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Sample records for acute alcohol withdrawal

  1. 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.

  2. 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

  3. Alcohol withdrawal

    MedlinePlus

    ... Seeing or feeling things that aren't there (hallucinations) Seizures Severe confusion ... alcohol withdrawal. You will be watched closely for hallucinations and other signs of delirium tremens. Treatment may ...

  4. 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

  5. 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

  6. Inpatient alcohol withdrawal syndrome.

    PubMed

    Monte-Secades, R; Rabuñal-Rey, R; Guerrero-Sande, H

    2015-03-01

    A 55-year-old man was admitted for a femur fracture; an alcohol fetor was noted on admission. The following day, the patient began to experience tremors and nervousness. Intravenous haloperidol was administered. Shortly afterwards, the patient experienced two generalized seizures and then began to experience delirium and uncontrollable agitation. The patient was diagnosed with alcohol withdrawal syndrome; high doses of intravenous midazolam were prescribed and infused. A few hours later, the patient presented signs of respiratory depression, requiring a transfer to the intensive care unit. After a review of the medical history, it was determined that the patient had been admitted on 3 previous occasions due to alcohol withdrawal and had progressed to delirium tremens after experiencing seizures. Can the risk of alcohol withdrawal syndrome and the need for prophylactic treatment be assessed on admission? Were appropriate monitoring and treatment measures employed? Would it have been possible to change his outcome? PMID:25559647

  7. [Ambulatory alcohol withdrawal].

    PubMed

    Grehl, Oliver

    2014-10-01

    Alcohol addiction is a common problem in daily life as well as in medicine. Apart from inpatient therapy programs, ambulatory withdrawal is a relatively new option, which may be done safely, efficient and cost-effective close to the domicile an without stigmatisation of the patient.

  8. Alcohol Withdrawal and Cerebellar Mitochondria.

    PubMed

    Jung, Marianna E

    2015-08-01

    Cerebellar disorders trigger the symptoms of movement problems, imbalance, incoordination, and frequent fall. Cerebellar disorders are shown in various CNS illnesses including a drinking disorder called alcoholism. Alcoholism is manifested as an inability to control drinking in spite of adverse consequences. Human and animal studies have shown that cerebellar symptoms persist even after complete abstinence from drinking. In particular, the abrupt termination (ethanol withdrawal) of long-term excessive ethanol consumption has shown to provoke a variety of neuronal and mitochondrial damage to the cerebellum. Upon ethanol withdrawal, excitatory neurotransmitter molecules such as glutamate are overly released in brain areas including cerebellum. This is particularly relevant to the cerebellar neuronal network as glutamate signals are projected to Purkinje neurons through granular cells that are the most populated neuronal type in CNS. This excitatory neuronal signal may be elevated by ethanol withdrawal stress, which promotes an increase in intracellular Ca(2+) level and a decrease in a Ca(2+)-binding protein, both of which result in the excessive entry of Ca(2+) to the mitochondria. Subsequently, mitochondria undergo a prolonged opening of mitochondrial permeability transition pore and the overproduction of harmful free radicals, impeding adenosine triphosphate (ATP)-generating function. This in turn provokes the leakage of mitochondrial molecule cytochrome c to the cytosol, which triggers a cascade of adverse cytosol reactions. Upstream to this pathway, cerebellum under the condition of ethanol withdrawal has shown aberrant gene modifications through altered DNA methylation, histone acetylation, or microRNA expression. Interplay between these events and molecules may result in functional damage to cerebellar mitochondria and consequent neuronal degeneration, thereby contributing to motoric deficit. Mitochondria-targeting research may help develop a powerful new

  9. Alcohol Withdrawal and Cerebellar Mitochondria.

    PubMed

    Jung, Marianna E

    2015-08-01

    Cerebellar disorders trigger the symptoms of movement problems, imbalance, incoordination, and frequent fall. Cerebellar disorders are shown in various CNS illnesses including a drinking disorder called alcoholism. Alcoholism is manifested as an inability to control drinking in spite of adverse consequences. Human and animal studies have shown that cerebellar symptoms persist even after complete abstinence from drinking. In particular, the abrupt termination (ethanol withdrawal) of long-term excessive ethanol consumption has shown to provoke a variety of neuronal and mitochondrial damage to the cerebellum. Upon ethanol withdrawal, excitatory neurotransmitter molecules such as glutamate are overly released in brain areas including cerebellum. This is particularly relevant to the cerebellar neuronal network as glutamate signals are projected to Purkinje neurons through granular cells that are the most populated neuronal type in CNS. This excitatory neuronal signal may be elevated by ethanol withdrawal stress, which promotes an increase in intracellular Ca(2+) level and a decrease in a Ca(2+)-binding protein, both of which result in the excessive entry of Ca(2+) to the mitochondria. Subsequently, mitochondria undergo a prolonged opening of mitochondrial permeability transition pore and the overproduction of harmful free radicals, impeding adenosine triphosphate (ATP)-generating function. This in turn provokes the leakage of mitochondrial molecule cytochrome c to the cytosol, which triggers a cascade of adverse cytosol reactions. Upstream to this pathway, cerebellum under the condition of ethanol withdrawal has shown aberrant gene modifications through altered DNA methylation, histone acetylation, or microRNA expression. Interplay between these events and molecules may result in functional damage to cerebellar mitochondria and consequent neuronal degeneration, thereby contributing to motoric deficit. Mitochondria-targeting research may help develop a powerful new

  10. Acute Ethanol Withdrawal Impairs Contextual Learning and Enhances Cued Learning

    PubMed Central

    Tipps, Megan E.; Raybuck, Jonathan D.; Buck, Kari J.; Lattal, K. Matthew

    2014-01-01

    Background Alcohol affects many of the brain regions and neural processes that support learning and memory, and these effects are thought to underlie, at least in part, the development of addiction. Although much work has been done regarding the effects of alcohol intoxication on learning and memory, little is known about the effects of acute withdrawal from a single alcohol exposure. Methods We assess the effects of acute ethanol withdrawal (6 h post-injection with 4 g/kg ethanol) on two forms of fear conditioning (delay and trace fear conditioning) in C57BL/6J and DBA/2J mice. The influence of a number of experimental parameters (pre- and post-training withdrawal exposure; foreground/background processing; training strength; non-associative effects) is also investigated. Results Acute ethanol withdrawal during training had a bidirectional effect on fear conditioned responses, decreasing contextual responses and increasing cued responses. These effects were apparent for both trace and delay conditioning in DBA/2J mice and for trace conditioning in C57BL/6J mice; however, C57BL/6J mice were selectively resistant to the effects of acute withdrawal on delay cued responses. Conclusions Our results show that acute withdrawal from a single, initial ethanol exposure is sufficient to alter long-term learning in mice. In addition, the differences between the strains and conditioning paradigms used suggest that specific learning processes can be differentially affected by acute withdrawal in a manner that is distinct from the reported effects of both alcohol intoxication and withdrawal following chronic alcohol exposure. Thus, our results suggest a unique effect of acute alcohol withdrawal on learning and memory processes. PMID:25684050

  11. Nicotinic Mechanisms Modulate Ethanol Withdrawal and Modify Time Course and Symptoms Severity of Simultaneous Withdrawal from Alcohol and Nicotine.

    PubMed

    Perez, Erika; Quijano-Cardé, Natalia; De Biasi, Mariella

    2015-09-01

    Alcohol and nicotine are among the top causes of preventable death in the United States. Unfortunately, people who are dependent on alcohol are more likely to smoke than individuals in the general population. Similarly, smokers are more likely to abuse alcohol. Alcohol and nicotine codependence affects health in many ways and leads to poorer treatment outcomes in subjects who want to quit. This study examined the interaction of alcohol and nicotine during withdrawal and compared abstinence symptoms during withdrawal from one of the two drugs only vs both. Our results indicate that simultaneous withdrawal from alcohol and nicotine produces physical symptoms that are more severe and last longer than those experienced during withdrawal from one of the two drugs alone. In animals experiencing withdrawal after chronic ethanol treatment, acute nicotine exposure was sufficient to prevent abstinence symptoms. Similarly, symptoms were prevented when alcohol was injected acutely in mice undergoing nicotine withdrawal. These experiments provide evidence for the involvement of the nicotinic cholinergic system in alcohol withdrawal. Furthermore, the outcomes of intracranial microinfusions of mecamylamine, a nonselective nicotinic receptor antagonist, highlight a major role for the nicotinic receptors expressed in medial habenula and interpeduncular nucleus during withdrawal. Overall, the data support the notion that modulating the nicotinic cholinergic system might help to maintain long-term abstinence from alcohol.

  12. Alcohol Withdrawal Syndrome: Benzodiazepines and Beyond

    PubMed Central

    Sachdeva, Ankur; Chandra, Mina

    2015-01-01

    Alcohol dependence is an increasing and pervasive problem. Alcohol withdrawal symptoms are a part of alcohol dependence syndrome and are commonly encountered in general hospital settings, in most of the departments. Alcohol withdrawal syndrome ranges from mild to severe. The severe complicated alcohol withdrawal may present with hallucinations, seizures or delirium tremens. Benzodiazepines have the largest and the best evidence base in the treatment of alcohol withdrawal, and are considered the gold standard. Others, such as anticonvulsants, barbiturates, adrenergic drugs, and GABA agonists have been tried and have evidence. Supportive care and use of vitamins is essential in the management. Symptom triggered regime is favoured over fixed tapering dose regime, although monitoring through scales is cumbersome. This article aims to review the evidence base for appropriate clinical management of the alcohol withdrawal syndrome. We searched Pubmed for articles published in English on ‘Alcohol withdrawal syndrome’ in humans during the last 10 years. A total of 1182 articles came up. Articles not relevant to clinical utility and management were excluded based on the titles and abstract available. Full text articles, meta-analyses, systematic reviews and randomized controlled trials were obtained from this list and were considered for review. PMID:26500991

  13. IDENTIFICATION AND MANAGEMENT OF ALCOHOL WITHDRAWAL SYNDROME

    PubMed Central

    Mirijello, Antonio; D’Angelo, Cristina; Ferrulli, Anna; Vassallo, Gabriele; Antonelli, Mariangela; Caputo, Fabio; Leggio, Lorenzo; Gasbarrini, Antonio; Addolorato, Giovanni

    2016-01-01

    Symptoms of alcohol withdrawal syndrome may develop within 6–24 hours after the abrupt discontinuation or decrease of alcohol consumption. Symptoms can vary from autonomic hyperactivity and agitation to delirium tremens. The gold-standard treatment for alcohol withdrawal syndrome is represented by benzodiazepines. Among them, different agents (i.e., long-acting or short-acting) and different regimens (front-loading, fixed dose or symptom-triggered) may be chosen on the basis of patient characteristics. Severe withdrawal could require ICU admission and the use of barbiturates or propofol. Other drugs, such as alpha2-agonists (clonidine and dexmetedomidine) and beta-blockers can be used as adjunctive treatments to control neuroautonomic hyperactivity. Furthermore, neuroleptics can help control hallucinations. Finally, other medications for the treatment for alcohol withdrawal syndrome have been investigated with promising results. These include carbamazepine, valproate, sodium oxybate, baclofen, gabapentin, and topiramate. The usefulness of these agents will be discussed in the text. PMID:25666543

  14. Increased pain sensitivity in alcohol withdrawal syndrome.

    PubMed

    Jochum, Thomas; Boettger, Michael K; Burkhardt, Christin; Juckel, Georg; Bär, Karl-Jürgen

    2010-08-01

    Withdrawal from analgesic and addictive substances such as opioids or ethanol is associated with increased sensitivity to sensory stimulation in animal models. Here, we investigated perception of innocuous and noxious thermal or electric stimuli applied to the left hand or sternum in 30 male patients undergoing withdrawal from alcohol, 30 male abstained alcoholics and matched controls. The alcohol withdrawal scale and the Banger score were obtained to estimate the severity of withdrawal. In addition, the Beck depression inventory was used to estimate the influence of depressive symptoms on pain perception. The data presented provide substantial evidence that subjects undergoing alcohol withdrawal show increased heat pain sensitivity. Interestingly, this effect was observed both on the left hand and sternum. Pain thresholds and tolerances of electric stimuli did not differ between groups. However, in a subgroup analysis, a higher sensitivity for electrical pain thresholds and tolerances was observed in those patients that were identified to require pharmacological treatment for withdrawal according to disease severity. Furthermore, the perceived painful thermal and electrical sensation was substantially influenced by the affective state of patients. No differences were found between patients of the abstained group and control subjects for any pain parameter. In conclusion, we demonstrate withdrawal-induced hyperalgesia upon thermal stimulation in patients. Since the influence of affective symptoms on pain perception during withdrawal is remarkable, we assume that peripheral and central mechanisms might account for this finding, which should be assessed in detail in future studies.

  15. 27 CFR 19.729 - Withdrawal of fuel alcohol.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 1 2011-04-01 2011-04-01 false Withdrawal of fuel alcohol. 19.729 Section 19.729 Alcohol, Tobacco Products and Firearms ALCOHOL AND TOBACCO TAX AND TRADE BUREAU..., Withdrawal, and Transfer of Spirits § 19.729 Withdrawal of fuel alcohol. (a) For each shipment or...

  16. 27 CFR 19.729 - Withdrawal of fuel alcohol.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 1 2012-04-01 2012-04-01 false Withdrawal of fuel alcohol. 19.729 Section 19.729 Alcohol, Tobacco Products and Firearms ALCOHOL AND TOBACCO TAX AND TRADE BUREAU..., Withdrawal, and Transfer of Spirits § 19.729 Withdrawal of fuel alcohol. (a) For each shipment or...

  17. 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.

  18. Acute withdrawal: diagnosis and treatment.

    PubMed

    Brust, John C M

    2014-01-01

    Symptoms of alcohol withdrawal range in severity from mild "hangover" to fatal delirium tremens (DTs). Tremor, hallucinosis, and seizures usually occur within 48 hours of abstinence. Seizures tend to be generalized without focality, occurring singly or in a brief cluster, but status epilepticus is not unusual. DTs usually appears after 48 hours of abstinence and consists of marked inattentiveness, agitation, hallucinations, fluctuating level of alertness, marked tremulousness, and sympathetic overactivity. The mainstay of treatment for alcohol withdrawal is benzodiazepine pharmacotherapy, which can be used to control mild early symptoms, to prevent progression to DTs, or to treat DTs itself. Alternative less evidence-based pharmacotherapies include phenobarbital, anticonvulsants, baclofen, gamma-hydroxybutyric acid, beta-blockers, alpha-2-agonists, and N-methyl-d-aspartate receptor blockers. Treatment of DTs is a medical emergency requiring heavy sedation in an intensive care unit, with close attention to autonomic instability, fever, fluid loss, and electrolyte imbalance. Frequent comorbid disorders include hypoglycemia, liver failure, pancreatitis, sepsis, meningitis, intracranial hemorrhage, and Wernicke-Korsakoff syndrome.

  19. Electrical amygdala kindling in alcohol-withdrawal kindled rats.

    PubMed

    Ulrichsen, J; Woldbye, D P; Madsen, T M; Clemmesen, L; Haugbøl, S; Olsen, C H; Laursen, H; Bolwig, T G; Hemmingsen, R

    1998-01-01

    Repeated alcohol withdrawal has been shown to kindle seizure activity. The purpose of the present investigation was to study electrical amygdala kindling in rats previously exposed to alcohol-withdrawal kindling. In three independent experiments, male Wistar rats were subjected to multiple episodes each consisting of 2 days of severe alcohol intoxication and 5 days of alcohol withdrawal. In the first experiment, the alcohol-withdrawal kindled animals were divided into two groups depending on whether spontaneous alcohol-withdrawal seizures were observed in episodes 10-13. In the second and third experiments, the alcohol-withdrawal kindled animals were compared to a group in which alcohol-withdrawal kindling was prevented by diazepam treatment during the withdrawal reactions in order to discriminate between the effect of withdrawal and intoxication. Electrical kindling was initiated 28-35 days after the last alcohol dose by exposing the animals to daily electrical stimulations of the right amygdala. The results showed that amygdala kindling was facilitated in alcohol-withdrawal kindled animals which showed spontaneous withdrawal seizure activity, compared with animals exposed to multiple episodes of alcohol withdrawal which did not develop withdrawal seizures or with animals exposed to a single episode of alcohol intoxication. When compared to the control group, the alcohol-withdrawal kindled group with seizures also kindled at a faster rate, but the difference did not reach statistical significance and therefore the results must be regarded as preliminary at present.

  20. Consequences of multiple withdrawals from alcohol.

    PubMed

    Duka, Theodora; Gentry, John; Malcolm, Robert; Ripley, Tamzin L; Borlikova, Gilyanna; Stephens, Dai N; Veatch, Lynn M; Becker, Howard C; Crews, Fulton T

    2004-02-01

    This article represents the proceedings of a symposium at the 2003 annual meeting of the Research Society on Alcoholism in Fort Lauderdale, FL, organized by Theodora Duka and chaired by Dai Stephens. The purpose of the symposium was to examine the effects of multiple experiences of withdrawal from alcohol in animals made dependent on alcohol and in humans who are alcohol dependent. Parallels were drawn to the effects of repeated short-lived high-content alcohol exposures in animals and in humans who are social drinkers but indulge in binge drinking. The presentations were (1) Multiple detoxifications and risk of relapse in abstinent alcoholics, by John Gentry and Robert Malcolm; (2) Emotional and cognitive impairments after long-term use of alcohol: relationship to multiple detoxifications and binge drinking, by Theodora Duka; (3) The effect of repeated withdrawal from ethanol on conditioning to appetitive stimuli, by Tamzin Ripley, Gilyanna Borlikova, and Dai Stephens; (4) Alcohol withdrawal kindling: electrographic measures in a murine model of behavioral seizure sensitization, by Lynn Veatch and Howard Becker; and (5) Binge drinking induced changes in CNS, by Fulton Crews. PMID:15112931

  1. A 'symptom-triggered' approach to alcohol withdrawal management.

    PubMed

    Murdoch, Jay; Marsden, Janet

    In acute hospital settings, alcohol withdrawal often causes significant management problems and complicates a wide variety of concurrent conditions, placing a huge burden on the NHS. A significant number of critical incidents around patients who were undergoing detoxification in a general hospital setting led to the need for a project to implement and evaluate an evidence-based approach to the management of alcohol detoxification-a project that included a pre-intervention case note audit, the implementation of an evidence-based symptom-triggered detoxification protocol, and a post-intervention case note audit. This change in practice resulted in an average reduction of almost 60% in length of hospital stay and a 66% reduction in the amount of chlordiazepoxide used in detoxification, as well as highlighting that 10% of the sample group did not display any signs of withdrawal and did not require any medication. Even with these reductions, no patient post-intervention developed any severe signs of withdrawal phenomena, such as seizures or delirium tremens. The savings to the trust (The Pennine Acute Hospital Trust) are obvious,but the development of a consistent, quality service will lead to fewer long-term negative effects for patients that can be caused by detoxification. This work is a project evaluation of a locally implemented strategy, which, it was hypothesised,would improve care by providing an individualised treatment plan for the management of alcohol withdrawal symptoms.

  2. 27 CFR 19.997 - Withdrawal of fuel alcohol.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 1 2010-04-01 2010-04-01 false Withdrawal of fuel alcohol. 19.997 Section 19.997 Alcohol, Tobacco Products and Firearms ALCOHOL AND TOBACCO TAX AND TRADE BUREAU... and Transfers § 19.997 Withdrawal of fuel alcohol. For each shipment or other removal of fuel...

  3. Polysomnographic study of sleeplessness and oneiricisms in the alcohol withdrawal syndrome.

    PubMed

    Plazzi, Giuseppe; Montagna, Pasquale; Meletti, Stefano; Lugaresi, Elio

    2002-05-01

    We describe a polysomnographic observation of the acute phase of the alcohol withdrawal syndrome, characterized by an alteration of the sleep-wake cycle and by the absence of non-rapid eye movement sleep. An atypical transitional state between rapid eye movement sleep and wake with hallucinations and enacting-dream behaviors represented the sole sleep pattern. Analogies of alcohol withdrawal syndrome with fatal familial insomnia and Morvan's fibrillary chorea suggest a common pathophysiological mechanism in these conditions. PMID:14592220

  4. Cognitive Impairment in Acute Cocaine Withdrawal

    PubMed Central

    Kelley, Brendan J.; Yeager, Kenneth R.; Pepper, Tom H.; Beversdorf, David Q.

    2005-01-01

    Objective To perform a pilot study to examine a range of cognitive flexibility tasks early in cocaine withdrawal. Background Previous neuropsychological investigations of cocaine withdrawal have conflicted regarding whether impaired cognitive flexibility occurs. However, most studies have examined patients later in withdrawal. Anxiety and yohimbine-induced panic are greatest early in withdrawal, and both anxiety and increased noradrenergic tone can impair cognitive flexibility. Method Twelve patients acutely withdrawing from cocaine were compared with gender-, age-, and estimated premorbid intelligence–matched control subjects on tests of cognitive flexibility as well as verbal fluency, verbal memory, spatial memory, and attention. Results As predicted, impairments were found on the cognitive flexibility tasks. Impairments also were present in verbal fluency and verbal memory but not spatial memory or attention. Conclusions We propose that the cognitive flexibility impairment may relate to the increased noradrenergic activation recently described in cocaine withdrawal. Impairments on verbal tasks may also relate to an impaired flexibility in the search of semantic networks. Further research will explore the effects of pharmacologic manipulation of the noradrenergic system on cognition in acute withdrawal. Recently, propranolol has been shown to benefit patients in cocaine withdrawal. Further research will explore whether impaired cognitive flexibility related to altered noradrenergic tone could serve as a mechanism for this treatment response. PMID:15970730

  5. Tobacco smoking interferes with GABAA receptor neuroadaptations during prolonged alcohol withdrawal.

    PubMed

    Cosgrove, Kelly P; McKay, Reese; Esterlis, Irina; Kloczynski, Tracy; Perkins, Evgenia; Bois, Frederic; Pittman, Brian; Lancaster, Jack; Glahn, David C; O'Malley, Stephanie; Carson, Richard E; Krystal, John H

    2014-12-16

    Understanding the effects of tobacco smoking on neuroadaptations in GABAA receptor levels over alcohol withdrawal will provide critical insights for the treatment of comorbid alcohol and nicotine dependence. We conducted parallel studies in human subjects and nonhuman primates to investigate the differential effects of tobacco smoking and nicotine on changes in GABAA receptor availability during acute and prolonged alcohol withdrawal. We report that alcohol withdrawal with or without concurrent tobacco smoking/nicotine consumption resulted in significant and robust elevations in GABAA receptor levels over the first week of withdrawal. Over prolonged withdrawal, GABAA receptors returned to control levels in alcohol-dependent nonsmokers, but alcohol-dependent smokers had significant and sustained elevations in GABAA receptors that were associated with craving for alcohol and cigarettes. In nonhuman primates, GABAA receptor levels normalized by 1 mo of abstinence in both groups--that is, those that consumed alcohol alone or the combination of alcohol and nicotine. These data suggest that constituents in tobacco smoke other than nicotine block the recovery of GABAA receptor systems during sustained alcohol abstinence, contributing to alcohol relapse and the perpetuation of smoking.

  6. 27 CFR 19.729 - Withdrawal of fuel alcohol.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 1 2013-04-01 2013-04-01 false Withdrawal of fuel alcohol. 19.729 Section 19.729 Alcohol, Tobacco Products and Firearms ALCOHOL AND TOBACCO TAX AND TRADE BUREAU, DEPARTMENT OF THE TREASURY ALCOHOL DISTILLED SPIRITS PLANTS Distilled Spirits for Fuel Use Rules for...

  7. 27 CFR 19.729 - Withdrawal of fuel alcohol.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 1 2014-04-01 2014-04-01 false Withdrawal of fuel alcohol. 19.729 Section 19.729 Alcohol, Tobacco Products and Firearms ALCOHOL AND TOBACCO TAX AND TRADE BUREAU, DEPARTMENT OF THE TREASURY ALCOHOL DISTILLED SPIRITS PLANTS Distilled Spirits for Fuel Use Rules for...

  8. UTILITY OF CIWA - A IN ALCOHOL WITHDRAWAL ASSESSMENT

    PubMed Central

    Manikant, S.; Tripathi, B.M.; Chavan, B.S.

    1992-01-01

    Fourty four patients of DSM-III-R diagnosis of alcohol withdrawal syndrome were assessed on CIWA-A scale. Most common withdrawal symptoms were tremors, sweating, arvdety, agitation, headache and flushing. Mostly symptoms subsided within four days. However, in half of the patients the symptoms like tremors, tactile disturbances, anxiety and headache persisted even beyond eight days. Usefulness of CIWA-A in alcohol withdrawal assessment is discussed. PMID:21776143

  9. Acamprosate and alcohol: II. Effects on alcohol withdrawal in the rat.

    PubMed

    Spanagel, R; Putzke, J; Stefferl, A; Schöbitz, B; Zieglgänsberger, W

    1996-06-01

    The suppressing effect of acamprosate (calcium-acetyl homotaurinate) on alcohol drinking is well established; however, little is known about its effects upon the alcohol-induced withdrawal syndrome. Male Wistar rats received as a sole drinking fluid a 20% (v/v) alcohol solution for one week. Animals consumed on average 5.3 +/- 0.3 g/kg per day alcohol, which resulted in blood alcohol levels of 38 +/- 14 mg/dl. For the quantification of alcohol withdrawal we used a new radio-telemetric system which enabled us to monitor body temperature, locomotor activity, food and water intake patterns constantly during alcohol withdrawal. Although alcohol intake and the resulting blood alcohol levels were low, clear signs of withdrawal could be observed. Thus, hyperthermia and hyperlocomotion occurred 18 h after the termination of forced alcohol drinking. Food intake was initially enhanced but dropped significantly below basal food intake in control animals one day after the termination of forced alcohol drinking. Acamprosate given twice a day (200 mg/kg, i.p., 8 a.m. and 8 p.m.) reduced hyperlocomotion and food intake significantly in the alcohol withdrawal animals, however, it did not change withdrawal-induced hyperthermia. When acamprosate was given to alcohol-naive animals, it increased locomotor activity and body temperature transiently, in particular during the rats' active night phase. In summary, (i) the radio-telemetric system used in the present study proved to be a very sensitive method for quantifying alcohol-induced withdrawal symptoms; (ii) acamprosate reduced alcohol-induced physical signs of withdrawal, however, this effect could not be observed for all parameters measured, which might be explained by the fact that (iii) acamprosate exerts a slight, transient psychomotor stimulant effects by itself.

  10. Recruitment of medial prefrontal cortex neurons during alcohol withdrawal predicts cognitive impairment and excessive alcohol drinking.

    PubMed

    George, Olivier; Sanders, Chelsea; Freiling, John; Grigoryan, Edward; Vu, Shayla; Allen, Camryn D; Crawford, Elena; Mandyam, Chitra D; Koob, George F

    2012-10-30

    Chronic intermittent access to alcohol leads to the escalation of alcohol intake, similar to binge drinking in humans. Converging lines of evidence suggest that impairment of medial prefrontal cortex (mPFC) cognitive function and overactivation of the central nucleus of the amygdala (CeA) are key factors that lead to excessive drinking in dependence. However, the role of the mPFC and CeA in the escalation of alcohol intake in rats with a history of binge drinking without dependence is currently unknown. To address this issue, we examined FBJ murine osteosarcoma viral oncogene homolog (Fos) expression in the mPFC, CeA, hippocampus, and nucleus accumbens and evaluated working memory and anxiety-like behavior in rats given continuous (24 h/d for 7 d/wk) or intermittent (3 d/wk) access to alcohol (20% vol/vol) using a two-bottle choice paradigm. The results showed that abstinence from alcohol in rats with a history of escalation of alcohol intake specifically recruited GABA and corticotropin-releasing factor (CRF) neurons in the mPFC and produced working memory impairments associated with excessive alcohol drinking during acute (24-72 h) but not protracted (16 -68 d) abstinence. Moreover, abstinence from alcohol was associated with a functional disconnection of the mPFC and CeA but not mPFC and nucleus accumbens. These results show that recruitment of a subset of GABA and CRF neurons in the mPFC during withdrawal and disconnection of the PFC-CeA pathway may be critical for impaired executive control over motivated behavior, suggesting that dysregulation of mPFC interneurons may be an early index of neuroadaptation in alcohol dependence.

  11. Treatment of Alcohol Withdrawal Syndrome with and without Dexmedetomidine

    PubMed Central

    Beg, Muna; Fisher, Sara; Siu, Dana; Rajan, Sudhir; Troxell, Lawrence; Liu, Vincent X

    2016-01-01

    Context: Studies suggest that dexmedetomidine—an intravenous central-acting α2-adrenergic agonist that effectively reduces anxiety among critically ill patients—is being used in patients with severe alcohol withdrawal. However, evidence supporting its use is limited, and it is not approved for this indication. Objective: To assess the effect of dexmedetomidine on severe alcohol withdrawal symptoms and to compare its use with benzodiazepines alone. Design: A retrospective, cohort study of 77 patients admitted to the adult medical intensive care unit with severe alcohol withdrawal between January 1, 2009, and October 31, 2013. Main Outcome Measures: The difference in lorazepam equivalents and Clinical Institute Withdrawal Assessment for Alcohol scores in the 24 hours before and after initiation of dexmedetomidine therapy. Results: The frequency of dexmedetomidine use increased dramatically between 2009 and 2013 (16.7% vs 82.4%; p = 0.01). Initiation of dexmedetomidine therapy was associated with significant improvements in Clinical Institute Withdrawal Assessment for Alcohol scores over corresponding 24-hour intervals (14.5 vs 8.5; p < 0.01). Benzodiazepine use also decreased, but the difference was not statistically significant at 24 hours (p = 0.10). Dexmedetomidine was well tolerated, requiring discontinuation of therapy in only 4 patients (10.5%). Dexmedetomidine use was also associated with significantly longer hospitalizations (p < 0.01). Conclusion: Dexmedetomidine initiation was associated with a reduction in short-term alcohol withdrawal symptoms in patients in the intensive care unit, with only a few patients experiencing adverse events. However, its use was also associated with longer hospitalizations. Further research is necessary to evaluate whether dexmedetomidine is efficacious or cost-effective in severe alcohol withdrawal. PMID:27168398

  12. Factor Structure of CIWA-Ar in Alcohol Withdrawal

    PubMed Central

    Bakhla, Ajay Kumar; Khess, Christoday R. J.; Verma, Vijay; Hembram, Mahesh; Praharaj, Samir Kumar; Soren, Subhas

    2014-01-01

    Objective. To identify the underlying factor structure of alcohol withdrawal syndrome, as measured with CIWA-Ar. Methods. Exploratory factor analysis was conducted on the items of CIWA-Ar. On 201 alcohol-dependent male patients seeking treatment for alcohol withdrawal at 36 hours of abstinence. Results. A three-factor solution was obtained that accounted for 68.74% of total variance. First factor had loading from four items (34.34% variance), second factor also had four items (24.25% variance), and the third had two items (10.04% variance). Conclusions. Factor analysis reveals the existence of multidimensionality of alcohol withdrawal as measured with CIWA-Ar and we found three factors that can be named as delirious, autonomic and nonspecific factors. PMID:24826372

  13. EFFECT OF FLUOXETINE AND BROMOCRIPTINE ON CRAVING OCCURRING DURING WITHDRAWAL FROM ALCOHOL

    PubMed Central

    Chatterjee, Sudipto; Isaac, Mohan K.

    1996-01-01

    Craving is an integral element in the understanding of alcohol dependence. Recent human and animal research implicates the serotonergic and dopaminergic systems in the mediation of excessive alcohol consumption. In this study, a cue-based approach was used to qualify and quantify craving occurring during acute withdrawal from alcohol. Fifty alcoholics were given either placebo, bromocriptine or fluoxetine in a randomised double-blind fashion and craving was sequentially measured over the next 15 days. Both fluoxetine and bromocriptine significantly attenuated total craving scores without similarly affecting withdrawal symptoms. The results suggest the importance of neurotransmitters in mediating craving. The significance of these data in the light of various behavioural and neurochemical models have been discussed. PMID:21584128

  14. Sodium valproate in the treatment of the alcohol withdrawal syndrome.

    PubMed

    Lambie, D G; Johnson, R H; Vijayasenan, M E; Whiteside, E A

    1980-09-01

    The value of sodium valproate in the management of patients during withdrawal from alcohol dependence has been assessed. Alcoholic inpatients were randomly allocated to two groups - one treated with sodium valproate and the other acting as a control. All patients received multivitamins and fluid and electrolyte replacement, and some received chlormethiazole or other tranquillisers. Treatment with sodium valproate (1200 mg daily) was continued for one week. The occurrence of seizures and other withdrawal symptoms (tremulousness, nausea, sweating, disorientation) were noted daily. Forty-nine episodes of withdrawal have been included in the trial - 22 in the sodium valproate group and 27 in the control group. Five patients, all in the control group, had seizures. Other withdrawal symptoms disappeared more quickly in the sodium valproate group even though fewer patients were receiving chlormethiazole.

  15. [Acute gamma-butyrolactone poisoning with withdrawal syndrome].

    PubMed

    Chwaluk, Paweł; Rejmak, Grazyna

    2011-01-01

    Gamma-butyrolactone (GBL) is a solvent that are part of many consumer products and in most countries can be legally purchased in the form of almost pure substance. After ingestion GBL is rapidly converted to gamma-hydroxybutyric acid (GHB). In recent years, GBL became a legal alternative to GHB, which is used widely since 1990s as a club drug and date rape drug. It is believed that abuse of GBL is not frequent in Europe, except for certain specific groups, mainly in urban centers in the west of the continent. We present a case of acute GBL poisoning with the withdrawal syndrome in 23-year-old man living in a rural area in eastern Poland. The patient was admitted to the Intensive Care Unit (ICU) because of coma of unknown origin. On admission erosions of the lips and mouth was seen. Ethyl alcohol was not present in blood sample, urine screening tests for drugs were negative. During his stay in the ICU patient required ventilatory support, was periodically agitated with muscular jerks and opisthotonos. The later medical history revealed that the patient from two years used GBL, which purchased as wheels cleaner. The tolerance developed, and the interruption of use of substance triggered symptoms of withdrawal. GBL abuse occurs in different social groups and is at risk for acute toxicity and the development of physical dependence. PMID:22010460

  16. Complicated alcohol withdrawal presenting as self mutilation.

    PubMed

    Patra, Bichitra Nanda; Sharma, Akhilesh; Mehra, Aseem; Singh, Shubhmohan

    2014-01-01

    Self-mutilation has been defined as deliberate self injury to body tissue without the intent to die. There has been an association between substance abuse and self mutilation. Alcoholic hallucinosis is usually in auditory modality and regarded as harmless. But patients can indulge in self harm behavior when the hallucinosis is commanding type. We are presenting a case in which the patient inflicted multiple stab injury to his own abdomen in response to alcoholic hallucinosis. This has clinical implication to enquire about substance abuse in patients presenting to emergency setting.

  17. Adrenergic Inhibition with Dexmedetomidine to Treat Stress Cardiomyopathy during Alcohol Withdrawal: A Case Report and Literature Review

    PubMed Central

    Harris, Zachary M.; Alonso, Alvaro; Kennedy, Thomas P.

    2016-01-01

    Stress (Takotsubo) cardiomyopathy is a form of reversible left ventricular dysfunction with a heightened risk of ventricular arrhythmia thought to be caused by high circulating catecholamines. We report a case of stress cardiomyopathy that developed during severe alcohol withdrawal successfully treated with dexmedetomidine. The case involves a 53-year-old man with a significant history of alcohol abuse who presented to a teaching hospital with new-onset seizures. His symptoms of acute alcohol withdrawal were initially treated with benzodiazepines, but the patient later developed hypotension, and stress cardiomyopathy was suspected based on ECG and echocardiographic findings. Adjunctive treatment with the alpha-2-adrenergic agonist, dexmedetomidine, was initiated to curtail excessive sympathetic outflow of the withdrawal syndrome, thereby targeting the presumed pathophysiology of the cardiomyopathy. Significant clinical improvement was observed within one day of initiation of dexmedetomidine. These findings are consistent with other reports suggesting that sympathetic dysregulation during alcohol withdrawal produces ideal pathobiology for stress cardiomyopathy and leads to ventricular arrhythmogenicity. Stress cardiomyopathy should be recognized as a complication of alcohol withdrawal that significantly increases cardiac-related mortality. By helping to correct autonomic dysregulation of the withdrawal syndrome, dexmedetomidine may be useful in the treatment of stress-induced cardiomyopathy. PMID:27006838

  18. Elevated tryptophan levels in post-withdrawal alcoholics.

    PubMed

    Farren, C K; Dinan, T G

    1996-12-01

    Changes in serotonin function and disturbances in tryptophan availability have been implicated in many psychiatric disorders, including alcoholism. In the present study we took serum free tryptophan samples from 31 healthy volunteer controls and from 42 DSM-III-R alcohol-dependent subjects who had abstained from alcohol for at least 2.5 weeks (range 2.5-104 weeks). We also measured the basal serum cortisol level at 09.00 hours for the same subjects and controls. There was a significant increase in the serum tryptophan level of the alcoholic subjects, by 43.7 mumol l-1 (range 29-63 mumol l-1), regardless of age of onset of alcoholism, family history of alcoholism or sociopathic traits, compared to the controls (33.0 mumol l-1, range 19-60 mumol l-1). There was also an increase in the basal serum cortisol level in the alcoholic subjects compared to the controls, but this was not related to the increase in tryptophan levels. These findings indicate a disturbance in serotonin precursor availability in post-withdrawal alcoholics, and contribute to the evidence for involvement of the serotonin system in alcoholism. PMID:9021001

  19. 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

  20. 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.

  1. The Effect of Intermittent Alcohol Vapor or Pulsatile Heroin on Somatic and Negative Affective Indices during Spontaneous Withdrawal in Wistar Rats

    PubMed Central

    Williams, Angela M.; Reis, Daniel J.; Powell, Alexa S.; Neira, Louis J.; Nealey, Kathryn A.; Ziegler, Cole E.; Kloss, Nina; Bilimoria, Jessica L.; Smith, Chelsea E.; Walker, Brendan M.

    2012-01-01

    Rationale Once dependent on alcohol or opioids, negative affect may accompany withdrawal. Dependent individuals are hypothesized to “self-medicate” in order to cope with withdrawal, which promotes escalated drug or alcohol use. Objectives The current study aimed to develop a reliable animal model to assess symptoms that occur during spontaneous alcohol and opioid withdrawal. Methods Dependence was induced using intermittent alcohol exposure or pulsatile heroin delivery and assessed for the presence of withdrawal symptoms during acute withdrawal by measuring somatic signs, behavior in the forced swim test (FST) and air-puff induced 22-kHz ultrasonic vocalizations (USVs). Additional animals subjected to eight weeks of alcohol vapor exposure were evaluated for altered somatic signs, operant alcohol self-administration and 22-kHz USV production, as well as performance in the elevated plus-maze (EPM). Results During spontaneous withdrawal from pulsatile heroin or intermittent alcohol vapor, animals displayed increased somatic withdrawal signs, FST immobility and 22-kHz USV production, but did not show any behavioral change in the EPM unless the duration of exposure was extended to four weeks. Following eight weeks of alcohol vapor exposure, animals displayed somatic withdrawal signs, escalated alcohol self-administration and increased 22-kHz USVs. Conclusions These paradigms provide consistent methods to evaluate the behavioral ramifications, and neurobiological substrates, of alcohol and opioid dependence during spontaneous withdrawal. As immobility in the FST and percent open-arm time in the EPM were dissociable, with 22-kHz USVs paralleling immobility in the FST, assessment of air-puff induced 22-kHz USVs could provide an ethologically-valid alternative to the FST. PMID:22461104

  2. 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

  3. Neural mechanisms underlying nicotine addiction: acute positive reinforcement and withdrawal.

    PubMed

    Watkins, S S; Koob, G F; Markou, A

    2000-02-01

    The neurobiology of nicotine addiction is reviewed within the context of neurobiological and behavioral theories postulated for other drugs of abuse. The roles of various neurotransmitter systems, including acetylcholine, dopamine, serotonin, glutamate, gamma-aminobutyric acid, and opioid peptides in acute nicotine reinforcement and withdrawal from chronic administration are examined followed by a discussion of potential neuroadaptations within these neurochemical systems that may lead to the development of nicotine dependence. The link between nicotine administration, depression and schizophrenia are also discussed. Finally, a theoretical model of the neurobiological mechanisms underlying acute nicotine withdrawal and protracted abstinence involves alterations within dopaminergic, serotonergic, and stress systems that are hypothesized to contribute to the negative affective state associated with nicotine abstinence.

  4. Preclinical and clinical pharmacology of cyamemazine: anxiolytic effects and prevention of alcohol and benzodiazepine withdrawal syndrome.

    PubMed

    Bourin, Michel; Dailly, Eric; Hascöet, Martine

    2004-01-01

    Several studies have suggested that the antipsychotic compound, cyamemazine, possesses anxiolytic properties in humans. The original pharmacological profile of cyamemazine (D(2), 5-HT(2A), 5-HT(2C), and 5-HT(3) receptor antagonist), which was established by binding, microdialysis and behavioral studies, is consistent with these observations. In the light/dark exploration test, cyamemazine demonstrated anxiolytic-like activity by acute, but not chronic administration. By chronic administration, however, cyamemazine increased the time spent in the open arms of the elevated plus maze (EPM) test demonstrating anxiolytic-like activity. The discrepancy between the results obtained in these tests by acute and chronic administration, could be due to a combination of dopamine D(2) receptor antagonism with antagonism of the 5-HT(2C) and 5-HT(3) receptors. The action of cyamemazine on both the dopaminergic system and 5-HT(3) receptors could also explain the activity of cyamemazine in the management of alcohol withdrawal demonstrated in preclinical studies. This potential indication for cyamemazine and its activity in benzodiazepine withdrawal syndrome have recently been investigated in clinical trials and the results of these studies are presented in this review.

