Effects of alcohol-induced working memory decline on alcohol consumption and adverse consequences of use.

Science.gov (United States)

Lechner, William V; Day, Anne M; Metrik, Jane; Leventhal, Adam M; Kahler, Christopher W

2016-01-01

Alcohol use appears to decrease executive function acutely in a dose-dependent manner, and lower baseline executive function appears to contribute to problematic alcohol use. However, no studies, to our knowledge, have examined the relationship between individual differences in working memory (a subcomponent of executive function) after alcohol consumption and drinking behaviors and consequences. The current study assessed the relationship between drinking behavior, alcohol-related consequences, and alcohol-induced changes in working memory (as assessed by Trail Making Test-B). Participants recruited from the community (n = 41), 57.3 % male, mean age 39.2, took part in a three-session, within-subjects, repeated-measures design. Participants were administered a placebo, 0.4 g/kg, or 0.8 g/kg dose of alcohol. Working memory, past 30-day alcohol consumption, and consequences of alcohol use were measured at baseline; working memory was measured again after each beverage administration. Poorer working memory after alcohol administration (controlling for baseline working memory) was significantly associated with a greater number of drinks consumed per drinking day. Additionally, we observed a significant indirect relationship between the degree of alcohol-induced working memory decline and adverse consequences of alcohol use, which was mediated through greater average drinks per drinking day. It is possible that greater individual susceptibility to alcohol-induced working memory decline may limit one's ability to moderate alcohol consumption as evidenced by greater drinks per drinking day and that this results in more adverse consequences of alcohol use.

Alcohol-Induced Impairment of Balance is Antagonized by Energy Drinks.

Science.gov (United States)

Marczinski, Cecile A; Fillmore, Mark T; Stamates, Amy L; Maloney, Sarah F

2018-01-01

The acute administration of alcohol reliably impairs balance and motor coordination. While it is common for consumers to ingest alcohol with other stimulant drugs (e.g., caffeine, nicotine), little is known whether prototypical alcohol-induced balance impairments are altered by stimulant drugs. The purpose of this study was to examine whether the coadministration of a high-caffeine energy drink with alcohol can antagonize expected alcohol-induced increases in body sway. Sixteen social drinkers (of equal gender) participated in 4 separate double-blind dose administration sessions that involved consumption of alcohol and energy drinks, alone and in combination. Following dose administration, participants completed automated assessments of balance stability (both eyes open and eyes closed) measured using the Biosway Portable Balance System. Participants completed several subjective measures including self-reported ratings of sedation, stimulation, fatigue, and impairment. Blood pressure and pulse rate were recorded repeatedly. The acute administration of alcohol increased body sway, and the coadministration of energy drinks antagonized this impairment. When participants closed their eyes, alcohol-induced body sway was similar whether or not energy drinks were ingested. While alcohol administration increased ratings of sedation and fatigue, energy drink administration increased ratings of stimulation and reduced ratings of fatigue. Modest increases in systolic and diastolic blood pressure following energy drink administration were also observed. Visual assessment of balance impairment is frequently used to indicate that an individual has consumed too much alcohol (e.g., as part of police-standardized field sobriety testing or by a bartender assessing when someone should no longer be served more alcohol). The current findings suggest that energy drinks can antagonize alcohol-induced increases in body sway, indicating that future work is needed to determine whether this

Reduction by the positive allosteric modulator of the GABAB receptor, GS39783, of alcohol self-administration in Sardinian alcohol-preferring rats exposed to the “sipper” procedure

Directory of Open Access Journals (Sweden)

Paola Maccioni

2010-07-01

Full Text Available The present study was designed to evaluate (a alcohol self-administration behavior of selectively bred, Sardinian alcohol-preferring (sP rats exposed to the so-called “sipper” procedure (characterized by the temporal separation between alcohol-seeking and -taking phases, and (b the effect of the positive allosteric modulator of the GABAB receptor, GS39783, on alcohol self-administration in sP rats exposed to this procedure. To this end, sP rats were initially trained to lever-respond under a reinforcement requirement (RR 55 (RR55 for alcohol. Achievement of RR55 resulted in the 20-min presentation of the alcohol (15%, v/v-containing sipper bottle. Once stable levels of lever-responding and alcohol consumption were reached, rats were treated with 0, 25, 50, and 100 mg/kg GS39783 (i.g. 60 min before the self-administration session. Rats displayed robust alcohol-seeking (as suggested by relatively short latencies to the first lever-response and high frequencies of lever-responding and -taking (as suggested by alcohol intakes averaging approximately 1.5 g/kg behaviors. Pretreatment with GS39783 inhibited both alcohol-seeking (the number of rats achieving RR55 and the mean RR value were virtually halved and -taking (the amount of self-administered alcohol was reduced by approximately 60%. The results of the present study suggest the power of the “sipper” procedure in triggering high levels of alcohol-seeking and -taking behavior in sP rats. Further, these results extend to this additional procedure of alcohol self-administration the capacity of GS39783 to reduce the motivational properties of alcohol and alcohol consumption in sP rats.

Reduction by the Positive Allosteric Modulator of the GABAB Receptor, GS39783, of Alcohol Self-Administration in Sardinian Alcohol-Preferring Rats Exposed to the “Sipper” Procedure

Science.gov (United States)

Maccioni, Paola; Flore, Paolo; Carai, Mauro A. M.; Mugnaini, Claudia; Pasquini, Serena; Corelli, Federico; Gessa, Gian Luigi; Colombo, Giancarlo

2010-01-01

The present study was designed to evaluate (a) alcohol self-administration behavior of selectively bred, Sardinian alcohol-preferring (sP) rats exposed to the so-called “sipper” procedure (characterized by the temporal separation between alcohol-seeking and -taking phases), and (b) the effect of the positive allosteric modulator of the GABAB receptor, GS39783, on alcohol self-administration in sP rats exposed to this procedure. To this end, sP rats were initially trained to lever-respond under a reinforcement requirement (RR) 55 (RR55) for alcohol. Achievement of RR55 resulted in the 20-min presentation of the alcohol (15%, v/v)-containing sipper bottle. Once stable levels of lever-responding and alcohol consumption were reached, rats were treated with 0, 25, 50, and 100 mg/kg GS39783 (i.g.) 60 min before the self-administration session. Rats displayed robust alcohol-seeking (as suggested by relatively short latencies to the first lever-response and high frequencies of lever-responding) and -taking (as suggested by alcohol intakes averaging approximately 1.5 g/kg) behaviors. Pretreatment with GS39783 inhibited both alcohol-seeking (the number of rats achieving RR55 and the mean RR value were virtually halved) and -taking (the amount of self-administered alcohol was reduced by approximately 60%). The results of the present study suggest the power of the “sipper” procedure in triggering high levels of alcohol-seeking and -taking behavior in sP rats. Further, these results extend to this additional procedure of alcohol self-administration the capacity of GS39783 to reduce the motivational properties of alcohol and alcohol consumption in sP rats. PMID:21423431

Changes in Patient-Reported Alcohol-Related Advice Following Veterans Health Administration Implementation of Brief Alcohol Interventions.

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Chavez, Laura J; Williams, Emily C; Lapham, Gwen T; Rubinsky, Anna D; Kivlahan, Daniel R; Bradley, Katharine A

2016-05-01

Brief alcohol interventions are recommended for primary care patients who screen positive for alcohol misuse, but implementation is challenging. The U.S. Veterans Health Administration (Veterans Affairs [VA]) implemented brief interventions for patients with alcohol misuse in 2008, and rates of brief interventions documented in the electronic medical record increased from 24% to 78% (2008-2011). This study examined whether an independent measure of brief interventions-patient-reported alcohol-related advice-also increased among VA outpatients who screened positive for alcohol misuse on a mailed survey. This retrospective cross-sectional study included VA outpatient respondents to the VA's Survey of Healthcare Experiences of Patients (SHEP; 2007-2011) who reported past-year alcohol use and answered a question about alcohol-related advice. Alcohol-related advice was defined as a report of past-year advice from a VA clinician to abstain from or reduce drinking. The adjusted prevalence of alcoholrelated advice among patients who screened positive for alcohol misuse (SHEP AUDIT-C ≥ 5) was estimated for each year. Among patients with alcohol misuse (n = 61,843), the adjusted prevalence of alcohol-related advice increased from 40.4% (95% CI [39.3%, 41.5%]) in 2007 to 55.5% (95% CI [53.3%, 57.8%]) in 2011. Rates of alcoholrelated advice increased significantly each year except the last. The VA's efforts to implement brief interventions were associated with increased patient-reported alcohol-related advice over time, with a majority of patients with alcohol misuse reporting its receipt. Other systems considering similar approaches to implementation may benefit from collecting patient-reported measures of brief interventions for an additional perspective on implementation.

Repeated light-dark phase shifts modulate voluntary ethanol intake in male and female high alcohol-drinking (HAD1) rats.

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Clark, James W; Fixaris, Michael C; Belanger, Gabriel V; Rosenwasser, Alan M

2007-10-01

Chronic disruption of sleep and other circadian biological rhythms, such as occurs in shift work or in frequent transmeridian travel, appears to represent a significant source of allostatic load, leading to the emergence of stress-related physical and psychological illness. Recent animal experiments have shown that these negative health effects may be effectively modeled by exposure to repeated phase shifts of the daily light-dark (LD) cycle. As chronobiological disturbances are thought to promote relapse in abstinent alcoholics, and may also be associated with increased risk of subsequent alcohol abuse in nonalcoholic populations, the present experiment was designed to examine the effects of repeated LD phase shifts on voluntary ethanol intake in rats. A selectively bred, high alcohol-drinking (HAD1) rat line was utilized to increase the likelihood of excessive alcoholic-like drinking. Male and female rats of the selectively bred HAD1 rat line were maintained individually under a LD 12:12 cycle with both ethanol (10% v/v) and water available continuously. Animals in the experimental group were subjected to repeated 6-hour LD phase advances at 3 to 4 week intervals, while control rats were maintained under a stable LD cycle throughout the study. Contact-sensing drinkometers were used to monitor circadian lick patterns, and ethanol and water intakes were recorded weekly. Control males showed progressively increasing ethanol intake and ethanol preference over the course of the study, but males exposed to chronic LD phase shifts exhibited gradual decreases in ethanol drinking. In contrast, control females displayed decreasing ethanol intake and ethanol preference over the course of the experiment, while females exposed to experimental LD phase shifts exhibited a slight increase in ethanol drinking. Chronic circadian desynchrony induced by repeated LD phase shifts resulted in sex-specific modulation of voluntary ethanol intake, reducing ethanol intake in males while

Activated mesenchymal stem cell administration inhibits chronic alcohol drinking and suppresses relapse-like drinking in high-alcohol drinker rats.

Science.gov (United States)

Ezquer, Fernando; Quintanilla, María Elena; Morales, Paola; Ezquer, Marcelo; Lespay-Rebolledo, Carolyne; Herrera-Marschitz, Mario; Israel, Yedy

2017-10-18

Neuroinflammation has been reported to follow chronic ethanol intake and may perpetuate alcohol consumption. Present studies determined the effect of human mesenchymal stem cells (hMSCs), known for their anti-inflammatory action, on chronic ethanol intake and relapse-like ethanol intake in a post-deprivation condition. Rats were allowed 12-17 weeks of chronic voluntary ethanol (10% and 20% v/v) intake, after which a single dose of activated hMSCs (5 × 10 5 ) was injected into a brain lateral ventricle. Control animals were administered vehicle. After assessing the effect of hMSCs on chronic ethanol intake for 1 week, animals were deprived of ethanol for 2 weeks and thereafter an ethanol re-access of 60 min was allowed to determine relapse-like intake. A single administration of activated hMSCs inhibited chronic alcohol consumption by 70% (P 80 mg/dl. The single hMSC administration reduced relapse-like blood ethanol levels to 20 mg/dl. Chronic ethanol intake increased by 250% (P chronic ethanol intake, an effect that was fully abolished by the administration of hMSCs. This study supports the neuroinflammation-chronic ethanol intake hypothesis and suggest that mesenchymal stem cell administration may be considered in the treatment of alcohol use disorders. © 2017 Society for the Study of Addiction.

Potentiation of amygdala AMPA receptor activity selectively promotes escalated alcohol self-administration in a CaMKII-dependent manner.

Science.gov (United States)

Cannady, Reginald; Fisher, Kristen R; Graham, Caitlin; Crayle, Jesse; Besheer, Joyce; Hodge, Clyde W

2017-05-01

Growing evidence indicates that drugs of abuse gain control over the individual by usurping glutamate-linked mechanisms of neuroplasticity in reward-related brain regions. Accordingly, we have shown that glutamate α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) activity in the amygdala is required for the positive reinforcing effects of alcohol, which underlie the initial stages of addiction. It is unknown, however, if enhanced AMPAR activity in the amygdala facilitates alcohol self-administration, which is a kernel premise of glutamate hypotheses of addiction. Here, we show that low-dose alcohol (0.6 g/kg/30 minutes) self-administration increases phosphorylation (activation) of AMPAR subtype GluA1 S831 (pGluA1 S831) in the central amygdala (CeA), basolateral amygdala and nucleus accumbens core (AcbC) of selectively bred alcohol-preferring P-rats as compared with behavior-matched (non-drug) sucrose controls. The functional role of enhanced AMPAR activity was assessed via site-specific infusion of the AMPAR positive modulator, aniracetam, in the CeA and AcbC prior to alcohol self-administration. Intra-CeA aniracetam increased alcohol-reinforced but not sucrose-reinforced responding and was ineffective following intra-AcbC infusion. Because GluA1 S831 is a Ca2+/calmodulin-dependent protein kinase II (CaMKII) substrate, we sought to determine if AMPAR regulation of enhanced alcohol self-administration is dependent on CaMKII activity. Intra-CeA infusion of the cell-permeable CaMKII peptide inhibitor myristolated autocamtide-2-related inhibitory peptide (m-AIP) dose-dependently reduced alcohol self-administration. A subthreshold dose of m-AIP also blocked the aniracetam-induced escalation of alcohol self-administration, demonstrating that AMPAR-mediated potentiation of alcohol reinforcement requires CaMKII activity in the amygdala. Enhanced activity of plasticity-linked AMPAR-CaMKII signaling in the amygdala may promote escalated alcohol use

Effect of repeated oral administration of levofloxacin, enrofloxacin, and meloxicam on antioxidant parameters and lipid peroxidation in rabbits.

Science.gov (United States)

Khan, Adil Mehraj; Rampal, Satyavan; Sood, Naresh Kumar

2016-03-09

The effect of 21 days of repeated oral administration of levofloxacin and enrofloxacin both alone and in combination with meloxicam, on the oxidative balance in blood was evaluated in rabbits. Rabbits were randomly allocated to six groups of four animals each. Control group was gavaged 5% dextrose and 2% benzyl alcohol. Three groups were exclusively gavaged meloxicam (0.2 mg/kg body weight o.d.), levofloxacin hemihydrate (10 mg/kg body weight b.i.d 12 h), and enrofloxacin (20 mg/kg body weight o.d.), respectively. Two other groups were co-gavaged meloxicam with levofloxacin hemihydrate and enrofloxacin, respectively. A reduction (p enrofloxacin. The activities of enzymes, glutathione peroxidase and superoxide dismutase, were induced (p enrofloxacin-meloxicam co-treated group. The activity of catalase was non-significantly different between various groups. Enrofloxacin-treated groups had higher (p enrofloxacin and meloxicam. © The Author(s) 2016.

Effects of repeated withdrawal from alcohol on recovery of cognitive impairment under abstinence and rate of relapse.

Science.gov (United States)

Loeber, Sabine; Duka, Theodora; Welzel Márquez, Helga; Nakovics, Helmut; Heinz, Andreas; Mann, Karl; Flor, Herta

2010-01-01

Several authors suggest that withdrawal from alcohol could cause neurotoxic lesions in the frontal lobe and thereby affect cognitive function. In line with this, previous studies have demonstrated greater cognitive impairment of alcohol-dependent patients with two or more previous detoxifications (Hi-detox) compared with patients with less than two detoxifications (Lo-detox). The aim of the present study was to investigate whether repeated withdrawal from alcohol affects recovery of cognitive function and is related to relapse. Forty-eight alcohol-dependent patients (Hi-detox: n = 31, Lo-detox: n = 17) and 36 healthy controls underwent a comprehensive neuropsychological test-battery. Patients were tested after completion of detoxification (T1) and 3 (T2, n = 35) and 6 (T3, n = 28) months after discharge. Healthy controls were tested at T1 (n = 36) and T2 (n = 16). Drinking behaviour was assessed at all times. Patients performed significantly worse than controls at T1 as well as T2 with regard to attention/executive function. Recovery of attention/executive function was observed within the second 3 months after discharge, but the Hi-detox group performed worse than the Lo-detox group. No association with relapse was observed. This study provides first evidence, that repeated withdrawal from alcohol might be associated with reduced brain plasticity as indicated by a delay of recovery from impairment of attention/executive function. However, little evidence was found for a direct influence of cognitive impairment on treatment success.

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

Science.gov (United States)

2010-07-01

... 28 Judicial Administration 1 2010-07-01 2010-07-01 false Federal Bureau of Investigation, Drug Enforcement Administration, Bureau of Alcohol, Tobacco, Firearms, and Explosives, Bureau of Prisons, Federal... Administrative Matters § 0.138 Federal Bureau of Investigation, Drug Enforcement Administration, Bureau of...

Sex differences in behavioral and PKA cascade responses to repeated cocaine administration.

Science.gov (United States)

Zhou, Luyi; Sun, Wei-Lun; Weierstall, Karen; Minerly, Ana Christina; Weiner, Jan; Jenab, Shirzad; Quinones-Jenab, Vanya

2016-10-01

Previous studies have shown sex different patterns in behavioral responses to cocaine. Here, we used between-subject experiment design to study whether sex differences exist in the development of behavioral sensitization and tolerance to repeated cocaine, as well as the role of protein kinase A (PKA) signaling cascade in this process. Ambulatory and rearing responses were recorded in male and female rats after 1 to 14 days of administration of saline or cocaine (15 mg/kg; ip). Correspondent PKA-associated signaling in the nucleus accumbens (NAc) and caudate-putamen (CPu) was measured at each time point. Our results showed that females exhibited higher cocaine-induced behavioral responses and developed behavioral sensitization and tolerance faster than males. Whereas females developed behavioral sensitization to cocaine after 2 days and tolerance after 14 days, male rats developed sensitization after 5 days. In addition, cocaine induced a sexual dimorphic pattern in the progression of neuronal adaptations on the PKA cascade signaling in region (NAc vs. CPu) and time (days of cocaine administration)-dependent manners. In general, more PKA signaling cascade changes were found in the NAc of males on day 5 and in the CPu of females with repeated cocaine injection. In addition, in females, behavioral activities positively correlated with FosB levels in the NAc and CPu and negatively correlated with Cdk5 and p35 in the CPu, while no correlation was observed in males. Our studies suggest that repeated cocaine administration induced different patterns of behavioral and molecular responses in the PKA cascade in male and female rats.

