcohol (0.75 and 1.5 g/kg) significantly reduced the behavioral and electrophysiological response to AS in adolescent and adult rats. Both 0.75 and 1.5 g/kg alcohol significantly enhanced the behavioral response to PPI in adolescent, but not in adult rats. During prepulse+pulse trials, 1.5 g/kg alcohol significantly increased the N10 pulse response in the adolescent frontal cortex. Acute alcohol (0.75 and 1.5 g/kg) also increased the N1 ERP pulse response to prepulse stimuli in frontal and parietal cortices in adult rats, but not in adolescent rats. Conclusions These data suggest that alcohol’s effect on behavioral and electrophysiological indices of AS do not differ between adults and adolescents whereas developmental stage does appear to significantly modify alcohol influenced response to PPI. PMID:18828807

  4. The influence of gastric pentadecapeptide BPC 157 on acute and chronic ethanol administration in mice.

    PubMed

    Blagaic, Alenka Boban; Blagaic, Vladimir; Romic, Zeljko; Sikiric, Predrag

    2004-09-24

    The stable gastric pentadecapeptide BPC 157 (GEPPPGKPADDAGLV, M.W.1419), which was promising in inflammatory bowel disease (PL-10, PLD-116, PL-14736, Pliva) trials, protects against both acute and chronic alcohol-induced lesions in stomach and liver, but also, given peripherally, affects various centrally mediated disturbances. Now, in male NMRI mice BPC 157 (10 pg intraperitoneally, 10 ng and 10 microg, intraperitoneally or intragastrically) (i) strongly opposed acute alcohol (4 g/kg intraperitoneally) intoxication (i.e., quickly produced and sustained anesthesia, hypothermia, increased ethanol blood values, 25% fatality, 90-min assessment period) given before or after ethanol, and (ii) when given after abrupt cessation of ethanol (at 0 or 3 or 7 h withdrawal time), attenuated withdrawal (assessed through 24 hours) after 20%-alcohol drinking (7.6 g/kg) through 13 days, with provocation on the 14th day. PMID:15381050

  5. Skeletal muscle protein synthesis and degradation exhibit sexual dimorphism after chronic alcohol consumption but not acute intoxication.

    PubMed

    Lang, Charles H; Frost, Robert A; Vary, Thomas C

    2007-06-01

    Epidemiological evidence suggests alcoholic myopathy is more severe in females than males, but comparable animal studies are lacking that make elucidating the biochemical locus for this defect problematic. The present study determined whether skeletal muscle protein synthesis and markers of degradation exhibit a sexual dimorphic response to either chronic alcohol consumption or acute intoxication. Male and female rats were fed an alcohol-containing diet, pair-fed for 26 wk (chronic), or received an intraperitoneal injection of alcohol (acute). In males, chronic alcohol decreased gastrocnemius protein synthesis by 20%. This reduction was associated with a twofold increase in the inactive eukaryotic initiation factor (eIF) 4E.4E-binding protein 1 (4E-BP1) complex and a 60% reduction in the active eIF4E.eIF4G complex. This redistribution of eIF4E was associated with decreased phosphorylation of both 4E-BP1 and eIF4G (50-55%). The phosphorylation of ribosomal protein S6 was also reduced 60% in alcohol-consuming male rats. In contrast, neither rates of protein synthesis nor indexes of translation initiation in muscle were altered in alcohol-fed female rats despite blood alcohol levels comparable to males. Chronic alcohol ingestion did not alter atrogin-1 or muscle RING finger-1 mRNA content (biomarkers of muscle proteolysis) in males but increased their expression in females 50-100%. Acute alcohol intoxication produced a comparable decrease in muscle protein synthesis and translation initiation in both male and female rats. Our data demonstrate a sexual dimorphism for muscle protein synthesis, translation initiation, and proteolysis in response to chronic, but not acute, alcohol intoxication; however, they do not support evidence indicating females are more sensitive toward the development of alcoholic skeletal muscle myopathy.

  6. [Effect of Bacillus natto-fermented product (BIOZYME) on blood alcohol, aldehyde concentrations after whisky drinking in human volunteers, and acute toxicity of acetaldehyde in mice].

    PubMed

    Sumi, H; Yatagai, C; Wada, H; Yoshida, E; Maruyama, M

    1995-04-01

    Effects of Bacillus natto-fermented product (BIOZYME) on blood alcohol and aldehyde concentrations after drinking whisky (corresponding to 30-65 ml ethanol) were studied in 21 healthy volunteers. When 100 ml of BIOZYME was orally administrated to the volunteers before drinking whisky, the time delay of both blood factors to attain maximum concentrations were observed. The maximum decrease in blood alcohol and aldehyde concentrations were about 23% and 45% (p < 0.005), respectively, at 1 hr after drinking whisky. The aldehyde lowering effect of BIOZYME was continued for at least 4 hr after whisky drinking. Concentration of the breath alcohol was also sharply decreased by BIOZYME administration. The breath alcohol concentration in the administered group (0.18 +/- 0.11 mg/l) was found to be lowered about 44% than that of the control group (0.32 +/- 0.11 mg/l) (p < 0.0005, n = 21), at 1 hr after drinking whisky. In acute toxicity experiments of aldehyde in mice (12 mmol AcH/mg), BIOZYME showed the survival effect as with alpha-D-Ala (134% increase of the living, at 40 min after i.p. administration) (p < 0.005, n = 22). These findings reveal the Bacillus natto produced BIOZYME as a reasonable, safety and useful anti-hangover agent.

  7. Laboratory alcohol self-administration experiments do not increase subsequent real-life drinking in young adult social drinkers

    PubMed Central

    Sommer, Christian; Seipt, Christian; Spreer, Maik; Blümke, Toni; Markovic, Alexandra; Jünger, Elisabeth; Plawecki, Martin H.; Zimmermann, Ulrich S.

    2015-01-01

    Background While the utility of experimental free-access alcohol self-administration paradigms is well-established, little data exist addressing the question of whether study participation influences subsequent natural alcohol consumption. We here present drinking reports of young adults before and after participation in intravenous alcohol self-administration studies. Methods Timeline Follow-back (TLFB) drinking reports for the 6 weeks immediately preceding the first, and the 6 weeks after the last experimental alcohol challenge were examined from subjects completing one of two similar alcohol self-administration paradigms. In study 1, eighteen social drinkers (9 females, mean age 24.1 years) participated in 3 alcohol self-infusion sessions up to a maximum blood alcohol concentration (BAC) of 160 mg%. Study 2 involved 60 participants (30 females, mean age 18.3 years) of the Dresden Longitudinal Study on Alcohol Use in Young Adults (D-LAYA), who participated in 2 sessions of alcohol self-infusion up to a maximum BAC of 120 mg%, and a non-exposed age- matched control group of 42 (28 females, mean age 18.4 years) subjects. Results In study 1, participants reported (3.7%) fewer heavy drinking days as well as a decrease of 2.5 drinks per drinking day after study participation compared to pre-study levels (p<.05 respectively).. In study 2, alcohol-exposed participants reported 7.1% and non- alcohol-exposed controls 6.5% fewer drinking days at post-study measurement (p<.001), while percent heavy drinking days and drinks per drinking day did not differ. Conclusion These data suggest that participation in intravenous alcohol self-administration experiments does not increase subsequent real-life drinking of young adults. PMID:25903217

  8. Social Stress and Escalated Drug Self-Administration in Mice I. Alcohol and Corticosterone

    PubMed Central

    Norman, Kevin J.; Seiden, Jacob A.; Klickstein, Jacob A.; Han, Xiao; Hwa, Lara S.; DeBold, Joseph F.; Miczek, Klaus A.

    2014-01-01

    Rationale Stress experiences have been shown to be a risk factor for alcohol abuse in humans; however, a reliable mouse model using episodic social stress has yet to be developed. Objectives The current studies investigated the effects of mild and moderate social defeat protocols on plasma corticosterone, voluntary alcohol drinking, and motivation to drink alcohol. Methods Outbred CFW mice were socially defeated for 10 days during which the intruder mouse underwent mild (15 bites: mean = 1.5 min), or moderate (30 bites: mean = 3.8 min) stress. Plasma corticosterone was measured on days 1 and 10 of the defeat. Ethanol drinking during continuous access to alcohol was measured 10 days following the defeat or 10 days prior to, during and 20 days after the defeat. Motivation to drink was determined using a PR operant conditioning schedule during intermittent access to ethanol. Results Plasma corticosterone was elevated in both stress groups on days 1 and 10. Ethanol consumption and preference following moderate social stress was higher than both the mild stress group and controls. Mice with previously acquired ethanol drinking showed decreased ethanol consumption during the moderate stress followed by an increase 20 days post-defeat. Moderately stressed mice also showed escalated ethanol intake (11g/kg/day) and ethanol self-administration during a schedule of intermittent access to alcohol. Conclusion Social defeat experiences of moderate intensity and duration led to increased ethanol drinking and preference in CFW mice. Ongoing work investigates the interaction between glucocorticoids and dopaminergic systems as neural mechanisms for stress-escalated alcohol consumption. PMID:25242256

  9. Serum Insulin Levels Are Reduced by Intravenous Ghrelin Administration but Do Not Correlate with Alcohol Craving in Alcohol-Dependent Individuals

    PubMed Central

    Giovenco, Danielle E.; Lee, Mary R.; Zywiak, William H.; de la Monte, Suzanne M.; Kenna, George A.; Swift, Robert M.

    2016-01-01

    Background: Increasing evidence supports a role for appetite-regulating pathways like ghrelin, insulin, and leptin in alcoholism. We previously reported that intravenous (i.v.) exogenous ghrelin increases alcohol craving. We also reported i.v. ghrelin reduces endogenous serum leptin, whose levels, in turn, negatively correlated with alcohol craving. Exogenous ghrelin administration decreases insulin secretion both in vitro and in vivo experiments. This study tested the hypothesis that i.v. ghrelin may also decrease endogenous serum insulin levels in alcoholic individuals. Additionally, we explored possible correlations between serum insulin and alcohol craving, since a correlation between insulin and alcohol craving was previously reported. Methods: This was a double-blind, placebo-controlled human laboratory study (n=43). Non-treatment-seeking, alcohol-dependent, heavy drinkers were randomized to receive i.v. ghrelin or placebo, followed by an alcohol cue-reactivity procedure. Results: There was a main effect for i.v. ghrelin, compared to placebo in reducing serum insulin (P<.05). There was also a time effect (P<.001) but not ghrelin x time interaction (P>.05). We did not find a correlation between the reduction of serum insulin and alcohol craving (P>.05). The change in serum insulin was consistent with a parallel reduction in serum connective-peptide in the ghrelin group compared with placebo, although this difference did not reach statistical significance (P=.076). No similar effects were found for other glucose-regulating hormones analyzed i.e. glucagon, glucagon-like peptide-1, and gastric inhibitory peptide (Ps>.05). Conclusions: These findings indicate i.v. ghrelin administration has an effect on reducing serum insulin in alcohol-dependent individuals; however, the reduction of insulin did not correlate with changes in alcohol cue-elicited craving. We speculate that, unlike for leptin, the interactions between ghrelin and insulin relationship are limited at

  10. Effects of acute alcohol consumption and vitamin E co-treatment on oxidative stress parameters in rats tongue.

    PubMed

    Carrard, V C; Pires, A S; Mendez, M; Mattos, F; Moreira, J C F; Sant'Ana Filho, M

    2009-06-01

    The aim of this study was to evaluate the effects of acute alcohol consumption and vitamin E co-treatment upon oxidative stress parameters in rats tongue. Thirty-eight, Wistar rats were separated into five groups (alcohol, alcohol/vitamin E, control, Tween, vitamin E). Alcohol and alcohol vitamin E groups had the standard diet, and 40% alcohol on drinking water. Other groups were fed with the same standard diet and water ad libitum. Vitamin E was given by gavage to vitamin E and alcohol/vitamin E rats twice a week. Alcohol and control groups were subjected to saline gavage and Tween group to 5% Tween 80 solution, the vitamin E vehicle. At day 14, the animals were anesthetized and specimens were obtained from tongue. Lipid peroxidation (TBARS), protein oxidative damage, catalase (CAT) and superoxide dismutase (SOD) activities were quantified. Alcohol group decreased TBARS in relation to control group and alcohol vitamin-treated animals decreased TBARS when compared to Tween and vitamin E groups. SOD activity was lower and CAT activity was higher in animals treated with both alcohol and vitamin E. These results suggest that short-term alcohol consumption decreases lipid peroxidation levels. Alternatively, alcohol/vitamin E group increased CAT, showing the toxicity of this association.

  11. Acute multiple focal neuropathies and delayed postanoxic encephalopathy after alcohol intoxication

    PubMed Central

    Wang, Wei-Che; Yang, Hsiu-Chun; Chen, Yao-Jen

    2015-01-01

    Acute-onset alcohol-associated neuropathy is only occasionally reported, and delayed postanoxic encephalopathy is rare. Here, we report a male who developed acute multiple focal neuropathies and later delayed postanoxic encephalopathy after alcohol intoxication. He had hypoxia and rhabdomyolysis, presenting with acute renal failure initially, and cardiopulmonary support, including mechanical ventilation, led to improvement of the patient at the acute stage. He suffered from bilateral hand numbness and mild weakness of the right lower limb thereafter. Nerve-conduction study revealed no pickup of compound muscle action potential or sensory nerve action potential in the bilateral ulnar nerve, but showed attenuated amplitude of compound muscle action potential in the right femoral nerve. Multiple focal neuropathies were suspected, and he received outpatient rehabilitation after being discharged. However, the patient developed gradual onset of weakness in four limbs and cognitive impairment 23 days after the hypoxia event. Brain computed tomography showed low attenuation over bilateral globus pallidus, and brain magnetic resonance imaging disclosed diffuse increased signal intensity on T2-weighted images and fluid-attenuated inversion recovery in bilateral white matter. He was admitted again under the impression of delayed postanoxic brain injury. Supportive treatment and active rehabilitation were given. He had gradual improvement in motor and functional status after rehabilitation. He could walk with festinating gait under supervision, and needed only minimal assistance in performing activities of daily living approximately 1 year later. PMID:26229472

  12. Maltol, a Food Flavoring Agent, Attenuates Acute Alcohol-Induced Oxidative Damage in Mice

    PubMed Central

    Han, Ye; Xu, Qi; Hu, Jiang-ning; Han, Xin-yue; Li, Wei; Zhao, Li-chun

    2015-01-01

    The purpose of this study was to evaluate the hepatoprotective effect of maltol, a food-flavoring agent, on alcohol-induced acute oxidative damage in mice. Maltol used in this study was isolated from red ginseng (Panax ginseng C.A Meyer) and analyzed by high performance liquid chromatography (HPLC) and mass spectrometry. For hepatoprotective activity in vivo, pretreatment with maltol (12.5, 25 and 50 mg/kg; 15 days) drastically prevented the elevated activities of aspartate transaminase (AST), alanine transaminase (ALT), alkaline phosphatase (ALP) and triglyceride (TG) in serum and the levels of malondialdehyde (MDA), tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β) in liver tissue (p < 0.05). Meanwhile, the levels of hepatic antioxidant, such as catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) were elevated by maltol pretreatment, compared to the alcohol group (p < 0.05). Histopathological examination revealed that maltol pretreatment significantly inhibited alcohol-induced hepatocyte apoptosis and fatty degeneration. Interestingly, pretreatment of maltol effectively relieved alcohol-induced oxidative damage in a dose-dependent manner. Maltol appeared to possess promising anti-oxidative and anti-inflammatory capacities. It was suggested that the hepatoprotective effect exhibited by maltol on alcohol-induced liver oxidative injury may be due to its potent antioxidant properties. PMID:25608939

  13. Dopamine dynamics associated with, and resulting from, schedule-induced alcohol self-administration: Analyses in dopamine transporter knockout mice

    PubMed Central

    Mittleman, Guy; Call, Stanford B.; Cockroft, Jody L.; Goldowitz, Dan; Matthews, Douglas B.; Blaha, Charles D.

    2011-01-01

    Preclinical and clinical evidence suggest an association between alcoholism and the primary regulator of extracellular dopamine concentrations, the dopamine transporter (DAT). However, the nature of this association is unclear. We determined if ten days of voluntary alcohol self-administration followed by withdrawal could directly alter DAT function, or if genetically-mediated changes in DAT function and/or availability could influence vulnerability to alcohol abuse. Heterozygous (DAT+/-) and homozygous mutant (DAT-/-) and wildtype (DAT+/+) mice were allowed to consume 5% alcohol in a schedule-induced polydipsia (SIP) task. In vivo fixed potential amperometry in anesthetized mice was used to (1) identify functional characteristics of mesoaccumbens dopamine neurons related to genotype, including dopamine autoreceptor (DAR) sensitivity, DAT efficiency, and DAT capacity, (2) determine if any of these characteristics correlated with alcohol drinking observed in DAT+/+ and DAT+/- animals, and (3) determine if SIP-alcohol self-administration altered DAR sensitivity, DAT efficiency, and DAT capacity by comparing these characteristics in wildtype (DAT+/+) mice that were SIP-alcohol naïve, with those that had undergone SIP-alcohol testing. DAT-/- mice consumed significantly less alcohol during testing and this behavioral difference was related to significant differences in DAR sensitivity, DAT efficiency, and DAT capacity. These functional characteristics were correlated to varying degrees with g/kg alcohol consumption in DAT+/+ and DAT+/- mice. DAR sensitivity was consistently reduced and DAT efficiency was enhanced in SIP-alcohol experienced DAT+/+ mice in comparison to naïve animals. These results indicate that DAR sensitivity is reduced by SIP-alcohol consumption and that DAT efficiency is modified by genotype as well as SIP-alcohol exposure. DAT capacity appeared to be strictly associated with SIP-alcohol consumption. PMID:21354763

  14. Acute Effects of Alcohol on Inhibitory Control and Simulated Driving in DUI Offenders

    PubMed Central

    Van Dyke, Nicholas; Fillmore, Mark T.

    2014-01-01

    Introduction The public health costs associated with alcohol-related traffic accidents have prompted considerable research aimed at identifying characteristics of individuals who drive under the influence (DUI) in order to improve treatment and prevention strategies. Survey studies consistently show that DUI offenders self-report higher levels of impulsivity compared to their nonoffending counterparts. However, little is known about how individuals with a DUI history respond under alcohol. Inhibitory control is a behavioral component of impulsivity thought to underlie risky drinking and driving behaviors. Method The present study examined the degree to which DUI drivers display deficits of inhibitory control in response to alcohol and the degree to which alcohol impaired their simulated driving performance. It was hypothesized that DUI offenders would display an increased sensitivity to the acute impairing effects of alcohol on simulated driving performance. Young adult drivers with a history of DUI and a demographically-comparable group of drivers with no history of DUI (controls) were tested following a 0.65 g/kg dose of alcohol and a placebo. Inhibitory control was measured using a cued go/no-go task. Drivers then completed a driving simulation task that yielded multiple indicators of driving performance, such as within-lane deviation, steering rate, centerline crossings and road edge excursions, and drive speed. Results Results showed that although DUI offenders self-reported greater levels of impulsivity than did controls, no group differences were observed in the degree to which alcohol impaired inhibitory control and driving performance. The findings point to the need to identify other aspects of behavioral dysfunction underlying the self-reported impulsivity among DUI offenders, and to better understand the specific driving situations that might pose greater risk to DUI offenders. PMID:24913486

  15. Alcohol

    MedlinePlus

    ... Text Size: A A A Listen En Español Alcohol Wondering if alcohol is off limits with diabetes? Most people with diabetes can have a moderate amount of alcohol. Research has shown that there can be some ...

  16. Alcohol

    MedlinePlus

    If you are like many Americans, you drink alcohol at least occasionally. For many people, moderate drinking ... risky. Heavy drinking can lead to alcoholism and alcohol abuse, as well as injuries, liver disease, heart ...

  17. Effects of stress, acute alcohol treatment, or both on pre-pulse inhibition in high- and low-alcohol preferring mice.

    PubMed

    Powers, M S; Chester, J A

    2014-03-01

    Pre-pulse inhibition of the acoustic startle reflex (PPI) is a measure of sensorimotor gating frequently used to assess information processing in both humans and rodents. Both alcohol and stress exposure can modulate PPI, making it possible to assess how stress and alcohol interact to influence information processing. Humans with an increased genetic risk for alcoholism are more reactive to stressful situations compared to those without a family history, and alcohol may have stress-dampening effects for those with high genetic risk. The purpose of the present study was to examine the effects of stress, acute alcohol exposure, or both on PPI in male and female mice selectively bred for high- (HAP2) and low- (LAP2) alcohol preference. Experiment 1 assessed the effects of various doses of acute alcohol on PPI. Experiments 2 and 3 assessed the effect of 10 days of restraint stress on subsequent PPI tested at 30 min (Experiment 2) or 24 h (Experiment 3) following the termination of stress exposure. Experiment 3 also examined the effects of acute alcohol treatment (0.75 g/kg) on PPI in mice previously exposed to stress or no stress. Results indicate that 0.75 and 1.0 g/kg doses of alcohol increased PPI in HAP2 but not LAP2 mice. When PPI was tested 30 min after stress exposure, stressed HAP2 mice showed a trend toward decreased PPI and stressed LAP2 mice showed a trend toward increased PPI. The combination of stress and alcohol treatment did not alter PPI in either line 24 h following the termination of stress exposure, suggesting that alcohol does not ameliorate the effect of stress on PPI. Stressed LAP2 mice had increased basal circulating corticosterone on the final stress exposure day compared to non-stressed LAP2 mice, and no difference was found between stressed and non-stressed HAP2 mice. The results suggest that high genetic risk for alcoholism may be related to increased sensitivity to alcohol and stress effects on PPI, and this sensitivity could signify

  18. The effects of acute ethanol administration on ethanol withdrawal-induced anxiety-like syndrome in rats: A biochemical study.

    PubMed

    Kumar, Jaya; Hapidin, Hermizi; Get Bee, Yvonne-Tee; Ismail, Zalina

    2016-02-01

    Withdrawal from long-term ethanol consumption results in overexcitation of glutamatergic neurotransmission in the amygdala, which induces an anxiety-like syndrome. Most alcoholics that suffer from such symptoms frequently depend on habitual drinking as self-medication to alleviate their symptoms. Metabotropic glutamate receptor subtype 5 (mGlu5) and protein kinase C (PKC) epsilon have been reported to mediate acute and chronic effects of ethanol. This study explores the changes in mGlu5 and PKC epsilon in the amygdala following acute administration of ethanol during ethanol withdrawal (EW) induced anxiety. Male Wistar rats were fed a modified liquid diet containing low-fat cow milk, sucrose, and maltodextrin, with a gradual introduction of 2.4%, 4.8% and 7.2% ethanol for 20 days. Six hours into EW, the rats were intraperitoneally injected with normal saline and ethanol (2.5 g/kg, 20% v/v), and exposed to open-field and elevated plus maze tests. Then, amygdala tissue was dissected from the rat brain for Western blot and gene expression studies. EW-induced anxiety was accompanied by a significant increase in mGlu5, total PKC epsilon, and phosphorylated PKC epsilon protein levels, and also of mRNA of mGlu5 (GRM5) in the amygdala. Acute administration of ethanol significantly attenuated EW-induced anxiety as well as an EW-induced increase in GRM5. The acute challenge of ethanol to EW rats had little effect on the phosphorylated and total protein levels of PKC epsilon in the amygdala. Our results demonstrate that amygdala PKC epsilon may not be directly involved in the development of anxiety following EW.

  19. Effect of exogenous administration of Candida albicans autoregulatory alcohols in a murine model of hematogenously disseminated candidiasis.

    PubMed

    Martins, Margarida; Lazzell, Anna L; Lopez-Ribot, Jose L; Henriques, Mariana; Oliveira, Rosário

    2012-08-01

    Candida albicans supernatants contain a mixture of autoregulatory alcohols. In vitro, when added individually or in combination, these alcohols inhibit the yeast to filamentous form conversion. Here we evaluate the in vivo effect of the exogenous administration of a Cocktail solution simulating the composition of alcohols present in a C. albicans culture supernatant (1 ml; 94 μmol l(-1) isoamyl alcohol, 70 μmol l(-1) 2-phenylethanol, 3.2 n mol l(-1) E -nerolidol, and 18 n mol l(-1) E,E -farnesol) using the well established murine model of hematogenously disseminated candidiasis. Mice injected intraperitoneally with the Cocktail solution demonstrated increased survival and decreased organ fungal burden compared to control mice. Histological observations suggest that the Cocktail, to some extent, has an inhibitory effect on cell filamentation within the kidney. These findings suggest that the exogenous administration of C. albicans autoregulatory alcohols displays a protective effect during disseminated candidiasis.

  20. The effect of acute alcohol intoxication on gut wall integrity in healthy male volunteers; a randomized controlled trial.

    PubMed

    de Jong, W J; Cleveringa, A M; Greijdanus, B; Meyer, P; Heineman, E; Hulscher, J B

    2015-02-01

    The aim of the study is to determine the effect of acute alcohol consumption on enterocytes. Chronic alcohol consumption has been known to induce a decrease in gut wall integrity in actively drinking alcoholics and patients with alcohol-induced liver disease. Data on the extent of the damage induced by acute alcohol consumption in healthy human beings is scarce. Studies show that heavy incidental alcohol consumption is a growing problem in modern society. Data on this matter may provide insights into the consequences of this behavior for healthy individuals. In a randomized clinical trial in crossover design, 15 healthy volunteers consumed water one day and alcohol the other. One blood sample was collected pre-consumption, five every hour post-consumption, and one after 24 h. Intestinal fatty acid binding protein (I-FABP) was used as a marker for enterocyte damage. Liver fatty acid binding protein (L-FABP), aspartate aminotransferase (AST), alanine aminotransferase (ALT), and gamma-glutamyl transferase (GGT) were used as markers for hepatocyte damage. Lipopolysaccharide binding protein (LBP) and soluble CD14 (sCD14) were used as a measure of translocation. Interleukin-6 (IL-6) was used to assess the acute inflammatory response to endotoxemia. Alcohol consumption caused a significant increase in serum I- and L-FABP levels, compared to water consumption. Levels increased directly post-consumption and decreased to normal levels within 4 h. LBP, sCD14, and IL-6 levels were not significantly higher in the alcohol group. Moderate acute alcohol consumption immediately damages the enterocyte but does not seem to cause endotoxemia. PMID:25559494

  1. The effect of acute alcohol intoxication on gut wall integrity in healthy male volunteers; a randomized controlled trial.

    PubMed

    de Jong, W J; Cleveringa, A M; Greijdanus, B; Meyer, P; Heineman, E; Hulscher, J B

    2015-02-01

    The aim of the study is to determine the effect of acute alcohol consumption on enterocytes. Chronic alcohol consumption has been known to induce a decrease in gut wall integrity in actively drinking alcoholics and patients with alcohol-induced liver disease. Data on the extent of the damage induced by acute alcohol consumption in healthy human beings is scarce. Studies show that heavy incidental alcohol consumption is a growing problem in modern society. Data on this matter may provide insights into the consequences of this behavior for healthy individuals. In a randomized clinical trial in crossover design, 15 healthy volunteers consumed water one day and alcohol the other. One blood sample was collected pre-consumption, five every hour post-consumption, and one after 24 h. Intestinal fatty acid binding protein (I-FABP) was used as a marker for enterocyte damage. Liver fatty acid binding protein (L-FABP), aspartate aminotransferase (AST), alanine aminotransferase (ALT), and gamma-glutamyl transferase (GGT) were used as markers for hepatocyte damage. Lipopolysaccharide binding protein (LBP) and soluble CD14 (sCD14) were used as a measure of translocation. Interleukin-6 (IL-6) was used to assess the acute inflammatory response to endotoxemia. Alcohol consumption caused a significant increase in serum I- and L-FABP levels, compared to water consumption. Levels increased directly post-consumption and decreased to normal levels within 4 h. LBP, sCD14, and IL-6 levels were not significantly higher in the alcohol group. Moderate acute alcohol consumption immediately damages the enterocyte but does not seem to cause endotoxemia.

  2. Alcohol

    MedlinePlus

    ... Got Homework? Here's Help White House Lunch Recipes Alcohol KidsHealth > For Kids > Alcohol Print A A A Text Size What's in ... What Is Alcoholism? Say No en español El alcohol Getting the Right Message "Hey, who wants a ...

  3. Spontaneous resolution of pancreatic masses (pseudocysts?)--Development and disappearance after acute alcoholic pancreatitis.

    PubMed

    Czaja, A J; Fisher, M; Marin, G A

    1975-04-01

    To determine the incidence and the natural history of retroperitoneal masses complicating acute pancreatitis, 104 cases of acute alcoholic pancreatitis were evaluated prospectively for mass formation. Abdominal masses detected by physical examination and serial x-ray films of the upper portion of the gastrointestinal tract were localized to the retroperitoneum by additional contrast studies, including abdominal angiography. Nonoperative management was urged only for patients with an asymptomatic mass. An abdominal mass developed in 19 patients (18%). In eight of these, it disappeared rapidly, but in 11 (11%), it persisted, and was considered to be a pancreatic pseudocyst. Eight of the 11 patients were treated nonoperatively, and the mass resolved without complication three weeks to three months after diagnosis. In three patients, a pseudocyst was confirmed at laparotomy. Exploration was justified by an unstable clinical course in only one instance. A routine surgical approach to an asymptomatic retroperitoneal mass developing after acute alcoholic pancreatitis may not be necessaary in patients who are improving clinically because the mass may resolve without complication.

  4. [Brain histaminergic neurons in rats subjected to the acute effect of alcohol].

    PubMed

    Zimatkin, S M; Fedina, E M; Kuznetsova, V B

    2012-01-01

    The purpose of the present investigation was to examine the effect of single injection of alcohol on histaminergic neurons of rat brain. The study included 41 male albino rats, histological, histochemical, electron microscopic and morphometric methods were used. It was found that 1 hour after the intraperitoneal administration of ethanol in a dose of 4 g/kg the neurons become more spherical, the activity of NADH and glucose-6-phosphate dehydrogenases in their cytoplasm decreased, but the activity of lactate dehydrogenase, type B monoaminooxidase and acid phosphatase increased, at the same time significant ultrastructural disturbances were observed. Six hours following alcohol administration, the signs of histaminergic neuronal damage were reduced while the features of structural and metabolic adaptation became more expressed.

  5. Necro-inflammatory response of pancreatic acinar cells in the pathogenesis of acute alcoholic pancreatitis.

    PubMed

    Gu, H; Werner, J; Bergmann, F; Whitcomb, D C; Büchler, M W; Fortunato, F

    2013-01-01

    The role of pancreatic acinar cells in initiating necro-inflammatory responses during the early onset of alcoholic acute pancreatitis (AP) has not been fully evaluated. We investigated the ability of acinar cells to generate pro- and anti-inflammatory mediators, including inflammasome-associated IL-18/caspase-1, and evaluated acinar cell necrosis in an animal model of AP and human samples. Rats were fed either an ethanol-containing or control diet for 14 weeks and killed 3 or 24 h after a single lipopolysaccharide (LPS) injection. Inflammasome components and necro-inflammation were evaluated in acinar cells by immunofluorescence (IF), histology, and biochemical approaches. Alcohol exposure enhanced acinar cell-specific production of TNFα, IL-6, MCP-1 and IL-10, as early as 3 h after LPS, whereas IL-18 and caspase-1 were evident 24 h later. Alcohol enhanced LPS-induced TNFα expression, whereas blockade of LPS signaling diminished TNFα production in vitro, indicating that the response of pancreatic acinar cells to LPS is similar to that of immune cells. Similar results were observed from acinar cells in samples from patients with acute/recurrent pancreatitis. Although morphologic examination of sub-clinical AP showed no visible signs of necrosis, early loss of pancreatic HMGB1 and increased systemic levels of HMGB1 and LDH were observed, indicating that this strong systemic inflammatory response is associated with little pancreatic necrosis. These results suggest that TLR-4-positive acinar cells respond to LPS by activating the inflammasome and producing pro- and anti-inflammatory mediators during the development of mild, sub-clinical AP, and that these effects are exacerbated by alcohol injury.

  6. Necro-inflammatory response of pancreatic acinar cells in the pathogenesis of acute alcoholic pancreatitis

    PubMed Central

    Gu, H; Werner, J; Bergmann, F; Whitcomb, D C; Büchler, M W; Fortunato, F

    2013-01-01

    The role of pancreatic acinar cells in initiating necro-inflammatory responses during the early onset of alcoholic acute pancreatitis (AP) has not been fully evaluated. We investigated the ability of acinar cells to generate pro- and anti-inflammatory mediators, including inflammasome-associated IL-18/caspase-1, and evaluated acinar cell necrosis in an animal model of AP and human samples. Rats were fed either an ethanol-containing or control diet for 14 weeks and killed 3 or 24 h after a single lipopolysaccharide (LPS) injection. Inflammasome components and necro-inflammation were evaluated in acinar cells by immunofluorescence (IF), histology, and biochemical approaches. Alcohol exposure enhanced acinar cell-specific production of TNFα, IL-6, MCP-1 and IL-10, as early as 3 h after LPS, whereas IL-18 and caspase-1 were evident 24 h later. Alcohol enhanced LPS-induced TNFα expression, whereas blockade of LPS signaling diminished TNFα production in vitro, indicating that the response of pancreatic acinar cells to LPS is similar to that of immune cells. Similar results were observed from acinar cells in samples from patients with acute/recurrent pancreatitis. Although morphologic examination of sub-clinical AP showed no visible signs of necrosis, early loss of pancreatic HMGB1 and increased systemic levels of HMGB1 and LDH were observed, indicating that this strong systemic inflammatory response is associated with little pancreatic necrosis. These results suggest that TLR-4-positive acinar cells respond to LPS by activating the inflammasome and producing pro- and anti-inflammatory mediators during the development of mild, sub-clinical AP, and that these effects are exacerbated by alcohol injury. PMID:24091659

  7. The Effect of Alcohol on Gastrointestinal Motility.

    PubMed

    Grad, Simona; Abenavoli, Ludovico; Dumitrascu, Dan L

    2016-01-01

    The Gastrointestinal (GI) tract is one of the most affected systems by alcohol consumption. Alcohol can affect the esophagus in several ways: induces mucosal inflammation, increases the risk for Barrett esophagus and esophageal cancer, and also impairs the esophageal motility. Numerous studies have reported an increased prevalence of Gastroesophageal Reflux Disease (GERD) or erosive esophagitis in alcoholics. Some alcoholics exhibit an abnormality of esophageal motility known as a "nutcracker esophagus". Alcohol effect on gastric motility depends on the alcohol concentration. In general, beverages with high alcohol concentrations (i.e., above 15 percent) appear to inhibit gastric motility and low alcohol doses (wine and beer) accelerate gastric emptying. Also, acute administration of ethanol inhibits the gastric emptying, while chronic administration of a large dose of alcohol accelerates gastric motility. The effect of alcohol on small bowel motility differs according to the type of consumption (acute or chronic). Acute administration of alcohol has been found to inhibit small bowel transit and chronic administration of a large dose of alcohol accelerates small bowel transit. This article reviews some of the below findings. PMID:27527893

  8. Effects of acute aspartame and acute alcohol ingestion upon the cognitive performance of pilots.

    PubMed

    Stokes, A F; Belger, A; Banich, M T; Taylor, H

    1991-07-01

    Anecdotal evidence has associated the artificial sweetener aspartame with a number of symptoms of central nervous system (CNS) dysfunction. There are, however, little scientific data concerning the effect of aspartame upon complex mental operations such as those necessary for flying an aircraft. Thirteen pilots were tested in a double-blind study using the SPARTANS cognitive test battery of aviation-relevant information-processing tasks. These tasks relate to perceptual-motor abilities, spatial abilities, working memory, attentional performance, risk taking, processing flexibility, planning and sequencing ability. Subjects were tested over five sessions consisting of pretest and posttest controls and three randomly ordered treatment sessions. The treatment conditions involved an aspartame dose of 50 mg/kg body weight, a placebo condition, and an ethyl alcohol (0.1% BAL) condition as the positive control. No detectable performance decrements were associated with the aspartame condition, although decrements in psychomotor and spatial abilities were detected in the ethanol condition. Results were found to be consistent with prior flight-simulator studies of alcohol, but do not appear to support the concerns expressed in anecdotal testimony regarding the deleterious effects of aspartame upon cognitive performance.

  9. Protective effects of C-phycocyanin on alcohol-induced acute liver injury in mice

    NASA Astrophysics Data System (ADS)

    Xia, Dong; Liu, Bing; Luan, Xiying; Sun, Junyan; Liu, Nana; Qin, Song; Du, Zhenning

    2016-03-01

    Excessive alcohol consumption leads to liver disease. Extensive evidence suggests that C-phycocyanin (C-PC), a chromophore phycocyanobilin derived from Spirulina platensis, exerts protective effects against chemical-induced organ damage. In this study, we investigated whether C-PC could protect against ethanol-induced acute liver injury. Serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), triglyceride (TG), total cholesterol (CHOL), low-density lipoprotein (LDL), liver homogenate malondialdehyde (MDA), superoxide dismutase (SOD) content were measured, and pathological examination of liver sections were examined. C-PC showed obvious inhibitory effects on serum ALT, AST, TG, CHOL, LDL and MDA, and SOD content significantly increased in the liver. The structure of hepatic lobules was clear, liver sinus returned to normal, and liver cell cords were arranged in neat rows. Cloudiness, swelling, inflammatory cell infiltration and spotty necrosis of liver cells were significantly reduced. Therefore, C-PC can significantly protect against ethanol-induced acute liver injury.

  10. Behavioral effects of acute and long-term administration of catnip (Nepeta cataria) in mice.

    PubMed

    Massoco, C O; Silva, M R; Gorniak, S L; Spinosa, M S; Bernardi, M M

    1995-12-01

    Catnip or catmint (Nepeta cataria) is a plant used extensively to treat human diseases and in toys for pets. We investigated the effects of acute and long-term administration of the plant on some behaviors of mice. The plant was fed as 10% of the normal diet for 2 h/d for 1 or 7 d. Acute and long-term dosing increased both rearing and locomotion frequencies observed in an open field. Acute exposure to catnip increased stereotyped behavior and susceptibility to seizures, did not interfere with haloperidol-induced catalepsy, and decreased sleeping time after sodium pentobarbital administration. Long-term exposure induced tolerance to stereotypic behavior, catalepsy and sleeping time, and increased the susceptibility to seizures induced by picrotoxin and strychnine. An amphetamine-like effect of catnip was suggested to explain the acute effects, while dispositional and functional adaptative changes were considered involved with the long-term effects.

  11. Mechanisms of Acute Alcohol Intoxication-Induced Modulation of Cyclic Mobilization of [Ca2+] in Rat Mesenteric Lymphatic Vessels

    PubMed Central

    Kerut, Edmund K.; Breslin, Jerome W.; Molina, Patricia E.

    2015-01-01

    Abstract Background: We have demonstrated that acute alcohol intoxication (AAI) increases the magnitude of Ca2+ transients in pumping lymphatic vessels. We tested the contribution of extracellular Ca2+ via L-type Ca2+ channels and intracellular Ca2+ release from the sarcoplasmic reticulum (SR) to the AAI-induced increase in Ca2+ transients. Methods and Results: AAI was produced by intragastric administration of 30% alcohol to conscious, unrestrained rats; isovolumic administration of water served as the control. Mesenteric lymphatic vessels were isolated, cannulated, and loaded with Fura-2 AM to measure changes in intracellular Ca2+. Measurements were made at intraluminal pressures of 2, 6, and 10 cm H2O. L-type Ca2+ channels were blocked with nifedipine; IP-3 receptors were inhibited with xestospongin C; and SR Ca2+ release and Ca2+ pool (Ca2+ free APSS) were achieved using caffeine. Nifedipine reduced lymphatic Ca2+ transient magnitude in both AAI and control groups at all pressures tested, but reduced lymphatic contraction frequency only in the control group. Xestospongin C did not significantly change any of the Ca2+ parameters in either group; however, fractional shortening increased in the controls at low transmural pressure. RyR (ryanodine receptor) activation with caffeine resulted in a single contraction with a greater Ca2+ transient in lymphatics from AAI than those from controls. SR Ca2+ pool was also greater in lymphatics isolated from AAI- than from control animals. Conclusions: These data suggest that 1) L-type Ca2+ channels contribute to the AAI-induced increase in lymphatic Ca2+ transient, 2) blockage of IP-3 receptors could increase calcium sensitivity, and 3) AAI increases Ca2+ storage in the SR in lymphatic vessels. PMID:26056854

  12. Self administration of cocaine in monkeys receiving LAAM acutely or chronically.

    PubMed

    Gerak, Lisa R; Galici, Ruggero; France, Charles P

    2008-01-28

    Polydrug abuse remains a common problem among opioid abusers as well as patients in opioid maintenance programs. Although cocaine abuse has been reported in patients receiving methadone, the incidence of cocaine use in patients receiving l-alpha-acetylmethadol (LAAM) has not been well established. The goal of this study was to determine whether acute or chronic administration of LAAM modified the reinforcing effects of cocaine using a self-administration procedure in rhesus monkeys. Four monkeys responded under a fixed ratio (FR) 30 schedule to receive i.v. infusions of cocaine (0.0032-0.32 mg/kg/infusion) in the absence of other treatment, after acute LAAM administration (0.1-1.0 mg/kg, s.c.), and during daily administration of 1.0 mg/kg of LAAM. Cocaine maintained self-administration responding that exceeded responding maintained by saline; acutely administered LAAM had small and variable effects on self administration of cocaine. Daily LAAM administration increased the number of infusions received of at least one dose of cocaine. These studies indicated that LAAM administration did not attenuate the reinforcing effects of cocaine, suggesting that LAAM would not likely alter cocaine abuse in patients undergoing treatment for opioid abuse. PMID:17764707

  13. Acute effects of traditional Japanese alcohol beverages on blood glucose and polysomnography levels in healthy subjects.

    PubMed

    Kido, Megumi; Asakawa, Akihiro; Koyama, Ken-Ichiro K; Takaoka, Toshio; Tajima, Aya; Takaoka, Shigeru; Yoshizaki, Yumiko; Okutsu, Kayu; Takamine, Kazunori T; Sameshima, Yoshihiro; Inui, Akio

    2016-01-01

    Background. Alcohol consumption is a lifestyle factor associated with type 2 diabetes. This relationship is reportedly different depending on the type of alcohol beverage. The purpose of this study was to examine the acute effects of traditional Japanese alcohol beverages on biochemical parameters, physical and emotional state, and sleep patterns. Methods. Six healthy subjects (three men and three women; age, 28.8 ± 9.5 years; body mass index, 21.4 ± 1.6 kg/m(2)) consumed three different types of alcohol beverages (beer, shochu, and sake, each with 40 g ethanol) or mineral water with dinner on different days in the hospital. Blood samples were collected before and 1, 2, and 12 h after drinking each beverage, and assessments of physical and emotional state were administered at the same time. In addition, sleep patterns and brain waves were examined using polysomnography. Results. Blood glucose levels at 1 h and the 12-h area under the curve (AUC) value after drinking shochu were significantly lower than that with water and beer. The 12-h blood insulin AUC value after drinking shochu was significantly lower than that with beer. Blood glucose × insulin level at 1 h and the 2-h blood glucose × insulin AUC value with shochu were significantly lower than that with beer. The insulinogenic indexes at 2 h with beer and sake, but not shochu, were significantly higher than that with water. The visual analogue scale scores of physical and emotional state showed that the tipsiness levels with beer, shochu, and sake at 1 h were significantly higher than that with water. These tipsiness levels were maintained at 2 h. The polysomnography showed that the rapid eye movement (REM) sleep latency with shochu and sake were shorter than that with water and beer. Conclusions. Acute consumption of alcohol beverages with a meal resulted in different responses in postprandial glucose and insulin levels as well as REM sleep latency. Alcohol beverage type should be taken into consideration

  14. Acute effects of traditional Japanese alcohol beverages on blood glucose and polysomnography levels in healthy subjects

    PubMed Central

    Kido, Megumi; Asakawa, Akihiro; Koyama, Ken-Ichiro K.; Takaoka, Toshio; Tajima, Aya; Takaoka, Shigeru; Yoshizaki, Yumiko; Okutsu, Kayu; Takamine, Kazunori T.; Sameshima, Yoshihiro

    2016-01-01

    Background. Alcohol consumption is a lifestyle factor associated with type 2 diabetes. This relationship is reportedly different depending on the type of alcohol beverage. The purpose of this study was to examine the acute effects of traditional Japanese alcohol beverages on biochemical parameters, physical and emotional state, and sleep patterns. Methods. Six healthy subjects (three men and three women; age, 28.8 ± 9.5 years; body mass index, 21.4 ± 1.6 kg/m2) consumed three different types of alcohol beverages (beer, shochu, and sake, each with 40 g ethanol) or mineral water with dinner on different days in the hospital. Blood samples were collected before and 1, 2, and 12 h after drinking each beverage, and assessments of physical and emotional state were administered at the same time. In addition, sleep patterns and brain waves were examined using polysomnography. Results. Blood glucose levels at 1 h and the 12-h area under the curve (AUC) value after drinking shochu were significantly lower than that with water and beer. The 12-h blood insulin AUC value after drinking shochu was significantly lower than that with beer. Blood glucose × insulin level at 1 h and the 2-h blood glucose × insulin AUC value with shochu were significantly lower than that with beer. The insulinogenic indexes at 2 h with beer and sake, but not shochu, were significantly higher than that with water. The visual analogue scale scores of physical and emotional state showed that the tipsiness levels with beer, shochu, and sake at 1 h were significantly higher than that with water. These tipsiness levels were maintained at 2 h. The polysomnography showed that the rapid eye movement (REM) sleep latency with shochu and sake were shorter than that with water and beer. Conclusions. Acute consumption of alcohol beverages with a meal resulted in different responses in postprandial glucose and insulin levels as well as REM sleep latency. Alcohol beverage type should be taken into consideration

  15. Effect of long-term, peroral administration of sugar alcohols on man.

    PubMed

    Mäkinen, K K

    1984-01-01

    Certain sugar alcohols (polyols), notably mannitol, sorbitol and xylitol have gained use in food manufacturing for sweetening and technical purposes. These compounds are natural polyols that occur in small amounts in animals and plants. Some sugar alcohols, like xylitol, appear as normal intermediates in the carbohydrate metabolism. Exogenous mannitol, sorbitol and xylitol are metabolized in the human body along pre-existing, physiological pathways. Moderate doses of least xylitol and sorbitol are almost totally absorbed and metabolized, chiefly in the liver cells, thereby eventually contributing to the formation of glucose and liver glycogen. Various slowly absorbed carbohydrates, including sugar alcohols, when taken in orally in large quantities, can give rise to osmotic diarrhea. The available data indicate that the severity of such gastro-intestinal disturbances, induced by large doses of polyols, decrease in the following order: mannitol, sorbitol, xylitol. This osmotic diarrhea resembles that caused by lactose in subjects with restricted or frank lactose intolerance. The quantities of xylitol, for example, required to elicit diarrhea are so high that the consumption of xylitol for dental purposes does not cause any problems in children or adults. Long-term feeding trials and peroral loading experiments on human subjects have been unable to show any clinically significant differences between chronic users of xylitol and comparative human material in factors related to various metabolic functions of the body. These subjects have not shown any delayed or acute reactions which could be distinguished from those caused by the consumption of a sucrose diet. The available clinical data generally suggest that moderate consumption of the above polyols is not harmful to human metabolism.

  16. Acute administration of l-tyrosine alters energetic metabolism of hippocampus and striatum of infant rats.

    PubMed

    Ramos, Andrea C; Ferreira, Gabriela K; Carvalho-Silva, Milena; Furlanetto, Camila B; Gonçalves, Cinara L; Ferreira, Gustavo C; Schuck, Patrícia F; Streck, Emilio L

    2013-08-01

    Tyrosinemia type II is an inborn error of metabolism caused by mutations in the gene that encodes tyrosine aminotransferase, which leads to increased blood tyrosine levels. Considering that tyrosine levels are highly elevated in fluids of patients with tyrosinemia type II, and that previous studies demonstrated significant alterations in brain energy metabolism of young rats caused by l-tyrosine, the present study aimed to evaluate the effect of acute administration of l-tyrosine on the activities of citrate synthase, malate dehydrogenase, succinate dehydrogenase, and mitochondrial respiratory chain complexes I, II, II-III, and IV in posterior cortex, hippocampus, and striatum of infant rats. Wistar rats (10 days old) were killed 1h after a single intraperitoneal injection of tyrosine (500 mg/kg) or saline. The activities of energy metabolism enzymes were evaluated in brain of rats. Our results demonstrated that acute administration of l-tyrosine inhibited the activity of citrate synthase activity in striatum and increased the activities of malate dehydrogenase and succinate dehydrogenase in hippocampus. On the other hand, these enzymes were not affected in posterior cortex. The activities of complex I and complex II were inhibited by acute administration of l-tyrosine in striatum. On the other hand, the acute administration of l-tyrosine increased the activity of activity of complex II-III in hippocampus. Complex IV was not affected by acute administration of l-tyrosine in infant rats. Our results indicate an alteration in the energy metabolism in hippocampus and striatum of infant rats after acute administration of l-tyrosine. If the same effects occur in the brain of the patients, it is possible that energy metabolism impairment may be contribute to possible damage in memory and cognitive processes in patients with tyrosinemia type II. PMID:23602810

  17. Acute administration of l-tyrosine alters energetic metabolism of hippocampus and striatum of infant rats.

    PubMed

    Ramos, Andrea C; Ferreira, Gabriela K; Carvalho-Silva, Milena; Furlanetto, Camila B; Gonçalves, Cinara L; Ferreira, Gustavo C; Schuck, Patrícia F; Streck, Emilio L

    2013-08-01

    Tyrosinemia type II is an inborn error of metabolism caused by mutations in the gene that encodes tyrosine aminotransferase, which leads to increased blood tyrosine levels. Considering that tyrosine levels are highly elevated in fluids of patients with tyrosinemia type II, and that previous studies demonstrated significant alterations in brain energy metabolism of young rats caused by l-tyrosine, the present study aimed to evaluate the effect of acute administration of l-tyrosine on the activities of citrate synthase, malate dehydrogenase, succinate dehydrogenase, and mitochondrial respiratory chain complexes I, II, II-III, and IV in posterior cortex, hippocampus, and striatum of infant rats. Wistar rats (10 days old) were killed 1h after a single intraperitoneal injection of tyrosine (500 mg/kg) or saline. The activities of energy metabolism enzymes were evaluated in brain of rats. Our results demonstrated that acute administration of l-tyrosine inhibited the activity of citrate synthase activity in striatum and increased the activities of malate dehydrogenase and succinate dehydrogenase in hippocampus. On the other hand, these enzymes were not affected in posterior cortex. The activities of complex I and complex II were inhibited by acute administration of l-tyrosine in striatum. On the other hand, the acute administration of l-tyrosine increased the activity of activity of complex II-III in hippocampus. Complex IV was not affected by acute administration of l-tyrosine in infant rats. Our results indicate an alteration in the energy metabolism in hippocampus and striatum of infant rats after acute administration of l-tyrosine. If the same effects occur in the brain of the patients, it is possible that energy metabolism impairment may be contribute to possible damage in memory and cognitive processes in patients with tyrosinemia type II.

  18. Alcoholism

    PubMed Central

    Girard, Donald E.; Carlton, Bruce E.