  5. MPDZ EXPRESSION IN THE CAUDOLATERAL SUBSTANTIA NIGRA PARS RETICULATA IS CRUCIALLY INVOLVED IN ALCOHOL WITHDRAWAL

    PubMed Central

    Kruse, L.C.; Walter, N.A.R.; Buck, K.J.

    2014-01-01

    Association studies implicate the multiple PDZ domain protein (MUPP1/MPDZ) gene in risk for alcoholism in humans and alcohol withdrawal in mice. Although manipulation of the Mpdz gene by homologous recombination and bacterial artificial chromosome transgenesis has suggested that its expression affects alcohol withdrawal risk, the potential confounding effects of linked genes and developmental compensation currently limit interpretation. Here, using RNA interference, we directly test the impact of Mpdz expression on alcohol withdrawal severity and provide brain regional mechanistic information. Lentiviral-mediated delivery of Mpdz short hairpin RNA (shRNA) to the caudolateral substantia nigra pars reticulata significantly reduces Mpdz expression and exacerbates alcohol withdrawal convulsions compared to control mice delivered a scrambled shRNA. Neither baseline nor pentylenetetrazol enhanced convulsions differed between Mpdz shRNA and control animals, indicating that Mpdz expression in the caudolateral substantia nigra pars reticulata does not generally affect seizure susceptibility. To our knowledge, these represent the first in vivo Mpdz RNA interference analyses, and provide the first direct evidence that Mpdz expression impacts behavior. Our results confirm that Mpdz is a quantitative trait gene for alcohol withdrawal and demonstrate that its expression in the caudolateral substantia nigra pars reticulata is crucially involved in risk for alcohol withdrawal. PMID:25109596

  6. Sex differences in acute ethanol withdrawal severity after adrenalectomy and gonadectomy in Withdrawal Seizure-Prone and Withdrawal Seizure-Resistant mice.

    PubMed

    Strong, Moriah N; Kaufman, Katherine R; Crabbe, John C; Finn, Deborah A

    2009-08-01

    Recent findings suggest that the ability of ethanol (EtOH) to increase the levels of neurosteroids with potent gamma-aminobutyric acid (GABA)ergic properties can influence measures of EtOH sensitivity. Earlier studies determined that removal of the adrenals and gonads diminished the steroidogenic effect of EtOH and significantly increased acute EtOH withdrawal severity in two inbred mouse strains that differed in withdrawal severity, suggesting the contribution of anticonvulsant GABAergic steroids to acute withdrawal in intact animals. Thus, the goal of the present study was to investigate the consequence of steroid removal on acute EtOH withdrawal through excision of the adrenals and gonads, in another genetic animal model of EtOH withdrawal differences, the Withdrawal Seizure-Prone (WSP) and Withdrawal Seizure-Resistant (WSR) selected lines. Male and female WSP and WSR mice underwent surgical removal of the adrenals and gonads or no organ removal (SHAM). One to 2 weeks later, baseline handling-induced convulsions (HICs) were assessed, mice were given a 4 g/kg dose of EtOH, and HICs were measured hourly for 12 h and then at 24 h. The combination surgery significantly increased EtOH withdrawal in WSP and WSR female mice, as measured by area under the curve (AUC) and peak HIC scores. The AUC was significantly positively correlated with plasma corticosterone levels and significantly negatively correlated with progesterone levels. In contrast, surgical status did not alter withdrawal severity in male WSP and WSR mice. Overall, the increase in acute EtOH withdrawal severity in female WSP and WSR mice after adrenalectomy and gonadectomy corroborate our recent evidence that withdrawal from a high dose of EtOH can be modulated by anticonvulsant steroids produced in the periphery.

  7. Use of potentiated preparations to relieve alcohol and opium withdrawal syndromes.

    PubMed

    Aleksandrova, N V; Gofman, A G; Krylov, E N; Epstein, O I

    2003-01-01

    The efficiency of potentiated preparations from ethanol and morphine hydrochloride in the therapy of patients with alcohol and opium withdrawal syndromes was compared in an open clinical trial. Potentiated ethanol relieved the major clinical manifestations, possessed hypnagogic properties, and reduced the severity of neurological and vegetative disorders in patients with the alcohol withdrawal syndrome. Potentiated morphine produced the anxiolytic, myorelaxing, and analgetic effects. Test preparations did not cause side effects.

  8. Functional connectivity during language processing in acute cocaine withdrawal-a pilot study

    PubMed Central

    Narayanan, Ananth; White, Catherine A.; Saklayen, Sanjida S.; Abduljalil, Amir; Schmalbrock, Petra; Pepper, Tom H.; Lander, Brad N.; Beversdorf, David Q.

    2011-01-01

    Recent research revealed decreased access to semantic and associative networks in acute cocaine withdrawal. In autism, such behavioral outcomes are associated with decreased functional connectivity using functional magnetic resonance imaging. Therefore, we wished to determine whether connectivity is also decreased in acute cocaine withdrawal. Eight subjects in acute cocaine withdrawal were compared to controls for connectivity in language areas while performing a task involving categorization of words according to semantic and phonological relatedness. Acute withdrawal subjects had significantly less overall connectivity during semantic relatedness, and a trend towards less connectivity during phonological relatedness. Of potential future interest is whether this might serve as an imaging marker for treatment in patients. PMID:22082460

  9. Ethylglucuronide determination in urine and hair from alcohol withdrawal patients.

    PubMed

    Concheiro, Marta; Cruz, Angelines; Mon, Marisol; de Castro, Ana; Quintela, Oscar; Lorenzo, Angeles; López-Rivadulla, Manuel

    2009-04-01

    Two methods for the determination of ethylglucuronide (EtG) in urine and in hair have been developed by liquid chromatography- tandem mass spectrometry. These two methods were fully validated, including linearity (0.25-100 microg/mL in urine; 0.05-5 ng/mg in hair; r(2) > 0.99, n = 5), limits of detection (0.1 microg/mL in urine, 0.025 ng/mg in hair) and quantitation (lowest level of the calibration curve), extraction efficiency (> 55%), within-day and between-day imprecision and bias (CV and mean relative error < 15%), matrix effect, and relative ion intensity. These methods have been applied to 541 urine samples and 17 hair specimens collected from 156 alcohol withdrawal patients. The determination of ethanol versus EtG in urine was compared, and also the convenience of EtG determination in hair. EtG in urine and in hair proved to be a powerful tool for monitoring abstinence in these patients. PMID:19371464

  10. Acamprosate attenuates the handling induced convulsions during alcohol withdrawal in Swiss Webster mice.

    PubMed

    Farook, Justin M; Krazem, Ali; Lewis, Ben; Morrell, Dennis J; Littleton, John M; Barron, Susan

    2008-09-01

    In the present study, we examined the effects of acamprosate for its ability to reduce handling induced convulsions (HICs) during alcohol withdrawal. Diazepam was used as a positive control. Swiss Webster male mice received three daily IP injections of alcohol (2.5 g/kg) or alcohol (2.5 g/kg)+methylpyrazole (4-MP) (9 mg/kg). (4-MP, being an alcohol dehydrogenase inhibitor slows down the breakdown of alcohol. 4-MP in combination with alcohol exhibits a dramatic increase in blood alcohol level compared to alcohol alone). Ten hours following the last alcohol injection, the mice were picked up by the tail and examined for their seizure susceptibility (HICs). Diazepam, a benzodiazepine known to reduce seizures during alcohol withdrawal, significantly reduced these HICs at doses of 0.25, 0.5 and 1 mg/kg (p's<0.001). Acamprosate, an anti-relapse compound used clinically in newly abstinent alcoholics, also reduced these HICs at doses of 100, 200 and 300 mg/kg (p's<0.05). This study supports the use of acamprosate during periods of alcohol withdrawal as well as during abstinence.

  11. Morphine suppression of ethanol withdrawal in mice.

    PubMed

    Blum, K; Wallace, J E; Schwerter, H A; Eubanks, J D

    1976-01-15

    The acute administration of morphine, alcohol or dopamine results in a pronounced suppression of the convulsions produced by alcohol in mice. The suppressive action of morphine on alcohol withdrawal in the mouse apparently is not a product of morphine intoxication, but rather to some other specific interaction between alcohol and morphine in the central nervous system. The conclusion suggest that dopamine may play a significant role as a modulator in convulsions produced during alcohol withdrawal.

  12. Investigation of allyphenyline efficacy in the treatment of alcohol withdrawal symptoms.

    PubMed

    Ubaldi, Massimo; Del Bello, Fabio; Domi, Esi; Pigini, Maria; Nasuti, Cinzia

    2015-08-01

    We have recently demonstrated that allyphenyline, behaving as α2C-adrenoceptor/serotonin 5-HT1A receptor agonist and α2A-adrenoceptor antagonist, in mice enhanced morphine analgesia, attenuated morphine withdrawal symptoms, showed significant antidepressant-like activity and was devoid of sedative side effects. Opioid and alcohol withdrawal shares several common neurobiological and molecular mechanisms. Therefore, in this study we expanded our analysis of the pharmacological properties of allyphenyline by investigating its ability to prevent the expression of somatic withdrawal signs, anxiety-like behavior and hyperlocomotion associated with chronic ethanol intoxication. Rats were subjected to induction of ethanol dependence via repeated daily intragastric ethanol (20%) administration for 4 consecutive days. Twelve hours after the last alcohol administration, somatic alcohol withdrawal signs were scored. Results revealed a significant expression of physical withdrawal signs that were not affected by intraperitoneal (i.p.) administration of allyphenyline at the doses of 0.05, 0.275 and 0.5 mg/kg. In contrast, allyphenyline (0.05 and 0.275 mg/kg i.p.) significantly reduced hyperanxiety-like behavior observed 6 days after alcohol intoxication as measured using the defensive burying test. Allyphenyline also reduced open field hyperlocomotor activity associated with alcohol withdrawal. Notably, the anxiolytic effect of the compound, as well as the already reported antidepressant action, was observed at very low doses, suggesting the involvement of its α2C-adrenoceptor/serotonin 5-HT1A receptor agonism. Therefore, the present investigation suggests that allyphenyline might represent an interesting pharmacological tool to investigate the potential of compounds exhibiting α2C-adrenoceptor/serotonin 5-HT1A receptor agonism and α2A-adrenoceptor antagonism in the treatment of hyperanxiety and hyperlocomotion occurring during alcohol withdrawal in dependent subjects.

  13. 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.

  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. Association of testosterone and BDNF serum levels with craving during alcohol withdrawal.

    PubMed

    Heberlein, Annemarie; Lenz, Bernd; Opfermann, Birgitt; Gröschl, Michael; Janke, Eva; Stange, Katrin; Groh, Adrian; Kornhuber, Johannes; Frieling, Helge; Bleich, Stefan; Hillemacher, Thomas

    2016-08-01

    Preclinical and clinical studies show associations between testosterone and brain-derived neurotrophic growth factor (BDNF) serum levels. BDNF and testosterone have been independently reported to influence alcohol consumption. Therefore, we aimed to investigate a possible interplay of testosterone and BDNF contributing to alcohol dependence. Regarding possible interplay of testosterone and BDNF and the activity of the hypothalamic pituitary axis (HPA), we included cortisol serum levels in our research. We investigated testosterone and BDNF serum levels in a sample of 99 male alcohol-dependent patients during alcohol withdrawal (day 1, 7, and 14) and compared them to a healthy male control group (n = 17). The testosterone serum levels were significantly (p < 0.001) higher in the patients' group than in the control group and decreased significantly during alcohol withdrawal (p < 0.001). The decrease of testosterone serum levels during alcohol withdrawal (days 1-7) was significantly associated with the BDNF serum levels (day 1: p = 0.008). In a subgroup of patients showing high cortisol serum levels (putatively mirroring high HPA activity), we found a significant association of BDNF and testosterone as well as with alcohol craving measured by the Obsessive and Compulsive Drinking Scale (OCDS). Our data suggest a possible association of BDNF and testosterone serum levels, which may be relevant for the symptomatology of alcohol dependence. Further studies are needed to clarify our results. PMID:27514572

  16. Attenuation of alcohol withdrawal syndrome and blood cortisol level with forced exercise in comparison with diazepam.

    PubMed

    Motaghinejad, Majid; Bangash, Mohammad Yasan; Motaghinejad, Ozra

    2015-01-01

    Relieving withdrawal and post-abstinence syndrome of alcoholism is one of the major strategies in the treatment of alcohol addicted patients. Diazepam, chlordiazepoxide, and topiramate are the approved medications that were used for this object. To assess the role of non-pharmacologic therapy in the management of alcohol withdrawal syndrome, we analyzed effects of forced exercise by treadmill on alcohol dependent mice as an animal model. A total of 60 adult male mice were divided into 5 groups, from which 4 groups became dependent to alcohol (2 g/kg/day) for 15 days. From day 16, treatment groups were treated by diazepam (0.5mg/kg), forced exercise, and diazepam (0.5 mg/kg) concurrent with forced exercise for two weeks; And the positive control group received same dose of alcohol (2 g/kg/day) for two weeks. The negative control group received normal saline for four weeks. Finally, on day 31, all animals were observed for withdrawal signs, and Alcohol Total Withdrawal Score (ATWS) was determined. Blood cortisol levels were measured in non-fasting situations as well. Present findings showed that ATWS significantly decrease in all treatment groups in comparison with positive control group (P<0.05 for groups received diazepam and treated by forced exercise and P<0.001 for group under treatment diazepam + forced exercise). Moreover, blood cortisol level significantly decreased in all treatment groups (P<0.001). This study suggested that forced exercise and physical activity can be useful as adjunct therapy in alcoholism and can ameliorate side effects and stress situation of withdrawal syndrome periods. PMID:26024707

  17. Attenuation of alcohol withdrawal syndrome and blood cortisol level with forced exercise in comparison with diazepam.

    PubMed

    Motaghinejad, Majid; Bangash, Mohammad Yasan; Motaghinejad, Ozra

    2015-01-01

    Relieving withdrawal and post-abstinence syndrome of alcoholism is one of the major strategies in the treatment of alcohol addicted patients. Diazepam, chlordiazepoxide, and topiramate are the approved medications that were used for this object. To assess the role of non-pharmacologic therapy in the management of alcohol withdrawal syndrome, we analyzed effects of forced exercise by treadmill on alcohol dependent mice as an animal model. A total of 60 adult male mice were divided into 5 groups, from which 4 groups became dependent to alcohol (2 g/kg/day) for 15 days. From day 16, treatment groups were treated by diazepam (0.5mg/kg), forced exercise, and diazepam (0.5 mg/kg) concurrent with forced exercise for two weeks; And the positive control group received same dose of alcohol (2 g/kg/day) for two weeks. The negative control group received normal saline for four weeks. Finally, on day 31, all animals were observed for withdrawal signs, and Alcohol Total Withdrawal Score (ATWS) was determined. Blood cortisol levels were measured in non-fasting situations as well. Present findings showed that ATWS significantly decrease in all treatment groups in comparison with positive control group (P<0.05 for groups received diazepam and treated by forced exercise and P<0.001 for group under treatment diazepam + forced exercise). Moreover, blood cortisol level significantly decreased in all treatment groups (P<0.001). This study suggested that forced exercise and physical activity can be useful as adjunct therapy in alcoholism and can ameliorate side effects and stress situation of withdrawal syndrome periods.

  18. 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

  19. INFANT EMOTIONAL WITHDRAWAL: A PRECURSOR OF AFFECTIVE AND COGNITIVE DISTURBANCE IN FETAL ALCOHOL SPECTRUM DISORDERS

    PubMed Central

    Molteno, Christopher D.; Jacobson, Joseph L.; Carter, R. Colin; Dodge, Neil C.; Jacobson, Sandra W.

    2013-01-01

    Objectives To test the hypothesis that emotional withdrawal is an early indicator of affective disorder in infants heavily exposed prenatally to alcohol, which is independent of alcohol-related effects on mother-infant interaction and temperament and discriminated between children later diagnosed with fetal alcohol syndrome (FAS) and partial FAS (PFAS) and predicted cognitive and affective outcomes at 5 and 9 years. Methods The sample consisted of Cape Coloured (mixed ancestry) infants, whose mothers were interviewed during pregnancy regarding their alcohol consumption using a timeline follow-back approach. Infant emotional withdrawal (n = 85) was assessed on the Alarm Distress Baby Scale at 6.5 months. Mother-infant interaction was evaluated from video recordings during free play and infant feeding at 6.5 months (n = 127). Infant temperament was assessed by maternal report on the EAS Temperament Survey at 13 months (n = 119). Socio-demographic and psychological correlates of maternal alcohol use and infant iron deficiency were examined as potential confounders. The children were diagnosed for FAS/PFAS by expert dysmorphologists at 5 years; cognitive and affective function, at 5 and 9 years. Results Prenatal alcohol exposure was associated with increased infant emotional withdrawal and decreased activity, but unrelated to mother-infant interaction or any other temperament measures. Children later diagnosed with FAS and PFAS at 5 years exhibited more emotional withdrawal and less responsivity and activity as infants. Infant withdrawal, responsivity, quality of interaction, and maternal sensitivity also predicted poorer IQ and affective response at 5 and 9 years. When all four infant affective measures were examined simultaneously in a regression analysis, only infant emotional withdrawal persisted as a significant predictor of 9-year IQ. Conclusions This study is the first to document a direct effect of fetal alcohol exposure on emotional withdrawal in infancy

  20. DNA methylation of the LEP gene is associated with craving during alcohol withdrawal.

    PubMed

    Hillemacher, Thomas; Weinland, Christian; Lenz, Bernd; Kraus, Thomas; Heberlein, Annemarie; Glahn, Alexander; Muschler, Marc A N; Bleich, Stefan; Kornhuber, Johannes; Frieling, Helge

    2015-01-01

    Different studies have described evidence for an association between leptin serum levels and craving in alcohol dependent patients. As leptin expression is regulated by DNA methylation we investigated changes of DNA methylation of the LEP gene promoter region in alcohol dependent patients undergoing withdrawal. Results show that low methylation status is associated with increasing serum leptin levels and elevation of craving for alcohol in the referring patients group. These findings point towards a pathophysiological relevance of changes in DNA methylation of the LEP gene promoter region in alcohol dependence.

  1. 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

  2. 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

  3. [A case of central pontine and extrapontine myelinolysis, without hyponatremia, during alcohol withdrawal with favorable outcome].

    PubMed

    de Lacerda, L; Van Durme, E; Verbanck, P

    2014-01-01

    Central pontine and extra-pontine myelinolysis (CPM/EPM) is a rare neurological disorder, well documented for more than 50 years but whose pathogenesis remains obscure. The existence of predisposing factors occurs in the most cases; chronic alcohol abuse is one of the most commonly encountered, among many others. Alcohol withdrawal represents an additional vulnerability factor, being responsible for electrolyte imbalances which are not always demonstrable but are certainly involved in the development of CPM and/or EPM. CPM/EPM may be responsible for severe morbidity and is potentially life-threatening. The diagnosis of CPM/ EPM remains mostly clinical and is confirmed by magnetic resonance imaging of the brain. It should be considered in the setting of any unexplained neurological symptoms during the course of alcohol withdrawal or for any patient with chronic alcohol abuse, as promptly as possible, given the potentially fatal outcome.

  4. 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

  5. Acute and chronic tianeptine treatments attenuate ethanol withdrawal syndrome in rats.

    PubMed

    Uzbay, Tayfun; Kayir, Hakan; Celik, Turgay; Yüksel, Nevzat

    2006-05-01

    Effects of acute and chronic tianeptine treatments on ethanol withdrawal syndrome were investigated in rats. Ethanol (7.2% v/v) was given to adult male Wistar rats by a liquid diet for 30 days. Acute or chronic (twice daily) tianeptine (5, 10 and 20 mg/kg) and saline were administered to rats intraperitoneally. Acute and last chronic tianeptine injections and saline were done 30 min before ethanol withdrawal testing. After 2nd, 4th and 6th hours of ethanol withdrawal, rats were observed for 5 min, and withdrawal signs which included locomotor hyperactivity, agitation, tremor, wet dog shakes, stereotyped behavior and audiogenic seizures were recorded or rated. Locomotor activity in naive (no ethanol-dependent rats) was also tested after acute tianeptine treatments. Acute but not chronic tianeptine treatment attenuated locomotor hyperactivity and agitation in ethanol-dependent rats. Both acute and chronic tianeptine treatment produced some significant inhibitory effects on tremor, wet dog shakes, stereotyped behaviors and audiogenic seizures during the ethanol withdrawal. Our results suggest that acute or chronic tianeptine treatment attenuates ethanol withdrawal syndrome in ethanol-dependent rats and this drug may be useful for treatment of ethanol-type dependence.

  6. Symptom-Triggered vs. Fixed-Dosing Management of Alcohol Withdrawal Syndrome.

    PubMed

    Skinner, Reagan T

    2014-01-01

    A literature review was conducted with the objective of creating evidence-based recommendations for use of symptom-triggered therapy (STT) or fixed-schedule dosing in treating alcohol withdrawal syndrome in inpatients. Use of STT reduced duration of therapy as well as the number of patients requiring treatment or medication, potentially reducing costs and risk of adverse medication reactions.

  7. Intrathecal Clonidine Pump Failure Causing Acute Withdrawal Syndrome With 'Stress-Induced' Cardiomyopathy.

    PubMed

    Lee, Hwee Min D; Ruggoo, Varuna; Graudins, Andis

    2016-03-01

    Clonidine is a central alpha(2)-agonist antihypertensive used widely for opioid/alcohol withdrawal, attention deficit hyperactivity disorder and chronic pain management. We describe a case of clonidine withdrawal causing life-threatening hypertensive crisis and stress-induced cardiomyopathy. A 47-year-old man with chronic back pain, treated with clonidine for many years via intrathecal pump (550 mcg/24 h), presented following a collapse and complaining of sudden worsening of back pain, severe headache, diaphoresis, nausea and vomiting. A few hours prior to presentation, his subcutaneous pump malfunctioned. On presentation, vital signs included pulse 100 bpm, BP 176/103 mmHg, temperature 37.8 °C and O2 saturation 100 % (room air). Acute clonidine withdrawal with hypertensive crisis was suspected. Intravenous clonidine loading dose and a 50 mcg/h infusion were commenced. Five hours later, severe chest pain, dyspnoea, tachycardia, hypoxia, with BP 180/120 mmHg and pulmonary edema ensued. ECG showed sinus tachycardia with no ST elevation. Repeated intravenous clonidine doses were given (25 mcg every 5-10 min), with ongoing clonidine infusion to control blood pressure. Glyceryl trinitrate infusion, positive pressure ventilation and intravenous benzodiazepines were added. Bedside echocardiogram showed stress-induced cardiomyopathy pattern. Serum troponin-I was markedly elevated. His coronary angiography showed minor irregularities in the major vessels. Over the next 3 days in the ICU, drug infusions were weaned. Discharge was 12 days later on oral clonidine, metoprolol, perindopril, aspirin and oxycodone-SR. Two months later, his echocardiogram was normal. The intrathecal pump was removed. We report a case of stress-induced cardiomyopathy resulting from the sudden cessation of long-term intrathecal clonidine. This was managed by re-institution of clonidine and targeted organ-specific therapies. PMID:26370679

  8. The search for insight: Clients' psychological experiences of alcohol withdrawal in a voluntary, residential, health care setting.

    PubMed

    Smith, Morgan

    2004-04-01

    This study utilized a life history approach to describe clients' psychological experiences of the alcohol withdrawal process while voluntarily residing in a specialist alcohol withdrawal facility. Reflection on the past and anticipation of the future frequently occupied the thoughts of participants as they sought insight in to their lives. These insights were associated with a range of emotions that included embarrassment, shame, optimism, feelings of support and a sense of loss of control. The findings provide additional information on the human experience of alcohol withdrawal and, thus, increase empathy, understanding and knowledge. This increased understanding can be utilized to improve the quality of nursing care provided to this complex client group. PMID:15056346

  9. Prazosin + naltrexone decreases alcohol drinking more effectively than does either drug alone in P rats with a protracted history of extensive voluntary alcohol drinking, dependence and multiple withdrawals

    PubMed Central

    Rasmussen, Dennis D; Kincaid, Carrie L; Froehlich, Janice C

    2015-01-01

    Background Prazosin (PRZ, an α1-adrenergic receptor antagonist) and naltrexone (NTX, a non-specific opioid receptor antagonist) each decrease alcohol drinking when administered to rats selectively-bred for high voluntary alcohol drinking (alcohol-preferring, or “P”), and the combination of PRZ+NTX decreases alcohol drinking more effectively than does either drug alone. Since drug responsiveness can depend on history of alcohol drinking and dependence, we investigated whether various schedules of PRZ and NTX administration, alone or in combination, are effective in decreasing alcohol drinking in male P rats with a history of protracted voluntary alcohol drinking, dependence and repeated withdrawals closely resembling human alcoholism. Methods Male P rats became alcohol-dependent during 1 year of ad libitum 24 h/day access to food, water and 20% alcohol with repetitive temporary alcohol withdrawals. Four sequential studies then addressed effects of oral PRZ (2 mg/kg) and NTX (10 mg/kg), alone or together, on alcohol drinking during: 1) daily alcohol access with daily drug treatment, 2) intermittent alcohol access with daily drug treatment, 3) intermittent alcohol access with occasional drug treatment, and 4) post-deprivation reinstatement of alcohol access. Results The combination of PRZ+NTX consistently suppressed alcohol drinking during daily or intermittent alcohol access conditions and when drug treatment was either daily or occasional. PRZ+NTX was consistently more effective than either drug alone. The reduction in alcohol drinking was not due to sedation, motor effects or malaise. Conclusions Both daily and “as-needed” treatment with PRZ+NTX are highly effective in suppressing daily, intermittent and post-deprivation alcohol drinking in male P rats with a protracted history of alcohol dependence and repeated withdrawals. This drug combination may be especially effective for treating individuals with long histories of heavy alcohol abuse, dependence and

  10. 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

  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. Clinical Evolution of Central Pontine Myelinolysis in a Patient with Alcohol Withdrawal: A Blurred Clinical Horizon.

    PubMed

    Mohammed, Abdul S; Boddu, Prajwal; Yazdani, Dina F

    2016-01-01

    Central pontine myelinolysis (CPM), a potentially fatal and debilitating neurological condition, was first described in 1959 in a study on alcoholic and malnourished patients. It is a condition most frequently related to rapid correction of hyponatremia. Chronic alcoholism associated CPM tends to be benign with a favorable prognosis compared to CPM secondary to rapid correction of hyponatremia. We describe a normonatremic, alcoholic patient who presented with CPM after a rapid rise in his sodium levels. Our case illustrates the fact that CPM can manifest even in patients who are normonatremic at baseline. Rapid rises in sodium levels should be promptly reversed before clinical symptoms manifest in patient with risk factors for CPM irrespective of their baseline sodium levels. Furthermore, clinical evolution of CPM can be difficult to discern from the natural course of alcohol withdrawal delirium, requiring astuteness and maintenance of a high degree of clinical suspicion on the part of the physician. PMID:27610136

  13. Clinical Evolution of Central Pontine Myelinolysis in a Patient with Alcohol Withdrawal: A Blurred Clinical Horizon

    PubMed Central

    Yazdani, Dina F.

    2016-01-01

    Central pontine myelinolysis (CPM), a potentially fatal and debilitating neurological condition, was first described in 1959 in a study on alcoholic and malnourished patients. It is a condition most frequently related to rapid correction of hyponatremia. Chronic alcoholism associated CPM tends to be benign with a favorable prognosis compared to CPM secondary to rapid correction of hyponatremia. We describe a normonatremic, alcoholic patient who presented with CPM after a rapid rise in his sodium levels. Our case illustrates the fact that CPM can manifest even in patients who are normonatremic at baseline. Rapid rises in sodium levels should be promptly reversed before clinical symptoms manifest in patient with risk factors for CPM irrespective of their baseline sodium levels. Furthermore, clinical evolution of CPM can be difficult to discern from the natural course of alcohol withdrawal delirium, requiring astuteness and maintenance of a high degree of clinical suspicion on the part of the physician.

  14. Clinical Evolution of Central Pontine Myelinolysis in a Patient with Alcohol Withdrawal: A Blurred Clinical Horizon

    PubMed Central

    Yazdani, Dina F.

    2016-01-01

    Central pontine myelinolysis (CPM), a potentially fatal and debilitating neurological condition, was first described in 1959 in a study on alcoholic and malnourished patients. It is a condition most frequently related to rapid correction of hyponatremia. Chronic alcoholism associated CPM tends to be benign with a favorable prognosis compared to CPM secondary to rapid correction of hyponatremia. We describe a normonatremic, alcoholic patient who presented with CPM after a rapid rise in his sodium levels. Our case illustrates the fact that CPM can manifest even in patients who are normonatremic at baseline. Rapid rises in sodium levels should be promptly reversed before clinical symptoms manifest in patient with risk factors for CPM irrespective of their baseline sodium levels. Furthermore, clinical evolution of CPM can be difficult to discern from the natural course of alcohol withdrawal delirium, requiring astuteness and maintenance of a high degree of clinical suspicion on the part of the physician. PMID:27610136

  15. 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.

  16. Cost-effectiveness analysis of baclofen and chlordiazepoxide in uncomplicated alcohol-withdrawal syndrome

    PubMed Central

    Reddy, Vikram K.; Girish, K.; Lakshmi, Pandit; Vijendra, R.; Kumar, Ajay; Harsha, R.

    2014-01-01

    Objectives: Benzodiazepines (BZDs) are the first-line drugs in alcohol-withdrawal syndrome (AWS). Baclofen, a gamma-aminobutyric acidB (GABAB) agonist, controls withdrawal symptoms without causing significant adverse effects. The objective of this study was to compare the cost-effectiveness of baclofen and chlordiazepoxide in the management of uncomplicated AWS. Materials and Methods: This was a randomized, open label, standard controlled, parallel group study of cost-effectiveness analysis (CEA) of baclofen and chlordiazepoxide in 60 participants with uncomplicated AWS. Clinical efficacy was measured by the Clinical Institute Withdrawal Assessment for alcohol (CIWA-Ar) scores. Lorazepam was used as supplement medication if withdrawal symptoms could not be controlled effectively by the study drugs alone. Both direct and indirect medical costs were considered and the CEA was analyzed in both patient's perspective and third-party perspective. Results: The average cost-effectiveness ratio (ACER) in patient's perspective of baclofen and chlordiazepoxide was Rs. 5,308.61 and Rs. 2,951.95 per symptom-free day, respectively. The ACER in third-party perspective of baclofen and chlordiazepoxide was Rs. 895.01 and Rs. 476.29 per symptom-free day, respectively. Participants on chlordiazepoxide had more number of symptom-free days when compared with the baclofen group on analysis by Mann-Whitney test (U = 253.50, P = 0.03). Conclusion: Both study drugs provided relief of withdrawal symptoms. Chlordiazepoxide was more cost-effective than baclofen. Baclofen was relatively less effective and more expensive than chlordiazepoxide. PMID:25097273

  17. Comparison of enteral ethanol and benzodiazepines for alcohol withdrawal in neurocritical care patients.

    PubMed

    Gipson, Gregory; Tran, Kim; Hoang, Cuong; Treggiari, Miriam

    2016-09-01

    We designed a study to evaluate the use of benzodiazepines and ethanol in patients being assessed for alcohol withdrawal and compare outcomes between the two agents. This is a retrospective chart review of patients admitted to neurocritical care or neurosurgical services who were at risk for ethanol withdrawal between June 2011 and September 2015. Patients were divided into two groups based on the first medication administered for alcohol withdrawal management, either benzodiazepine (n=50) or enteral ethanol (n=50). The primary endpoint was the maximum change in Clinical Institute Withdrawal Assessment of Alcohol scale (CIWA) score within the first 24hours. Secondary endpoints included maximum and minimum CIWA score in 5days, length of stay, and change in Glasgow Coma Scale. Study groups differed by mortality risk, level of coma at admission, and other clinical characteristics, with the ethanol group appearing less severely ill. There was no significant difference between the two groups in the maximum change in CIWA score at 24hours (-0.97, 95%CI: -3.21 to 1.27, p=0.39). Hospital and intensive care unit length of stay was 6.5 days and 1 day shorter for the ethanol group (p=0.03 and p=0.02, respectively). In summary, enteral ethanol was preferentially used in patients who are more likely to be capable of tolerating oral intake. We found that the change from baseline in CIWA score or other physiologic variables was not substantially different between the two agents. The overall utility of benzodiazepines and enteral ethanol remains unclear for this population and further study is needed to determine superiority.

  18. 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.

  19. 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

  20. [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.

  1. 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.

  2. Critical thoughts on current rodent models for evaluating potential treatments of alcohol addiction and withdrawal

    PubMed Central

    Ripley, Tamzin L; Stephens, David N

    2011-01-01

    Despite years of neurobiological research that have helped to identify potential therapeutic targets, we do not have a reliable pharmacological treatment for alcoholism. There are a range of possible explanations for this failure, including arguments that alcoholism is a spectrum disorder and that different population subtypes may respond to different treatments. This view is supported by categorisations such as early- and late-onset alcoholism, whilst multifactorial genetic factors may also alter responsivity to pharmacological agents. Furthermore, experience of alcohol withdrawal may play a role in future drinking in a way that may distinguish alcoholism from other forms of addiction. Additionally, our neurobiological models, based largely upon results from rodent studies, may not mimic specific aspects of the human condition and may reflect different underlying phenomena and biological processes from the clinical pattern. As a result, potential treatments may be targeting inappropriate aspects of alcohol-related behaviours. Instead, we suggest a more profitable approach is (a) to identify well-defined intermediate behavioural phenotypes in human experimental models that reflect defined aspects of the human clinical disorder and (b) to develop animal models that are homologous with those phenotypes in terms of psychological processes and underlying neurobiological mechanisms. This review describes an array of animal models currently used in the addiction field and what they tell us about alcoholism. We will then examine how established pharmacological agents have been developed using only a limited number of these models, before describing some alternative novel approaches to achieving homology between animal and human experimental measures. LINKED ARTICLES This article is part of a themed issue on Translational Neuropharmacology. To view the other articles in this issue visit http://dx.doi.org/10.1111/bph.2011.164.issue-4 PMID:21470204

  3. The effects of acute levodopa withdrawal on motor performance and dopaminergic receptor sensitivity in patients with Parkinson's disease.

    PubMed Central

    Turjanski, N; Fernandez, W; Lees, A J

    1993-01-01

    The effects of acute levodopa withdrawal were studied in nine patients with levodopa related on-off oscillations. One patient withdrew from the study due to off period confusion and hallucinations. A marked deterioration in motor disability occurred in all patients following overnight withdrawal of levodopa and a further mild delayed deterioration was present over a mean withdrawal period of 44 hours. Patients with more severe disease were able to tolerate levodopa withdrawal for a shorter period of time than those with milder disease severity. The minimum therapeutic dose of subcutaneous apomorphine needed to produce a similar improvement in patients' mobility, before and after several days of drug withdrawal, did not differ, thus providing no clinical evidence for alterations in striatal dopamine receptor sensitivity after acute levodopa withdrawal. PMID:8331352

  4. Aggression and increased glutamate in the mPFC during withdrawal from intermittent alcohol in outbred mice

    PubMed Central

    Hwa, Lara S.; Nathanson, Anna J.; Shimamoto, Akiko; Tayeh, Jillian K.; Wilens, Allison R.; Holly, Elizabeth N.; Newman, Emily L.; DeBold, Joseph F.; Miczek, Klaus A.

    2015-01-01

    Rationale Disrupted social behavior, including occasional aggressive outbursts, is characteristic of withdrawal from long-term alcohol (EtOH) use. Heavy EtOH use and exaggerated responses during withdrawal may be treated using glutamatergic N-methyl-D-aspartate receptor (NMDAR) antagonists. Objectives The current experiments explore aggression and medial prefrontal cortex (mPFC) glutamate as consequences of withdrawal from intermittent access to EtOH, and changes in aggression and mPFC glutamate caused by NMDAR antagonists memantine and ketamine. Methods Swiss male mice underwent withdrawal following 1-8 weeks of intermittent access to 20% EtOH. Aggressive and non-aggressive behaviors with a conspecific were measured 6-8 h into EtOH withdrawal after memantine or ketamine (0-30 mg/kg, i.p.) administration. In separate mice, extracellular mPFC glutamate after memantine was measured during withdrawal using in vivo microdialysis. Results At 6-8 h withdrawal from EtOH, mice exhibited more convulsions and aggression, and decreased social contact compared to age-matched water controls. Memantine, but not ketamine, increased withdrawal aggression at the 5 mg/kg dose in mice with a history of 8 weeks EtOH but not 1 or 4 weeks of EtOH or in water drinkers. Tonic mPFC glutamate was higher during withdrawal after 8 weeks EtOH compared to 1 week EtOH or 8 weeks water. Five mg/kg memantine increased glutamate in 8 week EtOH mice, but also in 1 week EtOH and water drinkers. Conclusions These studies reveal aggressive behavior as a novel symptom of EtOH withdrawal in outbred mice and confirm a role of NMDARs during withdrawal aggression and for disrupted social behavior. PMID:25899790

  5. Hostility as a Predictor of Affective Changes During Acute Tobacco Withdrawal

    PubMed Central

    Quinn, Austin; Sekimura, Stephanie

    2014-01-01

    Introduction: Hostility—a personality trait reflective of cynical attitudes and a general mistrust of others—is associated with smoking status and relapse risk. Yet, the mechanisms linking hostility and smoking are not entirely clear. In this lab study, we tested a socioaffective model that purports that high-hostility individuals smoke to cope with maladaptive social mood states (i.e., anger and low friendliness), which become expressed and exacerbated during acute tobacco withdrawal. Methods: Following a baseline visit at which trait hostility was assessed, adult smokers (n = 153, ≥10 cig/day) attended two counterbalanced lab visits: a deprived session following 16hr of deprivation, and a nondeprived session. At both lab visits, affect and withdrawal symptoms were assessed at a single time point. Results: Higher trait hostility predicted larger deprivation-induced increases in several forms of negative affect (anxiety, depression, confusion; βs ≥ .20, ps ≤ .01) and a composite tobacco withdrawal symptom index (β = .16, p = .04) but did not predict changes in positive emotions. These effects persisted after statistically controlling for gender, nicotine dependence, and depression. Other aspects of trait aggression (i.e., verbal aggression, physical aggression, anger) did not predict deprivation-induced changes in affect and withdrawal other than state anger. Discussion: High-hostility individuals appear to experience generalized exacerbations in several negative affective states during acute tobacco withdrawal. Increases in negative affect during tobacco withdrawal may motivate negative reinforcement-mediated smoking and could underlie tobacco addiction in high-hostility smokers. PMID:24113928

  6. Acute and chronic glue sniffing effects and consequences of withdrawal on aggressive behavior.

    PubMed

    Bouchatta, Otmane; Ouhaz, Zakaria; Ba-Mhamed, Saadia; Kerekes, Nóra; Bennis, Mohamed

    2016-05-01

    Drug abuse act on brain mechanisms that cause a high-risk individual to engage in aggressive and violent behavior. While a drug-violence relationship exists, the nature of this relationship is often complex, with intoxication, neurotoxic, and withdrawal effects often being confused and/or confounded. Glue sniffing is often a springboard to the abuse of more addictive drugs. Despite its high prevalence and serious consequences, we know relatively little about the aggressive behavioral effects of volatile inhalants abuse, especially glue. The aim of the present study was to investigate the link between the duration of glue exposure, a common substance abuse problem in Morocco, and the level of aggressive behavior during withdrawal. For this we used the isolation-induced aggression model "residents" in three groups of mice. The first group served as control resident animals (n=10, without exposure); the second group as experimental resident mice (n=10) tested before and after acute (first day) and chronic exposure to the glue, and at 1 and 2weeks of withdrawal; and the third group of 10 intruder animals. The results showed that the number of attacks decreased (halved) and the latency of the first attack increased (doubled) following acute glue sniffing. However, the effects of chronic exposure and of 1week of withdrawal led to an increase in the intensity of agonistic encounters. After 2weeks of withdrawal, the intensity of aggressive behavior decreased again. These results indicated that chronic glue exposure and the first week of withdrawal are associated with increased aggression in mice. PMID:26969766

  7. Manipulation of GABAergic Steroids: Sex Differences in the Effects on Alcohol Drinking- and Withdrawal-Related Behaviors

    PubMed Central

    Finn, Deborah A.; Beckley, Ethan H.; Kaufman, Katherine R.; Ford, Matthew M.