ACCUMULATION AND METABOLISM OF ARSENIC IN MICE AFTER REPEATED ADMINISTRATION OF ARSENATE

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Accumulation and metabolism of arsenic in mice after repeated oral administration of arsenate, Hughes, M. F., Kenyon, E. M., Edwards, B. C., Mitchell, C. T., Del Razo, L. M., and Thomas, D. J. The human carcinogen inorganic arsenic (iAs) is a pervasive environmental ...

Modeling the effects of repeated systemic administrations of small activity amounts In radionuclide therapy with beta emitters

International Nuclear Information System (INIS)

Calderon, Carlos; Gonzalez, Joaquin; Cepero, Janet; Colom, Camila; Rodriguez, Juan C.

2008-01-01

Full text: Good results for radionuclide therapy treatments where repeated short time spaced systemic injection of small activity amounts are given have been reported. Bone marrow and kidneys are usually considered as dose-limiting organs in radionuclide therapy. The treatments in radionuclide therapy with repeated administration could be optimized if irradiation effects in those one might be estimated. Xeno-grafted mice is the often biological model used during the evaluation of candidates for radionuclide therapy. A mathematical model of tumor cell kinetics was combined with another one reported for marrow cell kinetics which allows the calculation of marrow cell survival and proliferation in response to different irradiation schemes. Radionuclide therapy treatment with repeated administrations with radiopharmaceuticals labeled with beta emitters were simulated. The effects on fast-growing and slow-growing tumors were evaluated, as well as radiosensitive and radioresistant tumors. For more realistic estimation of absorbed dose in mice organs the cross-irradiation due to high energy beta particles was included into the MIRD's formula. Tumor and kidneys responses to the irradiation were estimated on the linear-quadratic model framework which was adapted for a multi-exponential dose rate function describing radionuclide therapy treatments with repeated administrations. Published values for murine tumors kinetics, marrows cellular turnover rates and radiosensitivities were used during the calculations. Iso-effective schemes were also determined varying the interval between fractions and the number of administration. For a given tolerated level of thrombocytopenia and absorbed dose in kidneys an optimal regime of radionuclide therapy with repeated administration could be found. The mathematical model presented here allows the prediction of the nadir and duration of thrombocytopenia, the effects on kidneys and the tumor cell response to various treatment schemes

Short-term repeated corticosterone administration enhances glutamatergic but not GABAergic transmission in the rat motor cortex.

Science.gov (United States)

Kula, Joanna; Blasiak, Anna; Czerw, Anna; Tylko, Grzegorz; Sowa, Joanna; Hess, Grzegorz

2016-04-01

It has been demonstrated that stress impairs performance of skilled reaching and walking tasks in rats due to the action of glucocorticoids involved in the stress response. Skilled reaching and walking are controlled by the primary motor cortex (M1); however, it is not known whether stress-related impairments in skilled motor tasks are related to functional and/or structural alterations within the M1. We studied the effects of single and repeated injections of corticosterone (twice daily for 7 days) on spontaneous excitatory and inhibitory postsynaptic currents (sEPSCs and sIPSCs) recorded from layer II/III pyramidal neurons in ex vivo slices of the M1, prepared 2 days after the last administration of the hormone. We also measured the density of dendritic spines on pyramidal cells and the protein levels of selected subunits of AMPA, NMDA, and GABAA receptors after repeated corticosterone administration. Repeatedly administered corticosterone induced an increase in the frequency but not in the amplitude of sEPSCs, while a single administration had no effect on the recorded excitatory currents. The frequency and amplitude of sIPSCs as well as the excitability of pyramidal cells were changed neither after single nor after repeated corticosterone administration. Treatment with corticosterone for 7 days did not modify the density of dendritic spines on pyramidal neurons. Corticosterone influenced neither the protein levels of GluA1, GluA2, GluN1, GluN2A, and GluN2B subunits of glutamate receptors nor those of α1, β2, and γ2 subunits of the GABAA receptor. The increase in sEPSCs frequency induced by repeated corticosterone administration faded out within 7 days. These data indicate that prolonged administration of exogenous corticosterone selectively and reversibly enhances glutamatergic, but not GABAergic transmission in the rat motor cortex. Our results suggest that corticosterone treatment results in an enhancement of spontaneous glutamate release from presynaptic

Alcohol and the sleeping brain.

Science.gov (United States)

Colrain, Ian M; Nicholas, Christian L; Baker, Fiona C

2014-01-01

Alcohol acts as a sedative that interacts with several neurotransmitter systems important in the regulation of sleep. Acute administration of large amounts of alcohol prior to sleep leads to decreased sleep-onset latency and changes in sleep architecture early in the night, when blood alcohol levels are high, with subsequent disrupted, poor-quality sleep later in the night. Alcohol abuse and dependence are associated with chronic sleep disturbance, lower slow-wave sleep, and more rapid-eye-movement sleep than normal, that last long into periods of abstinence and may play a role in relapse. This chapter outlines the evidence for acute and chronic alcohol effects on sleep architecture and sleep electroencephalogram, evidence for tolerance with repeated administration, and possible underlying neurochemical mechanisms for alcohol's effects on sleep. Also discussed are sex differences as well as effects of alcohol on sleep homeostasis and circadian regulation. Evidence for the role of sleep disruption as a risk factor for developing alcohol dependence is discussed in the context of research conducted in adolescents. The utility of sleep-evoked potentials in the assessment of the effects of alcoholism on sleep and the brain and in abstinence-mediated recovery is also outlined. The chapter concludes with a series of questions that need to be answered to determine the role of sleep and sleep disturbance in the development and maintenance of problem drinking and the potential beneficial effects of the treatment of sleep disorders for maintenance of abstinence in alcoholism. © 2014 Elsevier B.V. All rights reserved.

Effect of tramadol on metamizol pharmacokinetics and pharmacodynamics after single and repeated administrations in arthritic rats

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Luis Alfonso Moreno-Rocha

2016-11-01

Full Text Available Combined administration of certain doses of opioid compounds with a non-steroidal anti-inflammatory drug can produce additive or supra-additive effects while reducing unwanted effects. We have recently reported that co-administration of metamizol with tramadol produces antinociceptive effect potentiation, after acute treatment. However, none information about the effect produced by the combination after chronic or repeated dose administration exists. The aims of this study were to investigate whether the antinociceptive synergism produced by the combination of metamizol and tramadol (177.8 + 17.8 mg/kg, s.c. respectively is maintained after repeated treatment and whether the effects observed are primarily due to pharmacodynamic interactions or may be related to pharmacokinetics changes. Administration of metamizol plus tramadol acute treatment significantly enhanced the antinociceptive effect of the drugs given alone (P  0.05. The mechanism involved in the synergism of the antinociceptive effect observed with the combination of metamizol and tramadol in single dose cannot be attributed to a pharmacokinetic interaction, and other pharmacodynamic interactions have to be considered. On the other hand, when metamizol and tramadol were co-administered under repeated administrations, a pharmacokinetic interaction and tolerance development occurred. Differences found in metamizol active metabolites’ pharmacokinetics (P < 0.05 were related to the development of tolerance produced by the combination after repeated doses. This work shows an additional preclinical support for the combination therapy. The clinical utility of this combination in a suitable dose range should be evaluated in future studies.

The effects of repeated parenteral administration of chelating agents on the distribution and excretion of uranium

International Nuclear Information System (INIS)

Domingo, J.L.; Ortega, A.; Llobet, J.M.; Paternain, J.L.; Corbella, J.

1989-01-01

The effects of repeated ip administration of gallic acid, 4,5-dihydroxy-1,3-benzenedisulfonic acid (Tiron), diethylenetriaminepentaacetic acid (DTPA), and 5-aminosalicylic acid (5-AS) on the distribution and excretion of uranium were assessed in male Swiss mice. Only Tiron significantly increased the amount of uranium excreted into urine and feces. A significant decrease in the concentration of uranium in liver, spleen and bone was observed after administration of Tiron, whereas injection of gallic acid or DTPA resulted in a significant decrease in the concentration of the metal in the liver. The results show that Tiron was consistently the most effective chelator of those tested in the treatment of uranium poisoning after repeated daily administration of the metal

Enhanced self-administration of alcohol in muscarinic acetylcholine M₄ receptor knockout mice

DEFF Research Database (Denmark)

de la Cour, Cecilie; Sørensen, Gunnar; Wörtwein, Gitta

2015-01-01

% and 10% alcohol in 60min sessions, 6 days/week, after having undergone a standard sucrose fading training procedure on a fixed ratio schedule. The mice were further subjected to an extinction period followed by a 1 day reinstatement trial. M4-/- mice consumed more alcohol at 5% and 8% compared to their M......4+/+ littermates. The highest alcohol concentration used (10%) did not immediately result in divergent drinking patterns, but after 4 weeks of 10% alcohol self-administration, baseline levels as well as a pattern of M4-/- mice consuming more alcohol than their M4+/+ controls were re...

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

Directory of Open Access Journals (Sweden)

Maarten eLoos

2013-10-01

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

Compound list: allyl alcohol [Open TG-GATEs

Lifescience Database Archive (English)

Full Text Available allyl alcohol AA 00010 ftp://ftp.biosciencedbc.jp/archive/open-tggates/LATEST/Human/in_vitro/allyl_alcohol....Human.in_vitro.Liver.zip ftp://ftp.biosciencedbc.jp/archive/open-tggates/LATEST/Rat/in_vitro/allyl_alcohol...dbc.jp/archive/open-tggates/LATEST/Rat/in_vivo/Liver/Repeat/allyl_alcohol.Rat.in_vivo.Liver.Repeat.zip ftp:/.../ftp.biosciencedbc.jp/archive/open-tggates/LATEST/Rat/in_vivo/Kidney/Single/allyl_alcohol.Rat.in_vivo.Kidney....Single.zip ftp://ftp.biosciencedbc.jp/archive/open-tggates/LATEST/Rat/in_vivo/Kidney/Repeat/allyl_alcohol.Rat.in_vivo.Kidney.Repeat.zip ...

Polydatin administration improves serum biochemical parameters and oxidative stress markers during chronic alcoholism: a pilot study.

Science.gov (United States)

Pace, Maria Caterina; Passavanti, Maria Beatrice; Aurilio, Caterina; Sansone, Pasquale; Aurilio, Rossella; DE Maria, Salvatore; Lama, Stefania; Federico, Alessandro; Ravagnan, Gianpietro; Caraglia, Michele; Stiuso, Paola

2015-01-01

Polydatin, a hydroxystilbene derived from the rhizome of Polygonum cuspidatum, elicits hepatoprotective and neuroprotective effects through its anti-oxidant properties. The present study aimed to determine the effects of oral administration of polydatin in alcoholic patients in order to improve liver biochemical parameters, serum oxidative stress and mental state. We enrolled 20 chronic alcoholic patients hospitalized for rehabilitative therapy. The patients were divided into two groups receiving the following treatment regimes for two weeks: administration of an anti-oxidant nutritional supplement containing glutathione and vitamin C (group 1), or glutathione, vitamin C and polydatin (group 2). The results of the present study show that elevated plasma aspartate aminotransferase and alanine aminotransferase levels in patients after two weeks of alcohol withdrawal were significantly reduced by polydatin (group 2), when compared to group 1. Polydatin also significantly reduced lipid peroxidation levels. Finally, our preliminary data resulting from the analysis of the Mini-Mental Status suggest that polydatin improves cognitive performance. Daily dietary administration of polydatin should be considered for prevention and treatment of liver disease and cognitive impairment in alcoholic patients. Copyright © 2015 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

Web-Based Alcohol Intervention in First-Year College Students: Efficacy of Full-Program Administration Prior to Second Semester.

Science.gov (United States)

Gilbertson, Rebecca J; Norton, Tina R; Beery, Susan H; Lee, Kassandra R

2018-05-12

Commercially available, web-based interventions for the prevention of alcohol use are being adopted for universal use with first-year college students, yet few have received empirical evaluation. This randomized controlled trial investigated the effectiveness of a novel, commercially available, personalized web-based alcohol intervention, Alcohol-Wise (version 4.0, 3 rd Millennium Classrooms), on multiple measures of alcohol consumption, alcohol consequences, alcohol expectancies, academic achievement, and adaptation to college in first-year students. Participants received Alcohol-Wise either prior to first semester or were waitlisted and received the intervention second semester. As longitudinal effectiveness was of interest, follow-up surveys were conducted 10 weeks (n = 76) and 24 weeks (n = 64) following the web-based alcohol intervention. Completion of Alcohol-Wise had effects on academic achievement. Specifically, at the 24 week follow-up, academic achievement was higher in participants who received the intervention first semester of their freshman year as compared to the waitlist control. The incremental rise in heavy episodic drinking during the first semester of college was also reduced in waitlisted participants by Alcohol-Wise administration prior to second semester. Conclusion/Importance: Implications for the timing of web-based alcohol interventions to include administration prior to both first and second semesters of the freshman year are discussed.

Improved posttraumatic acquisition of a place learning task after repeated administration of a serotonergic agonist 8-OH-DPA

DEFF Research Database (Denmark)

Mala, Hana; Mogensen, Jesper

2008-01-01

specifically to 5-HT1A receptor subtypes. The effects were evaluated in terms of functional performance on an allocentric place learning task.    Participants/Materials/Methods: 68 animals served as experimental subjects. Initially, the rats were divided into 6 experimental groups, three of which were...... was given a single dose (5mg/kg/b.w.) of 8-OH-DPAT immediately after surgery (SINGLE TREATM), and one group was treated with daily administration of 8-OH-DPAT (5mg/kg/b.w.) for the six subsequent days (the first administration taking place immediately after surgery) (REPEATED TREATM). The acquisition...... of the water maze based place learning task started on the 8th day after surgery and continued daily for the next 25 days.   Results: The results show that within the lesioned groups, the group that was subjected to repeated administration of 8-OH-DPAT (REPEAT TREATM) showed a significantly improved...

Influence of repeated permanent coloring and bleaching on ethyl glucuronide concentrations in hair from alcohol-dependent patients.

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Crunelle, Cleo L; Yegles, Michel; De Doncker, Mireille; Dom, Geert; Cappelle, Delphine; Maudens, Kristof E; van Nuijs, Alexander L N; Covaci, Adrian; Neels, Hugo

2015-02-01

Ethyl glucuronide (EtG), a minor metabolite of alcohol, is used as a sensitive marker in hair to detect the retrospective consumption of alcohol. The proximal 0-3 cm hair segment is often used for analysis, providing information on alcohol consumption over the past 3 months. Using more distal segments would allow the detection of alcohol consumption over longer time periods, thereby addressing the chronicity of the consumption. In view of this, permanent coloring and bleaching were shown in vitro to alter EtG concentrations in hair, but no in vivo studies are available to prove or disprove this. To investigate the influence of repeated bleaching and permanent coloring on EtG concentrations in vivo and to assess the stability of EtG concentrations in distal compared to proximal hair segments. Hair samples from alcohol-dependent patients with uncolored/unbleached (N=4), permanent coloration (N=5) and bleached hair (N=5) were analyzed in two to six 3 cm long segments for EtG concentrations, and alcohol consumption and hair cosmetic treatments were assessed. We observed that hair bleaching and permanent coloring reduces EtG concentrations by 82±11% and 65±24%, respectively, with correlations between the number of cosmetic treatments and the decrease in EtG concentrations. EtG remained stable in untreated hair samples up to 18 cm. EtG is a sensitive marker to assess chronic alcohol consumption up to 18 months in alcohol-dependent patients with no cosmetic hair treatments. However, in alcohol-dependent patients who color or bleach their hair, care should be taken when interpreting EtG measurements. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Driving simulator sickness: Impact on driving performance, influence of blood alcohol concentration, and effect of repeated simulator exposures.

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Helland, Arne; Lydersen, Stian; Lervåg, Lone-Eirin; Jenssen, Gunnar D; Mørland, Jørg; Slørdal, Lars

2016-09-01

Simulator sickness is a major obstacle to the use of driving simulators for research, training and driver assessment purposes. The purpose of the present study was to investigate the possible influence of simulator sickness on driving performance measures such as standard deviation of lateral position (SDLP), and the effect of alcohol or repeated simulator exposure on the degree of simulator sickness. Twenty healthy male volunteers underwent three simulated driving trials of 1h's duration with a curvy rural road scenario, and rated their degree of simulator sickness after each trial. Subjects drove sober and with blood alcohol concentrations (BAC) of approx. 0.5g/L and 0.9g/L in a randomized order. Simulator sickness score (SSS) did not influence the primary outcome measure SDLP. Higher SSS significantly predicted lower average speed and frequency of steering wheel reversals. These effects seemed to be mitigated by alcohol. Higher BAC significantly predicted lower SSS, suggesting that alcohol inebriation alleviates simulator sickness. The negative relation between the number of previous exposures to the simulator and SSS was not statistically significant, but is consistent with habituation to the sickness-inducing effects, as shown in other studies. Overall, the results suggest no influence of simulator sickness on SDLP or several other driving performance measures. However, simulator sickness seems to cause test subjects to drive more carefully, with lower average speed and fewer steering wheel reversals, hampering the interpretation of these outcomes as measures of driving impairment and safety. BAC and repeated simulator exposures may act as confounding variables by influencing the degree of simulator sickness in experimental studies. Copyright © 2016 Elsevier Ltd. All rights reserved.

Repeated MDMA administration increases MDMA-produced locomotor activity and facilitates the acquisition of MDMA self-administration: role of dopamine D2 receptor mechanisms.

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van de Wetering, Ross; Schenk, Susan

2017-04-01

Repeated exposure to ±3, 4-methylenedioxymethamphetamine (MDMA) produces sensitization to MDMA-produced hyperactivity, but the mechanisms underlying the development of this sensitized response or the relationship to the reinforcing effects of MDMA is unknown. This study determined the effect of a sensitizing regimen of MDMA exposure on the acquisition of MDMA self-administration and investigated the role of dopamine D 2 receptor mechanisms. Rats received the selective D 2 antagonist, eticlopride (0.0 or 0.3 mg/kg, i.p.) and MDMA (0.0 or 10.0 mg/kg, i.p.) during a five-day pretreatment regimen. Two days following the final session, the locomotor activating effects of MDMA (5 mg/kg, i.p.) and the latency to acquisition of MDMA self-administration were determined. Pretreatment with MDMA enhanced the locomotor activating effects of MDMA and facilitated the acquisition of MDMA self-administration. Administration of eticlopride during MDMA pretreatment completely blocked the development of sensitization to MDMA-produced hyperactivity but failed to significantly alter the facilitated acquisition of MDMA self-administration. Pretreatment with eticlopride alone facilitated the acquisition of self-administration. These data suggest that repeated MDMA exposure sensitized both the locomotor activating and reinforcing effects of MDMA. Activation of D 2 receptors during MDMA pretreatment appears critical for the development of sensitization to MDMA-produced hyperactivity. The role of D 2 receptor mechanisms in the development of sensitization to the reinforcing effects of MDMA is equivocal.