    1978-01-01

    There are important measurements of alcoholism that are poorly understood by physicians. Professional attitudes toward alcoholic patients are often counterproductive. Americans spend about $30 billion on alcohol a year and most adults drink alcohol. Even though traditional criteria allow for recognition of the disease, diagnosis is often made late in the natural course, when intervention fails. Alcoholism is a major health problem and accounts for 10 percent of total health care costs. Still, this country's 10 million adult alcoholics come from a pool of heavy drinkers with well defined demographic characteristics. These social, cultural and familial traits, along with subtle signs of addiction, allow for earlier diagnosis. Although these factors alone do not establish a diagnosis of alcoholism, they should alert a physician that significant disease may be imminent. Focus must be directed to these aspects of alcoholism if containment of the problem is expected. PMID:685264

  19. Is rat liver affected by non-alcoholic steatosis more susceptible to the acute toxic effect of thioacetamide?

    PubMed

    Kučera, Otto; Lotková, Halka; Staňková, Pavla; Podhola, Miroslav; Roušar, Tomáš; Mezera, Vojtěch; Cervinková, Zuzana

    2011-08-01

    Non-alcoholic fatty liver disease (NAFLD) is the most common chronic condition of the liver in the western world. There is only little evidence about altered sensitivity of steatotic liver to acute toxic injury. The aim of this project was to test whether hepatic steatosis sensitizes rat liver to acute toxic injury induced by thioacetamide (TAA). Male Sprague-Dawley rats were fed ad libitum a standard pelleted diet (ST-1, 10% energy fat) and high-fat gelled diet (HFGD, 71% energy fat) for 6 weeks and then TAA was applied intraperitoneally in one dose of 100 mg/kg. Animals were sacrificed in 24-, 48- and 72-h interval after TAA administration. We assessed the serum biochemistry, the hepatic reduced glutathione, thiobarbituric acid reactive substances, cytokine concentration, the respiration of isolated liver mitochondria and histopathological samples (H+E, Sudan III, bromodeoxyuridine [BrdU] incorporation). Activities of alanine aminotransferase, aspartate aminotransferase and alkaline phosphatase and concentration of serum bilirubin were significantly higher in HFGD groups after application of TAA, compared to ST-1. There were no differences in activities of respiratory complexes I and II. Serum tumour necrosis factor alpha at 24 and 48 h, liver tissue interleukin-6 at 72 h and transforming growth factor β1 at 24 and 48 h were elevated in TAA-administrated rats fed with HFGD, but not ST-1. TAA-induced centrilobular necrosis and subsequent regenerative response of the liver were higher in HFGD-fed rats in comparison with ST-1. Liver affected by NAFLD, compared to non-steatotic liver, is more sensitive to toxic effect of TAA. PMID:21410800

  20. Murine Models of Acute Alcoholic Hepatitis and Their Relevance to Human Disease.

    PubMed

    Wilkin, Richard J W; Lalor, Patricia F; Parker, Richard; Newsome, Philip N

    2016-04-01

    Alcohol-induced liver damage is a major burden for most societies, and murine studies can provide a means to better understand its pathogenesis and test new therapies. However, there are many models reported with widely differing phenotypes, not all of which fully regenerate the spectrum of human disease. Thus, it is important to understand the implications of these variations to efficiently model human disease. This review critically appraises key articles in the field, detailing the spectrum of liver damage seen in different models, and how they relate to the phenotype of disease seen in patients. A range of different methods of alcohol administration have been studied, ranging from ad libitum consumption of alcohol and water to modified diets (eg, Lieber deCarli liquid diet). Other feeding regimens have taken more invasive routes using intragastric feeding tubes to infuse alcohol directly into the stomach. Notably, models using wild-type mice generally produce a milder phenotype of liver damage than those using genetically modified mice, with the exception of the chronic binge-feeding model. We recommend panels of tests for consideration to standardize end points for the evaluation of the severity of liver damage-key for comparison of models of injury, testing of new therapies, and subsequent translation of findings into clinical practice. PMID:26835538

  1. Gender Differences in Acute Alcohol Effects on Self-Regulation of Arousal in Response to Emotional and Alcohol-Related Picture Cues

    PubMed Central

    Udo, Tomoko; Bates, Marsha E.; Mun, Eun Young; Vaschillo, Evgeny G.; Vaschillo, Bronya; Lehrer, Paul; Ray, Suchismita

    2010-01-01

    Basic mechanisms through which men and women self-regulate arousal have received little attention in human experimental addiction research although stress-response-dampening and craving theories suggest an important role of emotional arousal in motivating alcohol use. This study examined gender differences in the effects of acute alcohol intoxication on psychophysiological and self-reported arousal in response to emotionally negative, positive, and neutral, and alcohol-related, picture cues. Thirty-six social drinkers (16 women) were randomly assigned to an alcohol, placebo, or control beverage group, and exposed to picture cues every 10 s (0.1 Hz presentation frequency). Psychophysiological arousal was assessed via a 0.1-Hz heart rate variability (HRV) index. A statistically significant beverage group-by-gender interaction effect on psychophysiological, but not self-reported, arousal was found. 0.1-Hz HRV responses to picture cues were suppressed by alcohol only in men. This gender-specific suppression pattern did not differ significantly across picture cue types. There were no significant gender differences in the placebo or control group. Greater dampening of arousal by alcohol intoxication in men, compared to women, may contribute to men's greater tendency to use alcohol to cope with stress. PMID:19586136

  2. Plasma glucose, lactate, sodium, and potassium levels in children hospitalized with acute alcohol intoxication.

    PubMed

    Tõnisson, Mailis; Tillmann, Vallo; Kuudeberg, Anne; Väli, Marika

    2010-09-01

    The aim of our research was to study prevalence of changes in plasma levels of lactate, potassium, glucose, and sodium in relation to alcohol concentration in children hospitalized with acute alcohol intoxication (AAI). Data from 194 under 18-year-old children hospitalized to the two only children's hospital in Estonia over a 2-year period were analyzed. The pediatrician on call filled in a special form on the clinical symptoms of AAI; a blood sample was drawn for biochemical tests, and a urine sample taken to exclude narcotic intoxication. The most common finding was hyperlactinemia occurring in 66% of the patients (n=128) followed by hypokalemia (<3.5 mmol/L) in 50% (n=97), and glucose above of reference value (>6.1 mmol/L) in 40.2% of the children (n=78). Hypernatremia was present in five children. In conclusion, hyperlactinemia, hypokalemia, and glucose levels above of reference value are common biochemical findings in children hospitalized with acute AAI. PMID:20846615

  3. Very Early Administration of Progesterone for Acute Traumatic Brain Injury

    PubMed Central

    Wright, David W.; Yeatts, Sharon D.; Silbergleit, Robert; Palesch, Yuko Y.; Hertzberg, Vicki S.; Frankel, Michael; Goldstein, Felicia C.; Caveney, Angela F.; Howlett-Smith, Harriet; Bengelink, Erin M.; Manley, Geoffrey T.; Merck, Lisa H.; Janis, L. Scott; Barsan, William G.

    2015-01-01

    BACKGROUND Traumatic brain injury (TBI) is a major cause of death and disability worldwide. Progesterone has been shown to improve neurologic outcome in multiple experimental models and two early-phase trials involving patients with TBI. METHODS We conducted a double-blind, multicenter clinical trial in which patients with severe, moderate-to-severe, or moderate acute TBI (Glasgow Coma Scale score of 4 to 12, on a scale from 3 to 15, with lower scores indicating a lower level of consciousness) were randomly assigned to intravenous progesterone or placebo, with the study treatment initiated within 4 hours after injury and administered for a total of 96 hours. Efficacy was defined as an increase of 10 percentage points in the proportion of patients with a favorable outcome, as determined with the use of the stratified dichotomy of the Extended Glasgow Outcome Scale score at 6 months after injury. Secondary outcomes included mortality and the Disability Rating Scale score. RESULTS A total of 882 of the planned sample of 1140 patients underwent randomization before the trial was stopped for futility with respect to the primary outcome. The study groups were similar with regard to baseline characteristics; the median age of the patients was 35 years, 73.7% were men, 15.2% were black, and the mean Injury Severity Score was 24.4 (on a scale from 0 to 75, with higher scores indicating greater severity). The most frequent mechanism of injury was a motor vehicle accident. There was no significant difference between the progesterone group and the placebo group in the proportion of patients with a favorable outcome (relative benefit of progesterone, 0.95; 95% confidence interval [CI], 0.85 to 1.06; P = 0.35). Phlebitis or thrombophlebitis was more frequent in the progesterone group than in the placebo group (relative risk, 3.03; CI, 1.96 to 4.66). There were no significant differences in the other prespecified safety outcomes. CONCLUSIONS This clinical trial did not show a

  4. The effect of acute alcohol on motor-related EEG asymmetries during preparation of approach or avoid alcohol responses.

    PubMed

    Korucuoglu, Ozlem; Gladwin, Thomas E; Wiers, Reinout W

    2016-02-01

    Alcohol-approach tendencies have been associated with heavy drinking and play a role in the transition to alcohol abuse. Such cognitive biases might predict future alcohol use better under a low dose of alcohol. The aim of this prospective study was to investigate both the magnitude and the predictive power of alcohol-induced changes on approach-avoidance bias and bias-related cortical asymmetries during response preparation across heavy and light drinking adolescents. In heavy drinking adolescents greater approach-related asymmetry index in the beta-band was observed for soft-drink cues compared to alcohol ones and this increase was associated with increase in difficulty to regulate alcohol intake. Earlier findings demonstrated that young heavy drinkers hold both positive and negative implicit alcohol associations, reflecting an ambiguity towards alcohol. The increase in approach related beta-lateralization for soft-drink cues measured in this study may represent a compensatory effort for the weaker S-R mapping (approaching soft drink). The MRAA findings in this study may highlight a mechanism related to overcompensation due to ambivalent attitudes towards drinking in our heavy drinking sample who had greater problems to limit their alcohol intake compared to light drinkers. Moreover, a relatively strong approach soft-drink and weak approach alcohol reaction-time bias after alcohol predicted decreasing drinking; suggesting that the capacity to control the bias under alcohol could be a protective factor. PMID:26762699

  5. Brain and muscle redox imbalance elicited by acute ethylmalonic acid administration.

    PubMed

    Schuck, Patrícia Fernanda; Milanez, Ana Paula; Felisberto, Francine; Galant, Leticia Selinger; Machado, Jéssica Luca; Furlanetto, Camila Brulezi; Petronilho, Fabricia; Dal-Pizzol, Felipe; Streck, Emilio Luiz; Ferreira, Gustavo Costa

    2015-01-01

    Ethylmalonic acid (EMA) accumulates in tissues and biological fluids of patients affected by short-chain acyl-CoA dehydrogenase deficiency (SCADD) and ethylmalonic encephalopathy, illnesses characterized by neurological and muscular symptoms. Considering that the mechanisms responsible for the brain and skeletal muscle damage in these diseases are poorly known, in the present work we investigated the effects of acute EMA administration on redox status parameters in cerebral cortex and skeletal muscle from 30-day-old rats. Animals received three subcutaneous injections of EMA (6 μmol/g; 90 min interval between injections) and were killed 1 h after the last administration. Control animals received saline in the same volumes. EMA administration significantly increased thiobarbituric acid-reactive substances levels in cerebral cortex and skeletal muscle, indicating increased lipid peroxidation. In addition, carbonyl content was increased in EMA-treated animal skeletal muscle when compared to the saline group. EMA administration also significantly increased 2',7'-dihydrodichlorofluorescein oxidation and superoxide production (reactive species markers), and decreased glutathione peroxidase activity in cerebral cortex, while glutathione levels were decreased only in skeletal muscle. On the other hand, respiratory chain complex I-III activity was altered by acute EMA administration neither in cerebral cortex nor in skeletal muscle. The present results show that acute EMA administration elicits oxidative stress in rat brain and skeletal muscle, suggesting that oxidative damage may be involved in the pathophysiology of the brain and muscle symptoms found in patients affected by SCADD and ethylmalonic encephalopathy.

  6. Brain and muscle redox imbalance elicited by acute ethylmalonic acid administration.

    PubMed

    Schuck, Patrícia Fernanda; Milanez, Ana Paula; Felisberto, Francine; Galant, Leticia Selinger; Machado, Jéssica Luca; Furlanetto, Camila Brulezi; Petronilho, Fabricia; Dal-Pizzol, Felipe; Streck, Emilio Luiz; Ferreira, Gustavo Costa

    2015-01-01

    Ethylmalonic acid (EMA) accumulates in tissues and biological fluids of patients affected by short-chain acyl-CoA dehydrogenase deficiency (SCADD) and ethylmalonic encephalopathy, illnesses characterized by neurological and muscular symptoms. Considering that the mechanisms responsible for the brain and skeletal muscle damage in these diseases are poorly known, in the present work we investigated the effects of acute EMA administration on redox status parameters in cerebral cortex and skeletal muscle from 30-day-old rats. Animals received three subcutaneous injections of EMA (6 μmol/g; 90 min interval between injections) and were killed 1 h after the last administration. Control animals received saline in the same volumes. EMA administration significantly increased thiobarbituric acid-reactive substances levels in cerebral cortex and skeletal muscle, indicating increased lipid peroxidation. In addition, carbonyl content was increased in EMA-treated animal skeletal muscle when compared to the saline group. EMA administration also significantly increased 2',7'-dihydrodichlorofluorescein oxidation and superoxide production (reactive species markers), and decreased glutathione peroxidase activity in cerebral cortex, while glutathione levels were decreased only in skeletal muscle. On the other hand, respiratory chain complex I-III activity was altered by acute EMA administration neither in cerebral cortex nor in skeletal muscle. The present results show that acute EMA administration elicits oxidative stress in rat brain and skeletal muscle, suggesting that oxidative damage may be involved in the pathophysiology of the brain and muscle symptoms found in patients affected by SCADD and ethylmalonic encephalopathy. PMID:26010931

  7. Brain and Muscle Redox Imbalance Elicited by Acute Ethylmalonic Acid Administration

    PubMed Central

    Schuck, Patrícia Fernanda; Milanez, Ana Paula; Felisberto, Francine; Galant, Leticia Selinger; Machado, Jéssica Luca; Furlanetto, Camila Brulezi; Petronilho, Fabricia; Dal-Pizzol, Felipe; Streck, Emilio Luiz; Ferreira, Gustavo Costa

    2015-01-01

    Ethylmalonic acid (EMA) accumulates in tissues and biological fluids of patients affected by short-chain acyl-CoA dehydrogenase deficiency (SCADD) and ethylmalonic encephalopathy, illnesses characterized by neurological and muscular symptoms. Considering that the mechanisms responsible for the brain and skeletal muscle damage in these diseases are poorly known, in the present work we investigated the effects of acute EMA administration on redox status parameters in cerebral cortex and skeletal muscle from 30-day-old rats. Animals received three subcutaneous injections of EMA (6 μmol/g; 90 min interval between injections) and were killed 1 h after the last administration. Control animals received saline in the same volumes. EMA administration significantly increased thiobarbituric acid-reactive substances levels in cerebral cortex and skeletal muscle, indicating increased lipid peroxidation. In addition, carbonyl content was increased in EMA-treated animal skeletal muscle when compared to the saline group. EMA administration also significantly increased 2’,7’-dihydrodichlorofluorescein oxidation and superoxide production (reactive species markers), and decreased glutathione peroxidase activity in cerebral cortex, while glutathione levels were decreased only in skeletal muscle. On the other hand, respiratory chain complex I-III activity was altered by acute EMA administration neither in cerebral cortex nor in skeletal muscle. The present results show that acute EMA administration elicits oxidative stress in rat brain and skeletal muscle, suggesting that oxidative damage may be involved in the pathophysiology of the brain and muscle symptoms found in patients affected by SCADD and ethylmalonic encephalopathy. PMID:26010931

  8. Ecological Momentary Assessment of Acute Alcohol Use Disorder Symptoms: Associations With Mood, Motives, and Use on Planned Drinking Days

    PubMed Central

    Dvorak, Robert D.; Pearson, Matthew R.; Day, Anne M.

    2015-01-01

    Several theories posit that alcohol is consumed both in relation to one’s mood and in relation to different motives for drinking. However, there are mixed findings regarding the role of mood and motives in predicting drinking. Ecological momentary assessment (EMA) methods provide an opportunity to evaluate near real-time changes in mood and motives within individuals to predict alcohol use. In addition, endorsement of criteria of an alcohol use disorder (AUD) may also be sensitive to changes within subjects. The current study used EMA with 74 moderate drinkers who responded to fixed and random mood, motive, alcohol use, and AUD criteria prompts over a 21-day assessment period. A temporal pattern of daytime mood, evening drinking motivation, and nighttime alcohol use and acute AUD symptoms on planned drinking days was modeled to examine how these associations unfold throughout the day. The results suggest considerable heterogeneity in drinking motivation across drinking days. Additionally, an affect regulation model of drinking to cope with negative mood was observed. Specifically, on planned drinking days, the temporal association between daytime negative mood and the experience of acute AUD symptoms was mediated via coping motives and alcohol use. The current study found that motives are dynamic, and that changes in motives may predict differential drinking patterns across days. Further, the study provides evidence that emotion-regulation-driven alcohol involvement may need to be examined at the event level to fully capture the ebb and flow of negative affect motivated drinking. PMID:24932896

  9. Ethanol administration dampens the prolactin response to psychosocial stress exposure in sons of alcohol-dependent fathers.

    PubMed

    Zimmermann, Ulrich S; Buchmann, Arlette F; Spring, Constance; Uhr, Manfred; Holsboer, Florian; Wittchen, Hans-Ulrich

    2009-08-01

    Genetic predisposition and exposure to alcohol and stress increase the risk for alcoholism, possibly by forming a threefold interaction. This is suggested by various aspects of alcohol-induced stress response dampening in offspring of alcoholics. We tested whether such an interaction is also revealed by prolactin secretion, which is predominantly controlled by hypothalamic dopamine. Plasma prolactin was measured during four experimental days in 26 young males with a paternal history of alcoholism (PHA) and in 22 family history negative (FHN) controls. A public speaking stress paradigm was applied on the first 2 days, and a non-stress acoustic startle experiment on the others. Before the tests, subjects drank alcohol (0.6 g/kg) or placebo in a randomized, double-blind crossover design. During placebo experiments, prolactin levels significantly increased after stress, but not after startle, and did not differ between risk groups. Alcohol administration significantly increased prolactin before stress and during startle in both groups, did not alter stress-induced prolactin stimulation in FHN, but significantly attenuated the prolactin stress response in PHA subjects. The alcohol effects on prolactin, cortisol, and adrenocorticotropin stress response were positively interrelated with each other. These data confirm that alcohol specifically dampens the stress response in PHA but not FHN subjects. Since prolactin responses to stress alone and alcohol alone were normal in PHA, we conclude that this genetic effect is not related to altered physiology of the hypothalamic dopaminergic system, but to risk-group specific alcohol effects on hierarchically higher brain areas controlling the stress response in general. PMID:19243891

  10. TISSUE DISPOSITION OF DIMETHYLARSINIC ACID IN THE MOUSE AFTER ACUTE ORAL ADMINISTRATION

    EPA Science Inventory

    TISSUE DISPOSITION OF DIMETHYLARSINIC ACID IN THE MOUSE
    AFTER ACUTE ORAL ADMINISTRATION

    Michael F. Hughes, Ph.D., Brenda C. Edwards, Carol T. Mitchell and Elaina M. Kenyon, Ph.D. United States Environmental Protection Agency, Office of Research and Development, Nation...

  11. Acute and subchronic administration of anandamide or oleamide increases REM sleep in rats.

    PubMed

    Herrera-Solís, Andrea; Vásquez, Khalil Guzmán; Prospéro-García, Oscar

    2010-03-01

    Anandamide and oleamide, induce sleep when administered acutely, via the CB1 receptor. Their subchronic administration must be tested to demonstrate the absence of tolerance to this effect, and that the sudden withdrawal of these endocannabinoids (eCBs) does not affect sleep negatively. The sleep-waking cycle of rats was evaluated for 24h, under the effect of an acute or subchronic administration of eCBs, and during sudden eCBs withdrawal. AM251, a CB1 receptor antagonist (CB1Ra) was utilized to block eCBs effects. Our results indicated that both acute and subchronic administration of eCBs increase REMS. During eCBs withdrawal, rats lack the expression of an abstinence-like syndrome. AM251 was efficacious to prevent REMS increase caused by both acute and subchronic administration of these eCBs, suggesting that this effect is mediated by the CB1 receptor. Our data further support a role of the eCBs in REMS regulation.

  12. Acute encephalomyelitis complicated with severe neurological sequelae after intrathecal administration of methotrexate in a patient with acute lymphoblastic leukemia.

    PubMed

    Nishikawa, Takuro; Okamoto, Yasuhiro; Maruyama, Shinsuke; Tanabe, Takayuki; Kurauchi, Koichiro; Kodama, Yuichi; Nakagawa, Shunsuke; Shinkoda, Yuichi; Kawano, Yoshifumi

    2014-11-01

    A four-year-old girl on maintenance therapy for acute lymphoblastic leukemia (ALL) complained of a headache and low back pain on the day she received her 21st intrathecal methotrexate (it-MTX) administration, and the next day experienced numbness and pain in her foot. This numbness gradually spread to her hand. She thereafter developed a fever and was hospitalized on day 8. After antibiotic therapy, the fever disappeared. However, her lower limbs became paralyzed, and she also developed urinary retention. On day 12, her paralysis progressed upwards, and she also developed paralysis of the upper limbs. Finally, she experienced convulsions with an impairment of consciousness. A magnetic resonance imaging study of the brain and spinal cord showed abnormal signals in the brain cortex and anterior horn. Accordingly, we diagnosed acute encephalomyelitis associated with it-MTX. High-dose intravenous immunoglobulin, steroid pulse therapy, plasma exchange, and dextromethorphan administration were initiated, while she received mechanical ventilation. Despite this intensive treatment, she suffered severe neurological damage and had to be maintained on mechanical ventilation due to persistent flaccid quadriplegia one year after the onset. When patients have symptoms of ascending paralysis during it-MTX treatment, clinicians should carefully consider the possibility of acute encephalomyelitis due to it-MTX. PMID:25501412

  13. Effects of varenicline on operant self-administration of alcohol and/or nicotine in a rat model of co-abuse.

    PubMed

    Funk, D; Lo, S; Coen, K; Lê, A D

    2016-01-01

    Alcohol and nicotine (in the form of tobacco) are often taken together, with increased negative health consequences. Co-use may modify intake of one or both of the drugs, or the effects of drugs used to treat nicotine or alcohol addiction. Varenicline is commonly prescribed as an aid to enhance quitting smoking. More recently it has been shown to reduce alcohol intake in humans and laboratory animals. There is little work investigating the role of co-exposure to alcohol and nicotine in the effects of varenicline. In pilot clinical studies, it has been reported that smoking enhances varenicline's effectiveness as a treatment for alcohol misuse, but this relationship has not been systematically investigated. To help resolve this, we examined if the effects of varenicline on alcohol and nicotine self-administration (SA) in rats are modified when the two drugs are taken together. Rats were trained on alcohol SA, and some were implanted with i.v. catheters for nicotine SA. Groups of animals then lever pressed for alcohol or nicotine alone, and another group lever pressed for alcohol and nicotine, using a two lever choice procedure. Varenicline did not affect alcohol SA. Varenicline reduced nicotine SA modestly. Access to both alcohol and nicotine reduced self-administration of either drug, but did not change the effects of varenicline. We found that in rats with a history of alcohol SA, varenicline reduced reinstatement of extinguished alcohol seeking induced by exposure to an alcohol prime combined with cues previously associated with alcohol.

  14. Effects of varenicline on operant self-administration of alcohol and/or nicotine in a rat model of co-abuse.

    PubMed

    Funk, D; Lo, S; Coen, K; Lê, A D

    2016-01-01

    Alcohol and nicotine (in the form of tobacco) are often taken together, with increased negative health consequences. Co-use may modify intake of one or both of the drugs, or the effects of drugs used to treat nicotine or alcohol addiction. Varenicline is commonly prescribed as an aid to enhance quitting smoking. More recently it has been shown to reduce alcohol intake in humans and laboratory animals. There is little work investigating the role of co-exposure to alcohol and nicotine in the effects of varenicline. In pilot clinical studies, it has been reported that smoking enhances varenicline's effectiveness as a treatment for alcohol misuse, but this relationship has not been systematically investigated. To help resolve this, we examined if the effects of varenicline on alcohol and nicotine self-administration (SA) in rats are modified when the two drugs are taken together. Rats were trained on alcohol SA, and some were implanted with i.v. catheters for nicotine SA. Groups of animals then lever pressed for alcohol or nicotine alone, and another group lever pressed for alcohol and nicotine, using a two lever choice procedure. Varenicline did not affect alcohol SA. Varenicline reduced nicotine SA modestly. Access to both alcohol and nicotine reduced self-administration of either drug, but did not change the effects of varenicline. We found that in rats with a history of alcohol SA, varenicline reduced reinstatement of extinguished alcohol seeking induced by exposure to an alcohol prime combined with cues previously associated with alcohol. PMID:26365457

  15. A randomised controlled trial of extended brief intervention for alcohol dependent patients in an acute hospital setting (ADPAC)

    PubMed Central

    2011-01-01

    Background Alcohol dependence affects approximately 3% of the English population, and accounts for significant medical and psychiatric morbidity. Only 5.6% of alcohol-dependent individuals ever access specialist treatment and only a small percentage ever seek treatment. As people who are alcohol dependent are more likely to have experienced health problems leading to frequent attendance at acute hospitals it would seem both sensible and practical to ensure that this setting is utilised as a major access point for treatment, and to test the effectiveness of these treatments. Methods/Design This is a randomised controlled trial with a primary hypothesis that extended brief interventions (EBI) delivered to alcohol-dependent patients in a hospital setting by an Alcohol Specialist Nurse (ASN) will be effective when compared to usual care in reducing overall alcohol consumption and improving on the standard measures of alcohol dependence. Consecutive patients will be screened for alcohol misuse in the Emergency Department (ED) of a district general hospital. On identification of an alcohol-related problem, following informed written consent, we aim to randomize 130 patients per group. The ASN will discharge to usual clinical care all control group patients, and plan a programme of EBI for treatment group patients. Follow-up interview will be undertaken by a researcher blinded to the intervention at 12 and 24 weeks. The primary outcome measure is level of alcohol dependence as determined by the Severity of Alcohol Dependence Questionnaire (SADQ) score. Secondary outcome measures include; Alcohol Use Disorders Identification Test (AUDIT) score, quantity and frequency of alcohol consumption, health-related quality of life measures, service utilisation, and patient experience. The trial will also allow an assessment of the cost-effectiveness of EBI in an acute hospital setting. In addition, patient experience will be assessed using qualitative methods. Discussion This paper

  16. Liver, plasma and erythrocyte levels of thiamine and its phosphate esters in rats with acute ethanol intoxication: a comparison of thiamine and benfotiamine administration.

    PubMed

    Portari, Guilherme Vannucchi; Vannucchi, Helio; Jordao, Alceu Afonso

    2013-03-12

    Thiamine and benfotiamine are vitamin B1 and pro-vitamin B1 substances, respectively. Vitamin B1 plays an essential role in energy metabolism, and its deficiency leads to neurologic and cardiovascular pathologies, as seen in alcoholics. This study presents new data about the effects of thiamine hydrochloride or benfotiamine treatment given to rats with acute alcohol intoxication, on the distribution of thiamine and its phosphate esters in liver, plasma and erythrocytes. The treatments were effective in increasing thiamine levels in plasma, erythrocytes and liver cells. The benfotiamine-treated group had its total plasma thiamine increased by 100%. In erythrocytes, thiamine levels were 4- and 25-fold higher in the groups treated with thiamine and benfotiamine, respectively, compared with the untreated groups. Liver thiamine was increased by 60% in the treated groups compared with the untreated groups. Thus, we verified the high bioavailability especially of benfotiamine within 6h of ethanol administration.

  17. Phosphorus-31 nuclear magnetic resonance spectroscopic study of the canine pancreas: applications to acute alcoholic pancreatitis

    SciTech Connect

    Janes, N.; Clemens, J.A.; Glickson, J.D.; Cameron, J.L.

    1988-01-01

    The first nuclear magnetic resonance spectroscopic study of the canine pancreas is described. Both in-vivo, ex-vivo protocols and NMR observables are discussed. The stability of the ex-vivo preparation based on the NMR observables is established for at least four hours. The spectra obtained from the in-vivo and ex-vivo preparations exhibited similar metabolite ratios, further validating the model. Metabolite levels were unchanged by a 50% increase in perfusion rate. Only trace amounts of phosphocreatine were observed either in the intact gland or in extracts. Acute alcoholic pancreatitis was mimicked by free fatty acid infusion. Injury resulted in hyperamylasemia, edema (weight gain), increased hematocrit and perfusion pressure, and depressed levels of high energy phosphates.

  18. Polyethylene glycol-polyvinyl alcohol grafted copolymer: study of the bioavailability after oral administration to rats.

    PubMed

    Heuschmid, Franziska F; Schuster, Paul; Lauer, Birthe; Fabian, Eric; Leibold, Edgar; van Ravenzwaay, Bennard

    2013-07-01

    The absorption, urinary excretion, and the biliary excretion of a single oral dose of 10 or 1000 mg/kg bw of (14)C-polyethylene glycol-polyvinyl alcohol (PEG-PVA) grafted copolymer were studied in adult male and female rats. In a balance/excretion experiment, the total excretion of ingested radioactivity was determined over a period of 168 h and residual radioactivity was detected in selected tissues and the carcass. In a biliary excretion experiment, excretion of radioactivity via the bile duct was determined over a period of 48 h after administration of the substance to cannulated rats. Most, if not all, of the radioactivity (>100%) was excreted within 48 h via the feces regardless of sex or dose. Urinary excretion was very limited: 0.45-0.50% of dose at the low dose and 0.22-0.27% of dose at the high dose. At both dose levels, residual radioactivity in the carcass and all organs and tissues after 168 h was ≤ 0.02% of dose. Biliary excretion was 0.01-0.02% of dose. Based on these findings, the bioavailability of PEG-PVA grafted copolymer was determined to be <1% demonstrating that absorption was virtually negligible following a single oral administration to male and female rats. PMID:23321424

  19. Polyethylene glycol-polyvinyl alcohol grafted copolymer: study of the bioavailability after oral administration to rats.

    PubMed

    Heuschmid, Franziska F; Schuster, Paul; Lauer, Birthe; Fabian, Eric; Leibold, Edgar; van Ravenzwaay, Bennard

    2013-07-01

    The absorption, urinary excretion, and the biliary excretion of a single oral dose of 10 or 1000 mg/kg bw of (14)C-polyethylene glycol-polyvinyl alcohol (PEG-PVA) grafted copolymer were studied in adult male and female rats. In a balance/excretion experiment, the total excretion of ingested radioactivity was determined over a period of 168 h and residual radioactivity was detected in selected tissues and the carcass. In a biliary excretion experiment, excretion of radioactivity via the bile duct was determined over a period of 48 h after administration of the substance to cannulated rats. Most, if not all, of the radioactivity (>100%) was excreted within 48 h via the feces regardless of sex or dose. Urinary excretion was very limited: 0.45-0.50% of dose at the low dose and 0.22-0.27% of dose at the high dose. At both dose levels, residual radioactivity in the carcass and all organs and tissues after 168 h was ≤ 0.02% of dose. Biliary excretion was 0.01-0.02% of dose. Based on these findings, the bioavailability of PEG-PVA grafted copolymer was determined to be <1% demonstrating that absorption was virtually negligible following a single oral administration to male and female rats.

  20. A case of acute respiratory failure in a rheumatoid arthritis patient after the administration of abatacept

    PubMed Central

    Doğu, Birsen; Atilla, Nurhan; Çetin, Gözde Yıldırım; Yılmaz, Nezir; Öksüz, Hafize

    2016-01-01

    Drug-induced pulmonary disease is an important consideration in the differential diagnosis of patients with rheumatoid arthritis (RA) who present with respiratory symptoms. We report a patient with RA who developed acute respiratory failure two weeks after the administration of abatacept. The clinical findings were consistent with drug-induced acute respiratory failure, most likely acute eosinophilic pneumonia. Pulse steroid was administered at 1000 mg/kg/day in the emergency department. Chest X-ray and arterial blood gas values revealed significant improvement on the second day of hospitalization. However, in the second week, the patient’s fever rose up to 40°C, procalcitonin level increased to 15 ng/mL (<0.5 ng/mL is normal), and the patient died because of sepsis in the fourth week. This is the second report of respiratory failure, after the abatacept administration in the literature. We have reported an acute respiratory failure that occurred after use of the biological agent abatacept. With the increasing use of novel immunomodulatory agents, it is important for clinicians and pathologists to add the possibility of a drug reaction to the traditional differentials of acute respiratory failures occurring in these settings. PMID:27733944

  1. Acute alcohol consumption aggravates the decline in muscle performance following strenuous eccentric exercise.

    PubMed

    Barnes, Matthew J; Mündel, Toby; Stannard, Stephen R

    2010-01-01

    This study investigated the effects of acute moderate alcohol intake on muscular performance during recovery from eccentric exercise-induced muscle damage. Eleven healthy males performed 300 maximal eccentric contractions of the quadriceps muscles of one leg on an isokinetic dynamometer. They then consumed a beverage containing 1g/kg bodyweight ethanol (as vodka and orange juice) (ALC). On another occasion they performed an equivalent bout of eccentric exercise on the contralateral leg after which they consumed an isocaloric quantity of orange juice (OJ). Measurement of maximal isokinetic (concentric and eccentric) and isometric torque produced across the knee, plasma creatine kinase (CK) concentrations and muscle soreness were made before and at 36 and 60h following each exercise bout. All measures of muscle performance were significantly reduced at 36 and 60h post-exercise compared to pre-exercise measures (all p<0.05). The greatest decreases in peak strength were observed at 36h with losses of 12%, 28% and 19% occurring for OJ isometric, concentric, and eccentric contractions, respectively. However, peak strength loss was significantly greater in ALC with the same performance measures decreasing by 34%, 40% and 34%, respectively. Post-exercise plasma creatine kinase activity and ratings of muscle soreness were not different between conditions (both p>0.05). These results indicate that consumption of even moderate amounts of alcohol following eccentric-based exercise magnifies the normally observed losses in dynamic and static strength. Therefore, to minimise exercise related losses in muscle function and expedite recovery, participants in sports involving eccentric muscle work should avoid alcohol-containing beverages in the post-event period. PMID:19230764

  2. Effects of acute and chronic administration of methylprednisolone on oxidative stress in rat lungs* **

    PubMed Central

    Torres, Ronaldo Lopes; Torres, Iraci Lucena da Silva; Laste, Gabriela; Ferreira, Maria Beatriz Cardoso; Cardoso, Paulo Francisco Guerreiro; Belló-Klein, Adriane

    2014-01-01

    Objective: To determine the effects of acute and chronic administration of methylprednisolone on oxidative stress, as quantified by measuring lipid peroxidation (LPO) and total reactive antioxidant potential (TRAP), in rat lungs. Methods: Forty Wistar rats were divided into four groups: acute treatment, comprising rats receiving a single injection of methylprednisolone (50 mg/kg i.p.); acute control, comprising rats i.p. injected with saline; chronic treatment, comprising rats receiving methylprednisolone in drinking water (6 mg/kg per day for 30 days); and chronic control, comprising rats receiving normal drinking water. Results: The levels of TRAP were significantly higher in the acute treatment group rats than in the acute control rats, suggesting an improvement in the pulmonary defenses of the former. The levels of lung LPO were significantly higher in the chronic treatment group rats than in the chronic control rats, indicating oxidative damage in the lung tissue of the former. Conclusions: Our results suggest that the acute use of corticosteroids is beneficial to lung tissue, whereas their chronic use is not. The chronic use of methylprednisolone appears to increase lung LPO levels. PMID:25029646

  3. Endovascular Treatment of Acute Arterial Hemorrhage in Trauma Patients Using Ethylene Vinyl Alcohol Copolymer (Onyx)

    SciTech Connect

    Mueller-Wille, R. Heiss, P.; Herold, T.; Jung, E. M. Schreyer, A. G. Hamer, O. W. Rennert, J. Hoffstetter, P. Stroszczynski, C.; Zorger, N.

    2012-02-15

    Purpose: This study was designed to determine the feasibility and efficacy of endovascular embolization with liquid embolic agent ethylene vinyl alcohol copolymer (Onyx) in patients with acute traumatic arterial bleeding. Methods: This is a retrospective review of 13 patients (9 men and 4 women; mean age 45 years) with severe trauma who underwent embolotherapy using Onyx from November 2003 to February 2009. Bleeding was located in the pelvis (5 patients), kidney (3 patients), mesenteric region (2 patients), retroperitoneal space (2 patients), neck (1 patient), and thigh (1 patient). In three cases (23.1%), Onyx was used in conjunction with coils. We evaluate the technical and clinical success, procedural and embolization time, occurrence of rebleeding, and embolotherapy-related complications, such as necrosis or migration of Onyx into nontarget vessels. Results: In all patients, embolotherapy was technically and clinically successful on the first attempt. Control of bleeding could be reached with a mean time of 19 (range, 4-63) min after correct placement of the microcatheter in the feeding artery. No recurrent bleeding was detected. No unintended necrosis or migration of Onyx into a nontarget region was observed. During the follow-up period, three patients (23.1%) died due to severe intracranial hemorrhage, cardiac arrest, and sepsis. Conclusions: Transcatheter embolization with new liquid embolic agent Onyx is technically feasible and effective in trauma patients with acute arterial hemorrhage.

  4. Vitamin D supplementation protects against bone loss associated with chronic alcohol administration in female mice

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Chronic alcohol consumption is detrimental to bone by decreasing bone mineral density (BMD) resulting in increased risk of osteoporosis risk and fracture, particularly in women. In moderation, alcohol is positively associated with increased BMD and reduced fracture risk. Alcohol's toxic effects ha...

  5. Alcohol.

    ERIC Educational Resources Information Center

    Schibeci, Renato

    1996-01-01

    Describes the manufacturing of ethanol, the effects of ethanol on the body, the composition of alcoholic drinks, and some properties of ethanol. Presents some classroom experiments using ethanol. (JRH)

  6. Acute versus subchronic pyridostigmine administration: Effects on the anticholinergic properties of atropine

    SciTech Connect

    Matthew, C.B.; Glenn, J.F.; Bowers, W.D.

    1993-05-13

    Acute, subchronic and chronic exposures to cholinergic compounds may result in differing effects. The efficacy of pyridostigmine bromide (PY) prophylaxis against organophosphorus poisoning depends on post exposure atropine (AT) administration. AT induces a dose-dependent increase in rate of rise of core temperature in heat exposed humans and rats. To determine whether AT's anticholinergic potency is altered following PY administration, we examined AT's effects following acute or subchronic (2 weeks) PY administration in the sedentary heat-stressed rat. Unrestrained rats were used in the following 8 groups of 12: acute (a,2 injections via tail vein) aSAL+SAL, aSAL+AT, aPY+SAL, aPY+AT; subchronic (c, osmotic pump + tail vein) cSAL+SAL, cSAL+AT, cPY+SAL, cPY+AT (SAL- saline, AT- 200 ug/kg, aPY- 100 ug/kg, cPY- 20 ug/hr.) Fifteen minutes following the final injection, rats were subjected to an ambient temperature of 41.5 deg C until a core temperature of 42.6 deg C was attained.

  7. Brief motivational intervention for adolescents treated in emergency departments for acute alcohol intoxication – a randomized-controlled trial

    PubMed Central

    2014-01-01

    Background Alcohol misuse among youth is a major public health concern and numbers of adolescents admitted to the emergency department for acute alcoholic intoxication in Germany are recently growing. The emergency setting offers an opportunity to reach at-risk alcohol consuming adolescents and provide brief interventions in a potential “teachable moment”. However, studies on brief interventions targeting adolescents in emergency care are scarce and little is known about their effectiveness when delivered immediately following hospitalization for acute alcohol intoxication. In this protocol we present the HaLT-Hamburg trial evaluating a brief motivational intervention for adolescents treated in the emergency department after an episode of acute alcoholic intoxication. Methods The trial design is a parallel two-arm cluster randomized-controlled trial with follow-up assessment after 3 and 6 months. N = 312 participants aged 17 years and younger will be recruited Fridays to Sundays in 6 pediatric clinics over a period of 30 months. Intervention condition is a manual-based brief motivational intervention with a telephone booster after 6 weeks and a manual-guided intervention for caregivers which will be compared to treatment as usual. Primary outcomes are reduction in binge drinking episodes, quantity of alcohol use on a typical drinking day and alcohol-related problems. Secondary outcome is further treatment seeking. Linear mixed models adjusted for baseline differences will be conducted according to intention-to-treat (ITT) and completers (per-protocol) principles to examine intervention effects. We also examine quantitative and qualitative process data on feasibility, intervention delivery, implementation and receipt from intervention providers, receivers and regular emergency department staff. Discussion The study has a number of strengths. First, a rigorous evaluation of HaLT-Hamburg is timely because variations of the HaLT project are widely used in

  8. Serum Metabolomic Profiling in Acute Alcoholic Hepatitis Identifies Multiple Dysregulated Pathways

    PubMed Central

    Rachakonda, Vikrant; Gabbert, Charles; Raina, Amit; Bell, Lauren N.; Cooper, Sara; Malik, Shahid; Behari, Jaideep

    2014-01-01

    Background and Objectives While animal studies have implicated derangements of global energy homeostasis in the pathogenesis of acute alcoholic hepatitis (AAH), the relevance of these findings to the development of human AAH remains unclear. Using global, unbiased serum metabolomics analysis, we sought to characterize alterations in metabolic pathways associated with severe AAH and identify potential biomarkers for disease prognosis. Methods This prospective, case-control study design included 25 patients with severe AAH and 25 ambulatory patients with alcoholic cirrhosis. Serum samples were collected within 24 hours of the index clinical encounter. Global, unbiased metabolomics profiling was performed. Patients were followed for 180 days after enrollment to determine survival. Results Levels of 234 biochemicals were altered in subjects with severe AAH. Random-forest analysis, principal component analysis, and integrated hierarchical clustering methods demonstrated that metabolomics profiles separated the two cohorts with 100% accuracy. Severe AAH was associated with enhanced triglyceride lipolysis, impaired mitochondrial fatty acid beta oxidation, and upregulated omega oxidation. Low levels of multiple lysolipids and related metabolites suggested decreased plasma membrane remodeling in severe AAH. While most measured bile acids were increased in severe AAH, low deoxycholate and glycodeoxycholate levels indicated intestinal dysbiosis. Several changes in substrate utilization for energy homeostasis were identified in severe AAH, including increased glucose consumption by the pentose phosphate pathway, altered tricarboxylic acid (TCA) cycle activity, and enhanced peptide catabolism. Finally, altered levels of small molecules related to glutathione metabolism and antioxidant vitamin depletion were observed in patients with severe AAH. Univariable logistic regression revealed 15 metabolites associated with 180-day survival in severe AAH. Conclusion Severe AAH is

  9. Effects of acute and chronic administration of neurosteroid dehydroepiandrosterone sulfate on neuronal excitability in mice

    PubMed Central

    Svob Strac, Dubravka; Vlainic, Josipa; Samardzic, Janko; Erhardt, Julija; Krsnik, Zeljka

    2016-01-01

    Background Neurosteroid dehydroepiandrosterone sulfate (DHEAS) has been associated with important brain functions, including neuronal survival, memory, and behavior, showing therapeutic potential in various neuropsychiatric and cognitive disorders. However, the antagonistic effects of DHEAS on γ-amino-butyric acidA receptors and its facilitatory action on glutamatergic neurotransmission might lead to enhanced brain excitability and seizures and thus limit DHEAS therapeutic applications. The aim of this study was to investigate possible age and sex differences in the neuronal excitability of the mice following acute and chronic DHEAS administration. Methods DHEAS was administered intraperitoneally in male and female adult and old mice either acutely or repeatedly once daily for 4 weeks in a 10 mg/kg dose. To investigate the potential proconvulsant properties of DHEAS, we studied the effects of acute and chronic DHEAS treatment on picrotoxin-, pentylentetrazole-, and N-methyl-D-aspartate-induced seizures in mice. The effects of acute and chronic DHEAS administration on the locomotor activity, motor coordination, and body weight of the mice were also studied. We also investigated the effects of DHEAS treatment on [3H]flunitrazepam binding to the mouse brain membranes. Results DHEAS did not modify the locomotor activity, motor coordination, body weight, and brain [3H]flunitrazepam binding of male and female mice. The results failed to demonstrate significant effects of single- and long-term DHEAS treatment on the convulsive susceptibility in both adult and aged mice of both sexes. However, small but significant changes regarding sex differences in the susceptibility to seizures were observed following DHEAS administration to mice. Conclusion Although our findings suggest that DHEAS treatment might be safe for various potential therapeutic applications in adult as well as in old age, they also support subtle interaction of DHEAS with male and female hormonal status

  10. Changes in heart rate variability associated with acute alcohol consumption: current knowledge and implications for practice and research.

    PubMed

    Romanowicz, Magdalena; Schmidt, John E; Bostwick, John M; Mrazek, David A; Karpyak, Victor M

    2011-06-01

    Alcohol consumption is associated with a broad array of physiologic and behavioral effects including changes in heart rate. However, the physiologic mechanisms of alcohol effects and the reasons for individual differences in the cardiac response remain unknown. Measuring changes in resting heart rate (measured as beats/min) has not been found to be as sensitive to alcohol's effects as changes in heart rate variability (HRV). HRV is defined as fluctuations in interbeat interval length which reflect the heart's response to extracardiac factors that affect heart rate. HRV allows simultaneous assessment of both sympathetic and parasympathetic activity and the interplay between them. Increased HRV has been associated with exercise and aerobic fitness, while decreased HRV has been associated with aging, chronic stress, and a wide variety of medical and psychiatric disorders. Decreased HRV has predictive value for mortality in general population samples and patients with myocardial infarction and used as an indicator of altered autonomic function. A significant inverse correlation was found between HRV and both the severity of depression and the duration of the depressive episode. HRV analysis provides insights into mechanisms of autonomic regulation and is extensively used to clarify relationships between depression and cardiovascular disease. This article will review the methodology of HRV measurements and contemporary knowledge about effects of acute alcohol consumption on HRV. Potential implications of this research include HRV response to alcohol that could serve as a marker for susceptibility to alcoholism. At present however there is almost no research data supporting this hypothesis. PMID:21332532

  11. Is albumin administration in the acutely ill associated with increased mortality? Results of the SOAP study

    PubMed Central

    Vincent, Jean-Louis; Sakr, Yasser; Reinhart, Konrad; Sprung, Charles L; Gerlach, Herwig; Ranieri, V Marco

    2005-01-01

    Introduction Albumin administration in the critically ill has been the subject of some controversy. We investigated the use of albumin solutions in European intensive care units (ICUs) and its relationship to outcome. Methods In a cohort, multicenter, observational study, all patients admitted to one of the participating ICUs between 1 May and 15 May 2002 were followed up until death, hospital discharge, or for 60 days. Patients were classified according to whether or not they received albumin at any time during their ICU stay. Results Of 3,147 admitted patients, 354 (11.2%) received albumin and 2,793 (88.8%) did not. Patients who received albumin were more likely to have cancer or liver cirrhosis, to be surgical admissions, and to have sepsis. They had a longer length of ICU stay and a higher mortality rate, but were also more severely ill, as manifested by higher simplified acute physiology score (SAPS) II and sequential organ failure assessment (SOFA) scores than the other patients. A Cox proportional hazard model indicated that albumin administration was significantly associated with decreased 30-day survival. Moreover, in 339 pairs matched according to a propensity score, ICU and hospital mortality rates were higher in the patients who had received albumin than in those who had not (34.8 versus 20.9% and 41.3 versus 27.7%, respectively, both p < 0.001). Conclusion Albumin administration was associated with decreased survival in this population of acutely ill patients. Further prospective randomized controlled trials are needed to examine the effects of albumin administration in sub-groups of acutely ill patients. PMID:16356223

  12. Reduced fear-recognition sensitivity following acute buprenorphine administration in healthy volunteers.

    PubMed

    Ipser, Jonathan C; Terburg, David; Syal, Supriya; Phillips, Nicole; Solms, Mark; Panksepp, Jaak; Malcolm-Smith, Susan; Thomas, Kevin; Stein, Dan J; van Honk, Jack

    2013-01-01

    In rodents, the endogenous opioid system has been implicated in emotion regulation, and in the reduction of fear in particular. In humans, while there is evidence that the opioid antagonist naloxone acutely enhances the acquisition of conditioned fear, there are no corresponding data on the effect of opioid agonists in moderating responses to fear. We investigated whether a single 0.2mg administration of the mu-opioid agonist buprenorphine would decrease fear sensitivity with an emotion-recognition paradigm. Healthy human subjects participated in a randomized placebo-controlled within-subject design, in which they performed a dynamic emotion recognition task 120min after administration of buprenorphine and placebo. In the recognition task, basic emotional expressions were morphed between their full expression and neutral in 2% steps, and presented as dynamic video-clips with final frames of different emotional intensity for each trial, which allows for a fine-grained measurement of emotion sensitivity. Additionally, visual analog scales were used to investigate acute effects of buprenorphine on mood. Compared to placebo, buprenorphine resulted in a significant reduction in the sensitivity for recognizing fearful facial expressions exclusively. Our data demonstrate, for the first time in humans, that acute up-regulation of the opioid system reduces fear recognition sensitivity. Moreover, the absence of an effect of buprenorphine on mood provides evidence of a direct influence of opioids upon the core fear system in the human brain. PMID:22651957

  13. Teaching About Alcohol in Connecticut Schools - A Guide for Teachers and Administrators.

    ERIC Educational Resources Information Center

    Sanders, William J.; Bloomberg, Wilfred

    Guidelines for secondary teachers involved in teaching about the use of alcohol are presented. Sections include (1) aims and objectives, (2) content, (3) facts about alcoholism, (4) suggested student activities and teaching procedures, and (5) methods of student evaluation. Selected teacher, student, and supplementary references are listed.…

  14. 78 FR 20890 - Polyvinyl Alcohol From Taiwan: Preliminary Results of Antidumping Duty Administrative Review...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-04-08

    ... established in the Antidumping Duty Order: Polyvinyl Alcohol From Taiwan, 76 FR 13982 (March 15, 2011). These... the antidumping duty order on polyvinyl alcohol (PVA) from Taiwan. The period of review (POR) is... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF...

  15. The effects of time following acute growth hormone administration on metabolic and power output measures during acute exercise.

    PubMed

    Irving, Brian A; Patrie, James T; Anderson, Stacey M; Watson-Winfield, Deidre D; Frick, Kirsten I; Evans, William S; Veldhuis, Johannes D; Weltman, Arthur

    2004-09-01

    We examined the effects of GH infusion on metabolism and performance measures during acute exercise. Nine males [(X+/-SEM): age 23.7+/-1.9 yr, height 182.6+/-1.6 cm, weight 77.3+/- 2.6 kg, percent fat 17.7+/-1.9%, peak oxygen consumption 37.9 +/- 2.9 ml/kg.min] completed six 30-min randomly assigned bicycle ergometer exercise trials at a power output midway between the lactate threshold and peak oxygen consumption. In five of the six trials, the subjects received a recombinant humanGHinfusion (10 microg/kg, 6-min square wave pulse) at 0800 h, followed by a 30-min exercise trial initiated at one of the following times: 0845, 0930, 1015, 1100, or 1145 h. During one of the six trials, the subject received a saline infusion followed by a 30-min exercise trial initiated at 0845 h. Mixed-effect, repeated-measures ANOVA analyses corrected for multiple comparisons revealed that there were no significant condition effects for total work, caloric expenditure, heart rate response, the blood lactate response, or ratings of perceived exertion response. However, acute GH administration resulted in a lower exercise oxygen consumption without a drop-off in power output. We conclude that the time of exercise initiation after GH infusion does not affect total work, caloric expenditure, heart rate response, blood lactate response, or ratings of perceived exertion but reduces oxygen consumption in response to 30 min of constant load exercise at an intensity above the lactate threshold. The last outcome may suggest that GH administration can improve exercise economy.