    2009-01-01

    Alcoholism is a complex disorder that represents an important contributor to health problems worldwide and that is difficult to encompass with a single preclinical model. Additionally, alcohol (ethanol) influences the function of many neurotransmitter systems, with the interaction at γ-aminobutyric acidA (GABAA) receptors being integral for ethanol's reinforcing and several withdrawal-related effects. Given that some steroid derivatives exert rapid membrane actions as potent positive modulators of GABAA receptors and exhibit a similar pharmacological profile to that of ethanol, studies in the laboratory manipulated GABAergic steroid levels and determined the impact on ethanol's rewarding- and withdrawal-related effects. Manipulations focused on the progesterone metabolite allopregnanolone (ALLO), since it is the most potent endogenous GABAergic steroid identified. The underlying hypothesis is that fluctuations in GABAergic steroid levels (and the resultant change in GABAergic inhibitory tone) alter sensitivity to ethanol, leading to changes in the positive motivational or withdrawal-related effects of ethanol. This review describes results that emphasize sex differences in the effects of ALLO and the manipulation of its biosynthesis on alcohol reward- versus withdrawal-related behaviors, with females being less sensitive to the modulatory effects of ALLO on ethanol-drinking behaviors but more sensitive to some steroid manipulations on withdrawal-related behaviors. These findings imply the existence of sex differences in the sensitivity of GABAA receptors to GABAergic steroids within circuits relevant to alcohol reward versus withdrawal. Thus, sex differences in the modulation of GABAergic neurosteroids may be an important consideration in understanding and developing therapeutic interventions in alcoholics. PMID:19615369

  8. Clinical applications of sodium oxybate (GHB): from narcolepsy to alcohol withdrawal syndrome.

    PubMed

    Busardò, F P; Kyriakou, C; Napoletano, S; Marinelli, E; Zaami, S

    2015-12-01

    Gamma-hydroxybutyrate (GHB) is a short chain fatty acid endogenously produced within the central nervous system (CNS) and acts as a precursor and metabolite of the inhibitory neurotransmitter γ-aminobutyric acid (GABA). Although, it is an illegal recreational drug of abuse, its sodium salt (sodium oxybate) has been utilized as a medication for a number of medical conditions. The first aim of this review was to focus on current applications of sodium oxybate for the treatment of narcolepsy, with a particular emphasis on the key symptoms of this disorder: cataplexy and excessive daytime sleepiness (EDS). Secondly, the effectiveness of sodium oxybate therapy for the treatment of alcohol withdrawal syndrome (AWS) and the maintenance of alcohol abstinence has been assessed. Nowadays, sodium oxybate is the first-line treatment for narcolepsy and it is highly effective in meliorating sleep architecture, decreasing EDS and the frequency of cataplexy attacks in narcoleptic patients. Sodium oxybate currently finds also application in the treatment of AWS and the maintenance of alcohol abstinence in alcoholics. Most of the studies evaluating the efficacy of GHB in the treatment of AWS use a dosage of 50 mg/kg divided in three or four administrations per day. Human studies showed that GHB (dose of 50 mg/kg, divided in three administrations per day) is capable to increase the number of abstinent days, reduce alcohol craving and decrease the number of drinks per day. However, there is limited randomized evidence and, thus, GHB cannot be reliably compared to clomethiazole or benzodiazepines. Some randomized data suggest that GHB is better than naltrexone and disulfiram regarding abstinence maintenance and prevention of craving in the medium term i.e. 3-12 months. It is recommended that GHB should be used only under strict medical supervision, since concerns about the abuse/misuse of the drug and the addiction potential have been arisen.

  9. Pharmacological Activation/Inhibition of the Cannabinoid System Affects Alcohol Withdrawal-Induced Neuronal Hypersensitivity to Excitotoxic Insults

    PubMed Central

    Rubio, Marina; Villain, Hélène; Docagne, Fabian; Roussel, Benoit D.; Ramos, José Antonio; Vivien, Denis; Fernandez-Ruiz, Javier; Ali, Carine

    2011-01-01

    Cessation of chronic ethanol consumption can increase the sensitivity of the brain to excitotoxic damages. Cannabinoids have been proposed as neuroprotectants in different models of neuronal injury, but their effect have never been investigated in a context of excitotoxicity after alcohol cessation. Here we examined the effects of the pharmacological activation/inhibition of the endocannabinoid system in an in vitro model of chronic ethanol exposure and withdrawal followed by an excitotoxic challenge. Ethanol withdrawal increased N-methyl-D-aspartate (NMDA)-evoked neuronal death, probably by altering the ratio between GluN2A and GluN2B NMDA receptor subunits. The stimulation of the endocannabinoid system with the cannabinoid agonist HU-210 decreased NMDA-induced neuronal death exclusively in ethanol-withdrawn neurons. This neuroprotection could be explained by a decrease in NMDA-stimulated calcium influx after the administration of HU-210, found exclusively in ethanol-withdrawn neurons. By contrast, the inhibition of the cannabinoid system with the CB1 receptor antagonist rimonabant (SR141716) during ethanol withdrawal increased death of ethanol-withdrawn neurons without any modification of NMDA-stimulated calcium influx. Moreover, chronic administration of rimonabant increased NMDA-stimulated toxicity not only in withdrawn neurons, but also in control neurons. In summary, we show for the first time that the stimulation of the endocannabinoid system is protective against the hyperexcitability developed during alcohol withdrawal. By contrast, the blockade of the endocannabinoid system is highly counterproductive during alcohol withdrawal. PMID:21886913

  10. Acute anti-emetic withdrawal associated with a hemorrhagic cerebellar arteriovenous malformation.

    PubMed

    Vadivelu, S; Tomlinson, K; Valles, J; Hundert, M; Bagdonas, R; Eisenberg, M

    2010-08-01

    We present a 67-year-old right-handed male with a brachium pontis arteriovenous malformation on continuous anti-emetic therapy who demonstrated acute withdrawal symptoms after the abrupt discontinuation of ondansetron, a 5-HT(3) receptor antagonist. Removal of anti-emetic therapy led to the development of extreme flushing and tremor, but subsequent return of ondansetron resulted in the resolution of these symptoms. This is the first clinical report demonstrating acute withdrawal from an anti-emetic agent and we further highlight the need for future studies evaluating not only arterial supply with pressure gradients and anatomical location, but also the association with periventricular venous drainage, venous drainage stenosis, and mass effect from venous stasis as this may contribute partly to the sensitivity of the serotonergic receptors seen here. PMID:20488707

  11. 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

  12. 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

  13. Ethical and Legal Aspects of Conducting Clinical Trials in Alcohol Withdrawal Syndrome

    PubMed Central

    R, Harsha

    2014-01-01

    Alcohol Withdrawal Syndrome (AWS) is a condition where the patients will be mentally unstable initially and where later, with therapy, they gradually return to normalcy. As AWS comprises two stages; a mentally unstable state and a normal state of mind, the ethical and legal issues behind recruitment of these subjects become a little ambiguous in a clinical trial. This study was taken up to clarify the uncertainty regarding the biphasic states of minds (i.e. unstable mind and sound mind) of the subjects who were involved in a clinical trial done on AWS. Law and ethics regarding the clinical trials which involve psychiatric subjects need to be strengthened and amended from time to time, in order to protect the interests of both patients and physicians. PMID:24995195

  14. [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.

  15. 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

  16. 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.

  17. Opium tincture versus methadone syrup in management of acute raw opium withdrawal: A randomized, double-blind, controlled trial.

    PubMed

    Tabassomi, Farzaneh; Zarghami, Mehran; Shiran, Mohammad-Reza; Farnia, Samaneh; Davoodi, Mohsen

    2016-01-01

    The aim of this study was to evaluate the effectiveness of opium tincture versus methadone syrup in the management of acute withdrawal syndrome in opium dependent patients during the detoxification period. In this double-blind randomized controlled study, a total of 74 adult male raw opium dependent patients were treated with opium tincture or methadone syrup 2 times daily for 5 consecutive days. Detoxification was initiated by tapered dose reductions to reach abstinence. At the end of the 10th day, the medications were discontinued. The Objective Opioid Withdrawal Scale was used to assess withdrawal symptoms every day. Significant decreases on the Objective Opioid Withdrawal Scale were found for both treatment methods during the study period (p < .0001). However, there was no significant difference between groups on the total Objective Opioid Withdrawal Scale, and adverse effects existed. Opium tincture can be considered as a potential substitute for methadone syrup for suppression of raw opium withdrawal symptoms, with minimal adverse effects.

  18. Opium tincture versus methadone syrup in management of acute raw opium withdrawal: A randomized, double-blind, controlled trial.

    PubMed

    Tabassomi, Farzaneh; Zarghami, Mehran; Shiran, Mohammad-Reza; Farnia, Samaneh; Davoodi, Mohsen

    2016-01-01

    The aim of this study was to evaluate the effectiveness of opium tincture versus methadone syrup in the management of acute withdrawal syndrome in opium dependent patients during the detoxification period. In this double-blind randomized controlled study, a total of 74 adult male raw opium dependent patients were treated with opium tincture or methadone syrup 2 times daily for 5 consecutive days. Detoxification was initiated by tapered dose reductions to reach abstinence. At the end of the 10th day, the medications were discontinued. The Objective Opioid Withdrawal Scale was used to assess withdrawal symptoms every day. Significant decreases on the Objective Opioid Withdrawal Scale were found for both treatment methods during the study period (p < .0001). However, there was no significant difference between groups on the total Objective Opioid Withdrawal Scale, and adverse effects existed. Opium tincture can be considered as a potential substitute for methadone syrup for suppression of raw opium withdrawal symptoms, with minimal adverse effects. PMID:26566681

  19. The Associations between Self-Consciousness, Depressive State and Craving to Drink among Alcohol Dependent Patients Undergoing Protracted Withdrawal

    PubMed Central

    Denoël, Catherine; Hebborn, Ludger; Derely, Marc; Desseilles, Martin; Luminet, Olivier

    2013-01-01

    Context In order to understand how certain personality traits influence the relation between depression symptoms and craving for alcohol, trait self-consciousness (trait SC) was examined during a withdrawal and detoxification program. Methods Craving (Obsessive and Compulsive Drinking Scale), depressive state (Beck Depression Inventory) and trait SC (Revised Self-Consciousness Scale) were assessed in alcohol-dependent inpatients (DSM-IV, N = 30) both at the beginning (T1: day 1 or 2) and at the end (T2: day 14 to18) of protracted withdrawal during rehabilitation. Results A significant decrease in craving and depressive symptoms was observed from T1 to T2, while SC scores remained stable. At both times, strong positive correlations were observed between craving and depression. Moreover, regression analyses indicated that trait SC significantly moderated the impact of depression on cravings for alcohol. Limitations This study was performed on a relatively small sample size. Administration of medications during detoxification treatment can also be a confounding factor. Finally, craving could have been evaluated through other types of measurements. Conclusions During protracted withdrawal, alcohol craving decreased with the same magnitude as depressive mood. Depressive symptoms were related to alcohol craving but only among patients with high trait SC scores. Our results suggest that metacognitive approaches targeting SC could decrease craving and, in turn, prevent future relapses. PMID:24013131

  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. Attenuation of acute morphine withdrawal in the neonatal rat by the competitive NMDA receptor antagonist LY235959.

    PubMed

    Jones, Kathy L; Zhu, Hongbo; Jenab, Shirzad; Du, Ted; Inturrisi, Charles E; Barr, Gordon A

    2002-03-01

    The present study examined the ability of LY235959, a competitive N-methyl-D-aspartate (NMDA) receptor antagonist, to attenuate behaviors and c-fos mRNA expression associated with acute morphine withdrawal in the infant rat. Rat pups were given a single dose of morphine (10.0 mg/kg, s.c.) or saline. Two hours later, pups were removed from the dam and injected with either LY235959 (10.0 mg/kg, s.c.) or saline. Fifteen minutes later acute morphine withdrawal was precipitated with naltrexone (10.0 mg/kg, s.c.) and behaviors were recorded every 15 s for the next 60 min. Immediately after behavioral testing, brain and spinal cord were assayed for c-fos mRNA analysis by solution hybridization. The intensity of the morphine withdrawal syndrome was reduced in pups pre-treated with LY235959. Withdrawal behaviors such as head moves, moving paws, rolling, and walking were decreased, and vocalizations were completely eliminated in pups pre-treated with LY2359559. Acute morphine withdrawal increased c-fos mRNA expression in the brain and the spinal cord, which was attenuated by pre-treatment of LY235959. Thus, in the 7-day-old rat, as in the adult, NMDA receptors play a role in the behavioral and molecular manifestations of acute morphine withdrawal. PMID:11850145

  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. 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

  4. 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

  5. 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

  6. Effects of age, but not sex, on elevated startle during withdrawal from acute morphine in adolescent and adult rats.

    PubMed

    Radke, Anna K; Gewirtz, Jonathan C; Carroll, Marilyn E

    2015-08-01

    Investigations into animal models of drug withdrawal have largely found that emotional signs of withdrawal (e.g. anxiety, anhedonia, and aversion) in adolescents are experienced earlier and less severely than in their adult counterparts. The majority of these reports have examined withdrawal from ethanol or nicotine. To expand our knowledge about the emotional withdrawal state in adolescent rats, we used potentiation of the acoustic startle reflex after an acute dose of morphine (10 mg/kg, subcutaneously) as a measure of opiate withdrawal. Startle was measured at four time points after morphine injection (2, 3, 4, and 5 h) in 28-day-old and 90-day-old male and female rats. The results of this experiment revealed that peak potentiation of the startle reflex occurred at 3 h in the adolescent rats and at 5 h in the adult rats, and that the magnitude of withdrawal was larger in the adults. No sex differences were observed. Overall, these results affirm that, similar to withdrawal from ethanol and nicotine, opiate withdrawal signs are less severe in adolescent than in adult rats.

  7. Effects of age, but not sex, on elevated startle during withdrawal from acute morphine in adolescent and adult rats

    PubMed Central

    Radke, Anna K.; Gewirtz, Jonathan C.; Carroll, Marilyn E.

    2015-01-01

    Investigations into animal models of drug withdrawal have largely found that emotional signs of withdrawal (e.g., anxiety, anhedonia, and aversion) in adolescents are experienced earlier and less severely than in their adult counterparts. The majority of these reports have examined withdrawal from ethanol or nicotine. In order to expand our knowledge about the emotional withdrawal state in adolescent rats, we used potentiation of the acoustic startle reflex after an acute dose of morphine (10 mg/kg, s.c.) as a measure of opioid withdrawal. Startle was measured at four time points after morphine injection (2, 3, 4, and 5 h) in 28 and 90 day old male and female rats. The results of this experiment revealed that peak potentiation of the startle reflex occurred at 3 h in the adolescent rats and at 5 h in the adult rats, and that the magnitude of withdrawal was larger in the adults. No sex differences were observed. Overall, these results affirm that, similar to withdrawal from ethanol and nicotine, opiate withdrawal signs are less severe in adolescent than in adult rats. PMID:26154436

  8. Adverse Effects of Synthetic Cannabinoids: Management of Acute Toxicity and Withdrawal.

    PubMed

    Cooper, Ziva D

    2016-05-01

    Although several chemical structural classes of synthetic cannabinoids (SCs) were recently classified as Schedule I substances, rates of use and cases of serious toxic effects remain high. While case reports and media bring attention to severe SC toxicity, daily SC use resulting in dependence and withdrawal is a significant concern that is often overlooked when discussing the risks of these drugs. There is a rich literature on evidence-based approaches to treating substance use disorders associated with most abused drugs, yet little has been published regarding how to best treat symptoms related to SC dependence given its recency as an emerging clinically significant issue. This review provides a background of the pharmacology of SCs, recent findings of adverse effects associated with both acute intoxication and withdrawal as a consequence of daily use, and treatment approaches that have been implemented to address these issues, with an emphasis on pharmacotherapies for managing detoxification. In order to determine prevalence of use in cannabis smokers, a population at high risk for SC use, we obtained data on demographics of SC users, frequency of use, and adverse effects over a 3.5-year period (2012-2015) in the New York City metropolitan area, a region with a recent history of high SC use. While controlled studies on the physiological and behavioral effects of SCs are lacking, it is clear that risks associated with using these drugs pertain not only to the unpredictable and severe nature of acute intoxication but also to the effects of long-term, chronic use. Recent reports in the literature parallel findings from our survey, indicating that there is a subset of people who use SCs daily. Although withdrawal has not been systematically characterized and effective treatments have yet to be elucidated, some symptom relief has been reported with benzodiazepines and the atypical antipsychotic, quetiapine. Given the continued use and abuse of SCs, empirical studies

  9. Adverse Effects of Synthetic Cannabinoids: Management of Acute Toxicity and Withdrawal

    PubMed Central

    2016-01-01

    Although several chemical structural classes of synthetic cannabinoids (SCs) were recently classified as Schedule I substances, rates of use and cases of serious toxic effects remain high. While case reports and media bring attention to severe SC toxicity, daily SC use resulting in dependence and withdrawal is a significant concern that is often overlooked when discussing the risks of these drugs. There is a rich literature on evidence-based approaches to treating substance use disorders associated with most abused drugs, yet little has been published regarding how to best treat symptoms related to SC dependence given its recency as an emerging clinically significant issue. This review provides a background of the pharmacology of SCs, recent findings of adverse effects associated with both acute intoxication and withdrawal as a consequence of daily use, and treatment approaches that have been implemented to address these issues, with an emphasis on pharmacotherapies for managing detoxification. In order to determine prevalence of use in cannabis smokers, a population at high risk for SC use, we obtained data on demographics of SC users, frequency of use, and adverse effects over a 3.5-year period (2012–2015) in the New York City metropolitan area, a region with a recent history of high SC use. While controlled studies on the physiological and behavioral effects of SCs are lacking, it is clear that risks associated with using these drugs pertain not only to the unpredictable and severe nature of acute intoxication but also to the effects of long-term, chronic use. Recent reports in the literature parallel findings from our survey, indicating that there is a subset of people who use SCs daily. Although withdrawal has not been systematically characterized and effective treatments have yet to be elucidated, some symptom relief has been reported with benzodiazepines and the atypical antipsychotic, quetiapine. Given the continued use and abuse of SCs, empirical studies

  10. Adverse Effects of Synthetic Cannabinoids: Management of Acute Toxicity and Withdrawal.

    PubMed

    Cooper, Ziva D

    2016-05-01

    Although several chemical structural classes of synthetic cannabinoids (SCs) were recently classified as Schedule I substances, rates of use and cases of serious toxic effects remain high. While case reports and media bring attention to severe SC toxicity, daily SC use resulting in dependence and withdrawal is a significant concern that is often overlooked when discussing the risks of these drugs. There is a rich literature on evidence-based approaches to treating substance use disorders associated with most abused drugs, yet little has been published regarding how to best treat symptoms related to SC dependence given its recency as an emerging clinically significant issue. This review provides a background of the pharmacology of SCs, recent findings of adverse effects associated with both acute intoxication and withdrawal as a consequence of daily use, and treatment approaches that have been implemented to address these issues, with an emphasis on pharmacotherapies for managing detoxification. In order to determine prevalence of use in cannabis smokers, a population at high risk for SC use, we obtained data on demographics of SC users, frequency of use, and adverse effects over a 3.5-year period (2012-2015) in the New York City metropolitan area, a region with a recent history of high SC use. While controlled studies on the physiological and behavioral effects of SCs are lacking, it is clear that risks associated with using these drugs pertain not only to the unpredictable and severe nature of acute intoxication but also to the effects of long-term, chronic use. Recent reports in the literature parallel findings from our survey, indicating that there is a subset of people who use SCs daily. Although withdrawal has not been systematically characterized and effective treatments have yet to be elucidated, some symptom relief has been reported with benzodiazepines and the atypical antipsychotic, quetiapine. Given the continued use and abuse of SCs, empirical studies

  11. [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.

  12. The discriminative stimulus properties of ethanol and acute ethanol withdrawal states in rats.

    PubMed

    Gauvin, D V; Harland, R D; Criado, J R; Michaelis, R C; Holloway, F A

    1989-10-01

    Twelve male Sprague-Dawley rats were trained in a standard two-choice Drug 1-Drug 2 discrimination task utilizing 3.0 mg/kg chlordiazepoxide (CDP, an anxiolytic drug) and 20 mg/kg pentylenetetrazol (PTZ, an anxiogenic drug) as discriminative stimuli under a VR 5-15 schedule of food reinforcement. Saline tests conducted at specific time points after acute high doses of ethanol (3.0 and 4.0 g/kg) indicated a delayed rebound effect, evidenced by a shift to PTZ-appropriate responding. Insofar as such a shift in lever selection indexes a delayed anxiety-like state, this acute 'withdrawal' reaction can be said to induce an affective state similar to that seen with chronic ethanol withdrawal states. Ethanol generalization tests: (1) resulted in a dose- and time-dependent biphasic generalization to CDP, (2) failed to block the PTZ stimulus and (3) failed to block the time- and dose-dependent elicitation of an ethanol-rebound effect. These data suggest that ethanol's anxiolytic effects are tenuous. PMID:2791886

  13. The TTTAn aromatase (CYP19A1) polymorphism is associated with compulsive craving of male patients during alcohol withdrawal.

    PubMed

    Lenz, Bernd; Heberlein, Annemarie; Bayerlein, Kristina; Frieling, Helge; Kornhuber, Johannes; Bleich, Stefan; Hillemacher, Thomas

    2011-09-01

    Alcoholism is associated with alterations of the hypothalamus-pituitary-gonadal hormone axis. We recently reported a leptin-mediated relation between the CAGn polymorphism of the androgen receptor and craving during alcohol withdrawal. This study investigated whether the TTTAn polymorphism of the aromatase (CYP19A1) is equally linked to craving. An association between TTTAn and compulsive craving (p=0.029) was revealed in our sample of 118 male alcohol addicts at day of hospital admission. Genotype-dependent subgroups showed differences in that the patients with short alleles suffered from lower compulsive craving during withdrawal than those with the longer alleles (p=0.027). The additional inclusion of leptin revealed no further significant association in the present study. Our finding is a further step on the way to elucidate the genesis of craving for alcohol with its extensive underlying interactions of different genetic and non-genetic factors. Future investigations should enrol women and consider sex hormone levels for further clarification of the observed TTTAn-craving relationship.

  14. Polymorphism of the long polyglutamine tract in the human androgen receptor influences craving of men in alcohol withdrawal.

    PubMed

    Lenz, Bernd; Jacob, Claudia; Frieling, Helge; Jacobi, Andrea; Hillemacher, Thomas; Muschler, Marc; Watson, Kathryn; Kornhuber, Johannes; Bleich, Stefan

    2009-08-01

    Until recently, genetic mechanisms influencing craving in alcohol withdrawal were poorly understood. Studies show that alcoholism is associated with dysregulation of sexual hormones. The androgen receptor is encoded by the trinucleotide repeat CAG. Long repeat regions have been shown to inhibit interactions between the androgen receptor and different co-activators. The aim of the present study was to determine whether or not this trinucleotide repeat is involved in the pathogenesis of alcohol dependence, withdrawal and craving. We included 112 male inpatients who were admitted for detoxification treatment. To measure the extent of craving we used the Obsessive Compulsive Drinking Scale on the day of hospital admission. Regarding total and obsessive craving we found a significant negative correlation for the androgen receptor repeat length. No significant difference between the group of patients and the control group was found. We found that reduced length of the investigated trinucleotide repeat might aggravate craving symptoms. Moreover, an elevated number of repeats might be protective against severe craving. In summary, the presented data points to an underestimated role of the genetic regulation of androgens in the pathogenesis of alcohol dependence and related disorders.

  15. [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.

  16. 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

  17. Effects of Beta-Blocker Withdrawal in Acute Decompensated Heart Failure

    PubMed Central

    Prins, Kurt W.; Neill, John M.; Tyler, John O.; Eckman, Peter M.; Duval, Sue

    2015-01-01

    OBJECTIVES This study sought to evaluate the effects of beta-blocker withdrawal in acute decompensated heart failure (ADHF). BACKGROUND Published reports showed trends for either no harm or increased risk of in-hospital mortality, short-term mortality, and rehospitalization rates in patients admitted for ADHF that discontinued beta-blockers; however, a comprehensive analysis has not been conducted. METHODS Relevant studies from January 2000 through January 2015 were identified in the PubMed, EMBASE, and COCHRANE electronic databases. Where appropriate data were available, weighted relative risks were estimated using random-effects meta-analysis techniques. RESULTS Five observational studies and 1 randomized clinical trial (n = 2,704 patients who continued beta-blocker therapy and n = 439 patients who discontinued beta-blocker therapy) that reported the short-term effects of beta-blocker withdrawal in ADHF were included in the analyses. In 2 studies, beta-blocker withdrawal significantly increased risk of in-hospital mortality (risk ratio: 3.72; 95% confidence interval [CI]: 1.51 to 9.14). Short-term mortality (relative risk: 1.61; 95% CI: 1.04 to 2.49; 4 studies) and combined short-term rehospitalization or death (relative risk: 1.59; 95% CI: 1.03 to 2.45; 4 studies) were also significantly increased. CONCLUSIONS Discontinuation of beta-blockers in patients admitted with ADHF was associated with significantly increased in-hospital mortality, short-term mortality, and the combined endpoint of short-term rehospitalization or mortality. These data suggest beta-blockers should be continued in ADHF patients if their clinical picture allows. PMID:26251094

  18. Hypothalamic-pituitary-gonadal axis, prolactin, and cortisol in alcoholics during withdrawal and after three weeks of abstinence: comparison with healthy control subjects.

    PubMed

    Heinz, A; Rommelspacher, H; Gräf, K J; Kürten, I; Otto, M; Baumgartner, A

    1995-01-31

    Serum concentrations of luteinizing hormone, follicle-stimulating hormone, testosterone, androstenedione, estradiol, sex hormone-binding globulin, cortisol, and prolactin were measured in 12 male chronic alcoholics once during withdrawal and once after 21 days of abstinence. The results were compared with those of 14 healthy volunteers. During withdrawal, luteinizing hormone, estradiol, and cortisol levels were significantly enhanced. Estradiol and cortisol concentrations fell significantly during abstinence, whereas luteinizing hormone concentrations remained elevated. The results may be interpreted as follows: the well-known inhibitory effect of alcohol on the biosynthesis of testosterone may have led to a compensatory increase in luteinizing hormone secretion, so that normal serum concentrations of testosterone were maintained. On the other hand, peripheral conversion from androstenedione to estradiol via aromatase pathways seemed to be enhanced in chronic alcoholics, at least during withdrawal. Whether this marked increase in estradiol concentrations is implicated in different clinical and psychological symptoms seen in chronic alcoholics remains to be investigated.

  19. Involvement of tissue plasminogen activator in stress responsivity during acute cocaine withdrawal in mice.

    PubMed

    Zhou, Yan; Maiya, Rajani; Norris, Erin H; Kreek, Mary Jeanne; Strickland, Sidney

    2010-11-01

    There is evidence that increased release of corticotropin-releasing factor (CRF) in the central nucleus of the amygdala (CeA) contributes to stress responsivity during cocaine withdrawal (WD). Recent studies suggest that tissue plasminogen activator (tPA) in the CeA is a downstream effector protein for CRF after acute "binge" cocaine administration. The purpose of this study was to determine if tPA modulates cocaine WD-induced stress responsivity. Wild-type (WT) and tPA-deficient (tPA - / - ) mice were subjected to chronic (14 days) "binge" cocaine (45 mg/kg per day) or its acute (1 day) WD. Extracellular tPA activity, CRF mRNA levels, and plasma corticosterone (CORT) levels were measured in tPA - / -  and WT mice. Extracellular tPA activity was reduced by 50% in the CeA and medial amygdala of WT mice after chronic cocaine and returned to basal levels after acute WD. Unlike WT mice, tPA - / -  mice did not display elevated amygdalar CRF mRNA levels during cocaine WD. In comparison to WT mice, tPA - / -  mice showed a blunted plasma CORT response during acute WD. These results demonstrate that tPA activity in the amygdala (Amy) is altered by chronic cocaine exposure, and further suggest an involvement of tPA in modulating amygdalar CRF stress responsive system and hypothalamic-pituitary-adrenal axis in response to acute cocaine WD.

  20. Involvement of tissue plasminogen activator in stress responsivity during acute cocaine withdrawal in mice

    PubMed Central

    Zhou, Yan; Maiya, Rajani; Norris, Erin H.; Kreek, Mary Jeanne; Strickland, Sidney

    2013-01-01

    There is evidence that increased release of corticotropin-releasing factor (CRF) in the central nucleus of the amygdala (CeA) contributes to stress responsivity during cocaine withdrawal (WD). Recent studies suggest that tissue plasminogen activator (tPA) in the CeA is a downstream effector protein for CRF after acute “binge” cocaine administration. The purpose of this study was to determine if tPA modulates cocaine WD-induced stress responsivity. Wild-type (WT) and tPA-deficient (tPA −/−) mice were subjected to chronic (14 days) “binge” cocaine (45 mg/kg per day) or its acute (1 day) WD. Extracellular tPA activity, CRF mRNA levels, and plasma corticosterone (CORT) levels were measured in tPA −/− and WT mice. Extracellular tPA activity was reduced by 50% in the CeA and medial amygdala of WT mice after chronic cocaine and returned to basal levels after acute WD. Unlike WT mice, tPA −/− mice did not display elevated amygdalar CRF mRNA levels during cocaine WD. In comparison to WT mice, tPA −/− mice showed a blunted plasma CORT response during acute WD. These results demonstrate that tPA activity in the amygdala (Amy) is altered by chronic cocaine exposure, and further suggest an involvement of tPA in modulating amygdalar CRF stress responsive system and hypothalamic–pituitary–adrenal axis in response to acute cocaine WD. PMID:20666641

  1. Acute effects of moderate intensity aerobic exercise on affective withdrawal symptoms and cravings among women smokers.

    PubMed

    Williams, David M; Dunsiger, Shira; Whiteley, Jessica A; Ussher, Michael H; Ciccolo, Joseph T; Jennings, Ernestine G

    2011-08-01

    A growing number of laboratory studies have shown that acute bouts of aerobic exercise favorably impact affect and cravings among smokers. However, randomized trials have generally shown exercise to have no favorable effect on smoking cessation or withdrawal symptoms during quit attempts. The purpose of the present study was to explore this apparent contradiction by assessing acute changes in affect and cravings immediately prior to and following each exercise and contact control session during an eight-week smoking cessation trial. Sixty previously low-active, healthy, female smokers were randomized to an eight-week program consisting of brief baseline smoking cessation counseling and the nicotine patch plus either three sessions/week of moderate intensity aerobic exercise or contact control. Findings revealed a favorable impact of exercise on acute changes in positive activated affect (i.e., energy), negative deactivated affect (i.e., tiredness), and cigarette cravings relative to contact control. However, effects dissipated from session to session. Results suggest that aerobic exercise has potential as a smoking cessation treatment, but that it must be engaged in frequently and consistently over time in order to derive benefits. Thus, it is not surprising that previous randomized controlled trials-in which adherence to exercise programs has generally been poor-have been unsuccessful in showing effects of aerobic exercise on smoking cessation outcomes.

  2. Amphetamine and morphine may produce acute-withdrawal related hypoactivity by initially activating a common dopamine pathway.

    PubMed

    White, Wesley; White, Ilsun M

    2016-10-15

    Rats given drugs of abuse such as amphetamine or morphine show longer-term effects, that is, signs of acute withdrawal, including hypoactivity, hypophagia, and blunted affect, sometime between 12 and 24h after treatment. This research explores the possibility that signs of acute withdrawal produced by different drugs of abuse are instigated by overlapping mechanisms. The specific objectives of the research were to see if amphetamine and morphine produced longer-term hypoactivity, and to see if any longer-term hypoactivity elicited by the drugs could be blocked by SCH23390, a dopamine D1 antagonist. Six groups of rats, with eight rats in each group, were exposed to a series of five-day tests. Near light onset of Test Day 1, each animal was given control administrations, consisting of a saline treatment (1.0ml/kg) followed 30m later by a saline posttreatment, and locomotor activity was monitored for the next 24h. On Test Day 3, each animal was given experimental administrations, and locomotor activity was again monitored for 24h. Each group received only one combination of experimental administrations across tests. Experimental administrations consisted of saline, amphetamine (2.0mg/kg), or morphine (5.0mg/kg), followed by saline or SCH23390 (0.05mg/kg). All administrations were subcutaneous. Amphetamine and morphine produced longer-term hypoactivity, having similar time courses and magnitudes. SCH23390 blocked the longer-term hypoactivity produced by both drugs. Saline and SCH23390 produced no changes in longer-term activity in their own right. The time course of amphetamine-elicited longer-term hypoactivity resembled that of amphetamine-elicited longer-term hypophagia observed in a prior study. Approximately 1/4 of the animals given amphetamine or morphine did not show longer-term hypoactivity ("low withdrawal" rats). Amphetamine and morphine may initiate the cascade of events resulting in signs of acute withdrawal by producing activation in a common pathway that

  3. 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.

  4. 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

  5. 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

  6. Repeated experience with naloxone facilitates acute morphine withdrawal: potential role for conditioning processes in acute opioid dependence.

    PubMed

    Schulteis, Gery; Morse, Andrew C; Liu, Jian

    2003-12-01

    Single injections with morphine can induce a state of acute opioid dependence in humans and animals, typically measured as precipitated withdrawal when an antagonist such as naloxone is administered 4-24 h after morphine. Repeated treatment with morphine at 24-h intervals can result in a progressive shift in potency of naloxone to produce such acute withdrawal signs, including suppression of operant responding for food reward. The current study characterized fully both morphine and naloxone dose-effect functions in an effort to establish the relative contributions of repeated morphine vs. repeated naloxone (Nal) experience to these potency shifts. Rats trained on an FR15 schedule for food received four vehicle or morphine injections (0.56-5.6 mg/kg sc), spaced 24 h apart. Four hours after each morphine pretreatment (Repeat Nal), or 4 h after the fourth and final morphine pretreatment only (Single Nal), a cumulative dose-effect function for naloxone-induced suppression of responding was determined. Vehicle-pretreated (Morphine Naive) rats showed little change in the naloxone dose effect function even after four cumulative dose-effect determinations. By contrast, a progressive increase in naloxone potency was observed following successive pretreatments with morphine under Repeat Nal conditions, and the magnitude of naloxone potency shift was morphine dose dependent. At a morphine dose of 5.6 mg/kg, repeated naloxone experience in the presence of morphine was not an absolute requirement to produce an increase in naloxone potency across days, but repeated naloxone could potentiate the magnitude of the observed shift, indicating both experience-independent and experience-dependent processes at work. At lower doses of morphine (1.0 and 3.3 mg/kg) no shift in naloxone potency was observed across days of morphine treatment in the absence of repeated naloxone experience (Single Nal conditions), indicating an increasing contribution of naloxone experience-dependent processes

  7. 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.

  8. 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

  9. Activation of adenosine A1 receptors reduces anxiety-like behavior during acute ethanol withdrawal (hangover) in mice.

    PubMed

    Prediger, Rui D S; da Silva, George E; Batista, Luciano C; Bittencourt, Alvorita L; Takahashi, Reinaldo N

    2006-10-01

    Elevated signs of anxiety are observed in both humans and rodents during withdrawal from chronic as well as acute ethanol exposure, and it represents an important motivational factor for ethanol relapse. Several reports have suggested the involvement of brain adenosine receptors in different actions produced by ethanol such as motor incoordination and hypnotic effects. In addition, we have recently demonstrated that adenosine A1 receptors modulate the anxiolytic-like effect induced by ethanol in mice. In the present study, we evaluated the potential of adenosine A1 and A2A receptor agonists in reducing the anxiety-like behavior during acute ethanol withdrawal (hangover) in mice. Animals received a single intraperitoneal administration of saline or ethanol (4 g/kg) and were tested in the elevated plus maze after an interval of 0.5-24 h. The results indicated that hangover-induced anxiety was most pronounced between 12 and 18 h after ethanol administration, as indicated by a significant reduction in the exploration of the open arms of the maze. At this time interval, ethanol was completely cleared. The acute administration of 'nonanxiolytic' doses of adenosine and the selective adenosine A1 receptor agonist 2-chloro-N6-cyclopentyladenosine (CCPA), but not the adenosine A2A receptor agonist N6-[2-(3,5-dimethoxyphenyl)-2-(2-methylphenyl)ethyl]adenosine (DPMA), at the onset of peak withdrawal (18 h), reduced this anxiogenic-like response. In addition, the effect of CCPA on the anxiety-like behavior of ethanol hangover was reversed by pretreatment with the selective adenosine A1 receptor antagonist 8-cyclopentyl-1,3-dipropylxanthine (DPCPX). These results reinforce the notion of the involvement of adenosine receptors in the anxiety-like responses and indicate the potential of adenosine A1 receptor agonists to reduce the anxiogenic effects during ethanol withdrawal.

  10. 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

  11. 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'.

  12. 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.

  13. Alcohol Withdrawal-Induced Seizure Susceptibility is Associated with an Upregulation of CaV1.3 Channels in the Rat Inferior Colliculus

    PubMed Central

    Akinfiresoye, Luli R.; Allard, Joanne S.; Lovinger, David M.

    2015-01-01

    Background: We previously reported increased current density through L-type voltage-gated Ca2+ (CaV1) channels in inferior colliculus (IC) neurons during alcohol withdrawal. However, the molecular correlate of this increased CaV1 current is currently unknown. Methods: Rats received three daily doses of ethanol every 8 hours for 4 consecutive days; control rats received vehicle. The IC was dissected at various time intervals following alcohol withdrawal, and the mRNA and protein levels of the CaV1.3 and CaV1.2 α1 subunits were measured. In separate experiments, rats were tested for their susceptibility to alcohol withdrawal–induced seizures (AWS) 3, 24, and 48 hours after alcohol withdrawal. Results: In the alcohol-treated group, AWS were observed 24 hours after withdrawal; no seizures were observed at 3 or 48 hours. No seizures were observed at any time in the control-treated rats. Compared to control-treated rats, the mRNA level of the CaV1.3 α1 subunit was increased 1.4-fold, 1.9-fold, and 1.3-fold at 3, 24, and 48 hours, respectively. In contrast, the mRNA level of the CaV1.2 α1 subunit increased 1.5-fold and 1.4-fold at 24 and 48 hours, respectively. At 24 hours, Western blot analyses revealed that the levels of the CaV1.3 and CaV1.2 α1 subunits increased by 52% and 32%, respectively, 24 hours after alcohol withdrawal. In contrast, the CaV1.2 and CaV1.3 α1 subunits were not altered at either 3 or 48 hours during alcohol withdrawal. Conclusions: Expression of the CaV1.3 α1 subunit increased in parallel with AWS development, suggesting that altered L-type CaV1.3 channel expression is an important feature of AWS pathogenesis. PMID:25556199

  14. A rapid increase in lipoprotein (a) levels after ethanol withdrawal in alcoholic men

    SciTech Connect

    Kervinen, K.; Savolainen, J.J.; Kesaeniemi, Y.A. )

    1991-01-01

    Plasma concentrations of lipoprotein (a) (Lp(a)) were studied in 11 male alcoholics at the end of a drinking period and monitored during subsequent abstinence. Lp(a) levels showed a daily increase for four consecutive days after the beginning of abstinence, the values for the third and the fourth day being significantly higher than those of the first day. The changes in Lp(a) showed no association with the changes in low density lipoprotein (LDL) and high density lipoprotein (HDL) cholesterol levels. In one alcoholic subject with a heterozygous form of familial hypercholesterolemia who was monitored for 11 days, the Lp(a) levels rose up to the fourth day and remained at a high level thereafter. These results suggest that ethanol ingestion may be associated with a lower of Lp(a) levels, which may contribute to the delayed progression of atherosclerosis observed in alcohol drinkers.

  15. The use of tramadol for acute heroin withdrawal: a comparison to clonidine.

    PubMed

    Sobey, Paul W; Parran, Theodore V; Grey, Scott F; Adelman, Christopher L; Yu, Jaehak

    2003-01-01

    Using a retrospective chart review, 59 patients detoxified with tramadol were compared to 85 patients detoxified with clonidine on rates of leaving against medical advice (AMA) and control of withdrawal symptoms. Patients detoxified with tramadol had 23% (95% CI, 0.09-0.59; P < .01) the risk of leaving AMA and scored an average of 0.24 points lower (95% CI, 0.08-0.41; P < .01) on a 0-3 point withdrawal symptom scale compared to patients detoxified with clonidine. This preliminary study indicates that tramadol is more effective in managing withdrawal than clonidine, and may be especially useful in outpatient detoxification. PMID:14723475

  16. Platelet uptake of serotonin (5-HT) during ethanol withdrawal in male alcoholics

    SciTech Connect

    Neiman, J.; Beving, H.; Malmgren, R.

    1987-06-15

    Changes in the kinetic variables of the platelet serotonin uptake, Km and Vmax, were studied in 7 male alcoholics, admitted for detoxification and in sex- and age-matched volunteers. On admission the alcoholics had lower Km values than reference subjects (p less than 0.05). During detoxification the Km values normalized. Vmax was normal throughout the study in spite of the changes in platelet count. The results of the study suggest that the affinity of serotonin to its uptake receptor is transiently increased after a period of heavy drinking.

  17. 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.

  18. [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.

  19. 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

  20. 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

  1. 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)

  2. Efficacy of transcranial magnetotherapy in the complex treatment of alcohol withdrawal syndrome.

    PubMed

    Staroverov, A T; Zhukov, O B; Raigorodskii, Yu M

    2009-11-01

    A total of 54 patients with alcoholism were studied during abstinence. Of these, 29 patients in the experimental group received basal therapy supplemented with physical treatment consisting of transcranial dynamic magnetotherapy (TcDMT), while the control group of 25 patients received only basal therapy. Comparison of the status of patients in the experimental and control groups during treatment demonstrated advantages of TcDMT in relation to improving the functional state of the CNS, memory, and attention, the autonomic nervous system, and the psychoemotional status of the patients (with decreases in the severity of anxiety and depression). PMID:19830574

  3. 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

  4. 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

  5. Phosphorylation of the N-methyl-d-aspartate receptor is increased in the nucleus accumbens during both acute and extended morphine withdrawal.