Improved recovery of repeat intoxicated drivers using fingernails and blood spots to monitor alcohol and other substance abuse.

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Bean, Pamela; Brown, Guida; Hallinan, Patricia; Becerra, Sergio; Lewis, Doug

2017-01-02

This study reports the results of a pilot program in Kenosha County that used a combination of direct biomarkers extracted from blood spots and nails to monitor repeat intoxicated drivers for their use of alcohol and drugs with a detection window spanning from 3 weeks to several months. The objectives were to test whether the direct biomarkers phosphatidylethanol (PEth), ethylglucuronide (EtG), and 5 drug metabolites would (1) help assessors obtain a more objective evaluation of repeat offenders during the assessment interview, (2) allow for timely identification of relapses and improve classification of drivers into risk categories, and (3) predict recidivism by identifying offenders most likely to obtain a subsequent operating while intoxicated (OWI) offense within 4 years of enrollment in the program. All (N = 261) repeat offenders were tested using PEth obtained from blood spots and EtG obtained from fingernails; 159 participants were also tested for a 5 drugs of abuse nail panel. Drivers were tested immediately after the assessment interview (baseline) and at 3, 6, 9, and 12 months after baseline. Based on biomarker results and self-reports of abstinence, offenders were classified into different risk categories and required to follow specific testing timelines based on the program's decision tree. The baseline analysis shows that 60% of drivers tested positive for alcohol biomarkers (EtG, PEth, or both) at the assessment interview, with lower detection rates (0-11%) for the 5 drug metabolites. The comparison of biomarkers results to self-reports of abstinence identified 28% of all offenders as high risk and assigned them to more frequent testing and more intense monitoring. The longitudinal analysis shows that 56% (completers) of participants completed the program successfully and the remaining 44% (noncompliant) terminated prematurely. Two thirds (68%) of the completers were able to reduce or control their drinking and one third relapsed at least one time

Repeated episodes of chronic intermittent ethanol promote insensitivity to devaluation of the reinforcing effect of ethanol.

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Lopez, M F; Becker, H C; Chandler, L J

2014-11-01

Studies in animal models have shown that repeated episodes of alcohol dependence and withdrawal promote escalation of drinking that is presumably associated with alterations in the addiction neurocircuitry. Using a lithium chloride-ethanol pairing procedure to devalue the reinforcing properties of ethanol, the present study determined whether multiple cycles of chronic intermittent ethanol (CIE) exposure by vapor inhalation also alters the sensitivity of drinking behavior to the devaluation of ethanol's reinforcing effects. The effect of devaluation on operant ethanol self-administration and extinction was examined in mice prior to initiation of CIE (short drinking history) and after repeated cycles of CIE or air control exposure (long drinking history). Devaluation significantly attenuated the recovery of baseline ethanol self-administration when tested either prior to CIE or in the air-exposed controls that had experienced repeated bouts of drinking but no CIE. In contrast, in mice that had undergone repeated cycles of CIE exposure that promoted escalation of ethanol drinking, self-administration was completely resistant to the effect of devaluation. Devaluation had no effect on the time course of extinction training in either pre-CIE or post-CIE mice. Taken together, these results are consistent with the suggestion that repeated cycles of ethanol dependence and withdrawal produce escalation of ethanol self-administration that is associated with a change in sensitivity to devaluation of the reinforcing properties of ethanol. Copyright © 2014 Elsevier Inc. All rights reserved.

COMPARATIVE METABOLISM OF ARSENIC IN MICE AFTER A SINGLE OR REPEATED ORAL ADMINISTRATION OF ARSENATE

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COMPARATIVE METABOLISM OF ARSENIC IN MICE AFTER A SINGLE OR REPEATED ORAL ADMINISTRATION OF ARSENATEMichael F. Hughes*1, Elaina M. Kenyon1, Brenda C. Edwards1, Carol T. Mitchell1, Luz Maria Del Razo2 and David J. Thomas11US EPA, ORD, NHEERL, ETD, PKB, Research Triangle Pa...

Short-term parenteral and peroral testosterone administration in men with alcoholic cirrhosis

DEFF Research Database (Denmark)

Gluud, C; Bennett, Patrick; Dietrichson, O

1981-01-01

other day, rather constant serum concentrations with median values of about 30 ng/ml were reached after 4 days. Peroral testosterone administration (800 mg micronized free testosterone) each day also resulted in fairly constant serum concentrations after 4 days, and the median values were about 50 ng......Serum concentrations of testosterone were measured in 24 male patients with alcoholic cirrhosis during testosterone administration. The purpose was to compare serum concentrations of testosterone during peroral with those during parenteral testosterone administration in these patients. Patients who...... were injected intramuscularly with a combination of short- and long-acting testosterone (Triolandren, 348 mg testosterone) had median peak values of serum testosterone of about 40 ng/ml, which fell to basal levels after a fortnight. During testosterone propionate injections (84 mg testosterone) every...

Repeated administration of amitriptyline reduces oxaliplatin-induced mechanical allodynia in rats.

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Sada, Hikaru; Egashira, Nobuaki; Ushio, Soichiro; Kawashiri, Takehiro; Shirahama, Masafumi; Oishi, Ryozo

2012-01-01

Oxaliplatin is a key drug in the treatment of colorectal cancer, but it causes acute and chronic neuropathies in patients. Amitriptyline has widely been used in patients with painful neuropathy. In this study, we investigated the effect of amitriptyline on the oxaliplatin-induced neuropathy in rats. Repeated administration of amitriptyline (5 and 10 mg/kg, p.o., once a day) reduced the oxaliplatin-induced mechanical allodynia but not cold hyperalgesia and reversed the oxaliplatin-induced increase in the expression of NR2B protein and mRNA in rat spinal cord. These results suggest that amitriptyline is useful for the treatment of oxaliplatin-induced neuropathy clinically.

Saccharin fading is not required for the acquisition of alcohol self-administration, and can alter the dynamics of cue-alcohol memory reconsolidation.

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Puaud, Mickaël; Ossowska, Zofia; Barnard, Jordan; Milton, Amy L

2018-04-01

Animal models of alcohol-seeking are useful for understanding alcohol addiction and for treatment development, but throughput in these models is limited by the extensive pretraining required to overcome the aversive taste of ethanol. Work by Augier et al. (Psychopharmacology 231: 4561-4568, 2014) indicates that Wistar rats will self-administer alcohol without water deprivation, exposure to sweetened ethanol solutions or intermittent access to ethanol. We sought to replicate and extend the work of Augier et al. by comparing the acquisition of instrumental self-administration of ethanol in Lister-Hooded rats that had been previously saccharin faded (SF group) or not (NSF group). We also aimed to determine whether NMDA receptor antagonism with MK-801, given at memory reactivation, reduced subsequent ethanol-seeking behaviour in both groups of animals. Finally, we assessed the ethanol preference of SF and NSF rats using the two-bottle choice procedure. Both SF and NSF groups acquired instrumental self-administration of ethanol, though SF rats consumed fewer of the earned reinforcers. MK-801, given at memory reactivation, had different effects on NSF and SF rats: impairing the capacity of an ethanol-paired conditioned stimulus (CS) to support reinstatement in NSF rats, and enhancing it in SF rats. Finally, neither SF nor NSF rats showed a preference for ethanol. Our data support those of Augier et al. (Psychopharmacology 231: 4561-4568, 2014) that pretraining is unnecessary for rats to acquire instrumental self-administration of ethanol. Indeed, saccharin fading may produce a weaker memory that extinguishes more readily, thus accounting for the different effects of MK-801 on SF and NSF rats.

The Rewarding and Locomotor-Sensitizing Effects of Repeated Cocaine Administration are Distinct and Separable in Mice

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Riday, Thorfinn T.; Kosofsky, Barry E.; Malanga, C.J.

2011-01-01

Repeated psychostimulant exposure progressively increases their potency to stimulate motor activity in rodents. This behavioral or locomotor sensitization is considered a model for some aspects of drug addiction in humans, particularly drug craving during abstinence. However, the role of increased motor behavior in drug reward remains incompletely understood. Intracranial self-stimulation (ICSS) was measured concurrently with locomotor activity to determine if acute intermittent cocaine administration had distinguishable effects on motor behavior and perception of brain stimulation-reward (BSR) in the same mice. Sensitization is associated with changes in neuronal activity and glutamatergic neurotransmission in brain reward circuitry. Expression of AMPA receptor subunits (GluR1 and GluR2) and CRE binding protein (CREB) was measured in the ventral tegmental area (VTA), dorsolateral striatum (STR) and nucleus accumbens (NAc) before and after a sensitizing regimen of cocaine, with and without ICSS. Repeated cocaine administration sensitized mice to its locomotor stimulating effects but not its ability to potentiate BSR. ICSS increased GluR1 in the VTA but not NAc or STR, demonstrating selective changes in protein expression with electrical stimulation of discrete brain structures. Repeated cocaine reduced GluR1, GluR2 and CREB expression in the NAc, and reductions of GluR1 and GluR2 but not CREB were further enhanced by ICSS. These data suggest that the effects of repeated cocaine exposure on reward and motor processes are dissociable in mice, and that reduction of excitatory neurotransmission in the NAc may predict altered motor function independently from changes in reward perception. PMID:22197517

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

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CSR, Inc., Washington, DC.

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

Comparative toxicokinetics of MMB4 DMS in rats, rabbits, dogs, and monkeys following single and repeated intramuscular administration.

Science.gov (United States)

Hong, S Peter; Gibbs, Seth T; Kobs, Dean J; Hawk, Michael A; Croutch, Claire R; Osheroff, Merrill R; Johnson, Jerry D; Burback, Brian L

2013-01-01

1,1'-Methylenebis[4-[(hydroxyimino)methyl]-pyridinium] (MMB4) dimethanesulfonate (DMS) is a bisquaternary pyridinium aldoxime that reactivates acetylcholinesterase inhibited by organophosphorus nerve agent. Time courses of MMB4 concentrations in plasma were characterized following 7-day repeated intramuscular (IM) administrations of MMB4 DMS to male and female Sprague-Dawley rats, New Zealand White rabbits, beagle dogs (single dose only), and rhesus monkeys at drug dose levels used in earlier toxicology studies. In general, there were no significant differences in MMB4 toxicokinetic (TK) parameters between males and females for all the species tested in these studies. After a single IM administration to rats, rabbits, dogs, and monkeys, MMB4 DMS was rapidly absorbed, resulting in average T max values ranging from 5 to 30 minutes. Although C max values did not increase dose proportionally, the overall exposure to MMB4 in these preclinical species, as indicated by area under the curve (AUC) extrapolated to the infinity (AUC∞) values, increased in an approximately dose-proportional manner. The MMB4 DMS was extensively absorbed into the systemic circulation after IM administration as demonstrated by greater than 80% absolute bioavailability values for rats, rabbits, and dogs. Repeated administrations of MMB4 DMS for 7 days did not overtly alter TK parameters for MMB4 in rats, rabbits, and monkeys (150 and 300 mg/kg/d dose groups only). However, C max and AUC values decreased in monkeys given 450 and 600 mg/kg IM doses of MMB4 DMS following repeated administrations for 7 days. Based on the TK results obtained from the current study and published investigations, it was found that the apparent volume of distribution and clearance values were similar among various preclinical species, except for the rat.

The effects of chronic alcohol self-administration in nonhuman primate brain networks.

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Telesford, Qawi K; Laurienti, Paul J; Davenport, April T; Friedman, David P; Kraft, Robert A; Daunais, James B

2015-04-01

Long-term alcohol abuse is associated with change in behavior, brain structure, and brain function. However, the nature of these changes is not well understood. In this study, we used network science to analyze a nonhuman primate model of ethanol self-administration to evaluate functional differences between animals with chronic alcohol use and animals with no exposure to alcohol. Of particular interest was how chronic alcohol exposure may affect the resting state network. Baseline resting state functional magnetic resonance imaging was acquired in a cohort of vervet monkeys. Animals underwent an induction period where they were exposed to an isocaloric maltose dextrin solution (control) or ethanol in escalating doses over three 30-day epochs. Following induction, animals were given ad libitum access to water and a maltose dextrin solution (control) or water and ethanol for 22 h/d over 12 months. Cross-sectional analyses examined region of interests in hubs and community structure across animals to determine differences between drinking and nondrinking animals after the 12-month free access period. Animals were classified as lighter (intake pattern during the 12-month ethanol free access period. Statistical analysis of hub connectivity showed significant differences in heavier drinkers for hubs in the precuneus, posterior parietal cortices, superior temporal gyrus, subgenual cingulate, and sensorimotor cortex. Heavier drinkers were also shown to have less consistent communities across the brain compared to lighter drinkers. The different level of consumption between the lighter and heavier drinking monkeys suggests that differences in connectivity may be intake dependent. Animals that consume alcohol show topological differences in brain network organization, particularly in animals that drink heavily. Differences in the resting state network were linked to areas that are associated with spatial association, working memory, and visuomotor processing. Copyright �

Suppressing effect of COR659 on alcohol, sucrose, and chocolate self-administration in rats: involvement of the GABAB and cannabinoid CB1 receptors.

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Maccioni, Paola; Colombo, Giancarlo; Lorrai, Irene; Zaru, Alessandro; Carai, Mauro A M; Gessa, Gian Luigi; Brizzi, Antonella; Mugnaini, Claudia; Corelli, Federico

2017-09-01

COR659 [methyl2-(4-chlorophenylcarboxamido)-4-ethyl-5-methylthiophene-3-carboxylate] is a new, positive allosteric modulator (PAM) of the GABA B receptor. This study evaluated whether COR659 shared with previously tested GABA B PAMs the capacity to reduce alcohol self-administration in rats. Treatment with non-sedative doses of COR659 (2.5, 5, and 10 mg/kg; i.p.) suppressed lever-responding for alcohol (15% v/v) in Sardinian alcohol-preferring (sP) rats under the fixed ratio (FR) 4 (FR4) and progressive ratio (PR) schedules of reinforcement; COR659 was more potent and effective than the reference GABA B PAM, GS39783. Treatment with COR659, but not GS39783, suppressed (a) lever-responding for a sucrose solution (1-3% w/v) in sP rats under the FR4 and PR schedules, (b) lever-responding for a chocolate solution [5% (w/v) Nesquik®] in Wistar rats under the FR10 and PR schedules, and (c) cue-induced reinstatement of chocolate seeking in Wistar rats. Treatment with COR659 was completely ineffective on lever-responding (FR10) for regular food pellets in food-deprived Wistar rats. Pretreatment with the GABA B receptor antagonist, SCH50911, partially blocked COR659-induced reduction of alcohol self-administration, being ineffective on reduction of chocolate self-administration. Pretreatment with the cannabinoid CB 1 receptor antagonist, AM4113, fully blocked COR659-induced reduction of chocolate self-administration, being ineffective on reduction of alcohol self-administration. COR659 might exert its behavioral effects via a composite mechanism: (i) positive allosteric modulation of the GABA B receptor, responsible for a large proportion of reduction of alcohol self-administration; (ii) an action at other receptor system(s), including the cannabinoid CB 1 receptor, through which COR659 affects seeking and consumption of highly palatable foods.

Mining the nucleus accumbens proteome for novel targets of alcohol self-administration in male C57BL/6J mice.

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Faccidomo, Sara; Swaim, Katarina S; Saunders, Briana L; Santanam, Taruni S; Taylor, Seth M; Kim, Michelle; Reid, Grant T; Eastman, Vallari R; Hodge, Clyde W

2018-03-03

There is a clear need for discovery of effective medications to treat behavioral pathologies associated with alcohol addiction, such as chronic drinking. The goal of this preclinical study was to assess effects of chronic alcohol drinking on the nucleus accumbens (NAcb) proteome to identify and validate novel targets for medications development. Two-dimensional difference in-gel electrophoresis (2D-DIGE) with matrix-assisted laser desorption ionization tandem time-of-flight (MALDI-TOF/TOF) was used to assess effects of chronic voluntary home-cage (24-h access) alcohol drinking on the NAcb proteome of C57BL/6J mice. To extend these findings to a model of alcohol self-administration and reinforcement, we investigated potential regulation of the positive reinforcing effects of alcohol by the target protein glutathione S-transferase Pi 1 (GSTP1) using a pharmacological inhibition strategy in mice trained to self-administer alcohol or sucrose. Expression of 52 unique proteins in the NAcb was changed by chronic alcohol drinking relative to water control (23 upregulated, 29 downregulated). Ingenuity Pathway Analysis showed that alcohol drinking altered an array of protein networks associated with neurological and psychological disorders, molecular and cellular functions, and physiological systems and development. DAVID functional annotation analysis identified 9 proteins (SNCA, GSTP1, PRDX3, PPP3R1, EIF5A, PHB, PEBP1/RKIP, GAPDH, AND SOD1) that were significantly overrepresented in a functional cluster that included the Gene Ontology categories "response to alcohol" and "aging." Immunoblots confirmed changes in Pebp1 (RKIP) and GSTP1 in NAcb with no change in amygdala or frontal cortex, suggesting anatomical specificity. Systemic inhibition of GSTP1 with Ezatiostat (0-30 mg/kg, i.p.) dose-dependently reduced the reinforcing effects of alcohol as measured by operant self-administration, in the absence of motor effects. Sucrose self-administration was also reduced but in a

Disruption of long-term alcohol-related memory reconsolidation: Role of β-adrenoceptors and NMDA receptors

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Jelte A Wouda

2010-11-01

Full Text Available Disrupting reconsolidation of drug-related memories may be effective in reducing the incidence of relapse. In the current study we examine whether alcohol- related memories are prone to disruption by the β -adrenergicreceptor antagonist propranolol (10 mg/kg and the NMDA receptor antagonist MK801 (0.1 mg/kg following their reactivation. In operant chambers, male Wistar rats were trained to self-administer a 12% alcohol solution. After 3 weeks of abstinence, the animals were placed in the self-administration cages and were reexposed to the alcohol-associated cues for a 20-min retrieval period, immediately followed by a systemic injection of either propranolol, MK801 or saline. Rats were tested for cue-induced alcohol seeking on the following day. Retrieval session, injection and test were repeated on 2 further occasions at weekly intervals. Both propranolol and MK801 administration upon reactivation did not reduce alcohol seeking after the first reactivation test. However, a significant reduction of alcohol seeking was observed over three post-training tests in propranolol treated animals, and MK801 treated animals showed a strong tendency towards reduced alcohol seeking (p=0.06. Our data indicate that reconsolidation of alcohol-related memories can be disrupted after a long post-training interval and that particularly β-adrenergic receptors may represent novel targets for pharmacotherapy of alcoholism, in combination with cue-exposure therapies.