  16. Acute aquatic toxicity of nine alcohol ethoxylate surfactants to fathead minnow and Daphnia magna

    SciTech Connect

    Wong, D.C.L.; Dorn, P.B.; Chai, E.Y.

    1995-12-31

    The aquatic toxicity of nine commercial-grade alcohol ethoxylate surfactants was studied in acute exposures to fathead minnow (Pimephales promelas) and Daphnia magna. All studies were conducted in accordance with USEPA TSCA Good Laboratory Practice Standards. Mean measured surfactant concentrations in exposure solutions showed good agreement with nominal concentrations for both fathead minnow and daphnid tests. Surfactant recoveries ranged from 59 to 97% and 67 to 106% in the fathead minnow and daphnid solutions, respectively. The response of both species to the surfactants was generally similar with the daphnids being slightly more sensitive to a few surfactants. Surfactant toxicity tended to increase with increasing alkyl chain lengths. The effect of low average EO groups on increased surfactant toxicity was more evident in the daphnid exposures. Quantitative structure-activity relationship (QSAR) models were developed form the data which relates surfactant structure to toxicity. The models predict increasing toxicity with decreasing EO number and increasing alkyl chain length. The models also indicate that alkyl chain length has a greater effect on toxicity than EO groups. Further, the models indicate that both species did not differ markedly in their sensitivity to alkyl chain length effects, while the number of EO groups had a stronger effect on daphnids than fathead minnow. Good agreement was found between QSAR model-predicted toxicity and reported toxicity values from the literature for several surfactants previously studied.

  17. [Impact of acute alcoholism on the women's mortality in the northern region of Slovak Republic].

    PubMed

    Straka, L; Stuller, F; Novomeský, F; Zelený, M

    2009-10-01

    Problem of women's alcoholism doesn't belong among main topics of Slovak or Czech public discussions. Though everyone meeting the phenomenon of women's alcoholism can feel the fatal consequences of this mistake, our society used to perceive alcoholism as a men's problem. The authors performed the complex analysis of the mortuary files with particular focusing on the cases of women's deaths caused by alcohol intoxication, and the cases of deaths where an alcohol played the dominating role, in the northern regions of Slovak republic. Submitted article is author's next referring to urgent need of public discussion concerning the alcohol consumption in Slovakia, the phenomenon being widely tolerated by the society. PMID:20302040

  18. Mu-opioid receptor activation in the medial shell of nucleus accumbens promotes alcohol consumption, self-administration and cue-induced reinstatement.

    PubMed

    Richard, Jocelyn M; Fields, Howard L

    2016-09-01

    Endogenous opioid signaling in ventral cortico-striatal-pallidal circuitry is implicated in elevated alcohol consumption and relapse to alcohol seeking. Mu-opioid receptor activation in the medial shell of the nucleus accumbens (NAc), a region implicated in multiple aspects of reward processing, elevates alcohol consumption while NAc opioid antagonists reduce it. However, the precise nature of the increases in alcohol consumption, and the effects of mu-opioid agonists on alcohol seeking and relapse are not clear. Here, we tested the effects of the mu-opioid agonist [D-Ala(2), N-MePhe(4), Gly-ol]-enkephalin (DAMGO) in rat NAc shell on lick microstructure in a free-drinking test, alcohol seeking during operant self-administration, extinction learning and expression, and cue-reinforced reinstatement of alcohol seeking. DAMGO enhanced the number, but not the size of drinking bouts. DAMGO also enhanced operant alcohol self-administration and cue-induced reinstatement, but did not affect extinction learning or elicit reinstatement in the absence of cues. Our results suggest that mu-opioid agonism in NAc shell elevates alcohol consumption, seeking and conditioned reinforcement primarily by enhancing the incentive motivational properties of alcohol and alcohol-paired cues, rather than by modulating palatability, satiety, or reinforcement. PMID:27089981

  19. Acute hemodynamic effects and blood pool kinetics of polystyrene microspheres following intravenous administration

    SciTech Connect

    Slack, J.D.; Kanke, M.; Simmons, G.H.; DeLuca, P.P.

    1981-06-01

    The acute hemodynamic effect of intravenous administration of polystyrene microspheres was investigated and correlated with their distribution pattern and kinetics. Microspheres of three diameters (3.4, 7.4, and 11.6 micrometer) were administered. The 7.4- and 11.6-micrometer diameter microspheres were filtered by the pulmonary capillary network following intravenous administration, the majority during the first pass. There was no significant hemodynamic effect following administrations of the 7.4- and 11.6-micrometer diameter microspheres in doses as high as 3.0 X 10(9) and 6.1 X 10(8) respectively (total cross-sectional area of 1.3 X 10(11) and 6.4 X 10(10) micrometer2, respectively). Intravenous administration of 3.4-micrometer diameter microspheres produced significant dose-dependent systemic hypotension and depression of myocardial performance at dosages as slow as 1.0 X 10(10) (cross-sectional area of 9.1 X 10(10) micrometer2). These differences in acute hemodynamic effect from the 7.4- and 11.6-micrometer diameter microspheres may be due to the differences in distribution kinetics and fate of the 3.4-micrometer diameter microspheres, which readily pass through the lungs to the spleen. Although elimination of the smaller spheres from the blood during the first 6-8 min was rapid, i.e., t 1/2 . 1.62 and 1.72 min from the venous and arterial blood circulation, respectively, levels of 10(3) spheres/g of blood were present in the circulation for greater than 1 hr. These findings must be considered in the planning of intravenous administration of microspheres as a drug delivery system to target organs.

  20. Serotonin-3 receptors in the posterior ventral tegmental area regulate ethanol self-administration of alcohol-preferring (P) rats.

    PubMed

    Rodd, Zachary A; Bell, Richard L; Oster, Scott M; Toalston, Jamie E; Pommer, Tylene J; McBride, William J; Murphy, James M

    2010-05-01

    Several studies indicated the involvement of serotonin-3 ([5-hydroxy tryptamine] 5-HT(3)) receptors in regulating alcohol-drinking behavior. The objective of this study was to determine the involvement of 5-HT(3) receptors within the ventral tegmental area (VTA) in regulating ethanol self-administration by alcohol-preferring (P) rats. Standard two-lever operant chambers (Coulbourn Instruments, Allentown, PA) were used to examine the effects of seven consecutive bilateral microinfusions of ICS 205-930 (ICS), a 5-HT(3) receptor antagonist, directly into the posterior VTA on the acquisition and maintenance of 15% (vol/vol) ethanol self-administration. P rats readily acquired ethanol self-administration by the fourth session. The three highest doses (0.125, 0.25, and 1.25 microg) of ICS prevented acquisition of ethanol self-administration. During the acquisition postinjection period, all rats treated with ICS demonstrated higher responding on the ethanol lever, with the highest dose producing the greatest effect. In contrast, during the maintenance phase, the three highest doses (0.75, 1.0, and 1.25 microg) of ICS significantly increased responding on the ethanol lever; after the 7-day dosing regimen, responding on the ethanol lever returned to control levels. Microinfusion of ICS into the posterior VTA did not alter the low responding on the water lever and did not alter saccharin (0.0125% wt/v) self-administration. Microinfusion of ICS into the anterior VTA did not alter ethanol self-administration. Overall, the results of this study suggest that 5-HT(3) receptors in the posterior VTA of the P rat may be involved in regulating ethanol self-administration. In addition, chronic operant ethanol self-administration and/or repeated treatments with a 5-HT(3) receptor antagonist may alter neuronal circuitry within the posterior VTA.

  1. Serotonin-3 Receptors in the Posterior Ventral Tegmental Area Regulate Ethanol Self-Administration of Alcohol-Preferring (P) Rats

    PubMed Central

    Rodd, Zachary A.; Bell, Richard L.; Oster, Scott M.; Toalston, Jamie E.; Pommer, Tylene J.; McBride, William J.; Murphy, James M.

    2015-01-01

    Several studies indicated the involvement of serotonin-3 (5-HT3) receptors in regulating alcohol-drinking behavior. The objective of this study was to determine the involvement of 5-HT3 receptors within the ventral tegmental area (VTA) in regulating ethanol self-administration by alcohol-preferring (P) rats. Standard two-lever operant chambers were used to examine the effects of 7 consecutive bilateral micro-infusions of ICS205-930 (ICS), a 5-HT3 receptor antagonist, directly into the posterior VTA on the acquisition and maintenance of 15% (v/v) ethanol self-administration. P rats readily acquired ethanol self-administration by the 4th session. The three highest doses (0.125, 0.25 and 1.25 ug) of ICS prevented acquisition of ethanol self-administration. During the acquisition post-injection period, all rats treated with ICS demonstrated higher responding on the ethanol lever, with the highest dose producing the greatest effect. In contrast, during the maintenance phase, the 3 highest doses (0.75, 1.0 and 1.25 ug) of ICS significantly increased responding on the ethanol lever; following the 7-day dosing regimen, responding on the ethanol lever returned to control levels. Micro-infusion of ICS into the posterior VTA did not alter the low responding on the water lever, and did not alter saccharin (0.0125% w/v) self-administration.. Micro-infusion of ICS into the anterior VTA did not alter ethanol self-administration. Overall, the results of this study suggest that 5-HT3 receptors in the posterior VTA of the P rat may be involved in regulating ethanol self-administration. In addition, chronic operant ethanol self-administration, and/or repeated treatments with a 5-HT3 receptor antagonist may alter neuronal circuitry within the posterior VTA. PMID:20682192

  2. Chronic alpha-tocopherol supplementation in rats does not ameliorate either chronic or acute alcohol-induced changes in muscle protein metabolism.

    PubMed

    Koll, Michael; Beeso, Julie A; Kelly, Frank J; Simanowski, Ulrich A; Seitz, Helmut K; Peters, Timothy J; Preedy, Victor R

    2003-03-01

    Chronic alcohol muscle disease is characterized by reduced skeletal muscle mass precipitated by acute reduction in protein synthesis. The pathogenic mechanisms remain obscure, but several lines of evidence suggest that increased oxidative stress occurs in muscle in response to alcohol and this may be associated with impaired alpha-tocopherol status. Potentially, this implies a therapeutic role for alpha-tocopherol, especially as we have shown that supplemental alpha-tocopherol may increase the rate of protein synthesis in normal rats [Reilly, Patel, Peters and Preedy (2000) J. Nutr. 130, 3045-3049]. We investigated the therapeutic effect of alpha-tocopherol on plantaris muscle protein synthesis in rats treated either acutely, chronically or chronically+acutely with ethanol. Protein synthesis rates were measured with a flooding dose of L-[4-(3)H]phenylalanine. Protein, RNA and DNA contents were determined by standard laboratory methods. Ethanol caused defined metabolic changes in muscle, including decreased protein, RNA and DNA contents in chronically treated rats. In acute or chronic+acute studies, ethanol suppressed fractional rates of protein synthesis. alpha-Tocopherol supplementation did not ameliorate the effects of either acute, chronic or chronic+acute alcohol on plantaris muscle protein content or rates of protein synthesis. In control animals (not treated with alcohol), alpha-tocopherol supplementation decreased muscle protein content owing to increases in protein turnover (both synthesis and degradation). alpha-Tocopherol supplementation is not protective against the deleterious effects of alcohol on protein metabolism in skeletal muscle.

  3. Differential effects of acute and chronic fructose administration on pyruvate dehydrogenase activity and lipogenesis

    SciTech Connect

    Wilson, L.

    1988-01-01

    These studies were undertaken to distinguish between the acute and chronic effects of fructose administration. In vivo, liver lipogenesis, as measured by {sup 3}H{sub 2}O incorporation, was greater in rats fed 60% fructose than in their glucose fed controls. Both fructose feeding, and fructose feeding plus intraperitoneal fructose injection increased the activities of 6-phosphogluconate dehydrogenase and malic enzyme. Liver PDH activity was increased by fructose feeding, and was increased even more by fructose feeding and injection of fructose, but this was not associated with any changes in hepatic ATP concentrations.

  4. 28 CFR 0.138 - Federal Bureau of Investigation, Drug Enforcement Administration, Bureau of Alcohol, Tobacco...

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... Prison Industries, Immigration and Naturalization Service, United States Marshals Service, Office of Justice Programs, Executive Office for Immigration Review, Executive Office for United States Attorneys... Alcohol, Tobacco, Firearms, and Explosives, Bureau of Prisons, Federal Prison Industries, Immigration...

  5. 28 CFR 0.138 - Federal Bureau of Investigation, Drug Enforcement Administration, Bureau of Alcohol, Tobacco...

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... Prison Industries, Immigration and Naturalization Service, United States Marshals Service, Office of Justice Programs, Executive Office for Immigration Review, Executive Office for United States Attorneys... Alcohol, Tobacco, Firearms, and Explosives, Bureau of Prisons, Federal Prison Industries, Immigration...

  6. 28 CFR 0.138 - Federal Bureau of Investigation, Drug Enforcement Administration, Bureau of Alcohol, Tobacco...

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... Prison Industries, Immigration and Naturalization Service, United States Marshals Service, Office of Justice Programs, Executive Office for Immigration Review, Executive Office for United States Attorneys... Alcohol, Tobacco, Firearms, and Explosives, Bureau of Prisons, Federal Prison Industries, Immigration...

  7. 28 CFR 0.138 - Federal Bureau of Investigation, Drug Enforcement Administration, Bureau of Alcohol, Tobacco...

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... Prison Industries, Immigration and Naturalization Service, United States Marshals Service, Office of Justice Programs, Executive Office for Immigration Review, Executive Office for United States Attorneys... Alcohol, Tobacco, Firearms, and Explosives, Bureau of Prisons, Federal Prison Industries, Immigration...

  8. 28 CFR 0.138 - Federal Bureau of Investigation, Drug Enforcement Administration, Bureau of Alcohol, Tobacco...

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... Prison Industries, Immigration and Naturalization Service, United States Marshals Service, Office of Justice Programs, Executive Office for Immigration Review, Executive Office for United States Attorneys... Alcohol, Tobacco, Firearms, and Explosives, Bureau of Prisons, Federal Prison Industries, Immigration...

  9. Amelioration of alcohol-induced hepatotoxicity by the administration of ethanolic extract of Sida cordifolia Linn.

    PubMed

    Rejitha, S; Prathibha, P; Indira, M

    2012-10-01

    Sida cordifolia Linn. (Malvaceae) is a plant used in folk medicine for the treatment of the inflammation of oral mucosa, asthmatic bronchitis, nasal congestion and rheumatism. We studied the hepatoprotective activity of 50 % ethanolic extract of S. cordifolia Linn. against alcohol intoxication. The duration of the experiment was 90 d. The substantially elevated levels of toxicity markers such as alanine aminotransferase, aspartate aminotransferase and γ-glutamyl transferase due to the alcohol treatment were significantly lowered in the extract-treated groups. The activity of antioxidant enzymes and glutathione content, which was lowered due to alcohol toxicity, was increased to a near-normal level in the co-administered group. Lipid peroxidation products, protein carbonyls, total collagen and hydroxyproline, which were increased in the alcohol-treated group, were reduced in the co-administered group. The mRNA levels of cytochrome P450 2E1, NF-κB, TNF-α and transforming growth factor-β1 were found to be increased in the alcohol-treated rats, and their expressions were found to be decreased in the co-administered group. These observations were reinforced by histopathological analysis. Thus, the present study clearly indicates that 50 % ethanolic extract of the roots of S. cordifolia Linn. has a potent hepatoprotective action against alcohol-induced toxicity, which was mediated by lowering oxidative stress and by down-regulating the transcription factors.

  10. Working Memory Moderates the Association Between Smoking Urge and Smoking Lapse Behavior After Alcohol Administration in a Laboratory Analogue Task

    PubMed Central

    Kahler, Christopher W.; Metrik, Jane; Spillane, Nichea S.; Tidey, Jennifer W.; Rohsenow, Damaris J.

    2015-01-01

    Introduction: Lapses after smoking cessation often occur in the context of alcohol use, possibly because alcohol increases urge to smoke. Poor working memory, or alcohol-induced decrements in working memory, may influence this relationship by making it more difficult for an individual to resist smoking in the face of smoking urges. Methods: Participants (n = 41) completed measures of working memory and urge to smoke before and after alcohol administration (placebo, 0.4g/kg, and 0.8g/kg, within subjects) and then participated in a laboratory analogue task in which smoking abstinence was monetarily incentivized. Results: Working memory moderated the relationship between smoking urge and latency to smoke: for those with relatively poorer working memory, urge to smoke was more strongly and negatively associated with latency to smoke (i.e., higher urges were associated with shorter latency). Conclusions: Those with weak working memory may need additional forms of treatment to help them withstand smoking urges. PMID:25481913

  11. A prospective study of the influence of acute alcohol intoxication versus chronic alcohol consumption on outcome following traumatic brain injury.

    PubMed

    Lange, Rael T; Shewchuk, Jason R; Rauscher, Alexander; Jarrett, Michael; Heran, Manraj K S; Brubacher, Jeffrey R; Iverson, Grant L

    2014-08-01

    The purpose of the study was to disentangle the relative contributions of day-of-injury alcohol intoxication and pre-injury alcohol misuse on outcome from TBI. Participants were 142 patients enrolled from a Level 1 Trauma Center (in Vancouver, Canada) following a traumatic brain injury (TBI; 43 uncomplicated mild TBI and 63 complicated mild-severe TBI) or orthopedic injury [36 trauma controls (TC)]. At 6-8 weeks post-injury, diffusion tensor imaging (DTI) of the whole brain was undertaken using a Phillips 3T scanner. Participants also completed neuropsychological testing, an evaluation of lifetime alcohol consumption (LAC), and had blood alcohol levels (BALs) taken at the time of injury. Participants in the uncomplicated mild TBI and complicated mild-severe TBI groups had higher scores on measures of depression and postconcussion symptoms (d = 0.45-0.83), but not anxiety, compared with the TC group. The complicated mild-severe TBI group had more areas of abnormal white matter on DTI measures (all p < .05; d = 0.54-0.61) than the TC group. There were no difference between groups on all neurocognitive measures. Using hierarchical regression analyses and generalized linear modeling, LAC and BAL did provide a unique contribution toward the prediction of attention and executive functioning abilities; however, the variance accounted for was small. LAC and BAL did not provide a unique and meaningful contribution toward the prediction of self-reported symptoms, DTI measures, or the majority of neurocognitive measures. In this study, BAL and LAC were not predictive of mental health symptoms, postconcussion symptoms, cognition, or white-matter changes at 6-8 weeks following TBI. PMID:24964748

  12. Cyproheptadine resembles clozapine in vivo following both acute and chronic administration in rats.

    PubMed

    Goudie, Andrew J; Cooper, Gillian D; Cole, Jon C; Sumnall, Harry R

    2007-03-01

    Cyproheptadine is a cheap, widely available anti-allergy drug with a broad receptor binding profile which resembles that of clozapine. In rats discriminating clozapine from vehicle cyproheptadine mimicked clozapine very closely. Acutely it induced full generalization in the absence of response suppression, as observed with clozapine. Chronic administration of clozapine and cyproheptadine induced tolerance and cross-tolerance respectively to the clozapine stimulus. This was characterized by circa 3.5-fold parallel shifts to the right in the clozapine generalization curves. Such tolerance and cross-tolerance was spontaneously reversible, suggesting that it was pharmacodynamic, and that clozapine and cyproheptadine induce similar neuroadaptations when administered chronically. Administration of chlordiazepoxide at a very high dose induced no cross-tolerance to the clozapine stimulus showing the pharmacological specificity of tolerance. The clozapine stimulus is a compound cue involving actions at various receptors, and various clozapine-like antipsychotic (APD) drugs generalize fully to it. These data demonstrate that in vivo cyproheptadine resembles clozapine both acutely and chronically. Our findings, in conjunction with other actions of cyproheptadine -- induction of weight gain, alleviation of clozapine withdrawal, anxiolytic actions, alleviation of 'typical' APD-induced motoric side effects, and some preliminary clinical findings -- suggest that further study of cyproheptadine in conjunction with a 'typical' APD for the possible treatment of schizophrenia is merited at both pre-clinical and clinical levels.

  13. Combined administration of hyperbaric oxygen and hydroxocobalamin improves cerebral metabolism after acute cyanide poisoning in rats.

    PubMed

    Hansen, M B; Olsen, N V; Hyldegaard, O

    2013-11-01

    Hyperbaric oxygen therapy (HBOT) or intravenous hydroxocobalamin (OHCob) both abolish cyanide (CN)-induced surges in interstitial brain lactate and glucose concentrations. HBOT has been shown to induce a delayed increase in whole blood CN concentrations, whereas OHCob may act as an intravascular CN scavenger. Additionally, HBOT may prevent respiratory distress and restore blood pressure during CN intoxication, an effect not seen with OHCob administration. In this report, we evaluated the combined effects of HBOT and OHCob on interstitial lactate, glucose, and glycerol concentrations as well as lactate-to-pyruvate ratio in rat brain by means of microdialysis during acute CN poisoning. Anesthetized rats were allocated to three groups: 1) vehicle (1.2 ml isotonic NaCl intra-arterially); 2) potassium CN (5.4 mg/kg intra-arterially); 3) potassium CN, OHCob (100 mg/kg intra-arterially) and subsequent HBOT (284 kPa in 90 min). OHCob and HBOT significantly attenuated the acute surges in interstitial cerebral lactate, glucose, and glycerol concentrations compared with the intoxicated rats given no treatment. Furthermore, the combined treatment resulted in consistent low lactate, glucose, and glycerol concentrations, as well as in low lactate-to-pyruvate ratios compared with CN intoxicated controls. In rats receiving OHCob and HBOT, respiration improved and cyanosis disappeared, with subsequent stabilization of mean arterial blood pressure. The present findings indicate that a combined administration of OHCob and HBOT has a beneficial and persistent effect on the cerebral metabolism during CN intoxication.

  14. Administration of Reconstituted Polyphenol Oil Bodies Efficiently Suppresses Dendritic Cell Inflammatory Pathways and Acute Intestinal Inflammation

    PubMed Central

    Cavalcanti, Elisabetta; Vadrucci, Elisa; Delvecchio, Francesca Romana; Addabbo, Francesco; Bettini, Simona; Liou, Rachel; Monsurrò, Vladia; Huang, Alex Yee-Chen; Pizarro, Theresa Torres

    2014-01-01

    Polyphenols are natural compounds capable of interfering with the inflammatory pathways of several in vitro model systems. In this study, we developed a stable and effective strategy to administer polyphenols to treat in vivo models of acute intestinal inflammation. The in vitro suppressive properties of several polyphenols were first tested and compared for dendritic cells (DCs) production of inflammatory cytokines. A combination of the polyphenols, quercetin and piperine, were then encapsulated into reconstituted oil bodies (OBs) in order to increase their stability. Our results showed that administration of low dose reconstituted polyphenol OBs inhibited LPS-mediated inflammatory cytokine secretion, including IL-6, IL-23, and IL-12, while increasing IL-10 and IL-1Rα production. Mice treated with the polyphenol-containing reconstituted OBs (ROBs) were partially protected from dextran sodium sulfate (DSS)-induced colitis and associated weight loss, while mortality and inflammatory scores revealed an overall anti-inflammatory effect that was likely mediated by impaired DC immune responses. Our study indicates that the administration of reconstituted quercetin and piperine-containing OBs may represent an effective and potent anti-inflammatory strategy to treat acute intestinal inflammation. PMID:24558444

  15. Scutellaria baicalensis Georgi extract protects against alcohol-induced acute liver injury in mice and affects the mechanism of ER stress

    PubMed Central

    DONG, QINGQING; CHU, FEI; WU, CHENGZHU; HUO, QIANG; GAN, HUAIYONG; LI, XIAOMING; LIU, HAO

    2016-01-01

    The aims of the present study were to examine the hepatoprotective effect of Scutellaria baicalensis Georgi extract (Scutellariae Radix extract; SRE) against acute alcohol-induced liver injury in mice, and investigate the mechanism of endoplasmic reticulum (ER) stress. High performance liquid chromatography was used for the phytochemical analysis of SRE. Animals were administered orally with 50% alcohol (12 ml/kg) 4 h following administration of doses of SRE every day for 14 days, with the exception of normal control group. The protective effect was investigated by measuring the levels of aspartate transaminase (AST), alanine transferase (ALT) and triglyceride (TG) in the serum, and the levels of glutathione (GSH) and malondialdehyde (MDA) in liver tissues. The levels of glucose-related protein 78 (GRP78) were detected using immunohistochemical localization and an enzyme-linked immunosorbent assay. Hepatocyte apoptosis was assessed using terminal-deoxynucleoitidyl transferase mediated nick end labeling. The SRE contained 31.2% baicalin. Pretreatment with SRE had a marked protective effect by reversing the levels of biochemical markers and levels of GRP78 in a dose-dependent manner. The results of the present study demonstrated that pretreatment with SRE exerted a marked hepatoprotective effect by downregulating the expression of GRP78, which is a marker of ER stress. PMID:26936686

  16. Differential peptidomics assessment of strain and age differences in mice in response to acute cocaine administration.

    PubMed

    Romanova, Elena V; Rubakhin, Stanislav S; Ossyra, John R; Zombeck, Jonathan A; Nosek, Michael R; Sweedler, Jonathan V; Rhodes, Justin S

    2015-12-01

    Neurochemical differences in the hypothalamic-pituitary axis between individuals and between ages may contribute to differential susceptibility to cocaine abuse. This study measured peptide levels in the pituitary gland (Pit) and lateral hypothalamus (LH) in adolescent (age 30 days) and adult (age 65 days) mice from four standard inbred strains, FVB/NJ, DBA/2J, C57BL/6J, and BALB/cByJ, which have previously been characterized for acute locomotor responses to cocaine. Individual peptide profiles were analyzed using mass spectrometric profiling and principal component analysis. Sequences of assigned peptides were verified by tandem mass spectrometry. Principal component analysis classified all strains according to their distinct peptide profiles in Pit samples from adolescent mice, but not adults. Select pro-opiomelanocortin-derived peptides were significantly higher in adolescent BALB/cByJ and DBA/2J mice than in FVB/NJ or C57BL/6J mice. A subset of peptides in the LH, but not in the Pit, was altered by cocaine in adolescents. A 15 mg/kg dose of cocaine induced greater peptide alterations than a 30 mg/kg dose, particularly in FVB/NJ animals, with larger differences in adolescents than adults. Neuropeptides in the LH affected by acute cocaine administration included pro-opiomelanocortin-, myelin basic protein-, and glutamate transporter-derived peptides. The observed peptide differences could contribute to differential behavioral sensitivity to cocaine among strains and ages. Peptides were measured using mass spectrometry (MALDI-TOF) in individual lateral hypothalamus and pituitary samples from four strains and two ages of inbred mice in response to acute cocaine administration. Principal component analyses (PCA) classified the strains according to their peptide profiles from adolescent mice, and a subset of peptides in the lateral hypothalamus was altered by cocaine in adolescents.

  17. 17β-Estradiol administration attenuates seawater aspiration-induced acute lung injury in rats.

    PubMed

    Fan, Qixin; Zhao, Pengtao; Li, Jiahuan; Xie, Xiaoyan; Xu, Min; Zhang, Yong; Mu, Deguang; Li, Wangping; Sun, Ruilin; Liu, Wei; Nan, Yandong; Zhang, Bo; Jin, Faguang; Li, Zhichao

    2011-12-01

    There is very little evidence on the value of administering estrogen in cases of seawater drowning which can induce acute lung injury/acute respiratory distress syndrome (ALI/ARDS). Therefore, this study aimed to investigate whether 17β-estradiol (E2) treatment can attenuate seawater aspiration-induced ALI in rats. In the experiment, ALI was induced by endotracheal instillation of seawater (4mL/kg) and the rats were then given intraperitoneal injection of E2 (5mg/kg) 20min after seawater instillation. Finally, the changes of arterial blood gases which contained hydrogen ion concentration (pH), arterial oxygen tension (PaO(2)) and arterial carbon dioxide tension (PaCO(2)) were measured and the measurement of extravascular lung water (EVLW) was observed. The pulmonary histological changes were evaluated by hematoxylin-eosin stain. The expression of aquaporins (AQPs) 1, AQP5, and estrogen receptor-β (ERβ) was measured by western blotting and immunohistochemical methods. The results showed that compared with normal saline water, seawater aspiration induced more serious ALI in rats which was markedly alleviated by E2 treatment. Meanwhile, the ERβ in lung tissues was activated after E2 administration. The seawater aspiration group also presented with severe pulmonary edema which was paralleled with over expressed AQP1 and AQP5. However, the up-regulation of AQP1 and AQP5 was suppressed by the administration of E2, resulting in an attenuation of lung edema. In conclusion, E2 treatment could effectively attenuate seawater aspiration-induced acute lung injury in rats by the down-regulation of AQP1 and AQP5.

  18. Reducing effect of saikosaponin A, an active ingredient of Bupleurum falcatum, on alcohol self-administration in rats: Possible involvement of the GABAB receptor.

    PubMed

    Maccioni, Paola; Lorrai, Irene; Carai, Mauro A M; Riva, Antonella; Morazzoni, Paolo; Mugnaini, Claudia; Corelli, Federico; Gessa, Gian Luigi; Colombo, Giancarlo

    2016-05-16

    Recent studies demonstrated that treatment with saikosaponin A (SSA) - an active ingredient of the medicinal herb, Bupleurum falcatum L. - selectively suppressed, likely via a GABAB receptor-mediated mechanism, intravenous self-administration of morphine and cocaine in rats [Yoon et al., 2012; 2013]. The present study was designed to investigate whether the capacity of SSA to suppress morphine and cocaine self-administration extends to oral alcohol self-administration. To this end, selectively bred Sardinian alcohol-preferring (sP) rats were trained to lever-respond on a Fixed Ratio (FR) 4 (FR4) schedule of reinforcement for alcohol (15%, v/v) in daily 30-min sessions. Once responding had stabilized, rats were tested under the FR4 (measure of alcohol reinforcing properties) and Progressive Ratio (PR; measure of alcohol motivational properties) schedules of reinforcement. The possible involvement of the GABAB receptor system was investigated testing the effect of (a) pretreatment with the GABAB receptor antagonist, SCH50911, and (b) combined treatment with the positive allosteric modulator of the GABAB receptor, GS39783. Treatment with SSA (0, 0.25, 0.5, and 1mg/kg, i.p.) markedly reduced lever-responding for alcohol, amount of self-administered alcohol, and breakpoint for alcohol (defined as the lowest response requirement not achieved in the PR experiment). Pretreatment with 2mg/kg SCH50911 (i.p.) resulted in a partial blockade of the reducing effect of 0.5mg/kg SSA on lever-responding for alcohol and amount of self-administered alcohol. Combination of per se ineffective doses of GS39783 (5mg/kg, i.g.) and SSA (0.1mg/kg, i.p.) reduced lever-responding for alcohol and amount of self-administered alcohol. These results (a) extend to alcohol self-administration the capacity of SSA to suppress morphine and cocaine self-administration in rats and (b) suggest that the GABAB receptor system is likely part of the neural substrate underlying the reducing effect of SSA on

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

    PubMed

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

    2015-01-01

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

  20. Acute caffeine administration effect on brain activation patterns in mild cognitive impairment.

    PubMed

    Haller, Sven; Montandon, Marie-Louise; Rodriguez, Cristelle; Moser, Dominik; Toma, Simona; Hofmeister, Jeremy; Sinanaj, Indrit; Lovblad, Karl-Olof; Giannakopoulos, Panteleimon

    2014-01-01

    Previous studies showed that acute caffeine administration enhances task-related brain activation in elderly individuals with preserved cognition. To explore the effects of this widely used agent on cognition and brain activation in early phases of cognitive decline, we performed a double-blinded, placebo-controlled functional magnetic resonance imaging (fMRI) study during an n-back working memory task in 17 individuals with mild cognitive impairment (MCI) compared to 17 age-matched healthy controls (HC). All individuals were regular caffeine consumers with an overnight abstinence and given 200 mg caffeine versus placebo tablets 30 minutes before testing. Analyses included assessment of task-related activation (general linear model), functional connectivity (tensorial-independent component analysis, TICA), baseline perfusion (arterial spin labeling, ASL), grey matter density (voxel-based morphometry, VBM), and white matter microstructure (tract-based spatial statistics, TBSS). Acute caffeine administration induced a focal activation of the prefrontal areas in HC with a more diffuse and posteromedial activation pattern in MCI individuals. In MCI, TICA documented a significant caffeine-related enhancement in the prefrontal cortex, supplementary motor area, ventral premotor and parietal cortex as well as the basal ganglia and cerebellum. The absence of significant group differences in baseline ASL perfusion patterns supports a neuronal rather than a purely vascular origin of these differences. The VBM and TBSS analyses excluded potentially confounding differences in grey matter density and white matter microstructure between MCI and HC. The present findings suggest a posterior displacement of working memory-related brain activation patterns after caffeine administration in MCI that may represent a compensatory mechanism to counterbalance a frontal lobe dysfunction.

  1. Acute Alcohol Intoxication Decreases Glucose Metabolism but Increases Acetate Uptake in the Human Brain

    PubMed Central

    Volkow, Nora D.; Kim, Sung Won; Wang, Gene-Jack; Alexoff, David; Logan, Jean; Muench, Lisa; Shea, Colleen; Telang, Frank; Fowler, Joanna S.; Wong, Christopher; Benveniste, Helene; Tomasi, Dardo

    2012-01-01

    Alcohol intoxication results in marked reductions in brain glucose metabolism, which we hypothesized reflect not just its GABAergic enhancing effects but also metabolism of acetate as an alternative brain energy source. To test this hypothesis we separately assessed the effects of alcohol intoxication on brain glucose and acetate metabolism using Positron Emission Tomography (PET). We found that alcohol intoxication significantly decreased whole brain glucose metabolism (measured with FDG) with the largest decrements in cerebellum and occipital cortex and the smallest in thalamus. In contrast, alcohol intoxication caused a significant increase in [1-11C]acetate brain uptake (measured as standard uptake value, SUV), with the largest increases occurring in cerebellum and the smallest in thalamus. In heavy alcohol drinkers [1-11C]acetate brain uptake during alcohol challenge trended to be higher than in occasional drinkers (p <0.06) and the increases in [1-11C]acetate uptake in cerebellum with alcohol were positively associated with the reported amount of alcohol consumed (r=0.66, p<0.01). Our findings corroborate a reduction of brain glucose metabolism during intoxication and document an increase in brain acetate uptake. The opposite changes observed between regional brain metabolic decrements and regional increases in [1-11C]acetate uptake support the hypothesis that during alcohol intoxication the brain may rely on acetate as an alternative brain energy source and provides preliminary evidence that heavy alcohol exposures may facilitate the use of acetate as an energy substrate. These findings raise the question of the potential therapeutic benefits that increasing plasma acetate concentration (ie ketogenic diets) may have in alcoholics undergoing alcohol detoxification. PMID:22947541

  2. Acute alcohol intoxication decreases glucose metabolism but increases acetate uptake in the human brain.

    PubMed

    Volkow, Nora D; Kim, Sung Won; Wang, Gene-Jack; Alexoff, David; Logan, Jean; Muench, Lisa; Shea, Colleen; Telang, Frank; Fowler, Joanna S; Wong, Christopher; Benveniste, Helene; Tomasi, Dardo

    2013-01-01

    Alcohol intoxication results in marked reductions in brain glucose metabolism, which we hypothesized reflect not just its GABAergic enhancing effects but also the metabolism of acetate as an alternative brain energy source. To test this hypothesis we separately assessed the effects of alcohol intoxication on brain glucose and acetate metabolism using Positron Emission Tomography (PET). We found that alcohol intoxication significantly decreased whole brain glucose metabolism (measured with FDG) with the largest decrements in cerebellum and occipital cortex and the smallest in the thalamus. In contrast, alcohol intoxication caused a significant increase in [1-(11)C]acetate brain uptake (measured as standard uptake value, SUV), with the largest increases occurring in the cerebellum and the smallest in the thalamus. In heavy alcohol drinkers [1-(11)C]acetate brain uptake during alcohol challenge tended to be higher than in occasional drinkers (p<0.06) and the increases in [1-(11)C]acetate uptake in cerebellum with alcohol were positively associated with the reported amount of alcohol consumed (r=0.66, p<0.01). Our findings corroborate a reduction of brain glucose metabolism during intoxication and document an increase in brain acetate uptake. The opposite changes observed between regional brain metabolic decrements and regional increases in [1-(11)C]acetate uptake support the hypothesis that during alcohol intoxication the brain may rely on acetate as an alternative brain energy source and provides preliminary evidence that heavy alcohol exposures may facilitate the use of acetate as an energy substrate. These findings raise the question of the potential therapeutic benefits that increasing plasma acetate concentration (i.e. ketogenic diets) may have in alcoholics undergoing alcohol detoxification. PMID:22947541

  3. Effects of naltrexone on alcohol self-administration in heavy drinkers.

    PubMed

    Davidson, D; Palfai, T; Bird, C; Swift, R

    1999-02-01

    The mechanisms underlying the suppressant effects of naltrexone (NTX) on ad libitum alcohol drinking in a bar/restaurant setting were investigated in heavy beer drinkers. Fifty-one male and female heavy drinkers (mean age = 22) received 50 mg of NTX or placebo (PBO), p.o., on two separate occasions in a randomized, double-blind crossover protocol. After 7 days of taking medication, subjects were provided with the opportunity to consume beer ad libitum during two, 90-min test sessions that were held 1 to 2 weeks apart. Blood samples were collected on test days to ensure medication compliance and to measure blood levels of NTX and the active beta-naltrexol. Less beer was consumed during NTX treatment. NTX decreased urges to consume alcohol. NTX-treated subjects also took significantly longer to finish each glass of beer and were more likely to terminate beer drinking early. Self-report stimulation and ratings of positive mood states were lower during NTX treatment. Negative side effects of NTX, such as nausea and headache, were reported more frequently with NTX. Not all of the subjects decreased their beer intake on NTX, and some subjects drank more beer. Nonresponders to NTX were not related to blood levels of the active metabolite beta-naltrexol or to a family history of alcoholism. Overall, the results of this study suggest that NTX affects a number of the components of alcohol drinking sequence, including lowering cravings, decreasing the positive reinforcing effects of alcohol, and increasing headache and nausea, each of which may contribute to reducing alcohol intake.

  4. A key role for the N/OFQ-NOP receptor system in modulating nicotine taking in a model of nicotine and alcohol co-administration

    PubMed Central

    Cippitelli, Andrea; Schoch, Jennifer; Debevec, Ginamarie; Brunori, Gloria; Zaveri, Nurulain T.; Toll, Lawrence

    2016-01-01

    Alcohol and nicotine are often co-abused. Although the N/OFQ-NOP receptor system is considered a potential target for development of drug abuse pharmacotherapies, especially for alcoholism, little is known about the role of this system in nicotine dependence. Furthermore, the effect of prior history of nicotine dependence on subsequent nicotine and alcohol taking is understudied. Using an operant co-administration paradigm, in which rats concurrently self-administer nicotine and alcohol, we found that nicotine dependent rats increased nicotine self-administration over time as compared to non-dependent animals, while patterns of alcohol lever pressing did not change between groups. Pretreatment with the potent NOP receptor agonist AT-202 (0.3–3 mg/kg) increased nicotine lever pressing of both dependent and non-dependent groups, whereas the selective antagonist SB612111 (1–10 mg/kg) elicited a clear reduction of nicotine responses, in both dependent and non-dependent rats. In parallel, AT-202 only produced minor changes on alcohol responses and SB612111 reduced alcohol taking at a dose that also reduced locomotor behavior. Results indicate that a history of nicotine dependence affects subsequent nicotine- but not alcohol-maintained responding, and that NOP receptor antagonism, rather than agonism, blocks nicotine self-administration, which strongly suggests a critical role for the endogenous N/OFQ in the modulation of nicotine reinforcement processes. PMID:27199205

  5. Assessing Women’s Sexual Arousal in the Context of Sexual Assault History and Acute Alcohol Intoxication

    PubMed Central

    Gilmore, Amanda K.; Schacht, Rebecca L.; George, William H.; Otto, Jacqueline M.; Davis, Kelly Cue; Heiman, Julia R.; Norris, Jeanette; Kajumulo, Kelly F.

    2011-01-01

    Introduction Few studies have examined differences in women’s sexual arousal based on sexual assault history (SAH) or in-the-moment alcohol intoxication. Only one has examined combined effects. Findings regarding the relationship between SAH and arousal are contradictory. Aim We aimed to determine the relationship between SAH, alcohol intoxication, and sexual arousal. Main Outcome Measures Genital response was measured by vaginal pulse amplitude (VPA) using vaginal photoplethysmography while watching erotic films. Self-reported sexual arousal was assessed after watching erotic films. Methods Women were randomly assigned to an alcohol (target blood alcohol level = .10%) or control condition and categorized as having a SAH or not. After beverage administration, all women watched erotic films while genital arousal (vaginal pulse amplitude; VPA) was measured. Afterwards self-reported sexual arousal was measured. Results Women with a SAH had smaller increases in genital arousal in response to the films than women without a SAH. Intoxicated women had smaller increases in genital arousal than sober women. However, no differences for SAH or intoxication were found in self-reported arousal. Conclusion SAH and alcohol intoxication are associated with smaller increases in genital arousal compared to women without a SAH and sober women, suggesting that these co-occurring factors impact sexual arousal. PMID:20367775

  6. Dormant Masculinity: Moderating Effects of Acute Alcohol Intoxication on the Relation Between Male Role Norms and Antigay Aggression

    PubMed Central

    Leone, Ruschelle M.; Parrott, Dominic J.

    2014-01-01

    Acute alcohol intoxication was examined as a moderator of the association between men’s adherence to traditional gender norms and aggression towards a gay male. Participants were 164 heterosexual drinking men between the ages of 21–30. Participants completed a battery of questionnaires that included a measure of adherence to male role norms (i.e., status, toughness, antifemininity), were randomly assigned to consume an alcohol or no-alcohol control beverage, and completed the Taylor Aggression Paradigm in which electric shocks were administered to, and received from, a fictitious gay or heterosexual male opponent. Results indicated a greater adherence to both the toughness (β = .50, p = .002) and antifeminine (β = .37, p = .023) norms predicted high levels of aggression towards a gay man only among participants who were intoxicated. This interaction effect was not detected for the status norm. Consistent with previous research, findings suggest that adherence to the toughness norm does not increase sober men’s risk of aggression toward gay men. However, this is the first study to demonstrate that alcohol intoxication may activate concepts of toughness, and thus influence men to act in line with this facet of the masculine concept. Importantly, these data support the view that men’s adherence to various dimensions of masculinity may be dormant in some contexts, only to be activated, and subsequently demonstrated, in other contexts. PMID:25750591

  7. Tlr4-mutant mice are resistant to acute alcohol-induced sterol-regulatory element binding protein activation and hepatic lipid accumulation.

    PubMed

    Zhang, Zhi-Hui; Liu, Xiao-Qian; Zhang, Cheng; He, Wei; Wang, Hua; Chen, Yuan-Hua; Liu, Xiao-Jing; Chen, Xi; Xu, De-Xiang

    2016-01-01

    Previous studies demonstrated that acute alcohol intoxication caused hepatic lipid accumulation. The present study showed that acute alcohol intoxication caused hepatic lipid accumulation in Tlr4-wild-type mice but not in Tlr4-mutant mice. Hepatic sterol-regulatory element binding protein (SREBP)-1, a transcription factor regulating fatty acid and triglyceride (TG) synthesis, was activated in alcohol-treated Tlr4-wild-type mice but not in Tlr4-mutant mice. Hepatic Fas, Acc, Scd-1 and Dgat-2, the key genes for fatty acid and TG synthesis, were up-regulated in alcohol-treated Tlr4-wild-type mice but not in Tlr4-mutant mice. Additional experiment showed that hepatic MyD88 was elevated in alcohol-treated Tlr4-wild-type mice but not in Tlr4-mutant mice. Hepatic NF-κB was activated in alcohol-treated Tlr4-wild-type mice but not in Tlr4-mutant mice. Moreover, hepatic GSH content was reduced and hepatic MDA level was elevated in alcohol-treated Tlr4-wild-type mice but not in Tlr4-mutant mice. Hepatic CYP2E1 was elevated in alcohol-treated Tlr4-wild-type mice but not in Tlr4-mutant mice. Hepatic p67phox and gp91phox, two NADPH oxidase subunits, were up-regulated in alcohol-treated Tlr4-wild-type mice but not in Tlr4-mutant mice. Alpha-phenyl-N-t-butylnitrone (PBN), a free radical spin-trapping agent, protected against alcohol-induced hepatic SREBP-1 activation and hepatic lipid accumulation. In conclusion, Tlr4-mutant mice are resistant to acute alcohol-induced hepatic SREBP-1 activation and hepatic lipid accumulation. PMID:27627966

  8. Tlr4-mutant mice are resistant to acute alcohol-induced sterol-regulatory element binding protein activation and hepatic lipid accumulation

    PubMed Central

    Zhang, Zhi-Hui; Liu, Xiao-Qian; Zhang, Cheng; He, Wei; Wang, Hua; Chen, Yuan-Hua; Liu, Xiao-Jing; Chen, Xi; Xu, De-Xiang

    2016-01-01

    Previous studies demonstrated that acute alcohol intoxication caused hepatic lipid accumulation. The present study showed that acute alcohol intoxication caused hepatic lipid accumulation in Tlr4-wild-type mice but not in Tlr4-mutant mice. Hepatic sterol-regulatory element binding protein (SREBP)-1, a transcription factor regulating fatty acid and triglyceride (TG) synthesis, was activated in alcohol-treated Tlr4-wild-type mice but not in Tlr4-mutant mice. Hepatic Fas, Acc, Scd-1 and Dgat-2, the key genes for fatty acid and TG synthesis, were up-regulated in alcohol-treated Tlr4-wild-type mice but not in Tlr4-mutant mice. Additional experiment showed that hepatic MyD88 was elevated in alcohol-treated Tlr4-wild-type mice but not in Tlr4-mutant mice. Hepatic NF-κB was activated in alcohol-treated Tlr4-wild-type mice but not in Tlr4-mutant mice. Moreover, hepatic GSH content was reduced and hepatic MDA level was elevated in alcohol-treated Tlr4-wild-type mice but not in Tlr4-mutant mice. Hepatic CYP2E1 was elevated in alcohol-treated Tlr4-wild-type mice but not in Tlr4-mutant mice. Hepatic p67phox and gp91phox, two NADPH oxidase subunits, were up-regulated in alcohol-treated Tlr4-wild-type mice but not in Tlr4-mutant mice. Alpha-phenyl-N-t-butylnitrone (PBN), a free radical spin-trapping agent, protected against alcohol-induced hepatic SREBP-1 activation and hepatic lipid accumulation. In conclusion, Tlr4-mutant mice are resistant to acute alcohol-induced hepatic SREBP-1 activation and hepatic lipid accumulation. PMID:27627966

  9. Baclofen effects on alcohol seeking, self-administration and extinction of seeking responses in a within-session design in baboons.

    PubMed

    Duke, Angela N; Kaminski, Barbara J; Weerts, Elise M

    2014-01-01

    Baclofen, a gamma-aminobutyric acidB receptor agonist, is currently under investigation as a potential treatment to prevent relapse to drinking in alcohol-dependent persons. In the current study, two groups of baboons were trained under a chained schedule of reinforcement (CSR), with three linked components, which were each correlated with different response requirements and cues. Fulfilling the requirement in the second link initiated the third link where either alcohol (n = 4) or a preferred non-alcoholic beverage (Tang, n = 5) was available for self-administration; failure to complete the response requirement in Link 2 ended the session (no access to alcohol or Tang). Seeking responses in Link 2 were used as indices of the motivational processes thought to be involved in relapse. The effects of baclofen (0.1-2.4 mg/kg) were examined under conditions with alcohol or Tang access and under extinction. Under the CSR, baclofen (1.8 and 2.4 mg/kg) significantly decreased (P < 0.05) alcohol self-administration responses and total g/kg alcohol intake. In contrast, only the highest dose of baclofen (2.4 mg/kg) reduced Tang self-administration and consumption. Under within-session extinction conditions, baclofen (1.8 and 2.4 mg/kg) facilitated extinction of responding for both alcohol and Tang, particularly during the first 10 minutes of extinction. Baclofen may be effective in reducing craving and alcohol drinking, although the facilitation of extinction and suppression of both alcohol and Tang self-administration by baclofen suggests these effects may be related to a more general suppression of consummatory and conditioned behaviors.

  10. Baclofen effects on alcohol seeking, self-administration and extinction of seeking responses in a within-session design in baboons

    PubMed Central

    Duke, Angela N.; Kaminski, Barbara J.; Weerts, Elise M.

    2012-01-01

    Baclofen, a GABAB receptor agonist, is currently under investigation as a potential treatment to prevent relapse to drinking in alcohol dependent persons. In the current study, two groups of baboons were trained under a chained schedule of reinforcement (CSR), with 3 linked components, which were each correlated with different response requirements and cues. Fulfilling the requirement in the 2nd link initiated the 3rd link where either alcohol (n=4) or a preferred non-alcoholic beverage (Tang, n=5) was available for self-administration; failure to complete the response requirement in Link 2 ended the session (no access to alcohol or Tang). Seeking responses in Link 2 were used as indices of the motivational processes thought to be involved in relapse. The effects of baclofen (0.1 – 2.4 mg/kg) were examined under conditions with alcohol or Tang access and under extinction. Under the CSR baclofen (1.8 and 2.4 mg/kg) significantly decreased (p<0.05) alcohol self-administration responses and total g/kg alcohol intake. In contrast, only the highest dose of baclofen (2.4 mg/kg) reduced Tang self-administration and consumption. Under within-session extinction conditions, baclofen (1.8 and 2.4 mg/kg) facilitated extinction of responding for both alcohol and Tang, particularly during the first 10 min of extinction. Baclofen may be effective in reducing craving and alcohol drinking, although the facilitation of extinction and suppression of both alcohol and Tang self-administration by baclofen suggests these effects may be related to a more general suppression of consummatory and conditioned behaviors. PMID:22458648

  11. 27 CFR 26.202 - Requirements of the Federal Alcohol Administration Act.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... AND TOBACCO TAX AND TRADE BUREAU, DEPARTMENT OF THE TREASURY ALCOHOL LIQUORS AND ARTICLES FROM PUERTO... political subdivision thereof or any officer or employee of any such agency, bringing liquors into the... copy thereof, and every person and any agency of a State or political subdivision thereof or...

  12. Effects of a new administration form of oxymetazoline on maxillary ostial patency in healthy individuals and patients with acute rhinitis.

    PubMed

    Ackerhans, M; Jannert, M; Tönnesson, M

    1994-01-01

    A new administration form of the nasal decongestant oxymetazoline and its effects on maxillary ostial patency were investigated in 5 healthy individuals and 20 patients with acute rhinitis. Registration and comparison of ostial patency after administration of placebo spray and oxymetazoline spray, placebo solution and oxymetazoline solution, were performed in healthy individuals. Patients with acute rhinitis were treated with either oxymetazoline solution or placebo solution, preceded and followed by registration of the equivalent maxillary ostial diameter. In both studies, solution was administered with a nasal bellows container. The results suggest that the administration of oxymetazoline solution with the nasal bellows container is a more effective way of increasing maxillary ostial patency in healthy individuals than oxymetazoline spray. In patients with acute rhinitis it also seems to be a way of increasing maxillary ostial patency.