    PubMed

    Anderson, Ethan M; Reeves, Turi; Kapernaros, Katherine; Neubert, John K; Caudle, Robert M

    2015-12-01

    Opioid withdrawal causes a dysphoric state that can lead to complications in pain patients and can propagate use in drug abusers and addicts. Opioid withdrawal changes the activity of neurons in the nucleus accumbens, an area rich in both opioid-binding mu opioid receptors and glutamate-binding NMDA receptors. Because the accumbens is an area important for reward and aversion, plastic changes in this area during withdrawal could alter future behaviors in animals. We discovered an increase in phosphorylation of serine 897 in the NR1 subunit of the NMDA receptor (pNR1) during acute morphine withdrawal. This serine can be phosphorylated by protein kinase A (PKA) and dephosphorylated by calcineurin. We next demonstrated that this increased pNR1 change is associated with an increase in NR1 surface expression. NR1 surface expression and pNR1 levels during acute withdrawal were both reduced by the NMDA receptor antagonist MK-801 (dizocilpine hydrogen maleate) and the PKA inhibitor H-89(N-[2-[[3-(4-bromophenyl)-2-propenyl]amino]ethyl]-5-isoquinolinesulfonamide dihydrochloride hydrate). We also found that pNR1 levels remained high after an extended morphine withdrawal period of 2 months, correlated with reward-seeking behavior for palatable food, and were associated with a decrease in accumbal calcineurin levels. These data suggest that NR1 phosphorylation changes during the acute withdrawal phase can be long lasting and may reflect a permanent change in NMDA receptors in the accumbens. These altered NMDA receptors in the accumbens could play a role in long-lasting behaviors associated with reward and opioid use.

  6. 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

  7. Glutamate receptors in the dorsal hippocampus mediate the acquisition, but not the expression, of conditioned place aversion induced by acute morphine withdrawal in rats

    PubMed Central

    Hou, Yuan-yuan; Liu, Yao; Kang, Shuo; Yu, Chuan; Chi, Zhi-qiang; Liu, Jing-gen

    2009-01-01

    Aim: To evaluate the role of glutamate receptors in the dorsal hippocampus (DH) in the motivational component of morphine withdrawal. Methods: NMDA receptor antagonist D-AP5 (5 μg/0.5 μL per side) or AMPA receptor antagonist NBQX (2 μg/0.5 μL per side) was microinjected into DH of rats. Conditioned place aversion (CPA) induced by naloxone-precipitated morphine withdrawal were assessed. Results: Preconditioning microinjection of D-AP5 or NBQX into the DH impaired the acquisition of CPA in acute morphine-dependent rats. However, intra-DH microinjection of D-AP5 or NBQX after conditioning but before the testing session had no effect on the expression of CPA. Conclusion: Our results suggest that NMDA and AMPA receptors in the dorsal hippocampus are involved in the acquisition, but not in the expression, of the negative motivational components of acute morphine withdrawal in rats. PMID:19767765

  8. 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.

  9. 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

  10. Sex differences in alcohol consumption and alterations in nucleus accumbens endocannabinoid mRNA in alcohol-dependent rats.

    PubMed

    Henricks, Angela M; Berger, Anthony L; Lugo, Janelle M; Baxter-Potter, Lydia N; Bieniasz, Kennedy V; Craft, Rebecca M; McLaughlin, Ryan J

    2016-10-29

    Chronic intermittent alcohol (CIA) exposure produces altered motivational states characterized by anxiety and escalated alcohol consumption during withdrawal. The endocannabinoid (ECB) system contributes to these symptoms, and sex differences in alcohol dependence, as well as bidirectional interactions between ECBs and gonadal hormones have been documented. Thus, we evaluated sex differences in alcohol consumption, anxiety-like behavior, and ECB mRNA expression in the nucleus accumbens (NAc) of alcohol-dependent rats during acute withdrawal. Male rats exposed to six weeks of CIA showed escalated alcohol consumption during acute withdrawal and reductions in NAc N-acyl phosphatidylethanolamine phospholipase D (NAPEPLD), DAG lipase alpha (DAGLα), and monoacylglycerol lipase (MAGL) mRNA. Intact alcohol-dependent female rats also escalated their consumption, but notably, this effect was also present in non-dependent females. No differences in NAc ECB mRNA were observed between CIA- and air-exposed females during acute withdrawal. However, when these data were analyzed according to estrous stage, significant differences in NAPEPLD and MAGL mRNA expression emerged in the NAc of air-exposed control rats, which were absent in alcohol-dependent females. We subsequently measured alcohol consumption and NAc ECB mRNA in ovariectomized (OVX) females with or without estradiol (E2) replacement during withdrawal. Neither E2 nor CIA altered alcohol consumption in OVX females. However, E2 reduced both DAGLα and MAGL mRNA, suggesting that E2 may influence the biosynthesis and degradation of 2-arachidonoylglycerol (2-AG) in the NAc. Collectively, these studies indicate sexual dimorphism in alcohol consumption in non-dependent rats and suggest that E2-mediated alterations in NAc ECB mRNA expression during withdrawal may be a mechanism by which sex differences in alcohol dependence emerge. PMID:27578612

  11. 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

  12. 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

  13. [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.

  14. 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

  15. 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.

  16. Identification of a QTL in Mus musculus for alcohol preference, withdrawal, and Ap3m2 expression using integrative functional genomics and precision genetics.

    PubMed

    Bubier, Jason A; Jay, Jeremy J; Baker, Christopher L; Bergeson, Susan E; Ohno, Hiroshi; Metten, Pamela; Crabbe, John C; Chesler, Elissa J

    2014-08-01

    Extensive genetic and genomic studies of the relationship between alcohol drinking preference and withdrawal severity have been performed using animal models. Data from multiple such publications and public data resources have been incorporated in the GeneWeaver database with >60,000 gene sets including 285 alcohol withdrawal and preference-related gene sets. Among these are evidence for positional candidates regulating these behaviors in overlapping quantitative trait loci (QTL) mapped in distinct mouse populations. Combinatorial integration of functional genomics experimental results revealed a single QTL positional candidate gene in one of the loci common to both preference and withdrawal. Functional validation studies in Ap3m2 knockout mice confirmed these relationships. Genetic validation involves confirming the existence of segregating polymorphisms that could account for the phenotypic effect. By exploiting recent advances in mouse genotyping, sequence, epigenetics, and phylogeny resources, we confirmed that Ap3m2 resides in an appropriately segregating genomic region. We have demonstrated genetic and alcohol-induced regulation of Ap3m2 expression. Although sequence analysis revealed no polymorphisms in the Ap3m2-coding region that could account for all phenotypic differences, there are several upstream SNPs that could. We have identified one of these to be an H3K4me3 site that exhibits strain differences in methylation. Thus, by making cross-species functional genomics readily computable we identified a common QTL candidate for two related bio-behavioral processes via functional evidence and demonstrate sufficiency of the genetic locus as a source of variation underlying two traits.

  17. Safety and efficacy of flumazenil for reversal of iatrogenic benzodiazepine-associated delirium toxicity during treatment of alcohol withdrawal, a retrospective review at one center.

    PubMed

    Moore, Philip W; Donovan, J Ward; Burkhart, Keith K; Waskin, Jeffrey A; Hieger, Michelle A; Adkins, Audrey R; Wert, Yijin; Haggerty, David A; Rasimas, J J

    2014-06-01

    Both alcohol withdrawal syndrome (AWS) and benzodiazepines can cause delirium. Benzodiazepine-associated delirium can complicate AWS and prolong hospitalization. Benzodiazepine delirium can be diagnosed with flumazenil, a GABA-A receptor antagonist. By reversing the effects of benzodiazepines, flumazenil is theorized to exacerbate symptoms of AWS and precludes its use. For patients being treated for alcohol withdrawal, flumazenil can diagnose and treat benzodiazepine delirium without precipitating serious or life-threatening adverse events. Hospital admission records were retrospectively reviewed for patients with the diagnosis of AWS who received both benzodiazepines and flumazenil from December 2006 to June 2012 at a university-affiliated inpatient toxicology center. The day of last alcohol consumption was estimated from available blood alcohol content or subjective history. Corresponding benzodiazepine, flumazenil, and adjunctive sedative pharmacy records were reviewed, as were demographic, clinical course, and outcome data. Eighty-five patients were identified (average age 50.3 years). Alcohol concentrations were detectable for 42 patients with average 261 mg/dL (10-530 mg/dL). Eighty patients were treated with adjunctive agents for alcohol withdrawal including antipsychotics (n = 57), opioids (n = 27), clonidine (n = 35), and phenobarbital (n = 23). Average time of flumazenil administration was 4.7 days (1-11 days) after abstinence, and average dose was 0.5 mg (0.2-1 mg). At the time of flumazenil administration, delirium was described as hypoactive (n = 21), hyperactive (n = 15), mixed (n = 41), or not specified (n = 8). Response was not documented in 11 cases. Sixty-two (72.9 %) patients had significant objective improvement after receiving flumazenil. Fifty-six patients required more than one dose (average 5.6 doses). There were no major adverse events and minor adverse effects included transiently increased anxiety

  18. Peroxisome proliferator-activated receptors α and γ are linked with alcohol consumption in mice and withdrawal and dependence in humans

    PubMed Central

    Blednov, Yuri A.; Benavidez, Jillian M.; Black, Mendy; Ferguson, Laura B.; Schoenhard, Grant L.; Goate, Alison M.; Edenberg, Howard J.; Wetherill, Leah; Hesselbrock, Victor; Foroud, Tatiana; Harris, R. Adron

    2014-01-01

    Background Peroxisome proliferator-activated receptor (PPAR) agonists reduce voluntary ethanol consumption in rat models and are promising therapeutics in the treatment of drug addictions. We studied the effects of different classes of PPAR agonists on chronic ethanol intake and preference in mice with a genetic predisposition for high alcohol consumption and then examined human genome wide association data for polymorphisms in PPAR genes in alcohol-dependent subjects. Methods Two different behavioral tests were used to measure intake of 15% ethanol in C57BL/6J male mice: 24-hour two-bottle choice and limited access (3-hour) two-bottle choice, drinking in the dark. We measured the effects of pioglitazone (10 and 30 mg/kg), fenofibrate (50 and 150 mg/kg), GW0742 (10 mg/kg), tesaglitazar (1.5 mg/kg) and bezafibrate (25 and 75 mg/kg) on ethanol intake and preference. Fenofibric acid, the active metabolite of fenofibrate, was quantified in mouse plasma, liver, and brain by LC-MS/MS. Data from a human genome wide association study (GWAS) completed in the Collaborative Study on the Genetics of Alcoholism (COGA) was then used to analyze the association of single nucleotide polymorphisms (SNPs) in different PPAR genes (PPARA, PPARD, PPARG, and PPARGC1A) with two phenotypes: DSM-IV alcohol dependence (AD) and the DSM-IV criterion of withdrawal. Results Activation of two isoforms of PPARs, α and γ, reduced ethanol intake and preference in the two different consumption tests in mice. However, a selective PPARδ agonist or a pan agonist for all three PPAR isoforms did not decrease ethanol consumption. Fenofibric acid, the active metabolite of the PPARα agonist fenofibrate, was detected in liver, plasma, and brain after 1 or 8 days of oral treatment. The GWAS from COGA supported an association of SNPs in PPARA and PPARG with alcohol withdrawal and PPARGC1A with AD but found no association for PPARD with either phenotype. Conclusions We provide convergent evidence using both

  19. 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

  20. Follow-up study of alcoholic hallucinosis

    PubMed Central

    Perme, Bojir; Vijaysagar, Kommu John; Chandrasekharan, R.

    2003-01-01

    Alcoholic hallucinosis is a pathological mental state characterized by an acute onset of predominant auditory hallucinations that occur either during or after a period of heavy alcohol consumption. In this study, 52 patients with a diagnosis of Psychotic disorder predominantly hallucinatory associated with alcohol use (F 10.52) were evaluated after a period of three years. Past history of withdrawal hallucinations was associated with alcoholic hallucinosis The study has found a wide spectrum of outcome confirming the earlier observations that alcoholic hallucinosis is a heterogeneous disorder. PMID:21206866

  1. GHB pharmacology and toxicology: acute intoxication, concentrations in blood and urine in forensic cases and treatment of the withdrawal syndrome.

    PubMed

    Busardò, Francesco P; Jones, Alan W

    2015-01-01

    The illicit recreational drug of abuse, γ-hydroxybutyrate (GHB) is a potent central nervous system depressant and is often encountered during forensic investigations of living and deceased persons. The sodium salt of GHB is registered as a therapeutic agent (Xyrem®), approved in some countries for the treatment of narcolepsy-associated cataplexy and (Alcover®) is an adjuvant medication for detoxification and withdrawal in alcoholics. Trace amounts of GHB are produced endogenously (0.5-1.0 mg/L) in various tissues, including the brain, where it functions as both a precursor and a metabolite of the major inhibitory neurotransmitter γ-aminobutyric acid (GABA). Available information indicates that GHB serves as a neurotransmitter or neuromodulator in the GABAergic system, especially via binding to the GABA-B receptor subtype. Although GHB is listed as a controlled substance in many countries abuse still continues, owing to the availability of precursor drugs, γ-butyrolactone (GBL) and 1,4-butanediol (BD), which are not regulated. After ingestion both GBL and BD are rapidly converted into GHB (t½ ~1 min). The Cmax occurs after 20-40 min and GHB is then eliminated from plasma with a half-life of 30-50 min. Only about 1-5% of the dose of GHB is recoverable in urine and the window of detection is relatively short (3-10 h). This calls for expeditious sampling when evidence of drug use and/or abuse is required in forensic casework. The recreational dose of GHB is not easy to estimate and a concentration in plasma of ~100 mg/L produces euphoria and disinhibition, whereas 500 mg/L might cause death from cardiorespiratory depression. Effective antidotes to reverse the sedative and intoxicating effects of GHB do not exist. The poisoned patients require supportive care, vital signs should be monitored and the airways kept clear in case of emesis. After prolonged regular use of GHB tolerance and dependence develop and abrupt cessation of drug use leads to unpleasant

  2. GHB Pharmacology and Toxicology: Acute Intoxication, Concentrations in Blood and Urine in Forensic Cases and Treatment of the Withdrawal Syndrome

    PubMed Central

    Busardò, Francesco P.; Jones, Alan W.

    2015-01-01

    The illicit recreational drug of abuse, γ-hydroxybutyrate (GHB) is a potent central nervous system depressant and is often encountered during forensic investigations of living and deceased persons. The sodium salt of GHB is registered as a therapeutic agent (Xyrem®), approved in some countries for the treatment of narcolepsy-associated cataplexy and (Alcover®) is an adjuvant medication for detoxification and withdrawal in alcoholics. Trace amounts of GHB are produced endogenously (0.5-1.0 mg/L) in various tissues, including the brain, where it functions as both a precursor and a metabolite of the major inhibitory neurotransmitter γ-aminobutyric acid (GABA). Available information indicates that GHB serves as a neurotransmitter or neuromodulator in the GABAergic system, especially via binding to the GABA-B receptor subtype. Although GHB is listed as a controlled substance in many countries abuse still continues, owing to the availability of precursor drugs, γ-butyrolactone (GBL) and 1,4-butanediol (BD), which are not regulated. After ingestion both GBL and BD are rapidly converted into GHB (t½ ~1 min). The Cmax occurs after 20-40 min and GHB is then eliminated from plasma with a half-life of 30-50 min. Only about 1-5% of the dose of GHB is recoverable in urine and the window of detection is relatively short (3-10 h). This calls for expeditious sampling when evidence of drug use and/or abuse is required in forensic casework. The recreational dose of GHB is not easy to estimate and a concentration in plasma of ~100 mg/L produces euphoria and disinhibition, whereas 500 mg/L might cause death from cardiorespiratory depression. Effective antidotes to reverse the sedative and intoxicating effects of GHB do not exist. The poisoned patients require supportive care, vital signs should be monitored and the airways kept clear in case of emesis. After prolonged regular use of GHB tolerance and dependence develop and abrupt cessation of drug use leads to unpleasant

  3. 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

  4. 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

  5. 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

  6. 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

  7. 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

  8. 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

  9. 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

  10. Effect of Acetaldehyde Intoxication and Withdrawal on NPY Expression: Focus on Endocannabinoidergic System Involvement.

    PubMed

    Plescia, Fulvio; Brancato, Anna; Marino, Rosa Anna Maria; Vita, Carlotta; Navarra, Michele; Cannizzaro, Carla

    2014-01-01

    Acetaldehyde (ACD), the first alcohol metabolite, plays a pivotal role in the rewarding, motivational, and addictive properties of the parental compound. Many studies have investigated the role of ACD in mediating neurochemical and behavioral effects induced by alcohol administration, but very little is known about the modulation of neuropeptide systems following ACD intoxication and withdrawal. Indeed, the neuropeptide Y (NPY) system is altered during alcohol withdrawal in key regions for cerebrocortical excitability and neuroplasticity. The primary goal of this research was to investigate the effects of ACD intoxication and withdrawal by recording rat behavior and by measuring NPY immunoreactivity in hippocampus and NAcc, two brain regions mainly involved in processes which encompass neuroplasticity in alcohol dependence. Furthermore, on the basis of the involvement of endocannabinoidergic system in alcohol and ACD reinforcing effects, the role of the selective CB1 receptor antagonist AM281 in modulating NPY expression during withdrawal was assessed. Our results indicate that (i) ACD intoxication induced a reduction in NPY expression in hippocampus and NAcc; (ii) symptoms of physical dependence, similar to alcohol's, were scored at 12 h from the last administration of ACD; and (iii) NPY levels increased in early and prolonged acute withdrawal in both brain regions examined. The administration of AM281 was able to blunt signs of ACD-induced physical dependence, to modulate NPY levels, and to further increase NPY expression during ACD withdrawal both in hippocampus and NAcc. In conclusion, the present study shows that complex plastic changes take place in NPY system during ACD intoxication and subsequent withdrawal in rat hippocampal formation and NAcc. The pharmacological inhibition of CB1 signaling could counteract the neurochemical imbalance associated with ACD, and alcohol withdrawal, likely boosting the setting up of homeostatic functional recovery.

  11. 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…

  12. 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

  13. 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.

  14. 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.

  15. 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

  16. 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

  17. The association of genetic polymorphisms in the κ-opioid receptor 1 gene with body weight, alcohol use, and withdrawal symptoms in patients with methadone maintenance.

    PubMed

    Wang, Sheng-Chang; Tsou, Hsiao-Hui; Chung, Ren-Hua; Chang, Yao-Sheng; Fang, Chiu-Ping; Chen, Chia-Hui; Ho, Ing-Kang; Kuo, Hsiang-Wei; Liu, Shu Chih; Shih, Yu-Huei; Wu, Hsiao-Yu; Huang, Bo-Hau; Lin, Keh-Ming; Chen, Andrew C H; Hsiao, Chin-Fu; Liu, Yu-Li

    2014-04-01

    Methadone is a synthetic opioid that binds to the κ-opioid receptor with a low affinity. This study tested the hypotheses that the genetic polymorphisms in the κ-opioid receptor 1 (OPRK1) gene region are associated with methadone treatment responses in a Taiwan methadone maintenance treatment (MMT) cohort. Seventeen single nucleotide polymorphisms (SNPs) in OPRK1 were selected and genotyped on DNA of 366 MMT patients. Six SNPs from rs7843965 to rs1051660 (intron 2 to exon 2) were significantly associated with body weight (P < 0.007). A haplotype of 4 SNPs rs7832417-rs16918853-rs702764-rs7817710 (exon 4 to intron 3) was associated with bone or joint aches (P ≤ 0.004) and with the amount of alcohol use (standard drinks per day; global P < 0.0001). The haplotype rs10958350-rs7016778-rs12675595 was associated with gooseflesh skin (global P < 0.0001), yawning (global P = 0.0001), and restlessness (global P < 0.0001) withdrawal symptoms. The findings suggest that genetic polymorphisms in OPRK1 were associated with the body weight, alcohol use, and opioid withdrawal symptoms in MMT patients.

  18. 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

  19. 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.

  20. 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.

  1. 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

  2. Alcohol disrupts sleep homeostasis.

    PubMed

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

    2015-06-01

    Alcohol is a potent somnogen and one of the most commonly used "over the counter" sleep aids. In healthy non-alcoholics, acute alcohol decreases sleep latency, consolidates and increases the quality (delta power) and quantity of NREM sleep during the first half of the night. However, sleep is disrupted during the second half. Alcoholics, both during drinking periods and during abstinences, suffer from a multitude of sleep disruptions manifested by profound insomnia, excessive daytime sleepiness, and altered sleep architecture. Furthermore, subjective and objective indicators of sleep disturbances are predictors of relapse. Finally, within the USA, it is estimated that societal costs of alcohol-related sleep disorders exceeds $18 billion. Thus, although alcohol-associated sleep problems have significant economic and clinical consequences, very little is known about how and where alcohol acts to affect sleep. In this review, we have described our attempts to unravel the mechanism of alcohol-induced sleep disruptions. We have conducted a series of experiments using two different species, rats and mice, as animal models. We performed microdialysis, immunohistochemical, pharmacological, sleep deprivation and lesion studies which suggest that the sleep-promoting effects of alcohol may be mediated via alcohol's action on the mediators of sleep homeostasis: adenosine (AD) and the wake-promoting cholinergic neurons of the basal forebrain (BF). Alcohol, via its action on AD uptake, increases extracellular AD resulting in the inhibition of BF wake-promoting neurons. Since binge alcohol consumption is a highly prevalent pattern of alcohol consumption and disrupts sleep, we examined the effects of binge drinking on sleep-wakefulness. Our results suggest that disrupted sleep homeostasis may be the primary cause of sleep disruption observed following binge drinking. Finally, we have also shown that sleep disruptions observed during acute withdrawal, are caused due to impaired

  3. The discriminative stimulus properties of acute ethanol withdrawal (hangover) in rats.

    PubMed

    Gauvin, D V; Youngblood, B D; Holloway, F A

    1992-04-01

    Twenty male Sprague-Dawley rats were trained to discriminate pentylenetetrazole (PTZ, 15 mg/kg, intraperitoneally) from saline (SAL) under a drug discrimination procedure. Test sessions were conducted with 10 randomly selected subjects. Tests with various doses of PTZ resulted in a dose-dependent increase in the percentage of total session responses emitted on the PTZ-appropriate lever without a significant change in response rates across a wide range of test PTZ doses. Rats did not generalize the PTZ stimulus to ethanol (ETOH) up to ETOH test doses that completely suppressed responding. High acute ETOH doses (2, 3, and 4 g/kg) administered at various time points prior to discrimination test sessions engendered responding on the PTZ-appropriate level in a quantitative fashion, that was dose- and time-dependent. This acute ETOH delayed effect from these high doses replicates our previously published study using a Drug 1-Drug 2 discrimination task with Chlordiazepoxide and PTZ. More importantly, we suggest that the present behavioral assay may be a sensitive animal analogue of human "hangover" phenomena.

  4. 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

  5. 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

  6. 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

  7. 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

  8. [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.

  9. 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 ...

  10. 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

  11. 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.

  12. Biphasic regulation of the acute μ-withdrawal and CCk-8 contracture responses by the ORL-1 system in guinea pig ileum.

    PubMed

    Marini, Pietro; Romanelli, Luca; Valeri, Daniela; Cascio, Maria Grazia; Tucci, Paolo; Valeri, Pacifico; Palmery, Maura

    2012-01-01

    The cloning of the opioid-receptor-like receptor (ORL-1) and the identification of the orphaninFQ/nociceptin (OFQ/N) as its endogenous agonist has revealed a new G-protein-coupled receptor signalling system. The structural and functional homology of ORL-1 to the opioid receptor systems has posed a number of challenges in the understanding the often competing physiological responses elicited by these G-protein-coupled receptors. We had previously shown that in guinea pig ileum (GPI), the acute μ-withdrawal response is under the inhibitory control of several systems. Specifically, we found that the exposure to a μ-opioid receptor agonist activates indirectly the κ-opioid, the A(1)-adenosine and the cannabinoid CB(1) systems, that in turn inhibit the withdrawal response. The indirect activation of these systems is prevented by the peptide cholecystokinin-8 (CCk-8). In the present study, we have investigated whether the ORL-1 system is also involved in the regulation of the acute μ-withdrawal response. Interestingly, we found that in GPI preparation, the ORL-1 system is not indirectly activated by the μ-opioid receptor stimulation, but instead the system is able by itself to directly regulate the acute μ-withdrawal response. Moreover, we have demonstrated that the ORL-1 system behaves both as anti-opioid or opioid-like system based on the level of activation. The same behaviour has also been observed in presence of CCk-8. Furthermore, in GPI, the existence of an endogenous tone of the ORL-1 system has been demonstrated. We concluded that the ORL-1 system acts as a neuromodulatory system, whose action is strictly related to the modulation of excitatory neurotrasmitters released in GPI enteric nervous system.

  13. Molecular basis of alcoholism.

    PubMed

    Most, Dana; Ferguson, Laura; Harris, R Adron

    2014-01-01

    Acute alcohol intoxication causes cellular changes in the brain that last for hours, while chronic alcohol use induces widespread neuroadaptations in the nervous system that can last a lifetime. Chronic alcohol use and the progression into dependence involve the remodeling of synapses caused by changes in gene expression produced by alcohol. The progression of alcohol use, abuse, and dependence can be divided into stages, which include intoxication, withdrawal, and craving. Each stage is associated with specific changes in gene expression, cellular function, brain circuits, and ultimately behavior. What are the molecular mechanisms underlying the transition from recreational use (acute) to dependence (chronic)? What cellular adaptations result in drug memory retention, leading to the persistence of addictive behaviors, even after prolonged drug abstinence? Research into the neurobiology of alcoholism aims to answer these questions. This chapter will describe the molecular adaptations caused by alcohol use and dependence, and will outline key neurochemical participants in alcoholism at the molecular level, which are also potential targets for therapy.

  14. Molecular basis of alcoholism.

    PubMed

    Most, Dana; Ferguson, Laura; Harris, R Adron

    2014-01-01

    Acute alcohol intoxication causes cellular changes in the brain that last for hours, while chronic alcohol use induces widespread neuroadaptations in the nervous system that can last a lifetime. Chronic alcohol use and the progression into dependence involve the remodeling of synapses caused by changes in gene expression produced by alcohol. The progression of alcohol use, abuse, and dependence can be divided into stages, which include intoxication, withdrawal, and craving. Each stage is associated with specific changes in gene expression, cellular function, brain circuits, and ultimately behavior. What are the molecular mechanisms underlying the transition from recreational use (acute) to dependence (chronic)? What cellular adaptations result in drug memory retention, leading to the persistence of addictive behaviors, even after prolonged drug abstinence? Research into the neurobiology of alcoholism aims to answer these questions. This chapter will describe the molecular adaptations caused by alcohol use and dependence, and will outline key neurochemical participants in alcoholism at the molecular level, which are also potential targets for therapy. PMID:25307570

  15. 27 CFR 31.137 - Withdrawal of partner(s).

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 1 2012-04-01 2012-04-01 false Withdrawal of partner(s). 31.137 Section 31.137 Alcohol, Tobacco Products and Firearms ALCOHOL AND TOBACCO TAX AND TRADE BUREAU... § 31.137 Withdrawal of partner(s). Withdrawal of partner(s) requires an amended registration. See §...

  16. 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

  17. 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

  18. 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

  19. [Causes of the people death from drunkenness and alcoholism].

    PubMed

    Erokhin, Iu A; Paukov, V S; Kirillov, Iu A

    2012-01-01

    We analyzed causes of 1008 people death, who abused by alcohol. Among them 2 groups were separated out: people died due to drunkenness and due to alcoholism. The structure of the death was similar in the both groups, however depended on alcoholism stages. The major cause of the death in group of drunkenness people was acute heart insufficiency, less commonly--lung pathology, and very rarely--brain vessels pathology and liver cirrhosis. In group of people, who died due to alcoholism, lung pathology was the major cause of these deaths, acute heart insufficiency was occurred less commonly, and very rare brain pathology because of delirium tremens or alcohol withdrawal syndrome, as so liver cirrhosis with complications. Hemorrhagic pancreonecrosis after alcoholic excess was found out in both groups, but it was more often in people, who died due to drunkenness. Obtained results show importance of chronic alcoholism identification as a disease with several stages including drunkenness and alcoholism.

  20. 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.

  1. 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.

  2. 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

  3. 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.

  4. 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

  5. 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

  6. 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 ...

  7. 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 ...

  8. 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

  9. 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

  10. 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

  11. 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.

  12. Opiate withdrawal.

    PubMed

    Farrell, M

    1994-11-01

    Opiate withdrawal is one of the longest studied and most well described withdrawal syndromes. Opiate withdrawal has been described as akin to a moderate to severe flu-like illness. Opiate withdrawal is appropriately described as subjectively severe but objectively mild. This paper describes the mechanisms of opiate dependence and opiate withdrawal and reviews the available instruments for the measurement of withdrawal. The time course of assisted and unassisted withdrawal is described and the range of options for the management of assisted withdrawal are described. This review concludes that the most effective and least time- and resource-consuming approach to opiate withdrawal will substantially contribute to the overall social management of opiate dependence.

  13. 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 ...

  14. Alcohol disrupts sleep homeostasis

    PubMed Central

    Thakkar, Mahesh M.; Sharma, Rishi; Sahota, Pradeep

    2014-01-01

    of alcohol consumption and disrupts sleep, we examined the effects of binge drinking on sleep-wakefulness. Our results suggest that disrupted sleep homeostasis may be the primary cause of sleep disruption observed following binge drinking. Finally, we have also shown that insomnia and associated sleep disruptions, observed during acute withdrawal, are caused due to impaired sleep homeostasis. Based on our findings, we suggest that alcohol may disrupt sleep homeostasis to cause sleep disruptions. PMID:25499829

  15. 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.

  16. 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.

  17. 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

  18. 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.

  19. 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.

  20. 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.

  1. 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

  2. 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

  3. 27 CFR 19.424 - Authorized withdrawals free of tax.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... free of tax. 19.424 Section 19.424 Alcohol, Tobacco Products and Firearms ALCOHOL AND TOBACCO TAX AND... Withdrawals Spirits Withdrawn Free of Tax § 19.424 Authorized withdrawals free of tax. A proprietor may withdraw spirits from bonded premises free of tax as provided in this chapter: (a) Upon receipt of a...

  4. 27 CFR 19.424 - Authorized withdrawals free of tax.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... free of tax. 19.424 Section 19.424 Alcohol, Tobacco Products and Firearms ALCOHOL AND TOBACCO TAX AND... Withdrawals Spirits Withdrawn Free of Tax § 19.424 Authorized withdrawals free of tax. A proprietor may withdraw spirits from bonded premises free of tax as provided in this chapter: (a) Upon receipt of a...

  5. 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

  6. 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

  7. 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

  8. 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

  9. 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

  10. 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

  11. 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

  12. High levels of the adhesion molecule CD44 on leukemic cells generate acute myeloid leukemia relapse after withdrawal of the initial transforming event.

    PubMed

    Quéré, R; Andradottir, S; Brun, A C M; Zubarev, R A; Karlsson, G; Olsson, K; Magnusson, M; Cammenga, J; Karlsson, S

    2011-03-01

    Multiple genetic hits are detected in patients with acute myeloid leukemia (AML). To investigate this further, we developed a tetracycline-inducible mouse model of AML, in which the initial transforming event, overexpression of HOXA10, can be eliminated. Continuous overexpression of HOXA10 is required to generate AML in primary recipient mice, but is not essential for maintenance of the leukemia. Transplantation of AML to secondary recipients showed that in established leukemias, ∼80% of the leukemia-initiating cells (LICs) in bone marrow stopped proliferating upon withdrawal of HOXA10 overexpression. However, the population of LICs in primary recipients is heterogeneous, as ∼20% of the LICs induce leukemia in secondary recipients despite elimination of HOXA10-induced overexpression. Intrinsic genetic activation of several proto-oncogenes was observed in leukemic cells resistant to inactivation of the initial transformation event. Interestingly, high levels of the adhesion molecule CD44 on leukemic cells are essential to generate leukemia after removal of the primary event. This suggests that extrinsic niche-dependent factors are also involved in the host-dependent outgrowth of leukemias after withdrawal of HOXA10 overexpression event that initiates the leukemia.

  13. 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

  14. 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

  15. 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.

  16. A dose for the wiser is enough: the alcohol benefits for associative learning in zebrafish.

    PubMed

    Chacon, Diana M; Luchiari, Ana C

    2014-08-01

    This study aimed to test seeking behavior caused by alcohol and the drug effects on learning in the zebrafish, Danio rerio. Three treatments were conducted: acute, chronic and withdrawal, using 0.10%, 0.25%, and 1.00% alcohol and control (0.00%) (vol/vol.%). For the drug seeking behavior, we used a place preference paradigm (shuttle box tank) before and after alcohol exposure in acute (single exposure) and chronic (7 days) treatments. We observed a change in the basal preference due to the association with alcohol only for 0.25% and 1.00% doses in both acute and chronic offering, indicating an alcohol-seeking behavior after the drug exposure. For the learning task, two treatments were tested: chronic alcohol exposure (26 days including the learning period) and alcohol withdrawal (15 days of alcohol exposure before the learning period). During the learning period, fish received light stimulus followed by food in a pre-defined area of the tank for 8 consecutive days. The low dose group (0.10%) learned the task by the 3rd day both in chronic and withdrawal treatments. The higher doses (0.25% and 1.00%) caused a learning impairment in the chronic treatment group, while fish from the alcohol withdrawal treatment displayed learning on the final testing day. Therefore, we suggest that high alcohol doses impair learning and cause drug seeking behavior, even after drug exposure cessation, while low doses positively affect learning and do not cause seeking behavior. Given our results we propose that the zebrafish is a promising model for identifying active compounds, antibodies or genes which modulate the alcohol dual effects: learning improvement and reinforcing behavior.

  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. 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

  19. 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.

  20. 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.

  1. 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

  2. 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.

  3. 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)

  4. 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

  5. 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

  6. 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.

  7. 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

  8. 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

  9. Label-Free Proteomic Analysis of Protein Changes in the Striatum during Chronic Ethanol Use and Early Withdrawal.

    PubMed

    Ayers-Ringler, Jennifer R; Oliveros, Alfredo; Qiu, Yanyan; Lindberg, Daniel M; Hinton, David J; Moore, Raymond M; Dasari, Surendra; Choi, Doo-Sup

    2016-01-01

    The molecular mechanisms underlying the neuronal signaling changes in alcohol addiction and withdrawal are complex and multifaceted. The cortico-striatal circuit is highly implicated in these processes, and the striatum plays a significant role not only in the early stages of addiction, but in the developed-addictive state as well, including withdrawal symptoms. Transcriptional analysis is a useful method for determining changes in gene expression, however, the results do not always accurately correlate with protein levels. In this study, we employ label-free proteomic analysis to determine changes in protein expression within the striatum during chronic ethanol use and early withdrawal. The striatum, composed primarily of medium spiny GABAergic neurons, glutamatergic and dopaminergic nerve terminals and astrocytes, is relatively homogeneous for proteomic analysis. We were able to analyze more than 5000 proteins from both the dorsal (caudate and putamen) and ventral (nucleus accumbens) striatum and identified significant changes following chronic intermittent ethanol exposure and acute (8 h) withdrawal compared to ethanol naïve and ethanol exposure groups respectively. Our results showed significant changes in proteins involved in glutamate and opioid peptide signaling, and also uncovered novel pathways including mitochondrial function and lipid/cholesterol metabolism, as revealed by changes in electron transport chain proteins and RXR activation pathways. These results will be useful in the development of novel treatments for alcohol withdrawal and thereby aid in recovery from alcohol use disorder. PMID:27014007

  10. Label-Free Proteomic Analysis of Protein Changes in the Striatum during Chronic Ethanol Use and Early Withdrawal

    PubMed Central

    Ayers-Ringler, Jennifer R.; Oliveros, Alfredo; Qiu, Yanyan; Lindberg, Daniel M.; Hinton, David J.; Moore, Raymond M.; Dasari, Surendra; Choi, Doo-Sup

    2016-01-01

    The molecular mechanisms underlying the neuronal signaling changes in alcohol addiction and withdrawal are complex and multifaceted. The cortico-striatal circuit is highly implicated in these processes, and the striatum plays a significant role not only in the early stages of addiction, but in the developed-addictive state as well, including withdrawal symptoms. Transcriptional analysis is a useful method for determining changes in gene expression, however, the results do not always accurately correlate with protein levels. In this study, we employ label-free proteomic analysis to determine changes in protein expression within the striatum during chronic ethanol use and early withdrawal. The striatum, composed primarily of medium spiny GABAergic neurons, glutamatergic and dopaminergic nerve terminals and astrocytes, is relatively homogeneous for proteomic analysis. We were able to analyze more than 5000 proteins from both the dorsal (caudate and putamen) and ventral (nucleus accumbens) striatum and identified significant changes following chronic intermittent ethanol exposure and acute (8 h) withdrawal compared to ethanol naïve and ethanol exposure groups respectively. Our results showed significant changes in proteins involved in glutamate and opioid peptide signaling, and also uncovered novel pathways including mitochondrial function and lipid/cholesterol metabolism, as revealed by changes in electron transport chain proteins and RXR activation pathways. These results will be useful in the development of novel treatments for alcohol withdrawal and thereby aid in recovery from alcohol use disorder. PMID:27014007

  11. 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.

  12. [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

  13. 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.

  14. Nicotine Withdrawal

    PubMed Central

    McLaughlin, Ian; Dani, John A.; De Biasi, Mariella

    2015-01-01

    An aversive abstinence syndrome manifests 4–24 h following cessation of chronic use of nicotine-containing products. Symptoms peak on approximately the 3rd day and taper off over the course of the following 3–4 weeks. While the severity of withdrawal symptoms is largely determined by how nicotine is consumed, certain short nucleotide polymorphisms (SNPs) have been shown to predispose individuals to consume larger amounts of nicotine more frequently—as well as to more severe symptoms of withdrawal when trying to quit. Additionally, rodent behavioral models and transgenic mouse models have revealed that specific nicotinic acetylcholine receptor (nAChR) subunits, cellular components, and neuronal circuits are critical to the expression of withdrawal symptoms. Consequently, by continuing to map neuronal circuits and nAChR subpopulations that underlie the nicotine withdrawal syndrome—and by continuing to enumerate genes that predispose carriers to nicotine addiction and exacerbated withdrawal symptoms—it will be possible to pursue personalized therapeutics that more effectively treat nicotine addiction. PMID:25638335

  15. 27 CFR 19.536 - Authorized withdrawals free of tax.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... free of tax. 19.536 Section 19.536 Alcohol, Tobacco Products and Firearms ALCOHOL AND TOBACCO TAX AND... Withdrawal of Spirits Free of Tax § 19.536 Authorized withdrawals free of tax. Pursuant to the regulations in this chapter, spirits may be withdrawn from bonded premises free of tax— (a) On receipt of a...

  16. 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

  17. 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.

  18. 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

  19. Epigenetics-beyond the genome in alcoholism.

    PubMed

    Starkman, Bela G; Sakharkar, Amul J; Pandey, Subhash C

    2012-01-01

    Genetic and environmental factors play a role in the development of alcoholism. Whole-genome expression profiling has highlighted the importance of several genes that may contribute to alcohol abuse disorders. In addition, more recent findings have added yet another layer of complexity to the overall molecular mechanisms involved in a predisposition to alcoholism and addiction by demonstrating that processes related to genetic factors that do not manifest as DNA sequence changes (i.e., epigenetic processes) play a role. Both acute and chronic ethanol exposure can alter gene expression levels in specific neuronal circuits that govern the behavioral consequences related to tolerance and dependence. The unremitting cycle of alcohol consumption often includes satiation and self-medication with alcohol, followed by excruciating withdrawal symptoms and the resultant relapse, which reflects both the positive and negative affective states of alcohol addiction. Recent studies have indicated that behavioral changes induced by acute and chronic ethanol exposure may involve chromatin remodeling resulting from covalent histone modifications and DNA methylation in the neuronal circuits involving a brain region called the amygdala. These findings have helped identify enzymes involved in epigenetic mechanisms, such as the histone deacetylase, histone acetyltransferase, and DNA methyltransferase enzymes, as novel therapeutic targets for the development of future pharmacotherapies for the treatment of alcoholism.

  20. 27 CFR 19.532 - Withdrawals of spirits for use in wine production.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... use in wine production. 19.532 Section 19.532 Alcohol, Tobacco Products and Firearms ALCOHOL AND... Withdrawals Withdrawal of Spirits Without Payment of Tax § 19.532 Withdrawals of spirits for use in wine production. Wine spirits may be withdrawn to a bonded wine cellar without payment of tax for use in...