Administration of memantine during withdrawal mitigates overactivity and spatial learning impairments associated with neonatal alcohol exposure in rats.

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Idrus, Nirelia M; McGough, Nancy N H; Riley, Edward P; Thomas, Jennifer D

2014-02-01

Prenatal alcohol exposure can disrupt central nervous system development, manifesting as behavioral deficits that include motor, emotional, and cognitive dysfunction. Both clinical and animal studies have reported binge drinking during development to be highly correlated with an increased risk of fetal alcohol spectrum disorders (FASD). We hypothesized that binge drinking may be especially damaging because it is associated with episodes of alcohol withdrawal. Specifically, we have been investigating the possibility that NMDA receptor-mediated excitotoxicity occurs during alcohol withdrawal and contributes to developmental alcohol-related neuropathology. Consistent with this hypothesis, administration of the NMDA receptor antagonists MK-801 or eliprodil during withdrawal attenuates behavioral alterations associated with early alcohol exposure. In this study, we investigated the effects of memantine, a clinically used NMDA receptor antagonist, on minimizing ethanol-induced overactivity and spatial learning deficits. Sprague-Dawley pups were exposed to 6.0 g/kg ethanol via intubation on postnatal day (PD) 6, a period of brain development that models late gestation in humans. Controls were intubated with a calorically matched maltose solution. During withdrawal, 24 and 36 hours after ethanol exposure, subjects were injected with a total of either 0, 20, or 30 mg/kg memantine. The subjects' locomotor levels were recorded in open field activity monitors on PDs 18 to 21 and on a serial spatial discrimination reversal learning task on PDs 40 to 43. Alcohol exposure induced overactivity and impaired performance in spatial learning. Memantine administration significantly attenuated the ethanol-associated behavioral alterations in a dose-dependent manner. Thus, memantine may be neuroprotective when administered during ethanol withdrawal. These data have important implications for the treatment of EtOH's neurotoxic effects and provide further support that ethanol withdrawal

Drunk bugs: Chronic vapour alcohol exposure induces marked changes in the gut microbiome in mice.

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Peterson, Veronica L; Jury, Nicholas J; Cabrera-Rubio, Raúl; Draper, Lorraine A; Crispie, Fiona; Cotter, Paul D; Dinan, Timothy G; Holmes, Andrew; Cryan, John F

2017-04-14

The gut microbiota includes a community of bacteria that play an integral part in host health and biological processes. Pronounced and repeated findings have linked gut microbiome to stress, anxiety, and depression. Currently, however, there remains only a limited set of studies focusing on microbiota change in substance abuse, including alcohol use disorder. To date, no studies have investigated the impact of vapour alcohol administration on the gut microbiome. For research on gut microbiota and addiction to proceed, an understanding of how route of drug administration affects gut microbiota must first be established. Animal models of alcohol abuse have proven valuable for elucidating the biological processes involved in addiction and alcohol-related diseases. This is the first study to investigate the effect of vapour route of ethanol administration on gut microbiota in mice. Adult male C57BL/6J mice were exposed to 4 weeks of chronic intermittent vapourized ethanol (CIE, N=10) or air (Control, N=9). Faecal samples were collected at the end of exposure followed by 16S sequencing and bioinformatic analysis. Robust separation between CIE and Control was seen in the microbiome, as assessed by alpha (pgut microbiota in mice. Significant increases in genus Alistipes (pgut-brain axis and align with previous research showing similar microbiota alterations in inflammatory states during alcoholic hepatitis and psychological stress. Copyright © 2017 Elsevier B.V. All rights reserved.

Comparative Pharmacokinetics of Cefquinome (Cobactan 2.5% following Repeated Intramuscular Administrations in Sheep and Goats

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Mohamed El-Hewaity

2014-01-01

Full Text Available The comparative pharmacokinetic profile of cefquinome was studied in sheep and goats following repeated intramuscular (IM administrations of 2 mg/kg body weight. Cefquinome concentrations in serum were determined by microbiological assay technique using Micrococcus luteus (ATCC 9341 as test organism. Following intramuscular injection of cefquinome in sheep and goats, the disposition curves were best described by two-compartment open model in both sheep and goats. The pharmacokinetics of cefquinome did not differ significantly between sheep and goats; similar intramuscular dose rate of cefquinome should therefore be applicable to both species. On comparing the data of serum levels of repeated intramuscular injections with first intramuscular injection, it was revealed that repeated intramuscular injections of cefquinome have cumulative effect in both species sheep and goats. The in vitro serum protein-binding tendency was 15.65% in sheep and 14.42% in goats. The serum concentrations of cefquinome along 24 h after injection in this study were exceeding the MICs of different susceptible microorganisms responsible for serious disease problems. These findings indicate successful use of cefquinome in sheep and goats.

Differences in the subjective and motivational properties of alcohol across alcohol use severity: application of a novel translational human laboratory paradigm.

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Bujarski, Spencer; Jentsch, J David; Roche, Daniel J O; Ramchandani, Vijay A; Miotto, Karen; Ray, Lara A

2018-05-08

The Allostatic Model proposes that Alcohol Use Disorder (AUD) is associated with a transition in the motivational structure of alcohol drinking: from positive reinforcement in early-stage drinking to negative reinforcement in late-stage dependence. However, direct empirical support for this preclinical model from human experiments is limited. This study tests predictions derived from the Allostatic Model in humans. Specifically, this study tested whether alcohol use severity (1) independently predicts subjective responses to alcohol (SR; comprised of stimulation/hedonia, negative affect, sedation and craving domains), and alcohol self-administration and 2) moderates associations between domains of SR and alcohol self-administration. Heavy drinking participants ranging in severity of alcohol use and problems (N = 67) completed an intravenous alcohol administration paradigm combining an alcohol challenge (target BrAC = 60 mg%), with progressive ratio self-administration. Alcohol use severity was associated with greater baseline negative affect, sedation, and craving but did not predict changes in any SR domain during the alcohol challenge. Alcohol use severity also predicted greater self-administration. Craving during the alcohol challenge strongly predicted self-administration and sedation predicted lower self-administration. Neither stimulation, nor negative affect predicted self-administration. This study represents a novel approach to translating preclinical neuroscientific theories to the human laboratory. As expected, craving predicted self-administration and sedation was protective. Contrary to the predictions of the Allostatic Model, however, these results were inconsistent with a transition from positively to negatively reinforced alcohol consumption in severe AUD. Future studies that assess negative reinforcement in the context of an acute stressor are warranted.

Pharmacokinetic evaluation of pamidronate after oral administration: a study on dose proportionality, absolute bioavailability, and effect of repeated administration

DEFF Research Database (Denmark)

Hyldstrup, Lars; Flesch, G; Hauffe, S A

1993-01-01

30 minutes at constant infusion rate. Repeated peroral doses (75 and 150 mg) were administered to 12 females (aged 51-70 years) for 10 consecutive days. Urinary excretion of pamidronate after peroral and i.v. administration was used for estimation of pamidronate absorption. Renal excretion...... of pamidronate ranged from 0.01% to 0.35% of dose, with mean values of 0.11, 0.16, and 0.18% for 75, 150, and 300 mg, respectively. After i.v. infusion, the renal excretion of pamidronate was 26-53% of the dose, lower than for other bisphosphonates. The absolute bioavailability was 0.31% (range 0.08-0.7%) after...

The effect of chronic alcohol administration on bone mineral content and bone strength in male rats.

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Broulík, P D; Vondrová, J; Růzicka, P; Sedlácek, R; Zíma, T

2010-01-01

Alcohol use has been identified as a risk factor for the development of osteoporosis. Eight male Wistar rats at two months of age were alcoho-fed (7.6 g 95 % ethanol/kg b.w. per day) to evaluate the effects of long-term administration (three months) of alcohol in drinking water. We have used a dose which is considered to be comparable to a dose of 1 liter of wine or 2.5 liters of 12(°) beer used in male adults daily. The bones were tested mechanically by a three-point bending test in a Mini Bionix (MTS) testing system. The bones from alcohol-fed rats were characterized by a reduction in bone density as well as in ash, calcium and phosphate content. In alcohol-fed rats the reduction in bone mineral density (10 %) was reflected by about 12 % reduction of mechanical strength of femur (158+/-5.5 vs. 178+/-3.2 N/mm(2)). Alcohol significantly altered femoral cortical thickness. In our experiment alcohol itself did not exert any antiandrogenic effect and it did not produce changes in the weight of seminal vesicles. Liver function test (GGT, ALP, AST) did not differ between alcohol-fed rats and control rats. Alcohol-induced bone loss is associated with increased bone resorption and decreased bone formation. These results document the efficacy of alcohol at the dose of 7.6 g 95 % ethanol/kg b.w. to cause bone loss and loss of bone mechanical strength in intact rats. The results of the present study may be interpreted as supporting the hypothesis of alcohol as a risk factor for osteoporosis.

Changes in the α4β2* nicotinic acetylcholine system during chronic controlled alcohol exposure in nonhuman primates.

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Hillmer, Ansel T; Tudorascu, Dana L; Wooten, Dustin W; Lao, Patrick J; Barnhart, Todd E; Ahlers, Elizabeth O; Resch, Leslie M; Larson, Julie A; Converse, Alexander K; Moore, Colleen F; Schneider, Mary L; Christian, Bradley T

2014-05-01

The precise nature of modifications to the nicotinic acetylcholine receptor (nAChR) system in response to chronic ethanol exposure is poorly understood. The present work used PET imaging to assay α4β2* nAChR binding levels of eight rhesus monkeys before and during controlled chronic ethanol intake. [(18)F]Nifene PET scans were conducted prior to alcohol exposure, and then again after at least 8 months controlled ethanol exposure, including 6 months at 1.5 g/kg/day following a dose escalation period. Receptor binding levels were quantified with binding potentials (BPND) using the cerebellum as a reference region. Alcohol self-administration was assessed as average daily alcohol intake during a 2 month free drinking period immediately following controlled alcohol. Significant decreases in α4β2* nAChR binding were observed in both frontal and insular cortex in response to chronic ethanol exposure. During chronic alcohol exposure, BPND in the lateral geniculate region correlated positively with the amount of alcohol consumed during free drinking. The observed decreases in nAChR availability following chronic alcohol consumption suggest alterations to this receptor system in response to repeated alcohol administration, making this an important target for further study in alcohol abuse and alcohol and nicotine codependence. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Water metabolism in rats subjected to chronic alcohol administration

DEFF Research Database (Denmark)

Parlesak, Alexandr; Pohl, C.; Bode, J.C.

2004-01-01

AIM: While the diuretic action of acute ingestion of alcohol has been studied extensively, the effect of chronic alcohol consumption has received less attention. The aim of the present study was to investigate the effect of chronic alcohol consumption on the balance of water intake and excretion ...... the body as hidden water loss increases after alcohol consumption by up to 25-26% over control values.......AIM: While the diuretic action of acute ingestion of alcohol has been studied extensively, the effect of chronic alcohol consumption has received less attention. The aim of the present study was to investigate the effect of chronic alcohol consumption on the balance of water intake and excretion...... and certain renal functions in rats during a period of 12 months. ANIMALS AND STUDY DESIGN: Male Wistar rats received either alcohol (15% v/v; group A, n = 65) or tap water (group C, n = 35) as drinking fluid. Urine and faeces were collected from 6 rats of each group during 7 days, at monthly intervals...

The Effect of Subchronic Administration of the Aqueous and Hydro-alcoholic Extracts of Crocus sativus from Estahbanat, Fars Province, on Mice

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M Emamghoreishi

2012-02-01

Full Text Available Background & aim: In Iranian traditional medicine, Crocus sativus L. has been defined as an exultant plant. The present study was undertaken to determine the effect of subchronic administration of aqueous and hydro-alcoholic extracts of Crocus sativus on mice. Methods: The effect of subchronic i.p. administration of different doses of the aqueous extract (50, 100, 200, 400 mg/kg or water and the hydro-alcoholic extract (100, 200, 400, 800 mg/kg or water of Crocus sativus stigma on immobility, climbing, and swimming behaviors were evaluated in the forced swimming test in mice. Fluoxetine (20 mg/kg and imipramine (15 mg/kg were used as reference drugs. Additionally, the effect of both plant preparations on spontaneous activity was examined. The collected data was analyzed using One-way ANOVA. Results: The aqueous extract at doses of 50 and 100 mg/kg produced a significant reduction in immobility along with an increase in climbing behavior which is similar to those which have been observed with imipramine. The hydro-alcoholic extract did not show significant effects on immobility, climbing and swimming behaviors of all studied doses, compared to control group. The aqueous extract of all studied doses and the hydro-alcoholic extract at dose of 1600 mg/kg decreased spontaneous activity. Conclusion: The results of this study suggests that the aqueous, but not hydro-alcoholic, extract of Crocus sativus stigma from Estahbanat in Fars province, in subchronic administration possess an antidepressant-like activity which may be mediated through norepinephrine system.

Repeated attempted homicide by administration of drugs documented by hair analysis.

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Baillif-Couniou, Valérie; Bartoli, Christophe; Sastre, Caroline; Chèze, Marjorie; Deveaux, Marc; Léonetti, Georges; Pélissier-Alicot, Anne-Laure

2018-02-01

Attempted murder by repeated poisoning is quite rare. The authors describe the case of a 62-year-old man who was admitted to an intensive care unit (ICU) for neurological disturbances complicated by inhalation pneumopathy. He presented a loss of consciousness while his wife was visiting him at the ICU (H0). Forty-eight hours later (H48), police officers apprehended the patient's wife pouring a liquid into his fruit salad at the hospital. Toxicological analyses of a blood sample and the infusion equipment (H0), as well as the fruit salad and its container (H48), confirmed the attempted poisoning with cyamemazine (H0) and hydrochloric acid (H48). In order to evaluate the anteriority of poisonings, hair analysis was requested and the medical records of the 6 previous months were also examined. Two 6-cm brown hair strands were sampled and the victim's medical record was seized in order to determine the treatments he had been given during the previous six months. Segmental hair testing on two 6-cm brown hair was conducted by GC-MS, LC-DAD and LC-MS/MS (0-2/2-4/4-6 cm; pg/mg). Haloperidol (9200/1391/227), amitriptyline (7450/1850/3260), venlafaxine (332/560/260), that had never been part of the victim's treatment were detected, as well as some benzodiazepines (alprazolam, bromazepam, nordazepam); cyamemazine was also detected in all the segments (9960/1610/2367) though only a single dose administration was reported in the medical records. The toxicological analyses performed at H0 and H48 confirmed the homicide attempts in the ICU. In addition, comparison of the results in hair analysis with the medical records confirmed repeated poisoning attempts over the previous six months, and thus explain the origin of the disorders presented by the victim. This case serves to remind us that repeated attempted murder can be difficult to diagnose and that hair analysis can be an effective way to detect such attempts. Copyright © 2018. Published by Elsevier Ltd.

Inhibitory effects of ginseng total saponin on up-regulation of cAMP pathway induced by repeated administration of morphine.

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Seo, Jeong-Ju; Lee, Jae-Woong; Lee, Wan-Kyu; Hong, Jin-Tae; Lee, Chong-Kil; Lee, Myung-Koo; Oh, Ki-Wan

2008-02-01

We have reported that ginseng total saponin (GTS) inhibited the development of physical and psychological dependence on morphine. However, the possible molecular mechanisms of GTS are unclear. Therefore, this study was undertaken to understand the possible molecular mechanism of GTS on the inhibitory effects of morphine-induced dependence. It has been reported that the up-regulated cAMP pathway in the LC of the mouse brain after repeated administration of morphine contributes to the feature of withdrawals. GTS inhibited up-regulation of cAMP pathway in the LC after repeated administration of morphine in this experiment. GTS inhibited cAMP levels and protein expression of protein kinase A (PKA). In addition, GTS inhibited the increase of cAMP response element binding protein (CREB) phosphorylation. Therefore, we conclude that the inhibitory effects of GTS on morphine-induced dependence might be mediated by the inhibition of cAMP pathway.

Associations of repeated high alcohol use with unsafe driving behaviors, traffic offenses, and traffic crashes among young drivers: Findings from the New Zealand Drivers Study.

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Begg, Dorothy; Brookland, Rebecca; Connor, Jennie

2017-02-17

The objective of this study was to describe self-reported high alcohol use at each of the 3 licensing stages of graduated driver licensing and its relationship to drink-driving behaviors, intentional risky driving, aggressive driving, alcohol traffic offenses, non-alcohol traffic offenses, and traffic crashes. The New Zealand Drivers Study (NZDS) is a multistage, prospective cohort study of newly licensed drivers interviewed at all 3 stages of the graduated driver licensing system: learner (baseline), restricted (intermediate), and full license. At each stage, alcohol use was self-reported using the Alcohol Use Disorders Identification Test (AUDIT-C), with high alcohol use defined as a score of ≥4 for males and ≥3 for females. Sociodemographic and personality data were obtained at the baseline interview. Alcohol-related, intentional risky, and aggressive driving behaviors were self-reported following each license stage. Traffic crashes and offenses were identified from police records. Crashes were also self-reported. Twenty-six percent (n = 397) reported no high alcohol use, 22% at one license stage, 30% at 2 stages, and 22% at 3 stages. Poisson regression results (unadjusted and adjusted) showed that the number of stages where high alcohol use was reported was significantly associated with each of the outcomes. For most outcomes, and especially the alcohol-involved outcomes, the relative risk increased with the number of stages of high alcohol use. We found that high alcohol use was common among young newly licensed drivers and those who repeatedly reported high alcohol use were at a significantly higher risk of unsafe driving behaviors. Recently introduced zero blood alcohol concentration (BAC) should help to address this problem, but other strategies are required to target persistent offenders.