  13. Purple sweet potato (Ipomoea batatas L.) anthocyanins: preventive effect on acute and subacute alcoholic liver damage and dealcoholic effect.

    PubMed

    Sun, Hongnan; Mu, Taihua; Liu, Xingli; Zhang, Miao; Chen, Jingwang

    2014-03-19

    This study aimed to investigate the dealcoholic effect and preventive effect of anthocyanins from purple sweet potato (PSPAs) on acute and subacute alcoholic liver damage (ALD). Seven-week-old male inbred mice were grouped into five groups: control group (without PSPAs and ethanol treatments), model group (with ethanol treatment only), low-dose group (50 mg PSPAs/kg body weight), middle-dose group (125 mg PSPAs/kg body weight), and high-dose group (375 mg PSPAs/kg body weight), and the mice in all groups were administered intragastrically. Biochemical parameters of serum and liver were determined, and the histopathological changes of liver tissue were also analyzed. Results showed that all tested parameters were ameliorated after consumption of PSPAs. Therefore, PSPAs have preventive effect on acute and subacute ALD. It is suggested that PSPAs could be used as a supplementary reagent during prophylactic and curative managements of ALD.

  14. Effects of acute ethanol administration on nocturnal pineal serotonin N-acetyltransferase activity

    SciTech Connect

    Creighton, J.A.; Rudeen, P.K.

    1988-01-01

    The effect of acute ethanol administration on pineal serotonin N-acetyltransferase (NAT) activity, norepinephrine and indoleamine content was examined in male rats. When ethanol was administered in two equal doses (2 g/kg body weight) over a 4 hour period during the light phase, the nocturnal rise in NAT activity was delayed by seven hours. The nocturnal pineal norepinephrine content was not altered by ethanol except for a delay in the reduction of NE with the onset of the following light phase. Although ethanol treatment led to a significant reduction in nocturnal levels of pineal serotonin content, there was no significant effect upon pineal content of 5-hydroxyindoleacetic acid (5-HIAA). The data indicate that ethanol delays the onset of the rise of nocturnal pineal NAT activity.

  15. Effects of acute administration of brotizolam in subjects with disturbed sleep

    PubMed Central

    Roehrs, T.; Zorick, F.; Koshorek, G. L.; Wittig, R.; Roth, T.

    1983-01-01

    1 Effects of ingestion of brotizolam (0.25 and 0.50 mg) over 1-3 days on polysomnographic measures of sleep were assessed in patients complaining of insomnia. 2 Brotizolam reduced latency to sleep, number of awakenings and wake during sleep, and increased total sleep time. It also increased stage 2 sleep and decreased slow wave and rapid eye movement sleep. 3 Increasing the dose from 0.25 to 0.50 mg increased hypnotic efficacy, and there was a more consistent and reliable effect. 4 Discontinuation of brotizolam had minimal effects on sleep compared with placebo over the 3 nights after acute administration. 5 No side-effects or disruption of daytime function was found using questionnaires and objective tests of performance. PMID:6661383

  16. Behavioral consequences of chelator administration in acute cadmium toxicity (journal version)

    SciTech Connect

    Peele, D.B.; Farmer, J.D.; MacPhail, R.C.

    1988-01-01

    The conditioned flavor-aversion paradigm was used to assess the toxicity of acutely administered cadmium and the interaction of cadmium with the heavy-metal chelating agents dimercaprol (BAL) and dimercaptosuccinic acid (DMSA). Shortly after consuming saccharin, rats received cadmium either alone or in combination with BAL or DMSA. When compared to rats receiving either nothing or the vehicle, rats receiving cadmium displayed significant reductions in saccharin preference (i.e., conditioned flavor aversions). BAL and DMSA were also capable of producing conditioned flavor aversions when given alone. Rats receiving cadmium in combination with either BAL or DMSA displayed significant, but not complete, attenuations of conditioned flavor aversions when compared to rats receiving cadmium alone. Chelator-induced blockade of cadmium-induced flavor-aversion conditioning was not obtained when BAL or DMSA administration was delayed by 4 hrs.

  17. Effects of acute administration of selective serotonin reuptake inhibitors on sympathetic nerve activity.

    PubMed

    Tiradentes, R V; Pires, J G P; Silva, N F; Ramage, A G; Santuzzi, C H; Futuro Neto, H A

    2014-07-01

    Serotonergic mechanisms have an important function in the central control of circulation. Here, the acute effects of three selective serotonin (5-HT) reuptake inhibitors (SSRIs) on autonomic and cardiorespiratory variables were measured in rats. Although SSRIs require 2-3 weeks to achieve their full antidepressant effects, it has been shown that they cause an immediate inhibition of 5-HT reuptake. Seventy male Wistar rats were anesthetized with urethane and instrumented to record blood pressure, heart rate, renal sympathetic nerve activity (RSNA), and respiratory frequency. At lower doses, the acute cardiovascular effects of fluoxetine, paroxetine and sertraline administered intravenously were insignificant and variable. At middle and higher doses, a general pattern was observed, with significant reductions in sympathetic nerve activity. At 10 min, fluoxetine (3 and 10 mg/kg) reduced RSNA by -33 ± 4.7 and -31 ± 5.4%, respectively, without changes in blood pressure; 3 and 10 mg/kg paroxetine reduced RSNA by -35 ± 5.4 and -31 ± 5.5%, respectively, with an increase in blood pressure +26.3 ± 2.5; 3 mg/kg sertraline reduced RSNA by -59.4 ± 8.6%, without changes in blood pressure. Sympathoinhibition began 5 min after injection and lasted approximately 30 min. For fluoxetine and sertraline, but not paroxetine, there was a reduction in heart rate that was nearly parallel to the sympathoinhibition. The effect of these drugs on the other variables was insignificant. In conclusion, acute peripheral administration of SSRIs caused early autonomic cardiovascular effects, particularly sympathoinhibition, as measured by RSNA. Although a peripheral action cannot be ruled out, such effects are presumably mostly central. PMID:25003632

  18. Progesterone inhibits behavioral responses and estrogen increases corticosterone levels after acute cocaine administration.

    PubMed

    Niyomchai, Tipyamol; Russo, Scott J; Festa, Eugene D; Akhavan, Alaleh; Jenab, Shirzad; Quiñones-Jenab, Vanya

    2005-04-01

    Accumulating evidence suggests that estrogen and progesterone contribute to the sexually dimorphic behavioral response to cocaine. In this study, we tested the hypothesis that varying the level of estrogen or progesterone affects cocaine-induced locomotive behavior in female rats. Ovariectomized (OVX) rats received estrogen (0, 5, 10, 20, or 50 microg) 48 h or progesterone (0, 50, 100, 250, or 500 microg) 24 h before acute saline or cocaine (15 mg/kg) administration. Although estrogen did not affect cocaine-induced ambulatory and rearing behaviors, it affected stereotypic behaviors regardless of cocaine administration (animals receiving 50 microg had higher stereotypic counts than did the OVX group). In contrast, progesterone affected rearing activity dose-dependently: 50 and 500 microg of progesterone inhibited, whereas 100 microg and 250 microg stimulated, rearing in response to cocaine. That estrogen and progesterone did not affect overall baseline behavioral activity suggests their effects are mediated in part through interactions with cocaine. Progesterone administration did not affect corticosterone levels in saline- or cocaine-treated rats. Estrogen administration, however, affected levels of corticosterone both at baseline and after cocaine treatment. After accounting for baseline differences, we found that rats receiving 5 or 10 microg of estrogen and cocaine had higher percentage increases in serum corticosterone levels than did the control group that did not receive estrogen. On the basis of these observations, we suggest that progesterone fluctuations during the estrous cycle impact cocaine-induced behavioral responses, whereas estrogen may affect activity in the hypothalamic-pituitary-adrenal axis. Thus, dose-dependent effects of gonadal hormones may underlie some of the reported sex differences and reproductive cycle effects of cocaine.

  19. Acute Alcohol Consumption Impairs Controlled but Not Automatic Processes in a Psychophysical Pointing Paradigm

    PubMed Central

    Johnston, Kevin; Timney, Brian; Goodale, Melvyn A.

    2013-01-01

    Numerous studies have investigated the effects of alcohol consumption on controlled and automatic cognitive processes. Such studies have shown that alcohol impairs performance on tasks requiring conscious, intentional control, while leaving automatic performance relatively intact. Here, we sought to extend these findings to aspects of visuomotor control by investigating the effects of alcohol in a visuomotor pointing paradigm that allowed us to separate the influence of controlled and automatic processes. Six male participants were assigned to an experimental “correction” condition in which they were instructed to point at a visual target as quickly and accurately as possible. On a small percentage of trials, the target “jumped” to a new location. On these trials, the participants’ task was to amend their movement such that they pointed to the new target location. A second group of 6 participants were assigned to a “countermanding” condition, in which they were instructed to terminate their movements upon detection of target “jumps”. In both the correction and countermanding conditions, participants served as their own controls, taking part in alcohol and no-alcohol conditions on separate days. Alcohol had no effect on participants’ ability to correct movements “in flight”, but impaired the ability to withhold such automatic corrections. Our data support the notion that alcohol selectively impairs controlled processes in the visuomotor domain. PMID:23861934

  20. Effects of acute doses of prosocial drugs methamphetamine and alcohol on plasma oxytocin levels.

    PubMed

    Bershad, Anya K; Kirkpatrick, Matthew G; Seiden, Jacob A; de Wit, Harriet

    2015-06-01

    Many drugs, including alcohol and stimulants, demonstrably increase sociability and verbal interaction and are recreationally consumed in social settings. One drug, 3,4-methylenedioxymethamphetamine (MDMA, ecstasy), seems to produce its prosocial effects by increasing plasma oxytocin levels, and the oxytocin system has been implicated in responses to several other drugs of abuse. Here, we sought to investigate the effects of 2 other "social" drugs on plasma oxytocin levels--methamphetamine and alcohol. Based on their shared capacity to enhance sociability, we hypothesized that both methamphetamine and alcohol would increase plasma oxytocin levels. In study 1, 11 healthy adult volunteers attended 3 sessions during which they received methamphetamine (10 mg or 20 mg) or placebo under double-blind conditions. Subjective drug effects, cardiovascular effects, and plasma oxytocin levels were measured at regular intervals throughout the sessions. In study 2, 8 healthy adult volunteers attended a single session during which they received 1 beverage containing placebo, and then a beverage containing alcohol (0.8 g/kg). Subjective effects, breath alcohol levels, and plasma oxytocin levels were measured at regular intervals. Both methamphetamine and alcohol produced their expected physiological and subjective effects, but neither of these drugs increased plasma oxytocin levels. The neurobiological mechanisms mediating the prosocial effects of drugs such as alcohol and methamphetamine remain to be identified.

  1. Neonatal finasteride administration decreases dopamine release in nucleus accumbens after alcohol and food presentation in adult male rats.

    PubMed

    Llidó, Anna; Bartolomé, Iris; Darbra, Sònia; Pallarès, Marc

    2016-08-01

    Endogenous levels of the neurosteroid (NS) allopregnanolone (AlloP) during neonatal stages are crucial for the correct development of the central nervous system (CNS). In a recent work we reported that the neonatal administration of AlloP or finasteride (Finas), an inhibitor of the enzyme 5α-reductase needed for AlloP synthesis, altered the voluntary consumption of ethanol and the ventrostriatal dopamine (DA) levels in adulthood, suggesting that neonatal NS manipulations can increase alcohol abuse vulnerability in adulthood. Moreover, other authors have associated neonatal NS alterations with diverse dopaminergic (DAergic) alterations. Thus, the aim of the present work is to analyse if manipulations of neonatal AlloP alter the DAergic response in the nucleus accumbens (NAcc) during alcohol intake in rats. We administered AlloP or Finas from postnatal day (PND) 5 to PND9. At PND98, we measured alcohol consumption using a two-bottle free-choice model (ethanol 10% (v/v)+glucose 3% (w/v), and glucose 3% (w/v)) for 12 days. On the last day of consumption, we measured the DA and 3,4-dihydroxyphenylacetic acid (DOPAC) release in NAcc in response to ethanol intake. The samples were obtained by means of in vivo microdialysis in freely moving rats, and DA and DOPAC levels were determined by means of high-performance liquid chromatography analysis (HPLC). The results revealed that neonatal Finas increased ethanol consumption in some days of the consumption phase, and decreased the DA release in the NAcc in response to solutions (ethanol+glucose) and food presentation. Taken together, these results suggest that neonatal NS alterations can affect alcohol rewarding properties. PMID:27139934

  2. Neonatal finasteride administration decreases dopamine release in nucleus accumbens after alcohol and food presentation in adult male rats.

    PubMed

    Llidó, Anna; Bartolomé, Iris; Darbra, Sònia; Pallarès, Marc

    2016-08-01

    Endogenous levels of the neurosteroid (NS) allopregnanolone (AlloP) during neonatal stages are crucial for the correct development of the central nervous system (CNS). In a recent work we reported that the neonatal administration of AlloP or finasteride (Finas), an inhibitor of the enzyme 5α-reductase needed for AlloP synthesis, altered the voluntary consumption of ethanol and the ventrostriatal dopamine (DA) levels in adulthood, suggesting that neonatal NS manipulations can increase alcohol abuse vulnerability in adulthood. Moreover, other authors have associated neonatal NS alterations with diverse dopaminergic (DAergic) alterations. Thus, the aim of the present work is to analyse if manipulations of neonatal AlloP alter the DAergic response in the nucleus accumbens (NAcc) during alcohol intake in rats. We administered AlloP or Finas from postnatal day (PND) 5 to PND9. At PND98, we measured alcohol consumption using a two-bottle free-choice model (ethanol 10% (v/v)+glucose 3% (w/v), and glucose 3% (w/v)) for 12 days. On the last day of consumption, we measured the DA and 3,4-dihydroxyphenylacetic acid (DOPAC) release in NAcc in response to ethanol intake. The samples were obtained by means of in vivo microdialysis in freely moving rats, and DA and DOPAC levels were determined by means of high-performance liquid chromatography analysis (HPLC). The results revealed that neonatal Finas increased ethanol consumption in some days of the consumption phase, and decreased the DA release in the NAcc in response to solutions (ethanol+glucose) and food presentation. Taken together, these results suggest that neonatal NS alterations can affect alcohol rewarding properties.

  3. Multifactorial comparative proteomic study of cytochrome P450 2E1 function in chronic alcohol administration.

    PubMed

    Wang, Yuan; Kou, Yan; Wang, Xiaodong; Cederbaum, Arthur; Wang, Rong

    2014-01-01

    With the use of iTRAQ technique, a multifactorial comparative proteomic study can be performed. In this study, to obtain an overview of ethanol, CYP2E1 and gender effects on liver injury and gain more insight into the underlying molecular mechanism, mouse liver proteomes were quantitatively analyzed using iTRAQ under eight conditions including mice of different genders, wild type versus CYP2E1 knockout, and normal versus alcohol diet. A series of statistical and bioinformatic analyses were explored to simplify and clarify multifactorial comparative proteomic data. First, with the Principle Component analysis, six proteins, CYP2E1, FAM25, CA3, BHMT, HIBADH and ECHS1, involved in oxidation reduction, energy and lipid metabolism and amino acid metabolism, were identified as the most differentially expressed gene products across all of the experimental conditions of our chronic alcoholism model. Second, hierarchical clustering analysis showed CYP2E1 knockout played a primary role in the overall differential protein expression compared with ethanol and gender factors. Furthermore, pair-wise multiple comparisons have revealed that the only significant expression difference lied in wild-type and CYP2E1 knockout mice both treated with ethanol. Third, K-mean clustering analysis indicated that the CYP2E1 knockout had the reverse effect on ethanol induced oxidative stress and lipid oxidation. More importantly, IPA analysis of proteomic data inferred that the gene expressions of two upstream regulators, NRF2 and PPARα, regulated by chronic alcohol feeding and CYP2E1 knockout, are involved in ethanol induced oxidative stress and lipid oxidation. The present study provides an effectively comprehensive data analysis strategy to compare multiple biological factors, contributing to biochemical effects of alcohol on the liver. The mass spectrometry proteomics data have been deposited to the ProteomeXchange with data set identifier of PXD000635.

  4. Reduced Contextual Discrimination following Alcohol Consumption or MDMA Administration in Mice.

    PubMed

    Johansson, Emily M; García-Gutiérrez, María S; Moscoso-Castro, María; Manzanares, Jorge; Valverde, Olga

    2015-01-01

    The recreational drugs, alcohol and 3,4-Methylenedioxymethamphetamine (MDMA, "Ecstasy") have both been shown to cause immune activation in vivo, and they are linked to cognitive impairment and anxiety-like behaviors in rodents. The neuronal effects of these drugs in the hippocampal area, an area that has been a focus of studies aiming to explain the mechanisms underlying anxiety related-disorders, remains poorly understood. Therefore we investigated the specific inflammatory impact of alcohol and MDMA on this area of the brain and on a hippocampal-related behavioral task. We centered our study on two inflammatory factors linked to anxiety-related disorders, namely Interleukin-1β (IL-1β) and brain-derived neurotrophic factor (BDNF). We subjected drug-consuming mice to a battery of behavioral tests to evaluate general activity, anxiety-like and depressive-live behaviors. We then introduced them to a contextual fear discrimination task and immune-related effects were examined by immunohistochemical and biochemical studies. Our results suggest that there is a relationship between the induction of immune activated pathways by voluntary alcohol consumption and a high-dose MDMA. Furthermore, the ability of mice to perform a contextual fear discrimination task was impaired by drug consumption and we report long term inflammatory alterations in the hippocampus even several weeks after drug intake. This information will be helpful for discovering new selective drug targets, and to develop treatments and preventive approaches for patients with anxiety-related disorders. PMID:26566284

  5. Reduced Contextual Discrimination following Alcohol Consumption or MDMA Administration in Mice

    PubMed Central

    Johansson, Emily M.; García-Gutiérrez, María S.; Moscoso-Castro, María; Manzanares, Jorge; Valverde, Olga

    2015-01-01

    The recreational drugs, alcohol and 3,4-Methylenedioxymethamphetamine (MDMA, “Ecstasy”) have both been shown to cause immune activation in vivo, and they are linked to cognitive impairment and anxiety-like behaviors in rodents. The neuronal effects of these drugs in the hippocampal area, an area that has been a focus of studies aiming to explain the mechanisms underlying anxiety related-disorders, remains poorly understood. Therefore we investigated the specific inflammatory impact of alcohol and MDMA on this area of the brain and on a hippocampal-related behavioral task. We centered our study on two inflammatory factors linked to anxiety-related disorders, namely Interleukin-1β (IL-1β) and brain-derived neurotrophic factor (BDNF). We subjected drug-consuming mice to a battery of behavioral tests to evaluate general activity, anxiety-like and depressive-live behaviors. We then introduced them to a contextual fear discrimination task and immune-related effects were examined by immunohistochemical and biochemical studies. Our results suggest that there is a relationship between the induction of immune activated pathways by voluntary alcohol consumption and a high-dose MDMA. Furthermore, the ability of mice to perform a contextual fear discrimination task was impaired by drug consumption and we report long term inflammatory alterations in the hippocampus even several weeks after drug intake. This information will be helpful for discovering new selective drug targets, and to develop treatments and preventive approaches for patients with anxiety-related disorders. PMID:26566284

  6. The pharmacokinetics of the antidepressant tianeptine and its main metabolite in healthy humans--influence of alcohol co-administration.

    PubMed

    Salvadori, C; Ward, C; Defrance, R; Hopkins, R

    1990-01-01

    A balanced 3 way cross-over study involving 12 young healthy volunteers (6 men and 6 women) was used to determine the pharmacokinetic parameters of the antidepressant tianeptine following a single dose administered by oral and intravenous route. The influence of alcohol on the pharmacokinetics of tianeptine when given per os was also investigated. Kinetic parameters of metabolite MC5, the C5 side chain beta-oxidation product of tianeptine, were simultaneously determined. Following intravenous administration total clearance and volume of distribution of tianeptine were 230 +/- 59 ml.min-1 and 0.47 +/- 0.14 l.kg-1 respectively. When given orally, tianeptine was absorbed rapidly (tmax = 0.94 +/- 0.47 h). The mean systemic availability was estimated to be 99 +/- 29%. Tianeptine was eliminated from plasma with a half-life of 2.5 +/- 1.1 h, mainly via extrarenal route since its renal clearance averaged 0.38 +/- 0.47 ml.min-1. Plasma levels of metabolite MC5 were lower than those of the parent drug but decreased with a longer half-life (7.2 +/- 5.7 h). Alcohol co-administration decreased tianeptine absorption rate and lowered tianeptine plasma levels by about 30% but did not affect those of the MC5 metabolite.

  7. The Acute Effects of Alcohol on Sleep Architecture in Late Adolescence

    PubMed Central

    Chan, Julia K. M.; Trinder, John; Andrewes, Holly E.; Colrain, Ian M.; Nicholas, Christian L.

    2013-01-01

    Background Alcohol consumption is prevalent in late adolescence, however little is known about its effect on sleep in this group. In mature adults, alcohol decreases sleep onset latency (SOL) and sleep efficiency (SE) and increases wake after sleep onset (WASO). It also increases slow wave sleep (SWS) and decreases REM sleep in the first half of the night, with the inverse occurring in the second half. Alcohol’s effect on sleep during late adolescence is of interest given that this age group shows both dramatic increases in alcohol consumption, and significant developmental changes in the central nervous system. This study examined the effect of alcohol on sleep architecture in women and men aged 18–21 years and whether previously reported sleep architecture effects may have been as an artificial result of changes to sleep cycle length. Methods 24 (12 female) healthy 18–21 year old light social drinkers (19.1±1.0yrs) underwent two conditions: pre-sleep alcohol (Target BAC 0.10%) and placebo administered under controlled conditions, followed by standard polysomnography. Results In the alcohol condition, mean breath alcohol concentration (BAC) at lights out was 0.084 ±0.016%. Time in bed, total sleep time and sleep onset latency (all p>.05) did not differ between conditions. However, there was less REM (p=.011) and more stage 2 sleep (p=.035) in the alcohol condition. Further, alcohol increased SWS (p=.02) and decreased REM sleep (p<.001) in the first half of the night and disrupted sleep in the second half, with increased WASO (interaction: p=.034), and decreased SE (p=.04) and SWS (p=.01) and no REM sleep rebound in the second half of the night (p=.262). Additionally, alcohol had no effect on sleep cycle length (p=.598). Conclusions The results were broadly consistent with the adult literature with the novel extension that half night sleep architecture effects could not be attributed to changes in sleep cycle length. However, alcohol did not reduce SOL, or

  8. Perillyl alcohol protects against ethanol induced acute liver injury in Wistar rats by inhibiting oxidative stress, NFκ-B activation and proinflammatory cytokine production.

    PubMed

    Khan, Abdul Quaiyoom; Nafees, Sana; Sultana, Sarwat

    2011-01-11

    Oxidative stress and inflammation are two major etiological factors that are suggested to play key roles in the development of ethanol induced liver injury. Release of proinflammatory cytokine like tumor necrosis factor alpha (TNF-α) and activation of nuclear factor kappa-B (NFκ-B) may strongly intensify inflammation and cell damage. Additionally, reactive oxygen species (ROS) also exerts significant effect in this whole cell signaling machinery. The present study was designed to investigate the protective effects of perillyl alcohol (POH) on ethanol-induced acute liver injury in Wistar rats and its probable mechanism. We have successfully demonstrated that pre-treatment with POH, besides exerting antioxidant activity might be able to modulate TNF-α release and NFκ-B activation. Rats were divided into five groups and treated with ethanol or POH via an intragastric tube for one week. Control group was treated with vehicle, and ethanol treated group was given ethanol (5 g/kg body wt). Animal of treatment groups were pretreated with POH (50 & 100 mg/kg body wt) and have been given ethanol. Serum aspartate aminotransferase, alanine aminotransferase and lactate dehydrogenase and hepatic malondialdehyde were increased significantly by ethanol treatment. Ethanol administration decreased hepatic reduced glutathione content and various antioxidant enzymes activity. TNF-α production and NFκ-B activation was also found to be increased after ethanol administration. POH pre-treatment significantly ameliorates ethanol induced acute liver injury possibly by inhibition of lipid peroxidation, replenishment of endogenous enzymatic and non-enzymatic defense system, downregulation of TNF-α as well as NFκ-B.

  9. The effect of acute stress and long-term corticosteroid administration on plasma metabolites in an urban and desert songbird.

    PubMed

    Davies, Scott; Rodriguez, Natalie S; Sweazea, Karen L; Deviche, Pierre

    2013-01-01

    In response to stressful stimuli, animals activate the hypothalamic-pituitary-adrenal axis, which can result in transition to the "emergency life history stage." A key adaptive characteristic of this life history stage is the mobilization of energy stores. However, few data are available on the metabolic response to acute stress in wild-caught, free-ranging birds. We quantified the effect of acute capture and restraint stress on plasma glucose, free fatty acid, and uric acid in free-ranging Abert's towhees Melozone aberti. Furthermore, birds were caught from urban and desert localities of Phoenix, Arizona, to investigate potential effects of urban versus desert habitats on the corticosterone (CORT) and metabolic response to acute stress. Complementing work on free-ranging birds, captive towhees received CORT-filled Silastic capsules to investigate the response of urban and desert conspecifics to long-term CORT administration. We quantified the effect of CORT administration on baseline plasma glucose and uric acid, liver and pectoralis muscle glycogen stores, kidney phosphoenolpyruvate carboxykinase (PEPCK-C, a key gluconeogenic enzyme), and body mass. Acute stress increased plasma CORT and glucose and decreased plasma uric acid but had no effect on plasma free fatty acid. There was no difference between urban and desert localities in body mass, fat scores, and the response to acute stress. CORT administration decreased body mass but had no effect on glucose and uric acid, pectoral muscle glycogen, or kidney PEPCK-C. However, liver glycogen of CORT-treated urban birds increased compared with corresponding controls, whereas glycogen decreased in CORT-treated desert birds. This study suggests that Abert's towhees principally mobilize glucose during acute stress but urban and desert towhees do not differ in their CORT and metabolic response to acute stress or long-term CORT administration.

  10. Effects of intracisternal administration of cannabidiol on the cardiovascular and behavioral responses to acute restraint stress.

    PubMed

    Granjeiro, Erica M; Gomes, Felipe V; Guimarães, Francisco S; Corrêa, Fernando M A; Resstel, Leonardo B M

    2011-10-01

    Systemic administration of cannabidiol (CBD), a non-psychotomimetic compound from Cannabis sativa, attenuates the cardiovascular and behavioral responses to restraint stress. Although the brain structures related to CBD effects are not entirely known, they could involve brainstem structures responsible for cardiovascular control. Therefore, to investigate this possibility the present study verified the effects of CBD (15, 30 and 60 nmol) injected into the cisterna magna on the autonomic and behavioral changes induced by acute restraint stress. During exposure to restraint stress (1h) there was a significant increase in mean arterial pressure (MAP) and heart rate (HR). Also, 24h later the animals showed a decreased percentage of entries onto the open arms of the elevated plus-maze. These effects were attenuated by CBD (30 nmol). The drug had no effect on MAP and HR baseline values. These results indicate that intracisternal administration of CBD can attenuate autonomic responses to stress. However, since CBD decreased the anxiogenic consequences of restraint stress, it is possible that the drug is also acting on forebrain structures. PMID:21771609

  11. Comparison of microcoils and polyvinyl alcohol particles in selective microcatheter angioembolization of non variceal acute gastrointestinal hemorrhage

    PubMed Central

    Tanveer-Ul-Haq; Idris, Muhammad; Salam, Basit; Akhtar, Waseem; Jamil, Yasir

    2015-01-01

    Objectives: To compare the efficacy of polyvinyl alcohol (PVA) particles with microcoils in angiembolisation of non variceal acute gastrointestinal haemorrhage. Methods: This is a retrospective cross-sectional study of patients who underwent transcatheter angioembolization from January, 1995 to December, 2013 at Aga Khan University Hospital, Karachi. Patients were divided into two groups on basis of use of either microcoils or PVA particles and compared in terms of technical success, clinical success, re-bleeding and ischemic complication rates. Chi (χ2) square and Fisher’s exact tests were applied and a P-value of less than 0.05 was considered statistically significant. Results: Fifty seven patients underwent angioembolization. Microcoil and PVA particles embolization was performed in 63% (36/57) and 35% (20/57) cases respectively. Technical success was achieved in all cases (100%). Clinical success rate was higher in microcoils group (92%) than PVA particles group (75%) with statistically significant P value (p=0.048). Ischemic complication was seen in one case (3%) in the microcoil group, while no such complications were seen in the PVA particles group. Conclusion: In angioembolization of non variceal acute gastrointestinal haemorrhage microcoils are better than Polyvinyl alcohol particles with higher clinical success and lower re-bleed rates. PMID:26430397

  12. [Acute alcohol intoxication among children and adolescents admitted to the Department of Pediatrics, Pediatric Endocrinology and Diabetes, Medical University of Silesia, Katowice during 2000-2010--preliminary study].

    PubMed

    Kamińska, Halla; Agnieszka, Zachurzok-Buczyńska; Gawlik, Aneta; Małecka-Tendera, Ewa

    2012-01-01

    The alcohol drinking at the young age is a risk factor of alcohol addiction later in life, and is connected with school problems, binge drinking, tobacco addiction, illegal drug use, violence, crime commitment, and risky sexual behaviors. Alcohol drinking in the last 12 months is declared by 78% Polish children. The aim of the study was to evaluate the frequency of admissions due to alcohol intoxication to the Department of Pediatrics, Pediatric Endocrinology and Diabetes, Pediatric Center of Silesia and the identification of the risk factors of the acute alcohol intoxication among Polish children and adolescents. Ten-year retrospective study includes investigation of patients medical records from the Department of Pediatrics. Among 8048 patients hospitalized in the Department of Pediatrics between the years 2000-2010, 220 (2.7%) cases of acute alcohol poisoning occurred The detailed data analysis from 139 patients [66 (47.5%) girls, 73 (52,5%) boys] was done. In the years 2006-2010 the number of girls admitted to the department increased in comparison to boys. The largest group of patients was at age between 14 and 16 years [61 (44%) children]. The blood alcohol concentration at the moment of admission to the hospital was 0.1 to 4.0 per thousand. In most cases (92.8%) the alcohol intoxication was intentional. Five percent of them were suicide attempts. In the youngest group of children alcohol abuse was unintentional. 23 (16.5%) of patients initially needed admission to the intensive care unit. In 30 (21.6%) patient the family was incomplete and five times more often father was absent. The alcohol addiction occurs in 18 (13.0%) fathers and 10 (7.2%) mothers of our patients. It is concluded that over the last decade the number of girls admitted due to alcohol abuse increased. Children at school grade between 7-9 are intoxicated most often. One six of intoxicated patents needed hospitalization at intensive care unit.

  13. Acute subjective response to alcohol as a function of reward and punishment sensitivity.

    PubMed

    Morris, David H; Treloar, Hayley; Tsai, Chia-Lin; McCarty, Kayleigh N; McCarthy, Denis M

    2016-09-01

    Individual differences in subjective response to alcohol play a crucial role in the development of heavy drinking and related problems. In light of this, a growing focus of research has been identifying factors that contribute to differences in response. The aim of the present study was to determine whether individual differences in the subjective experience of rewarding and aversive effects of alcohol are a specific manifestation of general differences in reward and punishment sensitivity. Eighty-nine participants (M age=22.4, SD=1.9; 47.2% women) consumed a moderate dose of alcohol, i.e., peak breath alcohol concentration (BrAC)≈0.080g%, and rated their level of stimulation and sedation at seven timepoints over the BrAC curve. Sensitivity to reward and punishment were assessed by a self-report questionnaire prior to consumption. Multilevel growth models showed that post-consumption changes in stimulation ratings varied as a function of participants' level of reward and punishment sensitivity. Drinkers more sensitive to reward reported feeling more stimulated shortly after drinking and exhibited an attenuated rate of decline in stimulation over the blood alcohol curve, relative to drinkers with less strong reward sensitivity. Reward sensitivity was not related to subjective ratings of sedation, and punishment sensitivity was not related to either stimulation or sedation ratings. Findings suggest that reward sensitivity may increase risk for alcohol misuse among young adult social drinkers by increasing their subjective feelings of stimulation while drinking. PMID:27104798

  14. Acute effects of alcohol on brain perfusion monitored with arterial spin labeling magnetic resonance imaging in young adults.

    PubMed

    Marxen, Michael; Gan, Gabriela; Schwarz, Daniel; Mennigen, Eva; Pilhatsch, Maximilian; Zimmermann, Ulrich S; Guenther, Matthias; Smolka, Michael N

    2014-03-01

    While a number of studies have established that moderate doses of alcohol increase brain perfusion, the time course of such an increase as a function of breath alcohol concentration (BrAC) has not yet been investigated, and studies differ about regional effects. Using arterial spin labeling (ASL) magnetic resonance imaging, we investigated (1) the time course of the perfusion increase during a 15-minute linear increase of BrAC up to 0.6 g/kg followed by a steady exposure of 100 minutes, (2) the regional distribution, (3) a potential gender effect, and (4) the temporal stability of perfusion effects. In 48 young adults who participated in the Dresden longitudinal study on alcohol effects in young adults, we observed (1) a 7% increase of global perfusion as compared with placebo and that perfusion and BrAC are tightly coupled in time, (2) that the increase reaches significance in most regions of the brain, (3) that the effect is stronger in women than in men, and (4) that an acute tolerance effect is not observable on the time scale of 2 hours. Larger studies are needed to investigate the origin and the consequences of the effect, as well as the correlates of inter-subject variations.

  15. Displacement of Cortisol From Human Heart by Acute Administration of a Mineralocorticoid Receptor Antagonist

    PubMed Central

    Iqbal, Javaid; Andrew, Ruth; Cruden, Nicholas L.; Kenyon, Christopher J.; Hughes, Katherine A.; Newby, David E.; Hadoke, Patrick W. F.; Walker, Brian R.

    2015-01-01

    Context Mineralocorticoid receptor (MR) antagonists have beneficial effects in patients with heart failure and myocardial infarction, often attributed to blocking aldosterone action in the myocardium. However, binding of aldosterone to MR requires local activity of the enzyme 11β-hydroxysteroid dehydrogenase type 2 (11β-HSD2), which inactivates cortisol to cortisone and thereby prevents receptor occupancy by cortisol. In vivo activity of 11β-HSD2 and potential occupancy of MR by cortisol in human heart have not been quantified. Objective This study aimed to measure in vivo activity of 11β-HSD2 and to establish whether cortisol binds MR in human heart. Participants and Interventions Nine patients without heart failure undergoing diagnostic coronary angiography were infused to steady state with the stable isotope tracers 9,11,12,12-[2H]4-cortisol and 1,2-[2H]2-cortisone to quantify cortisol and cortisone production. Samples were obtained from the femoral artery and coronary sinus before and for 40 minutes after bolus iv administration of an MR antagonist, potassium canrenoate. Coronary sinus blood flow was measured by venography and Doppler flow wire. Results There was no detectable production of cortisol or cortisone across the myocardium. After potassium canrenoate administration, plasma aldosterone concentrations increased substantially but aldosterone was not detectably released from the myocardium. In contrast, plasma cortisol concentrations did not change in the systemic circulation but tissue-bound cortisol was released transiently from the myocardium after potassium canrenoate administration. Conclusions Human cardiac 11β-HSD2 activity appears too low to inactivate cortisol to cortisone. Cortisol is displaced acutely from the myocardium by MR antagonists and may contribute to adverse MR activation in human heart. PMID:24423282

  16. Increased loss and decreased synthesis of hepatic glutathione after acute ethanol administration. Turnover studies.

    PubMed Central

    Speisky, H; MacDonald, A; Giles, G; Orrego, H; Israel, Y

    1985-01-01

    The effect of acute ethanol administration on rates of synthesis and utilization of hepatic glutathione (GSH) was studied in rats after a pulse of [35S]cysteine. A 35% decrease in hepatic GSH content 5h after administration of 4 g of ethanol/kg body wt. was accompanied by a 33% increase in the rate of GSH utilization. The decrease occurred without increases in hepatic oxidized glutathione (GSSG) or in the GSH/GSSG ratio. The rate of non-enzymic condensation of GSH with acetaldehyde could account for only 6% of the rate of hepatic GSH disappearance. The increased loss of [35S]GSH induced by ethanol was not accompanied by an increased turnover; rather, a 30% inhibition of GSH synthesis balanced the increased rate of loss, leaving the turnover rate unchanged. The rate of acetaldehyde condensation with cysteine in vitro occurred at about one-third of the rate of GSH loss in ethanol-treated animals. However, ethanol induced only a minor decrease in liver cysteine content, which did not precede, but followed, the decrease in GSH. The characteristics of 2-methylthiazolidine-4-carboxylic acid, the condensation product between acetaldehyde and cysteine, were studied and methodologies were developed to determine its presence in tissues. It was not found in the liver of ethanol-treated animals. Ethanol administration led to a marked increase (47%) in plasma GSH in the post-hepatic inferior vena cava, but not in its pre-hepatic segment. Data suggest that an increased loss of GSH from the liver constitutes an important mechanism for the decrease in GSH induced by ethanol. In addition, an inhibition of GSH synthesis is observed. PMID:3977847

  17. Effect of acute lithium administration on penile erection: involvement of nitric oxide system

    PubMed Central

    Sandoughdaran, Saleh; Sadeghipour, Hamed; Sadeghipour, Hamid Reza

    2016-01-01

    Background: Lithium has been the treatment of choice for bipolar disorder (BD) for many years. Although erectile dysfunction is a known adverse effect of this drug, the mechanism of action by which lithium affects erectile function is still unknown. Objective: The aim was to investigate the possible involvement of nitric oxide (NO) in modulatory effect of lithium on penile erection (PE). We further evaluated the possible role of Sildenafil in treatment of lithium-induced erectile dysfunction. Materials and Methods: Erectile function was determined using rat model of apomorphine-induced erections. For evaluating the effect of lithium on penile erection, rats received intraperitoneal injection of graded doses of lithium chloride 30 mins before subcutaneous injection of apomorphine. To determine the possible role of NO pathway, sub-effective dose of N (G)-nitro-L-arginine methyl ester (L-NAME), a nitric oxide synthase (NOS) inhibitor, was administered 15 min before administration of sub-effective dose of lithium chloride. In other separate experimental groups, sub- effective dose of the nitric oxide precursor, L-arginine, or Sildenafil was injected into the animals 15 min before administration of a potent dose of lithium. 30 min after administration of lithium chloride, animals were assessed in apomorphine test. Serum lithium levels were measured 30 min after administration of effective dose of lithium. Results: Lithium at 50 and 100 mg/kg significantly decreased number of PE (p<0.001), whereas at lower doses (5, 10 and 30 mg/kg) had no effect on apomorphine induced PE. The serum Li+ level of rats receiving 50 mg/kg lithium was 1±0.15 mmol/L which is in therapeutic range of lithium. The inhibitory effect of Lithium was blocked by administration of sub-effective dose of nitric oxide precursor L-arginine (100 mg/kg) (p<0.001) and sildenafil (3.5 mg/kg) (p<0.001) whereas pretreatment with a low and sub-effective dose of L-NAME (10mg/kg) potentiated sub-effective dose of

  18. Effects of acute and chronic administration of fenproporex on DNA damage parameters in young and adult rats.

    PubMed

    Gonçalves, Cinara L; Rezin, Gislaine T; Ferreira, Gabriela K; Jeremias, Isabela C; Cardoso, Mariane R; Valvassori, Samira S; Munhoz, Bruna J P; Borges, Gabriela D; Bristot, Bruno N; Leffa, Daniela D; Andrade, Vanessa M; Quevedo, João; Streck, Emilio L

    2013-08-01

    Obesity is a chronic and multifactorial disease, whose prevalence is increasing in many countries. Pharmaceutical strategies for the treatment of obesity include drugs that regulate food intake, thermogenesis, fat absorption, and fat metabolism. Fenproporex is the second most commonly consumed amphetamine-based anorectic worldwide; this drug is rapidly converted in vivo into amphetamine, which is associated with neurotoxicity. In this context, the present study evaluated DNA damage parameters in the peripheral blood of young and adult rats submitted to an acute administration and chronic administration of fenproporex. In the acute administration, both young and adult rats received a single injection of fenproporex (6.25, 12.5 or 25 mg/kg i.p.) or vehicle. In the chronic administration, both young and adult rats received one daily injection of fenproporex (6.25, 12.5, or 25 mg/kg i.p.) or Tween for 14 days. 2 h after the last injection, the rats were killed by decapitation and their peripheral blood removed for evaluation of DNA damage parameters by alkaline comet assay. Our study showed that acute administration of fenproporex in young and adult rats presented higher levels of damage index and frequency in the DNA. However, chronic administration of fenproporex in young and adult rats did not alter the levels of DNA damage in both parameters of comet assay. The present findings showed that acute administration of fenproporex promoted damage in DNA, in both young and adult rats. Our results are consistent with other reports which showed that other amphetamine-derived drugs also caused DNA damage. We suggest that the activation of an efficient DNA repair mechanism may occur after chronic exposition to fenproporex. Our results are consistent with other reports that showed some amphetamine-derived drugs also caused DNA damage. PMID:23636618

  19. Evaluation of chronic alcohol self-administration by a 3-bottle choice paradigm in adult male rats. Effects on behavioural reactivity, spatial learning and reference memory.

    PubMed

    Cacace, Silvana; Plescia, Fulvio; La Barbera, Marco; Cannizzaro, Carla

    2011-06-01

    Chronic ethanol consumption is able to modify emotional behaviour and cognition in humans. In particular, the effects exerted by alcohol may depend on doses, time and modalities of administration. In this study we investigated, in adult male rats, ethanol self-administration and preference patterns using a 3-bottle choice paradigm with water, 10% ethanol solution, and white wine (10%, v/v), along a four-week period. The influence of alcohol free-access on novelty-induced explorative behaviour in the open field, and on spatial learning and reference memory in the Morris water maze was also evaluated. Our results indicate that: (i) rats show a higher preference for alcohol, in the first two weeks of the paradigm, displaying a higher consumption of 10% ethanol solution than white wine; in the last two weeks, they reduce their alcoholic preference, drinking the same moderate amounts of the two alcoholic beverages; (ii) at the fourth week of the free-access paradigm rats show a high explorative behaviour in the central squares of the open field and an improvement in spatial information processing in the new-place learning task of the Morris water maze. In conclusion our data suggest that, interestingly, rats exposed to the free-access paradigm were able to self-regulate their alcoholic intake, and indicated that a moderate alcohol consumption was able to induce an increase in behavioural reactivity and an enhancement in spatial learning flexibility.

  20. Impact of acute guanfacine administration on stress and cue reactivity in cocaine-dependent individuals

    PubMed Central

    Moran-Santa Maria, Megan M.; Baker, Nathaniel L.; Ramakrishnan, Viswanathan; Brady, Kathleen T.; McRae-Clark, Aimee

    2014-01-01

    Background Stress and drug-paired cues increase drug craving and noradrenergic activity in cocaine-dependent individuals, thus medications that attenuate noradrenergic activity may be effective therapeutic treatment options for cocaine-dependent individuals. Objectives To examine the impact of acute administration of the α-2 adrenergic receptor agonist guanfacine on responses to multiple risk factors for relapse in cocaine-dependent individuals. Methods In a double-blind, placebo-controlled study, cocaine-dependent individuals (N=84), were randomized to receive either 2 mg guanfacine (n=50) or placebo (n=34). Within each treatment arm, subjects were randomized to either a stress (guanfacine n=26; placebo n=15) or a no-stress (guanfacine n=24; placebo n=19) group. Participants in the stress group performed the Trier Social Stress Test. Subjects in each group were exposed to a neutral cue and then to cocaine-related cues. Plasma cortisol and subjective responses were compared between the four groups. Results The no-stress guanfacine group reported greater craving in response to cocaine-cues as compared to the neutral cue (p<0.001). The guanfacine stress group reported greater subjective stress at the neutral cue than at baseline (p=0.032). The cocaine-cue increased subjective stress in the guanfacine (p<0.001) no-stress group. There were no effects of guanfacine on cortisol levels in either the stress or no stress groups (all p>0.70). Conclusion This study found no effects of a single 2 mg dose of guanfacine on reactivity to stress and cues alone or on the interaction of stress and drug cues. In cocaine-dependent individuals an acute 2 mg dose of guanfacine may not be an effective therapeutic treatment strategy. PMID:25140866

  1. Albumin Administration in Acute Ischemic Stroke: Safety Analysis of the ALIAS Part 2 Multicenter Trial

    PubMed Central

    Hill, Michael D.; Martin, Renee H.; Palesch, Yuko Y.; Moy, Claudia S.; Tamariz, Diego; Ryckborst, Karla J.; Jones, Elizabeth B.; Weisman, David; Pettigrew, Creed; Ginsberg, Myron D.

    2015-01-01

    Background Albumin treatment of ischemic stroke was associated with cardiopulmonary adverse events in previous studies and a low incidence of intracranial hemorrhage. We sought to describe the neurological and cardiopulmonary adverse events in the ALIAS Part 2 Multicenter Trial. Methods Ischemic stroke patients, aged 18–83 and a baseline NIHSS ≥ 6, were randomized to treatment with ALB or saline control within 5 hours of stroke onset. Neurological adverse events included symptomatic intracranial hemorrhage, hemicraniectomy, neurological deterioration and neurological death. Cardiopulmonary adverse events included pulmonary edema/congestive heart failure, acute coronary syndromes, atrial fibrillation, pneumonia and pulmonary thromboembolism. Results Among 830 patients, neurological and cardiopulmonary adverse events were not differentially associated with poor outcome between ALB and saline control subjects. The rate of symptomatic intracranial hemorrhage in the first 24h was low overall (2.9%, 24/830) but more common in the ALB treated subjects (RR = 2.4, CI95 1.01–5.8). The rate of pulmonary edema/CHF in the first 48h was 7.9% (59/830) and was more common among ALB treated subjects (RR = 10.7, CI95 4.3–26.6); this complication was expected and was satisfactorily managed with mandated diuretic administration and intravenous fluid guidelines. Troponin elevations in the first 48h were common, occurring without ECG change or cardiac symptoms in 52 subjects (12.5%). Conclusions ALB therapy was associated with an increase in symptomatic ICH and pulmonary edema/congestive heart failure but this did not affect final outcomes. Troponin elevation occurs routinely in the first 48 hours after acute ischemic stroke. Trial Registration ClincalTrials.gov NCT00235495 PMID:26325387

  2. Effects of Gelam and Acacia honey acute administration on some biochemical parameters of Sprague Dawley rats

    PubMed Central

    2014-01-01

    Background Since ancient times, honey has been used for medicinal purposes in many cultures; it is one of the oldest and most enduring substances used in wound management. Scientific evidence for its efficacy is widely studied, but systemic safety studies are still lacking. It is essential to study the impact of consumption of honey on the health and proper development of the consumer. Therefore, the present study was designed to observe the effects of acute administration (14 days) of Gelam honey (GH), a wild harvesting honey and Acacia honey (AH), a beekeeping honey, on male and female Sprague Dawley (SD) rats. Methods An acute oral study was performed following OECD test guideline 423, with minor modifications. In the study, GH, AH and sucrose (S) were administered at 2000 mg/kg body weight. Animals were observed for the next 14 days. Gross pathology was performed at the end of the study. Animals were observed for mortality, morbidity, body weight changes, feed and water intake. Clinical biochemistry, gross pathology, relative organ weight and histopathological examination were performed. Results Rats fed with honey did not exhibit any abnormal signs or deaths. Results showed a decrease in weight gain and energy efficiency, but significantly increased in total food intake and total calories in female rats fed with GH, compared to control (p < 0.05). Nevertheless, a significant increase in body weight was observed in male rats in all honey-treated groups. Male rats fed with AH significantly decreased in total food intake, total calories and energy efficiency. Both male and female rats fed with GH displayed a significant decrease in triglycerides compared to control group. Hepatic and renal function levels were within acceptable range. The gross necropsy analysis did not reveal changes in any of the organs examined. Conclusions Our results suggest that acute consumption of GH and AH at 2000 mg/kg body weight of male and female SD rats has some discrepancy

  3. Effect of alcohol extract of Achyranthes aspera Linn. on acute and subacute inflammation.

    PubMed

    Vetrichelvan, T; Jegadeesan, M

    2003-01-01

    The antiinflammatory activity of an alcohol extract of Achyranthes aspera was tested on carrageenin-induced hind paw oedema and cotton pellet granuloma models in albino male rats. The paw volume was measured plethysmometrically at 0, 1, 2, 3, 4 and 5 h. In the subacute model cotton pellet granuloma was produced by implantation of 50 +/- 1 mg sterile cotton in the axilla under ether anaesthesia. The animals were fed with an alcohol extract at various dose levels (125, 250, 375 and 500 mg/kg). Diclofenac sodium was used as a standard drug. The alcohol extract (375 and 500 mg/kg) showed the maximum inhibition of oedema of 65.38% and 72.37% at the end of 3 h with carrageenin-induced rat paw oedema, respectively. Using a chronic test, the extract exhibited a 40.03% and 45.32% reduction in granuloma weight.

  4. Hyperbilirubinaemia and haemolytic anaemia in acute alcoholic hepatitis: there's oil in them thar veins

    PubMed Central

    Hashmi, Salman; Allison, Michael G; McCurdy, Michael T; Reed, Robert M

    2014-01-01

    A Caucasian woman in her late 30s was evaluated after a period of binge drinking and found to have hyperbilirubinaemia for which she was referred for consideration of cholecystectomy. After exclusion of other possibilities, Zieve's syndrome was diagnosed. This is a condition of hyperbilirubinaemia, Coombs’ negative haemolytic anaemia and hyperlipidaemia associated with alcoholism. Abstinence from alcohol remains the only known effective treatment, and appreciation of the entity can prevent unnecessary biliary procedures. The patient improved with supportive measures and was discharged in stable condition. PMID:24748143

  5. Acute supra-therapeutic oral terbutaline administration has no ergogenic effect in non-asthmatic athletes.

    PubMed

    Sanchez, Anthony M J; Borrani, Fabio; Le Fur, Marie Amélie; Le Mieux, Anais; Lecoultre, Virgile; Py, Guillaume; Gernigon, Christophe; Collomp, Katia; Candau, Robin

    2013-02-01

    This study aimed to investigate the effects on a possible improvement in aerobic and anaerobic performance of oral terbutaline (TER) at a supra-therapeutic dose in 7 healthy competitive male athletes. On day 1, ventilatory threshold, maximum oxygen uptake [Formula: see text] and corresponding power output were measured and used to determine the exercise load on days 2 and 3. On days 2 and 3, 8 mg of TER or placebo were orally administered in a double-blind process to athletes who rested for 3 h, and then performed a battery of tests including a force-velocity exercise test, running sprint and a maximal endurance cycling test at Δ50 % (50 % between VT and [Formula: see text]). Lactatemia, anaerobic parameters and endurance performance ([Formula: see text] and time until exhaustion) were raised during the corresponding tests. We found that TER administration did not improve any of the parameters of aerobic performance (p > 0.05). In addition, no change in [Formula: see text] kinetic parameters was found with TER compared to placebo (p > 0.05). Moreover, no enhancement of the force-velocity relationship was observed during sprint exercises after TER intake (p > 0.05) and, on the contrary, maximal strength decreased significantly after TER intake (p < 0.05) but maximal power remained unchanged (p > 0.05). In conclusion, oral acute administration of TER at a supra-therapeutic dose seems to be without any relevant ergogenic effect on anaerobic and aerobic performances in healthy athletes. However, all participants experienced adverse side effects such as tremors. PMID:22767151

  6. Glutathione Depletion and Recovery After Acute Ethanol Administration in the Aging Mouse

    PubMed Central

    Vogt, Barbara L.; Richie, John P.