  1. Alcohol and Caffeine: The Perfect Storm

    PubMed Central

    O'Brien, Mary Claire

    2011-01-01

    Although it is widely believed that caffeine antagonizes the intoxicating effects of alcohol, the molecular mechanisms underlying their interaction are incompletely understood. It is known that both caffeine and alcohol alter adenosine neurotransmission, but the relationship is complex, and may be dose dependent. In this article, we review the available literature on combining caffeine and alcohol. Ethical constraints prohibit laboratory studies that would mimic the high levels of alcohol intoxication achieved by many young people in real-world settings, with or without the addition of caffeine. We propose a possible neurochemical mechanism for the increase in alcohol consumption and alcohol-related consequences that have been observed in persons who simultaneously consume caffeine. Caffeine is a nonselective adenosine receptor antagonist. During acute alcohol intake, caffeine antagonizes the “unwanted” effects of alcohol by blocking the adenosine A1 receptors that mediate alcohol's somnogenic and ataxic effects. The A1 receptor–mediated “unwanted” anxiogenic effects of caffeine may be ameliorated by alcohol-induced increase in the extracellular concentration of adenosine. Moreover, by means of interactions between adenosine A2A and dopamine D2 receptors, caffeine-mediated blockade of adenosine A2A receptors can potentiate the effects of alcohol-induced dopamine release. Chronic alcohol intake decreases adenosine tone. Caffeine may provide a “treatment” for the withdrawal effects of alcohol by blocking the effects of upregulated A1 receptors. Finally, blockade of A2A receptors by caffeine may contribute to the reinforcing effects of alcohol. PMID:24761263

  2. Advances in alcoholic liver disease: An update on alcoholic hepatitis

    PubMed Central

    Liang, Randy; Liu, Andy; Perumpail, Ryan B; Wong, Robert J; Ahmed, Aijaz

    2015-01-01

    Alcoholic hepatitis is a pro-inflammatory chronic liver disease that is associated with high short-term morbidity and mortality (25%-35% in one month) in the setting of chronic alcohol use. Histopathology is notable for micro- and macrovesicular steatosis, acute inflammation with neutrophil infiltration, hepatocellular necrosis, perivenular and perisinusoidal fibrosis, and Mallory hyaline bodies found in ballooned hepatocytes. Other findings include the characteristic eosinophilic fibrillar material (Mallory’s hyaline bodies) found in ballooned hepatocytes. The presence of focal intense lobular infiltration of neutrophils is what typically distinguishes alcoholic hepatitis from other forms of hepatitis, in which the inflammatory infiltrate is primarily composed of mononuclear cells. Management consists of a multidisciplinary approach including alcohol cessation, fluid and electrolyte correction, treatment of alcohol withdrawal, and pharmacological therapy based on the severity of the disease. Pharmacological treatment for severe alcoholic hepatitis, as defined by Maddrey’s discriminant factor ≥ 32, consists of either prednisolone or pentoxifylline for a period of four weeks. The body of evidence for corticosteroids has been greater than pentoxifylline, although there are higher risks of complications. Recently head-to-head trials between corticosteroids and pentoxifylline have been performed, which again suggests that corticosteroids should strongly be considered over pentoxifylline. PMID:26576078

  3. 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.

  4. Theoretical Frameworks and Mechanistic Aspects of Alcohol Addiction: Alcohol Addiction as a Reward Deficit Disorder

    PubMed Central

    2012-01-01

    Alcoholism can be defined by a compulsion to seek and take drug, loss of control in limiting intake, and the emergence of a negative emotional state when access to the drug is prevented. Alcoholism impacts multiple motivational mechanisms and can be conceptualized as a disorder that includes a progression from impulsivity (positive reinforcement) to compulsivity (negative reinforcement). The compulsive drug seeking associated with alcoholism can be derived from multiple neuroadaptations, but the thesis argued here is that a key component involves the construct of negative reinforcement. Negative reinforcement is defined as drug taking that alleviates a negative emotional state. The negative emotional state that drives such negative reinforcement is hypothesized to derive from dysregulation of specific neurochemical elements involved in reward and stress within the basal forebrain structures involving the ventral striatum and extended amygdala, respectively. Specific neurochemical elements in these structures include not only decreases in reward neurotransmission, such as decreased dopamine and γ-aminobutyric acid function in the ventral striatum, but also recruitment of brain stress systems, such as corticotropin-releasing factor (CRF), in the extended amygdala. Acute withdrawal from chronic alcohol, sufficient to produce dependence, increases reward thresholds, increases anxiety-like responses, decreases dopamine system function, and increases extracellular levels of CRF in the central nucleus of the amygdala. CRF receptor antagonists also block excessive drug intake produced by dependence. A brain stress response system is hypothesized to be activated by acute excessive drug intake, to be sensitized during repeated withdrawal, to persist into protracted abstinence, and to contribute to the compulsivity of alcoholism. Other components of brain stress systems in the extended amygdala that interact with CRF and that may contribute to the negative motivational state

  5. 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

  6. 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

  7. 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

  8. 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

  9. 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

  10. 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.

  11. Paracetamol, alcohol and the liver

    PubMed Central

    Prescott, Laurie F

    2000-01-01

    It is claimed that chronic alcoholics are at increased risk of paracetamol (acetaminophen) hepatotoxicity not only following overdosage but also with its therapeutic use. Increased susceptibility is supposed to be due to induction of liver microsomal enzymes by ethanol with increased formation of the toxic metabolite of paracetamol. However, the clinical evidence in support of these claims is anecdotal and the same liver damage after overdosage occurs in patients who are not chronic alcoholics. Many alcoholic patients reported to have liver damage after taking paracetamol with ‘therapeutic intent’ had clearly taken substantial overdoses. No proper clinical studies have been carried out to investigate the alleged paracetamol–alcohol interaction and acute liver damage has never been produced by therapeutic doses of paracetamol given as a challenge to a chronic alcoholic. The paracetamol–alcohol interaction is complex; acute and chronic ethanol have opposite effects. In animals, chronic ethanol causes induction of hepatic microsomal enzymes and increases paracetamol hepatotoxicity as expected (ethanol primarily induces CYP2E1 and this isoform is important in the oxidative metabolism of paracetamol). However, in man, chronic alcohol ingestion causes only modest (about twofold) and short-lived induction of CYP2E1, and there is no corresponding increase (as claimed) in the toxic metabolic activation of paracetamol. The paracetamol–ethanol interaction is not specific for any one isoform of cytochrome P450, and it seems that isoenzymes other than CYP2E1 are primarily responsible for the oxidative metabolism of paracetamol in man. Acute ethanol inhibits the microsomal oxidation of paracetamol both in animals and man. This protects against liver damage in animals and there is evidence that it also does so in man. The protective effect disappears when ethanol is eliminated and the relative timing of ethanol and paracetamol intake is critical. In many of the reports

  12. 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

  13. 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.

  14. 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

  15. 27 CFR 19.431 - Withdrawal of spirits on production gauge.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... production gauge. 19.431 Section 19.431 Alcohol, Tobacco Products and Firearms ALCOHOL AND TOBACCO TAX AND TRADE BUREAU, DEPARTMENT OF THE TREASURY ALCOHOL DISTILLED SPIRITS PLANTS Transfers, Receipts, and Withdrawals Spirits Withdrawn on Production Gauge § 19.431 Withdrawal of spirits on production gauge....

  16. 27 CFR 31.104 - Withdrawal of one or more partners.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 1 2010-04-01 2010-04-01 false Withdrawal of one or more partners. 31.104 Section 31.104 Alcohol, Tobacco Products and Firearms ALCOHOL AND TOBACCO TAX AND TRADE... one or more partners. When one or more partners withdraw from a partnership that has registered...

  17. 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

  18. [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.

  19. Consequences of amygdala kindling and repeated withdrawal from ethanol on amphetamine-induced behaviours.

    PubMed

    Ripley, Tamzin L; Dunworth, Sarah J; Stephens, David N

    2002-09-01

    It has been shown previously that chronic ethanol treatment in mice leads to accelerated behavioural sensitization to psychomotor stimulants [Manley & Little (1997) J. Pharmacol. Exp. Ther., 281, 1330-1339], whilst repeated experience of ethanol withdrawal sensitizes pathways underlying seizure activity (Becker & Hale (1993) Alcohol Clin. Exp. Res., 17, 94-98]. The aim of the current experiment was to investigate the consequences of repeated withdrawal from ethanol on amphetamine-induced behaviours in the rat and compare this with animals with electrical kindling of the amygdala, a procedure that has been shown to enhance alcohol withdrawal seizures [Pinel et al. (1975) Can. J. Neurol. Sci., 2, 467-475]. For the kindling experiments, electrodes were surgically implanted in the left basolateral amygdala and were stimulated daily at the afterdischarge threshold until a criterion of three consecutive stage 5 seizures was reached. Fully kindled rats showed a marginally significant reduction in sensitivity to the locomotor stimulant effects of acute amphetamine compared with sham and partially kindled rats which had experienced subthreshold stimulation of the amygdala. Sham and partially kindled rats sensitized readily to the locomotor activating effects of amphetamine (0.125 mg/kg) following repeated treatments, but the fully kindled rats did not. Fully kindled rats also failed to show place preference conditioning to amphetamine (0.5 mg/kg). Rats, withdrawn three times from chronic ethanol (liquid-diet), kindled more quickly to PTZ (30 mg/kg, i.p.) than rats with the same overall exposure to ethanol (24 days) followed by a single withdrawal or control animals. However, there was no difference in the locomotor stimulating effects of acute amphetamine (0.25-1 mg/kg, i.p.), the rate of sensitization to amphetamine (0.125 mg/kg, i.p.) or amphetamine induced conditioned place preference (1 mg/kg, i.p.). These observations suggest that, in rats, repeated withdrawal from a

  20. 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

  1. 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.

  2. 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

  3. 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

  4. The Central Amygdala and Alcohol: Role of γ-Aminobutyric Acid, Glutamate, and Neuropeptides

    PubMed Central

    Roberto, Marisa; Gilpin, Nicholas W.; Siggins, George R.

    2012-01-01

    Alcohol dependence is a chronically relapsing disorder characterized by compulsive drug seeking and drug taking, loss of control in limiting intake, and the emergence of a withdrawal syndrome in the absence of the drug. Accumulating evidence suggests an important role for synaptic transmission in the central amygdala (CeA) in mediating alcohol-related behaviors and neuroadaptative mechanisms associated with alcohol dependence. Acute alcohol facilitates γ-aminobutyric acid-ergic (GABAergic) transmission in CeA via both pre- and postsynaptic mechanisms, and chronic alcohol increases baseline GABAergic transmission. Acute alcohol inhibits glutamatergic transmission via effects at N-methyl-d-aspartate (NMDA) and AMPA receptors in CeA, whereas chronic alcohol up-regulates N-methyl-d-aspartate receptor (NMDAR)-mediated transmission. Pro- (e.g., corticotropin-releasing factor [CRF]) and anti-stress (e.g., NPY, nociceptin) neuropeptides affect alcohol- and anxiety-related behaviors, and also alter the alcohol-induced effects on CeA neurotransmission. Alcohol dependence produces plasticity in these neuropeptide systems, reflecting a recruitment of those systems during the transition to alcohol dependence. PMID:23085848

  5. Quantification of phosphatidylethanol 16:0/18:1, 18:1/18:1, and 16:0/16:0 in venous blood and venous and capillary dried blood spots from patients in alcohol withdrawal and control volunteers.

    PubMed

    Kummer, Natalie; Ingels, Ann-Sofie; Wille, Sarah M R; Hanak, Catherine; Verbanck, Paul; Lambert, Willy E E; Samyn, Nele; Stove, Christophe P

    2016-01-01

    Phosphatidylethanol species (PEths) are promising biomarkers of alcohol consumption. Here, we report on the set-up, validation, and application of a novel UHPLC-ESI-MS/MS method for the quantification of PEth 16:0/18:1, PEth 18:1/18:1, and PEth 16:0/16:0 in whole blood (30 μL) and in venous (V, 30 μL) or capillary (C, 3 punches (3 mm)) dried blood spots (DBS). The methods were linear from 10 (LLOQ) to 2000 ng/mL for PEth 16:0/18:1, from 10 (LLOQ) to 1940 ng/mL for PEth 18:1/18:1, and from 19 (LLOQ) to 3872 ng/mL for PEth 16:0/16:0. Extraction efficiencies were higher than 55% (RSD < 18%) and matrix effects compensated for by IS were between 77 and 125% (RSD < 10%). Accuracy, repeatability, and intermediate precision fulfilled acceptance criteria (bias and RSD below 13%). Validity of the procedure for determination of PEth 16:0/18:1 in blood was demonstrated by the successful participation in a proficiency test. The quantification of PEths in C-DBS was not significantly influenced by the hematocrit, punch localization, or spot volume. The stability of PEths in V-DBS stored at room temperature was demonstrated up to 6 months. The method was applied to authentic samples (whole blood, V-DBS, and C-DBS) from 50 inpatients in alcohol withdrawal and 50 control volunteers. Applying a cut-off value to detect inpatients at 221 ng/mL for PEth 16:0/18:1 provided no false positive results and a good sensitivity (86%). Comparison of quantitative results (Bland-Altman plot, Passing-Bablok regression, and Wilcoxon signed rank test) revealed that V-DBS and C-DBS were valid alternatives to venous blood for the detection of alcohol consumption. PMID:26597914

  6. Quantification of phosphatidylethanol 16:0/18:1, 18:1/18:1, and 16:0/16:0 in venous blood and venous and capillary dried blood spots from patients in alcohol withdrawal and control volunteers.

    PubMed

    Kummer, Natalie; Ingels, Ann-Sofie; Wille, Sarah M R; Hanak, Catherine; Verbanck, Paul; Lambert, Willy E E; Samyn, Nele; Stove, Christophe P

    2016-01-01

    Phosphatidylethanol species (PEths) are promising biomarkers of alcohol consumption. Here, we report on the set-up, validation, and application of a novel UHPLC-ESI-MS/MS method for the quantification of PEth 16:0/18:1, PEth 18:1/18:1, and PEth 16:0/16:0 in whole blood (30 μL) and in venous (V, 30 μL) or capillary (C, 3 punches (3 mm)) dried blood spots (DBS). The methods were linear from 10 (LLOQ) to 2000 ng/mL for PEth 16:0/18:1, from 10 (LLOQ) to 1940 ng/mL for PEth 18:1/18:1, and from 19 (LLOQ) to 3872 ng/mL for PEth 16:0/16:0. Extraction efficiencies were higher than 55% (RSD < 18%) and matrix effects compensated for by IS were between 77 and 125% (RSD < 10%). Accuracy, repeatability, and intermediate precision fulfilled acceptance criteria (bias and RSD below 13%). Validity of the procedure for determination of PEth 16:0/18:1 in blood was demonstrated by the successful participation in a proficiency test. The quantification of PEths in C-DBS was not significantly influenced by the hematocrit, punch localization, or spot volume. The stability of PEths in V-DBS stored at room temperature was demonstrated up to 6 months. The method was applied to authentic samples (whole blood, V-DBS, and C-DBS) from 50 inpatients in alcohol withdrawal and 50 control volunteers. Applying a cut-off value to detect inpatients at 221 ng/mL for PEth 16:0/18:1 provided no false positive results and a good sensitivity (86%). Comparison of quantitative results (Bland-Altman plot, Passing-Bablok regression, and Wilcoxon signed rank test) revealed that V-DBS and C-DBS were valid alternatives to venous blood for the detection of alcohol consumption.

  7. 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.

  8. Steroid withdrawal in renal transplantation.

    PubMed

    Grenda, Ryszard

    2013-11-01

    Over the last decade, steroid minimization became one of the major goals in pediatric renal transplantation. Different protocols have been used by individual centers and multicenter study groups, including early and late steroid withdrawal or even complete avoidance. The timing of steroid withdrawal determines if antibodies are used, as avoidance and early withdrawal require antibody induction, while late withdrawal typically does not. A monoclonal antibody was used in most protocols during an early steroid withdrawal together with tacrolimus and mycophenolate mofetil in low immunological risk patients. Polyclonal induction was reported as effective in high-risk patients. Cyclosporine A and mycophenolate mofetil were used in late steroid withdrawal with no induction. All described protocols were effective in terms of preventing acute rejection and preserving renal graft function. There was no superiority of any specific protocol in terms of clinical benefits of steroid withdrawal. Pre-puberty determined growth benefit while other clinical advantages, including better control of glycemia, lipids, and blood pressure, were age independent. It is not clear whether the steroid withdrawal increases the risk of recurrence of primary glomerular diseases post-transplant, however it cannot be excluded. There is no evidence to date for a higher risk of anti-HLA production in steroid-free children after renal transplantation. Key summary points--Current strategies to minimize the steroid-related adverse effects in pediatric renal graft recipients include steroid withdrawal, early or late after transplantation, or complete steroid avoidance--Early steroid withdrawal or avoidance is generally used following the induction therapy with mono- or polyclonal antibodies, while in late steroid withdrawal induction therapy was generally not used- Elimination of steroids (early or late) does not increase the risk of acute rejection and does not deteriorate long-term renal graft function

  9. 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

  10. 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

  11. Chronic Alcohol Treatment in Rats Alters Sleep by Fragmenting Periods of Vigilance Cycling in the Light Period with Extended Wakenings

    PubMed Central

    Mukherjee, Sanjib; Simasko, Steven M.

    2009-01-01

    Studies have shown that disturbed sleep produced by chronic alcohol abuse in humans can predict relapse drinking after periods of abstinence. How alcohol produces disturbed sleep remains unknown. In this study we used a novel analysis of sleep to examine the effects of alcohol on sleep patterns in rats. This analysis separates waking into multiple components and defines a period labeled vigilance cycling (VC) in which the rat rapidly cycles through various vigilance states. These VC episodes are separated by long duration wake periods (LDW). We find that 6 weeks of alcohol (6% in a liquid diet) caused fragmentation of extended VC episodes that normally occur in the light period. However, total daily amounts of slow-wave sleep (SWS) and rapid-eye movement sleep (REMS) remained constant. The daily amount of wake, SWS, and REMS remained constant because the alcohol treated rats increased the amount of VC in the dark period, and the sleep nature of VC in the dark period became more intense. In addition, we observed more wake and less REMS early in the light period in alcohol treated rats. All effects completely reversed by day 16 of alcohol withdrawal. Comparison of the effects of chronic alcohol to acute alcohol exposure demonstrated the effects of chronic alcohol are due to adaptation and not the acute presence of alcohol. The effects of chronic alcohol treatment in rats mimic the effects reported in humans (REMS suppression, difficulty falling asleep, and difficulty remaining asleep). PMID:19014977

  12. 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)

  13. Neurologic effects of alcoholism.

    PubMed Central

    Diamond, I; Messing, R O

    1994-01-01

    Alcoholism, a worldwide disorder, is the cause of a variety of neurologic disorders. In this article we discuss the cellular pathophysiology of ethanol addition and abuse as well as evidence supporting and refuting the role of inheritance in alcoholism. A genetic marker for alcoholism has not been identified, but neurophysiologic studies may be promising. Some neurologic disorders related to longterm alcoholism are due predominantly to inadequate nutrition (the thiamine deficiency that causes Wernicke's encephalopathy), but others appear to involve the neurotoxicity of ethanol on brain (alcohol withdrawal syndrome and dementia) and peripheral nerves (alcoholic neuropathy and myopathy). Images PMID:7975567

  14. 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.

  15. An NMDA antagonist (LY 235959) attenuates abstinence-induced withdrawal of planarians following acute exposure to a cannabinoid agonist (WIN 55212-2).

    PubMed

    Rawls, Scott M; Gomez, Teresa; Raffa, Robert B

    2007-03-01

    The mechanisms that facilitate the development and expression of cannabinoid physical dependence in humans and other mammals are poorly understood. The present experiments used a planarian model to provide evidence that pharmacological antagonism of NMDA receptors significantly attenuates the development of cannabinoid physical dependence. Abstinence-induced withdrawal from the cannabinoid agonist WIN 55212-2 (10 microM) was manifested as a significant (P<0.05) decrease in the rate of planarian spontaneous locomotor velocity (pLMV) when WIN 55212-2 (10 microM)-exposed planarians were placed into drug-free water. No change in pLMV occurred when WIN 55212-2 (10 microM)-exposed planarians were placed into water containing WIN 55212-2 (10 microM). WIN 55212-2 (10 microM)-exposed planarians placed into water containing LY 235959 (1 or 10 microM) did not display withdrawal (no significant difference, P>0.05, in pLMV). In addition, withdrawal was not observed (no significant difference, P>0.05, in pLMV) in planarians that were co-exposed to a solution containing WIN 55212-2 (10 microM) and LY 235959 (10 microM). The present results reveal that NMDA receptor activation mediates the development of cannabinoid physical dependence and the expression of cannabinoid withdrawal in planarians.

  16. 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

  17. Cannabinoid Ligands and Alcohol Addiction: A Promising Therapeutic Tool or a Humbug?

    PubMed

    Kleczkowska, Patrycja; Smaga, Irena; Filip, Małgorzata; Bujalska-Zadrozny, Magdalena

    2016-01-01

    The vast therapeutic potential of cannabinoids of both synthetic and plant-derived origins currently makes these compounds the focus of a growing interest. Although cannabinoids are still illicit drugs, their possible clinical usefulness, including treatment of acute or neuropathic pain, have been suggested by several studies. In addition, some observations indicate that cannabinoid receptor antagonists may be useful for the treatment of alcohol dependence and addiction, which is a major health concern worldwide. While the synergism between alcohol and cannabinoid agonists (in various forms) creates undesirable side effects when the two are consumed together, the administration of CB1 antagonists leads to a significant reduction in alcohol consumption. Furthermore, cannabinoid antagonists also mitigate alcohol withdrawal symptoms. Herein, we present an overview of studies focusing on the effects of cannabinoid ligands (agonists and antagonists) during acute or chronic consumption of ethanol.

  18. 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.

  19. [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.

  20. 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.

  1. 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

  2. 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

  3. 29 CFR 4219.11 - Withdrawal liability upon mass withdrawal.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 29 Labor 9 2014-07-01 2014-07-01 false Withdrawal liability upon mass withdrawal. 4219.11 Section... Redetermination of Withdrawal Liability Upon Mass Withdrawal § 4219.11 Withdrawal liability upon mass withdrawal. (a) Initial withdrawal liability. The plan sponsor of a multiemployer plan that experiences a...

  4. 29 CFR 4219.11 - Withdrawal liability upon mass withdrawal.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 29 Labor 9 2010-07-01 2010-07-01 false Withdrawal liability upon mass withdrawal. 4219.11 Section... Redetermination of Withdrawal Liability Upon Mass Withdrawal § 4219.11 Withdrawal liability upon mass withdrawal. (a) Initial withdrawal liability. The plan sponsor of a multiemployer plan that experiences a...

  5. 29 CFR 4219.11 - Withdrawal liability upon mass withdrawal.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 29 Labor 9 2011-07-01 2011-07-01 false Withdrawal liability upon mass withdrawal. 4219.11 Section... Redetermination of Withdrawal Liability Upon Mass Withdrawal § 4219.11 Withdrawal liability upon mass withdrawal. (a) Initial withdrawal liability. The plan sponsor of a multiemployer plan that experiences a...

  6. 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.

  7. 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

  8. 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.

  9. 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

  10. Diagnosis and Management of Alcoholic Liver Disease

    PubMed Central

    Dugum, Mohannad; McCullough, Arthur

    2015-01-01

    Alcohol is a leading cause of liver disease and is associated with significant morbidity and mortality. Several factors, including the amount and duration of alcohol consumption, affect the development and progression of alcoholic liver disease (ALD). ALD represents a spectrum of liver pathology ranging from fatty change to fibrosis to cirrhosis. Early diagnosis of ALD is important to encourage alcohol abstinence, minimize the progression of liver fibrosis, and manage cirrhosis-related complications including hepatocellular carcinoma. A number of questionnaires and laboratory tests are available to screen for alcohol intake. Liver biopsy remains the gold-standard diagnostic tool for ALD, but noninvasive accurate alternatives, including a number of biochemical tests as well as liver stiffness measurement, are increasingly being utilized in the evaluation of patients with suspected ALD. The management of ALD depends largely on complete abstinence from alcohol. Supportive care should focus on treating alcohol withdrawal and providing enteral nutrition while managing the complications of liver failure. Alcoholic hepatitis (AH) is a devastating acute form of ALD that requires early recognition and specialized tertiary medical care. Assessment of AH severity using defined scoring systems is important to allocate resources and initiate appropriate therapy. Corticosteroids or pentoxifylline are commonly used in treating AH but provide a limited survival benefit. Liver transplantation represents the ultimate therapy for patients with alcoholic cirrhosis, with most transplant centers mandating a 6 month period of abstinence from alcohol before listing. Early liver transplantation is also emerging as a therapeutic measure in specifically selected patients with severe AH. A number of novel targeted therapies for ALD are currently being evaluated in clinical trials. PMID:26356792

  11. 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.

  12. Double Dissociation of Monoacylglycerol Lipase Inhibition and CB1 Antagonism in the Central Amygdala, Basolateral Amygdala, and the Interoceptive Insular Cortex on the Affective Properties of Acute Naloxone-Precipitated Morphine Withdrawal in Rats.

    PubMed

    Wills, Kiri L; Petrie, Gavin N; Millett, Geneva; Limebeer, Cheryl L; Rock, Erin M; Niphakis, Micah J; Cravatt, Benjamin F; Parker, Linda A

    2016-06-01

    Both CB1 receptor antagonism and agonism, in particular by 2-arachidonyl glycerol (2-AG), have been shown to reduce somatic symptoms of morphine withdrawal (MWD). Here we evaluated the effects of both systemic pretreatment with the monoacylglycerol lipase (MAGL) inhibitor MJN110 (which selectively elevates 2-AG) and central administration of both MJN110 and the CB1 antagonist (AM251) on the affective properties of MWD. Acute MWD induced place aversion occurs when naloxone is administered 24 h following a single exposure to a high dose of morphine. Systemic pretreatment with the MAGL inhibitor, MJN110, prevented the aversive effects of acute MWD by a CB1 receptor-dependent mechanism. Furthermore, in a double dissociation, AM251 infusions into the central amygdala, but MJN110 infusions into the basolateral amygdala, interfered with the naloxone-precipitated MWD induced place aversion. As well, MJN110, but not AM251, infusions into the interoceptive insular cortex (a region known to be activated in acute MWD) also prevented the establishment of the place aversion by a CB1 mechanism of action. These findings reveal the respective sites of action of systemically administered MJN110 and AM251 in regulating the aversive effects of MWD.

  13. [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.

  14. 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 ...

  15. 27 CFR 19.537 - Withdrawal of spirits free of tax.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... of tax. 19.537 Section 19.537 Alcohol, Tobacco Products and Firearms ALCOHOL AND TOBACCO TAX AND... Withdrawal of Spirits Free of Tax § 19.537 Withdrawal of spirits free of tax. Spirits withdrawn free of tax... consignee, in accordance with § 19.779. Bulk conveyances used to transport spirits withdrawn free of...

  16. 27 CFR 19.502 - Withdrawal of spirits on production or filling gauge.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... production or filling gauge. 19.502 Section 19.502 Alcohol, Tobacco Products and Firearms ALCOHOL AND TOBACCO... Withdrawals General § 19.502 Withdrawal of spirits on production or filling gauge. When the production or... for any lawful purpose on the production or filling gauge. When the production or filling gauge...

  17. 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

  18. 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

  19. The thyrotropin releasing hormone stimulation test in alcoholism.

    PubMed

    Pienaar, W P; Roberts, M C; Emsley, R A; Aalbers, C; Taljaard, F J

    1995-09-01

    The mechanism for a blunted thyroid stimulating hormone (TSH) response to thyrotropin releasing hormone (TRH) in alcoholics is not known. We performed a combined TRH and gonadoliberin stimulation test on three well-defined groups of nondepressed alcoholic men. Group A comprised patients with acute withdrawal symptoms (n = 28), group B patients abstinent for 5-8 weeks (n = 29) and group C patients who had been abstinent for > 2 years (n = 16). Twenty-two healthy male volunteers were used for comparison. A blunted TSH response to TRH (delta TSH < 5 microU/l) occurred only in groups A (39%) and B (17%). In group A delta TSH showed a significant negative correlation with the severity of withdrawal symptoms and a significant positive correlation with serum magnesium levels. In group B, patients with a family history of alcoholism had significantly lower delta TSH levels than those without such a family history. Groups did not differ with respect to basal and delta prolactin, and TSH responses were not significantly associated with vitamin deficiency, cortisol levels or free thyroid hormone levels. We conclude that TRH stimulation test blunting appears to be related to factors operating in the withdrawal state and improves with continued abstinence. A possible role of genetic factors and serum magnesium needs to be further explored.

  20. [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.

  1. Non-invasive brain stimulation in the functional evaluation of alcohol effects and in the treatment of alcohol craving: a review.

    PubMed

    Nardone, Raffaele; Bergmann, Jürgen; Christova, Monica; Lochner, Piergiorgio; Tezzon, Frediano; Golaszewski, Stefan; Trinka, Eugen; Brigo, Francesco

    2012-12-01

    Acute and chronic consumption of alcohol have direct effects on central nervous system by altering predominantly gamma-aminobutyric acidergic and glutamatergic neurotransmission. Abnormalities in these neurotransmitter systems can be demonstrated by changes in cortical excitability parameters assessed with transcranial magnetic stimulation (TMS). Furthermore, integrated approaches utilizing TMS combined with electroencephalography (EEG) enable the evaluation of the focal effects of alcohol on the human cortex, providing useful information, different from that obtained using other functional brain imaging modalities. Alcohol was found to modulate EEG responses evoked by motor-cortex TMS, predominantly at the right prefrontal cortex, indicating that ethanol alters the functional connectivity between motor and prefrontal areas. Alcohol decreases amplitudes of EEG responses of anterior parts of the cortex after left prefrontal TMS, suggesting a decrease of prefrontal cortical excitability. High-frequency repetitive TMS (rTMS) revealed significant changes in short-term plasticity of the primary motor cortex after acute ethanol intake and in patients with chronic alcohol abuse. TMS findings also support the recently emerged theory that abnormal function of glutamate receptors plays a relevant role in the development of alcohol dependence and manifestation of the alcohol withdrawal syndrome. Finally, initial studies provide evidence that non-invasive brain stimulation techniques (rTMS and transcranial direct current stimulation) might represent a potential therapeutic tool to reduce alcohol craving. Future studies with larger sample size evaluating the clinical effects of these neuromodulatory approaches are required to confirm and extend the preliminary findings.

  2. 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

  3. 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

  4. 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

  5. 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

  6. 27 CFR 19.585 - Production and withdrawal records.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... BUREAU, DEPARTMENT OF THE TREASURY ALCOHOL DISTILLED SPIRITS PLANTS Records and Reports Production Records § 19.585 Production and withdrawal records. (a) Production of spirits. The following rules apply... 27 Alcohol, Tobacco Products and Firearms 1 2014-04-01 2014-04-01 false Production and...

  7. 27 CFR 22.111 - Withdrawals under permit.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ..., DEPARTMENT OF THE TREASURY LIQUORS DISTRIBUTION AND USE OF TAX-FREE ALCOHOL Withdrawal and Receipt of Tax... distilled spirits plant or, under the provisions of 26 U.S.C. 5688(a)(2)(B), receive alcohol from the... its permit, or amended permit, to a distilled spirits plant for the “initial order” from...

  8. 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

  9. 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

  10. 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.

  11. 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

  12. Memantine reduces alcohol drinking but not relapse in alcohol-dependent rats.

    PubMed

    Alaux-Cantin, Stéphanie; Buttolo, Romain; Houchi, Hakim; Jeanblanc, Jérôme; Naassila, Mickaël

    2015-09-01

    Alcoholism is a chronic relapsing disorder with consequences on health and that requires more effective treatments. Among alternative therapies, the therapeutic potential of the non-competitive N-methyl-D-aspartate receptor antagonist memantine has been suggested. Despite promising results, its efficiency in the treatment of alcoholism remains controversial. Currently, there is no pre-clinical data regarding its effects on the motivation for ethanol in post-dependent (PD) animals exposed to intermittent ethanol vapor, a validated model of alcoholism. Thus, the objectives of this study were to evaluate the effects of acute injections of memantine (0, 12.5, 25 and 50 mg/kg) on operant ethanol self-administration in non-dependent (ND) and PD rats tested either during acute withdrawal or relapse after protracted abstinence. Our results showed that memantine (25 mg/kg) abolished ethanol self-administration in ND rats and reduced by half the one of PD rats during acute withdrawal. While this effect was observed only 6 hours after treatment in ND rats, it was long lasting in PD rats (at least 30 hours after injection). Furthermore, our results indicated that memantine did not modify the breaking point for ethanol. This suggests that memantine probably act by potentiating the pharmacological effect of ethanol but not by reducing motivation for ethanol. Finally, memantine was also ineffective in reducing relapse after protracted abstinence. Altogether, our pre-clinical results highlighted a potential therapeutic use of memantine that may be used as a replacement therapy drug but not as relapse-preventing drug.

  13. Caffeine withdrawal syndrome in social interaction test in mice: effects of the NMDA receptor channel blockers, memantine and neramexane.

    PubMed

    Sukhotina, I A; Zvartau, E E; Danysz, W; Bespalov, A Y

    2004-05-01

    Antagonists acting at N-methyl-D-aspartate (NMDA) receptors have been demonstrated repeatedly to attenuate the expression of drug and alcohol withdrawal syndromes. The present study aimed to evaluate the effects of NMDA receptor blockade on the expression of behavioural signs of caffeine withdrawal syndrome, assessed using the social interaction paradigm. Adult male Swiss mice were treated with increasing doses of caffeine (40-100 mg/kg, i.p., twice daily) for 8 days. Twenty-four hours after the last injection of caffeine, there were significant increases in duration and frequency of defensive behaviours, as well as decreased locomotor activity. These changes faded within 72 hours. Pretreatment with a single dose of caffeine (1 mg/kg; 24 h after the end of repeated caffeine administration and 30 min prior to the test) completely reversed these withdrawal-related changes. Separate groups of mice were treated i.p. with different doses of memantine (1, 3 or 10 mg/kg) or neramexane (MRZ 2/579; 1, 3 or 10 mg/kg) 24 h after the last caffeine injection. Both compounds dose-dependently reduced the expression of defensive behaviours while increasing motor activity. These data suggest that NMDA receptor blockade may counteract the acute behavioural effects of caffeine withdrawal.

  14. Quantitative trait locus gene mapping: a new method for locating alcohol response genes.

    PubMed

    Crabbe, J C

    1996-01-01

    Alcoholism is a multigenic trait with important non-genetic determinants. Studies with genetic animal models of susceptibility to several of alcohol's effects suggest that several genes contributing modest effects on susceptibility (Quantitative Trait Loci, or QTLs) are important. A new technique of QTL gene mapping has allowed the identification of the location in mouse genome of several such QTLs. The method is described, and the locations of QTLs affecting the acute alcohol withdrawal reaction are described as an example of the method. Verification of these QTLs in ancillary studies is described and the strengths, limitations, and future directions to be pursued are discussed. QTL mapping is a promising method for identifying genes in rodents with the hope of directly extrapolating the results to the human genome. This review is based on a paper presented at the First International Congress of the Latin American Society for Biomedical Research on Alcoholism, Santiago, Chile, November 1994. PMID:12893462

  15. The contribution of electrophysiology to knowledge of the acute and chronic effects of ethanol.

    PubMed

    Little, H J

    1999-12-01

    This review describes the effects of ethanol on the components of neuronal transmission and the relationship of such effects to the behavioural actions of ethanol. The concentrations of ethanol with acute actions on voltage-sensitive ion channels are first described, then the actions of ethanol on ligand-gated ion channels, including those controlled by cholinergic receptors, 5-hydroxytryptamine receptors, the various excitatory amino acid receptors, and gamma-aminobutyric acid receptors. Acute effects of ethanol are then described on brain areas thought to be involved in arousal and attention, the reinforcing effects of ethanol, the production of euphoria, the actions of ethanol on motor control, and the amnesic effects of ethanol; the acute effects of ethanol demonstrated by EEG studies are also discussed. Chronic effects of alcohol on neuronal transmission are described in the context of the various components of the ethanol withdrawal syndrome, withdrawal hyperexcitability, dysphoria and anhedonia, withdrawal anxiety, craving, and relapse drinking. Electrophysiological studies on the genetic influences on the effects of ethanol are discussed, particularly the acute actions of ethanol and electrophysiological differences reported in individuals predisposed to alcoholism. The conclusion notes the concentration of studies on the classical transmitters, with relative neglect of the effects of ethanol on peptides and on neuronal interactions between brain areas and integrated patterns of neuronal activity. PMID:10665833

  16. Neonatal opioid withdrawal syndrome.

    PubMed

    Sutter, Mary Beth; Leeman, Lawrence; Hsi, Andrew

    2014-06-01

    Neonatal opioid withdrawal syndrome is common due to the current opioid addiction epidemic. Infants born to women covertly abusing prescription opioids may not be identified as at risk until withdrawal signs present. Buprenorphine is a newer treatment for maternal opioid addiction and appears to result in a milder withdrawal syndrome than methadone. Initial treatment is with nonpharmacological measures including decreasing stimuli, however pharmacological treatment is commonly required. Opioid monotherapy is preferred, with phenobarbital or clonidine uncommonly needed as adjunctive therapy. Rooming-in and breastfeeding may decease the severity of withdrawal. Limited evidence is available regarding long-term effects of perinatal opioid exposure.

  17. [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.

  18. 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

  19. Characteristics of heart rate variability in alcohol-dependent subjects and nondependent chronic alcohol users.

    PubMed

    Karpyak, Victor M; Romanowicz, Magdalena; Schmidt, John E; Lewis, Kriste A; Bostwick, John M

    2014-01-01

    Heart rate variability (HRV) is an objective and sensitive measure of integrated physiological functioning reflective of heart rhythm responsivity to internal and external demands. Reduced HRV is associated with vulnerability to stress and deterioration of medical and/or psychiatric conditions, while increased HRV is associated with a favorable treatment response and recovery from various medical and/or psychiatric conditions. Our previous review found that acute alcohol consumption caused decreased parasympathetic and increased sympathetic HRV effects in both nonalcoholic and chronic alcohol users. This review investigates the effects of chronic alcohol consumption on HRV in alcohol-dependent subjects and nondependent users. MEDLINE, Scopus, and PubMed were searched for human experimental and clinical trials that measured the effects of chronic alcohol use on HRV. Only publications that included a description of their study designs and clearly stated methodologies for data collections, and outcome measures were reviewed. We have reviewed a total of 24 articles. In nondependent users, low dose (approximating the recommended daily amount of 1 standard drink in women and 2 in men) use is associated with increased HRV parameters compared to those who drink less frequently or abstain altogether. A further increase in consumption is associated with decreased HRV compared to both abstainers and more moderate drinkers. HRV changes during withdrawal generally follow the same negative direction but are more complex and less understood. In dependent subjects, an improvement in HRV was seen following abstinence but remained reduced compared to nonalcoholic controls. This review demonstrates that HRV changes associated with chronic use follow a J-shaped curve. It supports recommendations that limit daily alcohol intake to no more than 2 drinks for men and 1 drink for women. Future studies should investigate HRV as a biomarker of alcoholism development and treatment response as

  20. Alcohol Usage and Abrupt Cessation Modulate Diurnal Activity

    PubMed Central

    Norrell, Stacy; Reyes-Vasquez, Cruz; Burau, Keith; Dafny, Nachum

    2010-01-01

    Alcohol has many effects throughout the body. The effect on circadian rhythms and the correlation of these effects to withdrawal effects of alcohol present interesting findings. By measuring 3 planes of activity of female Sprague-Dawley rats during alcohol usage and continuing study through the first two days following withdrawal of alcohol allow for the observation of a drastic modulation of the circadian pattern of activity. PMID:20615456

  1. 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

  2. Alcohol and violence: neuropeptidergic modulation of monoamine systems

    PubMed Central

    Miczek, Klaus A.; DeBold, Joseph F.; Hwa, Lara S.; Newman, Emily L.; de Almeida, Rosa M. M.

    2015-01-01

    Neurobiological processes underlying the epidemiologically-established link between alcohol and several types of social, aggressive, and violent behavior remain poorly understood. Acute low doses of alcohol, as well as withdrawal from long-term alcohol use, may lead to escalated aggressive behavior in a subset of individuals. An urgent task will be to disentangle the host of interacting genetic and environmental risk factors in individuals that are predisposed to engage in escalated aggressive behavior. The modulation of 5-hydroxytryptamine impulse flow by gamma-aminobutyric acid (GABA) and glutamate, acting via distinct ionotropic and metabotropic receptor subtypes in the dorsal raphe nucleus during alcohol consumption, is of critical significance in the suppression and escalation of aggressive behavior. In anticipation and reaction to aggressive behavior, neuropeptides such as corticotropin-releasing factor, neuropeptide Y, opioid peptides, and vasopressin interact with monoamines, GABA, and glutamate to attenuate and amplify aggressive behavior in alcohol-consuming individuals. These neuromodulators represent novel molecular targets for intervention that await clinical validation. Intermittent episodes of brief social defeat during aggressive confrontations are sufficient to cause long-lasting neuroadaptations that can lead to the escalation of alcohol consumption. PMID:26285061

  3. 27 CFR 22.113 - Receipt of tax-free alcohol.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 1 2013-04-01 2013-04-01 false Receipt of tax-free alcohol. 22.113 Section 22.113 Alcohol, Tobacco Products and Firearms ALCOHOL AND TOBACCO TAX AND TRADE BUREAU, DEPARTMENT OF THE TREASURY ALCOHOL DISTRIBUTION AND USE OF TAX-FREE ALCOHOL Withdrawal...

  4. 27 CFR 22.113 - Receipt of tax-free alcohol.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 1 2014-04-01 2014-04-01 false Receipt of tax-free alcohol. 22.113 Section 22.113 Alcohol, Tobacco Products and Firearms ALCOHOL AND TOBACCO TAX AND TRADE BUREAU, DEPARTMENT OF THE TREASURY ALCOHOL DISTRIBUTION AND USE OF TAX-FREE ALCOHOL Withdrawal...

  5. 27 CFR 19.531 - Authorized withdrawals without payment of tax.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 1 2010-04-01 2010-04-01 false Authorized withdrawals without payment of tax. 19.531 Section 19.531 Alcohol, Tobacco Products and Firearms ALCOHOL AND TOBACCO... authorized under 26 U.S.C. 5373; (g) Transfer to any university, college of learning, or institution...