Repeated Administration of D-Amphetamine Induces Distinct Alterations in Behavior and Metabolite Levels in 129Sv and Bl6 Mouse Strains

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Taavi Vanaveski

2018-06-01

Full Text Available The main goal of the study was to characterize the behavioral and metabolomic profiles of repeated administration (for 11 days of d-amphetamine (AMPH, 3 mg/kg i. p., indirect agonist of dopamine (DA, in widely used 129S6/SvEvTac (129Sv and C57BL/6NTac (Bl6 mouse strains. Acute administration of AMPH (acute AMPH induced significantly stronger motor stimulation in Bl6. However, repeated administration of AMPH (repeated AMPH caused stronger motor sensitization in 129Sv compared acute AMPH. Body weight of 129Sv was reduced after repeated saline and AMPH, whereas no change occurred in Bl6. In the metabolomic study, acute AMPH induced an elevation of isoleucine and leucine, branched chain amino acids (BCAA, whereas the level of hexoses was reduced in Bl6. Both BCAAs and hexoses remained on level of acute AMPH after repeated AMPH in Bl6. Three biogenic amines [asymmetric dimethylarginine (ADMA, alpha-aminoadipic acid (alpha-AAA, kynurenine] were significantly reduced after repeated AMPH. Acute AMPH caused in 129Sv a significant reduction of valine, lysophosphatidylcholines (lysoPC a C16:0, lysoPC a C18:2, lysoPC a C20:4, phosphatidylcholine (PC diacyls (PC aa C34:2, PC aa C36:2, PC aa C36:3, PC aa C36:4 and alkyl-acyls (PC ae C38:4, PC ae C40:4. However, repeated AMPH increased the levels of valine and isoleucine, long-chain acylcarnitines (C14, C14:1-OH, C16, C18:1, PC diacyls (PC aa C38:4, PC aa C38:6, PC aa C42:6, PC acyl-alkyls (PC ae C38:4, PC ae C40:4, PC ae C40:5, PC ae C40:6, PC ae C42:1, PC ae C42:3 and sphingolipids [SM(OHC22:1, SM C24:0] compared to acute AMPH in 129Sv. Hexoses and kynurenine were reduced after repeated AMPH compared to saline in 129Sv. The established changes probably reflect a shift in energy metabolism toward lipid molecules in 129Sv because of reduced level of hexoses. Pooled data from both strains showed that the elevation of isoleucine and leucine was a prominent biomarker of AMPH-induced behavioral sensitization

Strain-dependent sex differences in the effects of alcohol on cocaine-induced taste aversions.

Science.gov (United States)

Jones, Jermaine D; Busse, Gregory D; Riley, Anthony L

2006-04-01

Research using the conditioned taste aversion procedure has reported that a cocaine/alcohol combination induces a significantly stronger taste aversion than either cocaine or alcohol alone. These findings suggest that the co-administration of alcohol intensifies the aversive effects of cocaine. Although the behavioral interaction of cocaine and alcohol is well established, little is known about how the effects of this drug combination might be modulated by a variety of subject variables. The current investigation addressed this by assessing if the ability of alcohol to potentiate cocaine-induced taste aversions is dependent upon the strain and/or sex of the subject. In this series of studies, male and female rats of Long-Evans (Experiment 1) and Sprague-Dawley (Experiment 2) descent were given limited access to a novel saccharin solution to drink and were then injected with either vehicle, cocaine (20 mg/kg), alcohol (0.56 g/kg) or the alcohol/cocaine combination. This procedure was repeated every fourth day for a total of four conditioning trials. All subjects were then compared on an Aversion Test that followed the fourth conditioning cycle. In three of the groups tested (male Long-Evans; male and female Sprague-Dawley), cocaine induced a significant taste aversion that was unaffected by the co-administration of alcohol. However, in female Long-Evans subjects, the addition of alcohol significantly strengthened the avoidance of the saccharin solution. Although the effects of alcohol on cocaine-induced taste aversions are dependent upon an interaction of sex and strain, the basis for this SexxStrain interaction is not known. That such an interaction is evident suggests that attention to such factors in assessing the effects of drug combinations is important to understanding the likelihood of the use and abuse of such drugs.

Relationship between tonic and phasic craving for alcohol

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Emily E. Hartwell

2018-06-01

Full Text Available Background: Multiple measures are utilized to assess alcohol craving, often interchangeably. Little is known about the relationship between tonic and phasic craving. This study fills this gap in the literature by examining the association between tonic levels of alcohol craving and phasic craving for alcohol that is provoked by alcohol administration. Methods: Forty-three non-treatment seeking problem drinkers underwent an initial interview and two laboratory testing sessions, where either alcohol or a saline placebo was administered intravenously. Tonic craving was assessed via the Penn Alcohol Craving Scale (PACS and Obsessive Compulsive Drinking Scale (OCDS at the initial interview. Phasic craving was assessed during the laboratory sessions (i.e., alcohol and saline administrations, single blinded at baseline and at 3 subsequent breath alcohol concentrations (0.02, 0.04, and 0.06 g/dl. Results: There was a main effect of PACS in predicting phasic craving across both saline and alcohol administration conditions (p  0.10, predicted phasic craving during alcohol, as compared to saline administration. Conclusion: In sum, tonic craving captured by the OCDS was predictive of phasic craving during alcohol administration whereas the PACS more generally captured the increase in phasic craving. Therefore, these measures of tonic craving may function differently in capturing the experience of phasic craving. Implications for the utilization of the PACS and OCDS as well as assessments of craving in alcoholism research are discussed. Keywords: Alcohol, Craving, Assessment

Pharmacokinetics of repeated sodium salicylate administration to laying hens: evidence for time dependent increase in drug elimination from plasma and eggs.

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Błażej Poźniak

Full Text Available Salicylates were the first non-steroid anti-inflammatory drugs (NSAIDs to be used in any species and are still widely used in humans and livestock. However, the data on their pharmacokinetics in animals is limited, especially after repeated administration. Evidence exist that in chickens (Gallus gallus salicylate (SA may induce its own elimination. The aim of this study was to investigate salicylate pharmacokinetics and egg residues during repeated administration of sodium salicylate (SS to laying hens. Pharmacokinetics of SA was assessed during 14 d oral administration of SS at daily doses of 50 mg/kg and 200 mg/kg body weight to laying hens. On the 1st, 7th and 14th d a 24 h-long pharmacokinetic study was carried out, whereas eggs were collected daily. Salicylate concentrations in plasma and eggs were determined using high-performance liquid chromatography with ultraviolet detection and pharmacokinetic variables were calculated using a non-compartmental model. Mean residence time (MRT, minimal plasma concentration (Cmin, C16h and elimination half-life (T1/2el of SA showed gradual decrease in layers administered with a lower dose. Total body clearance (ClB increased. Layers administered with the higher dose showed a decrease only in the T1/2el. In the low dose group, SA was found only in the egg white and was low throughout the experiment. Egg whites from the higher dose group showed initially high SA levels which significantly decreased during the experiment. Yolk SA levels were lower and showed longer periods of accumulation and elimination. Repeated administration of SS induces SA elimination, although this effect may differ depending on the dose and production type of a chicken. Decreased plasma drug concentration may have clinical implications during prolonged SS treatment.

Administration of the metabotropic glutamate receptor subtype 5 allosteric modulator GET 73 with alcohol: A translational study in rats and humans.

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Haass-Koffler, Carolina L; Goodyear, Kimberly; Loche, Antonella; Long, Victoria M; Lobina, Carla; Tran, Harrison H; Cacciaglia, Roberto; Swift, Robert M; Colombo, Giancarlo; Leggio, Lorenzo

2018-02-01

Preclinical work suggests that GET 73 (N-[4-(trifluoromethyl)benzyl]-4-methoxybutyramide), a novel metabotropic glutamate receptor subtype 5 negative allosteric modulator, may represent a novel pharmacological treatment for alcohol use disorder. Two independent experiments evaluated the effect of acutely administered GET 73 (0, 30, and 100 mg/kg, intragastrically) on alcohol-induced hypolocomotion ( n=72) and sedation/hypnosis ( n=36) in rats. In healthy male volunteers ( n=14), an open-label, randomised, crossover study was conducted to compare adverse events and pharmacokinetic parameters, in two experiments in which 300 mg GET 73 was administered, with and without alcohol, once and thrice. In rats, when administered with alcohol-vehicle, 100 mg/kg, but not 30 mg/kg, GET 73 reduced spontaneous locomotor activity. When administered with alcohol, no dose of GET 73 altered either alcohol-induced hypolocomotion or sedation/hypnosis. In humans, both single and thrice 300 mg GET 73 administration were well tolerated, in the presence and absence of alcohol, with no differences in adverse events. There were no significant differences in relative bioavailability between administering 300 mg GET 73 in the presence or absence of alcohol.

Gadolinium deposition within the dentate nucleus and globus pallidus after repeated administrations of gadolinium-based contrast agents - current status

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Stojanov, Dragan [University of Nis, Faculty of Medicine, Nis (Serbia); Center for Radiology, Nis (Serbia); Aracki-Trenkic, Aleksandra [Center for Radiology, Nis (Serbia); Benedeto-Stojanov, Daniela [University of Nis, Faculty of Medicine, Nis (Serbia)

2016-05-15

Gadolinium-based contrast agents (GBCAs) have been used clinically since 1988 for contrast-enhanced magnetic resonance imaging (CE-MRI). Generally, GBCAs are considered to have an excellent safety profile. However, GBCA administration has been associated with increased occurrence of nephrogenic systemic fibrosis (NSF) in patients with severely compromised renal function, and several studies have shown evidence of gadolinium deposition in specific brain structures, the globus pallidus and dentate nucleus, in patients with normal renal function. Gadolinium deposition in the brain following repeated CE-MRI scans has been demonstrated in patients using T1-weighted unenhanced MRI and inductively coupled plasma mass spectroscopy. Additionally, rodent studies with controlled GBCA administration also resulted in neural gadolinium deposits. Repeated GBCA use is associated with gadolinium deposition in the brain. This is especially true with the use of less-stable, linear GBCAs. In spite of increasing evidence of gadolinium deposits in the brains of patients after multiple GBCA administrations, the clinical significance of these deposits continues to be unclear. Here, we discuss the current state of scientific evidence surrounding gadolinium deposition in the brain following GBCA use, and the potential clinical significance of gadolinium deposition. There is considerable need for further research, both to understand the mechanism by which gadolinium deposition in the brain occurs and how it affects the patients in which it occurs. (orig.)

21 CFR 177.1670 - Polyvinyl alcohol film.

Science.gov (United States)

2010-04-01

... 21 Food and Drugs 3 2010-04-01 2009-04-01 true Polyvinyl alcohol film. 177.1670 Section 177.1670... Components of Single and Repeated Use Food Contact Surfaces § 177.1670 Polyvinyl alcohol film. Polyvinyl alcohol film may be safely used in contact with food of the types identified in § 176.170(c) of this...

Treatment of Alcohol Use Disorder in Patients with Alcoholic Liver Disease

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Leggio, Lorenzo; Lee, Mary R.

2016-01-01

Alcohol is a leading cause of liver disease worldwide. Although alcohol abstinence is the crucial therapeutic goal for patients with alcoholic liver disease, these patients have less access to psychosocial, behavioral and/or pharmacological treatments for alcohol use disorder. Psychosocial and behavioral therapies include 12-step facilitation, brief interventions, cognitive behavioral therapy, and motivational enhancement therapy. In addition to medications approved by the Food and Drug Administration (FDA) for alcohol use disorder (disulfiram, naltrexone and acamprosate), recent efforts to identify potential new treatments have yielded promising candidate pharmacotherapies. Finally, more efforts are needed to integrate treatments across disciplines toward patient-centered approaches in the management of patients with alcohol use disorder and alcoholic liver disease. PMID:27984008

Assessment of Alcohol Use Disorders among Court-Mandated DWI Offenders

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Stasiewicz, Paul R.; Nochajski, Thomas H.; Homish, D. Lynn

2007-01-01

Convicted DWI offenders (N = 549) were assessed for alcohol use disorders. Repeat offenders had twice the rate of both lifetime and current alcohol use disorders compared with 1st-time offenders. Guidelines for determining alcohol problems in DWI offenders are recommended.

Effects of exercise conditioning on thermoregulatory responses to repeated administration of chlorpyrifos

International Nuclear Information System (INIS)

Rowsey, Pamela Johnson; Metzger, Bonnie L.; Arlson, John; Gordon, Christopher J.

2003-01-01

little is known about the effects of physical activity (i.e., exercise training) on susceptibility to environmental toxicants. Chloropyrifos (CHP), an organophosphate (OP) insecticide, affects thermoregulation, causing a cute period of hypothermia followed by a delayed fever. Since exercise conditioning alters the thermo regulatory responses of rodents, this study examined whether exercise training would alter the thermo regulatory response to repeated CHP administration in the female Sprague-Dawley rat. Core temperature (T c ) and motor activity (MA) were monitored by radio telemetry in rats housed at an ambient temperature (T a ) of 22 deg. C. The rats either were provided with continuous access to running wheels (exercise group) or were housed in standard cages without wheels (sedentary group). The exercise group rats ran predominately at night with an average of 7.6 km/24 h. After 8 weeks the rats in both groups were garaged daily with corn oil or 10 mg/kg HP (dissolved in corn oil) for 4 days. CHP induced an immediate hypothermic response followed by a delayed fever throughout the next day in the sedentary group rats after the first three doses of CHP. The exercise group rats showed no hypothermia after the first dose of CHP. However, they became hypothermic after the second and third doses of CHP. The exercise group rats developed a smaller daytime fever after each dose of CHP compared to the sedentary group rats. Overall, exercise training attenuated the hypothermic and febrile effects of repeated CHP. Thus, the data suggest that a sedentary lifestyle may increase the sensitivity to OP insecticides. Exercise training was also associated with a more rapid recovery of plasma cholinesterase activity

Is Forced Swimming Immobility a Good Endpoint for Modeling Negative Symptoms of Schizophrenia? - Study of Sub-Anesthetic Ketamine Repeated Administration Effects

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GILDA NEVES

2017-08-01

Full Text Available ABSTRACT Immobility time in the forced swimming has been described as analogous to emotional blunting or apathy and has been used for characterizing schizophrenia animal models. Several clinical studies support the use of NMDA receptor antagonists to model schizophrenia in rodents. Some works describe the effects of ketamine on immobility behavior but there is variability in the experimental design used leading to controversial results. In this study, we evaluated the effects of repeated administration of ketamine sub-anesthetic doses in forced swimming, locomotion in response to novelty and novel object recognition, aiming a broader evaluation of the usefulness of this experimental approach for modeling schizophrenia in mice. Ketamine (30 mg/kg/day i.p. for 14 days induced a not persistent decrease in immobility time, detected 24h but not 72h after treatment. This same administration protocol induced a deficit in novel object recognition. No change was observed in mice locomotion. Our results confirm that repeated administration of sub-anesthetic doses of ketamine is useful in modeling schizophrenia-related behavioral changes in mice. However, the immobility time during forced swimming does not seem to be a good endpoint to evaluate the modeling of negative symptoms in NMDAR antagonist animal models of schizophrenia.

Is Forced Swimming Immobility a Good Endpoint for Modeling Negative Symptoms of Schizophrenia? - Study of Sub-Anesthetic Ketamine Repeated Administration Effects.

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Neves, Gilda; Borsoi, Milene; Antonio, Camila B; Pranke, Mariana A; Betti, Andresa H; Rates, Stela M K

2017-01-01

Immobility time in the forced swimming has been described as analogous to emotional blunting or apathy and has been used for characterizing schizophrenia animal models. Several clinical studies support the use of NMDA receptor antagonists to model schizophrenia in rodents. Some works describe the effects of ketamine on immobility behavior but there is variability in the experimental design used leading to controversial results. In this study, we evaluated the effects of repeated administration of ketamine sub-anesthetic doses in forced swimming, locomotion in response to novelty and novel object recognition, aiming a broader evaluation of the usefulness of this experimental approach for modeling schizophrenia in mice. Ketamine (30 mg/kg/day i.p. for 14 days) induced a not persistent decrease in immobility time, detected 24h but not 72h after treatment. This same administration protocol induced a deficit in novel object recognition. No change was observed in mice locomotion. Our results confirm that repeated administration of sub-anesthetic doses of ketamine is useful in modeling schizophrenia-related behavioral changes in mice. However, the immobility time during forced swimming does not seem to be a good endpoint to evaluate the modeling of negative symptoms in NMDAR antagonist animal models of schizophrenia.

Chronic self-administration of alcohol results in elevated ΔFosB: comparison of hybrid mice with distinct drinking patterns

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Ozburn Angela R

2012-10-01

Full Text Available Abstract Background The inability to reduce or regulate alcohol intake is a hallmark symptom for alcohol use disorders. Research on novel behavioral and genetic models of experience-induced changes in drinking will further our knowledge on alcohol use disorders. Distinct alcohol self-administration behaviors were previously observed when comparing two F1 hybrid strains of mice: C57BL/6J x NZB/B1NJ (BxN show reduced alcohol preference after experience with high concentrations of alcohol and periods of abstinence while C57BL/6J x FVB/NJ (BxF show sustained alcohol preference. These phenotypes are interesting because these hybrids demonstrate the occurrence of genetic additivity (BxN and overdominance (BxF in ethanol intake in an experience dependent manner. Specifically, BxF exhibit sustained alcohol preference and BxN exhibit reduced alcohol preference after experience with high ethanol concentrations; however, experience with low ethanol concentrations produce sustained alcohol preference for both hybrids. In the present study, we tested the hypothesis that these phenotypes are represented by differential production of the inducible transcription factor, ΔFosB, in reward, aversion, and stress related brain regions. Results Changes in neuronal plasticity (as measured by ΔFosB levels were experience dependent, as well as brain region and genotype specific, further supporting that neuronal circuitry underlies motivational aspects of ethanol consumption. BxN mice exhibiting reduced alcohol preference had lower ΔFosB levels in the Edinger-Westphal nucleus than mice exhibiting sustained alcohol preference, and increased ΔFosB levels in central medial amygdala as compared with control mice. BxN mice showing sustained alcohol preference exhibited higher ΔFosB levels in the ventral tegmental area, Edinger-Westphal nucleus, and amygdala (central and lateral divisions. Moreover, in BxN mice ΔFosB levels in the Edinger-Westphal nucleus and ventral

Validation of key behaviourally based mental health diagnoses in administrative data: suicide attempt, alcohol abuse, illicit drug abuse and tobacco use

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Kim Hyungjin

2012-01-01

Full Text Available Abstract Background Observational research frequently uses administrative codes for mental health or substance use diagnoses and for important behaviours such as suicide attempts. We sought to validate codes (International Classification of Diseases, 9th edition, clinical modification diagnostic and E-codes entered in Veterans Health Administration administrative data for patients with depression versus a gold standard of electronic medical record text ("chart notation". Methods Three random samples of patients were selected, each stratified by geographic region, gender, and year of cohort entry, from a VHA depression treatment cohort from April 1, 1999 to September 30, 2004. The first sample was selected from patients who died by suicide, the second from patients who remained alive on the date of death of suicide cases, and the third from patients with a new start of a commonly used antidepressant medication. Four variables were assessed using administrative codes in the year prior to the index date: suicide attempt, alcohol abuse/dependence, drug abuse/dependence and tobacco use. Results Specificity was high (≥ 90% for all four administrative codes, regardless of the sample. Sensitivity was ≤75% and was particularly low for suicide attempt (≤ 17%. Positive predictive values for alcohol dependence/abuse and tobacco use were high, but barely better than flipping a coin for illicit drug abuse/dependence. Sensitivity differed across the three samples, but was highest in the suicide death sample. Conclusions Administrative data-based diagnoses among VHA records have high specificity, but low sensitivity. The accuracy level varies by different diagnosis and by different patient subgroup.