    2007-01-01

    Glutathione (GSH) plays an important role in the detoxification of ethanol (EtOH) and acute EtOH administration leads to GSH depletion in the liver and other tissues. Aging is also associated with a progressive decline in GSH levels and impairment in GSH biosynthesis in many tissues. Thus, the present study was designed to examine the effects of aging on EtOH-induced depletion and recovery of GSH in different tissues of the C57Bl/6NNIA mouse. EtOH (2-5 g/kg) or saline was administered i.p. to mice of ages 6 mo (young), 12 mo (mature), and 24 mo (old); and GSH and cyst(e)ine concentrations were measured 0-24 hours thereafter. EtOH administration (5g/kg) depleted hepatic GSH levels >50% by 6 hr in all animals. By 24 hr, levels remained low in both young and old mice, but recovered to baseline levels in mature mice. At 6 hr, the decrease in hepatic GSH was dose-dependent up to 3 g/kg EtOH, but not at higher doses. The extent of depletion at the 3 g/kg dose was dependent upon age, with old mice demonstrating significantly lower GSH levels than mature mice (P<0.001). Altogether these results indicate that aging was associated with a greater degree of EtOH and fasting-induced GSH depletion and subsequent impaired recovery in liver. An impaired ability to recover was also observed in young animals. Further studies are required to determine if an inability to recover from GSH depletion by EtOH is associated with enhanced toxicity. PMID:17343832

  7. Effects of Acute Cortisol Administration on Perceptual Priming of Trauma-Related Material

    PubMed Central

    Streb, Markus; Pfaltz, Monique; Michael, Tanja

    2014-01-01

    Intrusive memories are a hallmark symptom of posttraumatic stress disorder (PTSD). They reflect excessive and uncontrolled retrieval of the traumatic memory. Acute elevations of cortisol are known to impair the retrieval of already stored memory information. Thus, continuous cortisol administration might help in reducing intrusive memories in PTSD. Strong perceptual priming for neutral stimuli associated with a “traumatic” context has been shown to be one important learning mechanism that leads to intrusive memories. However, the memory modulating effects of cortisol have only been shown for explicit declarative memory processes. Thus, in our double blind, placebo controlled study we aimed to investigate whether cortisol influences perceptual priming of neutral stimuli that appeared in a “traumatic” context. Two groups of healthy volunteers (N = 160) watched either neutral or “traumatic” picture stories on a computer screen. Neutral objects were presented in between the pictures. Memory for these neutral objects was tested after 24 hours with a perceptual priming task and an explicit memory task. Prior to memory testing half of the participants in each group received 25 mg of cortisol, the other half received placebo. In the placebo group participants in the “traumatic” stories condition showed more perceptual priming for the neutral objects than participants in the neutral stories condition, indicating a strong perceptual priming effect for neutral stimuli presented in a “traumatic” context. In the cortisol group this effect was not present: Participants in the neutral stories and participants in the “traumatic” stories condition in the cortisol group showed comparable priming effects for the neutral objects. Our findings show that cortisol inhibits perceptual priming for neutral stimuli that appeared in a “traumatic” context. These findings indicate that cortisol influences PTSD-relevant memory processes and thus further support

  8. Dissociating Motivational From Physiological Withdrawal in Alcohol Dependence: Role of Central Amygdala κ-Opioid Receptors.

    PubMed

    Kissler, Jessica L; Walker, Brendan M

    2016-01-01

    Chronic intermittent alcohol vapor exposure leads to increased dynorphin (DYN) A-like peptide expression and heightened kappa-opioid receptor (KOR) signaling in the central nucleus of the amygdala (CeA) and these neuroadaptive responses differentiate alcohol-dependent from non-dependent phenotypes. Important for therapeutic development efforts is understanding the nature of the stimulus that drives dependence-like phenotypes such as escalated alcohol self-administration. Accordingly, the present study examined the impact of intra-CeA KOR antagonism on escalated operant alcohol self-administration and physiological withdrawal symptoms during acute withdrawal and protracted abstinence in rats previously exposed to chronic intermittent alcohol vapor. Following operant training, rats were implanted with intra-CeA guide cannula and exposed to long-term intermittent alcohol vapor exposure that resulted in escalated alcohol self-administration and elevated physiological withdrawal signs during acute withdrawal. Animals received intra-CeA infusions of the KOR antagonist nor-binaltorphimine (nor-BNI; 0, 2, 4, or 6 μg) prior to operant alcohol self-administration sessions and physiological withdrawal assessment during acute withdrawal and protracted abstinence. The results indicated that site-specific KOR antagonism in the CeA ameliorated escalated alcohol self-administration during both acute withdrawal and protracted abstinence test sessions, whereas KOR antagonism had no effect on physiological withdrawal scores at either time point. These results dissociate escalated alcohol self-administration from physiological withdrawal symptoms in relation to KOR signaling in the CeA and help clarify the nature of the stimulus that drives escalated alcohol self-administration during acute withdrawal and protracted abstinence.

  9. Acute but not chronic administration of pioglitazone promoted behavioral and neurochemical protective effects in the MPTP model of Parkinson's disease.

    PubMed

    Barbiero, Janaína K; Santiago, Ronise M; Lima, Marcelo M S; Ariza, Deborah; Morais, Lívia H; Andreatini, Roberto; Vital, Maria A B F

    2011-01-01

    The present study investigated the neurochemical, motor and cognitive effects of pioglitazone in a rat model of Parkinson's disease induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). In the first experiment, we administered MPTP, and 1h later administered a single oral dose of pioglitazone (5, 15 and 30 mg/kg). The following day, we performed the open-field test and neurochemical dose response curve. We demonstrated that 30 mg/kg of pioglitazone was capable of restoring striatal dopamine (DA) concentrations and motor behaviors. A second experiment was conducted to test the effects of two protocols (acute and chronic) of pioglitazone (30 mg/kg) administration in the open-field test, two-way active avoidance task and in the DA and metabolites levels. The acute protocol consisted of a single oral administration 1 h after MPTP, whereas the chronic protocol was performed with daily administrations starting 1 h after MPTP and ending 22 days after that. Results showed that neither protocol was able to reverse the cognitive impairment promoted by MPTP. We also demonstrated that acute treatment generated some level of neuroprotection, as confirmed by the absence of DA reduction in the group treated with pioglitazone in comparison to the sham group. By contrast, chronic treatment leaded to a reduction of striatal DA, close to MPTP administration alone. These findings suggest that acute administration of pioglitazone (30 mg/kg) was more efficient in generating beneficial effects on motor behaviors and in striatal DA levels. Nevertheless, we failed to demonstrate that pioglitazone administration improved performance on a dopamine-related cognitive task after MPTP.

  10. Spin-trapping studies of hepatic free radicals formed following the acute administration of ethanol to rats: In vivo detection of 1-hydroxyethyl radicals with PBN

    SciTech Connect

    Reinke, L.A.; Kotake, Y.; McCay, P.B.; Janzen, E.G. )

    1991-01-01

    The generation of free radicals in rat liver following the acute oral administration of ethanol was studied with the spin-trapping method, using a deuterated derivative of phenyl-N-tert-butylnitrone (PBN-d14) as the spin-trapping agent. After administration of ethanol and PBN-d14 to rats, organic extracts of the liver were prepared and subjected to ESR spectroscopy. In the case of ethanol-treated rats, the ESR spectra indicated that mixtures of radicals had been trapped, while spectra from control rats were essentially negative. The predominant spin adduct detected after ethanol treatment is proposed to be from a carbon-centered, primary alkyl radical, based on gamma-hydrogen hyperfine splitting patterns observed with PBN-d14. Oxygen-centered radicals also contributed to the ESR spectra. Liver extracts also contained low concentrations of the 1-hydroxyethyl radical spin adduct, which was indicated by weak spectral lines corresponding to those of the 1-13C-ethanol adduct. These data confirm previous suggestions that ethanol is metabolized to a free radical metabolite in rat liver. In addition, some information on types of lipid radicals generated during alcohol intoxication has been obtained.

  11. Vitamin E administration at the onset of fever prevents renal scarring in acute pyelonephritis.

    PubMed

    Sadeghi, Zhina; Kajbafzadeh, Abdol-Mohammad; Tajik, Parvin; Monajemzadeh, Maryam; Payabvash, Seyedmehdi; Elmi, Azadeh

    2008-09-01

    We evaluated the protective effects of antioxidant at the onset of fever on renal damage in a rat model of acute pyelonephritis. Twenty rats were allocated to four groups. In groups 1 to 3, the animals were given direct inoculation of Escherichia coli into the right kidney, and group four served as control. All rats in groups 1 to 3 were given once-daily intraperitoneal injections of ceftriaxon for five consecutive days, beginning on the third day after inoculation. The animals' body temperatures were monitored; as soon as body temperature reaches 38 degrees C, the rats in group 2 were given allopurinol co-treatment, whereas, in group 3, vitamin E co-treatment was started at fever onset. Both kidneys were excised 6 weeks later, for the evaluation of histopathologic changes, apoptotic damage, and concentrations of transforming growth factor-beta (TGF-beta). Only minimal changes were found in control samples. Pathologic scores of inflammation and fibrosis in group 1 were higher than in the vitamin E and allopurinol groups (P < 0.05). Apoptosis index was also decreased in groups 2 and 3, compared to group 1 (P < 0.05). There was no significant difference in average TGF-beta levels between study groups. These findings suggest that administration of vitamin E or allopurinol following the onset of fever can reduce renal damage in pyelonephritis. PMID:18523811

  12. Acute toxicity, histopathology, and coagulopathy in American kestrels (Falco sparverius) following administration of the rodenticie diphacinone

    USGS Publications Warehouse

    Rattner, Barnett A.; Horak, Katherine E.; Warner, Sarah E.; Day, Daniel D.; Meteyer, Carol U.; Voler, Steven F.; Eisemann, John D.; Johnston, John J.

    2011-01-01

    The acute oral toxicity of the anticoagulant rodenticide diphacinone was found to be over 20 times greater in American kestrels (Falco sparverius; median lethal dose 96.8 mg/kg body weight) compared with Northern bobwhite (Colinus virginianus) and mallards (Anas platyrhynchos). Modest evidence of internal bleeding was observed at necropsy, although histological examination of heart, liver, kidney, lung, intestine, and skeletal muscle revealed hemorrhage over a wide range of doses (35.1-675 mg/kg). Residue analysis suggests that the half-life of diphacinone in the liver of kestrels that survived was relatively short, with the majority of the dose cleared within 7 d of exposure. Several precise and sensitive clotting assays (prothrombin time, Russell's viper venom time, thrombin clotting time) were adapted for use in this species, and oral administration of diphacinone at 50 mg/kg increased prothrombin time and Russell?s viper venom time at 48 and 96 h postdose compared with controls. Prolongation of in vitro clotting time reflects impaired coagulation complex activity, and generally corresponded with the onset of overt signs of toxicity and lethality. In view of the toxicity and risk evaluation data derived from American kestrels, the involvement of diphacinone in some raptor mortality events, and the paucity of threshold effects data following short-term dietary exposure for birds of prey, additional feeding trials with captive raptors are warranted to characterize more fully the risk of secondary poisoning.

  13. Oral administration of sodium butyrate attenuates inflammation and mucosal lesion in experimental acute ulcerative colitis.

    PubMed

    Vieira, Erica L M; Leonel, Alda J; Sad, Alexandre P; Beltrão, Nathália R M; Costa, Thaís F; Ferreira, Talita M R; Gomes-Santos, Ana C; Faria, Ana M C; Peluzio, Maria C G; Cara, Denise C; Alvarez-Leite, Jacqueline I

    2012-05-01

    Butyrate is a four-carbon short-chain fatty acid that improves colonic trophism. Although several studies have shown the benefits of butyrate enemas in ulcerative colitis (UC), studies using the oral route are rare in the literature. In the present study, we evaluated the effect of butyrate intake in the immune response associated to UC. For that, mice were fed control or butyrate (0.5% sodium butyrate) diets for 14 days. Acute UC was induced by dextran sulphate sodium (DSS, 2.5%), replacing drinking water. The results showed that, in UC animals, oral butyrate significantly improved trophism and reduced leukocyte (eosinophil and neutrophil) infiltration in the colon mucosa and improved the inflammatory profile (activated macrophage, B and T lymphocytes) in cecal lymph nodes. In the small intestine, although mucosa histology was similar among groups, DSS treatment reduced duodenal transforming growth factor-β, increased interleukin-10 concentrations and increased memory T lymphocytes and dendritic cells in Peyer's patches. Butyrate supplementation was able to revert these alterations. When cecal butyrate concentration was analyzed in cecal content, it was still higher in the healthy animals receiving butyrate than in the UC+butyrate and control groups. In conclusion, our results show that oral administration of sodium butyrate improves mucosa lesion and attenuates the inflammatory profile of intestinal mucosa, local draining lymph nodes and Peyer's patches of DSS-induced UC. Our results also highlight the potential use of butyrate supplements as adjuvant in UC treatment.

  14. Individual differences in hyperlipidemia and vitamin E status in response to chronic alcohol self-administration in cynomolgus monkeys

    PubMed Central

    Lebold, Katie M.; Grant, Kathleen A.; Freeman, Willard M; Wiren, Kristine M.; Miller, Galen W.; Kiley, Caitlin; Leonard, Scott W.; Traber, Maret G.

    2011-01-01

    Background Chronic ethanol self-administration induces oxidative stress and exacerbates lipid peroxidation. α-Tocopherol is a potent lipid antioxidant and vitamin that is dependent upon lipoprotein transport for tissue delivery. Methods To evaluate the extent to which vitamin E status is deranged by excessive alcohol consumption, monkeys voluntarily drinking ethanol (1.36 to 3.98 g/kg/day for 19 months, n=11) were compared with non-drinkers (n=5, control) Results Three alcohol drinking animals developed hyperlipidemia with plasma triglyceride levels (1.8 ± 0.9 mmol/L) double those of normolipidemic (NL) drinkers (0.6 ± 0.2) and controls (0.6 ± 0.3, p<0.05); elevated plasma cholesterol (3.6 ± 0.5 mmol/L) compared with NL drinkers (2.3 ± 0.2, p<0.05) and controls (2.9 ± 0.3); and lower plasma α-tocopherol per triglycerides (14 ± 6 mmol/mol) than controls (27 ± 8) and NL drinkers (23 ± 6 p<0.05). Hyperlipidemic monkey liver α-tocopherol (47 ± 15 nmol/g) was lower than NL drinkers (65 ± 13) and controls (70 ± 15, p=0.080), as was adipose α-tocopherol (84 ± 37nmol/g) compared with controls (224 ± 118) and NL drinkers (285 ± 234, p<0.05). Plasma apolipoprotein (apo) CIII increased compared to baseline at both 12 and 19 months in the normolipidemic (P=0.0016 and P=0.0028, respectively) and in the hyperlipidemic drinkers (P<0.05 and P<0.05, respectively). Plasma apo H concentrations at 19 months were elevated hyperlipidemics (P<0.05) relative to concentrations in control animals. C-reactive protein (CRP), a marker of inflammation, was increased compared to baseline at both the 12- and 19-month time points in the normolipidemic (P=0.005 and P=0.0153, respectively) and hyperlipidemic drinkers (P=0.016 and P=0.0201, respectively). Conclusion A subset of alcohol drinking monkeys showed a predisposition to alcohol-induced hyperlipidemia. The defect in lipid metabolism resulted in lower plasma α-tocopherol per triglycerides and depleted adipose tissue

  15. Pentoxifylline Treatment in Acute Pancreatitis (AP)

    ClinicalTrials.gov

    2016-09-14

    Acute Pancreatitis (AP); Gallstone Pancreatitis; Alcoholic Pancreatitis; Post-ERCP/Post-procedural Pancreatitis; Trauma Acute Pancreatitis; Hypertriglyceridemia Acute Pancreatitis; Idiopathic (Unknown) Acute Pancreatitis; Medication Induced Acute Pancreatitis; Cancer Acute Pancreatitis; Miscellaneous (i.e. Acute on Chronic Pancreatitis)

  16. 76 FR 44599 - National Institute on Alcohol Abuse and Alcoholism; Notice of Closed Meeting

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    2011-07-26

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  1. Oral administration of lactulose: a novel therapy for acute carbon monoxide poisoning via increasing intestinal hydrogen production.

    PubMed

    Fan, Dan-Feng; Hu, Hui-Jun; Sun, Xue-Jun; Meng, Xiang-En; Zhang, Yu; Pan, Shu-Yi

    2016-01-01

    It has been known that the pathophysiology of carbon monoxide (CO) poisoning is related to hypoxia, the increased production of reactive oxygen species (ROS) and oxidative stress. Studies have shown that the novel, safe and effective free radical scavenger, hydrogen, has neuroprotective effects in both acute CO poisoning and delayed neuropsychological sequelae in CO poisoning. Orally administered lactulose, which may be used by some intestinal bacteria as a food source to produce endogenous hydrogen, can ameliorate oxidative stress. Based on the available findings, we hypothesize that oral administration of lactulose may be a novel therapy for acute CO poisoning via increasing intestinal hydrogen production.

  2. Effect of acute administration of L-tyrosine on oxidative stress parameters in brain of young rats.

    PubMed

    Macêdo, Livia G R P; Carvalho-Silva, Milena; Ferreira, Gabriela K; Vieira, Júlia S; Olegário, Natália; Gonçalves, Renata C; Vuolo, Francieli S; Ferreira, Gustavo C; Schuck, Patrícia F; Dal-Pizzol, Felipe; Streck, Emilio L

    2013-12-01

    Tyrosinemia type II, also known as Richner-Hanhart syndrome, is an autosomal recessive inborn error of metabolism caused by a deficiency of hepatic cytosolic tyrosine aminotransferase, and is associated with neurologic and development difficulties in numerous patients. Considering that the mechanisms underlying the neurological dysfunction in hypertyrosinemic patients are poorly known and that studies demonstrated that high concentrations of tyrosine provoke oxidative stress in vitro and in vivo in the cerebral cortex of rats, in the present study we investigate the oxidative stress parameters (enzymatic antioxidant defenses, thiobarbituric acid-reactive substances and protein carbonyl content) in cerebellum, hippocampus and striatum of 30-old-day rats after acute administration of L-tyrosine. Our results demonstrated that the acute administration of L-tyrosine increased the thiobarbituric acid reactive species levels in hippocampus and the carbonyl levels in cerebellum, hippocampus and striatum. In addition, acute administration of L-tyrosine significantly decreased superoxide dismutase activity in cerebellum, hippocampus and striatum, while catalase was increased in striatum. In conclusion, the oxidative stress may contribute, along with other mechanisms, to the neurological dysfunction characteristic of hypertyrosinemia and the administration of antioxidants may be considered as a potential adjuvant therapy for tyrosinemia, especially type II. PMID:24135880

  3. Effect of acute administration of L-tyrosine on oxidative stress parameters in brain of young rats.

    PubMed

    Macêdo, Livia G R P; Carvalho-Silva, Milena; Ferreira, Gabriela K; Vieira, Júlia S; Olegário, Natália; Gonçalves, Renata C; Vuolo, Francieli S; Ferreira, Gustavo C; Schuck, Patrícia F; Dal-Pizzol, Felipe; Streck, Emilio L

    2013-12-01

    Tyrosinemia type II, also known as Richner-Hanhart syndrome, is an autosomal recessive inborn error of metabolism caused by a deficiency of hepatic cytosolic tyrosine aminotransferase, and is associated with neurologic and development difficulties in numerous patients. Considering that the mechanisms underlying the neurological dysfunction in hypertyrosinemic patients are poorly known and that studies demonstrated that high concentrations of tyrosine provoke oxidative stress in vitro and in vivo in the cerebral cortex of rats, in the present study we investigate the oxidative stress parameters (enzymatic antioxidant defenses, thiobarbituric acid-reactive substances and protein carbonyl content) in cerebellum, hippocampus and striatum of 30-old-day rats after acute administration of L-tyrosine. Our results demonstrated that the acute administration of L-tyrosine increased the thiobarbituric acid reactive species levels in hippocampus and the carbonyl levels in cerebellum, hippocampus and striatum. In addition, acute administration of L-tyrosine significantly decreased superoxide dismutase activity in cerebellum, hippocampus and striatum, while catalase was increased in striatum. In conclusion, the oxidative stress may contribute, along with other mechanisms, to the neurological dysfunction characteristic of hypertyrosinemia and the administration of antioxidants may be considered as a potential adjuvant therapy for tyrosinemia, especially type II.

  4. Amphetamine sensitization and cross-sensitization with acute restraint stress: impact of prenatal alcohol exposure in male and female rats

    PubMed Central

    Uban, Kristina A.; Comeau, Wendy L.; Bodnar, Tamara; Yu, Wayne K.; Weinberg, Joanne; Galea, Liisa A. M.

    2014-01-01

    Rationale Individuals with fetal alcohol spectrum disorder (FASD) are at increased risk for substance use disorders (SUD). In typically developing individuals, susceptibility to SUD is associated with alterations in dopamine and hypothalamic-pituitary-adrenal (HPA) systems, and their interactions. Prenatal alcohol exposure (PAE) alters dopamine and HPA systems, yet effects of PAE on dopamine-HPA interactions are unknown. Amphetamine-stress cross-sensitization paradigms were utilized to investigate sensitivity of dopamine and stress (HPA) systems, and their interactions following PAE. Methods Adult Sprague-Dawley offspring from PAE, pair-fed, and ad libitum-fed control groups were assigned to amphetamine-(1–2mg/kg) or saline-treated conditions, with injections every other day for 15 days. 14 days later, all animals received an amphetamine challenge (1mg/kg) and 5 days later, hormones were measured under basal or acute stress conditions. Amphetamine sensitization (augmented locomotion, days 1–29) and cross-sensitization with acute restraint stress (increased stress hormones, day 34) were assessed. Results PAE rats exhibited a lower threshold for amphetamine sensitization compared to controls, suggesting enhanced sensitivity of dopaminergic systems to stimulant-induced changes. Cross-sensitization between amphetamine (dopamine) and stress (HPA hormone) systems was evident in PAE, but not in control rats. PAE males exhibited increased dopamine receptor expression (mPFC) compared to controls. Conclusions PAE alters induction and expression of sensitization/cross-sensitization, as reflected in locomotor, neural, and endocrine changes, in a manner consistent with increased sensitivity of dopamine and stress systems. These results provide insight into possible mechanisms that could underlie increased prevalence of SUD, as well as the impact of widely prescribed stimulant medications among adolescents with FASD. PMID:25420606

  5. Sumatriptan (subcutaneous route of administration) for acute migraine attacks in adults

    PubMed Central

    Derry, Christopher J; Derry, Sheena; Moore, R Andrew

    2014-01-01

    Background Migraine is a highly disabling condition for the individual and also has wide-reaching implications for society, healthcare services, and the economy. Sumatriptan is an abortive medication for migraine attacks, belonging to the triptan family. Subcutaneous administration may be preferable to oral for individuals experiencing nausea and/or vomiting Objectives To determine the efficacy and tolerability of subcutaneous sumatriptan compared to placebo and other active interventions in the treatment of acute migraine attacks in adults. Search methods We searched Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, online databases, and reference lists for studies through 13 October 2011. Selection criteria We included randomised, double-blind, placebo- and/or active-controlled studies using subcutaneous sumatriptan to treat a migraine headache episode, with at least 10 participants per treatment arm. Data collection and analysis Two review authors independently assessed trial quality and extracted data. We used numbers of participants achieving each outcome to calculate relative risk (or ‘risk ratio’) and numbers needed to treat to benefit (NNT) or harm (NNH) compared to placebo or a different active treatment. Main results Thirty-five studies (9365 participants) compared subcutaneous sumatriptan with placebo or an active comparator. Most of the data were for the 6 mg dose. Sumatriptan surpassed placebo for all efficacy outcomes. For sumatriptan 6 mg versus placebo the NNTs were 2.9, 2.3, 2.2, and 2.1 for pain-free at one and two hours, and headache relief at one and two hours, respectively, and 6.1 for sustained pain-free at 24 hours. Results for the 4 mg and 8 mg doses were similar to the 6 mg dose, with 6 mg significantly better than 4 mg only for pain-free at one hour, and 8 mg significantly better than 6 mg only for headache relief at one hour. There was no evidence of increased migraine relief if a second dose of sumatriptan 6

  6. A major QTL for acute ethanol sensitivity in the alcohol tolerant and non-tolerant selected rat lines.

    PubMed

    Radcliffe, R A; Erwin, V G; Bludeau, P; Deng, X; Fay, T; Floyd, K L; Deitrich, R A

    2009-08-01

    The Alcohol Tolerant and Alcohol Non-Tolerant rats (AT, ANT) were selectively bred for ethanol-induced ataxia as measured on the inclined plane. Here we report on a quantitative trait locus (QTL) study in an F(2) intercross population derived from inbred AT and ANT (IAT, IANT) and a follow-up study of congenics that were bred to examine one of the mapped QTLs. Over 1200 F(2) offspring were tested for inclined plane sensitivity, acute tolerance on the inclined plane, duration of the loss of righting reflex (LORR) and blood ethanol at regain of the righting reflex (BECRR). F(2) rats that were in the upper and lower 20% for inclined plane sensitivity were genotyped with 78 SSLP markers. Significant QTLs for inclined plane sensitivity were mapped on chromosomes 8 and 20; suggestive QTLs were mapped on chromosomes 1, 2 and 3. Highly significant QTLs for LORR duration (LOD = 12.4) and BECRR (LOD = 5.7) were mapped to the same locus on chromosome 1. Breeding and testing of reciprocal congenic lines confirmed the chromosome 1 LORR/BECRR QTL. A series of recombinant congenic sub-lines were bred to fine-map this QTL. Current results have narrowed the QTL to an interval of between 5 and 20 Mb. We expect to be able to narrow the interval to less than 5 Mb with additional genotyping and continued breeding of recombinant sub-congenic lines.

  7. Vitamin C Deficiency of Korean Homeless Patients Visiting to Emergency Department with Acute Alcohol Intoxication.

    PubMed

    Lee, Hui Jai; Shin, Jonghwan; Hong, Kijeong; Jung, Jin Hee

    2015-12-01

    Vitamins are essential micronutrients for maintenance of tissue functions. Vitamin deficiency is one of the most serious and common health problems among both chronic alcoholics and the homeless. However, the vitamin-level statuses of such people have been little studied. We evaluated the actual vitamin statuses of alcoholic homeless patients who visited an emergency department (ED). In this study the blood levels of vitamins B1, B12, B6, and C of 217 alcoholic homeless patients were evaluated retrospectively in a single urban teaching hospital ED. Vitamin C deficiency was observed in 84.3% of the patients. The vitamin B1, B12, and B6 deficiency rates, meanwhile, were 2.3%, 2.3%, and 23.5%, respectively. Comparing the admitted patients with those who were discharged, only the vitamin C level was lower. (P=0.003) In fact, the patients' vitamin C levels were markedly diminished, vitamin C replacement therapy for homeless patients should be considered in EDs.

  8. Vitamin C Deficiency of Korean Homeless Patients Visiting to Emergency Department with Acute Alcohol Intoxication

    PubMed Central

    2015-01-01

    Vitamins are essential micronutrients for maintenance of tissue functions. Vitamin deficiency is one of the most serious and common health problems among both chronic alcoholics and the homeless. However, the vitamin-level statuses of such people have been little studied. We evaluated the actual vitamin statuses of alcoholic homeless patients who visited an emergency department (ED). In this study the blood levels of vitamins B1, B12, B6, and C of 217 alcoholic homeless patients were evaluated retrospectively in a single urban teaching hospital ED. Vitamin C deficiency was observed in 84.3% of the patients. The vitamin B1, B12, and B6 deficiency rates, meanwhile, were 2.3%, 2.3%, and 23.5%, respectively. Comparing the admitted patients with those who were discharged, only the vitamin C level was lower. (P=0.003) In fact, the patients' vitamin C levels were markedly diminished, vitamin C replacement therapy for homeless patients should be considered in EDs. PMID:26713065

  9. Regarding the fitness to ride a bicycle under the acute influence of alcohol.

    PubMed

    Hartung, Benno; Mindiashvili, Nona; Maatz, Rüdiger; Schwender, Holger; Roth, Eckhard H; Ritz-Timme, Stefanie; Moody, Justin; Malczyk, Axel; Daldrup, Thomas

    2015-05-01

    To determine the threshold for the absolute inability to ride a bicycle, practical cycling tests and medical examinations at different blood alcohol concentrations were performed. Special attention was given to additional medical examinations, reaction tests and alcohol consumption under real-life conditions. Seventy-eight test subjects were included in the trials (37 females, 41 males). Five test subjects participated twice; thus, there were a total of 83 evaluable trials. Alcohol-related deficits were already identifiable at very low BACs. A significant increase in gross motoric disturbances compared to the soberness state did not regularly occur until a BAC of at least 0.8 g/kg was reached. At the BAC of 1.4 g/kg and above, no test subjects were able to achieve or surpass their sober driving results. Isolated highly alcoholised test subjects rode the bike in a manner that was not conspicuously different than the other sober test persons. Contrary to the assumptions of current German legal practise, it cannot be stated that all people are 'absolutely impaired' to the point of being incapable of riding bicycle at BACs of at least 1.6 g/kg. PMID:25428289

  10. Effects of Alcohol and Saccharin Deprivations on Concurrent Ethanol and Saccharin Operant Self-Administration by Alcohol-Preferring (P) Rats

    PubMed Central

    Toalston, Jamie E.; Oster, Scott M.; Kuc, Kelly A.; Pommer, Tylene J.; Murphy, James M.; Lumeng, Lawrence; Bell, Richard L.; McBride, William J.; Rodd, Zachary A.

    2008-01-01

    Consumption of sweet solutions has been associated with a reduction in withdrawal symptoms and alcohol craving in humans. The objective of the present study was to determine the effects of EtOH and saccharin (SACC) deprivations on operant oral self-administration. P rats were allowed to lever press concurrently self-administer EtOH (15% v/v) and SACC (0.0125% g/v) for 8 weeks. Rats were then maintained on daily operant access (non-deprived), deprived of both fluids (2 weeks), deprived of SACC and given 2 ml of EtOH daily, or deprived of EtOH and given 2 ml of SACC daily. All groups were then given two weeks of daily operant access to EtOH and SACC, followed by an identical second deprivation period. P rats responded more for EtOH than SACC. All deprived groups increased responding on the EtOH lever, but not on the SACC lever. Daily consumption of 2 ml EtOH decreased the duration of the ADE. Home cage access to 2 ml SACC also decreased the ADE but to a lesser extent than access to EtOH. A second deprivation period further increased and prolonged the expression of an ADE. These results show EtOH is a more salient reinforcer than SACC. With concurrent access to EtOH and SACC, P rats do not display a saccharin deprivation effect. Depriving P rats of both EtOH and SACC had the most pronounced effect on the magnitude and duration of the ADE, suggesting that there may be some interactions between EtOH and SACC in their CNS reinforcing effects. PMID:18400451

  11. Enforcing the Minimum Drinking Age Law: A Survey of College Administrators and Security Chiefs. Current Research Summary. Bulletin Series: Alcohol and Other Drug Prevention.

    ERIC Educational Resources Information Center

    Wechsler, Henry; Moeykens, Barbara A.; DeJong, William

    This bulletin reviews the results of a survey of college administrators and security officials by the Harvard School of Public Health concerning their schools' policies regarding alcohol problems on campus. A total of 529 respondents from 347 public and private four-year institutions were asked to complete a mailed questionnaire which examined…

  12. Acute care for alcohol intoxication. Be prepared to consider clinical dilemmas.

    PubMed

    Yost, David A

    2002-12-01

    The clinical assessment of an acutely intoxicated patient should be performed with meticulous care and include repetitive examinations to properly determine the patient's condition. Multiple factors, such as trauma and concomitant use of other drugs, can confuse the diagnostic picture and affect the choice of therapy. In this article, Dr Yost reviews the diagnostic considerations, appropriate treatment, and clinic discharge for the intoxicated patient.

  13. Acute cadmium administration to rats exerts both immunosuppressive and proinflammatory effects in spleen.

    PubMed

    Demenesku, Jelena; Mirkov, Ivana; Ninkov, Marina; Popov Aleksandrov, Aleksandra; Zolotarevski, Lidija; Kataranovski, Dragan; Kataranovski, Milena

    2014-12-01

    Conflicting data (both suppression and augmentation as well as lack of the effect) exist in respect to cadmium (Cd) and splenic T cell-based immune cell activity. Spleen is also the site of innate immune responses but impact of Cd on this type of immunity has been less explored. In the present study the effects of acute Cd administration on basic aspects of both T cell-based and innate immune spleen cell activity were examined in rats. Intraperitoneal injection of 1mg of Cd/kg resulted in decrease in concanavalin A (ConA) induced proliferation which seems to be more related to altered spleen cells responsiveness to IL-2 than to apoptosis. Differential effects on proinflammatory T cell derived cytokines were observed (decreases of IFN-γ gene expression and ConA-stimulated production, but increases in IL-17 mRNA levels with no effect on concentrations of protein product). Reduction of IFN-γ production seemed not to rely on IL-4 and IL-10, but at least partly on nitric oxide (NO). Increased activity relevant for innate immunity (granulocyte and CD11b(+) cell accumulation in the spleen, inducible nitric oxide synthase/iNOS expression and NO production by spleen cells) was observed, but there was a decrease in respiratory burst (dihydrorhodamine/DHR oxidation and nitroblue tetrazolium/NBT reduction). Increases of TNF-α and IL-1β gene expression and IL-1β protein product were noted as well. Administration of 0.5mg Cd/kg resulted in less pronounced (ConA-induced proliferation) or lack of the effect (IFN-γ production) on spleen T cell activities and on innate activities (granulocyte accumulation, NO production) as well. However, increases of spleen cell respiratory burst activity and IL-1β production were observed. Effects of lower cadmium doses (5ppm and 50ppm) on several aspects of spleen cell immune activity were observed in intermediate period of exposure (30 days, oral intake) as well. Differential effects of Cd on immune activities of spleen cells might

  14. Acute third ventricular administration of leptin decreases protein and fat in self-selecting rats.

    PubMed

    Wetzler, Sandrine; Jean-Joseph, Gwladys; Even, Patrick; Tomé, Daniel; Larue-Achagiotis, Christiane

    2005-04-15

    The peripheral administration of leptin reduces food intake (FI) body weight gain (BWG) and modifies food choice. The aim of this study was to examine the effect of acute cerebral injections of leptin on food selection in rats. Male rats were first adapted to the food choice paradigm (protein, carbohydrate, fat) for 3 weeks. They were then implanted with a cannula in the third ventricle. Leptin (leptin group=L) or saline (control group=C) injections were performed at either the beginning or the end of the night at 4-day intervals. FI was recorded continuously, 3 days before, during and then after injections. Rats were sacrificed 86 h after the second injection. After both injections, BWG and FI were reduced. The reduction in FI concerned only nocturnal intake, whatever the timing of the injection. When the injection was given at the beginning of the night, the reductions after a 1-h latency period were -45% and -27.5% during the first and second days, respectively. Following the second injection, the same effects were observed immediately (-16% and -41%, respectively). Only the fat and protein intakes were significantly reduced. This lower FI was due to a reduction in meal size and duration. The reduction resulted in a lower BWG and total white adipose tissue mass. At the time of sacrifice, 6 h after food deprivation, leptinemia and insulinemia were reduced in leptin-treated rats. Glycemia values were identical. It was thus demonstrated that central leptin was a satiation factor rather than a satiety factor.

  15. Acute Administration of Methionine Affects Performance of Swiss Mice in Learning and Memory Paradigms.

    PubMed

    Abi, I; Magaji, R A; Magaji, M G

    2015-12-20

    Methionine, an essential amino acid, plays an essential role in the central nervous system CNS development. It serves as a crucial intermediate in the methylation, trans-sulfuration and amino- phosphorylationpathways,necessary for the synthesis of nucleic acids, phospholipids, hormones, neurotransmitters, antioxidants, polyamines, catecholamines and other biogenic amines. The effect of methionine on learning and memory in mice was investigated using Morris water maze (MWM), Elevated plus maze(EPM) and Y maze (YM). Animals were administered with distilled water (control), methionine (1,700mg/kg); folate (3mg/kg) or methionine (1700mg/kg) plus folate (3mg/kg) for 14 days. Escape latency and time spent in target quadrants; transfer latency and percentage spontaneous alternations were measured in the MWM, EPM and YM respectively. The animals were anaesthetized with inhalational chloroform and their brains subsequently harvested, homogenized and assayed for acetylcholinesterase24 hours after the experiment.Folate significantly(p<0.05) increased transfer latency (53.33 ± 12.62) as compared to control (20.1 ± 5.01) and reduced spontaneous alternations significantly (25.0 ± 8.9) when compared to control (44.33 ± 3.07). When folate was combined with methionine there was also a significant increase in transfer latency (43.0 ± 14.39) when compared with control (20.1 ± 5.01). Folate-methionine combination also significantly reduced spontaneous alternations (20.4 ± 8.4) as compared to the control (44.33 ± 3.07) much more than folate alone. Acetylcholinesterase activities in all groups were not statistically significant. It can be concluded that acute methionine administration has some benefits in memory enhancement. However, a short course folate supplementation impairslearning and working memory especially when combined with methioninewhich may be as a result of sudden overwhelming of the methylation cycle, leading to homocysteinemia which is pro-dementia.

  16. Acute Administration of Methionine Affects Performance of Swiss Mice in Learning and Memory Paradigms.

    PubMed

    Abi, I; Magaji, R A; Magaji, M G

    2015-01-01

    Methionine, an essential amino acid, plays an essential role in the central nervous system CNS development. It serves as a crucial intermediate in the methylation, trans-sulfuration and amino- phosphorylationpathways,necessary for the synthesis of nucleic acids, phospholipids, hormones, neurotransmitters, antioxidants, polyamines, catecholamines and other biogenic amines. The effect of methionine on learning and memory in mice was investigated using Morris water maze (MWM), Elevated plus maze(EPM) and Y maze (YM). Animals were administered with distilled water (control), methionine (1,700mg/kg); folate (3mg/kg) or methionine (1700mg/kg) plus folate (3mg/kg) for 14 days. Escape latency and time spent in target quadrants; transfer latency and percentage spontaneous alternations were measured in the MWM, EPM and YM respectively. The animals were anaesthetized with inhalational chloroform and their brains subsequently harvested, homogenized and assayed for acetylcholinesterase24 hours after the experiment.Folate significantly(p<0.05) increased transfer latency (53.33 ± 12.62) as compared to control (20.1 ± 5.01) and reduced spontaneous alternations significantly (25.0 ± 8.9) when compared to control (44.33 ± 3.07). When folate was combined with methionine there was also a significant increase in transfer latency (43.0 ± 14.39) when compared with control (20.1 ± 5.01). Folate-methionine combination also significantly reduced spontaneous alternations (20.4 ± 8.4) as compared to the control (44.33 ± 3.07) much more than folate alone. Acetylcholinesterase activities in all groups were not statistically significant. It can be concluded that acute methionine administration has some benefits in memory enhancement. However, a short course folate supplementation impairslearning and working memory especially when combined with methioninewhich may be as a result of sudden overwhelming of the methylation cycle, leading to homocysteinemia which is pro-dementia. PMID

  17. Modulation of mood and cognitive performance following acute administration of Melissa officinalis (lemon balm).

    PubMed

    Kennedy, D O; Scholey, Andrew B; Tildesley, N T J; Perry, E K; Wesnes, K A

    2002-07-01

    Melissa officinalis (lemon balm) is a traditional herbal medicine, which enjoys contemporary usage as a mild sedative, spasmolytic and antibacterial agent. It has been suggested, in light of in vitro cholinergic binding properties, that Melissa extracts may effectively ameliorate the cognitive deficits associated with Alzheimer's disease. To date, no study has investigated the effects on cognition and mood of administration of Melissa to healthy humans. The present randomised, placebo-controlled, double-blind, balanced-crossover study investigated the acute effects on cognition and mood of a standardised extract of M. officinalis. Twenty healthy, young participants received single doses of 300, 600 and 900 mg of M. officinalis (Pharmaton) or a matching placebo at 7-day intervals. Cognitive performance was assessed using the Cognitive Drug Research (CDR) computerised test battery and two serial subtraction tasks immediately prior to dosing and at 1, 2.5, 4 and 6 h thereafter. In vitro IC(50) concentrations for the displacement of [3H]-(N)-nicotine and [3H]-(N)-scopolamine from nicotinic and muscarinic receptors in human occipital cortex tissue were also calculated. Results, utilising the cognitive factors previously derived from the CDR battery, included a sustained improvement in Accuracy of Attention following 600 mg of Melissa and time- and dose-specific reductions in both Secondary Memory and Working Memory factors. Self-rated "calmness," as assessed by Bond-Lader mood scales, was elevated at the earliest time points by the lowest dose, whilst "alertness" was significantly reduced at all time points following the highest dose. Both nicotinic and muscarinic binding were found to be low in comparison to the levels found in previous studies.

  18. Changes in brain oxidative metabolism induced by inhibitory avoidance learning and acute administration of amitriptyline.

    PubMed

    González-Pardo, Héctor; Conejo, Nélida M; Arias, Jorge L; Monleón, Santiago; Vinader-Caerols, Concepción; Parra, Andrés

    2008-05-01

    The effects of antidepressant drugs on memory have been somewhat ignored, having been considered a mere side effect of these compounds. However, the memory impairment caused by several antidepressants could be considered to form part of their therapeutic effects. Amitriptyline is currently one of the most prescribed tricyclic antidepressants, and exerts marked anticholinergic and antihistaminergic effects. In this study, we evaluated the effects of inhibitory avoidance (IA) learning and acute administration of amitriptyline on brain oxidative metabolism. Brain oxidative metabolism was measured in several limbic regions using cytochrome oxidase (CO) quantitative histochemistry. Amitriptyline produced a clear impairment in the IA task. In animals exposed only to the apparatus, amitriptyline decreased CO activity in nine brain regions, without affecting the remaining regions. In animals that underwent the IA training phase, amitriptyline reduced CO activity in only three of these nine regions. In animals treated with saline, IA acquisition increased CO activity in the medial prefrontal cortex, the prelimbic cortex, and the medial mammillary body, and diminished it in the medial septum and the nucleus basalis of Meynert with respect to animals exposed only to the IA apparatus. In animals treated with amitriptyline, IA acquisition did not modify CO activity in any of these regions, but increased it in the anteromedial nucleus of the thalamus, the diagonal band of Broca, and the dentate gyrus. The results reveal a pattern of changes in brain oxidative metabolism induced by IA training in saline-treated animals that was clearly absent in animals submitted to the same behavioural training but treated with amitriptyline. PMID:18313125

  19. Effects of naltrexone on alcohol drinking patterns and extinction of alcohol seeking in baboons

    PubMed Central

    Kaminski, Barbara J.; Duke, Angela N.; Weerts, Elise M.

    2012-01-01

    Rationale Understanding naltrexone’s effect on motivation to drink and pattern of drinking is important for better treatment outcomes and for comparison with novel medications. Objectives Naltrexone’s effects on number and pattern of seeking, self-administration, and extinction responses were evaluated in two groups of baboons trained under a 3 component chained schedule of reinforcement (CSR). Methods Alcohol (4% w/v; n=4; Alcohol Group) or a preferred non-alcoholic beverage (n=4; Control Group) was available for self-administration only in Component 3 of the CSR. Responses in Component 2 provided indices of motivation to drink (seeking). Naltrexone (0.32 – 3.2 mg/kg) and saline were administered before drinking and Component 2 extinction sessions. Results Acute doses of naltrexone significantly decreased total self-administration responses (p<0.01), intake volume (p<0.001) and g/kg of alcohol (p<0.01) in the Alcohol Group only. Pattern of drinking did not change, but number of drinks during the initial drinking bout was decreased significantly by naltrexone for both groups (P<0.05). During within-session extinction tests, acute naltrexone significantly decreased time to reach extinction (p<0.01) and number of seeking responses (p<0.05), particularly early in the extinction period in the Alcohol Group only. When administered chronically, naltrexone did not decrease progressive-ratio breaking points to gain access to alcohol, but dose-dependently reduced alcohol self-administration (p<0.05) by decreasing the magnitude of the initial drinking bout. Conclusions The results support clinical observations that naltrexone may be most effective at reducing self-administration in the context of ongoing alcohol availability and may reduce motivation to drink in the presence of alcohol-related cues. PMID:22451093

  20. Acute Alcohol Intoxication and Suicide Among U.S. Ethnic/Racial Groups: Findings from the National Violent Death Reporting System

    PubMed Central

    Caetano, Raul; Kaplan, Mark S.; Huguet, Nathalie; McFarland, Bentson H.; Conner, Kenneth; Giesbrecht, Norman; Nolte, Kurt B.

    2012-01-01

    Background To assess the prevalence and sociodemographic correlates of suicide involving acute alcohol intoxication among U.S. ethnic minorities. Methods Data were derived from the restricted 2003–2009 National Violent Death Reporting System (NVDRS). The study focused on the sociodemographic and toxicological information of 59,384 male and female suicide decedents for 16 states of the U.S. Acute alcohol intoxication was defined as having a blood alcohol content (BAC) ≥ 0.08 g/dl. Overall, 76% of decedents were tested for the presence of alcohol. Results The proportion of suicide decedents with a positive BAC ranged from 47% among American Indians/Alaska Natives (AIs/ANs) to 23% among Asians/Pacific Islanders (PIs). Average BAC was highest among AIs/ANs. Among those who were tested for BAC, the proportion of decedents legally intoxicated prior to suicide was: Blacks, 15%; AIs/ANs, 36%; Asians/PIs, 13%; Hispanics, 28%. Bivariate associations showed that most suicide decedents who were legally intoxicated were male, younger than 30 years of age, with a high school education, not married, non-veterans, lived in metropolitan areas, and used a firearm to complete suicide. However, with the exception of Whites, most of these associations became not statistically significant in multivariate analysis. Conclusions Alcohol use and legal intoxication prior to completing suicide are common among U.S. ethnic groups, especially among males and those who are younger than 30 years of age. The AI/AN group had the highest mean BAC, the highest rate of legal intoxication and decedents who were particularly young. Suicide prevention strategies should address alcohol use as a risk factor. Alcohol problems prevention strategies should focus on suicide as a consequence of alcohol use, especially among AI/AN youth and young adults. PMID:23384174

  1. Dose-response relationship of an environmental mixture of pyrethroids following an acute oral administration in the rat

    EPA Science Inventory

    Dose-response relationship of an environmental mixture of pyrethroids following an acute oral administration in the rat M.F. Hughes1, D.G. Ross1, J.M. Starr1, E.J. Scollon1,2, M.J. Wolansky1,3, K.M. Crofton1, M.J. DeVito1,4 1U.S. EPA, ORD, Research Triangle Park, NC, 2U.S. EPA,...

  2. Influence of drugs of abuse and alcohol upon patients admitted to acute psychiatric wards: physician's assessment compared to blood drug concentrations.

    PubMed

    Mordal, Jon; Medhus, Sigrid; Holm, Bjørn; Mørland, Jørg; Bramness, Jørgen G

    2013-06-01

    In acute psychiatric services, rapid and accurate detection of psychoactive substance intake may be required for appropriate diagnosis and intervention. The aim of this study was to investigate the relationship between (a) drug influence as assessed by physicians and (b) blood drug concentrations among patients admitted to acute psychiatric wards. We also explored the possible effects of age, sex, and psychotic symptoms on physician's assessment of drug influence. In a cross-sectional study, the sample comprised 271 consecutive admissions from 2 acute psychiatric wards. At admission, the physician on call performed an overall judgment of drug influence. Psychotic symptoms were assessed with the positive subscale of the Positive and Negative Syndrome Scale. Blood samples were screened for a wide range of psychoactive substances, and quantitative results were used to calculate blood drug concentration scores. Patients were judged as being under the influence of drugs and/or alcohol in 28% of the 271 admissions. Psychoactive substances were detected in 56% of the blood samples. Altogether, 15 different substances were found; up to 8 substances were found in samples from 1 patient. Markedly elevated blood drug concentration scores were estimated for 15% of the patients. Physician's assessment was positively related to the blood drug concentration scores (r = 0.52; P < 0.001), to symptoms of excitement, and to the detection of alcohol, cannabis, and amphetamines. The study demonstrates the major impact of alcohol and drugs in acute psychiatric settings and illustrates the challenging nature of the initial clinical assessment.

  3. Effect of acute lindane and alcohol intoxication on serum concentration of enzymes and fatty acids in rats.

    PubMed

    Radosavljević, T; Mladenović, D; Vucević, D; Petrović, J; Hrncić, D; Djuric, D; Loncar-Stevanović, H; Stanojlović, O

    2008-05-01

    This study examines possible synergistic effects of lindane and ethanol on inducing liver injury and serum fatty acid derangement in adult male Wistar rats. When administered together, ethanol and lindane-induced even more pronounced increase of alanine aminotransferase (165 +/- 10 U/L) and gamma-glutamyltranspeptidase activity (10.3 +/- 0.6 U/L) than after isolated administration of either substance. In addition, separate administration of lindane and ethanol was followed by a significant decrease of linoleic acid level in the serum (301 +/- 38 mg/L, 276 +/- 35 mg/L vs. 416 +/- 48 mg/L). However, when ethanol administration was followed by lindane injection, serum linoleic acid was at the similar level found in the control group (516 +/- 62 mg/L). Ethanol-treated rats that received lindane 30 min after ethanol administration have shown a marked increase of palmitic (421 +/- 27 mg/L) and linolic acid level (43 +/- 5 mg/L) in comparison with rats that have been treated only with ethanol (316+/-26 mg/L for palmitic and 32 +/- 2 mg/L for linolic acid) or lindane (295 +/- 26 mg/L for palmitic and 301 +/- 38 mg/L for linolic acid). Linolic acid level was significantly greater in comparison with control group (29 +/- 1 mg/L). In conclusion, this study found enough evidence to support the hypothesis that acute ethanol intoxication potentiates lindane-induced liver injury and enhances lipid derangement.

  4. [Characteristics of the pharmacological treatment of toxic liver damage in patients with an alcohol abused syndrome and an acute severe ethanol poison].

    PubMed

    Shilov, V V; Shikalova, I A; Vasil'ev, S A; Loladze, A T; Batotsyrenov, B V

    2012-01-01

    The examination of 130 patients with an alcohol abused syndrome and a severe ethanol poison have revealed that ethanol action are accompanied by significant metabolic disturbances. The comparative evaluation of the inclusion of heptral and remaxol in the treatment has shown that remaxol improves the clinical course of mentioned disorders decreasing the frequency and duration of alcohol delirium. Patients treated with this drug spent less time in acute care and their treatment duration was shorter. Remaxol reduces more effectively the severity of metabolic disorders.

  5. Alcohol and Migraine

    MedlinePlus

    ... on Pinterest Follow us on Instagram DONATE TODAY Alcohol and Migraine Abuse, Maltreatment, and PTSD and Their ... to Migraine Altitude, Acute Mountain Sickness and Headache Alcohol and Migraine Anxiety and Depression Caffeine and Migraine ...