  6. Molecular mechanisms of synaptic remodeling in alcoholism.

    PubMed

    Kyzar, Evan J; Pandey, Subhash C

    2015-08-01

    Alcohol use and alcohol addiction represent dysfunctional brain circuits resulting from neuroadaptive changes during protracted alcohol exposure and its withdrawal. Alcohol exerts a potent effect on synaptic plasticity and dendritic spine formation in specific brain regions, providing a neuroanatomical substrate for the pathophysiology of alcoholism. Epigenetics has recently emerged as a critical regulator of gene expression and synaptic plasticity-related events in the brain. Alcohol exposure and withdrawal induce changes in crucial epigenetic processes in the emotional brain circuitry (amygdala) that may be relevant to the negative affective state defined as the "dark side" of addiction. Here, we review the literature concerning synaptic plasticity and epigenetics, with a particular focus on molecular events related to dendritic remodeling during alcohol abuse and alcoholism. Targeting epigenetic processes that modulate synaptic plasticity may yield novel treatments for alcoholism.

  7. 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.

  8. 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 ...

  9. Withdrawing Nutrition, Hydration

    Cancer.gov

    Module eleven of the EPEC-O Self-Study Original Version discusses the general aspects of withholding or withdrawing of life-sustaining therapies, and presents a specific application to artificial nutrition and hydration.

  10. 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

  11. 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

  12. 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.

  13. 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

  14. 27 CFR 22.113 - Receipt of tax-free alcohol.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 1 2011-04-01 2011-04-01 false Receipt of tax-free alcohol. 22.113 Section 22.113 Alcohol, Tobacco Products and Firearms ALCOHOL AND TOBACCO TAX AND TRADE BUREAU, DEPARTMENT OF THE TREASURY LIQUORS DISTRIBUTION AND USE OF TAX-FREE ALCOHOL Withdrawal...

  15. 27 CFR 22.113 - Receipt of tax-free alcohol.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 1 2010-04-01 2010-04-01 false Receipt of tax-free alcohol. 22.113 Section 22.113 Alcohol, Tobacco Products and Firearms ALCOHOL AND TOBACCO TAX AND TRADE BUREAU, DEPARTMENT OF THE TREASURY LIQUORS DISTRIBUTION AND USE OF TAX-FREE ALCOHOL Withdrawal...

  16. 27 CFR 22.113 - Receipt of tax-free alcohol.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 1 2012-04-01 2012-04-01 false Receipt of tax-free alcohol. 22.113 Section 22.113 Alcohol, Tobacco Products and Firearms ALCOHOL AND TOBACCO TAX AND TRADE BUREAU, DEPARTMENT OF THE TREASURY LIQUORS DISTRIBUTION AND USE OF TAX-FREE ALCOHOL Withdrawal...

  17. 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

  18. 19 CFR 24.4 - Optional method for payment of estimated import taxes on alcoholic beverages upon entry, or...

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... taxes on alcoholic beverages upon entry, or withdrawal from warehouse, for consumption. 24.4 Section 24... estimated import taxes on alcoholic beverages upon entry, or withdrawal from warehouse, for consumption. (a) Application to defer. An importer, including a transferee of alcoholic beverages in a Customs bonded...

  19. 19 CFR 24.4 - Optional method for payment of estimated import taxes on alcoholic beverages upon entry, or...

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... taxes on alcoholic beverages upon entry, or withdrawal from warehouse, for consumption. 24.4 Section 24... estimated import taxes on alcoholic beverages upon entry, or withdrawal from warehouse, for consumption. (a) Application to defer. An importer, including a transferee of alcoholic beverages in a Customs bonded...

  20. 19 CFR 24.4 - Optional method for payment of estimated import taxes on alcoholic beverages upon entry, or...

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... taxes on alcoholic beverages upon entry, or withdrawal from warehouse, for consumption. 24.4 Section 24... estimated import taxes on alcoholic beverages upon entry, or withdrawal from warehouse, for consumption. (a) Application to defer. An importer, including a transferee of alcoholic beverages in a Customs bonded...

  1. [Electrophysiological features (EEG) of ethanol withdrawal syndromes on isolated perfused rat brain].

    PubMed

    Tezikov, E B; Litvicki, P F

    2015-01-01

    On isolated rat brains we studied native EEC and its derivates (mean EEC amplitude and power spectrums - Fourier transformation) during perfusion with ethanol (65 Mm/ L) and after its withdrawal. Previously rats were undergone ethanol burden for 6 days according to Majchrowicz procedures to get alcohol withdrawal syndrome. Duration perfusion without ethanol was 5, 10 and 20 min depending on the experimental schedule. Ethanol infusion between periods of withdrawal comprised 20 min. 55% of isolated brains shown epileptiform activity after 1-2 min of ethanol withdrawal but others manifested only increased mean amplitude and the power spectrums of EEC as well as an appearance of single or batch spikes. Differences between in vivo and in vitro conditions can be explained by the accelerated rate of ethanol elimination. The high positive correlation was obtained between EEC findings at the 5-th min of the first ethanol withdrawal and the same findings at the 5-th min of ethanol withdrawal in the second and the third episodes of ethanol withdrawal. Prolongation of withdrawal period more than 5th min caused brain death showing epileptiform activity. Isolated rat brain is the convenient subject to study pathogenesis of excitability of neurons and examination of drugs to treat alcohol withdrawal syndrome.

  2. The window of opportunity for treatment withdrawal.

    PubMed

    Wilkinson, Dominic

    2011-03-01

    Physicians sometimes refer to a "window of opportunity" for withdrawing life-sustaining treatment in patients with acute severe brain injury. There is a period of critical illness and physiological instability when treatment withdrawal is likely to be followed by death but prognosis is uncertain. If decisions are delayed, greater prognostic certainty can be achieved, but with the risk that the patient is no longer dependent on life support and survives with very severe disability. In this article I draw on the example of birth asphyxia and highlight the role that the window of opportunity sometimes plays in decisions about life-sustaining treatment in intensive care. I outline the potential arguments in favor of and against taking the window into account. I argue that it is, at least sometimes, ethical and appropriate for physicians and parents to be influenced by the window of opportunity in their decisions about life-sustaining treatment.

  3. Student Withdrawal Study.

    ERIC Educational Resources Information Center

    Hayward, Craig

    This document addresses the problem of students withdrawing from courses before completion and in the process attempts to devise ways that Mendocino College can aid students complete their courses. The report uses findings from two research reports. The first report was completed at the Florida Community College (FCC), which discovered that 75% of…

  4. Hypertension after clonidine withdrawal.

    PubMed

    Husserl, F E; deCarvalho, J G; Batson, H M; Frohlich, E D

    1978-05-01

    Rebound hypertension occurred in two patients upon clonidine withdrawal. Treatment of the hypertensive crisis consists of both alpha- and beta-adrenergic receptor blockade, reserpine, or the reintroduction of clonidine. With effective control of pressure during the crisis, long-term antihypertensive therapy must be resumed.

  5. 77 FR 34052 - Pfizer, Inc.; Withdrawal of Approval of Familial Adenomatous Polyposis Indication for CELEBREX

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-06-08

    ... years and older, ankylosing spondylitis, primary dysmenorrhea, and for the management of acute pain in adults. Withdrawal of approval of the FAP indication does not affect any other approved indication...

  6. gamma-Hydroxybutyric acid (GHB) suppresses alcohol's motivational properties in alcohol-preferring rats.

    PubMed

    Maccioni, Paola; Pes, Daniela; Fantini, Noemi; Carai, Mauro A M; Gessa, Gian Luigi; Colombo, Giancarlo

    2008-03-01

    gamma-Hydroxybutyric acid (GHB) reduces alcohol drinking, promotes abstinence from alcohol, suppresses craving for alcohol, and ameliorates alcohol withdrawal syndrome in alcoholics. At preclinical level, GHB suppresses alcohol withdrawal signs and alcohol intake in rats. The present study was designed to investigate whether GHB administration was capable of affecting alcohol's motivational properties (the possible animal correlate of human craving for alcohol) in selectively bred Sardinian alcohol-preferring rats. To this aim, rats were initially trained to lever press for alcohol (15%, vol/vol) under a procedure of operant, oral alcohol self-administration (fixed ratio 4 in 30-min daily sessions). Once responding for alcohol had stabilized, rats were divided into two groups and allocated to two independent experiments. Experiment 1 assessed the effect of GHB (0, 25, 50, and 100mg/kg, i.p.) on breakpoint for alcohol, defined as the lowest response requirement not achieved by each rat when exposed to a single-session progressive ratio schedule of reinforcement. Experiment 2 assessed the effect of GHB (0, 25, 50, and 100mg/kg, i.p.) on single-session extinction responding for alcohol (alcohol was absent and unreinforced responding was recorded). Breakpoint and extinction responding for alcohol are reliable indexes of alcohol's motivational strength. In Experiment 1, all doses of GHB reduced--by approximately 20% in comparison to saline-treated rats--breakpoint for alcohol. In Experiment 2, administration of 25, 50, and 100mg/kg GHB reduced--by approximately 25%, 40%, and 50%, respectively, in comparison to saline-treated rats--extinction responding for alcohol. Conversely, no dose of GHB altered breakpoint and extinction responding for sucrose (3%, wt/vol) in two independent subsets of Sardinian alcohol-preferring rats. Together, these data suggest that GHB administration specifically suppressed alcohol's motivational properties in Sardinian alcohol-preferring rats

  7. Serotonin's Complex Role in Alcoholism: Implications for Treatment and Future Research.

    PubMed

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

    2016-06-01

    Current pharmacological treatments for alcohol dependence have focused on reducing alcohol consumption, but to date there are few treatments that also address the negative affective symptoms during acute and protracted alcohol withdrawal which are often exacerbated in people with comorbid anxiety and depression. Selective serotonin reuptake inhibitors (SSRIs) are sometimes prescribed to ameliorate these symptoms but can exacerbate anxiety and cravings in a select group of patients. In this critical review, we discuss recent literature describing an association between alcohol dependence, the SERT linked polymorphic region (5-HTTLPR), and pharmacological response to SSRIs. Given the heterogeneity in responsiveness to serotonergic drugs across the spectrum of alcoholic subtypes, we assess the contribution of specific 5-HT circuits to discrete endophenotypes of alcohol dependence. 5-HT circuits play a distinctive role in reward, stress, and executive function which may account for the variation in response to serotonergic drugs. New optogenetic and chemogenetic methods for dissecting 5-HT circuits in alcohol dependence may provide clues leading to more effective pharmacotherapies. Although our current understanding of the role of 5-HT systems in alcohol dependence is incomplete, there is some evidence to suggest that 5-HT3 receptor antagonists are effective in people with the L/L genotype of the 5-HTTLPR polymorphism while SSRIs may be more beneficial to people with the S/L or S/S genotype. Studies that assess the impact of serotonin transporter polymorphisms on 5-HT circuit function and the subsequent development of alcohol use disorders will be an important step forward in treating alcohol dependence. PMID:27161942

  8. Diet influences cocaine withdrawal behaviors in the forced swimming test.

    PubMed

    Loebens, M; Barros, H M T

    2003-01-01

    The effects of drugs of abuse might depend on several environmental factors, among them the individual's feeding habits. It was our objective to study the influence of the diet on cocaine acute behavioral effects and during the first 5 days of withdrawal after prolonged treatment. Rats were fed a balanced diet, high-protein diet, high-carbohydrate diet or high-fat diet from weaning to adulthood. Adult rats were injected with 15 mg/kg cocaine 24, 5 and 1 h before the forced swimming retest or the drug was administered daily during 15 days and the animals were evaluated in the forced swimming test on five daily occasions after drug withdrawal. Diets alone did not induce significant behavioral differences in locomotion, immobility, swimming, climbing or head shakes. Acute cocaine reduced immobility during the forced swimming test and increased locomotion demonstrating a nonspecific antiimmobility effect related to hyperactivity. Acute cocaine reduced head shakes of rats fed high-protein and high-carbohydrate diets. After cocaine withdrawal, head shakes were decreased for rats fed any of the diets and rats were more immobile if fed a high-fat diet and were less immobile if fed a high-protein or high-carbohydrate diet. In conclusion, differences in the amounts of macronutrients in the diet may cause different behavioral outcomes after acute cocaine and during cocaine withdrawal.

  9. Tobacco Withdrawal Symptoms Mediate Motivation to Reinstate Smoking During Abstinence

    PubMed Central

    Aguirre, Claudia; Madrid, Jillian; Leventhal, Adam M.

    2015-01-01

    Withdrawal-based theories of addiction hypothesize that motivation to reinstate drug use following acute abstinence is mediated by withdrawal symptoms. Experimental tests of this hypothesis in the tobacco literature are scant and may be subject to methodological limitations. This study utilized a robust within-subject laboratory experimental design to investigate the extent to which composite tobacco withdrawal symptomatology level and three unique withdrawal components (i.e., low positive affect, negative affect, and urge to smoke) mediated the effect of smoking abstinence on motivation to reinstate smoking. Smokers (10≥cig/day; N=286) attended two counterbalanced sessions at which abstinence duration was differentially manipulated (1-hour vs. 17-hours). At both sessions, participants reported current withdrawal symptoms and subsequently completed a task in which they were monetarily rewarded proportional to the length of time they delayed initiating smoking, with shorter latency reflecting stronger motivation to reinstate smoking. Abstinence reduced latency to smoking initiation and positive affect and increased composite withdrawal symptom level, urge, and negative affect. Abstinence-induced reductions in latency to initiating smoking were mediated by each withdrawal component, with stronger effects operating through urge. Combined analyses suggested that urge, negative affect, and low positive affect operate through empirically-unique mediational pathways. Secondary analyses suggested similar effects on smoking quantity, few differences among specific urge and affect subtypes, and that dependence amplifies some abstinence effects. This study provides the first experimental evidence that within-person variation in abstinence impacts motivation to reinstate drug use through withdrawal. Urge, negative affect, and low positive affect may reflect unique withdrawal-mediated mechanisms underlying tobacco addiction. PMID:25961814

  10. Tobacco withdrawal symptoms mediate motivation to reinstate smoking during abstinence.

    PubMed

    Aguirre, Claudia G; Madrid, Jillian; Leventhal, Adam M

    2015-08-01

    Withdrawal-based theories of addiction hypothesize that motivation to reinstate drug use following acute abstinence is mediated by withdrawal symptoms. Experimental tests of this hypothesis in the tobacco literature are scant and may be subject to methodological limitations. This study utilized a robust within-subject laboratory experimental design to investigate the extent to which composite tobacco withdrawal symptomatology level and 3 unique withdrawal components (i.e., low positive affect, negative affect, and urge to smoke) mediated the effect of smoking abstinence on motivation to reinstate smoking. Smokers (≥10 cigarettes per day; N = 286) attended 2 counterbalanced sessions at which abstinence duration was differentially manipulated (1 hr vs. 17 hr). At both sessions, participants reported current withdrawal symptoms and subsequently completed a task in which they were monetarily rewarded proportional to the length of time they delayed initiating smoking, with shorter latency reflecting stronger motivation to reinstate smoking. Abstinence reduced latency to smoking initiation and positive affect and increased composite withdrawal symptom level, urge, and negative affect. Abstinence-induced reductions in latency to initiating smoking were mediated by each withdrawal component, with stronger effects operating through urge. Combined analyses suggested that urge, negative affect, and low positive affect operate through empirically unique mediational pathways. Secondary analyses suggested similar effects on smoking quantity, few differences among specific urge and affect subtypes, and that dependence amplifies some abstinence effects. This study provides the first experimental evidence that within-person variation in abstinence impacts motivation to reinstate drug use through withdrawal. Urge, negative affect, and low positive affect may reflect unique withdrawal-mediated mechanisms underlying tobacco addiction.

  11. Tianeptine and alcohol dependence.

    PubMed

    Favre, J D; Guelfi-Sozzi, C; Delalleau, B; Lôo, H

    1997-10-01

    Several arguments are in favour of the use of antidepressant drugs in alcohol-dependent patients, especially those acting on the serotoninergic system: (1) neurochemical data indicate the interaction between alcohol and 5-HT metabolism, (2) pharmacological studies show an improvement in the behaviour of alcoholized animals treated with antidepressants, (3) depression is a frequent disease in alcoholic patients. Tianeptine has been shown to be active in the treatment of depression in patients with history of alcohol abuse or dependence. In a first double-blind study performed versus amitryptiline, depression after withdrawal was improved by tianeptine, and biological abnormalities usually related to chronic alcohol intake tended to decrease. Similar results were found in an open study carried out on 277 alcoholic patients treated for 1 year. As these patients were depressed, no definite conclusion could be drawn from these results in respect of a specific action of tianeptine on alcohol dependence. Thus, a multicentre double-blind study has been performed which compared tianeptine (12.5 mg t.i.d) and placebo in 342 non-depressed patients fulfilling DSM-III-R criteria for Psychoactive Substance Dependence (alcohol). Other inclusion criteria were: daily alcohol intake higher than 80 g, minimum score of 3 on the Short-Mast Questionnaire, mean corpuscular volume above 98 fl and/or gamma Gt more than twice the upper limit of normal. The patients were treated for 9 months. The intention-to-treat population and the per protocol population were made up of 327 patients and 111 patients, respectively. The main efficacy criterion was the absence of alcoholic relapse (abstinence) defined by the patient's statements, the investigators clinical judgement and some biological parameters: alcohol blood levels, gamma Gt levels. Secondary criteria were the evolution of the alcohol consumption in the patients who relapsed, cumulative abstinence duration, a visual analogue scale for the

  12. Circadian wheel-running activity during withdrawal from chronic intermittent ethanol exposure in mice

    PubMed Central

    Logan, Ryan W.; Seggio, Joseph A.; Robinson, Stacy L.; Richard, Gregory R.; Rosenwasser, Alan M.

    2010-01-01

    Alcohol withdrawal is associated with affective-behavioral disturbances in both human alcoholics and in animal models. In general, these phenomena are potentiated by increased alcohol exposure duration and by prior withdrawal episodes. Previous studies have also reported locomotor hypoactivity during ethanol withdrawal in rats and mice, but only in novel test environments, not in the home-cage. In the present study, we examined the effects of withdrawal from chronic intermittent ethanol (CIE) vapor exposure on the level and circadian periodicity of wheel-running activity in C57BL/6J mice. CIE treatment resulted in reductions in wheel-running activity relative to plain-air controls that persisted for about one week after withdrawal. Analysis of circadian waveforms indicated that reduced activity occurred throughout the night phase, but that daily activity patterns were otherwise unaltered. CIE failed to alter free-running circadian period or phase in animals maintained under constant darkness. These results show that ethanol withdrawal can result in locomotor hypoactivity even in the habitual, home-cage environment, and suggest that withdrawal-related reductions in wheel-running activity may reflect the specific motivational significance of this behavior. PMID:20682191

  13. 27 CFR 19.420 - Withdrawals of spirits without payment of tax for experimental or research use.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... Withdrawals of spirits without payment of tax for experimental or research use. A scientific university, college of learning, or institution of scientific research qualified under § 19.35 may withdraw spirits... without payment of tax for experimental or research use. 19.420 Section 19.420 Alcohol, Tobacco...

  14. 27 CFR 19.420 - Withdrawals of spirits without payment of tax for experimental or research use.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... Withdrawals of spirits without payment of tax for experimental or research use. A scientific university, college of learning, or institution of scientific research qualified under § 19.35 may withdraw spirits... without payment of tax for experimental or research use. 19.420 Section 19.420 Alcohol, Tobacco...

  15. 27 CFR 19.420 - Withdrawals of spirits without payment of tax for experimental or research use.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... Withdrawals of spirits without payment of tax for experimental or research use. A scientific university, college of learning, or institution of scientific research qualified under § 19.35 may withdraw spirits... without payment of tax for experimental or research use. 19.420 Section 19.420 Alcohol, Tobacco...

  16. 27 CFR 19.420 - Withdrawals of spirits without payment of tax for experimental or research use.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... Withdrawals of spirits without payment of tax for experimental or research use. A scientific university, college of learning, or institution of scientific research qualified under § 19.35 may withdraw spirits... without payment of tax for experimental or research use. 19.420 Section 19.420 Alcohol, Tobacco...

  17. New Drugs of Abuse and Withdrawal Syndromes.

    PubMed

    Andrabi, Sara; Greene, Spencer; Moukaddam, Nidal; Moukkadam, Nidal; Li, Benjamin

    2015-11-01

    New drugs of abuse continue to emerge, including synthetic cannabinoids, synthetic cathinones, and hallucinogens. It is important to recognize their individual psychopharmacologic properties, symptoms of intoxication, and symptoms of withdrawal. Providers must be vigilant of acute medical or psychiatric complications that may arise from use of these substances. Treatment of the patient also includes recognition of any substance use disorders as well as comorbid psychiatric disorders. Although pharmacologic treatments for substance use disorder (of the drugs included in this article) are limited, there are a variety of psychotherapeutic modalities that may be of some benefit.

  18. Alcoholism, Alcohol, and Drugs

    ERIC Educational Resources Information Center

    Rubin, Emanuel; Lieber, Charles S.

    1971-01-01

    Describes research on synergistic effects of alcohol and other drugs, particularly barbiturates. Proposes biochemical mechanisms to explain alcoholics' tolerance of other drugs when sober, and increased sensitivity when drunk. (AL)

  19. 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.

  20. Social Withdrawal in Childhood

    PubMed Central

    Rubin, Kenneth H.; Coplan, Robert J.; Bowker, Julie C.

    2013-01-01

    Socially withdrawn children frequently refrain from social activities in the presence of peers. The lack of social interaction in childhood may result from a variety of causes, including social fear and anxiety or a preference for solitude. From early childhood through to adolescence, socially withdrawn children are concurrently and predictively at risk for a wide range of negative adjustment outcomes, including socio-emotional difficulties (e.g., anxiety, low self-esteem, depressive symptoms, and internalizing problems), peer difficulties (e.g., rejection, victimization, poor friendship quality), and school difficulties (e.g., poor-quality teacher-child relationships, academic difficulties, school avoidance). The goals of the current review are to (a) provide some definitional, theoretical, and methodological clarity to the complex array of terms and constructs previously employed in the study of social withdrawal; (b) examine the predictors, correlates, and consequences of child and early-adolescent social withdrawal; and (c) present a developmental framework describing pathways to and from social withdrawal in childhood. PMID:18851686

  1. Update on Alcoholic Hepatitis.

    PubMed

    Torok, Natalie J

    2015-11-02

    Alcoholic liver disease is one of the most prevalent liver diseases worldwide, and a major cause of morbidity and mortality. Alcoholic hepatitis is a severe form of liver injury in patients with alcohol abuse, can present as an acute on chronic liver failure associated with a rapid decline in liver synthetic function, and consequent increase in mortality. Despite therapy, about 30%-50% of patients with severe alcoholic hepatitis eventually die. The pathogenic pathways that lead to the development of alcoholic hepatitis are complex and involve oxidative stress, gut dysbiosis, and dysregulation of the innate and adaptive immune system with injury to the parenchymal cells and activation of hepatic stellate cells. As accepted treatment approaches are currently limited, a better understanding of the pathophysiology would be required to generate new approaches that improve outcomes. This review focuses on recent advances in the diagnosis, pathogenesis of alcoholic hepatitis and novel treatment strategies.

  2. Update on Alcoholic Hepatitis

    PubMed Central

    Torok, Natalie J.

    2015-01-01

    Alcoholic liver disease is one of the most prevalent liver diseases worldwide, and a major cause of morbidity and mortality. Alcoholic hepatitis is a severe form of liver injury in patients with alcohol abuse, can present as an acute on chronic liver failure associated with a rapid decline in liver synthetic function, and consequent increase in mortality. Despite therapy, about 30%–50% of patients with severe alcoholic hepatitis eventually die. The pathogenic pathways that lead to the development of alcoholic hepatitis are complex and involve oxidative stress, gut dysbiosis, and dysregulation of the innate and adaptive immune system with injury to the parenchymal cells and activation of hepatic stellate cells. As accepted treatment approaches are currently limited, a better understanding of the pathophysiology would be required to generate new approaches that improve outcomes. This review focuses on recent advances in the diagnosis, pathogenesis of alcoholic hepatitis and novel treatment strategies. PMID:26540078

  3. Narp regulates long-term aversive effects of morphine withdrawal

    PubMed Central

    Reti, Irving M.; Crombag, Hans S.; Takamiya, Kogo; Sutton, Jeffrey M.; Guo, Ning; Dinenna, Megan L.; Huganir, Richard L.; Holland, Peter C.; Baraban, Jay M.

    2008-01-01

    Although long-lasting effects of drug withdrawal are thought to play a key role in motivating continued drug use, the mechanisms mediating this type of drug-induced plasticity are unclear. As Narp is an immediate early gene product that is secreted at synaptic sites and binds to AMPA receptors, it has been implicated in mediating enduring forms of synaptic plasticity. In previous studies, we found that Narp is selectively induced by morphine withdrawal in the extended amygdala, a group of limbic nuclei that mediate aversive behavioral responses. Accordingly, in this study, we evaluated whether long-term aversive effects of morphine withdrawal are altered in Narp KO mice. We found that acute physical signs of morphine withdrawal are unaffected by Narp deletion. However, Narp KO mice acquire and sustain more aversive responses to the environment conditioned with morphine withdrawal than WT controls. Paradoxically, Narp KO mice undergo accelerated extinction of this heightened aversive response. Taken together, these studies suggest that Narp modulates both acquisition and extinction of aversive responses to morphine withdrawal and, therefore, may regulate plasticity processes underlying drug addiction. PMID:18729628

  4. Cannabis Withdrawal in Patients With and Without Opioid Dependence

    PubMed Central

    Chauchard, Emeline; Goncharov, Oleg; Krupitsky, Evgeny; Gorelick, David A.

    2014-01-01

    Background Cannabis use is common among opioid-dependent individuals, but little is known about cannabis withdrawal in this population. Method Thirty inpatients (57% men) completed the Marijuana Quit Questionnaire (MJQQ) after completing acute heroin detoxification treatment in St. Petersburg, Russia. The MJQQ collected data on motivations for quitting, withdrawal symptoms, and coping strategies used to help maintain abstinence during their most “userious” (self-defined) quit attempt made without formal treatment outside a controlled environment. Results At the start of their quit attempt, 70% of participants smoked cannabis at least weekly (40% daily), averaging [SD] 2.73 [1.95] joints daily; 60% were heroin-dependent. Subjects with heroin dependence were significantly older at the start of their quit attempt (22.9 [3.6] years vs. 19.1 [2.9] years), were significantly less likely to report withdrawal irritability/anger/aggression (22% vs. 58%), restlessness (0% vs. 25%), or physical symptoms (6% vs. 33%), or to meet diagnostic criteria for DSM-5 cannabis withdrawal syndrome (6% vs. 33%), and had shorter duration of abstinence (29.6 [28.7] months vs. 73.7 [44.1] months) than those without heroin dependence. Conclusion Cannabis users with opioid dependence are less likely to experience cannabis withdrawal, suggesting that opiate use may prevent or mask the experience of cannabis withdrawal. Results should be considered preliminary due to small convenience sample and retrospective data. PMID:24745656

  5. Observing nurses has improved my alcohol dependency care.

    PubMed

    Jaques, Ellise

    2016-09-21

    My first placement in my first year of nursing training was on a gastrointestinal/hepatology ward. Alongside my mentor, I was caring for a patient who had been withdrawing from alcohol since admission to hospital the previous evening.

  6. [Nutritional management of patients with acute pancreatitis: when the past is present].

    PubMed

    García Almansa, A; García Peris, P

    2008-05-01

    Patients with acute pancreatitis usually present nutritional status impairment. In alcoholic pancreatitis this impairment is usually presented before hospital admission. In patients with long-term complicated pancreatitis, malnutrition develops during the course of the disease. Besides, these patients present an increased stress and protein hypercatabolism. Treatment of acute pancreatitis usually maintains patients in a short period of starvation. In mild pancreatitis, starvation is needed for a few days, beginning progressively oral feeding. These patients don't need special nutritional support, unless they were previously malnourished. Patients with severe acute pancreatitis should always receive artificial nutritional support in order to preserve the nutritional status as starvation will be maintained for more than one week. In this paper, we review the nutritional treatment in these situations, trying to answer some different questions: type of nutritional support, when it should be started and when it is indicated to withdraw.

  7. Pharmacogenetics of alcohol response and alcoholism: the interplay of genes and environmental factors in thresholds for alcoholism.

    PubMed

    Radel, M; Goldman, D

    2001-04-01

    Recent advances in neuroscience and genetics have enabled a better understanding of genetically influenced differences in ethanol ("alcohol")-related responses and differential vulnerability to alcohol dependence at the cellular and molecular levels. Heritability studies reveal that the role of genetic factors in alcoholism is largely substance-specific, with the exception of nicotine. One focus of genetic research in alcoholism is the study of functional polymorphisms influencing alcohol metabolism, such as the aldehyde dehydrogenase type 2 Glu487Lys and alcohol dehydrogenase type 2 His47Arg polymorphisms, which affect vulnerability to alcoholism via pharmacokinetic mechanisms, and cross-population studies have begun to reveal important gene-environment interactions. The other focus is on functional genetic variants of proteins involved in the neuronal response to alcohol, including alcohol sensitivity, reward, tolerance, and withdrawal. Studies on the roles of GABA(A) alpha6-amino acid substitutions in rodents in alcohol and benzodiazepine sensitivity, and potential roles in human alcohol and benzodiazepine sensitivity are reviewed. These studies, together with recently developed knowledge on a GABA(A) receptor gene cluster at a quantitative trait loci for alcohol withdrawal on mouse chromosome 11, indicate that research investigation of variation at GABA(A) neurotransmission is a promising area in the pharmacodynamics of alcohol and in differential susceptibility to alcoholism. Genes for proteins involved in alcohol-mediated reward include genes for transporters and receptors for dopamine, serotonin, opioids, and GABA. These genes and their functional variants also represent important targets for understanding alcohol's effects in humans. Identification of genes for alcoholism vulnerability is important in the near future, not only for prevention, but also for development and targeting treatments.

  8. 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.

  9. Cocaine withdrawal in Planaria.

    PubMed

    Raffa, R B; Valdez, J M

    2001-10-26

    Cocaine-exposed planarians displayed abstinence-induced withdrawal behavior when placed into cocaine-free, but not cocaine-containing, water. The effect, manifested and quantified using a new spontaneous locomotor velocity metric, was dose-dependently related to cocaine exposure (8x10(-9) to 8x10(-5) M). Ultraviolet light (254 nm=7.83x10(-19) J), which was previously shown to interfere with drug-receptor interactions in Planaria, enhanced the abstinence-induced decreased locomotor velocity.

  10. 29 CFR 4219.11 - Withdrawal liability upon mass withdrawal.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... LIABILITY FOR MULTIEMPLOYER PLANS NOTICE, COLLECTION, AND REDETERMINATION OF WITHDRAWAL LIABILITY.... (a) Initial withdrawal liability. The plan sponsor of a multiemployer plan that experiences a mass... that has completely or partially withdrawn from the plan and for whom the liability has not...

  11. 29 CFR 4219.11 - Withdrawal liability upon mass withdrawal.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... LIABILITY FOR MULTIEMPLOYER PLANS NOTICE, COLLECTION, AND REDETERMINATION OF WITHDRAWAL LIABILITY.... (a) Initial withdrawal liability. The plan sponsor of a multiemployer plan that experiences a mass... that has completely or partially withdrawn from the plan and for whom the liability has not...

  12. An attempt to evaluate diagnostic and prognostic significance of blood endogenous ethanol in alcoholics and their relatives.

    PubMed

    Ostrovsky, Y M; Pronko, P S; Shishkin, S N; Kolesnikov, V B; Volynets, S I

    1989-01-01

    Endogenous ethanol in the blood of human subjects was measured by gas chromatography. In healthy males, 12-13-year-old boys (sons of alcoholic and nonalcoholic fathers), and alcoholic inpatients (after cessation of all drugs), the endogenous ethanol levels ranged from 0 to 4.3 mg/l. The results showed no significant differences between the groups. At the period of alcohol withdrawal reactions the concentrations of endogenous ethanol were minimal in patients with delirium tremens and maximal in patients with mild alcohol withdrawal syndrome, the dynamics of this parameter being dependent on the severity of the alcohol withdrawal syndrome and the nature of the drugs prescribed.

  13. Alcohol Alert

    MedlinePlus

    ... Us You are here Home » Alcohol Alert Alcohol Alert The NIAAA Alcohol Alert is a quarterly bulletin that disseminates important research ... text. To order single copies of select Alcohol Alerts, see ordering Information . To view publications in PDF ...

  14. Alcoholism - resources

    MedlinePlus

    Resources - alcoholism ... The following organizations are good resources for information on alcoholism : Alcoholics Anonymous -- www.aa.org Al-Anon/Alateen -- www.al-anon.org/home National Institute on Alcohol ...

  15. Alcoholic neuropathy

    MedlinePlus

    Neuropathy - alcoholic; Alcoholic polyneuropathy ... The exact cause of alcoholic neuropathy is unknown. It likely includes both a direct poisoning of the nerve by the alcohol and the effect of poor nutrition ...

  16. Alcohol Facts

    MedlinePlus

    ... raquo Alcohol Facts Alcohol Facts Listen Drinks like beer, malt liquor, wine, and hard liquor contain alcohol. Alcohol is the ingredient that gets you drunk. Hard liquor—such as whiskey, rum, or gin—has more ...

  17. Alternative sampling strategies for the assessment of alcohol intake of living persons.

    PubMed

    Kummer, Natalie; Lambert, Willy E E; Samyn, Nele; Stove, Christophe P

    2016-09-01

    Monitoring of alcohol consumption by living persons takes place in various contexts, amongst which workplace drug testing, driving under the influence of alcohol, driving licence regranting programs, alcohol withdrawal treatment, diagnosis of acute intoxication or fetal alcohol ingestion. The matrices that are mostly used today include blood, breath and urine. The aim of this review is to present alternative sampling strategies that allow monitoring of the alcohol consumption in living subjects. Ethanol itself, indirect (carbohydrate deficient transferrin, CDT%) as well as direct biomarkers (ethyl glucuronide, EtG; ethyl sulphate, EtS; fatty acid ethyl esters, FAEEs and phosphatidylethanol species, PEths) of ethanol consumption will be considered. This review covers dried blood spots (CDT%, EtG/EtS, PEths), dried urine spots (EtG/EtS), sweat and skin surface lipids (ethanol, EtG, FAEEs), oral fluid (ethanol, EtG), exhaled breath (PEths), hair (EtG, FAEEs), nail (EtG), meconium (EtG/EtS, FAEEs), umbilical cord and placenta (EtG/EtS and PEth 16:0/18:1). Main results, issues and considerations specific to each matrix are reported. Details about sample preparation and analytical methods are not within the scope of this review.

  18. Alternative sampling strategies for the assessment of alcohol intake of living persons.

    PubMed

    Kummer, Natalie; Lambert, Willy E E; Samyn, Nele; Stove, Christophe P

    2016-09-01

    Monitoring of alcohol consumption by living persons takes place in various contexts, amongst which workplace drug testing, driving under the influence of alcohol, driving licence regranting programs, alcohol withdrawal treatment, diagnosis of acute intoxication or fetal alcohol ingestion. The matrices that are mostly used today include blood, breath and urine. The aim of this review is to present alternative sampling strategies that allow monitoring of the alcohol consumption in living subjects. Ethanol itself, indirect (carbohydrate deficient transferrin, CDT%) as well as direct biomarkers (ethyl glucuronide, EtG; ethyl sulphate, EtS; fatty acid ethyl esters, FAEEs and phosphatidylethanol species, PEths) of ethanol consumption will be considered. This review covers dried blood spots (CDT%, EtG/EtS, PEths), dried urine spots (EtG/EtS), sweat and skin surface lipids (ethanol, EtG, FAEEs), oral fluid (ethanol, EtG), exhaled breath (PEths), hair (EtG, FAEEs), nail (EtG), meconium (EtG/EtS, FAEEs), umbilical cord and placenta (EtG/EtS and PEth 16:0/18:1). Main results, issues and considerations specific to each matrix are reported. Details about sample preparation and analytical methods are not within the scope of this review. PMID:27208822

  19. 42 CFR 457.170 - Withdrawal process.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... Plans for Child Health Insurance Programs and Outreach Strategies § 457.170 Withdrawal process. (a... by providing written notice to CMS of the withdrawal. (b) Withdrawal of approved State plans. A...

  20. Confined Selective Withdrawal

    NASA Astrophysics Data System (ADS)

    Evangelio, Alvaro; Campo-Cortes, Francisco; Gordillo, Jose Manuel

    2014-11-01

    It is well known that the controlled production of monodisperse simple and composite emulsions possesses uncountable applications in medicine, pharmacy, materials science and industry. Here we present both experiments and slender-body theory regarding the generation of simple emulsions using a configuration that we have called Confined Selective Withdrawal, since it is an improved configuration of the classical Selective Withdrawal. We consider two different situations, namely, the cases when the outer flow Reynolds number is high and low, respectively. Several geometrical configurations and a wide range of viscosity ratios are analyzed so that the physics behind the phenomenon can be fully understood. In addition, we present both experiments and theory regarding the generation of composite emulsions. This phenomenon is only feasible when the outer flow Reynolds number is low enough. In this case, we propose a more complex theory which requires the simultaneous resolution of two interfaces in order to predict the shape of the jet and the sizes of the drops formed. The excellent agreement between our slender-body approximation and the experimental evidence fully validates our theories.

  1. Repeated seizures in an elderly patient with alcohol dependence and mild cognitive impairment.

    PubMed

    Ishii, Nobuyoshi; Terao, Takeshi; Araki, Yasuo; Hatano, Koji

    2013-11-22

    A 69-year-old man with alcohol dependence and mild cognitive impairment (MCI) suffered from repeated tonic-clonic seizures. The seizures typically occurred several hours after his last alcohol intake at home (early withdrawal seizure) and 22 days after his last intake of alcohol (14 days after the last dose of diazepam substituting for alcohol: late withdrawal seizure) on the ward. Psychiatrists in charge of this patient found it difficult to attribute his seizures to alcohol withdrawal syndrome (AWS) because of the atypical onset. The patient responded to diazepam resumption and valproate combination. This case highlights the need to always consider AWS as a possible cause of seizures and to gradually decrease diazepam as a substitute for alcohol. Moreover, in this patient, MCI may have induced vulnerability in the brain for AWS and the patients' older age might have decreased liver function leading to delayed onset of the seizures after diazepam withdrawal.

  2. Cuesta College Student Withdrawal Survey.

    ERIC Educational Resources Information Center

    Hagen, Peter F.; Cartnal, Ryan

    The spring 1999 student withdrawal survey was made available for approximately two weeks before the final withdrawal deadline to all students who formally dropped a class through the admissions office at either the North County or San Luis Obsipo campus of Cuesta College in California. A total of 438 useable surveys were collected. The identical…

  3. Expression Profiling in Alcoholism Research.

    PubMed

    Bergeson, Susan E; Berman, Ari E; Dodd, Peter R; Edenberg, Howard J; Hitzemann, Robert J; Lewohl, Joanne M; Lodowski, Kerrie H; Sommer, Wolfgang H

    2005-06-01

    This article represents the proceedings of a symposium at the 2004 International Society for Biomedical Research on Alcoholism in Mannheim, Germany, organized and co-chaired by Susan E. Bergeson and Wolfgang Sommer. The presentations and presenter were (1) Gene Expression in Brains of Alcohol-Preferring and Non-Preferring Rats, by Howard J. Edenberg (2) Candidate Treatment Targets for Alcoholism: Leads from Functional Genomics Approaches, by Wolfgang Sommer (3) Microarray Analysis of Acute and Chronic Alcohol Response in Brain, by Susan E. Bergeson (4) On the Integration of QTL and Gene Expression Analysis, by Robert J. Hitzemann (5) Microarray and Proteomic Analysis of the Human Alcoholic Brain, by Peter R. Dodd.

  4. Alcohol Alert: Genetics of Alcoholism

    MedlinePlus

    ... and Reports » Alcohol Alert » Alcohol Alert Number 84 Alcohol Alert Number 84 Print Version The Genetics of ... immune defense system. Genes Encoding Enzymes Involved in Alcohol Breakdown Some of the first genes linked to ...

  5. Alcohol-medical drug interactions.

    PubMed

    Johnson, Bankole A; Seneviratne, Chamindi

    2014-01-01

    Concomitant use of alcohol and medications may lead to potentially serious medical conditions. Increasing prescription medication abuse in today's society necessitates a deeper understanding of the mechanisms involved in alcohol-medication interactions in order to help prevent adverse events. Interactions of medications with alcohol result in altered bioavailability of the medication or alcohol (pharmacokinetic interactions) or modification of the effects at receptor or ion channel sites to alter behavioral or physical outcome (pharmacodynamic interactions). The nature of pharmacokinetic or pharmacodynamic interactions involved in alcohol-medication interactions may differ between acute and chronic alcohol use and be influenced by race, gender, or environmental or genetic factors. This review focuses on the mechanisms underlying pharmacokinetic and pharmacodynamic interactions between alcohol and medications and provides examples for such interactions from replicated research studies. In conclusion, further translational research is needed to address several gaps in our current knowledge of alcohol-medication interactions, including those under various pathologic conditions.