Validation of key behaviourally based mental health diagnoses in administrative data: suicide attempt, alcohol abuse, illicit drug abuse and tobacco use.

Science.gov (United States)

Kim, Hyungjin Myra; Smith, Eric G; Stano, Claire M; Ganoczy, Dara; Zivin, Kara; Walters, Heather; Valenstein, Marcia

2012-01-23

Observational research frequently uses administrative codes for mental health or substance use diagnoses and for important behaviours such as suicide attempts. We sought to validate codes (International Classification of Diseases, 9th edition, clinical modification diagnostic and E-codes) entered in Veterans Health Administration administrative data for patients with depression versus a gold standard of electronic medical record text ("chart notation"). Three random samples of patients were selected, each stratified by geographic region, gender, and year of cohort entry, from a VHA depression treatment cohort from April 1, 1999 to September 30, 2004. The first sample was selected from patients who died by suicide, the second from patients who remained alive on the date of death of suicide cases, and the third from patients with a new start of a commonly used antidepressant medication. Four variables were assessed using administrative codes in the year prior to the index date: suicide attempt, alcohol abuse/dependence, drug abuse/dependence and tobacco use. Specificity was high (≥ 90%) for all four administrative codes, regardless of the sample. Sensitivity was ≤75% and was particularly low for suicide attempt (≤ 17%). Positive predictive values for alcohol dependence/abuse and tobacco use were high, but barely better than flipping a coin for illicit drug abuse/dependence. Sensitivity differed across the three samples, but was highest in the suicide death sample. Administrative data-based diagnoses among VHA records have high specificity, but low sensitivity. The accuracy level varies by different diagnosis and by different patient subgroup.

Repeated administration of the monoamine reuptake inhibitor BTS 74 398 induces ipsilateral circling in the 6-hydroxydopamine lesioned rat without sensitizing motor behaviours.

Science.gov (United States)

Lane, E L; Cheetham, S C; Jenner, P

2005-01-01

BTS 74 398 (1-[1-(3,4-dichlorophenyl)cyclobutyl]-2-(3-diaminethylaminopropylthio)ethanone monocitrate) is a monoamine reuptake inhibitor that reverses motor deficits in MPTP-treated (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) common marmosets without provoking established dyskinesia. However, it is not known whether BTS 74 398 primes the basal ganglia for dyskinesia induction. In this study, the ability of BTS 74 398 to sensitize 6-hydroxydopamine (6-OHDA)-lesioned rats for the production of abnormal motor behaviours and the induction of striatal DeltaFosB were determined in comparison with l-3,4-dihydroxyphenylalanine methyl ester (L-dopa). Acute administration of BTS 74 398 induced a dose-dependent ipsilateral circling response in unilaterally 6-OHDA-lesioned rats whereas L-dopa produced dose-dependent contraversive rotation. The ipsilateral circling response to BTS 74 398 did not alter during 21 days of administration. In contrast, L-dopa treatment for 21 days caused a marked increase in rotational response. Repeated administration of both L-dopa and BTS 74 398 increased general motor activity and stereotypic behaviour. In L-dopa-treated rats, orolingual, locomotive, forelimb and axial abnormal movements developed whereas BTS 74 398 produced only locomotion with a side bias but no other abnormal movements. Sensitization of circling responses and the development of abnormal movements in 6-OHDA-lesioned rats have been associated with the potential of dopaminergic drugs to induce dyskinesia. Furthermore, striatal DeltaFosB immunoreactivity, shown to correlate with dyskinesia induction, was increased by L-dopa but was unaffected by repeated BTS 74 398 administration. The lack of such changes following repeated BTS 74 398 treatment suggests that it may be an effective antiparkinsonian therapy that is unlikely to produce involuntary movements.

Distribution and excretion of arsenic in cynomolgus monkey following repeated administration of diphenylarsinic acid

Energy Technology Data Exchange (ETDEWEB)

Kobayashi, Yayoi [National Institute for Environmental Studies, Environmental Health Sciences Division, Tsukuba, Ibaraki (Japan); Negishi, Takayuki [Aoyama Gakuin University, Department of Chemistry and Biological Science, Tokyo (Japan); Mizumura, Ayano; Watanabe, Takayuki [Chiba University, Graduate School of Pharmaceutical Sciences, Chiba (Japan); Hirano, Seishiro [Chiba University, Graduate School of Pharmaceutical Sciences, Chiba (Japan); National Institute for Environmental Studies, Research Center for Environmental Risk, Tsukuba, Ibaraki (Japan)

2008-08-15

Diphenylarsinic acid (DPAA), a possible product of degradation of arsenic-containing chemical weapons, was detected in well water in Kamisu City, Ibaraki Prefecture, Japan, in 2003. Although some individuals in this area have been affected by drinking DPAA-containing water, toxicological findings on DPAA are limited. To elucidate the mechanism of its toxicity, it is necessary to determine the metabolic behavior of DPAA in the body. In this study, pregnant cynomolgus monkeys at the 50th day of pregnancy were used. The monkeys were treated daily with 1.0 mg DPAA/kg body weight using a nasogastric tube, and the distribution and excretion of arsenic were examined after the repeated administration and 198-237 days after the last administration of DPAA. Fecal excretion was higher than urinary excretion (ca. 3:2 ratio), and arsenic accumulated in the hair and erythrocytes. Distribution of DAPP to plasma and hemolyzed erythrocytes was also examined by high-performance liquid chromatography-inductively coupled argon plasma mass spectrometry (HPLC-ICP MS). Two peaks were found in the elution profile of arsenic, due to free and probably protein-bound DPAA. The protein-bound arsenic compounds were presumably trivalent diphenylarsenic compounds, since free DPAA was recovered after treatment of heat-denatured samples with hydrogen peroxide. (orig.)

Effects of repeated potassium iodide administration on genes involved in synthesis and secretion of thyroid hormone in adult male rat.

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Lebsir, Dalila; Manens, Line; Grison, Stephane; Lestaevel, Philippe; Ebrahimian, Teni; Suhard, David; Phan, Guillaume; Dublineau, Isabelle; Tack, Karine; Benderitter, Marc; Pech, Annick; Jourdain, Jean-Rene; Souidi, Maâmar

2018-02-26

A single dose of potassium iodide (KI) is recommended to reduce the risk of thyroid cancer during nuclear accidents. However in case of prolonged radioiodine exposure, more than one dose of KI may be necessary. This work aims to evaluate the potential toxic effect of repeated administration of KI. Adult Wistar rats received an optimal dose of KI 1 mg/kg over a period of 1, 4 or 8 days. hormonal status (TSH, FT4) of treated rats was unaffected. Contrariwise, a sequential Wolff-Chaikoff effect was observed, resulting in a prompt decrease of NIS and MCT8 mRNA expression (-58% and -26% respectively), followed by a delayed decrease of TPO mRNA expression (-33%) in conjunction with a stimulation of PDS mRNA expression (+62%). we show for the first time that repeated administration of KI at 1 mg/kg/24h doesn't cause modification of thyroid hormones level, but leads to a reversible modification of the expression of genes involved in the synthesis and secretion of thyroid hormones. Copyright © 2018 Elsevier B.V. All rights reserved.

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

Science.gov (United States)

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

76 FR 13982 - Antidumping Duty Order: Polyvinyl Alcohol From Taiwan

Science.gov (United States)

2011-03-15

...: Polyvinyl Alcohol From Taiwan AGENCY: Import Administration, International Trade Administration, Department... on polyvinyl alcohol (PVA) from Taiwan. DATES: Effective Date: March 15, 2011. FOR FURTHER... from Taiwan. See Polyvinyl Alcohol From Taiwan: Final Determination of Sales at Less Than Fair Value...

DRD4 polymorphism moderates the effect of alcohol consumption on social bonding.

Directory of Open Access Journals (Sweden)

Kasey G Creswell

Full Text Available Development of interpersonal relationships is a fundamental human motivation, and behaviors facilitating social bonding are prized. Some individuals experience enhanced reward from alcohol in social contexts and may be at heightened risk for developing and maintaining problematic drinking. We employed a 3 (group beverage condition ×2 (genotype design (N = 422 to test the moderating influence of the dopamine D4 receptor gene (DRD4 VNTR polymorphism on the effects of alcohol on social bonding. A significant gene x environment interaction showed that carriers of at least one copy of the 7-repeat allele reported higher social bonding in the alcohol, relative to placebo or control conditions, whereas alcohol did not affect ratings of 7-absent allele carriers. Carriers of the 7-repeat allele were especially sensitive to alcohol's effects on social bonding. These data converge with other recent gene-environment interaction findings implicating the DRD4 polymorphism in the development of alcohol use disorders, and results suggest a specific pathway by which social factors may increase risk for problematic drinking among 7-repeat carriers. More generally, our findings highlight the potential utility of employing transdisciplinary methods that integrate genetic methodologies, social psychology, and addiction theory to improve theories of alcohol use and abuse.

DRD4 polymorphism moderates the effect of alcohol consumption on social bonding.

Science.gov (United States)

Creswell, Kasey G; Sayette, Michael A; Manuck, Stephen B; Ferrell, Robert E; Hill, Shirley Y; Dimoff, John D

2012-01-01

Development of interpersonal relationships is a fundamental human motivation, and behaviors facilitating social bonding are prized. Some individuals experience enhanced reward from alcohol in social contexts and may be at heightened risk for developing and maintaining problematic drinking. We employed a 3 (group beverage condition) ×2 (genotype) design (N = 422) to test the moderating influence of the dopamine D4 receptor gene (DRD4 VNTR) polymorphism on the effects of alcohol on social bonding. A significant gene x environment interaction showed that carriers of at least one copy of the 7-repeat allele reported higher social bonding in the alcohol, relative to placebo or control conditions, whereas alcohol did not affect ratings of 7-absent allele carriers. Carriers of the 7-repeat allele were especially sensitive to alcohol's effects on social bonding. These data converge with other recent gene-environment interaction findings implicating the DRD4 polymorphism in the development of alcohol use disorders, and results suggest a specific pathway by which social factors may increase risk for problematic drinking among 7-repeat carriers. More generally, our findings highlight the potential utility of employing transdisciplinary methods that integrate genetic methodologies, social psychology, and addiction theory to improve theories of alcohol use and abuse.

Impact of repeated intravenous cocaine administration on incentive motivation depends on mode of drug delivery.

Science.gov (United States)

LeBlanc, Kimberly H; Maidment, Nigel T; Ostlund, Sean B

2014-11-01

The incentive sensitization theory of addiction posits that repeated exposure to drugs of abuse, like cocaine, can lead to long-term adaptations in the neural circuits that support motivated behavior, providing an account of pathological drug-seeking behavior. Although pre-clinical findings provide strong support for this theory, much remains unknown about the conditions that support incentive sensitization. The current study examined whether the mode of cocaine administration is an important factor governing that drug's long-term impact on behavior. Separate groups of rats were allowed either to self-administer intravenous cocaine or were given an equivalent number and distribution of unsignaled cocaine or saline infusions. During the subsequent test of incentive motivation (Pavlovian-to-instrumental transfer), we found that rats with a history of cocaine self-administration showed strong cue-evoked food seeking, in contrast to rats given unsignaled cocaine or saline. This finding indicates that the manner in which cocaine is administered can determine its lasting behavioral effects, suggesting that subjective experiences during drug use play a critical role in the addiction process. Our findings may therefore have important implications for the study and treatment of compulsive drug seeking. © 2013 Society for the Study of Addiction.

Alcohol warnings in TV beer advertisements.

Science.gov (United States)

Slater, M D; Domenech, M M

1995-05-01

Mandated warnings are among the few steps Congress has taken to influence the use of legal substances such as alcohol. The usefulness of such warnings in discouraging abuse of alcohol is, however, controversial. This study examines the impact of televised warnings on probable antecedents of belief change not examined in previous research: confidence in beliefs about beer risks or benefits, and cognitive responses to the advertisements. The present study (N = 75 male and female college students) tests four of the warnings recommended in Senate Bill 674 (1993--the "Thurmond bill") edited into randomly sampled television beer advertisements, using a between-subjects treatment-and-control experimental design. The four advertisements or advertisement/warning pairs were counterbalanced and analyzed as a repeated measures factor. The study indicated, as hypothesized, that subjects exposed to warnings tended to have less confidence in their generally skeptical assessments of beer risks--a likely precursor to belief change in resistant populations. Repeated exposure to the advertisements alone also appeared to lead to increased confidence in generally positive assessments of beer benefits, whereas repeated exposure to warnings led to decreased confidence in such assessments. Repeated exposure to warnings also may have primed negative reactions to subsequent beer advertisements. These results suggest mechanisms by which alcohol warnings may over time influence beliefs. Measures used here may serve as useful criterion variables in future studies on warnings. Further attention to optimizing warning content and presentation is recommended.

In vitro interactions with repeated grapefruit juice administration--to peel or not to peel?

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Brill, Shlomo; Zimmermann, Christian; Berger, Karin; Drewe, Juergen; Gutmann, Heike

2009-03-01

Interactions of acutely administered grapefruit juice (GFJ) with cytochrome P450 isoform 3A4 (CYP3A4) and P-glycoprotein (Pgp) function are well established. In this study, we investigated in vitro the effect of repeated administration of GFJ and its major constituents (the flavonoid naringin, its aglycone naringenin and the furanocoumarin bergamottin) on mRNA expression of MDR1 and CYP3A4 in LS180 cells. Since the bergamottin content is higher in the peel than in the fruit, we compared GFJ containing peel (GFJP+) with juice without any peel extract (GFJP-). GFJP- (1%) showed no significant effect on MDR1 and CYP3A4 mRNA expression, whereas 1% GFJP+ increased expression of MDR1 3.7-fold (Pextract may have a lower potential for interactions with CYP3A4 or P-glycoprotein.

21 CFR 177.1360 - Ethylene-vinyl acetate-vinyl alcohol copolymers.

Science.gov (United States)

2010-04-01

... 21 Food and Drugs 3 2010-04-01 2009-04-01 true Ethylene-vinyl acetate-vinyl alcohol copolymers... for Use as Basic Components of Single and Repeated Use Food Contact Surfaces § 177.1360 Ethylene-vinyl acetate-vinyl alcohol copolymers. Ethylene-vinyl acetate-vinyl alcohol copolymers (CAS Reg. No. 26221-27-2...

Ethanol up-regulates nucleus accumbens neuronal activity dependent pentraxin (Narp): implications for alcohol-induced behavioral plasticity.

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Ary, Alexis W; Cozzoli, Debra K; Finn, Deborah A; Crabbe, John C; Dehoff, Marlin H; Worley, Paul F; Szumlinski, Karen K

2012-06-01

Neuronal activity dependent pentraxin (Narp) interacts with α-amino-3-hydroxyl-5-methyl-4-isoxazole-propionate (AMPA) glutamate receptors to facilitate excitatory synapse formation by aggregating them at established synapses. Alcohol is well-characterized to influence central glutamatergic transmission, including AMPA receptor function. Herein, we examined the influence of injected and ingested alcohol upon Narp protein expression, as well as basal Narp expression in mouse lines selectively bred for high blood alcohol concentrations under limited access conditions. Alcohol up-regulated accumbens Narp levels, concomitant with increases in levels of the GluR1 AMPA receptor subunit. However, accumbens Narp or GluR1 levels did not vary as a function of selectively bred genotype. We next employed a Narp knock-out (KO) strategy to begin to understand the behavioral relevance of alcohol-induced changes in protein expression in several assays of alcohol reward. Compared to wild-type mice, Narp KO animals: fail to escalate daily intake of high alcohol concentrations under free-access conditions; shift their preference away from high alcohol concentrations with repeated alcohol experience; exhibit a conditioned place-aversion in response to the repeated pairing of 3 g/kg alcohol with a distinct environment and fail to exhibit alcohol-induced locomotor hyperactivity following repeated alcohol treatment. Narp deletion did not influence the daily intake of either food or water, nor did it alter any aspect of spontaneous or alcohol-induced motor activity, including the development of tolerance to its motor-impairing effects with repeated treatment. Taken together, these data indicate that Narp induction, and presumably subsequent aggregation of AMPA receptors, may be important for neuroplasticity within limbic subcircuits mediating or maintaining the rewarding properties of alcohol. Published by Elsevier Inc.

Alcohol and radionuclide metabolism

International Nuclear Information System (INIS)

Mahlum, D.D.; Hess, J.O.

1978-01-01

The effect of ethanol administration on the deposition and retention of polymeric 239 Pu and 241 Am citrate was studied in the rat. Only in the case of polymeric Pu was there an effect of alcohol administration

Changes in the influence of alcohol-paired stimuli on alcohol seeking across extended training.

Directory of Open Access Journals (Sweden)

Laura H. Corbit

2016-10-01

Full Text Available Previous work has demonstrated that goal-directed control of alcohol seeking and other drug-related behaviors is reduced following extended self-administration and drug exposure. Here we examined how the magnitude of stimulus influences on responding changes across similar training and drug exposure. Rats self-administered alcohol or sucrose for two or eight weeks. Previous work has shown that eight, but not two weeks of self-administration produces habitual alcohol seeking. Next, all animals received equivalent Pavlovian conditioning sessions where a discrete stimulus predicted the delivery of alcohol or sucrose. Finally, the impact of the stimuli on ongoing instrumental responding was examined in a Pavlovian-instrumental transfer (PIT test. While a significant PIT effect was observed following two weeks of either alcohol or sucrose self-administration, the magnitude of this effect was greater following eight weeks of training. The specificity of the PIT effect appeared unchanged by extended training. While it is well established that evaluation of the outcome of responding contributes less to behavioral control following extended training and/or drug exposure, our data indicate that reward-predictive stimuli have a stronger contribution to responding after extended training. Together, these findings provide insight into the factors that control behavior after extended drug use which will be important for developing effective methods for controlling and ideally reducing these behaviors.

Changes in the Influence of Alcohol-Paired Stimuli on Alcohol Seeking across Extended Training

Science.gov (United States)

Corbit, Laura H.; Janak, Patricia H.

2016-01-01

Previous work has demonstrated that goal-directed control of alcohol-seeking and other drug-related behaviors is reduced following extended self-administration and drug exposure. Here, we examined how the magnitude of stimulus influences on responding changes across similar training and drug exposure. Rats self-administered alcohol or sucrose for 2 or 8 weeks. Previous work has shown that 8 weeks, but not 2 weeks of self-administration produces habitual alcohol seeking. Next, all animals received equivalent Pavlovian conditioning sessions where a discrete stimulus predicted the delivery of alcohol or sucrose. Finally, the impact of the stimuli on ongoing instrumental responding was examined in a Pavlovian–instrumental transfer (PIT) test. While a significant PIT effect was observed following 2 weeks of either alcohol or sucrose self-administration, the magnitude of this effect was greater following 8 weeks of training. The specificity of the PIT effect appeared unchanged by extended training. While it is well established that evaluation of the outcome of responding contributes less to behavioral control following extended training and/or drug exposure, our data indicate that reward–predictive stimuli have a stronger contribution to responding after extended training. Together, these findings provide insight into the factors that control behavior after extended drug use, which will be important for developing effective methods for controlling and ideally reducing these behaviors. PMID:27777560

Prazosin Prevents Increased Anxiety Behavior That Occurs in Response to Stress During Alcohol Deprivations.