  6. Effect of acute and chronic administration of L-tyrosine on nerve growth factor levels in rat brain.

    PubMed

    Ferreira, Gabriela K; Jeremias, Isabela C; Scaini, Giselli; Carvalho-Silva, Milena; Gomes, Lara M; Furlanetto, Camila B; Morais, Meline O; Schuck, Patrícia F; Ferreira, Gustavo C; Streck, Emilio L

    2013-08-01

    Most inborn errors of tyrosine catabolism produce hypertyrosinemia. Neurological manifestations are variable and some patients are developmentally normal, while others show different degrees of developmental retardation. Considering that current data do not eliminate the possibility that elevated levels of tyrosine and/or its derivatives may have noxious effects on central nervous system development in some patients, the present study evaluated nerve growth factor (NGF) levels in hippocampus, striatum and posterior cortex of young rats. In our acute protocol, Wistar rats (10 and 30 days old) were killed 1 h after a single intraperitoneal administration of L-tyrosine (500 mg/kg) or saline. Chronic administration consisted of L-tyrosine (500 mg/kg) or saline injections 12 h apart for 24 days in Wistar rats (7 days old); the rats were killed 12 h after the last injection. NGF levels were then evaluated. Our findings showed that acute administration of L-tyrosine decreased NGF levels in striatum of 10-day-old rats. In the 30-day-old rats, NGF levels were decreased in hippocampus and posterior cortex. On the other hand, chronic administration of L-tyrosine increased NGF levels in posterior cortex. Decreased NGF may impair growth, differentiation, survival and maintenance of neurons. PMID:23690230

  7. MR Imaging Findings in Alcoholic and Nonalcoholic Acute Wernicke's Encephalopathy: A Review

    PubMed Central

    Manzo, Gaetana; De Gennaro, Angela; Cozzolino, Attilio; Serino, Antonietta; Fenza, Giacomo; Manto, Andrea

    2014-01-01

    Wernicke's encephalopathy (WE) is a severe neurological syndrome caused by thiamine (vitamin B1) deficiency and clinically characterized by the sudden onset of mental status changes, ocular abnormalities, and ataxia. Apart from chronic alcoholism, the most common cause of WE, a lot of other conditions causing malnutrition and decreasing thiamine absorption such as gastrointestinal surgical procedures and hyperemesis gravidarum must be considered as predisposing factors. Due to its low prevalence and clinical heterogeneity, WE is often misdiagnosed, leading to persistent dysfunctions and, in some cases, to death. Nowadays, MR imaging of the brain, showing T2 and FLAIR hyperintensities in typical (thalami, mammillary bodies, tectal plate, and periaqueductal area) and atypical areas (cerebellum, cranial nerve nuclei, and cerebral cortex), is surely the most important and effective tool in the diagnostic assessment of WE. The aim of this paper is to propose a state of the art of the role of MR imaging in the early diagnosis of this complex disease. PMID:25050351

  8. [Pecularities of correction of alcohol affctions of liver in patients with acute ethanol poisoning in the setting of consequence of toxic effect of ethanol].

    PubMed

    Shilov, V V; batotsyrenov, B V; Vasil'ev, S A; Shikalova, I A; Kuznetsov, O A

    2012-06-01

    The aim of this work was to test the usage of infusion of hepatoprotector "remaxol" in intensive therapy of acute ethanol poisoning accompanied with severe alcohol affections of the lever. In the result of the examination and treatment of 130 patients it was established that severe alcohol poisonings registered on alcohol abused patients with toxic hepatopathy, are always accompanied with serious metabolic violations. In the process of a comparative valuation of the using of heptral (ademethionin) and remaxol in the intensive therapy of alcohol poisonings it has been revealed that the using of remaxol led to improvement of the clinic of that poisonings, what had been registered as a decrease of frequency and duration of an alcohol delirium from 33,9% to 10,8%, a decrease of frequency of secondary lung complication from 18,5 to 3,1%, a decrease of a duration of treatment in intensive care unit from 7,3 +/- 0,6 to 5,6 +/- 0,3 and a hospital treatment duration from 11,8 +/- 0,5 to 9,0 +/- 0,3 days. Biochemical investigation has shown that using as heptral, as remaxol led to improvement of lever damages due to alcohol. However remaxol compared with heptral was better in the treatment of metabolic violations.

  9. Pilot study of the safety of starting administration of low-dose aspirin and cilostazol in acute ischemic stroke.

    PubMed

    Fujita, Keishi; Komatsu, Yoji; Sato, Naoaki; Higuchi, Osamu; Kujiraoka, Yuji; Kamezaki, Takao; Suzuki, Kensuke; Matsumura, Akira

    2011-01-01

    Progressive stroke is a serious problem due to the associated morbidity and mortality. Aspirin is recommended for acute ischemic stroke, but does not reduce the frequency of stroke progression. No standard treatment has been approved for the prevention of stroke progression. Cilostazol, which reduces platelet aggregation about 3 hours after single administration, does not increase the frequency of bleeding events when compared with aspirin or a placebo. Moreover, the combination of 100 mg aspirin and 200 mg cilostazol does not increase the frequency of bleeding events compared with only 100 mg aspirin, and thus is expected to prevent stroke progression with a high degree of safety. The present study investigated the safety of this combination of two drugs administered at the above concentrations in 54 patients with acute ischemic stroke within 48 hours of stroke onset. Modified National Institutes of Health Stroke Scale (NIHSS) measurements were performed at baseline and again on day 4 to 7. Progressive stroke was defined as an increase greater than or equal to 1 point on NIHSS. Patient scores on the modified Rankin Scale (mRS) were evaluated at baseline and 3 months after enrollment. Stroke progression occurred in 11.1% of the patients. The percentages of patients with mRS score from 0 to 2 were 42.6% and 75% at baseline and 3 months, respectively. No symptomatic intracranial hemorrhage or major extracranial hemorrhage occurred. These results suggest that administration of aspirin and cilostazol is safe for acute ischemic stroke.

  10. Effects of alcohol on beta-endorphin and reproductive hormones in the male rat.

    PubMed

    Adams, M L; Cicero, T J

    1991-08-01

    In an attempt to examine the relationship between alcohol-induced alterations in immunoreactive beta-endorphin (i-beta E) levels in the hypothalamic-pituitary-gonadal axis and the synthesis and release of reproductive hormones, male rats were treated with either an acute intraperitoneal injection of alcohol or were chronically exposed to an alcohol-containing liquid diet. Hypothalamic, pituitary, serum, and testicular levels of immunoreactive beta-endorphin (i-beta E) and serum levels of luteinizing hormone (LH) and testosterone were measured at various times after initiation of these treatments. Testicular interstitial fluid (TIF) volumes and levels of TIF i-beta E and testosterone were also measured 4 hr after acute treatment as an index of testicular release of these substances. Acute alcohol decreased pituitary levels of i-beta E and increased serum levels of the peptide for up to 1 hr after its injection, but did not alter hypothalamic or testicular levels. Acute alcohol markedly increased TIF i-beta E and decreased TIF testosterone and TIF volume. Sharp decreases in serum LH and testosterone were observed in association with these acute changes in i-beta E levels in the pituitary, blood, and testes. During chronic alcohol exposure serum testosterone levels were substantially depressed, but tolerance appeared to develop quickly to the chronic effects of alcohol on serum LH. Similarly, tolerance to alcohol's effects on i-beta E levels in the pituitary and serum also appeared to develop during chronic alcohol administration. However, hypothalamic and testicular i-beta E levels were markedly suppressed by chronic alcohol administration in contrast to the lack of effect observed after acute alcohol administration.(ABSTRACT TRUNCATED AT 250 WORDS)

  11. Acute Morphine Administration Reduces Cell-Mediated Immunity and Induces Reactivation of Latent Herpes Simplex Virus Type 1 in BALB/c Mice

    PubMed Central

    Mojadadi, Shafi; Jamali, Abbas; Khansarinejad, Behzad; Soleimanjahi, Hoorieh; Bamdad, Taravat

    2009-01-01

    Acute morphine administration is known to alter the course of herpes simplex virus infection. In this study, the effect of acute morphine administration on the reactivation of latent herpes was investigated in a mouse model. Because of the important role of cytolytic T lymphocyte (CTL) activity in the inhibition of herpes simplex virus type 1 (HSV-1) reactivation, the effect of acute morphine administration on CTL responses was also evaluated. Furthermore, lymphocyte proliferation and IFN-γ production were evaluated for their roles in the induction of the CTL response. The findings showed that acute morphine administration significantly reduced CTL responses, lymphocyte proliferation, and IFN-γ production. Furthermore, acute morphine administration has been shown to reactivate latent HSV-1. Previous studies have shown that cellular immune responses have important roles in the inhibition of HSV reactivation. These findings suggest that suppression of a portion of the cellular immune response after acute morphine administration may constitute one part of the mechanism that induces HSV reactivation. PMID:19403060

  12. Acute Carnosine Administration Increases Respiratory Chain Complexes and Citric Acid Cycle Enzyme Activities in Cerebral Cortex of Young Rats.

    PubMed

    Macedo, Levy W; Cararo, José H; Maravai, Soliany G; Gonçalves, Cinara L; Oliveira, Giovanna M T; Kist, Luiza W; Guerra Martinez, Camila; Kurtenbach, Eleonora; Bogo, Maurício R; Hipkiss, Alan R; Streck, Emilio L; Schuck, Patrícia F; Ferreira, Gustavo C

    2016-10-01

    Carnosine (β-alanyl-L-histidine) is an imidazole dipeptide synthesized in excitable tissues of many animals, whose biochemical properties include carbonyl scavenger, anti-oxidant, bivalent metal ion chelator, proton buffer, and immunomodulating agent, although its precise physiological role(s) in skeletal muscle and brain tissues in vivo remain unclear. The aim of the present study was to investigate the in vivo effects of acute carnosine administration on various aspects of brain bioenergetics of young Wistar rats. The activity of mitochondrial enzymes in cerebral cortex was assessed using a spectrophotometer, and it was found that there was an increase in the activities of complexes I-III and II-III and succinate dehydrogenase in carnosine-treated rats, as compared to vehicle-treated animals. However, quantitative real-time RT-PCR (RT-qPCR) data on mRNA levels of mitochondrial biogenesis-related proteins (nuclear respiratory factor 1 (Nrf1), peroxisome proliferator-activated receptor-γ coactivator 1-α (Ppargc1α), and mitochondrial transcription factor A (Tfam)) were not altered significantly and therefore suggest that short-term carnosine administration does not affect mitochondrial biogenesis. It was in agreement with the finding that immunocontent of respiratory chain complexes was not altered in animals receiving carnosine. These observations indicate that acute carnosine administration increases the respiratory chain and citric acid cycle enzyme activities in cerebral cortex of young rats, substantiating, at least in part, a neuroprotector effect assigned to carnosine against oxidative-driven disorders. PMID:26476839

  13. Acute Carnosine Administration Increases Respiratory Chain Complexes and Citric Acid Cycle Enzyme Activities in Cerebral Cortex of Young Rats.

    PubMed

    Macedo, Levy W; Cararo, José H; Maravai, Soliany G; Gonçalves, Cinara L; Oliveira, Giovanna M T; Kist, Luiza W; Guerra Martinez, Camila; Kurtenbach, Eleonora; Bogo, Maurício R; Hipkiss, Alan R; Streck, Emilio L; Schuck, Patrícia F; Ferreira, Gustavo C

    2016-10-01

    Carnosine (β-alanyl-L-histidine) is an imidazole dipeptide synthesized in excitable tissues of many animals, whose biochemical properties include carbonyl scavenger, anti-oxidant, bivalent metal ion chelator, proton buffer, and immunomodulating agent, although its precise physiological role(s) in skeletal muscle and brain tissues in vivo remain unclear. The aim of the present study was to investigate the in vivo effects of acute carnosine administration on various aspects of brain bioenergetics of young Wistar rats. The activity of mitochondrial enzymes in cerebral cortex was assessed using a spectrophotometer, and it was found that there was an increase in the activities of complexes I-III and II-III and succinate dehydrogenase in carnosine-treated rats, as compared to vehicle-treated animals. However, quantitative real-time RT-PCR (RT-qPCR) data on mRNA levels of mitochondrial biogenesis-related proteins (nuclear respiratory factor 1 (Nrf1), peroxisome proliferator-activated receptor-γ coactivator 1-α (Ppargc1α), and mitochondrial transcription factor A (Tfam)) were not altered significantly and therefore suggest that short-term carnosine administration does not affect mitochondrial biogenesis. It was in agreement with the finding that immunocontent of respiratory chain complexes was not altered in animals receiving carnosine. These observations indicate that acute carnosine administration increases the respiratory chain and citric acid cycle enzyme activities in cerebral cortex of young rats, substantiating, at least in part, a neuroprotector effect assigned to carnosine against oxidative-driven disorders.

  14. Structural characterization, molecular modification and hepatoprotective effect of melanin from Lachnum YM226 on acute alcohol-induced liver injury in mice.

    PubMed

    Song, Sheng; Li, Shenglan; Su, Nana; Li, Jinglei; Shi, Fang; Ye, Ming

    2016-08-10

    In this paper, the possible structural formula of the intracellular homogeneous melanin of Lachnum YM226 (LM) was concluded based on an elemental assay, ultraviolet-visible spectroscopy (UV-Vis), Fourier transform infrared spectroscopy (FTIR), nuclear magnetic resonance (NMR), mass spectrometry (MS) and equivalent series resistance (ESR). Meanwhile, a d-glucosamine melanin derivative (GLM) was also prepared and its cytotoxicity was evaluated using the MTT assay. The hepatoprotective effect of LM and GLM was evaluated in an acute alcohol-induced liver injury model. The results showed that pretreatments with LM and GLM markedly decreased subsequent alcohol elicited acute hepatic oxidative and inflammatory stress via improving the activity of antioxidant enzymes (glutathione (GSH), catalase (CAT), glutathione peroxidase (GPX), and total superoxide dismutase (SOD)), reducing hepatic levels of nuclear transcription factor (NF-κB), cytokines related to its activation (interleukin (IL)-6, tumor necrosis factor (TNF)-α and macrophage chemoattractant protein (MCP)-1) and hepatic activities of inducible nitric oxide synthase (iNOS) and cyclooxygenase (COX)-2. The protection properties of alcoholic liver injury of GLM were more obvious than that of LM at the same dose. The present findings recommend that LM and GLM may be used as a prototype for the prevention of alcoholic liver injury. PMID:27485489

  15. Protective effects of patchouli alcohol isolated from Pogostemon cablin on lipopolysaccharide-induced acute lung injury in mice

    PubMed Central

    SU, ZUQING; LIAO, JINBIN; LIU, YUHONG; LIANG, YONGZHUO; CHEN, HAIMING; CHEN, XIAOYING; LAI, XIAOPING; FENG, XUEXUAN; WU, DIANWEI; ZHENG, YIFENG; ZHANG, XIAOJUN; LI, YUCUI

    2016-01-01

    Patchouli alcohol (PA) is a tricyclic sesquiterpene isolated from Pogostemon cablin, which exerts anti-inflammatory, anti-influenza and cognitive-enhancing bioactivities. The present study aimed to investigate the protective effects of PA on acute lung injury (ALI) induced by intratracheal instillation of lipopolysaccharide (LPS) in mice. Dexamethasone was used as a positive drug for protection against LPS-induced ALI. The results of the present study demonstrated that pretreatment with PA significantly increased survival rate, attenuated histopathologic damage and lung edema, and decreased the protein content in the bronchoalveolar lavage fluid (BALF) of mice with ALI. Furthermore, PA significantly inhibited the expression levels of proinflammatory cytokines, including tumor necrosis factor (TNF)-α and interleukin (IL)-6 in the BALF, downregulated the levels of myeloperoxidase and malondialdehyde, and upregulated the activity levels of superoxide dismutase and glutathione peroxidase in lung tissue. These results indicated that PA may exert potent protective effects against LPS-induced ALI in mice, the mechanisms of which are possibly associated with the anti-inflammatory and antioxidative activities of PA. PMID:26893665

  16. Acute Alcohol Consumption and Secondary Psychopathic Traits Increase Ratings of the Attractiveness and Health of Ethnic Ingroup Faces but Not Outgroup Faces

    PubMed Central

    Mitchell, Ian J.; Gillespie, Steven M.; Leverton, Monica; Llewellyn, Victoria; Neale, Emily; Stevenson, Isobel

    2015-01-01

    Studies have consistently shown that both consumption of acute amounts of alcohol and elevated antisocial psychopathic traits are associated with an impaired ability for prepotent response inhibition. This may manifest as a reduced ability to inhibit prepotent race biased responses. Here, we tested the effects of acute alcohol consumption, and elevated antisocial psychopathic traits, on judgments of the attractiveness and health of ethnic ingroup and outgroup faces. In the first study, we show that following acute alcohol consumption, at a dose that is sufficient to result in impaired performance on tests of executive function, Caucasian participants judged White faces to be more attractive and healthier compared to when sober. However, this effect did not extend to Black faces. A similar effect was found in a second study involving sober Caucasian participants where secondary psychopathic traits were related to an intergroup bias in the ratings of attractiveness for White versus Black faces. These results are discussed in terms of a model which postulates that poor prefrontal functioning leads to increases in ingroup liking as a result of impaired abilities for prepotent response inhibition. PMID:25745403

  17. The validity of ICD codes coupled with imaging procedure codes for identifying acute venous thromboembolism using administrative data.

    PubMed

    Alotaibi, Ghazi S; Wu, Cynthia; Senthilselvan, Ambikaipakan; McMurtry, M Sean

    2015-08-01

    The purpose of this study was to evaluate the accuracy of using a combination of International Classification of Diseases (ICD) diagnostic codes and imaging procedure codes for identifying deep vein thrombosis (DVT) and pulmonary embolism (PE) within administrative databases. Information from the Alberta Health (AH) inpatients and ambulatory care administrative databases in Alberta, Canada was obtained for subjects with a documented imaging study result performed at a large teaching hospital in Alberta to exclude venous thromboembolism (VTE) between 2000 and 2010. In 1361 randomly-selected patients, the proportion of patients correctly classified by AH administrative data, using both ICD diagnostic codes and procedure codes, was determined for DVT and PE using diagnoses documented in patient charts as the gold standard. Of the 1361 patients, 712 had suspected PE and 649 had suspected DVT. The sensitivities for identifying patients with PE or DVT using administrative data were 74.83% (95% confidence interval [CI]: 67.01-81.62) and 75.24% (95% CI: 65.86-83.14), respectively. The specificities for PE or DVT were 91.86% (95% CI: 89.29-93.98) and 95.77% (95% CI: 93.72-97.30), respectively. In conclusion, when coupled with relevant imaging codes, VTE diagnostic codes obtained from administrative data provide a relatively sensitive and very specific method to ascertain acute VTE. PMID:25834115

  18. Nanostructured lipid carriers-based flurbiprofen gel after topical administration: acute skin irritation, pharmacodynamics, and percutaneous absorption mechanism.

    PubMed

    Song, Aihua; Su, Zhen; Li, Sanming; Han, Fei

    2015-01-01

    In order to assess the preliminary safety and effectiveness of nanostructured lipid carriers-based flurbiprofen gel (FP NLC-gel), the acute irritation test, in vivo pharmacodynamics evaluation and pharmacokinetic study were investigated after topical application. No dropsy and erythema were observed after continuous dosing 7 d of FP NLC-gel on the rabbit skin, and the xylene-induced ear drossy could be inhibited by FP NLC-gel at different dosages. The maximum concentration of FP in rats muscle was 2.03 μg/g and 1.55 μg/g after oral and topical administration, respectively. While the peak concentration in untreated muscle after topical administration was only 0.37 μg/mL. And at any time, following topical administration the mean muscle-plasma concentration ratio Cmuscle/CPlasma was obviously higher than that following oral administration. Results indicated that FP could directly penetrate into the subcutaneous muscle tissue from the administration site. Thus, the developed FP NLC-gel could be a safe and effective vehicle for topical delivery of FP.

  19. 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.

    PubMed

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

    2015-01-01

    We describe an interdisciplinary comparison of the effects of acute and chronic alcohol exposure in terms of their disturbance of light, dark and color preferences and the occurrence of Parkinson-like behavior in zebrafish through computer visual tracking, data mining, and behavioral and physiological analyses. We found that zebrafish in anxiolytic and anxious states, which are induced by acute and chronic repeated alcohol exposure, respectively, display distinct emotional reactions in light/dark preference tests as well as distinct learning and memory abilities in color-enhanced conditional place preference (CPP) tests. Additionally, compared with the chronic alcohol (1.0%) treatment, acute alcohol exposure had a significant, dose-dependent effect on anxiety, learning and memory (color preference) as well as locomotive activities. Acute exposure doses (0.5%, 1.0%, and 1.5%) generated an "inverted V" dose-dependent pattern in all of the behavioral parameters, with 1.0% having the greatest effect, while the chronic treatment had a moderate effect. Furthermore, by measuring locomotive activity, learning and memory performance, the number of dopaminergic neurons, tyrosine hydroxylase expression, and the change in the photoreceptors in the retina, we found that acute and chronic alcohol exposure induced varying degrees of Parkinson-like symptoms in zebrafish. Taken together, these results illuminated the behavioral and physiological mechanisms underlying the changes associated with learning and memory and the cause of potential Parkinson-like behaviors in zebrafish due to acute and chronic alcohol exposure. PMID:26558894

  20. 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

    PubMed Central

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

    2015-01-01

    We describe an interdisciplinary comparison of the effects of acute and chronic alcohol exposure in terms of their disturbance of light, dark and color preferences and the occurrence of Parkinson-like behavior in zebrafish through computer visual tracking, data mining, and behavioral and physiological analyses. We found that zebrafish in anxiolytic and anxious states, which are induced by acute and chronic repeated alcohol exposure, respectively, display distinct emotional reactions in light/dark preference tests as well as distinct learning and memory abilities in color-enhanced conditional place preference (CPP) tests. Additionally, compared with the chronic alcohol (1.0%) treatment, acute alcohol exposure had a significant, dose-dependent effect on anxiety, learning and memory (color preference) as well as locomotive activities. Acute exposure doses (0.5%, 1.0%, and 1.5%) generated an “inverted V” dose-dependent pattern in all of the behavioral parameters, with 1.0% having the greatest effect, while the chronic treatment had a moderate effect. Furthermore, by measuring locomotive activity, learning and memory performance, the number of dopaminergic neurons, tyrosine hydroxylase expression, and the change in the photoreceptors in the retina, we found that acute and chronic alcohol exposure induced varying degrees of Parkinson-like symptoms in zebrafish. Taken together, these results illuminated the behavioral and physiological mechanisms underlying the changes associated with learning and memory and the cause of potential Parkinson-like behaviors in zebrafish due to acute and chronic alcohol exposure. PMID:26558894

  1. 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.

    PubMed

    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.

  2. Acute and chronic administration of the branched-chain amino acids decreases nerve growth factor in rat hippocampus.

    PubMed

    Scaini, Giselli; Mello-Santos, Lis Mairá; Furlanetto, Camila B; Jeremias, Isabela C; Mina, Francielle; Schuck, Patrícia F; Ferreira, Gustavo C; Kist, Luiza W; Pereira, Talita C B; Bogo, Maurício R; Streck, Emilio L

    2013-12-01

    Maple syrup urine disease (MSUD) is a neurometabolic disorder caused by deficiency of the activity of the mitochondrial enzyme complex branched-chain α-keto acid dehydrogenase leading to accumulation of the branched-chain amino acids (BCAA) and their corresponding branched-chain α-keto acids. In this study, we examined the effects of acute and chronic administration of BCAA on protein levels and mRNA expression of nerve growth factor (NGF) considering that patients with MSUD present neurological dysfunction and cognitive impairment. Considering previous observations, it is suggested that oxidative stress may be involved in the pathophysiology of the neurological dysfunction of MSUD. We also investigated the influence of antioxidant treatment (N-acetylcysteine and deferoxamine) in order to verify the influence of oxidative stress in the modulation of NGF levels. Our results demonstrated decreased protein levels of NGF in the hippocampus after acute and chronic administration of BCAA. In addition, we showed a significant decrease in the expression of ngf in the hippocampus only following acute administration in 10-day-old rats. Interestingly, antioxidant treatment was able to prevent the decrease in NGF levels by increasing ngf expression. In conclusion, the results suggest that BCAA is involved in the regulation of NGF in the developing rat. Thus, it is possible that alteration of neurotrophin levels during brain maturation could be of pivotal importance in the impairment of cognition provoked by BCAA. Moreover, the decrease in NGF levels was prevented by antioxidant treatment, reinforcing that the hypothesis of oxidative stress can be an important pathophysiological mechanism underlying the brain damage observed in MSUD. PMID:23559405

  3. The acute and the long-term effects of nigral lipopolysaccharide administration on dopaminergic dysfunction and glial cell activation.

    PubMed

    Iravani, Mahmoud M; Leung, Clement C M; Sadeghian, Mona; Haddon, Claire O; Rose, Sarah; Jenner, Peter

    2005-07-01

    Sustained reactive microgliosis may contribute to the progressive degeneration of nigral dopaminergic neurons in Parkinson's disease (PD), in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) exposed human and in non-human primates. However, the temporal relationship between glial cell activation and nigral cell death is relatively unexplored. Consequently, the effects of acute (24 h) and chronic (30 days) glial cell activation induced by unilateral supranigral lipopolysaccharide (LPS) administration were studied in rats. At 24 h, LPS administration caused a marked reduction in the number of tyrosine hydroxylase-immunoreactive (TH-ir) neurons in the substantia nigra (SN) but striatal TH-ir was unaffected. By 30 days, the loss of TH-positive neurons in the LPS-treated nigra was no greater than at 24 h although a heterogeneous loss of striatal TH-ir was present. The loss of nigrostriatal neurons was of functional significance, as at 30 days, LPS-treated rats exhibited ipsiversive circling in response to (+)-amphetamine administration. At 24 h, there was a moderate increase in glial fibrillary acidic protein (GFAP)-ir astrocytes in the SN but a marked elevation of p47phox positive OX-42-ir microglia, and intense inducible nitric oxide synthase (iNOS)-ir and 3-nitrotyrosine (3-NT)-ir was present. However, by 30 days the morphology of OX-42-ir microglia returned to a resting state, the numbers were greatly reduced and no 3-NT-ir was present. At 30 days, GFAP-ir astrocytes were markedly increased in number and iNOS-ir was present in fibrillar astrocyte-like cells. This study shows that acute glial activation leading to dopaminergic neuron degeneration is an acute short-lasting response that does not itself perpetuate cell death or lead to prolonged microglial activation.

  4. Comparison of Student Self-Reported and Administrative Data regarding Intercession into Alcohol Misuse among College Freshmen Dormitory Residents

    ERIC Educational Resources Information Center

    Novik, Melinda G.; Boekeloo, Bradley O.

    2013-01-01

    Intercession into collegiate alcohol misuse by the Department of Resident Life (DRL) in freshmen dormitories at one large Mid-Atlantic, diverse, public university was examined. Freshmen dormitory resident drinkers (n = 357), 71% of whom reported alcohol misuse, were surveyed. Student self-report and DRL documentation, respectively, revealed that…

  5. 2D spatiotemporal visualization system of expired gaseous ethanol after oral administration for real-time illustrated analysis of alcohol metabolism.

    PubMed

    Wang, Xin; Ando, Eri; Takahashi, Daishi; Arakawa, Takahiro; Kudo, Hiroyuki; Saito, Hirokazu; Mitsubayashi, Kohji

    2010-08-15

    A novel 2-dimensional spatiotemporal visualization system of expired gaseous ethanol after oral administration for real-time illustrated analysis of alcohol metabolism has been developed, which employed a low level light CCD camera to detect chemiluminescence (CL) generated by catalytic reactions of standard gaseous ethanol and expired gaseous ethanol after oral administration. First, the optimization of the substrates for visualization and the concentration of luminol solution for CL were investigated. The cotton mesh and 5.0 mmol L(-1) luminol solution were selected for further investigations and this system is useful for 0.1-20.0 mmol L(-1) of H(2)O(2) solution. Then, the effect of pH condition of Tris-HCl buffer solution was also evaluated with CL intensity and under the Tris-HCl buffer solution pH 10.1, a wide calibration range of standard gaseous ethanol (30-400 ppm) was obtained. Finally, expired air of 5 healthy volunteers after oral administration was measured at 15, 30, 45, 60, 75, 90, 105 and 120 min after oral administration, and this system showed a good sensitivity on expired gaseous ethanol for alcohol metabolism. The peaks of expired gaseous ethanol concentration appeared within 30 min after oral administration. During the 30 min after oral administration, the time variation profile based on mean values showed the absorption and distribution function, and the values onward showed the elimination function. The absorption and distribution of expired gaseous ethanol in 5 healthy volunteers following first-order absorption process were faster than the elimination process, which proves efficacious of this system for described alcohol metabolism in healthy volunteers. This system is expected to be used as a non-invasive method to detect VOCs as well as several other drugs in expired air for clinical purpose.

  6. 78 FR 21615 - National Institute on Alcohol Abuse and Alcoholism; Notice of Closed Meeting

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-04-11

    ... HUMAN SERVICES National Institutes of Health National Institute on Alcohol Abuse and Alcoholism; Notice... personal privacy. Name of Committee: National Institute on Alcohol Abuse and Alcoholism Initial ] Review... Foster, Ph.D., Scientific Review Administrator, National Institutes on Alcohol Abuse &...

  7. N-Acetylcysteine Administration Prevents Nonthyroidal Illness Syndrome in Patients With Acute Myocardial Infarction: A Randomized Clinical Trial

    PubMed Central

    Vidart, Josi; Wajner, Simone Magagnin; Leite, Rogério Sarmento; Manica, André; Schaan, Beatriz D.; Larsen, P. Reed

    2014-01-01

    Context: The acute phase of the nonthyroidal illness syndrome (NTIS) is characterized by low T3 and high rT3 levels, affecting up to 75% of critically ill patients. Oxidative stress has been implicated as a causative factor of the disturbed peripheral thyroid hormone metabolism. Objective: The objective of the study was to investigate whether N-acetylcysteine (NAC), a potent intracellular antioxidant, can prevent NTIS in patients with acute myocardial infarction. Design: This was a randomized, multicenter clinical trial. Settings: Consecutive patients admitted to the emergency and intensive care units of two tertiary hospitals in southern Brazil were recruited. Patients and intervention included 67 patients were randomized to receive NAC or placebo during 48 hours. Baseline characteristics and blood samples for thyroid hormones and oxidative parameters were collected. Main Outcome: Variation of serum T3 and rT3 levels was measured. Results: Baseline characteristics were similar between groups (all P > .05). T3 levels decreased in the placebo group at 12 hours of follow-up (P = .002) but not in NAC-treated patients (P = .10). Baseline rT3 levels were elevated in both groups and decreased over the initial 48 hours in the NAC-treated patients (P = .003) but not in the control group (P = .75). The free T4 and TSH levels were virtually identical between the groups throughout the study period (P > .05). Measurement of total antioxidant status and total carbonyl content demonstrated that oxidative balance was deranged in acute myocardial infarction patients, whereas NAC corrected these alterations (P < .001). Conclusions: NAC administration prevents the derangement in thyroid hormone concentrations commonly occurring in the acute phase of acute myocardial infarction, indicating that oxidative stress is involved in the NTIS pathophysiology. PMID:25148231

  8. Acute renal failure, thrombocytopenia, and elevated liver enzymes after concurrent abuse of alcohol and cocaine

    PubMed Central

    Hosseinnezhad, Alireza; Vijayakrishnan, Rajakrishnan; Farmer, Mary Jo S.

    2011-01-01

    Cocaine has been associated with known adverse effects on cardiac, cerebrovascular and pulmonary systems. However, the effect of cocaine on other organs has not been extensively reported. A middle age man presented with abdominal pain and nausea after inhalation of crack cocaine. On admission, he was found to be hypertensive and tachycardic. Physical examination revealed mild abdominal tenderness without rebound. Laboratory investigations were significant for acute kidney failure with elevated serum creatinine (3.72 mg/dL), thrombocytopenia (platelet count 74,000/UL), elevated alanine and aspartate transaminases (ALT 331 U/L; AST 462 U/L) and elevated creatine phosphokinase (CPK 5885 U/L). Urine toxicology screening solely revealed cocaine. A clinical diagnosis of cocaine toxicity was made and patient was admitted to the intensive care unit because of multi organ failure. Despite downward trending of liver enzymes during the hospital course, he continued to have residual renal insufficiency and a low platelet count at the time of discharge. In a patient with history of recent cocaine use presenting with these manifestations, cocaine itself should be considered as a likely cause. PMID:24765297

  9. HINDBRAIN AND CRANIAL NERVE DYSMORPHOGENESIS RESULT FROM ACUTE MATERNAL ETHANOL ADMINISTRATION

    EPA Science Inventory

    Acute exposure of mouse embryos to ethanol during stages of hindbrain segmentation results in excessive cell death in specific cell populations. This study details the ethanol-induced cell loss and defines the subsequent effects of this early insult on rhombomere and cranial ner...

  10. Prophylactic Administration of Silybin Ameliorates L-Arginine-Induced Acute Pancreatitis

    PubMed Central

    Uçmak, Feyzullah; Ekin, Nazım; İbiloğlu, İbrahim; Arslan, Serkan; Kaplan, İbrahim; Şenateş, Ebubekir

    2016-01-01

    Background Oxidative stress have been shown to play a role in the pathogenesis of acute pancreatitis. The aim of this study was to investigate the potential effect of silybin, a potent antioxidant, on L-arginine-induced acute pancreatitis in an experimental rat model. Material/Methods Forty female Wistar Albino rats were divided into 5 groups as follows: Group 1 (C): control group (n=8), Group 2 (SL): silybin group (n=8), Group 3 (LA): acute pancreatitis group (n=8), Group 4 (SLLA): prophylaxis group (n=8), and Group 5 (LASL): treatment group (n=8). Group C (control) received 2 intraperitoneal (i.p.) injections of physiological saline at an interval of 1 h. Group SL received only a single i.p. injection of silybin. The SLLA group received a single i.p. injection of silybin before the induction of acute pancreatitis with L-arginine, whereas the LASL group received the same injection after the induction of acute pancreatitis with L-arginine. Pancreatic tissues were histopathologically examined. Levels of amylase and oxidative stress markers (total oxidant status and total anti-oxidant status) were determined in the blood samples. Oxidative stress index was calculated. Results In comparison to the LA, the prophylaxis and treatment groups showed significant improvements in serum oxidative stress parameters (p=0.001 and p=0.005, respectively). Histopathological analysis showed that the treatment group had significant improvements in edema scores only (p=0.006), whereas the prophylaxis group had the same improvements in inflammation and necrosis scores as well as in total scores (p=0.004, 0.006, and 0.004, respectively). Conclusions When used for prophylactic rather than therapeutic purposes, silybin ameliorates serum oxidative stress parameters and improves histopathological results via its antioxidant and anti-inflammatory properties. PMID:27725627

  11. Different actions for acute and chronic administration of mirtazapine on serotonergic transmission associated with raphe nuclei and their innervation cortical regions.

    PubMed

    Yamamura, Satoshi; Abe, Masao; Nakagawa, Masanori; Ochi, Shinichiro; Ueno, Shu-ichi; Okada, Motohiro

    2011-03-01

    The atypical antidepressant, mirtazapine enhances noradrenergic transmission, but its effects on serotonergic transmission remain to be clarified. The present study determined the effects of acute and chronic administration of mirtazapine on serotonergic transmissions in raphe nuclei and their innervation regions, frontal and entorhinal cortex, using multiple-probes microdialysis with real-time PCR and western blotting. Acute administration of mirtazapine did not affect extracellular serotonin level in raphe nuclei or cortex; however, chronic administration increased extracellular serotonin level in raphe nuclei without affecting that in cortex. Blockade of 5-HT1A receptor, but not that of the 5-HT2A/2C receptor, enhanced the effects of acute administration of mirtazapine on extracellular serotonin level in raphe nuclei. Chronic mirtazapine administration reduced the inhibitory function associated with somatodendritic 5-HT1A receptor in raphe nuclei, but enhanced postsynaptic 5-HT1A receptor in serotonergic innervated cortical regions. Chronic administration reduced the expression of mRNA and protein of serotonin transporter and 5-HT1A receptor in raphe nuclei, but not in the cortices. These results suggested that acute administration of mirtazapine probably activated serotonergic transmission, but its stimulatory action was abolished by activated inhibitory 5-HT1A receptor. Chronic administration of mirtazapine resulted in increased extracellular serotonin level via reduction of serotonin transporter with reduction of somatodendritic 5-HT1A autoreceptor function in raphe nuclei. These pharmacological actions of mirtazapine include its serotonergic profiles as noradrenergic and specific serotonergic antidepressant (NaSSA). PMID:21195096

  12. Effects of acute or chronic administration of novel 3,4-dimethoxyphenylethylamine derivates on anxiety-like behavior

    PubMed Central

    Fedotova, Julia; Barishpolec, Victoria; Zulli, Anthony; Büsselberg, Dietrich; Gaspar, Ludovit; Kruzliak, Peter

    2015-01-01

    Novel anxiolytic medications are necessary to broaden treatment therapy. Thus, the aim of the present study was to compare the clinically effective anxiolytic, diazepam with the novel 3,4-dimethoxyphenylethylamine derivates. The novel 3,4-dimethoxyphenylethylamine derivates (PK, 0.1, 1.0, 10.0 mg/kg, i.p.) and diazepam (1.0 mg/kg) were injected acutely or chronically in animals subjected to the black-white model and the open field test. The acute administration of PK-2122 (0.1 mg/kg, i.p.) exerted anxiogenic-like effect, while in the middle or high doses PK-2122 exerted anxiolytic-like effect compared with the control group (p<0.05). The repeated treatment with PK-2111 was followed by anxiolytic-like effect in doses of 0.1 or 1.0 mg/kg which was more significant compared not only with control group, but with comparison to group treated with diazepam (p<0.05). Chronic treatment with PK-2123 or PK-2122 in all tested doses produced anxiolytic-like effect (p<0.05), compared with control group and diazepam group. These results demonstrate that PK-2126, but not PK-2122, is dose independent and may be effective in experimental model of anxiety in rats when administered acutely or repeatedly. PMID:26807191

  13. [Acute lung injury as a consequence of fresh frozen plasma administration in a patient with factor XII deficiency].

    PubMed

    San Juan-Álvarez, M; Sánchez-Zamora, P; de la Flor-Robledo, M

    2014-10-01

    Along with the complete blood count, the coagulation tests are those most demanded before a surgical procedure. The activated partial thromboplastin time (APPT) quantifies the intrinsic and common coagulation pathways, including factors XII, XI, IX, VIII, X, V and II. Factor XII deficiency is associated with a prolonged APPT and an increase in thromboembolic phenomena, without increasing the intraoperative bleeding risk. A 20 year old man with factor XII deficiency was receiving two units of fresh frozen plasma because of an APPT of 100 seconds, with the intention of normalizing it before an urgent surgery procedure, and the fear of intraoperative bleeding. An hour after starting the transfusion the patient developed an acute lung injury (ALI) compatible with the diagnosis of a transfusion related acute lung injury (TRALI). The surgery continued without complications, and the patient was admitted to the resuscitation unit for 72 h, needing respiratory support. If the APTT is prolonged in the absence of bleeding, the presence of a non-specific circulating anticoagulant, a deficiency of factor XI, XII and VIII (associated to Von Willebrand disease) must be ruled out. Therefore, in the case presented here, the administration of hemoderivatives was unnecessary and can have consequences as serious as the one that the patient presented, a transfusion related acute lung injury.

  14. Differences in the effect of chronic and acute caffeine on self-administration of cocaine in mice.

    PubMed

    Kuzmin, A; Johansson, B; Semenova, S; Fredholm, B B

    2000-08-01

    We have compared the ability of an acute injection of caffeine (3 mg/kg, i.p.) and long-term peroral caffeine consumption for 10 days ( approximately 150 mg/kg/day in tap water) to affect cocaine self-administration in mice. The peak plasma and brain levels of caffeine and its metabolites were similar in the two experimental set-ups. Moreover, the levels reached are close to those obtained in humans upon coffee ingestion. Neither type of caffeine administration affected the reinforcing effect of cocaine, defined as a selective increase in nose-poke responses in mice self-administering cocaine compared to their yoked controls. However, caffeine injection increased the amount of cocaine self-administered whereas caffeine drinking reduced it. A low dose of cocaine, by itself essentially ineffective, produced an increase in c-fos and NGFI-A mRNA in the cerebral cortex in mice that had been drinking caffeine. An acute caffeine injection also enhanced the immediate early gene response to cocaine, but to a lesser degree. Cocaine and caffeine also synergistically increased NGFI-A expression in caudate-putamen. Thus, regular caffeine drinking decreased the cocaine intake without significantly affecting its reinforcing properties, perhaps because it enhanced the activation of the predominantly inhibitory frontal cortical areas produced by low doses of cocaine. PMID:10971643

  15. Irish coffee: Effects of alcohol and caffeine on object discrimination in zebrafish.

    PubMed

    Santos, Luana C; Ruiz-Oliveira, Julia; Oliveira, Jéssica J; Silva, Priscila F; Luchiari, Ana C

    2016-04-01

    Many studies regarding the effects of drugs investigate the acute and chronic use of alcohol, but only a few address the effects of caffeine and alcohol combined to the performance of the zebrafish in cognitive tasks. The zebrafish is an important model for studying the effects of drugs on learning, because it has large genetic similarities to humans and the non-invasive administration of the substances favors translational bias of research. In this study, we observed the effects of alcohol and caffeine on zebrafish cognition through an object discrimination test. We noticed that animals subjected to acute alcohol dose and those under alcohol or caffeine withdrawal did not show discrimination. When fish were treated with associated alcohol and caffeine, those chronically treated with alcohol and subjected to moderate acute dose of caffeine showed learning of the task. Our results reinforce the harmful effects of the alcohol use on cognitive tasks, and suggest that continued use of high doses of caffeine cause cognitive impairment during withdrawal of the substance. However, the acute use of caffeine appears to reverse the harmful effects of alcohol withdrawal, allowing discriminative performance equivalent to control fish. Finally, we reiterate the use of zebrafish as a model for drug effects screening and search for active compounds that modulate the alcohol and caffeine effects. PMID:26850919

  16. Acute corticosterone administration during meiotic segregation stimulates females to produce more male offspring.

    PubMed

    Pinson, Sara E; Parr, Christina M; Wilson, Jeanna L; Navara, Kristen J

    2011-01-01

    Birds have demonstrated a remarkable ability to manipulate offspring sex. Previous studies suggest that treatment with hormones can stimulate females to manipulate offspring sex before ovulation. For example, chronic treatments with corticosterone, the primary stress hormone produced by birds, stimulated significant skews toward female offspring. It has been suggested that corticosterone acts by influencing which sex chromosome is donated by the heterogametic female bird into the ovulated ovarian follicle. However, it is difficult to pinpoint when in developmental time corticosterone affects offspring sex, because in previous studies corticosterone treatment was given over a long period of time. We treated laying hens with acute high-dose corticosterone injections 5 h before the predicted time of ovulation and quantified the sexes of the subsequently ovulated eggs to determine whether mechanisms exist by which corticosterone can skew offspring sex ratios just before ovulation. We hypothesized that an injection of corticosterone coincident with segregation of the sex chromosomes would stimulate hens to produce more female than male offspring. Contrary to our predictions, hens injected with corticosterone produced a significant bias toward male offspring, nearly 83%. These results suggest that acute corticosterone treatment during meiosis I can influence primary sex ratios in birds, potentially through nonrandom chromosome segregation. Furthermore, acute corticosterone exposure, compared with chronic exposure, may act through different mechanisms to skew offspring sex.

  17. Differential modulation of antipredator defensive behavior in Swiss-Webster mice following acute or chronic administration of imipramine and fluoxetine.

    PubMed

    Griebel, G; Blanchard, D C; Agnes, R S; Blanchard, R J

    1995-07-01

    The Mouse Defense Test Battery (MDTB) has been designed to assess defensive reactions in Swiss-Webster mice to situations associated with a natural predator, the rat. Primary measures taken before, during and after predator confrontation comprise escape attempts, predator assessment, defensive attack and flight. Previous reports from this laboratory have shown that the panic-promoting drug yohimbine potentiated flight behavior, while long-term treatment with the panicolytic agent alprazolam reduced this response. In order to evaluate further the possibility that the MDTB may represent an effective animal model of panic attacks, the present study investigated the behavioral effect of imipramine and fluoxetine, two serotonin reuptake inhibitors (SRIs) known to alleviate panic symptoms when given on a repeated basis. Both drugs were administered acutely and chronically (one daily IP injection for 21 days) at 5, 10 and 15 mg/kg. Our results showed that a single dose of imipramine or fluoxetine strongly potentiated flight reactions in response to an approaching predator and increased defensive attack toward the rat. This was in contrast to chronic treatment with each drug which dramatically decreased flight responses and defensive attack behaviors. In addition, long-term administration with both SRIs produced a reliable attenuation of predator assessment activities. Taken together, these findings suggest an acute anxiogenic-like effect of imipramine and fluoxetine followed by a fear/anxiety reducing effect after repeated administrations. These results support clinical observations revealing an acute anxiogenic effect of SRIs followed by an anxiolytic and/or panicolytic effect after chronic use, and support previous results suggesting that the MDTB may be useful for the investigation of panic-modulating agents.

  18. Acute Administration of Branched-Chain Amino Acids Increases the Pro-BDNF/Total-BDNF Ratio in the Rat Brain.

    PubMed

    Scaini, Giselli; Morais, Meline O S; Furlanetto, Camila B; Kist, Luiza W; Pereira, Talita C B; Schuck, Patrícia F; Ferreira, Gustavo C; Pasquali, Matheus A B; Gelain, Daniel P; Moreira, José Cláudio F; Bogo, Maurício R; Streck, Emilio L

    2015-05-01

    Maple syrup urine disease (MSUD) is caused by an inborn error in metabolism resulting from a deficiency in the branched-chain α-keto acid dehydrogenase complex activity. This blockage leads to accumulation of the branched-chain amino acids (BCAA) leucine, isoleucine and valine, as well as their corresponding α-keto acids and α-hydroxy acids. High levels of BCAAs are associated with neurological dysfunction and the role of pro- and mature brain-derived neurotrophic factor (BDNF) in the neurological dysfunction of MSUD is still unclear. Thus, in the present study we investigated the effect of an acute BCAA pool administration on BDNF levels and on the pro-BDNF cleavage-related proteins S100A10 and tissue plasminogen activator (tPA) in rat brains. Our results demonstrated that acute Hyper-BCAA (H-BCAA) exposure during the early postnatal period increases pro-BDNF and total-BDNF levels in the hippocampus and striatum. Moreover, tPA levels were significantly decreased, without modifications in the tPA transcript levels in the hippocampus and striatum. On the other hand, the S100A10 mRNA and S100A10 protein levels were not changed in the hippocampus and striatum. In the 30-day-old rats, we observed increased pro-BDNF, total-BDNF and tPA levels only in the striatum, whereas the tPA and S100A10 mRNA expression and the immunocontent of S100A10 were not altered. In conclusion, we demonstrated that acute H-BCAA administration increases the pro-BDNF/total-BDNF ratio and decreases the tPA levels in animals, suggesting that the BCAA effect may depend, at least in part, on changes in BDNF post-translational processing. PMID:25681161

  19. Self-Rating of the Effects of Alcohol (SRE): Predictive utility and reliability across interview and self-report administrations.

    PubMed

    Ray, Lara A; Hart, Eliza J; Chin, Pauline F

    2011-03-01

    The Self-Rating of the Effects of Alcohol (SRE) is a widely used and well-established measure of the level of response to alcohol. Although the SRE has been successfully used in studies of alcoholism etiology, including genetics, studies to date have not compared the self-report and interview formats. The objectives of this study are to: (a) test the predictive utility of the subscales of the SRE in relation to alcohol problems; and (b) test the reliability of the SRE in interview versus self-report formats. A sample of college drinkers (n=446) completed the SRE in a self-report format along with the Alcohol Use Disorders Identification Test (AUDIT). A subset of participants (n=34) returned to the laboratory and completed the SRE in a face-to-face interview format. All subscales of the SRE were robust predictors of alcohol problems accounting for as much as 25% of the variance in AUDIT scores. In addition, scores obtained via self-report and interview-based SRE were highly correlated (r=.70 to .80). Results support the predictive utility of the SRE and provide initial evidence that the self-report and interview formats produce reliable results and may be combined and/or used interchangeably. PMID:21095629

  20. Effects of oral acute administration and subchronic feeding of several levels of D-psicose in rats.

    PubMed

    Matsuo, Tatsuhiro; Tanaka, Tomohiro; Hashiguchi, Mineo; Izumori, Ken; Suzuki, Hiroo

    2002-12-01

    The effects of oral acute administration and subchronic (34 d) feeding of several levels of D-psicose, a C3-epimer of D-fructose, were studied in rats. In the acute administration test, five groups of eight male Wistar rats (3 wk old) were orally given D-psicose in doses of 8, 11, 14, 17, and 20 g/kg. Three rats receiving 14 g/kg, three rats receiving 17 g/kg and eight rats receiving 20 g/kg of D-psicose died within 2 d after administration. The calculated LD50 values were 16.3 g/kg by the Behrens-Karber method and 15.8 g/kg by the Litchfield-Wilcoxon method. In the subcronic feeding test, eight groups of seven male Wistar rats (3 wk old) were fed diets containing 0 (control), 10, 20, 30, and 40% for 34 d. One rat fed 30% D-psicose diet and five rats fed 40% D-psicose diet died during the experimental period. Body weight gain, food intake and food efficiency were more extensively suppressed by the higher D-psicose diets. The weights of heart, spleen and abdominal adipose tissue were smaller in the order of dietary D-psicose concentration. Cecal weight increased with increasing D-psicose concentration in the diets. Cecal hypertrophy was observed in rats fed 10-40% D-psicose diets. These results suggest that D-psicose differs in nutritional characteristics from D-glucose or D-fructose. The feeding of diets extremely high in D-psicose seems to be harmful to the intestinal tract.

  1. Increase in cocaine- and amphetamine-regulated transcript (CART) in specific areas of the mouse brain by acute caffeine administration.

    PubMed

    Cho, Jin Hee; Cho, Yun Ha; Kim, Hyo Young; Cha, Seung Ha; Ryu, Hyun; Jang, Wooyoung; Shin, Kyung Ho

    2015-04-01

    Caffeine produces a variety of behavioral effects including increased alertness, reduced food intake, anxiogenic effects, and dependence upon repeated exposure. Although many of the effects of caffeine are mediated by its ability to block adenosine receptors, it is possible that other neural substrates, such as cocaine- and amphetamine-regulated transcript (CART), may be involved in the effects of caffeine. Indeed, a recent study demonstrated that repeated caffeine administration increases CART in the mouse striatum. However, it is not clear whether acute caffeine administration alters CART in other areas of the brain. To explore this possibility, we investigated the dose- and time-dependent changes in CART immunoreactivity (CART-IR) after a single dose of caffeine in mice. We found that a high dose of caffeine (100 mg/kg) significantly increased CART-IR 2 h after administration in the nucleus accumbens shell (AcbSh), dorsal bed nucleus of the stria terminalis (dBNST), central nucleus of the amygdala (CeA), paraventricular hypothalamic nucleus (PVN), arcuate hypothalamic nucleus (Arc), and locus coeruleus (LC), and returned to control levels after 8 h. But this increase was not observed in other brain areas. In addition, caffeine administration at doses of 25 and 50 mg/kg appears to produce dose-dependent increases in CART-IR in these brain areas; however, the magnitude of increase in CART-IR observed at a dose of 50 mg/kg was similar or greater than that observed at a dose of 100 mg/kg. This result suggests that CART-IR in AcbSh, dBNST, CeA, PVN, Arc, and LC is selectively affected by caffeine administration.