  6. Behavioral Neuroadaptation to Alcohol: From Glucocorticoids to Histone Acetylation

    PubMed Central

    Mons, Nicole; Beracochea, Daniel

    2016-01-01

    A prime mechanism that contributes to the development and maintenance of alcoholism is the dysregulation of the hypothalamic–pituitary–adrenal axis activity and the release of glucocorticoids (cortisol in humans and primates, corticosterone in rodents) from the adrenal glands. In the brain, sustained, local elevation of glucocorticoid concentration even long after cessation of chronic alcohol consumption compromises functional integrity of a circuit, including the prefrontal cortex (PFC), the hippocampus (HPC), and the amygdala (AMG). These structures are implicated in learning and memory processes as well as in orchestrating neuroadaptive responses to stress and anxiety responses. Thus, potentiation of anxiety-related neuroadaptation by alcohol is characterized by an abnormally AMG hyperactivity coupled with a hypofunction of the PFC and the HPC. This review describes research on molecular and epigenetic mechanisms by which alcohol causes distinct region-specific adaptive changes in gene expression patterns and ultimately leads to a variety of cognitive and behavioral impairments on prefrontal- and hippocampal-based tasks. Alcohol-induced neuroadaptations involve the dysregulation of numerous signaling cascades, leading to long-term changes in transcriptional profiles of genes, through the actions of transcription factors such as [cAMP response element-binding protein (CREB)] and chromatin remodeling due to posttranslational modifications of histone proteins. We describe the role of prefrontal–HPC–AMG circuit in mediating the effects of acute and chronic alcohol on learning and memory, and region-specific molecular and epigenetic mechanisms involved in this process. This review first discusses the importance of brain region-specific dysregulation of glucocorticoid concentration in the development of alcohol dependence and describes how persistently increased glucocorticoid levels in PFC may be involved in mediating working memory impairments and

  7. CHRONIC ALCOHOL NEUROADAPTATION AND STRESS CONTRIBUTE TO SUSCEPTIBILITY FOR ALCOHOL CRAVING AND RELAPSE

    PubMed Central

    BREESE, GEORGE R.; SINHA, RAJITA; HEILIG, MARKUS

    2010-01-01

    Alcoholism is a chronic relapsing disorder. Major characteristics observed in alcoholics during an initial period of alcohol abstinence are altered physiological functions and a negative emotional state. Evidence suggests that a persistent, cumulative adaptation involving a kindling/allostasis-like process occurs during the course of repeated chronic alcohol exposures that is critical for the negative symptoms observed during alcohol withdrawal. Basic studies have provided evidence for specific neurotransmitters within identified brain sites being responsible for the negative emotion induced by the persistent cumulative adaptation following intermittent-alcohol exposures. After an extended period of abstinence, the cumulative alcohol adaptation increases susceptibility to stress- and alcohol cue-induced negative symptoms and alcohol seeking, both of which can facilitate excessive ingestion of alcohol. In the alcoholic, stressful imagery and alcohol cues alter physiological responses, enhance negative emotion, and induce craving. Brain fMRI imaging following stress and alcohol cues has documented neural changes in specific brain regions of alcoholics not observed in social drinkers. Such altered activity in brain of abstinent alcoholics to stress and alcohol cues is consistent with a continuing ethanol adaptation being responsible. Therapies in alcoholics found to block responses to stress and alcohol cues would presumably be potential treatments by which susceptibility for continued alcohol abuse can be reduced. By continuing to define the neurobiological basis of the sustained alcohol adaptation critical for the increased susceptibility of alcoholics to stress and alcohol cues that facilitate craving, a new era is expected to evolve in which the high rate of relapse in alcoholism is minimized. 250 PMID:20951730

  8. Different neural systems mediate morphine reward and its spontaneous withdrawal aversion.

    PubMed

    Vargas-Perez, Hector; Ting-A-Kee, Ryan; van der Kooy, Derek

    2009-05-01

    The opponent-process theory posits that the aversive state of acute opiate withdrawal is a consequence of, and depends on, the previous rewarding state evoked by acute morphine reward. Although the brainstem tegmental pedunculopontine nucleus (TPP) is crucial for the rewarding component of morphine, the source of the later aversive component is not known. It is possible that (i) the second aversive process takes place within the TPP itself or (ii) morphine reward in the TPP activates an unconditioned opponent motivational process in another region of the brain. The effects of reversible inactivation of the TPP on the motivational properties of acute morphine and its spontaneous withdrawal effects in non-drug-dependent rats were examined using a place-conditioning paradigm. Reversible inactivation of the TPP with lidocaine or bupivacaine immediately before the morphine injection blocked the rewarding properties of morphine in non-dependent rats. Blocking the rewarding effects of morphine also blocked the opponent aversive effects of acute morphine withdrawal. In contrast, reversible inactivation of the TPP during the acute morphine withdrawal did not block this opponent aversive process. Our results confirm that the TPP is a critical neural substrate underlying the acute rewarding effects of morphine in non-dependent rats. Furthermore, the opponent aversive process of acute morphine withdrawal is induced by the acute rewarding effects of morphine. However, the TPP does not directly mediate the spontaneous withdrawal aversion (the opponent process), suggesting that a different system, triggered by the changes in the TPP after the primary drug response, produces the aversion itself.

  9. Different neural systems mediate morphine reward and its spontaneous withdrawal aversion.

    PubMed

    Vargas-Perez, Hector; Ting-A-Kee, Ryan; van der Kooy, Derek

    2009-05-01

    The opponent-process theory posits that the aversive state of acute opiate withdrawal is a consequence of, and depends on, the previous rewarding state evoked by acute morphine reward. Although the brainstem tegmental pedunculopontine nucleus (TPP) is crucial for the rewarding component of morphine, the source of the later aversive component is not known. It is possible that (i) the second aversive process takes place within the TPP itself or (ii) morphine reward in the TPP activates an unconditioned opponent motivational process in another region of the brain. The effects of reversible inactivation of the TPP on the motivational properties of acute morphine and its spontaneous withdrawal effects in non-drug-dependent rats were examined using a place-conditioning paradigm. Reversible inactivation of the TPP with lidocaine or bupivacaine immediately before the morphine injection blocked the rewarding properties of morphine in non-dependent rats. Blocking the rewarding effects of morphine also blocked the opponent aversive effects of acute morphine withdrawal. In contrast, reversible inactivation of the TPP during the acute morphine withdrawal did not block this opponent aversive process. Our results confirm that the TPP is a critical neural substrate underlying the acute rewarding effects of morphine in non-dependent rats. Furthermore, the opponent aversive process of acute morphine withdrawal is induced by the acute rewarding effects of morphine. However, the TPP does not directly mediate the spontaneous withdrawal aversion (the opponent process), suggesting that a different system, triggered by the changes in the TPP after the primary drug response, produces the aversion itself. PMID:19453632

  10. Carbohydrate deficient transferrin: a marker for alcohol abuse.

    PubMed Central

    Kapur, A.; Wild, G.; Milford-Ward, A.; Triger, D. R.

    1989-01-01

    OBJECTIVE--To assess the value of serum carbohydrate deficient transferrin as detected by isoelectric focusing on agarose as an indicator of alcohol abuse. DESIGN--Coded analysis of serum samples taken from patients with carefully defined alcohol intake both with and without liver disease. Comparison of carbohydrate deficient transferrin with standard laboratory tests for alcohol abuse. SETTING--A teaching hospital unit with an interest in general medicine and liver disease. PATIENTS--22 "Self confessed" alcoholics admitting to a daily alcohol intake of at least 80 g for a minimum of three weeks; 15 of the 22 self confessed alcoholics admitted to hospital for alcohol withdrawal; 68 patients with alcoholic liver disease confirmed by biopsy attending outpatient clinics and claiming to be drinking less than 50 g alcohol daily; 47 patients with non-alcoholic liver disorders confirmed by biopsy; and 38 patients with disorders other than of the liver and no evidence of excessive alcohol consumption. INTERVENTION--Serial studies performed on the 15 patients undergoing alcohol withdrawal in hospital. MAIN OUTCOME measure--Determination of relative value of techniques for detecting alcohol abuse. RESULTS--Carbohydrate deficient transferrin was detected in 19 of the 22 (86%) self confessed alcohol abusers, none of the 47 patients with non-alcoholic liver disease, and one of the 38 (3%) controls. Withdrawal of alcohol led to the disappearance of carbohydrate deficient transferrin at a variable rate, though in some subjects it remained detectable for up to 15 days. Carbohydrate deficient transferrin was considerably superior to the currently available conventional markers for alcohol abuse. CONCLUSION--As the technique is fairly simple, sensitive, and inexpensive we suggest that it may be valuable in detecting alcohol abuse. Images FIG 1 PMID:2571374

  11. Topographic quantitative EEG amplitude in recovered alcoholics.

    PubMed

    Pollock, V E; Schneider, L S; Zemansky, M F; Gleason, R P; Pawluczyk, S

    1992-05-01

    Topographic measures of electroencephalographic (EEG) amplitude were used to compare recovered alcoholics (n = 14) with sex- and age-matched control subjects. Delta, alpha, and beta activity did not distinguish the groups, but regional differences in theta distribution did. Recovered alcoholics showed more uniform distributions of theta amplitudes in bilateral anterior and posterior regions compared with controls. Because a minimum of 5 years had elapsed since the recovered alcoholic subjects fulfilled DSM-III-R criteria for alcohol abuse or dependence, it is unlikely these EEG theta differences reflect the effects of withdrawal.

  12. 19 CFR 24.4 - Optional method for payment of estimated import taxes on alcoholic beverages upon entry, or...

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... taxes on alcoholic beverages upon entry, or withdrawal from warehouse, for consumption. 24.4 Section 24... estimated import taxes on alcoholic beverages upon entry, or withdrawal from warehouse, for consumption. (a..., or withdrawn from warehouse, for consumption by him during such a period may apply by letter to...

  13. 19 CFR 24.4 - Optional method for payment of estimated import taxes on alcoholic beverages upon entry, or...

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... taxes on alcoholic beverages upon entry, or withdrawal from warehouse, for consumption. 24.4 Section 24... estimated import taxes on alcoholic beverages upon entry, or withdrawal from warehouse, for consumption. (a..., or withdrawn from warehouse, for consumption by him during such a period may apply by letter to...

  14. Alcohol Impairment and Social Drinking.

    ERIC Educational Resources Information Center

    Bates, Marsha E.

    Cognitive abilities of social drinkers are generally thought to be affected by alcohol only during acute intoxication, but several studies suggest that sober-state performance may be affected by the quantity of alcohol consumed per drinking episode. Although the findings regarding sober-state mental deficits in social drinkers are inconclusive,…

  15. HSP-4 endoplasmic reticulum (ER) stress pathway is not activated in a C. elegans model of ethanol intoxication and withdrawal.

    PubMed

    Ient, Ben; Edwards, Richard; Mould, Richard; Hannah, Matthew; Holden-Dye, Lindy; O'Connor, Vincent

    2012-12-01

    Acute and chronic exposure of Caenorhabditis elegans to concentrations of ethanol in the range 250-350 mM elicits distinct behaviours. Previous genetic analysis highlights specific neurobiological substrates for these effects. However, ethanol may also elicit cellular stress responses which may contribute to the repertoire of ethanol-induced behaviours. Here, we have studied the effect of ethanol on an important arm of the cellular stress pathways, which emanates from the endoplasmic reticulum (ER) in response to several conditions including heat shock and chemical or genetic perturbations that lead to protein misfolding. HSP-4 is a heat shock protein and homologue of mammalian BiP. It is a pivotal upstream component of the ER stress response. Therefore, we used a C. elegans heat shock protein mutant, hsp-4, and a strain carrying a transcriptional reporter, Phsp-4::gfp, to test the role of the ER following chronic ethanol conditioning. We found no evidence for an overt ER response during acute or prolonged exposure to concentrations of ethanol that lead to defined ethanol-induced behaviours. Furthermore, whilst hsp-4 was strongly induced by tunicamycin, pre-exposure of C. elegans to low doses of tunicamycin followed by ethanol was not sufficient to induce an additive ER stress response. Behavioural analysis of an hsp-4 mutant indicated no difference compared to wild type in susceptibility to ethanol intoxication and withdrawal. There is a clear precedent for a significance of ER stress pathways particularly in clinical conditions associated with toxic or pathological effects of high doses of alcohol consumption. The concentrations of ethanol used in this C. elegans study equate to the highest blood alcohol levels measured in patients with chronic alcohol dependency. Taken together, these observations imply that the classic ER stress pathway in C. elegans is relatively refractory to induction by ethanol.

  16. Caffeine withdrawal and high-intensity endurance cycling performance.

    PubMed

    Irwin, Christopher; Desbrow, Ben; Ellis, Aleisha; O'Keeffe, Brooke; Grant, Gary; Leveritt, Michael

    2011-03-01

    In this study, we investigated the impact of a controlled 4-day caffeine withdrawal period on the effect of an acute caffeine dose on endurance exercise performance. Twelve well-trained and familiarized male cyclists, who were caffeine consumers (from coffee and a range of other sources), were recruited for the study. A double-blind placebo-controlled cross-over design was employed, involving four experimental trials. Participants abstained from dietary caffeine sources for 4 days before the trials and ingested capsules (one in the morning and one in the afternoon) containing either placebo or caffeine (1.5 mg · kg(-1) body weight · day(-1)). On day 5, capsules containing placebo or caffeine (3 mg · kg(-1) body weight) were ingested 90 min before completing a time trial, equivalent to one hour of cycling at 75% peak sustainable power output. Hence the study was designed to incorporate placebo-placebo, placebo-caffeine, caffeine-placebo, and caffeine-caffeine conditions. Performance time was significantly improved after acute caffeine ingestion by 1:49 ± 1:41 min (3.0%, P = 0.021) following a withdrawal period (placebo-placebo vs. placebo-caffeine), and by 2:07 ± 1:28 min (3.6%, P = 0.002) following the non-withdrawal period (caffeine-placebo vs. caffeine-caffeine). No significant difference was detected between the two acute caffeine trials (placebo-caffeine vs. caffeine-caffeine). Average heart rate throughout exercise was significantly higher following acute caffeine administration compared with placebo. No differences were observed in ratings of perceived exertion between trials. A 3 mg · kg(-1) dose of caffeine significantly improves exercise performance irrespective of whether a 4-day withdrawal period is imposed on habitual caffeine users. PMID:21279864

  17. Diagnostic characteristics and application of alcohol biomarkers.

    PubMed

    Topic, Aleksandra; Djukic, Mirjana

    2013-01-01

    Alcohol biomarkers play a significant role in the early diagnosis of alcohol intoxication/abuse, alcohol-related organ damages, assessment of alcoholism therapy outcomes, and in forensic medicine. Laboratory detection of excessive alcohol consumption can be carried out by direct measuring of the ethanol and/or metabolites in biological samples which is of particular importance in the cases of acute ethanol intoxication/controlling and/or monitoring of alcohol consumption, or indirectly, by using biomarkers. Preferred diagnostic characteristics of alcohol biomarkers, specificity and sensitivity dependent on the particular demands such as: prevention and treatment of alcoholism in primary and social care, criminal justice, workplace health and safety screening, trafficking control, etc. Alcohol biomarkers traditionally used in clinical practice [blood alcohol concentration (BAC), gamma-glutamyl transferase (GGT), carbohydrate-deficient transferrin (CDT), the ratio GGT/CDT, alanine aminotransferase (ALT), aspartate aminotransferase (AST), the rati. AST/ALT, mean cbrpuscular volume (MCV), phosphatidylethanol (PEth)] are well validated. They are used as screening/monitoring markers of acute/chronic excessive alcohol intake, alcoholism in pregnancy, and other disorders/conditions related to alcohol abuse. Numerous potential alcohol biomarkers have been discovered, but few are validated. Potential alcohol biomarkers (ethanol and serotonin metabolites, sialic acids, etc.) have good diagnostic characteristics, but their application in clinical practice is limited due to the costly equipment necessary for their measurement. Significant progress has been made in the development of sensitive and practical alcohol transdermal devices that can instantly/continuously measure BAC through human skin. Transdermal sensing of alcohol may become a valuable method for monitoring abstinence. A special aspect of alcoholism is genetic predisposition to alcohol abuse and alcoholism, or

  18. Diagnostic characteristics and application of alcohol biomarkers.

    PubMed

    Topic, Aleksandra; Djukic, Mirjana

    2013-01-01

    Alcohol biomarkers play a significant role in the early diagnosis of alcohol intoxication/abuse, alcohol-related organ damages, assessment of alcoholism therapy outcomes, and in forensic medicine. Laboratory detection of excessive alcohol consumption can be carried out by direct measuring of the ethanol and/or metabolites in biological samples which is of particular importance in the cases of acute ethanol intoxication/controlling and/or monitoring of alcohol consumption, or indirectly, by using biomarkers. Preferred diagnostic characteristics of alcohol biomarkers, specificity and sensitivity dependent on the particular demands such as: prevention and treatment of alcoholism in primary and social care, criminal justice, workplace health and safety screening, trafficking control, etc. Alcohol biomarkers traditionally used in clinical practice [blood alcohol concentration (BAC), gamma-glutamyl transferase (GGT), carbohydrate-deficient transferrin (CDT), the ratio GGT/CDT, alanine aminotransferase (ALT), aspartate aminotransferase (AST), the rati. AST/ALT, mean cbrpuscular volume (MCV), phosphatidylethanol (PEth)] are well validated. They are used as screening/monitoring markers of acute/chronic excessive alcohol intake, alcoholism in pregnancy, and other disorders/conditions related to alcohol abuse. Numerous potential alcohol biomarkers have been discovered, but few are validated. Potential alcohol biomarkers (ethanol and serotonin metabolites, sialic acids, etc.) have good diagnostic characteristics, but their application in clinical practice is limited due to the costly equipment necessary for their measurement. Significant progress has been made in the development of sensitive and practical alcohol transdermal devices that can instantly/continuously measure BAC through human skin. Transdermal sensing of alcohol may become a valuable method for monitoring abstinence. A special aspect of alcoholism is genetic predisposition to alcohol abuse and alcoholism, or

  19. Fetal Alcohol Syndrome: A Behavioral Teratology.

    ERIC Educational Resources Information Center

    Kavale, Kenneth A.; Karge, Belinda D.

    1986-01-01

    The review examines the literature on the behaviorally teratogenic aspects of Fetal Alcohol Syndrome, including: (1) prevalence of alcohol abuse among women, (2) acute and chronic effects of alcohol on the fetus, (3) genetic susceptibility, (4) neuropathology, (5) correlative conditions, and (6) animal studies. (Author/DB)

  20. 40 CFR 74.18 - Withdrawal.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... opt-in source may request to withdraw from the Acid Rain Program by submitting an administrative... paragraph (f)(1) of this section. (b) Requesting withdrawal. To withdraw from the Acid Rain Program, the...-in source's prior violations. An opt-in source that withdraws from the Acid Rain Program shall...

  1. 40 CFR 74.18 - Withdrawal.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... opt-in source may request to withdraw from the Acid Rain Program by submitting an administrative... paragraph (f)(1) of this section. (b) Requesting withdrawal. To withdraw from the Acid Rain Program, the...-in source's prior violations. An opt-in source that withdraws from the Acid Rain Program shall...

  2. 40 CFR 74.18 - Withdrawal.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... opt-in source may request to withdraw from the Acid Rain Program by submitting an administrative... paragraph (f)(1) of this section. (b) Requesting withdrawal. To withdraw from the Acid Rain Program, the...-in source's prior violations. An opt-in source that withdraws from the Acid Rain Program shall...

  3. 40 CFR 74.18 - Withdrawal.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... opt-in source may request to withdraw from the Acid Rain Program by submitting an administrative... paragraph (f)(1) of this section. (b) Requesting withdrawal. To withdraw from the Acid Rain Program, the...-in source's prior violations. An opt-in source that withdraws from the Acid Rain Program shall...

  4. 40 CFR 74.18 - Withdrawal.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... opt-in source may request to withdraw from the Acid Rain Program by submitting an administrative... paragraph (f)(1) of this section. (b) Requesting withdrawal. To withdraw from the Acid Rain Program, the...-in source's prior violations. An opt-in source that withdraws from the Acid Rain Program shall...

  5. 5 CFR 1650.11 - Withdrawal elections.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 5 Administrative Personnel 3 2011-01-01 2011-01-01 false Withdrawal elections. 1650.11 Section 1650.11 Administrative Personnel FEDERAL RETIREMENT THRIFT INVESTMENT BOARD METHODS OF WITHDRAWING FUNDS FROM THE THRIFT SAVINGS PLAN Post-Employment Withdrawals § 1650.11 Withdrawal elections....

  6. 5 CFR 1650.11 - Withdrawal elections.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 5 Administrative Personnel 3 2012-01-01 2012-01-01 false Withdrawal elections. 1650.11 Section 1650.11 Administrative Personnel FEDERAL RETIREMENT THRIFT INVESTMENT BOARD METHODS OF WITHDRAWING FUNDS FROM THE THRIFT SAVINGS PLAN Post-Employment Withdrawals § 1650.11 Withdrawal elections....

  7. 5 CFR 1650.11 - Withdrawal elections.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 5 Administrative Personnel 3 2013-01-01 2013-01-01 false Withdrawal elections. 1650.11 Section 1650.11 Administrative Personnel FEDERAL RETIREMENT THRIFT INVESTMENT BOARD METHODS OF WITHDRAWING FUNDS FROM THE THRIFT SAVINGS PLAN Post-Employment Withdrawals § 1650.11 Withdrawal elections....

  8. 5 CFR 1650.11 - Withdrawal elections.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 5 Administrative Personnel 3 2014-01-01 2014-01-01 false Withdrawal elections. 1650.11 Section 1650.11 Administrative Personnel FEDERAL RETIREMENT THRIFT INVESTMENT BOARD METHODS OF WITHDRAWING FUNDS FROM THE THRIFT SAVINGS PLAN Post-Employment Withdrawals § 1650.11 Withdrawal elections....

  9. 5 CFR 1650.11 - Withdrawal elections.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 5 Administrative Personnel 3 2010-01-01 2010-01-01 false Withdrawal elections. 1650.11 Section 1650.11 Administrative Personnel FEDERAL RETIREMENT THRIFT INVESTMENT BOARD METHODS OF WITHDRAWING FUNDS FROM THE THRIFT SAVINGS PLAN Post-Employment Withdrawals § 1650.11 Withdrawal elections....

  10. Glutamatergic targets for new alcohol medications

    PubMed Central

    Spanagel, Rainer; Krystal, John H.

    2013-01-01

    Rationale An increasingly compelling literature points to a major role for the glutamate system in mediating the effects of alcohol on behavior and the pathophysiology of alcoholism. Preclinical studies indicate that glutamate signaling mediates certain aspects of ethanol’s intoxicating and rewarding effects, and undergoes adaptations following chronic alcohol exposure that may contribute to the withdrawal, craving and compulsive drug-seeking that drive alcohol abuse and alcoholism. Objectives We discuss the potential for targeting the glutamate system as a novel pharmacotherapeutic approach to treating alcohol use disorders, focusing on five major components of the glutamate system: the N-methyl-D-aspartate (NMDA) receptor and specific NMDA subunits, the glycineB site on the NMDA receptors (NMDAR), L-alpha-amino-3-hydroxy-5-methyl-isoxazole-4-propionic acid ionotropic (AMPA) and kainate (KAR) receptors, metabotropic receptors (mGluR), and glutamate transporters. Results Chronic alcohol abuse produces a hyperglutamatergic state, characterized by elevated extracellular glutamate and altered glutamate receptors and transporters. Pharmacologically manipulating glutamatergic neurotransmission alters alcohol-related behaviors including intoxication, withdrawal, and alcohol-seeking, in rodents and human subjects. Blocking NMDA and AMPA receptors reduces alcohol consumption in rodents, but side-effects may limit this as a therapeutic approach. Selectively targeting NMDA and AMPA receptor subunits (e.g., GluN2B, GluA3), or the NMDAR glycineB site offers an alternative approach. Blocking mGluR5 potently affects various alcohol-related behaviors in rodents, and mGluR2/3 agonism also suppresses alcohol consumption. Finally, glutamate transporter upregulation may mitigate behavioral and neurotoxic sequelae of excess glutamate caused by alcohol. Conclusions Despite the many challenges that remain, targeting the glutamate system offers genuine promise for developing new

  11. [Survival by a young woman with malnutrition due to alcoholism and eating disorders and with acute respiratory distress syndrome due to severe pneumonia who showed increased serum neutrophil elastase activity].

    PubMed

    Nakajima, Hirokazu; Sawaguchi, Hirochiyo; Nakajima, Shigenori

    2006-11-01

    A 30-year-old woman with malnutrition due to alcoholism and eating disorders was found to have acute respiratory distress syndrome (ARDS) and sepsis due to severe Streptococcus pneumoniae pneumonia. S. pneumoniae was detected by an in vitro rapid immunochromatographic assay for S. pneumoniae antigen in urine on the day of admission and by blood culture 2 days after admission. Symptoms and laboratory findings improved after treatment with sivelestat sodium hydrate, antibiotics, and mechanical ventilation. Treatment with sivelestat sodium hydrate also decreased serum neutrophil elastase activity. This case demonstrates the usefulness of early treatment with sivelestat sodium hydrate in ARDS due to severe pneumonia.

  12. Withdrawal: Expanding a Key Addiction Construct.

    PubMed

    Piper, Megan E

    2015-12-01

    Withdrawal is an essential component of classical addiction theory; it is a vital manifestation of dependence and motivates relapse. However, the traditional conceptualization of withdrawal as a cohesive collection of symptoms that emerge during drug deprivation and decline with either the passage of time or reinstatement of drug use, may be inadequate to explain scientific findings or fit with modern theories of addiction. This article expands the current understanding of tobacco withdrawal by examining: (1) withdrawal variability; (2) underlying causes of withdrawal variability, including biological and person factors, environmental influences, and the influence of highly routinized behavioral patterns; (3) new withdrawal symptoms that allow for enhanced characterization of the withdrawal experience; and (4) withdrawal-related cognitive processes. These topics provide guidance regarding the optimal assessment of withdrawal and illustrate the potential impact modern withdrawal conceptualization and assessment could have on identifying treatment targets.

  13. Withdrawal: Expanding a Key Addiction Construct.

    PubMed

    Piper, Megan E

    2015-12-01

    Withdrawal is an essential component of classical addiction theory; it is a vital manifestation of dependence and motivates relapse. However, the traditional conceptualization of withdrawal as a cohesive collection of symptoms that emerge during drug deprivation and decline with either the passage of time or reinstatement of drug use, may be inadequate to explain scientific findings or fit with modern theories of addiction. This article expands the current understanding of tobacco withdrawal by examining: (1) withdrawal variability; (2) underlying causes of withdrawal variability, including biological and person factors, environmental influences, and the influence of highly routinized behavioral patterns; (3) new withdrawal symptoms that allow for enhanced characterization of the withdrawal experience; and (4) withdrawal-related cognitive processes. These topics provide guidance regarding the optimal assessment of withdrawal and illustrate the potential impact modern withdrawal conceptualization and assessment could have on identifying treatment targets. PMID:25744958

  14. Restlessness related to SSRI withdrawal.

    PubMed

    Hirose, S

    2001-02-01

    There are reports that abrupt withdrawal of various selective serotonin re-uptake inhibitors, such as fluvoxamine, can elicit in patients various withdrawal symptoms. Fluvoxamine has been widely used in Japan for approximately 1 year. However, there have been no case reports of withdrawal symptoms following abrupt fluvoxamine discontinuation in Japan. The author reports a case where the abrupt discontinuation of fluvoxamine produced restlessness in a depressed patient. The restlessness disappeared soon after the reinstatement of treatment with fluvoxamine. This case report suggests that clinicians should carefully scrutinize a patient's compliance to fluvoxamine as the withdrawal symptoms observed following abrupt discontinuation might be regarded as a relapse of depression or side-effects of the medicine. PMID:11235863

  15. Water withdrawals in Florida, 2012

    USGS Publications Warehouse

    Marella, Richard L.

    2015-01-01

    The largest percentage of freshwater withdrawals was from the South Florida Water Management District (46 percent), followed by the St. Johns River Water Management District (20 percent), Southwest Florida Water Management District (19 percent), Northwest Florida Water Management District (9 percent), and Suwannee River Water Management District (6 percent). The South Florida Water Management District accounted for the largest percentage of freshwater withdrawals for public-supply use (46 percent), commercial-industrial-mining self-supplied use (24 percent), agricultural self-supplied use (59 percent), and recreational-landscape irrigation use (63 percent). The Northwest Florida Water Management District accounted for the largest percentage of freshwater withdrawals for power-generation use (44 percent), and the Southwest Florida Water Management District accounted for the largest percentage of saline-water withdrawals for power-generation use (58 percent).

  16. Water withdrawals in Florida, 2012

    USGS Publications Warehouse

    Marella, Richard L.

    2015-09-01

    The largest percentage of freshwater withdrawals was from the South Florida Water Management District (46 percent), followed by the St. Johns River Water Management District (20 percent), Southwest Florida Water Management District (19 percent), Northwest Florida Water Management District (9 percent), and Suwannee River Water Management District (6 percent). The South Florida Water Management District accounted for the largest percentage of freshwater withdrawals for public-supply use (46 percent), commercial-industrial-mining self-supplied use (24 percent), agricultural self-supplied use (59 percent), and recreational-landscape irrigation use (63 percent). The Northwest Florida Water Management District accounted for the largest percentage of freshwater withdrawals for power-generation use (44 percent), and the Southwest Florida Water Management District accounted for the largest percentage of saline-water withdrawals for power-generation use (58 percent).

  17. Alcohol hangover: mechanisms and mediators.

    PubMed

    Swift, R; Davidson, D

    1998-01-01

    Hangovers are a frequent, though unpleasant, experience among people who drink to intoxication. Despite the prevalence of hangovers, however, this condition is not well understood scientifically. Multiple possible contributors to the hangover state have been investigated, and researchers have produced evidence that alcohol can directly promote hangover symptoms through its effects on urine production, the gastrointestinal tract, blood sugar concentrations, sleep patterns, and biological rhythms. In addition, researchers postulate that effects related to alcohol's absence after a drinking bout (i.e., withdrawal), alcohol metabolism, and other factors (e.g., biologically active, nonalcohol compounds in beverages; the use of other drugs; certain personality traits; and a family history of alcoholism) also may contribute to the hangover condition. Few of the treatments commonly described for hangover have undergone scientific evaluation.

  18. Neurobiological mechanisms contributing to alcohol-stress-anxiety interactions.

    PubMed

    Silberman, Yuval; Bajo, Michal; Chappell, Ann M; Christian, Daniel T; Cruz, Maureen; Diaz, Marvin R; Kash, Thomas; Lack, Anna K; Messing, Robert O; Siggins, George R; Winder, Danny; Roberto, Marisa; McCool, Brian A; Weiner, Jeff L

    2009-11-01

    This article summarizes the proceedings of a symposium that was presented at a conference entitled "Alcoholism and Stress: A Framework for Future Treatment Strategies." The conference was held in Volterra, Italy on May 6-9, 2008 and this symposium was chaired by Jeff L. Weiner. The overall goal of this session was to review recent findings that may shed new light on the neurobiological mechanisms that underlie the complex relationships between stress, anxiety, and alcoholism. Dr. Danny Winder described a novel interaction between D1 receptor activation and the corticotrophin-releasing factor (CRF) system that leads to an increase in glutamatergic synaptic transmission in the bed nucleus of the stria terminalis. Dr. Marisa Roberto presented recent data describing how protein kinase C epsilon, ethanol, and CRF interact to alter GABAergic inhibition in the central nucleus of the amygdala. Dr. Jeff Weiner presented recent advances in our understanding of inhibitory circuitry within the basolateral amygdala (BLA) and how acute ethanol exposure enhances GABAergic inhibition in these pathways. Finally, Dr. Brian McCool discussed recent findings on complementary glutamatergic and GABAergic adaptations to chronic ethanol exposure and withdrawal in the BLA. Collectively, these investigators have identified novel mechanisms through which neurotransmitter and neuropeptide systems interact to modulate synaptic activity in stress and anxiety circuits. Their studies have also begun to describe how acute and chronic ethanol exposure influence excitatory and inhibitory synaptic communication in these pathways. These findings point toward a number of novel neurobiological targets that may prove useful for the development of more effective treatment strategies for alcohol use disorders.

  19. Bone Changes in Alcoholics

    PubMed Central

    Pierce, Raymond O.

    1979-01-01

    Man has consumed alcohol for its euphoric and sedative effect down through the ages. Attention in the medical literature has been primarily focused on the effects of alcohol on the nervous system and liver. In the past few years, isolated reports have appeared in the medical literature concerning the effects of alcohol on the bony skeleton. The purpose of this paper is to classify these lesions, discuss their pathophysiology, and briefly review their clinical course. The lesions discussed include osteoporosis, hip fractures, aseptic necrosis of the hip, and fat embolism. For the purpose of this discussion these lesions are divided into two groups. Group I includes the battered alcoholic syndrome. Group II includes fat embolism, both acute and chronic, and aseptic necrosis of the hip. ImagesFigure 1Figure 2Figure 3Figure 4Figure 5 PMID:522187

  20. Neuroendocrine consequences of alcohol abuse in women.

    PubMed

    Mello, N K; Mendelson, J H; Teoh, S K

    1989-01-01

    Alcohol abuse and alcoholism are associated with a broad spectrum of reproductive system disorders. Amenorrhea, anovulation, luteal phase dysfunction, and ovarian pathology may occur in alcohol-dependent women and alcohol abusers. Luteal phase dysfunction, anovulation and persistent hyperprolactinemia have also been observed in social drinkers studied under clinical research ward conditions. The mechanisms underlying alcohol-related disruptions of the hypothalamic-pituitary-ovarian-adrenal axis are unknown. The reproductive consequences of alcohol abuse and alcoholism range from infertility and increased risk for spontaneous abortion to impaired fetal growth and development. Recent studies of alcohol's effects on pituitary gonadotropins and on gonadal, steroid and adrenal hormones in women are reviewed. Research on the acute effects of alcohol on opioid antagonist and synthetic LHRH-stimulated pituitary gonadotropins is summarized. The implications of alcohol's effects on reproductive hormones for impairment of fetal growth and development are discussed.

  1. Myths about drinking alcohol

    MedlinePlus

    ... to. I spend a lot of time getting alcohol, drinking alcohol, or recovering from the effects of alcohol. ... Institute on Alcohol Abuse and Alcoholism. Overview of Alcohol Consumption. www.niaaa.nih.gov/alcohol-health/overview-alcohol- ...

  2. Pharmacotherapeutic Treatment of Alcohol Dependence: An Overview

    ERIC Educational Resources Information Center

    Graves, Erin; Goodwin, Lloyd R., Jr.

    2008-01-01

    Pharmacotherapy medications can reduce the likelihood of relapse, decrease craving intensity and severity of withdrawal symptoms, and bolster the likelihood of achieving and maintaining recovery goals for many individuals seeking recovery from alcohol dependence. An overview of the benefits and concerns of integrating pharmacotherapeutic…

  3. Alcohol, athletic performance and recovery.

    PubMed

    Vella, Luke D; Cameron-Smith, David

    2010-08-01

    Alcohol consumption within elite sport has been continually reported both anecdotally within the media and quantitatively in the literature. The detrimental effects of alcohol on human physiology have been well documented, adversely influencing neural function, metabolism, cardiovascular physiology, thermoregulation and skeletal muscle myopathy. Remarkably, the downstream effects of alcohol consumption on exercise performance and recovery, has received less attention and as such is not well understood. The focus of this review is to identify the acute effects of alcohol on exercise performance and give a brief insight into explanatory factors. PMID:22254055

  4. Alcohol, athletic performance and recovery.

    PubMed

    Vella, Luke D; Cameron-Smith, David

    2010-08-01

    Alcohol consumption within elite sport has been continually reported both anecdotally within the media and quantitatively in the literature. The detrimental effects of alcohol on human physiology have been well documented, adversely influencing neural function, metabolism, cardiovascular physiology, thermoregulation and skeletal muscle myopathy. Remarkably, the downstream effects of alcohol consumption on exercise performance and recovery, has received less attention and as such is not well understood. The focus of this review is to identify the acute effects of alcohol on exercise performance and give a brief insight into explanatory factors.

  5. 77 FR 15378 - Agency Information Collection Activities: Application for Withdrawal of Bonded Stores for Fishing...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-03-15

    ... previously published in the Federal Register (77 FR 1497) on January 10, 2012, allowing for a 60-day comment... permission of the CBP port director for the withdrawal and lading of bonded merchandise (especially alcoholic beverages) for use on board fishing vessels involved in international trade. The applicant must certify...

  6. Twenty-one year mortality in a dialysis unit: changing effect of withdrawal from dialysis.

    PubMed

    Bordenave, K; Tzamaloukas, A H; Conneen, S; Adler, K; Keller, L K; Murata, G H

    1998-01-01

    To characterize the factors affecting the decision to withdraw from dialysis, the authors compared patients withdrawing from dialysis (n=62) with patients dying from all other causes (n=242) over 21 years (1976-1996) in a single dialysis unit. Compared with those who died from other causes, patients who withdrew were older (67+/-11 vs 61+/-11 years); were more likely to have severe physical impairment (87% vs 62%) and severe restriction of activities of daily living (77% vs 46%); and had higher frequencies of congestive heart failure (81 % vs 62%), myocardial infarction (60% vs 42%), peripheral vascular disease (71 % vs 40%), and diabetes mellitus (66% vs 36%) (p < or = 0.014). Dialysis modality; duration of dialysis; the degree of family support; index of disease severity; the use of tobacco, alcohol, or illicit drugs; and the frequency of ischemic heart disease, dysrhythmia, pericarditis, cardiac arrest, cerebrovascular accident, hypertension, obstructive lung disease, cancer, and human immunodeficiency virus did not differ between the two groups. Stepwise logistic regression showed that dialysis during 1990-1996, severe limitation of activities of daily living, and diabetes mellitus were independent risk factors for withdrawal. During 1990-1996, 44% of the deaths were caused by withdrawal from treatment. In addition to other factors, dialysis in the 1990s is a strong predictor of withdrawal from dialysis. The reasons for the increased rate of withdrawal from dialysis in recent years, and the effect of this increased rate of withdrawal on mortality, need further evaluation.

  7. Who withdraws? Psychological individual differences and employee withdrawal behaviors.

    PubMed

    Zimmerman, Ryan D; Swider, Brian W; Woo, Sang Eun; Allen, David G

    2016-04-01

    Psychological individual differences, such as personality, affectivity, and general mental ability, have been shown to predict numerous work-related behaviors. Although there is substantial research demonstrating relationships between psychological individual differences and withdrawal behaviors (i.e., lateness, absenteeism, and turnover), there is no integrative framework providing scholars and practitioners a guide for conceptualizing how, why, and under what circumstances we observe such relationships. In this integrative conceptual review we: (a) utilize the Cognitive-Affective Processing System framework (Mischel & Shoda, 1995) to provide an overarching theoretical basis for how psychological individual differences affect withdrawal behaviors; (b) create a theoretical model of the situated person that summarizes the existing empirical literature examining the effect of psychological differences on withdrawal behavior; and (c) identify future research opportunities based on our review and integrative framework. PMID:26595754

  8. 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

  9. Alcohol Related Changes in Regulation of NMDA Receptor Functions

    PubMed Central

    Nagy, József

    2008-01-01

    Long-term alcohol exposure may lead to development of alcohol dependence in consequence of altered neurotransmitter functions. Accumulating evidence suggests that the N-methyl-D-aspartate (NMDA) type of glutamate receptors is a particularly important site of ethanol’s action. Several studies showed that ethanol potently inhibits NMDA receptors (NMDARs) and prolonged ethanol exposition leads to a compensatory “up-regulation” of NMDAR mediated functions. Therefore, alterations in NMDAR function are supposed to contribute to the development of ethanol tolerance, dependence as well as to the acute and late signs of ethanol withdrawal. A number of publications report alterations in the expression and phosphorylation states of NMDAR subunits, in their interaction with scaffolding proteins or other receptors in consequence of chronic ethanol treatment. Our knowledge on the regulatory processes, which modulate NMDAR functions including factors altering transcription, protein expression and post-translational modifications of NMDAR subunits, as well as those influencing their interactions with different regulatory proteins or other downstream signaling elements are incessantly increasing. The aim of this review is to summarize the complex chain of events supposedly playing a role in the up-regulation of NMDAR functions in consequence of chronic ethanol exposure. PMID:19305787

  10. Role of the satiety factor oleoylethanolamide in alcoholism.

    PubMed

    Bilbao, Ainhoa; Serrano, Antonia; Cippitelli, Andrea; Pavón, Francisco J; Giuffrida, Andrea; Suárez, Juan; García-Marchena, Nuria; Baixeras, Elena; Gómez de Heras, Raquel; Orio, Laura; Alén, Francisco; Ciccocioppo, Roberto; Cravatt, Benjamin F; Parsons, Loren H; Piomelli, Daniele; Rodríguez de Fonseca, Fernando

    2016-07-01

    Oleoylethanolamide (OEA) is a satiety factor that controls motivational responses to dietary fat. Here we show that alcohol administration causes the release of OEA in rodents, which in turn reduces alcohol consumption by engaging peroxisome proliferator-activated receptor-alpha (PPAR-α). This effect appears to rely on peripheral signaling mechanisms as alcohol self-administration is unaltered by intracerebral PPAR-α agonist administration, and the lesion of sensory afferent fibers (by capsaicin) abrogates the effect of systemically administered OEA on alcohol intake. Additionally, OEA is shown to block cue-induced reinstatement of alcohol-seeking behavior (an animal model of relapse) and reduce the severity of somatic withdrawal symptoms in alcohol-dependent animals. Collectively, these findings demonstrate a homeostatic role for OEA signaling in the behavioral effects of alcohol exposure and highlight OEA as a novel therapeutic target for alcohol use disorders and alcoholism.