Science.gov (United States)

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

2017-01-01

Stress-induced anxiety is a risk factor for relapse to alcohol drinking. The aim of this study was to test the hypothesis that the central nervous system (CNS)-active α 1 -adrenergic receptor antagonist, prazosin, would block the stress-induced increase in anxiety that occurs during alcohol deprivations. Selectively bred male alcohol-preferring (P) rats were given three cycles of 5 days of ad libitum voluntary alcohol drinking interrupted by 2 days of alcohol deprivation, with or without 1 h of restraint stress 4 h after the start of each of the first two alcohol deprivation cycles. Prazosin (1.0 or 1.5 mg/kg, IP) or vehicle was administered before each restraint stress. Anxiety-like behavior during alcohol deprivation following the third 5-day cycle of alcohol drinking (7 days after the most recent restraint stress ± prazosin treatment) was measured by performance in an elevated plus-maze and in social approach/avoidance testing. Rats that received constant alcohol access, or alcohol access and deprivations without stress or prazosin treatments in the first two alcohol deprivations did not exhibit augmented anxiety-like behavior during the third deprivation. In contrast, rats that had been stressed during the first two alcohol deprivations exhibited increased anxiety-like behavior (compared with control rats) in both anxiety tests during the third deprivation. Prazosin given before stresses in the first two cycles of alcohol withdrawal prevented increased anxiety-like behavior during the third alcohol deprivation. Prazosin treatment before stresses experienced during alcohol deprivations may prevent the increased anxiety during subsequent deprivation/abstinence that is a risk factor for relapse to alcohol drinking. Administration of prazosin before stresses during repetitive alcohol deprivations in male alcohol-preferring (P) rats prevents increased anxiety during a subsequent deprivation without further prazosin treatment. Prazosin treatment during repeated

Repeated intravenous administration of gadobutrol does not lead to increased signal intensity on unenhanced T1-weighted images - a voxel-based whole brain analysis

Energy Technology Data Exchange (ETDEWEB)

Langner, Soenke; Kromrey, Marie-Luise [University Medicine Greifswald, Institute of Diagnostic Radiology and Neuroradiology, Greifswald (Germany); Kuehn, Jens-Peter [University Medicine Greifswald, Institute of Diagnostic Radiology and Neuroradiology, Greifswald (Germany); University Hospital, Carl Gustav Carus University Dresden, Institute for Radiology, Dresden (Germany); Grothe, Matthias [University Medicine Greifswald, Department of Neurology, Greifswald (Germany); Domin, Martin [University Medicine Greifswald, Functional Imaging Unit, Institute of Diagnostic Radiology and Neuroradiology, Greifswald (Germany)

2017-09-15

To identify a possible association between repeated intravenous administration of gadobutrol and increased signal intensity in the grey and white matter using voxel-based whole-brain analysis. In this retrospective single-centre study, 217 patients with a clinically isolated syndrome underwent baseline brain magnetic resonance imaging and at least one annual follow-up examination with intravenous administration of 0.1 mmol/kg body weight of gadobutrol. Using the ''Diffeomorphic Anatomical Registration using Exponentiated Lie algebra'' (DARTEL) normalisation process, tissue templates for grey matter (GM), white matter (WM), and cerebrospinal fluid (CSF) were calculated, as were GM-CSF and WM-CSF ratios. Voxel-based whole-brain analysis was used to calculate the signal intensity for each voxel in each data set. Paired t-test was applied to test differences to baseline MRI for significance. Voxel-based whole-brain analysis demonstrated no significant changes in signal intensity of grey and white matter after up to five gadobutrol administrations. There was no significant change in GM-CSF and grey WM-CSF ratios. Voxel-based whole-brain analysis did not demonstrate increased signal intensity of GM and WM on unenhanced T1-weighted images after repeated gadobutrol administration. The molecular structure of gadolinium-based contrast agent preparations may be an essential factor causing SI increase on unenhanced T1-weighted images. (orig.)

Top priorities for alcohol regulators in the United States: protecting public health or the alcohol industry?

Science.gov (United States)

Mart, Sarah M

2012-02-01

This paper describes alcohol industry involvement in the 2010 annual conference proceedings of the National Conference of State Liquor Administrators (NCSLA) in the United States. The author attended the conference, observed conference attendees and panelists and identified key themes in the panel sessions. The NCSLA Annual Meeting took place 20-24 June 2010 in New Orleans, Louisiana. NCSLA meeting attendees and panelists were professionals from state alcohol control systems; federal government agencies; and companies representing the alcohol industry. The total number of conference attendees and participants were counted as well as the number of attendees and participants from regulator, industry and public health sectors. More than two-thirds (72.2%) of the 187 conference attendees were from alcohol producers, importers, wholesalers, retailers or their attorneys. Nearly two-thirds (65.0%) of the 40 panelists were from the alcohol industry. The author of this paper was the only attendee, and the only panelist, representing public health policy. The National Conference of State Liquor Administrators in the United States is dominated by the global companies that produce, import, distribute and sell alcohol, highlighting a lack of public health considerations within the Association's liquor control agenda [corrected]. © 2012 Alcohol Justice.

Disruption of spindle checkpoint function in rats following 28 days of repeated administration of renal carcinogens.

Science.gov (United States)

Kimura, Masayuki; Mizukami, Sayaka; Watanabe, Yousuke; Hasegawa-Baba, Yasuko; Onda, Nobuhiko; Yoshida, Toshinori; Shibutani, Makoto

2016-02-01

We previously reported that 28-day exposure to hepatocarcinogens that facilitate cell proliferation specifically alters the expression of G1/S checkpoint-related genes and proteins, induces aberrant early expression of ubiquitin D (UBD) at the G2 phase, and increases apoptosis in the rat liver, indicating G1/S and spindle checkpoint dysfunction. The present study aimed to determine the time of onset of carcinogen-specific cell-cycle disruption after repeated administration of renal carcinogens for up to 28 days. Rats were orally administered the renal carcinogens nitrofurantoin (NFT), 1-amino-2,4-dibromoantraquinone (ADAQ), and 1,2,3-trichloropropane (TCP) or the non-carcinogenic renal toxicants 1-chloro-2-propanol, triamterene, and carboxin for 3, 7 or 28 days. Both immunohistochemical single-molecule analysis and real-time RT-PCR analysis revealed that carcinogen-specific expression changes were not observed after 28 days of administration. However, the renal carcinogens ADAQ and TCP specifically reduced the number of cells expressing phosphorylated-histone H3 at Ser10 in both UBD(+) cells and proliferating cells, suggestive of insufficient UBD expression at the M phase and early transition of proliferating cells from the M phase, without increasing apoptosis, after 28 days of administration. In contrast, NFT, which has marginal carcinogenic potential, did not induce such cellular responses. These results suggest that it may take 28 days to induce spindle checkpoint dysfunction by renal carcinogens; however, induction of apoptosis may not be essential. Thus, induction of spindle checkpoint dysfunction may be dependent on carcinogenic potential of carcinogen examined, and marginal carcinogens may not exert sufficient responses even after 28 days of administration.

27 CFR 17.136 - Compliance with Food and Drug Administration requirements.

Science.gov (United States)

2010-04-01

... 27 Alcohol, Tobacco Products and Firearms 1 2010-04-01 2010-04-01 false Compliance with Food and Drug Administration requirements. 17.136 Section 17.136 Alcohol, Tobacco Products and Firearms ALCOHOL... Compliance with Food and Drug Administration requirements. A product is not a medicine, medicinal preparation...

Preoperative alcoholism and postoperative morbidity

DEFF Research Database (Denmark)

Tonnesen, H; Kehlet, H

1999-01-01

BACKGROUND: Preoperative risk assessment has become part of daily clinical practice, but preoperative alcohol abuse has not received much attention. METHODS: A Medline search was carried out to identify original papers published from 1967 to 1998. Relevant articles on postoperative morbidity...... in alcohol abusers were used to evaluate the evidence. RESULTS: Prospective and retrospective studies demonstrate a twofold to threefold increase in postoperative morbidity in alcohol abusers, the most frequent complications being infections, bleeding and cardiopulmonary insufficiency. Wound complications...... to postoperative morbidity. CONCLUSION: Alcohol consumption should be included in the preoperative assessment of likely postoperative outcome. Reduction of postoperative morbidity in alcohol abusers may include preoperative alcohol abstinence to improve organ function, or perioperative alcohol administration...

Combined alcohol and energy drink use: hedonistic motives, adenosine, and alcohol dependence.

Science.gov (United States)

Marczinski, Cecile A

2014-07-01

Consumption of alcohol mixed with energy drinks (AmED) has been associated with both short- and long-term risks beyond those observed with alcohol alone. AmED use has been associated with heavy episodic (binge) drinking, risky behaviors, and risk of alcohol dependence. Laboratory research has demonstrated that AmED beverages lead to greater motivation to drink versus the same amount of alcohol consumed alone. However, the reason consumers find AmED beverages particularly appealing has been unclear. A recent report by Droste and colleagues (Alcohol Clin Exp Res 2014; 38:2087-2095) is the first study to investigate motivations related to AmED consumption and to determine which motives predict AmED consumption patterns, experience of drinking-related harms, and risk of alcohol dependence. The findings of this study significantly enhance our understanding of why AmED consumption is related to the risk of alcohol dependence and change our understanding of why consumers choose AmED beverages. The authors report that hedonistic motives strongly predicted AmED use and the harms associated with use. While intoxication-reduction motives predicted self-reported accidents and injuries, these motives did not predict AmED consumption patterns and risk of dependence. The risk of alcohol dependence may arise from repeated experiences when drinking alcohol is more pleasurable when energy drinks are consumed with the alcohol. This commentary will focus on why energy drinks might increase the rewarding properties of alcohol in social drinkers. In addition, discussion is provided explaining why more research on the neurotransmitter, adenosine, may actually inform us about the mechanisms contributing to the development of alcohol dependence. Copyright © 2014 by the Research Society on Alcoholism.

Differential regulation of proopiomelanocortin (POMC mRNA expression in hypothalamus and anterior pituitary following repeated cyanamide with ethanol administration

Directory of Open Access Journals (Sweden)

Kinoshita Hiroshi

2005-01-01

Full Text Available Background/Aim. We have investigated proopiomelanocortin (POMC mRNA expression in the arcuate nucleus of the hypothalamus (ARC and the anterior lobe of the pituitary (AL following repeated cyanamide-ethanol reaction (CER. Methods. Adult male Sprague -Dawley rats (250 −290 gr were housed in a temperature and humidity controlled environment with free access to food and water. Four experimental groups were used as follows: saline (as control, cyanamide alone, ethanol alone and ethanol with cyanamide. The animals received daily intraperitoneal injections (i.p. of cyanamide (10mg/kg, 60 min before ethanol dosing with or without ethanol (1g/kg for 5 consecutive days, and were sacrificed 60 min after the last dosing of ethanol. The results were presented as the mean ± SEM for each group. All groups within each data set were compared by one-way ANOVA followed by Fisher PLSD test for multiple comparisons. A value of p<0.05 was considered significant. Results. The POMC mRNA levels in ARC were significantly decreased with cyanamide compared to the control and ethanol alone (p<0.05 and p<0.05 respectively, but increased in AL following repeated CER. Conclusion. We speculate that this differential regulation of POMC mRNA expression may be partially involved in the preventive effects on alcohol intake in response to CER.

Combined Alcohol and Energy Drink Use: Hedonistic Motives, Adenosine, and Alcohol Dependence

Science.gov (United States)

Marczinski, Cecile A.

2014-01-01

Consumption of alcohol mixed with energy drinks (AmED) has been associated with both short and long-term risks beyond those observed with alcohol alone. AmED use has been associated with heavy episodic (binge) drinking, risky behaviors, and risk of alcohol dependence. Laboratory research has demonstrated that AmED beverages lead to greater motivation to drink versus the same amount of alcohol consumed alone. However, the reason consumers find AmED beverages particularly appealing has been unclear. A recent report by Droste and colleagues (2014) is the first study to investigate motivations related to AmED consumption and to determine which motives predict AmED consumption patterns, experience of drinking-related harms, and risk of alcohol dependence. The findings of this study significantly enhance our understanding of why AmED consumption is related to the risk of alcohol dependence and change our understanding of why consumers chose AmED beverages. The authors report that hedonistic motives strongly predicted AmED use and the harms associated with use. While intoxication-reduction motives predicted self-reported accidents and injuries, these motives did not predict AmED consumption patterns and risk of dependence. The risk of alcohol dependence may arise from repeated experiences when drinking alcohol is more pleasurable when energy drinks are consumed with the alcohol. This commentary will focus on why energy drinks might increase the rewarding properties of alcohol in social drinkers. In addition, discussion is provided explaining why more research on the neurotransmitter, adenosine, may actually inform us about the mechanisms contributing to the development of alcohol dependence. PMID:25040590

Joint effect of alcohol consumption and educational level on alcohol-related medical events

DEFF Research Database (Denmark)

Nordahl Christensen, Helene; Diderichsen, Finn; Hvidtfeldt, Ulla Arthur

2017-01-01

alcohol consumption at baseline using self-administrated questionnaires. Information on highest attained education 1 year before study entry and hospital and mortality data on alcohol-related medical events were obtained through linkage to nationwide registries. We performed analyses using the Aalen...... may also play a role. We investigated the joint effect of alcohol consumption and educational level on the rate of alcohol-related medical events.Methods: We pooled seven prospective cohorts from Denmark that enrolled 74,278 men and women age 30–70 years (study period, 1981 to 2009). We measured...... additive hazards model.Results: During follow-up (1,085,049 person-years), a total of 1718 alcohol-related events occurred. The joint effect of very high alcohol consumption (>21 [>28] drinks per week in women [men]) and low education on alcohol-related events exceeded the sum of their separate effects...

Repeated administration of mazindol reduces spontaneous pain-related behaviors without modifying bone density and microarchitecture in a mouse model of complete Freund’s adjuvant-induced knee arthritis

Science.gov (United States)

Robledo-González, LE; Martínez-Martínez, A; Vargas-Muñoz, VM; Acosta-González, RI; Plancarte-Sánchez, R; Anaya-Reyes, M; Fernández del Valle-Laisequilla, C; Reyes-García, JG; Jiménez-Andrade, JM

2017-01-01

Background The role of dopaminergic system in the development of rheumatoid arthritis-related pain, a major symptom in this disease, has not been explored. Therefore, the anti-nociceptive effect of mazindol, a dopamine uptake inhibitor, was evaluated in a model of complete Freund’s adjuvant (CFA)-induced arthritis. Furthermore, as studies have shown that the dopaminergic system regulates bone metabolism, the effect of mazindol on bone mass and microarchitecture was determined. Methods Adult ICR male mice received intra-articular injections of either CFA or saline into the right knee joint every week. Spontaneous pain-like behaviors (flinching and guarding) and locomotor activity were assessed at day 26 post-first CFA, following which, a single intraperitoneally (i.p.) administered dose of mazindol was given (1, 3 and 10 mg/kg). Then, the antinociceptive effect of a repeated administration of 3 mg/kg mazindol (daily, i.p.; day 15–day 26) was evaluated. Additionally, at day 26, the participation of D1-like, D2-like or opioid receptors in the antinociceptive effect of mazindol was evaluated. The effect of mazindol on bone density and microarchitecture was evaluated by micro-computed tomography. Results Acute administration of mazindol decreased the spontaneous pain-like behaviors in a dose-dependent manner without reducing the knee edema. However, mazindol at 10 mg/kg significantly increased the locomotor activity; therefore, 3 mg/kg mazindol was used for further studies. Repeated administration of 3 mg/kg mazindol significantly decreased the pain-like behaviors without modifying locomotor activity. The antinociceptive effect of mazindol was blocked by administration of a D2-like receptor antagonist (haloperidol), but not by administration of D1-like receptor antagonist (SCH 23390) or an opioid receptor antagonist (naloxone). Repeated administration of mazindol did not significantly modify the density and microarchitecture of periarticular bone of the arthritic

Chronic Binge Alcohol Administration Dysregulates Hippocampal Genes Involved in Immunity and Neurogenesis in Simian Immunodeficiency Virus-Infected Macaques

Directory of Open Access Journals (Sweden)

John K. Maxi

2016-11-01

Full Text Available Alcohol use disorders (AUD exacerbate neurocognitive dysfunction in Human Immunodeficiency Virus (HIV+ patients. We have shown that chronic binge alcohol (CBA administration (13–14 g EtOH/kg/wk prior to and during simian immunodeficiency virus (SIV infection in rhesus macaques unmasks learning deficits in operant learning and memory tasks. The underlying mechanisms of neurocognitive alterations due to alcohol and SIV are not known. This exploratory study examined the CBA-induced differential expression of hippocampal genes in SIV-infected (CBA/SIV+; n = 2 macaques in contrast to those of sucrose administered, SIV-infected (SUC/SIV+; n = 2 macaques. Transcriptomes of hippocampal samples dissected from brains obtained at necropsy (16 months post-SIV inoculation were analyzed to determine differentially expressed genes. MetaCore from Thomson Reuters revealed enrichment of genes involved in inflammation, immune responses, and neurodevelopment. Functional relevance of these alterations was examined in vitro by exposing murine neural progenitor cells (NPCs to ethanol (EtOH and HIV trans-activator of transcription (Tat protein. EtOH impaired NPC differentiation as indicated by decreased βIII tubulin expression. These findings suggest a role for neuroinflammation and neurogenesis in CBA/SIV neuropathogenesis and warrant further investigation of their potential contribution to CBA-mediated neurobehavioral deficits.

21 CFR 862.3040 - Alcohol test system.

Science.gov (United States)

2010-04-01

... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Alcohol test system. 862.3040 Section 862.3040 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED....3040 Alcohol test system. (a) Identification. An alcohol test system is a device intented to measure...

21 CFR 582.5580 - D-Pantothenyl alcohol.

Science.gov (United States)

2010-04-01

... 21 Food and Drugs 6 2010-04-01 2010-04-01 false D-Pantothenyl alcohol. 582.5580 Section 582.5580 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL... Supplements 1 § 582.5580 D-Pantothenyl alcohol. (a) Product. D-Pantothenyl alcohol. (b) Conditions of use...

Effects of the repeated administration of adenosine and heparin on myocardial perfusion in patients with chronic stable angina pectoris.