  2. Increase in cocaine- and amphetamine-regulated transcript (CART) in specific areas of the mouse brain by acute caffeine administration.

    PubMed

    Cho, Jin Hee; Cho, Yun Ha; Kim, Hyo Young; Cha, Seung Ha; Ryu, Hyun; Jang, Wooyoung; Shin, Kyung Ho

    2015-04-01

    Caffeine produces a variety of behavioral effects including increased alertness, reduced food intake, anxiogenic effects, and dependence upon repeated exposure. Although many of the effects of caffeine are mediated by its ability to block adenosine receptors, it is possible that other neural substrates, such as cocaine- and amphetamine-regulated transcript (CART), may be involved in the effects of caffeine. Indeed, a recent study demonstrated that repeated caffeine administration increases CART in the mouse striatum. However, it is not clear whether acute caffeine administration alters CART in other areas of the brain. To explore this possibility, we investigated the dose- and time-dependent changes in CART immunoreactivity (CART-IR) after a single dose of caffeine in mice. We found that a high dose of caffeine (100 mg/kg) significantly increased CART-IR 2 h after administration in the nucleus accumbens shell (AcbSh), dorsal bed nucleus of the stria terminalis (dBNST), central nucleus of the amygdala (CeA), paraventricular hypothalamic nucleus (PVN), arcuate hypothalamic nucleus (Arc), and locus coeruleus (LC), and returned to control levels after 8 h. But this increase was not observed in other brain areas. In addition, caffeine administration at doses of 25 and 50 mg/kg appears to produce dose-dependent increases in CART-IR in these brain areas; however, the magnitude of increase in CART-IR observed at a dose of 50 mg/kg was similar or greater than that observed at a dose of 100 mg/kg. This result suggests that CART-IR in AcbSh, dBNST, CeA, PVN, Arc, and LC is selectively affected by caffeine administration. PMID:25820086

  3. Impairment of Electron Transfer Chain Induced by Acute Carnosine Administration in Skeletal Muscle of Young Rats

    PubMed Central

    Macarini, José Roberto; Maravai, Soliany Grassi; Cararo, José Henrique; Dimer, Nádia Webber; Gonçalves, Cinara Ludvig; Kist, Luiza Wilges; Bogo, Mauricio Reis; Schuck, Patrícia Fernanda; Streck, Emilio Luiz; Ferreira, Gustavo Costa

    2014-01-01

    Serum carnosinase deficiency is an inherited disorder that leads to an accumulation of carnosine in the brain tissue, cerebrospinal fluid, skeletal muscle, and other tissues of affected patients. Considering that high levels of carnosine are associated with neurological dysfunction and that the pathophysiological mechanisms involved in serum carnosinase deficiency remain poorly understood, we investigated the in vivo effects of carnosine on bioenergetics parameters, namely, respiratory chain complexes (I–III, II, and II-III), malate dehydrogenase, succinate dehydrogenase, and creatine kinase activities and the expression of mitochondrial-specific transcription factors (NRF-1, PGC-1α, and TFAM) in skeletal muscle of young Wistar rats. We observed a significant decrease of complexes I–III and II activities in animals receiving carnosine acutely, as compared to control group. However, no significant alterations in respiratory chain complexes, citric acid cycle enzymes, and creatine kinase activities were found between rats receiving carnosine chronically and control group animals. As compared to control group, mRNA levels of NRF-1, PGC-1α, and TFAM were unchanged. The present findings indicate that electron transfer through the respiratory chain is impaired in skeletal muscle of rats receiving carnosine acutely. In case these findings are confirmed by further studies and ATP depletion is also observed, impairment of bioenergetics could be considered a putative mechanism responsible for the muscle damage observed in serum carnosinase-deficient patients. PMID:24877122

  4. Impairment of electron transfer chain induced by acute carnosine administration in skeletal muscle of young rats.

    PubMed

    Macarini, José Roberto; Maravai, Soliany Grassi; Cararo, José Henrique; Dimer, Nádia Webber; Gonçalves, Cinara Ludvig; Kist, Luiza Wilges; Bogo, Mauricio Reis; Schuck, Patrícia Fernanda; Streck, Emilio Luiz; Ferreira, Gustavo Costa

    2014-01-01

    Serum carnosinase deficiency is an inherited disorder that leads to an accumulation of carnosine in the brain tissue, cerebrospinal fluid, skeletal muscle, and other tissues of affected patients. Considering that high levels of carnosine are associated with neurological dysfunction and that the pathophysiological mechanisms involved in serum carnosinase deficiency remain poorly understood, we investigated the in vivo effects of carnosine on bioenergetics parameters, namely, respiratory chain complexes (I-III, II, and II-III), malate dehydrogenase, succinate dehydrogenase, and creatine kinase activities and the expression of mitochondrial-specific transcription factors (NRF-1, PGC-1α , and TFAM) in skeletal muscle of young Wistar rats. We observed a significant decrease of complexes I-III and II activities in animals receiving carnosine acutely, as compared to control group. However, no significant alterations in respiratory chain complexes, citric acid cycle enzymes, and creatine kinase activities were found between rats receiving carnosine chronically and control group animals. As compared to control group, mRNA levels of NRF-1, PGC-1α , and TFAM were unchanged. The present findings indicate that electron transfer through the respiratory chain is impaired in skeletal muscle of rats receiving carnosine acutely. In case these findings are confirmed by further studies and ATP depletion is also observed, impairment of bioenergetics could be considered a putative mechanism responsible for the muscle damage observed in serum carnosinase-deficient patients. PMID:24877122

  5. Alterations in attentional mechanisms in response to acute inflammatory pain and morphine administration.

    PubMed

    Boyette-Davis, J A; Thompson, C D; Fuchs, P N

    2008-01-24

    Research indicates that pain negatively impacts attention; however, the extent of this impact and the mechanisms of the effect of pain on normal attentional processing remain unclear. This study 1) examined the impact of acute inflammatory pain on attentional processing, 2) examined the impact of morphine on attentional processing, and 3) determined if an analgesic dose of morphine would return attentional processing to normal levels. Male Sprague-Dawley rats were trained on the 5 choice serial reaction time task (5CSRTT), a test commonly used to assess the attentional mechanisms of rodents. Animals were injected with saline or 1, 3, or 6 mg/kg of morphine. Twenty minutes later, animals received a formalin (or saline) injection into one hind paw to induce an inflammatory condition and were then immediately tested in the 5CSRTT. The results show that the formalin injection significantly impaired performance, as measured by an increase in the number of trials in which the animal failed to attend to the task. Likewise, a high dose of morphine (6 mg/kg) produced similar decrements in task performance. Of primary importance is that 3 mg/kg of morphine produced analgesia with only mild sedation, and performance in the 5CSRTT was improved with this dose. This is the first study to use an animal model of acute pain to demonstrate the negative impact of pain on attention, and provides a novel approach to examine the neural correlates that underlie the disruptive impact of pain on attention.

  6. Assessing the Representativeness of Population-Sampled Health Surveys Through Linkage to Administrative Data on Alcohol-Related Outcomes

    PubMed Central

    Gorman, Emma; Leyland, Alastair H.; McCartney, Gerry; White, Ian R.; Katikireddi, Srinivasa Vittal; Rutherford, Lisa; Graham, Lesley; Gray, Linsay

    2014-01-01

    Health surveys are an important resource for monitoring population health, but selective nonresponse may impede valid inference. This study aimed to assess nonresponse bias in a population-sampled health survey in Scotland, with a focus on alcohol-related outcomes. Nonresponse bias was assessed by examining whether rates of alcohol-related harm (i.e., hospitalization or death) and all-cause mortality among respondents to the Scottish Health Surveys (from 1995 to 2010) were equivalent to those in the general population, and whether the extent of any bias varied according to sociodemographic attributes or over time. Data from consenting respondents (aged 20–64 years) to 6 Scottish Health Surveys were confidentially linked to death and hospitalization records and compared with general population counterparts. Directly age-standardized incidence rates of alcohol-related harm and all-cause mortality were lower among Scottish Health Survey respondents compared with the general population. For all years combined, the survey-to-population rate ratios were 0.69 (95% confidence interval: 0.61, 0.76) for the incidence of alcohol-related harm and 0.89 (95% confidence interval: 0.83, 0.96) for all-cause mortality. Bias was more pronounced among persons residing in more deprived areas; limited evidence was found for regional or temporal variation. This suggests that corresponding underestimation of population rates of alcohol consumption is likely to be socially patterned. PMID:25227767

  7. Acute administration of diosgenin or dioscorea improves hyperglycemia with increases muscular steroidogenesis in STZ-induced type 1 diabetic rats.

    PubMed

    Sato, K; Fujita, S; Iemitsu, M

    2014-09-01

    Acute dehydroepiandrosterone (DHEA) administration improves hyperglycemia in rats with streptozotocin (STZ)-induced type 1 diabetes mellitus. Diosgenin, a steroid structurally similar to DHEA (dehydroepiandrosterone), is contained highly levels in dioscorea; however, it is still unclear whether this natural product improves hyperglycemia in the type 1 diabetes model rats through an increase muscular GLUT4 signaling. After 1 week of STZ injection, fasting glucose level was measured in blood taken from the tail vein every 30 min for 150 min after injection of diosgenin or dioscorea (3mg/kg). On another day, muscle was resected 150 min after diosgenin or dioscorea injections. Serum DHEA level increased significantly 120 min after diosgenin or dioscorea injections; concomitantly, blood glucose level decreased significantly. Moreover, GLUT4 translocation, as well as phosphorylation of Akt and PKC ζ/λ, increased significantly by diosgenin or dioscorea administration. However, these effects of diosgenin and dioscorea were blocked by a 5α-reductase inhibitor that inhibits synthesizing dehydrotestosterone (DHT) from testosterone. Additionally, significant correlations were observed between blood glucose level, GLUT4 translocation level, and muscular sex steroid hormone level 150 min after the administrations. These results suggest that the diosgenin-induced increase in the DHEA level may contribute to the improvement of hyperglycemia by activating the muscular GLUT4 signaling pathway in type 1 diabetes model rats.

  8. Time-course of changes in the social interaction test of anxiety following acute and chronic administration of nicotine.

    PubMed

    Irvine, E E; Cheeta, S; File, S E

    1999-11-01

    The purpose of these experiments was to explore the hypothesis that the effects of nicotine on anxiety depend on the time since administration and the duration of treatment. In the social interaction test of anxiety, acute nicotine administration (0.1 mg/kg, subcutaneously) decreased social interaction when rats were tested 5 min after injection, but increased it when they were tested 30 min after injection. Social interaction was also decreased 1 h post-injection, but levels returned to baseline between 3 and 30 h. As these changes were independent of any changes in locomotor activity, nicotine seemed to be having both anxiogenic and anxiolytic effects at different times after injection. An anxiolytic effect was also observed 30 min after the second nicotine injection, and the anxiogenic effect observed 5 min after injection remained after 4 days of nicotine administration. However, after 7 days of nicotine treatment, tolerance was observed to both these effects. When rats were tested 72 h after the last of 7 or 14 days of nicotine treatment, an anxiogenic withdrawal response was observed. Thus, an oppositional mechanism may underlie tolerance to the anxiolytic effects, whereas there is as yet no evidence for this type of mechanism mediating tolerance to the anxiogenic effects.

  9. Effects of ALDH2 Genotype, PPI Treatment and L-Cysteine on Carcinogenic Acetaldehyde in Gastric Juice and Saliva after Intragastric Alcohol Administration

    PubMed Central

    Maejima, Ryuhei; Iijima, Katsunori; Kaihovaara, Pertti; Hatta, Waku; Koike, Tomoyuki; Imatani, Akira; Shimosegawa, Tooru; Salaspuro, Mikko

    2015-01-01

    Acetaldehyde (ACH) associated with alcoholic beverages is Group 1 carcinogen to humans (IARC/WHO). Aldehyde dehydrogenase (ALDH2), a major ACH eliminating enzyme, is genetically deficient in 30–50% of Eastern Asians. In alcohol drinkers, ALDH2-deficiency is a well-known risk factor for upper aerodigestive tract cancers, i.e., head and neck cancer and esophageal cancer. However, there is only a limited evidence for stomach cancer. In this study we demonstrated for the first time that ALDH2 deficiency results in markedly increased exposure of the gastric mucosa to acetaldehyde after intragastric administration of alcohol. Our finding provides concrete evidence for a causal relationship between acetaldehyde and gastric carcinogenesis. A plausible explanation is the gastric first pass metabolism of ethanol. The gastric mucosa expresses alcohol dehydrogenase (ADH) enzymes catalyzing the oxidation of ethanol to acetaldehyde, especially at the high ethanol concentrations prevailing in the stomach after the consumption of alcoholic beverages. The gastric mucosa also possesses the acetaldehyde-eliminating ALDH2 enzyme. Due to decreased mucosal ALDH2 activity, the elimination of ethanol-derived acetaldehyde is decreased, which results in its accumulation in the gastric juice. We also demonstrate that ALDH2 deficiency, proton pump inhibitor (PPI) treatment, and L-cysteine cause independent changes in gastric juice and salivary acetaldehyde levels, indicating that intragastric acetaldehyde is locally regulated by gastric mucosal ADH and ALDH2 enzymes, and by oral microbes colonizing an achlorhydric stomach. Markedly elevated acetaldehyde levels were also found at low intragastric ethanol concentrations corresponding to the ethanol levels of many foodstuffs, beverages, and dairy products produced by fermentation. A capsule that slowly releases L-cysteine effectively eliminated acetaldehyde from the gastric juice of PPI-treated ALDH2-active and ALDH2-deficient subjects. These

  10. Acute and chronic effects of alcohol exposure on skeletal muscle c-myc, p53, and Bcl-2 mRNA expression.

    PubMed

    Nakahara, Tatsuo; Hashimoto, Kijiro; Hirano, Makoto; Koll, Michael; Martin, Colin R; Preedy, Victor R

    2003-12-01

    Skeletal muscle atrophy is a common feature in alcoholism that affects up to two-thirds of alcohol misusers, and women appear to be particularly susceptible. There is also some evidence to suggest that malnutrition exacerbates the effects of alcohol on muscle. However, the mechanisms responsible for the myopathy remain elusive, and some studies suggest that acetaldehyde, rather than alcohol, is the principal pathogenic perturbant. Previous reports on rats dosed acutely with ethanol (<24 h) have suggested that increased proto-oncogene expression (i.e., c-myc) may be a causative process, possibly via activating preapoptotic or transcriptional pathways. We hypothesized that 1) increases in c-myc mRNA levels also occur in muscle exposed chronically to alcohol, 2) muscle of female rats is more sensitive than that from male rats, 3) raising acetaldehyde will also increase c-myc, 4) prior starvation will cause further increases in c-myc mRNA expression in response to ethanol, and 5) other genes involved in apoptosis (i.e., p53 and Bcl-2) would also be affected by alcohol. To test this, we measured c-myc mRNA levels in skeletal muscle of rats dosed either chronically (6-7 wk; ethanol as 35% of total dietary energy) or acutely (2.5 h; ethanol as 75 mmol/kg body wt ip) with ethanol. All experiments were carried out in male Wistar rats (approximately 0.1-0.15 kg body wt) except the study that examined gender susceptibility in male and female rats. At the end of the studies, rats were killed, and c-myc, p53, and Bcl-2 mRNA was analyzed in skeletal muscle by RT-PCR with an endogenous internal standard, GAPDH. The results showed that 1) in male rats fed ethanol chronically, there were no increases in c-myc mRNA; 2) increases, however, occurred in c-myc mRNA in muscle from female rats fed ethanol chronically; 3) raising endogenous acetaldehyde with cyanamide increased c-myc mRNA in acute studies; 4) starvation per se increased c-myc mRNA levels and at 1 day potentiated the acute

  11. Conditioned place aversion to the "hangover" phase of acute ethanol administration in the rat.

    PubMed

    Morse, A C; Schulteis, G; Holloway, F A; Koob, G F

    2000-08-01

    The purpose of this study was to examine ethanol's delayed effects (termed hangover) using conditioned place testing. Four groups of rats received a single pairing of a distinctive environment (tactile and visual) 10 h after injection with ethanol (0, 2, 3, 4 g/kg, i.p. ) or saline in a counterbalanced design. Rats receiving 3 and 4 g/kg ethanol showed a conditioned place aversion to ethanol hangover. Conditioning 10 h after 0 or 2 g/kg ethanol did not produce a significant place preference or aversion. The results suggest that the hangover following an acute injection of high doses of ethanol (3-4 g/kg) produces a significant and dose-related conditioned place aversion in the rat.

  12. Sequential Administration of Methotrexate and Asparaginase in Relapsed or Refractory Pediatric Acute Myeloid Leukemia

    PubMed Central

    Buaboonnam, Jassada; Cao, Xueyuan; Pauley, Jennifer L.; Pui, Ching-Hon; Ribeiro, Raul C.; Rubnitz, Jeffrey E.; Inaba, Hiroto

    2014-01-01

    Background The efficacy of combination chemotherapy with methotrexate (MTX) and asparaginase is not well known in relapsed and refractory acute leukemia after contemporary therapy. Procedure A retrospective study of pediatric patients with relapsed or refractory acute myeloid leukemia (AML) who received MTX and asparaginase as a salvage therapy at St. Jude Children Research Hospital was performed. MTX was given intravenously followed by a dose of asparaginase intramuscularly or intravenously 24 hours later. The chemotherapy cycle was repeated every 7-10 days. Response, survival, and toxicities were evaluated. Results Fifteen patients, median age 10.5 years (range, 1.1-18.5 years), were treated. Median number of previous therapeutic regimens was 3 (range, 1-4). Six patients responded to treatment (3 had morphologic complete remission with incomplete blood count recovery, 2 had partial remission, and 1 had stable disease for 16 months), and 4 are still alive. Three of 6 responders had monoblastic leukemia, and also developed tumor lysis syndrome. The 1- and 2-year overall survival rates are 35.6% and 17.8%, respectively. The most common adverse event was transient elevation of transaminases (9 patients). Two patients developed pancreatitis. Episodes of febrile neutropenia were rare (2 patients), and most courses (75 out of 93 total courses) were given in an outpatient setting. Conclusions Combination chemotherapy with MTX and asparaginase appears to be an effective salvage therapy and well tolerated in patients with relapsed or refractory childhood AML, even in those heavily pretreated with contemporary frontline or salvage therapy. PMID:23335430

  13. Effects of inhaled CO administration on acute lung injury in baboons with pneumococcal pneumonia

    PubMed Central

    Kraft, Bryan D.; Hess, Dean R.; Harris, R. Scott; Wolf, Monroe A.; Suliman, Hagir B.; Roggli, Victor L.; Davies, John D.; Winkler, Tilo; Stenzler, Alex; Baron, Rebecca M.; Thompson, B. Taylor; Choi, Augustine M.; Welty-Wolf, Karen E.; Piantadosi, Claude A.

    2015-01-01

    Inhaled carbon monoxide (CO) gas has therapeutic potential for patients with acute respiratory distress syndrome if a safe, evidence-based dosing strategy and a ventilator-compatible CO delivery system can be developed. In this study, we used a clinically relevant baboon model of Streptococcus pneumoniae pneumonia to 1) test a novel, ventilator-compatible CO delivery system; 2) establish a safe and effective CO dosing regimen; and 3) investigate the local and systemic effects of CO therapy on inflammation and acute lung injury (ALI). Animals were inoculated with S. pneumoniae (108-109 CFU) (n = 14) or saline vehicle (n = 5); in a subset with pneumonia (n = 5), we administered low-dose, inhaled CO gas (100–300 ppm × 60–90 min) at 0, 6, 24, and/or 48 h postinoculation and serially measured blood carboxyhemoglobin (COHb) levels. We found that CO inhalation at 200 ppm for 60 min is well tolerated and achieves a COHb of 6–8% with ambient CO levels ≤ 1 ppm. The COHb level measured at 20 min predicted the 60-min COHb level by the Coburn-Forster-Kane equation with high accuracy. Animals given inhaled CO + antibiotics displayed significantly less ALI at 8 days postinoculation compared with antibiotics alone. Inhaled CO was associated with activation of mitochondrial biogenesis in the lung and with augmentation of renal antioxidative programs. These data support the feasibility of safely delivering inhaled CO gas during mechanical ventilation and provide preliminary evidence that CO may accelerate the resolution of ALI in a clinically relevant nonhuman primate pneumonia model. PMID:26320156

  14. Acute and chronic caffeine administration increases physical activity in sedentary adults.

    PubMed

    Schrader, Patrick; Panek, Leah M; Temple, Jennifer L

    2013-06-01

    Caffeine is a commonly used stimulant thought to have ergogenic properties. Most studies on the ergogenic effects of caffeine have been conducted in athletes. The purpose of this study was to test the hypothesis that caffeine reduces ratings of perceived exertion and increases liking of physical activity in sedentary adults. Participants completed treadmill walking at 60% to 70% of their maximal heart rate at baseline and for 6 subsequent visits, during which half of the participants were given caffeine (3 mg/kg) and half given placebo in a sports drink vehicle. To investigate the potential synergistic effects of acute and chronic caffeine on self-determined exercise duration, participants were rerandomized to either the same or different condition for the last visit, creating 4 chronic/acute treatment groups (placebo/placebo, placebo/caffeine, caffeine/placebo, caffeine/caffeine). Participants rated how much they liked the activity and perceived exertion at each visit. There was a main effect of time on liking of physical activity, with liking increasing over time and an interaction of sex and caffeine treatment on liking, with liking of activity increasing in female participants treated with caffeine, but not with placebo. There was no effect of caffeine on ratings of perceived exertion. Individuals who received caffeine on the final test day exercised for significantly longer than those who received placebo. These data suggest that repeated exposure to physical activity significantly increases liking of exercise and reduces ratings of perceived exertion and that caffeine does little to further modify these effects.

  15. Effects of Intracoronary Administration of Autologous Adipose Tissue-Derived Stem Cells on Acute Myocardial Infarction in a Porcine Model

    PubMed Central

    Lee, Hye Won; Park, Jong Ha; Kim, Bo Won; Ahn, Jinhee; Kim, Jin Hee; Park, Jin Sup; Oh, Jun-Hyok; Choi, Jung Hyun; Cha, Kwang Soo; Hong, Taek Jong; Park, Tae Sik; Kim, Sang-Pil; Song, Seunghwan; Kim, Ji Yeon; Park, Mi Hwa; Jung, Jin Sup

    2015-01-01

    Purpose Adipose-derived stem cells (ADSCs) are known to be potentially effective in regeneration of damaged tissue. We aimed to assess the effectiveness of intracoronary administration of ADSCs in reducing the infarction area and improving function after acute transmural myocardial infarction (MI) in a porcine model. Materials and Methods ADSCs were obtained from each pig's abdominal subcutaneous fat tissue by simple liposuction. After 3 passages of 14-days culture, 2 million ADSCs were injected into the coronary artery 30 min after acute transmural MI. At baseline and 4 weeks after the ADSC injection, 99mTc methoxyisobutylisonitrile-single photon emission computed tomography (MIBI-SPECT) was performed to evaluate the left ventricular volume, left ventricular ejection fraction (LVEF; %), and perfusion defects as well as the myocardial salvage (%) and salvage index. At 4 weeks, each pig was sacrificed, and the heart was extracted and dissected. Gross and microscopic analyses with specific immunohistochemistry staining were then performed. Results Analysis showed improvement in the perfusion defect, but not in the LVEF in the ADSC group (n=14), compared with the control group (n=14) (perfusion defect, -13.0±10.0 vs. -2.6±12.0, p=0.019; LVEF, -8.0±15.4 vs. -15.9±14.8, p=0.181). There was a tendency of reducing left ventricular volume in ADSC group. The ADSCs identified by stromal cell-derived factor-1 (SDF-1) staining were well co-localized by von Willebrand factor and Troponin T staining. Conclusion Intracoronary injection of cultured ADSCs improved myocardial perfusion in this porcine acute transmural MI model. PMID:26446632

  16. Central nervous system activity of acute administration of isopulegol in mice.

    PubMed

    Silva, Maria Izabel Gomes; de Aquino Neto, Manuel Rufino; Teixeira Neto, Paulo Florentino; Moura, Brinell Arcanjo; do Amaral, Jeferson Falcão; de Sousa, Damião Pergentino; Vasconcelos, Silvânia Maria Mendes; de Sousa, Francisca Cléa Florenço

    2007-12-01

    Isopulegol is a monoterpene alcohol intermediate in the preparation of (-)-menthol and it is present in the essential oils of various plants. This work presents behavioral effects of isopulegol in animal models of open field, elevated plus maze (EPM), rota rod, hole board, barbiturate-induced sleeping time, tail suspension and forced swimming tests in mice. Isopulegol was administered intraperitoneally to male mice at single doses of 25 and 50 mg/kg, while diazepam 1 or 2 mg/kg and imipramine 10 or 30 mg/kg were used as standard drugs. The results showed that, similar to diazepam (1 mg/kg), both doses of isopulegol significantly modified all the observed parameters in the EPM test, without alter the general motor activity in the open field test. In the same way, both doses of isopulegol increased the number of head dips in the hole-board test. Forced swimming and tail suspension tests showed that isopulegol (25 and 50 mg/kg) was able to induce a significant increase in the immobility time, in opposite to imipramine, a recognized antidepressant drug. There was a decrease in the sleep latency time and prolongation of the pentobarbital-induced sleeping time with both doses of Isopulegol. Different from diazepam (2 mg/kg), isopulegol (25 e 50 mg/kg) had no effect on the motor coordination of animals in the rota rod test. These results showed that isopulegol presented depressant- and anxiolytic-like effects. PMID:17716715

  17. Intra-Peritoneal Administration of Mitochondrial DNA Provokes Acute Lung Injury and Systemic Inflammation via Toll-Like Receptor 9.

    PubMed

    Zhang, Lemeng; Deng, Songyun; Zhao, Shuangping; Ai, Yuhang; Zhang, Lina; Pan, Pinhua; Su, Xiaoli; Tan, Hongyi; Wu, Dongdong

    2016-01-01

    The pathogenesis of sepsis is complex. Mitochondrial dysfunction, which is responsible for energy metabolism, intrinsic apoptotic pathway, oxidative stress, and systemic inflammatory responses, is closely related with severe sepsis induced death. Mitochondria DNA (mtDNA) contain un-methylated cytosine phosphate guanine (CpG) motifs, which exhibit immune stimulatory capacities. The aim of this study was to investigate the role and mechanism of mtDNA release on lipopolysaccharide (LPS) induced acute lung injury (ALI) and systemic inflammation. Following LPS injection, plasma mtDNA copies peak at 8 h. Compared with wild-type (WT) mice, mtDNA in toll like receptor 4 knockout (TLR4 KO) mice were significantly decreased. MtDNA intra-peritoneal administration causes apparent ALI as demonstrated by increased lung injury score, bronchoalveolar lavage fluid (BALF) total protein and wet/dry (W/D) ratio; mtDNA injection also directly provokes systemic inflammation, as demonstrated by increased IL-1β, IL-6, high-mobility group protein B1 (HMGB1) level; while nuclear DNA (nDNA) could not induce apparent ALI and systemic inflammation. However, compared with WT mice, TLR4 KO could not protect from mtDNA induced ALI and systemic inflammation. Specific TLR9 inhibitor, ODN 2088 pretreatment can significantly attenuate mtDNA induced ALI and systemic inflammation, as demonstrated by improved lung injury score, decreased lung wet/dry ratio, BALF total protein concentration, and decreased systemic level of IL-1β, IL-6 and HMGB1. MtDNA administration activates the expression of p-P38 mitogen-activated protein kinases (MAPK) in lung tissue and specific TLR9 inhibitor pretreatment can attenuate this activation. Thus, LPS-induced mtDNA release occurs in a TLR4-dependent manner, and mtDNA causes acute lung injury and systemic inflammation in a TLR9-dependent and TLR4-independent manner. PMID:27589725

  18. Intra-Peritoneal Administration of Mitochondrial DNA Provokes Acute Lung Injury and Systemic Inflammation via Toll-Like Receptor 9

    PubMed Central

    Zhang, Lemeng; Deng, Songyun; Zhao, Shuangping; Ai, Yuhang; Zhang, Lina; Pan, Pinhua; Su, Xiaoli; Tan, Hongyi; Wu, Dongdong

    2016-01-01

    The pathogenesis of sepsis is complex. Mitochondrial dysfunction, which is responsible for energy metabolism, intrinsic apoptotic pathway, oxidative stress, and systemic inflammatory responses, is closely related with severe sepsis induced death. Mitochondria DNA (mtDNA) contain un-methylated cytosine phosphate guanine (CpG) motifs, which exhibit immune stimulatory capacities. The aim of this study was to investigate the role and mechanism of mtDNA release on lipopolysaccharide (LPS) induced acute lung injury (ALI) and systemic inflammation. Following LPS injection, plasma mtDNA copies peak at 8 h. Compared with wild-type (WT) mice, mtDNA in toll like receptor 4 knockout (TLR4 KO) mice were significantly decreased. MtDNA intra-peritoneal administration causes apparent ALI as demonstrated by increased lung injury score, bronchoalveolar lavage fluid (BALF) total protein and wet/dry (W/D) ratio; mtDNA injection also directly provokes systemic inflammation, as demonstrated by increased IL-1β, IL-6, high-mobility group protein B1 (HMGB1) level; while nuclear DNA (nDNA) could not induce apparent ALI and systemic inflammation. However, compared with WT mice, TLR4 KO could not protect from mtDNA induced ALI and systemic inflammation. Specific TLR9 inhibitor, ODN 2088 pretreatment can significantly attenuate mtDNA induced ALI and systemic inflammation, as demonstrated by improved lung injury score, decreased lung wet/dry ratio, BALF total protein concentration, and decreased systemic level of IL-1β, IL-6 and HMGB1. MtDNA administration activates the expression of p-P38 mitogen-activated protein kinases (MAPK) in lung tissue and specific TLR9 inhibitor pretreatment can attenuate this activation. Thus, LPS-induced mtDNA release occurs in a TLR4-dependent manner, and mtDNA causes acute lung injury and systemic inflammation in a TLR9-dependent and TLR4-independent manner. PMID:27589725

  19. Alcohol Consumption as a Risk Factor for Acute and Chronic Pancreatitis: A Systematic Review and a Series of Meta-analyses

    PubMed Central

    Samokhvalov, Andriy V.; Rehm, Jürgen; Roerecke, Michael

    2015-01-01

    Background Pancreatitis is a highly prevalent medical condition associated with a spectrum of endocrine and exocrine pancreatic insufficiencies. While high alcohol consumption is an established risk factor for pancreatitis, its relationship with specific types of pancreatitis and a potential threshold have not been systematically examined. Methods We conducted a systematic literature search for studies on the association between alcohol consumption and pancreatitis based on PRISMA guidelines. Non-linear and linear random-effect dose–response meta-analyses using restricted cubic spline meta-regressions and categorical meta-analyses in relation to abstainers were conducted. Findings Seven studies with 157,026 participants and 3618 cases of pancreatitis were included into analyses. The dose–response relationship between average volume of alcohol consumption and risk of pancreatitis was monotonic with no evidence of non-linearity for chronic pancreatitis (CP) for both sexes (p = 0.091) and acute pancreatitis (AP) in men (p = 0.396); it was non-linear for AP in women (p = 0.008). Compared to abstention, there was a significant decrease in risk (RR = 0.76, 95%CI: 0.60–0.97) of AP in women below the threshold of 40 g/day. No such association was found in men (RR = 1.1, 95%CI: 0.69–1.74). The RR for CP at 100 g/day was 6.29 (95%CI: 3.04–13.02). Interpretation The dose–response relationships between alcohol consumption and risk of pancreatitis were monotonic for CP and AP in men, and non-linear for AP in women. Alcohol consumption below 40 g/day was associated with reduced risk of AP in women. Alcohol consumption beyond this level was increasingly detrimental for any type of pancreatitis. Funding The work was financially supported by a grant from the National Institute on Alcohol Abuse and Alcoholism (R21AA023521) to the last author. PMID:26844279

  20. Alcohol myopathy: impairment of protein synthesis and translation initiation.

    PubMed

    Lang, C H; Kimball, S R; Frost, R A; Vary, T C

    2001-05-01

    Alcohol consumption leads to numerous morphological, biochemical and functional changes in skeletal and cardiac muscle. One such change observed in both tissues after either acute alcohol intoxication or chronic alcohol consumption is a characteristic decrease in the rate of protein synthesis. A decrease in translation efficiency appears to be responsible for at least part of the reduction. This review highlights advances in determining the molecular mechanisms by which alcohol impairs protein synthesis and places these observations in context of earlier studies on alcoholic myopathy. Both acute and chronic alcohol administration impairs translational control by modulating various aspects of peptide-chain initiation. Moreover, this alcohol-induced impairment in initiation is associated with a decreased availability of eukaryotic initiation factor (eIF) 4E in striated muscle, as evidenced by an increase in the amount of the inactive eIF4E.4E-BP1 complex and decrease in the active eIF4E.eIF4G complex. In contrast, alcohol does not produce consistent alterations in the control of translation initiation by the eIF2 system. The etiology of these changes remain unresolved. However, defects in the availability or effectiveness of various anabolic hormones, particularly insulin-like growth factor-I, are consistent with the alcohol-induced decrease in protein synthesis and translation initiation.

  1. [Effect of alcohol on vascular function].

    PubMed

    Kudo, Risa; Yuui, Katsuya; Kasuda, Shogo; Hatake, Katsuhiko

    2015-06-01

    Vascular function is regulated by a balance of vasoconstriction and vasorelaxation. Disorder in this balance due to alcohol consumption causes various clinical conditions. In this review, we discuss the effects of acute and chronic ethanol consumption on vascular responses, including vasoconstriction, endothelium-dependent vasorelaxation, and nerve-mediated vasorelaxation. Acute ethanol administration induces vasoconstriction in ethanol-naive animals in vitro. Furthermore, ethanol can both potentiate and suppress agonist-induced Ca(2+)-dependent vasoconstriction. Moreover, ethanol augments Ca(2+)-independent vasoconstriction by increasing Ca2+ sensitivity. Endothelium-dependent relaxation is mediated by the nitric oxide (NO) pathway and the endothelium-derived hyperpolarizing factor (EDHF) pathway. Acute ethanol treatment inhibits both NO- and EDHF-mediated relaxation. Furthermore, acute ethanol ingestion can also potentiate and suppress calcitonin gene-related peptide (CGRP)-induced nerve-mediated relaxation. These opposing effects may be due to differences in species or vascular beds. Thus, acute ethanol treatment decreases vasorelaxation, thereby shifting the contraction-relaxation balance towards contraction. Combined, these effects are one mechanism by which acute heavy alcohol consumption causes circulatory disturbances such as vasospasms or ischemic heart disease. In contrast, chronic low-dose ethanol has no effect on vasoconstriction, whereas chronic high-dose ethanol increases vasoconstriction. Additionally, chronic ethanol intake has diminished, unchanged, and even increased effects on nerve-mediated relaxation; therefore, conclusions on these effects are not possible at present. Interestingly, chronic low-dose ethanol administration enhanced endothelium-dependent relaxation; however, higher doses inhibited these responses. Therefore, regular or light-to-moderate alcohol intake increases vasorelaxation and may suppress elevated blood pressure, whereas

  2. The `One-Two Punch' of Alcoholism: Role of Central Amygdala Dynorphins / Kappa-Opioid Receptors

    PubMed Central

    Kissler, Jessica L.; Sirohi, Sunil; Reis, Daniel J.; Jansen, Heiko T.; Quock, Raymond M.; Smith, Daniel G.; Walker, Brendan M.

    2013-01-01

    Background The dynorphin (DYN)/κ-opioid receptor (KOR) system undergoes neuroadaptations following chronic alcohol exposure that promote excessive operant self-administration and negative affective-like states; however, the exact mechanisms are unknown. The present studies tested the hypothesis that an upregulated DYN/KOR system mediates excessive alcohol self-administration that occurs during withdrawal in alcohol-dependent rats by assessing DYN A peptide expression and KOR function, in combination with site-specific pharmacological manipulations. Methods Male Wistar rats were trained to self-administer alcohol using operant behavioral strategies and subjected to intermittent alcohol vapor- or air-exposure. Changes in self-administration were assessed by pharmacological challenges during acute withdrawal. In addition, 22-kHz ultrasonic vocalizations were utilized to measure negative affective-like states. Immunohistochemical techniques assessed DYN A peptide expression and [35S]GTPγS coupling assays were performed to assess KOR function. Results Alcohol-dependent rats displayed increased alcohol self-administration, negative affective-like behavior, DYN A-like immunoreactivity and KOR signaling in the amygdala compared to non-dependent controls. Site-specific infusions of a KOR antagonist selectively attenuated self-administration in dependent rats whereas, a MOR/DOR antagonist cocktail selectively reduced self-administration in non-dependent rats. A MOR antagonist/partial KOR agonist attenuated self-administration in both cohorts. Conclusion Increased DYN A and increased KOR signaling could set the stage for a `one-two punch' during withdrawal that drives excessive alcohol consumption in alcohol-dependence. Importantly, intra-CeA pharmacological challenges functionally confirmed a DYN/KOR system involvement in the escalated alcohol self-administration. Together, the DYN/KOR system is heavily dysregulated in alcohol dependence and contributes to the excessive

  3. Fast and delayed locomotor response to acute high-dose nicotine administration in adult male rats.

    PubMed

    Jandová, K; Marešová, D; Pokorný, J

    2013-01-01

    The aim of the present study was to compare the immediate and delayed locomotor response to high-dose nicotine (NIC) administration in rats. The vertical and horizontal activity of behavior in adult male rats exposed to 1 mg/kg NIC or saline (SAL) were tested in a Laboras apparatus for one hour after drug application. Animals were then returned to their cages and housed for another seven days. After this period all animals were placed in Laboras again and their behavioral pattern was retested for another period of one hour (delayed response). Horizontal activity: immediately after nicotine administration animal were less mobile (first 2-minutes interval), when compared with controls. The immobilization effect of nicotine disappeared within 4 minutes and during whole first 10-minutes interval time spent by locomotion did not differ from controls. Locomotion activity of animals treated with nicotine increased robustly in following 10 minutes and remained significantly higher in 2nd, 3rd and 5th 10-minutes interval. Vertical activity: Rearing frequency was significantly lowered by NIC administration in first two minutes of the experiment and the same was found when the duration of rearing was analyzed. Lower rearing intensity of NIC treated animals disappeared in 4 minutes and was finally higher during whole test session as compared with controls. When duration of rearing was analyzed it was significantly longer in NIC treated animals. In majority of observed behavioral aspects there were no differences between NIC treated rats and controls seven days after NIC or SAL treatment. Our results reflect effect of NIC and we conclude that NIC significantly influences behavior of experimental animals.

  4. Acute effects of oxygen administration on transmural pulmonary artery pressure in obstructive sleep apnea.

    PubMed

    Marrone, O; Bellia, V; Pieri, D; Salvaggio, A; Bonsignore, G

    1992-04-01

    In order to investigate the role of hypoxia on the cyclic oscillation of transmural pulmonary artery pressure (PAP) in obstructive sleep apnea, oxygen was administered during one half of the night to six patients affected by obstructive sleep apnea syndrome during a nocturnal polysomnographic study. In each patient, transmural PAP measurements were performed on 15 randomly selected apneas recorded while breathing room air, and on 15 during O2 administration. During O2 administration in all patients, apneas were associated with a higher oxyhemoglobin saturation (SaO2), a smaller SaO2 swing, and a higher transcutaneous PCO2. The mean highest level of transmural PAP in the apneic episodes, commonly reached at their end, was significantly lower than while breathing room air in only two patients; however, due to a decrease in the mean lowest PAP level (at the beginning of apneas), the extent of the PAP increase within apneas did not differ between air and O2 breathing; these patients showed the smallest increase in transcutaneous PCO2 in our sample. End-apneic transmural PAP during O2 administration was significantly higher in one subject (for systolic values) and was not significantly different in the remaining three subjects. The extent of the increase in transmural PAP within apneas was greater in one patient; it was smaller in another one, but only for the diastolic values; and it did not differ significantly with respect to the value observed while breathing room air in all of the other subjects. The results suggest that hypoxia in obstructive apneas, at least in some patients, may lead to a steady increase in PAP, detectable both at the beginning and at the end of the episodes; conversely, the increase in PAP within apneas does not seem to be influenced by the simultaneous decrease in SaO2. PMID:1555416

  5. Persistent penile prolapse associated with acute blood loss and acepromazine maleate administration in a horse.

    PubMed

    Nie, G J; Pope, K C

    1997-09-01

    Prolonged penile prolapse in horses has been reported in association with administration of phenothiazine tranquilizers, trauma, neuropathies, severe general debilitation or exhaustion, starvation, rabies, herpes myeloencephalitis, equine infectious anemia, and purpura hemorrhagica. A 5-year-old gelding was admitted for treatment of prolonged penile prolapse of 12 days' duration that developed after acepromazine maleate was administered to allow examination of a laceration that had resulted in severe blood loss. The horse was sedated, and the penis was replaced in the preputial cavity by use of a combination of massage and bandaging. Treatment was successful, and recovery was complete.

  6. The role of glycerol-3-phosphate dehydrogenase 1 in the progression of fatty liver after acute ethanol administration in mice

    SciTech Connect

    Sato, Tomoki; Morita, Akihito; Mori, Nobuko; Miura, Shinji

    2014-02-21

    Highlights: • Ethanol administration increased GPD1 mRNA expression. • Ethanol administration increased glucose incorporation into TG glycerol moieties. • No increase in hepatic TG levels was observed in ethanol-injected GPD1 null mice. • We propose that GPD1 is required for ethanol-induced TG accumulation in the liver. - Abstract: Acute ethanol consumption leads to the accumulation of triglycerides (TGs) in hepatocytes. The increase in lipogenesis and reduction of fatty acid oxidation are implicated as the mechanisms underlying ethanol-induced hepatic TG accumulation. Although glycerol-3-phosphate (Gro3P), formed by glycerol kinase (GYK) or glycerol-3-phosphate dehydrogenase 1 (GPD1), is also required for TG synthesis, the roles of GYK and GPD1 have been the subject of some debate. In this study, we examine (1) the expression of genes involved in Gro3P production in the liver of C57BL/6J mice in the context of hepatic TG accumulation after acute ethanol intake, and (2) the role of GPD1 in the progression of ethanol-induced fatty liver using GPD1 null mice. As a result, in C57BL/6J mice, ethanol-induced hepatic TG accumulation began within 2 h and was 1.7-fold greater than that observed in the control group after 6 h. The up-regulation of GPD1 began 2 h after administering ethanol, and significantly increased 6 h later with the concomitant escalation in the glycolytic gene expression. The incorporation of {sup 14}C-labelled glucose into TG glycerol moieties increased during the same period. On the other hand, in GPD1 null mice carrying normal GYK activity, no significant increase in hepatic TG level was observed after acute ethanol intake. In conclusion, GPD1 and glycolytic gene expression is up-regulated by ethanol, and GPD1-mediated incorporation of glucose into TG glycerol moieties together with increased lipogenesis, is suggested to play an important role in ethanol-induced hepatic TG accumulation.

  7. Chronic glial activation, neurodegeneration, and APP immunoreactive deposits following acute administration of double-stranded RNA.

    PubMed

    Melton, Lisa M; Keith, Alexander B; Davis, Sue; Oakley, Arthur E; Edwardson, James A; Morris, Christopher M

    2003-10-01

    Several neurodegenerative disorders, including Alzheimer's and Parkinson's diseases, are associated with immunocompetent microglia, leading to the suggestion that chronic glial-mediated inflammation contributes to the neurodegeneration seen in these diseases. Little direct evidence supports this hypothesis, and no suitable rodent models exist that do not involve the use of blunt trauma or ischaemia, events that are infrequently encountered in the human disease state. In the present study, we report that administration of double-stranded RNA, a classical inducer of interferon-gamma (IFN-gamma), causes rapid and persistent activation of microglia and astrocytes, as well as induction of interleukin-1beta (IL-beta) and nitric oxide synthase. In close temporal succession to glial activation, there is neurodegeneration, with neuron loss involving apoptosis in selected brain regions including the septal nucleus, hippocampus, cortex and thalamus, along with hippocampal atrophy. This neuronal loss is accompanied by punctate deposits of material that are immunoreactive for amyloid precursor protein, beta-amyloid peptide (Abeta), and apolipoprotein E. The findings may have clinical relevance, since the administration of the nonsteroidal antiinflammatory agent (NSAID) ibuprofen markedly reduces the neurodegeneration observed in the absence of significant glial inhibition. These findings may be relevant to the pathogenesis of Alzheimer's disease in particular, and to other neurodegenerative diseases involving inflammation.

  8. Effects of acute administration of caffeine on local cerebral glucose utilization in the rat.

    PubMed

    Nehlig, A; Lucignani, G; Kadekaro, M; Porrino, L J; Sokoloff, L

    1984-05-18

    The quantitative 2-[14C]deoxyglucose autoradiographic method was used to study the effects of acute intravenous injections (15 min prior to study) of caffeine on brain energy metabolism. With doses of 0.1 mg/kg the effects of caffeine on cerebral glucose utilization were limited to the habenula, spinal trigeminal and paraventricular nuclei. After the 1.0 mg/kg dose significant increases were additionally seen in the caudate, ventral tegmental area and medial septum. After the injection of 10 mg/kg of caffeine, average glucose utilization of the brain as a whole was increased by 15%, and of 71 structures examined 31 structures were statistically significantly affected. Among these were all brainstem monoaminergic cell groupings, components of the extrapyramidal motor system, anterior cingulate, and medial prefrontal cortex. In the hypothalamus glucose utilization increased only in the paraventricular nucleus, arcuate nucleus, and median eminence. This study demonstrates that there is a correlation between the known stimulant effects of caffeine on behavior and widespread increases in glucose utilization throughout the brain.

  9. Differential effects of acute morphine administrations on polymorphonuclear cell metabolism in various mouse strains.

    PubMed

    Di Francesco, P; Tavazzi, B; Gaziano, R; Lazzarino, G; Casalinuovo, I A; Di Pierro, D; Garaci, E

    1998-01-01

    This paper shows that an acute morphine treatment dose-dependently alters the energetic and oxidative metabolism of polymorphonuclear leukocytes obtained from BALB/c and DBA/2 mice, while phagocytic cells from C57BL/6 were not affected. In sensitive mouse strains, i.e. BALB/c and DBA/2, morphine decreased both ATP concentration and energy charge potential. At the same time, ATP catabolic products, i.e. nucleosides (inosine+adenosine) and oxypurines (hypoxanthine+xanthine+uric acid), significantly increased, indicating an imbalance between energy production and consumption. Morphine treatment also induced malondialdehyde and superoxide anions production in leukocyte cells from sensitive mice. The opiate antagonist naloxone blocked morphine-induced modifications by the lower morphine dose. The same parameters in cells from C57BL/6 mice were not affected. These findings confirm that: i) the phagocytic cells are an important target for the in vivo effects of morphine, and ii) the genotype-dependent variation influences the immunological responsiveness to opiates.

  10. Paradoxical glucose-sensitizing yet proinflammatory effects of acute ASP administration in mice.

    PubMed

    Fisette, Alexandre; Poursharifi, Pegah; Oikonomopoulou, Katerina; Munkonda, Mercedes N; Lapointe, Marc; Cianflone, Katherine

    2013-01-01

    Acylation stimulating protein (ASP) is an adipokine derived from the immune complement system, which stimulates fat storage and is typically increased in obesity, type 2 diabetes, and cardiovascular disease. Using a diet-induced obesity (DIO) mouse model, the acute effects of ASP on energy metabolism and inflammatory processes in vivo were evaluated. We hypothesized that ASP would specifically exert proinflammatory effects. C57Bl/6 wild-type mice were put on a high-fat-high-sucrose diet for 12 weeks. Mice were then subjected to both glucose and insulin tolerance tests, each manipulation being preceded by recombinant ASP or vehicle (control) bolus injection. ASP supplementation increased whole-body glucose excursion, and this was accomplished with reduced concomitant insulin levels. However, ASP did not directly alter insulin sensitivity. ASP supplementation induced a proinflammatory phenotype, with higher levels of cytokines including IL-6 and TNF-α in plasma and in adipose tissue, liver, and skeletal muscle mRNA. Additionally, ASP increased M1 macrophage content of these tissues. ASP exerted a direct concentration-dependent role in the migration and M1 activation of cultured macrophages. Altogether, the in vivo and in vitro experiments demonstrate that ASP plays a role in both energy metabolism and inflammation, with paradoxical whole-body glucose-sensitizing yet proinflammatory effects.

  11. Suppression of alcohol consumption by fenfluramine in Fawn-Hooded rats with serotonin dysfunction.

    PubMed

    Rezvani, A H; Grady, D R

    1994-05-01

    The high preference for alcohol intake observed in Fawn-Hooded rats has been attributed to the central serotonin (5-HT) dysfunction in this strain. To further characterize the involvement of 5-HT in alcohol-seeking behavior in Fawn-Hooded rats, the effect of both acute and subchronic administration of fenfluramine, a 5-HT releaser, on alcohol intake and preference was determined. Rats were individually housed and provided free access to a solution of 10% alcohol, food, and water. After establishing a stable baseline, rats were injected twice daily for 1 day or for 5 consecutive days either with saline or 0.1, 0.25, 0.5, and 1.0 mg/kg of fenfluramine at 0930 h and 1600 h, and their consumption of alcohol, food, and water was measured for 24 h. Another group of rats scheduled with a limited access (1 h/day) to alcohol and free access to food and water were injected with either saline or 0.25, 0.5, 0.75, and 1.0 mg/kg fenfluramine 20 min before exposure to alcohol, and their alcohol consumption was measured at the end of 1 h exposure. Further, to determine the effect of fenfluramine on alcohol metabolism, rats were injected with 1.0 mg/kg fenfluramine or saline and 15 min later with 2.5 g/kg alcohol (16%, v/v). Blood alcohol levels were then measured at 1, 3, and 5 h after alcohol administration. Our results demonstrate that both acute and subchronic administration of fenfluramine dose-dependently attenuate alcohol intake and increased water intake without a significant effect on food intake. Fenfluramine did not affect the pharmacokinetics of alcohol, indicating a central effect.(ABSTRACT TRUNCATED AT 250 WORDS)

  12. Acute effects of alcohol on stimulus-induced gamma oscillations in human primary visual and motor cortices.

    PubMed

    Campbell, Anne E; Sumner, Petroc; Singh, Krish D; Muthukumaraswamy, Suresh D

    2014-08-01

    Alcohol is a rich drug affecting both the γ-amino butyric acid (GABA) and glutamatergic neurotransmitter systems. Recent findings from both modeling and pharmacological manipulation have indicated a link between GABAergic activity and oscillations measured in the gamma frequency range (30-80 Hz), but there are no previous reports of alcohol's modulation of gamma-band activity measured by magnetoencephalography (MEG) or electroencephalography (EEG). In this single-blind, placebo-controlled crossover study, 16 participants completed two study days, on one day of which they consumed a dose of 0.8 g/kg alcohol, and on the other day a placebo. MEG recordings of brain activity were taken before and after beverage consumption, using visual grating and finger abduction paradigms known to induce gamma-band activity in the visual and motor cortices respectively. Time-frequency analyses of beamformer source reconstructions in the visual cortex showed that alcohol increased peak gamma amplitude and decreased peak frequency. For the motor task, alcohol increased gamma amplitude in the motor cortex. These data support the notion that gamma oscillations are dependent, in part, on the balance between excitation and inhibition. Disruption of this balance by alcohol, by increasing GABAergic inhibition at GABAA receptors and decreasing glutamatergic excitation at N-methyl-D-aspartic acid receptors, alters both the amplitude and frequency of gamma oscillations. The findings provide further insight into the neuropharmacological action of alcohol.