  11. Alcoholics who drink mouthwash: the spectrum of nonbeverage alcohol use.

    PubMed

    Egbert, A M; Reed, J S; Powell, B J; Liskow, B I; Liese, B S

    1985-11-01

    Nonbeverage alcohol (NBA), or substitutes for traditional forms of beverage alcohol, includes such substances as mouthwash, aftershave lotion and alcohol-based fuels. Literature pertaining to the prevalence, clinical significance and toxicity of this practice is reviewed, using illustrative cases from a series of 48 NBA consumers. It was found that 10-15% of alcoholics hospitalized in detoxication units have consumed NBA; half of these patients are regular consumers. Addiction to NBA itself may occur. Its use is primarily related to easy accessibility, rather than social or monetary factors. Polydrug misuse and antisocial personality disorder are more frequent in NBA users, but use is not pathognomic of end-stage alcoholism. The 48 NBA users reported surprisingly few toxic symptoms from acute ingestion, perhaps because tolerance to some substances in NBA may occur. Isopropyl alcohol was the exception, reproducibly causing symptoms suggestive of severe gastritis.

  12. Suicidal Behavior and Alcohol Abuse

    PubMed Central

    Pompili, Maurizio; Serafini, Gianluca; Innamorati, Marco; Dominici, Giovanni; Ferracuti, Stefano; Kotzalidis, Giorgio D.; Serra, Giulia; Girardi, Paolo; Janiri, Luigi; Tatarelli, Roberto; Sher, Leo; Lester, David

    2010-01-01

    Suicide is an escalating public health problem, and alcohol use has consistently been implicated in the precipitation of suicidal behavior. Alcohol abuse may lead to suicidality through disinhibition, impulsiveness and impaired judgment, but it may also be used as a means to ease the distress associated with committing an act of suicide. We reviewed evidence of the relationship between alcohol use and suicide through a search of MedLine and PsychInfo electronic databases. Multiple genetically-related intermediate phenotypes might influence the relationship between alcohol and suicide. Psychiatric disorders, including psychosis, mood disorders and anxiety disorders, as well as susceptibility to stress, might increase the risk of suicidal behavior, but may also have reciprocal influences with alcohol drinking patterns. Increased suicide risk may be heralded by social withdrawal, breakdown of social bonds, and social marginalization, which are common outcomes of untreated alcohol abuse and dependence. People with alcohol dependence or depression should be screened for other psychiatric symptoms and for suicidality. Programs for suicide prevention must take into account drinking habits and should reinforce healthy behavioral patterns. PMID:20617037

  13. Alcohol and Alcoholism.

    ERIC Educational Resources Information Center

    National Inst. of Mental Health (DHEW), Chevy Chase, MD. National Clearinghouse for Mental Health Information.

    This concise survey presents some of the highlights of modern research on drinking and alcoholism, as based on technical articles published in the scientific literature and the views expressed by leading authorities in the field. Contents include discussions about: (1) the nature and scope of the problem; (2) the chemical composition of alcoholic…

  14. Withdrawal-like behavior in planarians is dependent on drug exposure duration.

    PubMed

    Sacavage, Steve; Patel, Hiren; Zielinski, Mike; Acker, Jeneane; Phillips, Austin G; Raffa, Robert B; Rawls, Scott M

    2008-07-01

    Planarians display a concentration-related reduction in locomotor activity following their spontaneous withdrawal from opioids, cannabinoids, stimulants and benzodiazepines. This suggests that planarians display a withdrawal-like behavior that can be quantified as a reduction in locomotor activity. Because withdrawal-like behavior in previous studies has been quantified only following the cessation of a 60-min drug exposure, it is unclear whether the withdrawal response varies with drug exposure duration. Therefore, the goal of this study is to determine if the duration of drug exposure (0, 5, 15, 30, 45, 60min and 24h) to three different drugs - methamphetamine, cocaine and caffeine - affects the magnitude of withdrawal-like behavior (i.e., reduced locomotor activity) in planarians. Experiments revealed that methamphetamine (10microM) produced significant withdrawal-like behavior regardless of the exposure time (P<0.05). An exposure time of only 5min resulted in a significant reduction in locomotor activity. The peak effect, although occurring following a 24-h exposure, was only slightly greater than that caused by a 30-min exposure. For cocaine (10microM), a longer exposure time (15min) was required for the manifestation of significant withdrawal-like behavior. The peak cocaine effect was observed following a 24-h exposure. Caffeine (10microM) did not produce significant changes in locomotor activity during withdrawal or alter locomotor activity during acute exposure. The present results suggest that the magnitude of withdrawal-like behavior in planarians is dependent on both the duration and type of drug exposure, and that planarians do not display withdrawal to caffeine.

  15. Uncommon cause of acute encephalopathy in liver cirrhosis.

    PubMed

    Dieuvil, Monique; Malaty, John

    2016-01-01

    A 49-year-old woman with a medical history of alcoholic cirrhosis status post-transjugular intrahepatic portosystemic shunt (post-TIPS) in 2012, and ongoing alcohol abuse, presented to the hospital, with haematuria. CT intravenous pyelogram (IVP) was normal except for 'a large intrahepatic cystic mass adjacent to the TIPS, causing intrahepatic biliary duct dilation'. The patient also presented with acute encephalopathy, jaundice, right upper quadrant abdominal pain and hyperbilirubinaemia (total bilirubin of 8.1 mg/dL with direct bilirubin of 3.0 mg/dL). She remained encephalopathic despite adequate treatment for alcohol withdrawal, hepatic encephalopathy and enterococcus urinary tract infection. MRI of the abdomen later confirmed presence of an obstructing biloma. The biloma, drained by CT-guided percutaneous drains, demonstrated an Escherichia coli and ESBL Klebsiella infection. The patient's encephalopathy completely resolved after treatment of the infected biloma. With adequate drainage, her hyperbilirubinaemia resolved to her post-TIPS baseline (total bilirubin of 3.7 mg/dL with direct bilirubin of 3.3 mg/dL). PMID:27194673

  16. Alcohol use disorder

    MedlinePlus

    ... Alcohol abuse; Problem drinking; Drinking problem; Alcohol addiction; Alcoholism - alcohol use; Substance use - alcohol ... The National Institute on Alcohol Abuse and Alcoholism ... 1 drink per day Men should not drink more than 2 drinks per day

  17. Estimated freshwater withdrawals in Texas, 1990

    USGS Publications Warehouse

    Lurry, Dee L.

    1994-01-01

    This report presents 1990 freshwater withdrawal estimates for Texas by source and category. Withdrawal source is either ground water or surface water. Withdrawal categories include: self-supplied irrigation, thermoelectric-power generation, water supply, industrial and mining, and other (domestic, commercial, livestock). Withdrawal data are aggregated by county, major aquifer, and principal river basin. Only the four major categories of irrigation, thermoelectric-power generation, water supply, and industrial and mining are illustrated in this report, although all data are tabulated.

  18. Alcohol Effects on Stress Pathways

    PubMed Central

    Blaine, Sara K.; Milivojevic, Verica; Fox, Helen

    2016-01-01

    A significant amount of neurobiological research regarding the development of alcohol use disorders (AUDs) has focused on alcohol-related activation and long-term alterations in the mesocortical dopaminergic reward pathways. However, alcohol does not only interact with brain reward systems. Many of its acute and chronic effects may be related to allostatic adaptations in hypothalamic and extrahypothalamic stress regulation pathways. For example, acute binge intoxication is associated with hypothalamically driven increases in blood cortisol, norepinephrine, and sex steroid metabolite levels. This may contribute to the development of mesocortical sensitization to alcohol. Furthermore, chronic alcohol exposure is associated with systemic dysregulation of the hypothalamic pituitary adrenal axis, sympathetic adrenal medullary system, and sex steroid systems. This dysregulation appears to manifest as neuroendocrine tolerance. In this review, we first summarize the literature suggesting that alcohol-induced alterations in these hypothalamic systems influence craving and contribute to the development of AUDs. We note that for women, the effects of alcohol on these neuroendocrine stress regulation systems may be influenced by the rhythmic variations of hormones and steroids across the menstrual cycle. Second, we discuss how changes in these systems may indicate progression of AUDs and increased risk of relapse in both sexes. Specifically, neuroendocrine tolerance may contribute to mesocortical sensitization, which in turn may lead to decreased prefrontal inhibitory control of the dopaminergic reward and hypothalamic stress systems. Thus, pharmacological strategies that counteract alcohol-associated changes in hypothalamic and extrahypothalamic stress regulation pathways may slow the development and progression of AUDs. PMID:27254089

  19. The benzodiazepine withdrawal syndrome and its management.

    PubMed Central

    Onyett, S R

    1989-01-01

    The literature on benzodiazepine dependence and withdrawal is reviewed with an emphasis on social and psychological considerations. The problems of when to prescribe, identifying withdrawal symptoms, effective communication with the patient, the structure of withdrawal programmes, and the use of drugs, psychological approaches and other services are discussed. PMID:2576073

  20. A Detection Model of College Withdrawal

    ERIC Educational Resources Information Center

    Pleskac, Timothy J.; Keeney, Jessica; Merritt, Stephanie M.; Schmitt, Neal; Oswald, Frederick L.

    2011-01-01

    Many students during their college careers consider withdrawing from their respective college or university. Understanding why some students decide to withdraw yet others persist has implications for both the well being of students as well as for institutes of higher education. The present study develops a model of the decision to withdraw drawing…

  1. 42 CFR 1008.40 - Withdrawal.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 42 Public Health 5 2010-10-01 2010-10-01 false Withdrawal. 1008.40 Section 1008.40 Public Health... OPINIONS BY THE OIG Submission of a Formal Request for an Advisory Opinion § 1008.40 Withdrawal. The requestor of an advisory opinion may withdraw the request prior to the issuance of a formal advisory...

  2. [The addicted patient in anaesthesia -screening, diagnosis and treatment of alcohol use disorders].

    PubMed

    Neumann, Tim

    2015-06-01

    Patients consuming > 60g/d of alcohol (e.g. 1.5l of beer), are 2-5 times more likely to suffer post-operative complications such as infectious, bleeding or cardiac complications or an alcohol withdrawal syndrome. By screening and a systematic evaluation risk patients can be identified that may benefit from interventions such as counseling, brief interventions, abstinence, tailored anesthesia, prophylactic treatment of withdrawal symptoms, stress reduction, harm reduction, psychosocial therapy, addiction therapy, multidisciplinary treatment.

  3. Alcohol use disorders in pregnancy.

    PubMed

    DeVido, Jeffrey; Bogunovic, Olivera; Weiss, Roger D

    2015-01-01

    Alcohol use disorders (AUDs) are less prevalent in pregnant women than in nonpregnant women, but these disorders can create a host of clinical challenges when encountered. Unfortunately, little evidence is available to guide clinical decision making in this population. Drinking alcohol during pregnancy can have negative consequences on both fetus and mother, but it remains controversial as to the volume of alcohol consumption that correlates with these consequences. Likewise, little evidence is available to support the use of particular pharmacologic interventions for AUDs during pregnancy or to guide the management of alcohol detoxification in pregnant women. The use of benzodiazepines (the mainstay of most alcohol detoxification protocols) in pregnant women is controversial. Nevertheless, despite the lack of robust data to guide management of AUDs in pregnancy, clinicians need to make management decisions when confronted with these challenging situations. In that context, this article reviews the epidemiology of AUDs in pregnancy and the pharmacologic management of both AUDs and alcohol withdrawal in pregnant women, with the goal of informing clinicians about what is known about managing these co-occurring conditions. PMID:25747924

  4. Alcohol Use Disorders in Pregnancy

    PubMed Central

    DeVido, Jeffrey; Bogunovic, Olivera; Weiss, Roger D.

    2015-01-01

    Alcohol use disorders (AUD) during pregnancy are less prevalent than in non-pregnant women, but they can create a host of clinical challenges when encountered. Unfortunately, there is little research information available to guide clinical decision-making in this population. Drinking alcohol during pregnancy can have negative consequences on both fetus and mother, but there is controversy regarding the volume of alcohol consumption that correlates with these consequences. There is little evidence to support the use of pharmacologic interventions for AUD during pregnancy. Similarly, there are few data to guide management of alcohol detoxification in pregnant women, and the use of benzodiazepines (the mainstay of most alcohol detoxification protocols) in pregnant women is controversial. Despite a lack of robust data to guide management of AUDs in pregnancy, clinicians must nonetheless make management decisions when confronted with these challenging situations. Therefore, this paper reviews the epidemiology of AUDs in pregnancy, and the pharmacologic management of both AUDs and alcohol withdrawal in pregnant women, to better inform clinicians about what is known about managing these co-occurring conditions. PMID:25747924

  5. [Treatment processes of pre-alcoholism and alcohol dependence targeted towards drinking reduction].

    PubMed

    Yoshimura, Atsushi; Maesato, Hitoshi; Hisatomi, Nobuko; Higuchi, Susumu

    2013-02-01

    Since the 1990s, we have suggested the concept of pre-alcoholism which encompasses patients who have drunk a great deal of alcohol leading to alcohol related problems such as health issues, domestic violence, drunken driving and black-outs. Pre-alcoholism excludes alcohol-dependent patients who have experienced continuous drinking or withdrawal symptoms. We have treated many outpatients with pre-alcoholism for several years. Our regimen demands that the patients must be abstinent for half a year at the beginning of their treatment. After half a year they can choose whether they will continue to be abstinent or they will resume drinking with the aim of reducing their total alcohol consumption. The study clarified the character of pre-alcoholism by investigation of the patients' background and re-diagnosis of the patients based on the International Classification of Diseases, 10th Revision (ICD-10). A remarkable ratio of pre-alcoholic patients was diagnosed with alcohol dependence under ICD-10. We classified pre-alcoholic patients into two groups, one diagnosed as having ICD-10-classed alcohol dependence and the other which did not fulfill the ICD-10 diagnostic criteria of alcohol dependence, and examined the therapeutic processes of the two groups. It was shown that most pre-alcoholic patients could finally take required courses of treatment by themselves without regard to diagnosis under ICD-10, even if they chose any treatment and made alcohol related mistakes on the way. Our findings suggested that pre-alcoholic patients, a portion of whom may have exhibited mild alcohol dependence, could select drinking reduction as a primary goal of treatment after a certain period of abstinence.

  6. Effectiveness of a drinking-motive-tailored emergency-room intervention among adolescents admitted to hospital due to acute alcohol intoxication - A randomized controlled trial.

    PubMed

    Wurdak, Mara; Wolstein, Jörg; Kuntsche, Emmanuel

    2016-06-01

    The aim of this study is to develop and test the effectiveness of a drinking-motive-tailored intervention for adolescents hospitalized due to alcohol intoxication in eight cities in Germany between December 2011 and May 2012 against a similar, non-motive-tailored intervention. In a randomized controlled trial, 254 adolescents received a psychosocial intervention plus motive-tailored (intervention group; IG) or general exercises (control group; CG). Adolescents in the IG received exercises in accordance with their drinking motives as indicated at baseline (e.g. alternative ways of spending leisure time or dealing with stress). Exercises for the CG contained alcohol-related information in general (e.g. legal issues). The data of 81 adolescents (age: M = 15.6, SD = 1.0; 42.0% female) who participated in both the baseline and the follow-up were compared using ANOVA with repeated measurements and effect sizes (available case analyses). Adolescents reported lower alcohol use at the four-week follow-up independently of the kind of intervention. Significant interaction effects between time and IG were found for girls in terms of drinking frequency (F = 7.770, p < 0.01) and binge drinking (F = 7.0005, p < 0.05) but not for boys. For the former, the proportional reductions and corresponding effect sizes of drinking frequency (d = - 1.18), binge drinking (d = - 1.61) and drunkenness (d = - 2.87) were much higher than the .8 threshold for large effects. Conducting psychosocial interventions in a motive-tailored way appears more effective for girls admitted to hospital due to alcohol intoxication than without motive-tailoring. Further research is required to address the specific needs of boys in such interventions. (German Clinical Trials Register, DRKS ID: DRKS00005588).

  7. Effectiveness of a drinking-motive-tailored emergency-room intervention among adolescents admitted to hospital due to acute alcohol intoxication — A randomized controlled trial

    PubMed Central

    Wurdak, Mara; Wolstein, Jörg; Kuntsche, Emmanuel

    2015-01-01

    The aim of this study is to develop and test the effectiveness of a drinking-motive-tailored intervention for adolescents hospitalized due to alcohol intoxication in eight cities in Germany between December 2011 and May 2012 against a similar, non-motive-tailored intervention. In a randomized controlled trial, 254 adolescents received a psychosocial intervention plus motive-tailored (intervention group; IG) or general exercises (control group; CG). Adolescents in the IG received exercises in accordance with their drinking motives as indicated at baseline (e.g. alternative ways of spending leisure time or dealing with stress). Exercises for the CG contained alcohol-related information in general (e.g. legal issues). The data of 81 adolescents (age: M = 15.6, SD = 1.0; 42.0% female) who participated in both the baseline and the follow-up were compared using ANOVA with repeated measurements and effect sizes (available case analyses). Adolescents reported lower alcohol use at the four-week follow-up independently of the kind of intervention. Significant interaction effects between time and IG were found for girls in terms of drinking frequency (F = 7.770, p < 0.01) and binge drinking (F = 7.0005, p < 0.05) but not for boys. For the former, the proportional reductions and corresponding effect sizes of drinking frequency (d = − 1.18), binge drinking (d = − 1.61) and drunkenness (d = − 2.87) were much higher than the .8 threshold for large effects. Conducting psychosocial interventions in a motive-tailored way appears more effective for girls admitted to hospital due to alcohol intoxication than without motive-tailoring. Further research is required to address the specific needs of boys in such interventions. (German Clinical Trials Register, DRKS ID: DRKS00005588). PMID:26844193

  8. A STUDY ON THE COPING BEHAVIOURS OF WIVES OF ALCOHOLICS

    PubMed Central

    Rao, T.S. Sathyanarayana; Kuruvilla, K.

    1992-01-01

    A study was conducted on 30 wives of alcoholics using Orford-Guthrie's ‘coping with drinking’ questionnaire. Tlie commonest coping behaviour reported was discord, avoidance, indulgence and fearful withdrawal while marital breakdown, taking special action, assertion and sexual withdrawal were least frequent. There was no significant correlation between the coping behaviours and the variables like duration of marriage, duration of husband’s alcoholism, socio-economic and educational status. Implications of these findings are discussed and a cross cultural comparison is made. PMID:21776145

  9. Alcohol Use and Firearm Violence.

    PubMed

    Branas, Charles C; Han, SeungHoon; Wiebe, Douglas J

    2016-01-01

    Although the misuse of firearms is necessary to the occurrence of firearm violence, there are other contributing factors beyond simply firearms themselves that might also be modified to prevent firearm violence. Alcohol is one such key modifiable factor. To explore this, we undertook a 40-year (1975-2014) systematic literature review with meta-analysis. One large group of studies showed that over one third of firearm violence decedents had acutely consumed alcohol and over one fourth had heavily consumed alcohol prior to their deaths. Another large group of studies showed that alcohol was significantly associated with firearm use as a suicide means. Two controlled studies showed that gun injury after drinking, especially heavy drinking, was statistically significant among self-inflicted firearm injury victims. A small group of studies investigated the intersection of alcohol and firearms laws and alcohol outlets and firearm violence. One of these controlled studies found that off-premise outlets selling takeout alcohol were significantly associated with firearm assault. Additional controlled, population-level risk factor and intervention studies, including randomized trials of which only 1 was identified, are needed. Policies that rezone off-premise alcohol outlets, proscribe blood alcohol levels and enhance penalties for carrying or using firearms while intoxicated, and consider prior drunk driving convictions as a more precise criterion for disqualifying persons from the purchase or possession of firearms deserve further study.

  10. Drinking practices among black and white alcoholics and alcoholics of different personality types.

    PubMed

    Robyak, J E; Prange, M; Sands, M

    1988-01-01

    In order to examine the effects that race and personality type have on self-reported drinking practices, samples of 49 White and 49 Black male alcoholics were matched on age and education, and classified into two personality types according to MMPI scores. The results of multivariate and univariate analyses of variance yielded significant main effects. White alcoholics reported a greater: (a) use of alcohol for symptomatic relief of psychological distress, (b) loss of motor control and tendency to engage in destructive acts, and (c) daily consumption of beverage alcohol than Black alcoholics. Alcoholics with psychiatric-appearing MMPI profiles reported greater: (a) social benefits of alcohol use, (b) alcohol use for symptomatic relief of psychological distress, and (c) perceptual distortions associated with alcohol withdrawal than alcoholics with characterlogical-appearing MMPIs. Results were discussed in terms of need to control confounding effects of biosocial variables in cross-cultural research and implications that these effects may have on the generalizability of alcoholic personality typologies.

  11. The current situation of treatment systems for alcoholism in Korea.

    PubMed

    Kim, Jee Wook; Lee, Boung Chul; Kang, Tae-Cheon; Choi, Ihn-Geun

    2013-02-01

    Alcoholism is becoming one of the most serious issues in Korea. The purpose of this review article was to understand the present status of the treatment system for alcoholism in Korea compared to the United States and to suggest its developmental direction in Korea. Current modalities of alcoholism treatment in Korea including withdrawal treatment, pharmacotherapy, and psychosocial treatment are available according to Korean evidence-based treatment guidelines. Benzodiazepines and supportive care including vitamin and nutritional support are mainly used to treat alcohol withdrawal in Korea. Naltrexone and acamprosate are the drugs of first choice to treat chronic alcoholism. Psychosocial treatment methods such as individual psychotherapy, group psychotherapy, family therapy, cognitive behavior therapy, cue exposure therapy, 12-step facilitation therapy, self-help group therapy, and community-based treatment have been carried out to treat chronic alcoholism in Korea. However, current alcohol treatment system in Korea is not integrative compared to that in the United States. To establish the treatment system, it is important to set up an independent governmental administration on alcohol abuse, to secure experts on alcoholism, and to conduct outpatient alcoholism treatment programs and facilities in an open system including some form of continuing care.

  12. Targeting glutamate uptake to treat alcohol use disorders

    PubMed Central

    Rao, P.S.S.; Bell, Richard L.; Engleman, Eric A.; Sari, Youssef

    2015-01-01

    Alcoholism is a serious public health concern that is characterized by the development of tolerance to alcohol's effects, increased consumption, loss of control over drinking and the development of physical dependence. This cycle is often times punctuated by periods of abstinence, craving and relapse. The development of tolerance and the expression of withdrawal effects, which manifest as dependence, have been to a great extent attributed to neuroadaptations within the mesocorticolimbic and extended amygdala systems. Alcohol affects various neurotransmitter systems in the brain including the adrenergic, cholinergic, dopaminergic, GABAergic, glutamatergic, peptidergic, and serotonergic systems. Due to the myriad of neurotransmitter and neuromodulator systems affected by alcohol, the efficacies of current pharmacotherapies targeting alcohol dependence are limited. Importantly, research findings of changes in glutamatergic neurotransmission induced by alcohol self- or experimenter-administration have resulted in a focus on therapies targeting glutamatergic receptors and normalization of glutamatergic neurotransmission. Glutamatergic receptors implicated in the effects of ethanol include the ionotropic glutamate receptors (AMPA, Kainate, and NMDA) and some metabotropic glutamate receptors. Regarding glutamatergic homeostasis, ceftriaxone, MS-153, and GPI-1046, which upregulate glutamate transporter 1 (GLT1) expression in mesocorticolimbic brain regions, reduce alcohol intake in genetic animal models of alcoholism. Given the hyperglutamatergic/hyperexcitable state of the central nervous system induced by chronic alcohol abuse and withdrawal, the evidence thus far indicates that a restoration of glutamatergic concentrations and activity within the mesocorticolimbic system and extended amygdala as well as multiple memory systems holds great promise for the treatment of alcohol dependence. PMID:25954150

  13. Alcoholic hepatitis.

    PubMed

    Damgaard Sandahl, Thomas

    2014-10-01

    Alcoholic hepatitis (AH) is an acute inflammatory syndrome causing significant morbidity and mortality. The prognosis is strongly dependent on disease severity, as assessed by clinical scoring systems. Reliable epidemiological data as well as knowledge of the clinical course of AH are essential for planning and resource allocation within the health care system. Likewise, individual evaluation of risk is desirable in the clinical handling of patients with AH as it can guide treatment, improve patient information, and serve as strata in clinical trials. The present PhD thesis is based on three studies using a cohort of nearly 2000 patients diagnosed with AH in Denmark from 1999 to 2008 as a cohort, in a population-based study design. The aims of this thesis were as follows. (1) To describe the incidence and short- and long-term mortality, of AH in Denmark (Study I). (2) To validate and compare the ability of the currently available prognostic scores to predict mortality in AH (Study II). (3) To investigate the short- and long-term causes of death of patients with AH (Study III). During the study decade, the annual incidence rate in the Danish population rose from 37 to 46 per 106 for men and from 24 to 34 per 106 for women. Both short- and long-term mortality rose for men and women, and the increase in short-term mortality was attributable to increasing patient age and prevalence of cirrhosis. Our evaluation of the most commonly used prognostic scores for predicting the mortality of patients with AH showed that all scores performed similarly, with Area under the Receiver Operator Characteristics curves giving values between 0.74 and 0.78 for 28-day mortality assessed on admission. Our study on causes of death showed that in the short-term (< 84 days after diagnosis), patients with AH were likely to die from liver-related events and infections. In the long-term (≥ 84 days after diagnosis), those who developed cirrhosis mainly died from liver-related causes, and

  14. Alcoholic myopathy and acetaldehyde.

    PubMed

    Preedy, Victor R; Crabb, David W; Farrés, Jaume; Emery, Peter W

    2007-01-01

    Alcoholic myopathy is characterized by biochemical and morphological lesions within muscle, ranging from impairment of muscle strength and loss of lean tissue to cellular disturbances and altered gene expression. The chronic form of the disease is five times more common than cirrhosis and is characterized by selective atrophy of type 11 (anaerobic) fibres: type I (aerobic) fibres are relatively protected. Although the causative agent is known (i.e. ethanol), the intervening steps between alcohol ingestion and the development of symptoms and lesions are poorly understood. However, acetaldehyde appears to have an important role in the aetiology of the disease. For example, alcohol is a potent perturbant of muscle protein synthesis in vivo, and this effect is exacerbated by cyanamide pre-dosage, which raises acetaldehyde concentrations. Acetaldehyde alone also reduces muscle protein synthesis in vivo and proteolytic activity in vitro. The formation of acetaldehyde protein adducts is another mechanism of putative importance in alcoholic myopathy. These adducts are formed within muscle in response to either acute or chronic alcohol exposure and the adducts are located preferentially within the sarcolemmal and sub-sarcolemmal regions. However, the significance of protein adduct formation is unclear since we do not currently know the identity of the adducted muscle proteins nor whether adduction alters the biochemical or functional properties of skeletal muscle proteins.

  15. Understanding the Effects of Stress and Alcohol Cues on Motivation for Alcohol via Behavioral Economics

    PubMed Central

    Amlung, Michael; MacKillop, James

    2014-01-01

    Background Psychological stress and alcohol cues are common antecedents of both ongoing drinking and relapse. One candidate mechanism of risk from these factors is acute increases in craving, but experimental support for this hypothesis is mixed. Furthermore, the combination of stress and cues has been largely unstudied. The current study employed a behavioral economic approach to investigate the combined roles of psychosocial stress and alcohol cues on motivation for alcohol. Methods In a sample of 84 adult heavy drinkers, we examined the effects of an acute laboratory stress induction and an alcohol cue exposure on subjective craving and stress, arousal, and behavioral economic decision-making. Primary dependent measures included an intertemporal cross-commodity multiple choice procedure (ICCMCP), incorporating both price and delay elements; an alcohol purchase task (APT), measuring alcohol demand; and a monetary delay discounting task (DDT), measuring intertemporal choice. Results The stress induction significantly increased stress, craving, and the incentive value of alcohol on the ICCMCP and APT. Stress-related increases in value on the ICCMCP were mediated by increased alcohol demand. Exposure to alcohol cues only significantly affected craving, APT breakpoint, and arousal. Delay discounting was not affected by either stress or cues. Conclusions These results reveal unique behavioral economic dimensions of motivation for alcohol following acute stress and an alcohol cue exposure. More broadly, as the first application of this approach to understanding the role of stress in drug motivation, these findings support its utility and potential in future applications. PMID:24890323

  16. Overview of Alcohol Consumption

    MedlinePlus

    ... Search Alcohol & Your Health Overview of Alcohol Consumption Alcohol's Effects on the Body Alcohol Use Disorder Fetal Alcohol ... other questions about alcohol. Here’s what we know: Alcohol’s effects vary from person to person, depending on a ...

  17. Alcohol and pregnancy

    MedlinePlus

    Drinking alcohol during pregnancy; Fetal alcohol syndrome - pregnancy; FAS - fetal alcohol syndrome ... When a pregnant woman drinks alcohol, the alcohol travels through her blood and into the baby's blood, tissues, and organs. Alcohol breaks down much more slowly in ...

  18. Discovering genes involved in alcohol dependence and other alcohol responses: role of animal models.

    PubMed

    Buck, Kari J; Milner, Lauren C; Denmark, Deaunne L; Grant, Seth G N; Kozell, Laura B

    2012-01-01

    The genetic determinants of alcoholism still are largely unknown, hindering effective treatment and prevention. Systematic approaches to gene discovery are critical if novel genes and mechanisms involved in alcohol dependence are to be identified. Although no animal model can duplicate all aspects of alcoholism in humans, robust animal models for specific alcohol-related traits, including physiological alcohol dependence and associated withdrawal, have been invaluable resources. Using a variety of genetic animal models, the identification of regions of chromosomal DNA that contain a gene or genes which affect a complex phenotype (i.e., quantitative trait loci [QTLs]) has allowed unbiased searches for candidate genes. Several QTLs with large effects on alcohol withdrawal severity in mice have been detected, and fine mapping of these QTLs has placed them in small intervals on mouse chromosomes 1 and 4 (which correspond to certain regions on human chromosomes 1 and 9). Subsequent work led to the identification of underlying quantitative trait genes (QTGs) (e.g., Mpdz) and high-quality QTG candidates (e.g., Kcnj9 and genes involved in mitochondrial respiration and oxidative stress) and their plausible mechanisms of action. Human association studies provide supporting evidence that these QTLs and QTGs may be directly relevant to alcohol risk factors in clinical populations.

  19. Alcohol and Memory: Storage and State Dependency

    ERIC Educational Resources Information Center

    Parker, Elizabeth S.; And Others

    1976-01-01

    Effects of acute alcohol intoxication on the storage phase of memory were evaluated with two tasks that minimized response retrieval: unpaced paired-associate learning with highly available responses and forced-choice picture recognition. It was concluded that storage processes are sensitive to disruption by alcohol. (CHK)

  20. Effects of alcohol abuse on reproductive function in women.

    PubMed

    Mello, N K

    1988-01-01

    Alcohol abuse and alcoholism are associated with disorders of reproductive function in both men and women. Amenorrhea, anovulation, and luteal phase dysfunction may occur in alcohol-dependent women and alcohol abusers. Yet there has been relatively little research on the consequences of alcohol abuse for female reproductive function. Recent clinical and survey studies of alcohol effects on pituitary gonadotropins and gonadal steroid hormones in women are reviewed. Experimental studies of the acute and chronic effects of alcohol on the hypothalamic-pituitary-gonadal axis in normal women and in animal models are also described. Recent studies of the acute effects of alcohol on opioid antagonist and synthetic LHRH-stimulated pituitary gonadotropins are summarized. Possible mechanisms underlying alcohol-induced disruptions of menstrual cycle regularity are discussed.

  1. Changes in immunologic cell surface markers during cocaine withdrawal in pregnant women.

    PubMed

    Johnson, T R; Knisely, J S; Christmas, J T; Schnoll, S H; Ruddy, S

    1996-12-01

    To evaluate the effects of acute cocaine withdrawal on the immune system of pregnant women, we analyzed changes in a panel of cell surface markers and plasma proteins that have immunological importance. The cell surface markers included complement receptors [CR1 (CD35), CR2 (CD21), CR3 (CD11b, CD18)], immunoglobulin Fc receptors [FcgammaRII (CD32), FcgammaRIII (CD16)], proteins important for lymphocyte function [CD3, CD4, CD8, CD19, CD25, CD45RA], and the framework antigen HLA-ABC. We also measured levels of the plasma proteins C3, C4, IgG, IgM, and IgA, along with the cytokine interleukin-2, soluble lymphocyte markers sCD25, sCD4, sCD8, IL-2, and soluble immune complexes. While no significant changes were seen in the levels of plasma proteins, changes paralleling the course of acute withdrawal were seen in complement receptors and immunoglobulin Fc receptors on leukocyte subpopulations. By contrast, proteins important for lymphocyte function were relatively unperturbed. There was an increase in receptor expression at the onset of withdrawal that peaked 3-5 days after last cocaine use, followed by a decrease in expression to initial (pre-withdrawal) levels. These changes in cell surface receptors may reflect altered immune function in the women who were withdrawing from cocaine.

  2. Alcohol and marijuana: effects on epilepsy and use by patients with epilepsy.

    PubMed

    Gordon, E; Devinsky, O

    2001-10-01

    We review the safety of alcohol or marijuana use by patients with epilepsy. Alcohol intake in small amounts (one to two drinks per day) usually does not increase seizure frequency or significantly affect serum levels of antiepileptic drugs (AEDs). Adult patients with epilepsy should therefore be allowed to consume alcohol in limited amounts. However, exceptions may include patients with a history of alcohol or substance abuse, or those with a history of alcohol-related seizures. The most serious risk of seizures in connection with alcohol use is withdrawal. Alcohol withdrawal lowers the seizure threshold, an effect that may be related to alcohol dose, rapidity of withdrawal, and chronicity of exposure. Individuals who chronically abuse alcohol are at significantly increased risk of developing seizures, which can occur during withdrawal or intoxication. Alcohol abuse predisposes to medical and metabolic disorders that can lower the seizure threshold or cause symptoms that mimic seizures. Therefore, in evaluating a seizure in a patient who is inebriated or has abused alcohol, one must carefully investigate to determine the cause. Animal and human research on the effects of marijuana on seizure activity are inconclusive. There are currently insufficient data to determine whether occasional or chronic marijuana use influences seizure frequency. Some evidence suggests that marijuana and its active cannabinoids have antiepileptic effects, but these may be specific to partial or tonic-clonic seizures. In some animal models, marijuana or its constituents can lower the seizure threshold. Preliminary, uncontrolled clinical studies suggest that cannabidiol may have antiepileptic effects in humans. Marijuana use can transiently impair short-term memory, and like alcohol use, may increase noncompliance with AEDs. Marijuana use or withdrawal could potentially trigger seizures in susceptible patients.

  3. Amphetamine Withdrawal Differentially Increases the Expression of Organic Cation Transporter 3 and Serotonin Transporter in Limbic Brain Regions

    PubMed Central

    Solanki, Rajeshwari R.; Scholl, Jamie L.; Watt, Michael J.; Renner, Kenneth J.; Forster, Gina L.

    2016-01-01

    Amphetamine withdrawal increases anxiety and stress sensitivity related to blunted ventral hippocampus (vHipp) and enhances the central nucleus of the amygdala (CeA) serotonin responses. Extracellular serotonin levels are regulated by the serotonin transporter (SERT) and organic cation transporter 3 (OCT3), and vHipp OCT3 expression is enhanced during 24 hours of amphetamine withdrawal, while SERT expression is unaltered. Here, we tested whether OCT3 and SERT expression in the CeA is also affected during acute withdrawal to explain opposing regional alterations in limbic serotonergic neurotransmission and if respective changes continued with two weeks of withdrawal. We also determined whether changes in transporter expression were confined to these regions. Male rats received amphetamine or saline for two weeks followed by 24 hours or two weeks of withdrawal, with transporter expression measured using Western immunoblot. OCT3 and SERT expression increased in the CeA at both withdrawal timepoints. In the vHipp, OCT3 expression increased only at 24 hours of withdrawal, with an equivalent pattern seen in the dorsomedial hypothalamus. No changes were evident in any other regions sampled. These regionally specific changes in limbic OCT3 and SERT expression may partially contribute to the serotonergic imbalance and negative affect during amphetamine withdrawal. PMID:27478387

  4. Acute Pancreatitis

    PubMed Central

    Geokas, Michael C.

    1972-01-01

    For many decades two types of acute pancreatitis have been recognized: the edematous or interstitial and the hemorrhagic or necrotic. In most cases acute pancreatitis is associated with alcoholism or biliary tract disease. Elevated serum or urinary α-amylase is the most important finding in diagnosis. The presence of methemalbumin in serum and in peritoneal or pleural fluid supports the diagnosis of the hemorrhagic form of the disease in patients with a history and enzyme studies suggestive of pancreatitis. There is no characteristic clinical picture in acute pancreatitis, and its complications are legion. Pancreatic pseudocyst is probably the most common and pancreatic abscess is the most serious complication. The pathogenetic principle is autodigestion, but the precise sequence of biochemical events is unclear, especially the mode of trypsinogen activation and the role of lysosomal hydrolases. A host of metabolic derangements have been identified in acute pancreatitis, involving lipid, glucose, calcium and magnesium metabolism and changes of the blood clotting mechanism, to name but a few. Medical treatment includes intestinal decompression, analgesics, correction of hypovolemia and other supportive and protective measures. Surgical exploration is advisable in selected cases, when the diagnosis is in doubt, and is considered imperative in the presence of certain complications, especially pancreatic abscess. PMID:4559467

  5. Human alcohol-related neuropathology

    PubMed Central

    Kril, Jillian J.

    2015-01-01

    Alcohol-related diseases of the nervous system are caused by excessive exposures to alcohol, with or without co-existing nutritional or vitamin deficiencies. Toxic and metabolic effects of alcohol (ethanol) vary with brain region, age/developmental stage, dose, and duration of exposures. In the mature brain, heavy chronic or binge alcohol exposures can cause severe debilitating diseases of the central and peripheral nervous systems, and skeletal muscle. Most commonly, long-standing heavy alcohol abuse leads to disproportionate loss of cerebral white matter and impairments in executive function. The cerebellum (especially the vermis), cortical-limbic circuits, skeletal muscle, and peripheral nerves are also important targets of chronic alcohol-related metabolic injury and degeneration. Although all cell types within the nervous system are vulnerable to the toxic, metabolic, and degenerative effects of alcohol, astrocytes, oligodendrocytes, and synaptic terminals are major targets, accounting for the white matter atrophy, neural inflammation and toxicity, and impairments in synaptogenesis. Besides chronic degenerative neuropathology, alcoholics are predisposed to develop severe potentially life-threatening acute or subacute symmetrical hemorrhagic injury in the diencephalon and brainstem due to thiamine deficiency, which exerts toxic/metabolic effects on glia, myelin, and the microvasculature. Alcohol also has devastating neurotoxic and teratogenic effects on the developing brain in association with fetal alcohol spectrum disorder/fetal alcohol syndrome. Alcohol impairs function of neurons and glia, disrupting a broad array of functions including neuronal survival, cell migration, and glial cell (astrocytes and oligodendrocytes) differentiation. Further progress is needed to better understand the pathophysiology of this exposure-related constellation of nervous system diseases and better correlate the underlying pathology with in vivo imaging and biochemical lesions

  6. A potential role for adiponectin receptor 2 (AdipoR2) in the regulation of alcohol intake.

    PubMed

    Repunte-Canonigo, Vez; Berton, Fulvia; Cottone, Pietro; Reifel-Miller, Anne; Roberts, Amanda J; Morales, Marisela; Francesconi, Walter; Sanna, Pietro Paolo

    2010-06-21

    The anterior cingulate cortex (ACC) has been implicated in alcohol and drug addiction. We recently identified the small G protein K-ras as an alcohol-regulated gene in the ACC by gene expression analysis. We show here that the adiponectin receptor 2 (AdipoR2) was differentially regulated by alcohol in the ACC in a K-ras-dependent manner. Additionally, withdrawal-associated increased drinking was attenuated in AdipoR2 null mice. Intracellular recordings revealed that adiponectin increased the excitability of ACC neurons and that this effect was more pronounced during alcohol withdrawal, suggesting that AdipoR2 signaling may contribute to increased ACC activity. Altogether, the data implicate K-ras-regulated pathways involving AdipoR2 in the cellular and behavioral actions of alcohol that may contribute to overactivity of the ACC during withdrawal and excessive alcohol drinking.

  7. Cardiac arrest due to baclofen withdrawal syndrome

    PubMed Central

    Cardoso, Ana Luísa; Quintaneiro, Claudio; Seabra, Helena; Teixeira, Carla

    2014-01-01

    A 41-year-old man presented with postcervical traumatic complete quadriparesis under intrathecal baclofen therapy (ITB) for refractory spasticity. Less than 24 h after having his baclofen pump substituted, he develops hyperthermia, seizures, cognitive depression, acute hypoxaemic respiratory failure and cardiovascular instability leading to mechanical ventilation and vasopressor support. He was transferred to an intensive care unit with diagnosis of community-acquired pneumonia leading to septic shock. He evolved with progressive clinical worsening and multisystem organ failure and cardiac arrest in non-shockable rhythm (pulseless electrical activity)—4 min resuscitation with return of spontaneous circulation. Considering the possible diagnosis of baclofen withdrawal syndrome