  13. Alcoholism and Alcohol Abuse

    MedlinePlus

    ... This means that their drinking causes distress and harm. It includes alcoholism and alcohol abuse. Alcoholism, or ... brain, and other organs. Drinking during pregnancy can harm your baby. Alcohol also increases the risk of ...

  14. National Veterans Health Administration inpatient risk stratification models for hospital-acquired acute kidney injury

    PubMed Central

    Cronin, Robert M; VanHouten, Jacob P; Siew, Edward D; Eden, Svetlana K; Fihn, Stephan D; Nielson, Christopher D; Peterson, Josh F; Baker, Clifton R; Ikizler, T Alp; Speroff, Theodore

    2015-01-01

    Objective Hospital-acquired acute kidney injury (HA-AKI) is a potentially preventable cause of morbidity and mortality. Identifying high-risk patients prior to the onset of kidney injury is a key step towards AKI prevention. Materials and Methods A national retrospective cohort of 1,620,898 patient hospitalizations from 116 Veterans Affairs hospitals was assembled from electronic health record (EHR) data collected from 2003 to 2012. HA-AKI was defined at stage 1+, stage 2+, and dialysis. EHR-based predictors were identified through logistic regression, least absolute shrinkage and selection operator (lasso) regression, and random forests, and pair-wise comparisons between each were made. Calibration and discrimination metrics were calculated using 50 bootstrap iterations. In the final models, we report odds ratios, 95% confidence intervals, and importance rankings for predictor variables to evaluate their significance. Results The area under the receiver operating characteristic curve (AUC) for the different model outcomes ranged from 0.746 to 0.758 in stage 1+, 0.714 to 0.720 in stage 2+, and 0.823 to 0.825 in dialysis. Logistic regression had the best AUC in stage 1+ and dialysis. Random forests had the best AUC in stage 2+ but the least favorable calibration plots. Multiple risk factors were significant in our models, including some nonsteroidal anti-inflammatory drugs, blood pressure medications, antibiotics, and intravenous fluids given during the first 48 h of admission. Conclusions This study demonstrated that, although all the models tested had good discrimination, performance characteristics varied between methods, and the random forests models did not calibrate as well as the lasso or logistic regression models. In addition, novel modifiable risk factors were explored and found to be significant. PMID:26104740

  15. Acute liver failure in a term neonate after repeated paracetamol administration

    PubMed Central

    Bucaretchi, Fábio; Fernandes, Carla Borrasca; Branco, Maíra Migliari; Capitani, Eduardo Mello De; Hyslop, Stephen; Caldas, Jamil Pedro S.; Moreno, Carolina Araújo; Porta, Gilda

    2014-01-01

    Objective: Severe hepatotoxicity caused by paracetamol is rare in neonates. We report a case of paracetamol-induced acute liver failure in a term neonate. Case description: A 26-day-old boy was admitted with intestinal bleeding, shock signs, slight liver enlargement, coagulopathy, metabolic acidosis (pH=7.21; bicarbonate: 7.1mEq/L), hypoglycemia (18mg/dL), increased serum aminotransferase activity (AST=4,039IU/L; ALT=1,087IU/L) and hyperbilirubinemia (total: 9.57mg/dL; direct: 6.18mg/dL) after receiving oral paracetamol (10mg/kg/dose every 4 hours) for three consecutive days (total dose around 180mg/kg; serum concentration 36-48 hours after the last dose of 77µg/ mL). Apart from supportive measures, the patient was successfully treated with intravenous N-acetylcysteine infusion during 11 consecutive days, and was discharged on day 34. The follow-up revealed full recovery of clinical and of laboratory findings of hepatic function. Comments: The paracetamol pharmacokinetics and pharmacodynamics in neonates and infants differ substantially from those in older children and adults. Despite the reduced rates of metabolism by the P-450 CYP2E1 enzyme system and the increased ability to synthesize glutathione - which provides greater resistance after overdoses -, it is possible to produce hepatotoxic metabolites (N-acetyl-p-benzoquinone) that cause hepatocellular damage, if glutathione sources are depleted. Paracetamol clearance is reduced and the half-life of elimination is prolonged. Therefore, a particular dosing regimen should be followed due to the toxicity risk of cumulative doses. This report highlights the risk for severe hepatotoxicity in neonates after paracetamol multiple doses for more than two to three days. PMID:24676202

  16. RAB GTPASES ASSOCIATE WITH ISOLATED LIPID DROPLETS (LDS) AND SHOW ALTERED CONTENT AFTER ETHANOL ADMINISTRATION: POTENTIAL ROLE IN ALCOHOL-IMPAIRED LD METABOLISM

    PubMed Central

    Rasineni, Karuna; McVicker, Benita L.; Tuma, Dean J.; McNiven, Mark A.; Casey, Carol A.

    2013-01-01

    Background Alcoholic liver disease is manifested by the presence of fatty liver, primarily due to accumulation of hepatocellular lipid droplets (LDs). The presence of membrane-trafficking proteins (e.g. Rab GTPases) with LDs indicates that LDs may be involved in trafficking pathways known to be altered in ethanol damaged hepatocytes. Since these Rab GTPases are crucial regulators of protein trafficking, we examined the effect ethanol administration has on hepatic Rab protein content and association with LDs. Methods Male Wistar rats were pair-fed Lieber-DeCarli diets for 5 to 8 weeks. Whole liver and isolated LD fractions were analyzed. Identification of LDs and associated Rab proteins was performed in frozen liver or paraffin-embedded sections followed by immunohistochemical analysis. Results Lipid accumulation was characterized by larger LD vacuoles and increased total triglyceride content in ethanol-fed rats. Rabs 1, 2, 3d, 5, 7 and 18 were analyzed in post-nuclear supernatant (PNS) as well as LDs. All of the Rabs were found in the PNS, and Rabs 1, 2, 5 and 7 did not show alcohol-altered content, while Rab 3d content was reduced by over 80%, and Rab 18 also showed ethanol-induced reduction in content. Rab 3d was not found to associate with LDs, while all other Rabs were found in the LD fractions, and several showed an ethanol-related decrease (Rabs 2, 5, 7, 18). Immunohistochemical analysis revealed the enhanced content of a LD-associated protein, perilipin 2 (PLIN2) that was paralleled with an associated decrease of Rab 18 in ethanol-fed rat sections. Conclusion Chronic ethanol feeding was associated with increased PLIN2 and altered Rab GTPase content in enriched LD fractions. Although mechanisms driving these changes are not established, further studies on intracellular protein trafficking and LD biology after alcohol administration will likely contribute to our understanding of fatty liver disease. PMID:24117505

  17. Acute and carryover effects in mice of MDMA ("ecstasy") administration during periadolescence.

    PubMed

    Morley-Fletcher, Sara; Bianchi, Mauro; Gerra, Gilberto; Laviola, Giovanni

    2002-07-12

    In spite of the increasing evidence concerning its neurotoxicity, young human individuals are often involved in the recreational use of amphetamine-type stimulants such as 3,4-methylenedioxymethamphetamine (MDMA or "ecstasy"). A study aimed to investigate short- and long-term consequences of a repeated and intermittent MDMA administration (0, 5 or 10 mg/kg i.p., 3 days treatment history) was conducted in mice. Mice were injected at different phases in development, namely at early (28 days old), middle (38 days old) or late (52 days old) adolescence. When assessed for nociceptive response, a dose-dependent analgesia was found in middle and late adolescent mice. Carryover consequences of previous MDMA treatment were then investigated at adulthood (80 days old). In a social interaction test, levels of environment exploration and social behaviour resulted markedly increased in drug-free state as a function of drug exposure during development, whereas others behaviours were reduced. MDMA challenge (5-mg/kg dose) produced the expected hyperactivity, as well as a marked increment of hypothalamic serotonin (5-hydroxyhyptamine, 5-HT) levels. Mice treated chronically with MDMA during middle and late adolescence were associated with important reductions of the indoleamine. As a whole, these results indicate a differential long-term vulnerability to behavioural and neurotoxicant effects of MDMA as a function of the developmental stage of exposure.

  18. Induction treatment of acute myeloid leukemia in an elderly patient with intramarrow injection/administration of cytarabine: first report of a case.

    PubMed

    Islam, Anwarul

    2015-12-01

    We have used intramarrow injection/administration of cytarabine (Ara-C) instead of conventional intravenous approach to induce remission in an elderly patient with acute myelogenous leukemia. We show for the first time that the intramarrow injection of chemotherapeutic agents such as Ara-C can be used safely and effectively.

  19. Evidence for a defect in pituitary secretion of luteinizing hormone in chronic alcoholic men.

    PubMed

    Van Thiel, D H; Lester, R; Vaitukaitis, J

    1978-09-01

    To characterize the defect in the hypothalamic-pituitary-gonadal axis of alcoholic men, acute and chronic LRF responses were evaluated in 22 chronic alcoholic men with varying degrees of biochemically and histologically confirmed liver disease. In addition, acute LRF responses in 14 normal men, before and at the end of 72 h of administration of 2 ml/kg/day 95% ethanol, were evaluated. The alcoholics hd significantly reduced basal testosterone and elevated gonadotropin levels (both FSH and LH) compared to the normal volunteers (P less than 0.02). Serum concentrations of estradiol and PRL did not differ between alcoholics and normal volunteers. A 100-micrograms bolus of LRF resulted in a 3-fold increase of LH in alcoholic men as compared to a 6-fold increase of serum LH in normal volunteers. No significant difference in the LRF-induced FSH responses was observed. When the response of normal volunteers to LRF before and after ethanol administration was evaluated, basal levels of both gonadotropins were increased after alcohol administration and a reduced LRF-induced LH response was observed. Based upon these results, we conclude that: 1) the central hypothalamic-pituitary defect known to exist for LH secretion is in part due to inadequate pituitary secretion and 2) acute alcohol ingestion in normal men suppresses the LRF-induced LH but not the FSH response.

  20. Altered distribution of regulatory lymphocytes by oral administration of soy-extracts exerts a hepatoprotective effect alleviating immune mediated liver injury, non-alcoholic steatohepatitis and insulin resistance

    PubMed Central

    Khoury, Tawfik; Ben Ya'acov, Ami; Shabat, Yehudit; Zolotarovya, Lidya; Snir, Ram; Ilan, Yaron

    2015-01-01

    AIM: To determine the immune-modulatory and the hepatoprotective effects of oral administration of two soy extracts in immune mediated liver injury and non-alcoholic steatohepatitis (NASH). METHODS: Two soy extracts, M1 and OS, were orally administered to mice with concanavalin A (ConA) immune-mediated hepatitis, to high-fat diet (HFD) mice and to methionine and choline reduced diet combined with HFD mice. Animals were followed for disease and immune biomarkers. RESULTS: Oral administration of OS and M1 had an additive effect in alleviating ConA hepatitis manifested by a decrease in alanine aminotransferase and aspartate aminotransferase serum levels. Oral administration of the OS and M1 soy derived fractions, ameliorated liver injury in the high fat diet model of NASH, manifested by a decrease in hepatic triglyceride levels, improvement in liver histology, decreased serum cholesterol and triglycerides and improved insulin resistance. In the methionine and choline reduced diet combined with the high fat diet model, we noted a decrease in hepatic triglycerides and improvement in blood glucose levels and liver histology. The effects were associated with reduced serum tumor necrosis factor alpha and alteration of regulatory T cell distribution. CONCLUSION: Oral administration of the combination of OS and M1 soy derived extracts exerted an adjuvant effect in the gut-immune system, altering the distribution of regulatory T cells, and alleviating immune mediated liver injury, hyperlipidemia and insulin resistance. PMID:26139990

  1. Effects of Acute and Repeated Administration of Oxycodone and Naloxone-Precipitated Withdrawal on Intracranial Self-Stimulation in Rats.

    PubMed

    Wiebelhaus, Jason M; Walentiny, D Matthew; Beardsley, Patrick M

    2016-01-01

    Incidence of prescription opioid abuse and overdose, often led by oxycodone, continues to increase, producing twice as many overdose deaths as heroin. Surprisingly, preclinical reports relevant to oxycodone's abuse-related effects are relatively sparse considering its history and patient usage. The goal of this study was to characterize dose- and time-dependent effects of acute and repeated oxycodone administration in a frequency-rate intracranial self-stimulation (ICSS) procedure, an assay often predictive of drug-related reinforcing effects, in male Sprague-Dawley rats. We hypothesized that oxycodone would produce a biphasic profile of rate-increasing and rate-decreasing effects maintained by ICSS similar to μ-opioid receptor agonists. Oxycodone (0.03, 0.3, 1, and 3 mg/kg, s.c.) produced dose- and time-dependent alterations on ICSS, with the predicted biphasic profile of rate-increasing effects at lower stimulation frequencies followed by rate-decreasing effects at higher frequencies. Peak effects were observed between 30 and 60 minutes, which were reversed by naloxone pretreatment (30 minutes). Tolerance to rate-decreasing effects was observed over a 5-day period when rats were treated with 1 mg/kg oxycodone twice a day. Subsequently, the dosing regimen was increased to 3 mg/kg twice a day over 10 days, although further marked tolerance did not develop. When then challenged with 10 mg/kg naloxone, a significant suppression below baseline levels of ICSS-maintained responding occurred indicative of dependence that recovered to baseline within 5 hours. The results of this study provide the first report of acute and chronic effects of oxycodone on responding maintained by ICSS presentation and the use of ICSS-maintained responding to characterize its tolerance and dependence effects.

  2. Downstream signaling pathways in mouse adipose tissues following acute in vivo administration of fibroblast growth factor 21.

    PubMed

    Muise, Eric S; Souza, Sandra; Chi, An; Tan, Yejun; Zhao, Xuemei; Liu, Franklin; Dallas-Yang, Qing; Wu, Margaret; Sarr, Tim; Zhu, Lan; Guo, Hongbo; Li, Zhihua; Li, Wenyu; Hu, Weiwen; Jiang, Guoqiang; Paweletz, Cloud P; Hendrickson, Ronald C; Thompson, John R; Mu, James; Berger, Joel P; Mehmet, Huseyin

    2013-01-01

    FGF21 is a novel secreted protein with robust anti-diabetic, anti-obesity, and anti-atherogenic activities in preclinical species. In the current study, we investigated the signal transduction pathways downstream of FGF21 following acute administration of the growth factor to mice. Focusing on adipose tissues, we identified FGF21-mediated downstream signaling events and target engagement biomarkers. Specifically, RNA profiling of adipose tissues and phosphoproteomic profiling of adipocytes, following FGF21 treatment revealed several specific changes in gene expression and post-translational modifications, specifically phosphorylation, in several relevant proteins. Affymetrix microarray analysis of white adipose tissues isolated from both C57BL/6 (fed either regular chow or HFD) and db/db mice identified over 150 robust potential RNA transcripts and over 50 potential secreted proteins that were changed greater than 1.5 fold by FGF21 acutely. Phosphoprofiling analysis identified over 130 phosphoproteins that were modulated greater than 1.5 fold by FGF21 in 3T3-L1 adipocytes. Bioinformatic analysis of the combined gene and phosphoprotein profiling data identified a number of known metabolic pathways such as glucose uptake, insulin receptor signaling, Erk/Mapk signaling cascades, and lipid metabolism. Moreover, a number of novel events with hitherto unknown links to FGF21 signaling were observed at both the transcription and protein phosphorylation levels following treatment. We conclude that such a combined "omics" approach can be used not only to identify robust biomarkers for novel therapeutics but can also enhance our understanding of downstream signaling pathways; in the example presented here, novel FGF21-mediated signaling events in adipose tissue have been revealed that warrant further investigation.

  3. Downstream Signaling Pathways in Mouse Adipose Tissues Following Acute In Vivo Administration of Fibroblast Growth Factor 21

    PubMed Central

    Chi, An; Tan, Yejun; Zhao, Xuemei; Liu, Franklin; Dallas-yang, Qing; Wu, Margaret; Sarr, Tim; Zhu, Lan; Guo, Hongbo; Li, Zhihua; Li, Wenyu; Hu, Weiwen; Jiang, Guoqiang; Paweletz, Cloud P.; Hendrickson, Ronald C.; Thompson, John R.; Mu, James; Berger, Joel P.; Mehmet, Huseyin

    2013-01-01

    FGF21 is a novel secreted protein with robust anti-diabetic, anti-obesity, and anti-atherogenic activities in preclinical species. In the current study, we investigated the signal transduction pathways downstream of FGF21 following acute administration of the growth factor to mice. Focusing on adipose tissues, we identified FGF21-mediated downstream signaling events and target engagement biomarkers. Specifically, RNA profiling of adipose tissues and phosphoproteomic profiling of adipocytes, following FGF21 treatment revealed several specific changes in gene expression and post-translational modifications, specifically phosphorylation, in several relevant proteins. Affymetrix microarray analysis of white adipose tissues isolated from both C57BL/6 (fed either regular chow or HFD) and db/db mice identified over 150 robust potential RNA transcripts and over 50 potential secreted proteins that were changed greater than 1.5 fold by FGF21 acutely. Phosphoprofiling analysis identified over 130 phosphoproteins that were modulated greater than 1.5 fold by FGF21 in 3T3-L1 adipocytes. Bioinformatic analysis of the combined gene and phosphoprotein profiling data identified a number of known metabolic pathways such as glucose uptake, insulin receptor signaling, Erk/Mapk signaling cascades, and lipid metabolism. Moreover, a number of novel events with hitherto unknown links to FGF21 signaling were observed at both the transcription and protein phosphorylation levels following treatment. We conclude that such a combined "omics" approach can be used not only to identify robust biomarkers for novel therapeutics but can also enhance our understanding of downstream signaling pathways; in the example presented here, novel FGF21-mediated signaling events in adipose tissue have been revealed that warrant further investigation. PMID:24039848

  4. Acute oral administration of a tyrosine and phenylalanine-free amino acid mixture reduces exercise capacity in the heat.

    PubMed

    Tumilty, Les; Davison, Glen; Beckmann, Manfred; Thatcher, Rhys

    2013-06-01

    Acute tyrosine administration is associated with increased exercise capacity in the heat. To explore whether reduced plasma tyrosine and phenylalanine (tyrosine precursor) is associated with impaired exercise capacity in the heat, eight healthy, moderately trained male volunteers, unacclimated to exercise in the heat, performed two tests in a crossover design separated by at least 7 days. In a randomised, double-blind fashion, subjects ingested 500 mL flavoured, sugar-free water containing amino acids [(TYR-free; isoleucine 15 g, leucine 22.5 g, valine 17.5 g, lysine 17.5 g, methionine 5 g, threonine 10 g, tryptophan 2.5 g)] to lower the ratio of plasma tyrosine plus phenylalanine:amino acids competing for blood-brain barrier uptake (CAA), a key determinant of brain uptake, or a balanced mixture (BAL; TYR-free plus 12.5 g tyrosine and 12.5 g phenylalanine). One hour later, subjects cycled to exhaustion at 63 ± 5 % [Formula: see text]O2peak in 30 °C and 60 % relative humidity. Pre-exercise ratio of plasma tyrosine plus phenylalanine:ΣCAA declined 75 ± 5 % from rest in TYR-free (P < 0.001), but was unchanged in BAL (P = 0.061). Exercise time was shorter in TYR-free (59.8 ± 19.0 min vs. 66.2 ± 16.9 min in TYR-free and BAL respectively; P = 0.036). Heart rate (P = 0.298), core (P = 0.134) and skin (P = 0.384) temperature, RPE (P > 0.05) and thermal sensation (P > 0.05) were similar at exhaustion in both trials. These data indicate that acutely depleting plasma catecholamine precursors:ΣCAA is associated with reduced submaximal exercise capacity in the heat.

  5. Behavioral deficits in rats following acute administration of glimepiride: Relationship with brain serotonin and dopamine.

    PubMed

    Sheikh, Shehnaz Abdul; Ikram, Huma; Haleem, Darakhshan Jabeen

    2015-07-01

    A considerable body of literature suggests that depression and diabetes mellitus are co-morbid. The present study was designed to test any possible behavioral deficits and/or neurochemical changes in the brain as induced by the anti-diabetic drugs. Twenty-four rats were divided into four groups: (i) saline (ii) glimepiride (2.5mg/kg)- (iii) glimepiride (5.0mg/kg)- and (iv) glimepiride (10 mg/kg) injected animals. Behavioral activities in Skinner's box, open field and elevated plus maze were monitored 20, 35 and 45 minutes post injection respectively. Animals were decapitated 60 minutes post injection to collect brain samples. Samples were kept at -70°C until neurochemical analysis by HPLC-EC. Results from the present study show decreased time spent in the open arm of the elevated plus maze (p<0.05) at all the three doses. A decrease in the HVA (Homovanillic acid) levels at all three doses (p<0.01) was also observed along with decreased 5-HT (5-Hydroxytryptamine) (p<0.05 at 5.0 and 10mg/kg) and 5-HIAA (5-Hydroxyindoleacetic acid) (p<0.05 at all three doses) levels. Since a decrease in 5-HT metabolism can induce depression-like effects, the present study therefore suggests that the occurrence of depression in diabetic patients is due to the use of glimipride. Effects of long-term administration of smaller doses of glimipride are to be explored further to monitor tolerance in glimipride-induced deficits of serotonin. The finding may help to explore the cause of depression in diabetics for improving pharmacotherapy in diabetes. PMID:26142509

  6. Acute effects of alcohol on inhibitory control and information processing in high and low sensation-seekers

    PubMed Central

    Fillmore, Mark T.; Ostling, Erik W.; Martin, Catherine A.; Kelly, Thomas H.

    2009-01-01

    Sensation-seeking is a personality characteristic that has been associated with drug abuse. Some evidence suggests that sensation-seekers might experience increased rewarding effects from drugs of abuse, possibly contributing to the association between sensation-seeking and risk for drug abuse. The present study examined the effects of three doses of alcohol (0.0 g/kg, 0.45 g/kg, and 0.65 g/kg) on inhibitory control, information processing, and subjective ratings in a group of high sensation-seekers and a group of low sensation-seekers (N = 20). Inhibitory control was measured by a cued go/no-go task and speed of information processing was assessed by the Rapid Information Processing (RIP) task. Alcohol impaired inhibitory control and information processing. Group differences were also observed. Compared with their low sensation-seeking counterparts, high sensation-seekers demonstrated increased sensitivity to the subjective rewarding effects of alcohol and a poorer degree of inhibitory control that was further impaired by alcohol. The findings highlight reward- and cognitive-based mechanisms by which sensation-seeking could operate to increase risk for alcohol abuse. PMID:19004578

  7. Failure of acute and chronic administration of delta 9-tetrahydrocannabinol to affect the repeated acquisition of serial position response in pigeons.

    PubMed

    McMillan, D E

    1988-01-01

    Pigeons were trained to acquire a new four-response position sequence each day by pecking three response keys in a predetermined order. The key color varied after each correct response prior to food delivery. Acute administration of delta 9-tetrahydrocannabinol (delta 9-THC) up to a dose that completely eliminated responding, had no effect on total acquisition errors, or on within session patterns of error elimination. Chronic administration of delta 9-THC (3-10 mg/kg/day), either before or after the session for 4-7 weeks, also did not affect these error measures, although rates of responding were markedly suppressed and at times no responding occurred. Discontinuation of delta 9-THC administration for periods of 4-6 weeks also was without effect on errors. These experiments suggest that neither acute nor chronic delta 9-THC produce specific effects on the repeated acquisition of serial position responses in pigeons.

  8. Acute porcine renal metabolic effect of endogastric soft drink administration assessed with hyperpolarized [1‐13c]pyruvate

    PubMed Central

    Hansen, Esben Søvsø Szocska; Kjærgaard, Uffe; Bertelsen, Lotte Bonde; Ringgaard, Steffen; Stødkilde‐Jørgensen, Hans

    2015-01-01

    Purpose Our aim was to determine the quantitative reproducibility of metabolic breakdown products in the kidney following intravenous injection of hyperpolarized [1‐13C]pyruvate and secondly to investigate the metabolic effect on the pyruvate metabolism of oral sucrose load using dissolution dynamic nuclear polarization. By this technique, metabolic alterations in several different metabolic related diseases and their metabolic treatment responses can be accessed. Methods In four healthy pigs the lactate‐to‐pyruvate, alanine‐to‐pyruvate and bicarbonate‐to‐pyruvate ratio was measured following administration of regular cola and consecutive injections of hyperpolarized [1‐13C]pyruvate four times within an hour. Results The overall lactate‐to‐pyruvate metabolic profile changed significantly over one hour following an acute sucrose load leading to a significant rise in blood glucose. Conclusion The reproducibility of hyperpolarized magnetic resonance spectroscopy in the healthy pig kidney demonstrated a repeatability of more than 94% for all metabolites and, furthermore, that the pyruvate to lactate conversion and the blood glucose level is elevated following endogastric sucrose administration. Magn Reson Med 74:558–563, 2015. © 2015 The Authors Magnetic Resonance in Medicine published by Wiley Periodicals, Inc. on behalf of International Society for Magnetic Resonance in Medicine. This is an open access article under the terms of the Creative Commons Attribution‐NonCommercial‐NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made. PMID:26014387

  9. Acute Coronary Syndromes, Gastrointestinal Protection, and Recommendations Regarding Concomitant Administration of Proton-Pump Inhibitors (Omeprazol/Esomeprazole) and Clopidogrel.

    PubMed

    Lozano, Iñigo; Sanchez-Insa, Esther; de Leiras, Sergio Rodríguez; Carrillo, Pilar; Ruiz-Quevedo, Valeriano; Pinar, Eduardo; Gopar-Gopar, Silvia; Bayon, Jeremías; Mañas, Pilar; Lasa, Garikoitz; CruzGonzalez, Ignacio; Hernandez, Felipe; Fernandez-Portales, Javier; Fernandez-Fernandez, Javier; Pérez-Serradilla, Ana; de la Torre Hernandez, José M; Gomez-Jaume, Alfredo

    2016-02-01

    The Food and Drug Administration and the European Medicines Agency sent a warning in 2010 discouraging the concomitant use of clopidogrel with omeprazole or esomeprazole. The purpose is to know the gastroprotective approach in patients with acute coronary syndrome (ACS) and the level of follow-up of the alert. In 17 hospitals with catheterization laboratory in Spain, 1 per region, we studied 25 consecutive patients per hospital whose diagnosis of discharge since October 1, 2013, had been any type of ACS. We analyzed their baseline clinical profile, the gatroprotective agents at admission and discharge and the antiplatelet therapy at discharge. The number of patients included was 425: age 67.2 ± 12.5 years, women 29.8%, diabetes 36.5%. The patients presented unstable angina in 21.6%, non-ST-elevation myocardial infarction in 35.3% and ST-elevation myocardial infarction in 43.1%. Conservative approach was chosen in 17.9%, bare-metal stents 32.2%, ≥ 1 drug-eluting stent 48.5%, and surgery 1.4%. Aspirin was indicated in 1.9%, aspirin + clopidogrel 73.6%, aspirin + prasugrel 17.6%, and aspririn + ticagrelor 6.8%. Gastroprotective agents were present in 40.2% patients at admission and this percentage increased to 93.7% at discharge. Of the 313 (73.6%) on clopidogrel in 96 (30.6%) was combined with omeprazole and 3 (0.95%) with esomeprazole, whereas the most commonly used was pantoprazole with 190 patients (44.7%). In conclusion, almost the totality of the patients with an ACS receive gastroprotective agents at the moment of discharge, most of them with proton-pump inhibitors. In one every 3 cases of the patients who are on clopidogrel, the recommendation of the Food and Drug Administration and the European Medicines Agency is not followed.

  10. The kappa opioid receptor antagonist JDTic attenuates alcohol seeking and withdrawal anxiety.

    PubMed

    Schank, Jesse R; Goldstein, Andrea L; Rowe, Kelly E; King, Courtney E; Marusich, Julie A; Wiley, Jenny L; Carroll, F Ivy; Thorsell, Annika; Heilig, Markus

    2012-05-01

    The role of kappa-opioid receptors (KOR) in the regulation of alcohol-related behaviors is not completely understood. For example, alcohol consumption has been reported to increase following treatment with KOR antagonists in rats, but was decreased in mice with genetic deletion of KOR. Recent studies have further suggested that KOR antagonists may selectively decrease alcohol self-administration in rats following a history of dependence. We assessed the effects of the KOR antagonist JDTic on alcohol self-administration, reinstatement of alcohol seeking induced by alcohol-associated cues or stress, and acute alcohol withdrawal-induced anxiety ('hangover anxiety'). JDTic dose-dependently reversed hangover anxiety when given 48 hours prior to testing, a time interval corresponding to the previously demonstrated anxiolytic efficacy of this drug. In contrast, JDTic decreased alcohol self-administration and cue-induced reinstatement of alcohol seeking when administered 2 hours prior to testing, but not at longer pre-treatment times. For comparison, we determined that the prototypical KOR antagonist nor-binaltorphimine can suppress self-administration of alcohol at 2 hours pre-treatment time, mimicking our observations with JDTic. The effects of JDTic were behaviorally specific, as it had no effect on stress-induced reinstatement of alcohol seeking, self-administration of sucrose, or locomotor activity. Further, we demonstrate that at a 2 hours pre-treatment time JDTic antagonized the antinociceptive effects of the KOR agonist U50,488H but had no effect on morphine-induced behaviors. Our results provide additional evidence for the involvement of KOR in regulation of alcohol-related behaviors and provide support for KOR antagonists, including JDTic, to be evaluated as medications for alcoholism.

  11. The effect of acute administration of Vitamin D on micro vascular endothelial function in Caucasians and South Asian Indians

    PubMed Central

    Petrofsky, Jerrold; Alshammari, Faris; Khowailed, Iman Akef; Rodrigues, Sophia; Potnis, Pooja; Akerkar, Siddhesh; Shah, Jinal; Chung, Guyeon; Save, Rakhi

    2013-01-01

    Background Vitamin D is a modulator of the immune system. There is some limited evidence that it also increases local blood flow in response to stress. Material/Methods In the present study, we examined 20 age matched subjects; 10 whom were from India and 10 Caucasians from the United States. Subjects were administered 4000 IU of Vitamin D3 for 3 weeks at breakfast. The function of the endothelial cells was evaluated in 2 ways; first, the response to 4 minutes of vascular occlusion was measured with a laser Doppler flow meter and second, the blood flow response to local heat at 42°C for 6 minutes. Results The results of the experiments showed that, as reported previously, the endothelial function in people from India was less than their Caucasian counterparts. The blood flow response to heat was reduced after 3 weeks administration of vitamin D in both groups and the response to vascular occlusion in the Caucasian group. But there was only a 20% reduction in the blood flow response to heat in the Caucasian group and a 50% reduction in the group from India. Conclusions Thus acute doses of vitamin D may increase vascular tone and reduce blood flow to tissue during stressors. Dosages administered for a longer duration may have beneficial effects on endothelial function but this was not examined here. PMID:23917403

  12. Selective alterations in cerebral metabolism within the mesocorticolimbic dopaminergic system produced by acute cocaine administration in rats.

    PubMed

    Porrino, L J; Domer, F R; Crane, A M; Sokoloff, L

    1988-05-01

    The 2-[14C]deoxyglucose method was used to examine the effects of acute intravenous administration of cocaine on local cerebral glucose utilization in rats. These effects were correlated with the effects of cocaine on locomotor activity assessed simultaneously in the same animals. At the lowest dose of cocaine, 0.5 mg/kg (1.47 mumol/kg), alterations in glucose utilization were restricted to the medial prefrontal cortex and nucleus accumbens. Metabolic activity at 1.0 mg/kg (2.9 mumol/kg) was altered in these structures, but in the substantia nigra reticulata and lateral habenula as well. The selectivity of cocaine's effects at low doses demonstrates the particular sensitivity of these structures to cocaine's actions in the brain. In contrast, 5.0 mg/kg (14.7 mumol/kg) produced widespread changes in glucose utilization, particularly in the extrapyramidal system. Only this dose significantly increased locomotor activity above levels in vehicle-treated controls. Rates of glucose utilization were positively correlated with locomotor activity in the globus pallidus, substantia nigra reticulata, and subthalamic nucleus, and negatively correlated in the lateral habenula.

  13. Selective alterations in cerebral metabolism within the mesocorticolimbic dopaminergic system produced by acute cocaine administration in rats

    SciTech Connect

    Porrino, L.J.; Domer, F.R.; Crane, A.M.; Sokoloff, L.

    1988-05-01

    The 2-(/sup 14/C)deoxyglucose method was used to examine the effects of acute intravenous administration of cocaine on local cerebral glucose utilization in rats. These effects were correlated with the effects of cocaine on locomotor activity assessed simultaneously in the same animals. At the lowest dose of cocaine, 0.5 mg/kg (1.47 mumol/kg), alterations in glucose utilization were restricted to the medial prefrontal cortex and nucleus accumbens. Metabolic activity at 1.0 mg/kg (2.9 mumol/kg) was altered in these structures, but in the substantia nigra reticulata and lateral habenula as well. The selectivity of cocaine's effects at low doses demonstrates the particular sensitivity of these structures to cocaine's actions in the brain. In contrast, 5.0 mg/kg (14.7 mumol/kg) produced widespread changes in glucose utilization, particularly in the extrapyramidal system. Only this dose significantly increased locomotor activity above levels in vehicle-treated controls. Rates of glucose utilization were positively correlated with locomotor activity in the globus pallidus, substantia nigra reticulata, and subthalamic nucleus, and negatively correlated in the lateral habenula.

  14. Neuropeptide Y administration acutely increases hypothalamic corticotropin-releasing factor immunoreactivity: lack of effect in other rat brain regions

    SciTech Connect

    Haas, D.A.; George, S.R.

    1987-12-21

    The effect of acute central administration of Neuropeptide Y (NPY) to adult male rats on the brain content of corticotropin-releasing factor immunoreactivity (CRF-ir) was investigated. The brain regions studied included frontal cortex, hippocampus, medulla-pons, midbrain-thalamus, cerebellum, neurointermediate lobe of pituitary, median eminence and the remaining hypothalamus. CRF-ir was determined in each of these regions using radioimmunoassay specific for rat CRF. CRF-ir was found to be significantly increased in the major site of CRF localization in the brain, the hypothalamus, in NPY-treated rats as compared to vehicle-treated controls either 15 minutes (p<0.025) or 45 minutes (p<0.005) post-injection. This increase was localized to the median eminence (p<0.05 after 15 minutes, p<0.01 after 45 minutes). No statistically significant differences were noted in any of the other brain regions assessed. Plasma adrenocorticotropin levels were also found to increase following NPY treatment, an effect which became significant after 45 minutes (p<0.05). These data show that NPY can alter the content of hypothalamic CRF and may play a role in its regulation. 33 references, 4 figures.

  15. Non-administration of thrombolytic agents in acute myocardial infarction patients in Hajar hospital, Shahrekord, Iran: prevalence rate and causes

    PubMed Central

    Samieinasab, Mohammadreza; Shirani, Shahin; Hashemi, Sayyed Mohammad; Pourmoghaddas, Ali; Hekmat, Mostafa

    2013-01-01

    BACKGROUND Cardiovascular diseases are the major causes of mortality worldwide and acute myocardial infarction (AMI) is the leading cause of mortality among cardiovascular diseases. Thrombolytic therapies, especially during the first few hours after the disease onset, can significantly reduce AMI-related mortality. METHODS The current study aimed to determine the prevalence and causes of non-administration of thrombolytic therapy for AMI patients admitted to Hajar Hospital, Shahrekord, Iran, from May until November 2000. Non-probability convenient sampling method was used to select 106 subjects with Q-wave AMI. Data was collected by completing a questionnaire, reviewing medical records, and interviewing with patients. SPSS7.5 was for data analysis. RESULTS A total number of 106 AMI patients were studied among whom 62 (59%) individuals received thrombolytic therapy. Delayed referral to the hospital was the major cause of failure to provide thrombolytic therapy. The cause of non-treatment could not be identified in 15 (19.5%) subjects eligible to receive therapy. CONCLUSION Training general practitioners and individuals involved in this regard along with accelerating the process of patient referral to hospitals can reduce AMI-related mortality. PMID:23696767

  16. Anxiolytic-like effects of antidepressants after acute administration in a four-plate test in mice.

    PubMed

    Hascoët, M; Bourin, M; Colombel, M C; Fiocco, A J; Baker, G B

    2000-02-01

    The four-plate test (FPT) is an animal model of anxiety based on stress caused by unconditioned fear. An increase of spontaneous punished behavior was used as a measure to determine the anxiolytic effects of various antidepressants (ADs). In the present study. ADs with different mechanisms of action, including tricyclics, selective serotonin reuptake inhibitors (SSRIs), a monoamine oxidase inhibitor (MAOI), and atypicals, were studied in the FPT to evaluate their anxiolytic-like effects following acute administration. The number of punished crossings was dramatically increased by the SSRIs citalopram, fluvoxamine, and paroxetine, but not fluoxetine. The mixed 5-HT/NE reuptake inhibitors, milnacipran and venlafaxine, also demonstrated strong antipunishment effects. The specific NE reuptake inhibitors, desipramine and maprotiline, and the atypical AD trazodone, enhanced freezing behavior, suggesting anxiogenic-like behavior. It was concluded that, in the FPT, a model based on spontaneous response, where animals are exposed to an aversive environment from which they can only escape by being motionless, this kind of behavior might be related to anticipatory anxiety. In this situation, ADs acting preferentially on 5-HT transmission possessed clear anxiolytic like effects. The balance between the two transmitters, 5-HT and NE, seemed to be a crucial factor.

  17. MRI measurement of angiogenesis and the therapeutic effect of acute marrow stromal cell administration on traumatic brain injury.

    PubMed

    Li, Lian; Chopp, Michael; Ding, Guang Liang; Qu, Chang Sheng; Li, Qing Jiang; Lu, Mei; Wang, Shiyang; Nejad-Davarani, Siamak P; Mahmood, Asim; Jiang, Quan

    2012-11-01

    Using magnetic resonance imaging (MRI), the present study was undertaken to investigate the therapeutic effect of acute administration of human bone marrow stromal cells (hMSCs) on traumatic brain injury (TBI) and to measure the temporal profile of angiogenesis after the injury with or without cell intervention. Male Wistar rats (300 to 350 g, n=18) subjected to controlled cortical impact TBI were intravenously injected with 1 mL of saline (n=9) or hMSCs in suspension (n=9, 3 × 10(6) hMSCs) 6 hours after TBI. In-vivo MRI acquisitions of T2-weighted imaging, cerebral blood flow (CBF), three-dimensional (3D) gradient echo imaging, and blood-to-brain transfer constant (Ki) of contrast agent were performed on all animals 2 days after injury and weekly for 6 weeks. Sensorimotor function and spatial learning were evaluated. Volumetric changes in the trauma-induced brain lesion and the lateral ventricles were tracked and quantified using T2 maps, and hemodynamic alteration and blood-brain barrier permeability were monitored by CBF and Ki, respectively. Our data show that transplantation of hMSCs 6 hours after TBI leads to reduced cerebral atrophy, early and enhanced cerebral tissue perfusion and improved functional outcome compared with controls. The hMSC treatment increases angiogenesis in the injured brain, which may promote neurologic recovery after TBI.

  18. Neuroimmunomodulatory effects of transcranial laser therapy combined with intravenous tPA administration for acute cerebral ischemic injury

    PubMed Central

    Peplow, Philip V.

    2015-01-01

    At present, the only FDA approved treatment for ischemic strokes is intravenous administration of tissue plasminogen activator within 4.5 hours of stroke onset. Owing to this brief window only a small percentage of patients receive tissue plasminogen activator. Transcranial laser therapy has been shown to be effective in animal models of acute ischemic stroke, resulting in significant improvement in neurological score and function. NEST-1 and NEST-2 clinical trials in human patients have demonstrated the safety and positive trends in efficacy of transcranial laser therapy for the treatment of ischemic stroke when initiated close to the time of stroke onset. Combining intravenous tissue plasminogen activator treatment with transcranial laser therapy may provide better functional outcomes. Statins given within 4 weeks of stroke onset improve stroke outcomes at 90 days compared to patients not given statins, and giving statins following transcranial laser therapy may provide an effective treatment for patients not able to be given tissue plasminogen activator due to time constraints. PMID:26487831

  19. Disseminated intravascular coagulation associated with acute hemoglobinemia or hemoglobinuria following Rh(0)(D) immune globulin intravenous administration for immune thrombocytopenic purpura.

    PubMed

    Gaines, Ann Reed

    2005-09-01

    The Food and Drug Administration (FDA) licensed Rh(o)(D) immune globulin intravenous (anti-D IGIV) on March 24, 1995, for treatment of immune thrombocytopenic purpura (ITP). A previous review described data on 15 patients who experienced acute hemoglobinemia or hemoglobinuria following anti-D IGIV administration for ITP or secondary thrombocytopenia. Eleven of those patients also experienced clinically compromising anemia, transfusion with packed red blood cells, renal insufficiency, dialysis, or death. That review suggested that patients receiving anti-D IGIV be monitored for those and other potential complications of hemoglobinemia, particularly disseminated intravascular coagulation (DIC). Through November 30, 2004, the FDA received 6 reports of DIC associated with "acute hemolysis" (or similar terms), 5 of which involved fatalities. The attending or consulting physicians assessed that acute hemolysis or DIC caused or contributed to each death. This review presents the first case series of DIC associated with acute hemoglobinemia or hemoglobinuria following anti-D IGIV administration for ITP. The purpose of this review is to increase awareness among physicians and other health care professionals that DIC may be a rare but potentially severe complication of anti-D IGIV treatment. Increased awareness of DIC as a diagnostic possibility may enable prompt recognition and medical intervention in affected patients.

  20. The effect of prior alcohol consumption on the ataxic response to alcohol in high-alcohol preferring mice.

    PubMed

    Fritz, Brandon M; Boehm, Stephen L

    2014-12-01

    We have previously shown that ethanol-naïve high-alcohol preferring (HAP) mice, genetically predisposed to consume large quantities of alcohol, exhibited heightened sensitivity and more rapid acute functional tolerance (AFT) to alcohol-induced ataxia compared to low-alcohol preferring mice. The goal of the present study was to evaluate the effect of prior alcohol self-administration on these responses in HAP mice. Naïve male and female adult HAP mice from the second replicate of selection (HAP2) underwent 18 days of 24-h, 2-bottle choice drinking for 10% ethanol vs. water, or water only. After 18 days of fluid access, mice were tested for ataxic sensitivity and rapid AFT following a 1.75 g/kg injection of ethanol on a static dowel apparatus in Experiment 1. In Experiment 2, a separate group of mice was tested for more protracted AFT development using a dual-injection approach where a second, larger (2.0 g/kg) injection of ethanol was given following the initial recovery of performance on the task. HAP2 mice that had prior access to alcohol exhibited a blunted ataxic response to the acute alcohol challenge, but this pre-exposure did not alter rapid within-session AFT capacity in Experiment 1 or more protracted AFT capacity in Experiment 2. These findings suggest that the typically observed increase in alcohol consumption in these mice may be influenced by ataxic functional tolerance development, but is not mediated by a greater capacity for ethanol exposure to positively influence within-session ataxic tolerance.

  1. The effect of prior alcohol consumption on the ataxic response to alcohol in high-alcohol preferring mice

    PubMed Central

    Fritz, Brandon M.; Boehm, Stephen L.

    2014-01-01

    We have previously shown that ethanol-naïve high-alcohol preferring (HAP) mice, genetically predis-posed to consume large quantities of alcohol, exhibited heightened sensitivity and more rapid acute functional tolerance (AFT) to alcohol-induced ataxia compared to low-alcohol preferring mice. The goal of the present study was to evaluate the effect of prior alcohol self-administration on these responses in HAP mice. Naïve male and female adult HAP mice from the second replicate of selection (HAP2) underwent 18 days of 24-h, 2-bottle choice drinking for 10% ethanol vs. water, or water only. After 18 days of fluid access, mice were tested for ataxic sensitivity and rapid AFT following a 1.75 g/kg injection of ethanol on a static dowel apparatus in Experiment 1. In Experiment 2, a separate group of mice was tested for more protracted AFT development using a dual-injection approach where a second, larger (2.0 g/kg) injection of ethanol was given following the initial recovery of performance on the task. HAP2 mice that had prior access to alcohol exhibited a blunted ataxic response to the acute alcohol challenge, but this pre-exposure did not alter rapid within-session AFT capacity in Experiment 1 or more protracted AFT capacity in Experiment 2. These findings suggest that the typically observed increase in alcohol consumption in these mice may be influenced by ataxic functional tolerance development, but is not mediated by a greater capacity for ethanol exposure to positively influence within-session ataxic tolerance. PMID:25454537

  2. 78 FR 37794 - Polyvinyl Alcohol from Taiwan: Final Results of Antidumping Duty Administrative Review; 2010-2012

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-06-24

    ... commercial levels of defoamer or boric acid. PVA in fiber form and PVB-grade low-ash PVA are not included in... Administrative Review, 78 FR 20890 (April 8, 2013) (Preliminary Results) and the accompanying Preliminary... Dumping Margin and Assessment Rate in Certain Antidumping Duty Proceedings; Final Modification, 77 FR...

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

    PubMed

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

    2016-09-15

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

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

    PubMed

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

    2016-09-15

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

  5. Adolescent alcohol exposure reduces behavioral flexibility, promotes disinhibition, and increases resistance to extinction of ethanol self-administration in adulthood.

    PubMed

    Gass, Justin T; Glen, William Bailey; McGonigal, Justin T; Trantham-Davidson, Heather; Lopez, Marcelo F; Randall, Patrick K; Yaxley, Richard; Floresco, Stan B; Chandler, L Judson

    2014-10-01

    The prefrontal cortex (PFC) is a brain region that is critically involved in cognitive function and inhibitory control of behavior, and adolescence represents an important period of continued PFC development that parallels the maturation of these functions. Evidence suggests that this period of continued development of the PFC may render it especially vulnerable to environmental insults that impact PFC function in adulthood. Experimentation with alcohol typically begins during adolescence when binge-like consumption of large quantities is common. In the present study, we investigated the effects of repeated cycles of adolescent intermittent ethanol (AIE) exposure (postnatal days 28-42) by vapor inhalation on different aspects of executive functioning in the adult rat. In an operant set-shifting task, AIE-exposed rats exhibited deficits in their ability to shift their response strategy when the rules of the task changed, indicating reduced behavioral flexibility. There were no differences in progressive ratio response for the reinforcer suggesting that AIE did not alter reinforcer motivation. Examination of performance on the elevated plus maze under conditions designed to minimize stress revealed that AIE exposure enhanced the number of entries into the open arms, which may reflect either reduced anxiety and/or disinhibition of exploratory-like behavior. In rats that trained to self-administer ethanol in an operant paradigm, AIE increased resistance to extinction of ethanol-seeking behavior. This resistance to extinction was reversed by positive allosteric modulation of mGluR5 during extinction training, an effect that is thought to reflect promotion of extinction learning mechanisms within the medial PFC. Consistent with this, CDPPB was also observed to reverse the deficits in behavioral flexibility. Finally, diffusion tensor imaging with multivariate analysis of 32 brain areas revealed that while there were no differences in the total brain volume, the volume of

  6. Perception Versus Actual Performance in Timely Tissue Plasminogen Activation Administration in the Management of Acute Ischemic Stroke

    PubMed Central

    Lin, Cheryl B; Cox, Margueritte; Olson, DaiWai M; Britz, Gavin W; Constable, Mark; Fonarow, Gregg C; Schwamm, Lee; Peterson, Eric D; Shah, Bimal R

    2015-01-01

    Background Timely thrombolytic therapy can improve stroke outcomes. Nevertheless, the ability of US hospitals to meet guidelines for intravenous tissue plasminogen activator (tPA) remains suboptimal. What is unclear is whether hospitals accurately perceive their rate of tPA “door-to-needle” (DTN) time within 60 minutes and how DTN rates compare across different hospitals. Methods and Results DTN performance was defined by the percentage of treated patients who received tPA within 60 minutes of arrival. Telephone surveys were obtained from staff at 141 Get With The Guidelines hospitals, representing top, middle, and lowDTN performance. Less than one-third (29.1%) of staff accurately identified their DTN performance. Among middle- and low-performing hospitals (n=92), 56 sites (60.9%) overestimated their performance; 42% of middle performers and 85% of low performers overestimated their performance. Sites that overestimated tended to have lower annual volumes of tPA administration (median 8.4 patients [25th to 75th percentile 5.9 to 11.8] versus 10.2 patients [25th to 75th percentile 8.2 to 17.3], P=0.047), smaller percentages of eligible patients receiving tPA (84.7% versus 89.8%, P=0.008), and smaller percentages of DTN ≤60 minutes among treated patients (10.6% versus 16.6%, P=0.002). Conclusions Hospitals often overestimate their ability to deliver timely tPA to treated patients. Our findings indicate the need to routinely provide comparative provider performance rates as a key step to improving the quality of acute stroke care. PMID:26201547

  7. Improving Effect of the Acute Administration of Dietary Fiber-Enriched Cereals on Blood Glucose Levels and Gut Hormone Secretion

    PubMed Central

    2016-01-01

    Dietary fiber improves hyperglycemia in patients with type 2 diabetes through its physicochemical properties and possible modulation of gut hormone secretion, such as glucagon-like peptide 1 (GLP-1). We assessed the effect of dietary fiber-enriched cereal flakes (DC) on postprandial hyperglycemia and gut hormone secretion in patients with type 2 diabetes. Thirteen participants ate isocaloric meals based on either DC or conventional cereal flakes (CC) in a crossover design. DC or CC was provided for dinner, night snack on day 1 and breakfast on day 2, followed by a high-fat lunch. On day 2, the levels of plasma glucose, GLP-1, glucose-dependent insulinotropic polypeptide (GIP), and insulin were measured. Compared to CC, DC intake exhibited a lower post-breakfast 2-hours glucose level (198.5±12.8 vs. 245.9±15.2 mg/dL, P<0.05) and a lower incremental peak of glucose from baseline (101.8±9.1 vs. 140.3±14.3 mg/dL, P<0.001). The incremental area under the curve (iAUC) of glucose after breakfast was lower with DC than with CC (P<0.001). However, there were no differences in the plasma insulin, glucagon, GLP-1, and GIP levels. In conclusion, acute administration of DC attenuates postprandial hyperglycemia without any significant change in the representative glucose-regulating hormones in patients with type 2 diabetes (ClinicalTrials.gov. NCT 01997281). PMID:26839476

  8. Salutary effect of adjunctive intracoronary nicorandil administration on restoration of myocardial blood flow and functional improvement in patients with acute myocardial infarction.

    PubMed

    Sakata, Y; Kodama, K; Komamura, K; Lim, Y J; Ishikura, F; Hirayama, A; Kitakaze, M; Masuyama, T; Hori, M

    1997-06-01

    Salutary effect of nicorandil, a K+ adenosine triphosphate channel opener, on restoration of myocardial blood flow and functional improvement after coronary revascularization was investigated in 20 patients with first anterior acute myocardial infarction. Ten patients received intracoronary administration of nicorandil (2 mg) after coronary revascularization; the other 10 patients received coronary revascularization only and served as control subjects. Myocardial contra