Science.gov (United States)

Barron, H V; Sciammarella, M G; Lenihan, K; Michaels, A D; Botvinick, E H

2000-01-01

The mechanism by which ischemia stimulates angiogenesis is unknown. Adenosine is released during myocardial ischemia and may be a mediator of this process. Experimental data suggest that heparin may enhance this effect. The purpose of this open-labeled, placebo-controlled trial was to determine whether repeated intravenous administration of adenosine and heparin could mimic physiologic angiogenesis and reduce the amount of exercise-induced myocardial ischemia in patients with coronary artery disease. Subjects with chronic stable angina refractory to conventional medical therapy and not suitable for revascularization received either adenosine (140 microg/kg/min for 6 minutes) and heparin (10,000 U bolus), (n = 14), or placebo, (n = 7) daily for 10 days. All patients underwent baseline and follow-up exercise testing with thallium-201 single-photon emission computed tomography myocardial perfusion imaging. A semiquantitative assessment of the extent and severity of the perfusion abnormalities was calculated by 2 blinded investigators. There was no significant change in exercise duration or in the peak heart rate systolic blood pressure product associated with adenosine and heparin compared with placebo treatment. There was, however, a 9% reduction in the extent (60.6 +/- 4.0 vs 54.9 +/- 4.1, p = 0.03) and a 14% improvement in severity (41.5 +/- 3.2 vs 35.7 +/- 2.9, p = 0.01) of the myocardial perfusion abnormalities seen in patients who received adenosine and heparin compared with placebo. Thus, in this pilot study, repeated administration of adenosine and heparin reduced the amount of exercise-induced ischemia in patients with chronic stable angina refractory to conventional treatment.

Telomere shortening unrelated to smoking, body weight, physical activity, and alcohol intake: 4,576 general population individuals with repeat measurements 10 years apart.

Directory of Open Access Journals (Sweden)

Maren Weischer

2014-03-01

Full Text Available Cross-sectional studies have associated short telomere length with smoking, body weight, physical activity, and possibly alcohol intake; however, whether these associations are due to confounding is unknown. We tested these hypotheses in 4,576 individuals from the general population cross-sectionally, and with repeat measurement of relative telomere length 10 years apart. We also tested whether change in telomere length is associated with mortality and morbidity in the general population. Relative telomere length was measured with quantitative polymerase chain reaction. Cross-sectionally at the first examination, short telomere length was associated with increased age (P for trend across quartiles = 3 × 10(-77, current smoking (P = 8 × 10(-3, increased body mass index (P = 7 × 10(-14, physical inactivity (P = 4 × 10(-17, but not with increased alcohol intake (P = 0.10. At the second examination 10 years later, 56% of participants had lost and 44% gained telomere length with a mean loss of 193 basepairs. Change in leukocyte telomere length during 10 years was associated inversely with baseline telomere length (P<1 × 10(-300 and age at baseline (P = 1 × 10(-27, but not with baseline or 10-year inter-observational tobacco consumption, body weight, physical activity, or alcohol intake. Prospectively during a further 10 years follow-up after the second examination, quartiles of telomere length change did not associate with risk of all-cause mortality, cancer, chronic obstructive pulmonary disease, diabetes mellitus, ischemic cerebrovascular disease, or ischemic heart disease. In conclusion, smoking, increased body weight, and physical inactivity were associated with short telomere length cross-sectionally, but not with telomere length change during 10 years observation, and alcohol intake was associated with neither. Also, change in telomere length did not associate prospectively with mortality or morbidity in the general population.

Alcohol-induced histone acetylation reveals a gene network involved in alcohol tolerance.

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Alfredo Ghezzi

Full Text Available Sustained or repeated exposure to sedating drugs, such as alcohol, triggers homeostatic adaptations in the brain that lead to the development of drug tolerance and dependence. These adaptations involve long-term changes in the transcription of drug-responsive genes as well as an epigenetic restructuring of chromosomal regions that is thought to signal and maintain the altered transcriptional state. Alcohol-induced epigenetic changes have been shown to be important in the long-term adaptation that leads to alcohol tolerance and dependence endophenotypes. A major constraint impeding progress is that alcohol produces a surfeit of changes in gene expression, most of which may not make any meaningful contribution to the ethanol response under study. Here we used a novel genomic epigenetic approach to find genes relevant for functional alcohol tolerance by exploiting the commonalities of two chemically distinct alcohols. In Drosophila melanogaster, ethanol and benzyl alcohol induce mutual cross-tolerance, indicating that they share a common mechanism for producing tolerance. We surveyed the genome-wide changes in histone acetylation that occur in response to these drugs. Each drug induces modifications in a large number of genes. The genes that respond similarly to either treatment, however, represent a subgroup enriched for genes important for the common tolerance response. Genes were functionally tested for behavioral tolerance to the sedative effects of ethanol and benzyl alcohol using mutant and inducible RNAi stocks. We identified a network of genes that are essential for the development of tolerance to sedation by alcohol.

Permanent relief from intermittent cold stress-induced fibromyalgia-like abnormal pain by repeated intrathecal administration of antidepressants

Directory of Open Access Journals (Sweden)

Mukae Takehiro

2011-09-01

Full Text Available Abstract Background Fibromyalgia (FM is characterized by chronic widespread pain, which is often refractory to conventional painkillers. Numerous clinical studies have demonstrated that antidepressants are effective in treating FM pain. We previously established a mouse model of FM-like pain, induced by intermittent cold stress (ICS. Results In this study, we find that ICS exposure causes a transient increase in plasma corticosterone concentration, but not in anxiety or depression-like behaviors. A single intrathecal injection of an antidepressant, such as milnacipran, amitriptyline, mianserin or paroxetine, had an acute analgesic effect on ICS-induced thermal hyperalgesia at post-stress day 1 in a dose-dependent manner. In addition, repeated daily antidepressant treatments during post-stress days 1-5 gradually reversed the reduction in thermal pain threshold, and this recovery was maintained for at least 7 days after the final treatment. In addition, relief from mechanical allodynia, induced by ICS exposure, was also observed at day 9 after the cessation of antidepressant treatment. In contrast, the intravenous administration of these antidepressants at conventional doses failed to provide relief. Conclusions These results suggest that the repetitive intrathecal administration of antidepressants permanently cures ICS-induced FM pain in mice.

Alcohol biosensing by polyamidoamine (PAMAM)/cysteamine/alcohol oxidase-modified gold electrode.

Science.gov (United States)

Akin, Mehriban; Yuksel, Merve; Geyik, Caner; Odaci, Dilek; Bluma, Arne; Höpfner, Tim; Beutel, Sascha; Scheper, Thomas; Timur, Suna

2010-01-01

A highly stable and sensitive amperometric alcohol biosensor was developed by immobilizing alcohol oxidase (AOX) through Polyamidoamine (PAMAM) dendrimers on a cysteamine-modified gold electrode surface. Ethanol determination is based on the consumption of dissolved oxygen content due to the enzymatic reaction. The decrease in oxygen level was monitored at -0.7 V vs. Ag/AgCl and correlated with ethanol concentration. Optimization of variables affecting the system was performed. The optimized ethanol biosensor showed a wide linearity from 0.025 to 1.0 mM with 100 s response time and detection limit of (LOD) 0.016 mM. In the characterization studies, besides linearity some parameters such as operational and storage stability, reproducibility, repeatability, and substrate specificity were studied in detail. Stability studies showed a good preservation of the bioanalytical properties of the sensor, 67% of its initial sensitivity was kept after 1 month storage at 4 degrees C. The analytical characteristics of the system were also evaluated for alcohol determination in flow injection analysis (FIA) mode. Finally, proposed biosensor was applied for ethanol analysis in various alcoholic beverage as well as offline monitoring of alcohol production through the yeast cultivation. Copyright 2010 American Institute of Chemical Engineers

Alcohol during Pregnancy

Science.gov (United States)

... Disease Control and Prevention (CDC) National Council on Alcoholism and Drug Dependence (NCADD) Substance Abuse and Mental Health Services Administration (SAMSHA) Last reviewed: April, 2016 Pregnancy Is it safe? Other Pregnancy topics ') document.write(' ...

Administrative Circulars

CERN Document Server

Département des Ressources humaines

2004-01-01

Administrative Circular N° 2 (Rev. 2) - May 2004 Guidelines and procedures concerning recruitment and probation period of staff members This circular has been revised. It cancels and replaces Administrative Circular N° 2 (Rev. 1) - March 2000. Administrative Circular N° 9 (Rev. 3) - May 2004 Staff members contracts This circular has been revised. It cancels and replaces Administrative Circular N° 9 (Rev. 2) - March 2000. Administrative Circular N° 26 (Rev. 4) - May 2004 Procedure governing the career evolution of staff members This circular has also been revised. It Administrative Circulars Administrative Circular N° 26 (Rev. 3) - December 2001 and brings up to date the French version (Rev. 4) published on the HR Department Web site in January 2004. Operational Circular N° 7 - May 2004 Work from home This circular has been drawn up. Operational Circular N° 8 - May 2004 Dealing with alcohol-related problems...

21 CFR 862.3050 - Breath-alcohol test system.

Science.gov (United States)

2010-04-01

... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Breath-alcohol test system. 862.3050 Section 862.3050 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED....3050 Breath-alcohol test system. (a) Identification. A breath-alcohol test system is a device intened...

Alcohol, cardiac arrhythmias and sudden death.

Science.gov (United States)

Kupari, M; Koskinen, P

1998-01-01

Studies in experimental animals have shown varying and apparently opposite effects of alcohol on cardiac rhythm and conduction. Given acutely to non-alcoholic animals, ethanol may even have anti-arrhythmic properties whereas chronic administration clearly increases the animals' susceptibility to cardiac arrhythmias. Chronic heavy alcohol use has been incriminated in the genesis of cardiac arrhythmias in humans. The evidence has come from clinical observations, retrospective case-control studies, controlled studies of consecutive admissions for arrhythmias, and prospective epidemiological investigations. Furthermore, electrophysiological studies have shown that acute alcohol administration facilitates the induction of tachyarrhythmias in selected heavy drinkers. The role of alcohol appears particularly conspicuous in idiopathic atrial fibrillation. Occasionally, ventricular tachyarrhythmias have also been provoked by alcohol intake. Several lines of evidence suggest that heavy drinking increases the risk of sudden cardiac death with fatal arrhythmia as the most likely mechanism. According to epidemiological studies this effect appears most prominent in middle-aged men and is only partly explained by confounding traits such as smoking and social class. The basic arrhythmogenic effects of alcohol are still insufficiently delineated. Subclinical heart muscle injury from chronic heavy use may be instrumental in producing patchy delays in conduction. The hyperadrenergic state of drinking and withdrawal may also contribute, as may electrolyte abnormalities, impaired vagal heart rate control, repolarization abnormalities with prolonged QT intervals and worsening of myocardial ischaemia or sleep apnoea. Most of what we know about alcohol and arrhythmias relates to heavy drinking. The effect of social drinking on clinical arrhythmias in non-alcoholic cardiac patients needs to be addressed further.

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

Science.gov (United States)

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

2016-08-01

Endogenous levels of the neurosteroid (NS) allopregnanolone (AlloP) during neonatal stages are crucial for the correct development of the central nervous system (CNS). In a recent work we reported that the neonatal administration of AlloP or finasteride (Finas), an inhibitor of the enzyme 5α-reductase needed for AlloP synthesis, altered the voluntary consumption of ethanol and the ventrostriatal dopamine (DA) levels in adulthood, suggesting that neonatal NS manipulations can increase alcohol abuse vulnerability in adulthood. Moreover, other authors have associated neonatal NS alterations with diverse dopaminergic (DAergic) alterations. Thus, the aim of the present work is to analyse if manipulations of neonatal AlloP alter the DAergic response in the nucleus accumbens (NAcc) during alcohol intake in rats. We administered AlloP or Finas from postnatal day (PND) 5 to PND9. At PND98, we measured alcohol consumption using a two-bottle free-choice model (ethanol 10% (v/v)+glucose 3% (w/v), and glucose 3% (w/v)) for 12 days. On the last day of consumption, we measured the DA and 3,4-dihydroxyphenylacetic acid (DOPAC) release in NAcc in response to ethanol intake. The samples were obtained by means of in vivo microdialysis in freely moving rats, and DA and DOPAC levels were determined by means of high-performance liquid chromatography analysis (HPLC). The results revealed that neonatal Finas increased ethanol consumption in some days of the consumption phase, and decreased the DA release in the NAcc in response to solutions (ethanol+glucose) and food presentation. Taken together, these results suggest that neonatal NS alterations can affect alcohol rewarding properties. Copyright © 2016 Elsevier B.V. All rights reserved.

The Alcohol Environment Protocol: A new tool for alcohol policy.

Science.gov (United States)

Casswell, Sally; Morojele, Neo; Williams, Petal Petersen; Chaiyasong, Surasak; Gordon, Ross; Gray-Philip, Gaile; Viet Cuong, Pham; MacKintosh, Anne-Marie; Halliday, Sharon; Railton, Renee; Randerson, Steve; Parry, Charles D H

2018-01-04

To report data on the implementation of alcohol policies regarding availability and marketing, and drink driving, along with ratings of enforcement from two small high-income to three high-middle income countries, and one low-middle income country. This study uses the Alcohol Environment Protocol, an International Alcohol Control study research tool, which documents the alcohol policy environment by standardised collection of data from administrative sources, observational studies and interviews with key informants to allow for cross-country comparison and change over time. All countries showed adoption to varying extents of key effective policy approaches outlined in the World Health Organization Global Strategy to Reduce the Harmful Use of Alcohol (2010). High-income countries were more likely to allocate resources to enforcement. However, where enforcement and implementation were high, policy on availability was fairly liberal. Key Informants judged alcohol to be very available in both high- and middle-income countries, reflecting liberal policy in the former and less implementation and enforcement and informal (unlicensed) sale of alcohol in the latter. Marketing was largely unrestricted in all countries and while drink-driving legislation was in place, it was less well enforced in middle-income countries. In countries with fewer resources, alcohol policies are less effective because of lack of implementation and enforcement and, in the case of marketing, lack of regulation. This has implications for the increase in consumption taking place as a result of the expanding distribution and marketing of commercial alcohol and consequent increases in alcohol-related harm. © 2018 The Authors Drug and Alcohol Review published by John Wiley & Sons Australia, Ltd on behalf of Australasian Professional Society on Alcohol and other Drugs.

Alcohol Outcome Expectancies and Drinking to Cope with Social Situations

OpenAIRE

Carrigan, Maureen H.; Ham, Lindsay S.; Thomas, Suzanne E.; Randall, Carrie L.

2008-01-01

Repeated use of alcohol as a coping strategy to reduce anxiety or discomfort increases one's risk of developing alcohol dependence. Previous studies have found alcohol outcome expectancies (AOE) strongly predict drinking behavior, in general, and also are related to drinking to cope. The purpose of the current study was to examine AOE that may be related to drinking to cope with discomfort in social situations. It was hypothesized that positive AOE, especially related to assertion and tension...

27 CFR 4.4 - Delegations of the Administrator.

Science.gov (United States)

2010-04-01

... 27 Alcohol, Tobacco Products and Firearms 1 2010-04-01 2010-04-01 false Delegations of the Administrator. 4.4 Section 4.4 Alcohol, Tobacco Products and Firearms ALCOHOL AND TOBACCO TAX AND TRADE BUREAU, DEPARTMENT OF THE TREASURY LIQUORS LABELING AND ADVERTISING OF WINE Scope § 4.4 Delegations of the...

Interaction between repeated restraint stress and concomitant midazolam administration on sweet food ingestion in rats

Directory of Open Access Journals (Sweden)

Silveira P.P.

2000-01-01

Full Text Available Emotional changes can influence feeding behavior. Previous studies have shown that chronically stressed animals present increased ingestion of sweet food, an effect reversed by a single dose of diazepam administered before testing the animals. The aim of the present study was to evaluate the response of animals chronically treated with midazolam and/or submitted to repeated restraint stress upon the ingestion of sweet food. Male adult Wistar rats were divided into two groups: controls and exposed to restraint 1 h/day, 5 days/week for 40 days. Both groups were subdivided into two other groups treated or not with midazolam (0.06 mg/ml in their drinking water during the 40-day treatment. The animals were placed in a lighted area in the presence of 10 pellets of sweet food (Froot loops®. The number of ingested pellets was measured during a period of 3 min, in the presence or absence of fasting. The group chronically treated with midazolam alone presented increased ingestion when compared to control animals (control group: 2.0 ± 0.44 pellets and midazolam group: 3.60 ± 0.57 pellets. The group submitted to restraint stress presented an increased ingestion compared to controls (control group: 2.0 ± 0.44 pellets and stressed group: 4.18 ± 0.58 pellets. Chronically administered midazolam reduced the ingestion in stressed animals (stressed/water group: 4.18 ± 0.58 pellets; stressed/midazolam group: 3.2 ± 0.49 pellets. Thus, repeated stress increases appetite for sweet food independently of hunger and chronic administration of midazolam can decrease this behavioral effect.

49 CFR 219.701 - Standards for drug and alcohol testing.

Science.gov (United States)

2010-10-01

... 49 Transportation 4 2010-10-01 2010-10-01 false Standards for drug and alcohol testing. 219.701... ADMINISTRATION, DEPARTMENT OF TRANSPORTATION CONTROL OF ALCOHOL AND DRUG USE Drug and Alcohol Testing Procedures § 219.701 Standards for drug and alcohol testing. (a) Drug testing required or authorized by subparts B...

Genes and Alcohol Consumption: Studies with Mutant Mice

Science.gov (United States)

Mayfield, Jody; Arends, Michael A.; Harris, R. Adron; Blednov, Yuri A.

2017-01-01

In this chapter, we review the effects of global null mutant and overexpressing transgenic mouse lines on voluntary self-administration of alcohol. We examine approximately 200 publications pertaining to the effects of 155 mouse genes on alcohol consumption in different drinking models. The targeted genes vary in function and include neurotransmitter, ion channel, neuroimmune, and neuropeptide signaling systems. The alcohol self-administration models include operant conditioning, two- and four-bottle choice continuous and intermittent access, drinking in the dark limited access, chronic intermittent ethanol, and scheduled high alcohol consumption tests. Comparisons of different drinking models using the same mutant mice are potentially the most informative, and we will highlight those examples. More mutants have been tested for continuous two-bottle choice consumption than any other test; of the 137 mouse genes examined using this model, 97 (72%) altered drinking in at least one sex. Overall, the effects of genetic manipulations on alcohol drinking often depend on the sex of the mice, alcohol concentration and time of access, genetic background, as well as the drinking test. PMID:27055617

Stress history increases alcohol intake in relapse: relation to phosphodiesterase 10A.

Science.gov (United States)

Logrip, Marian L; Zorrilla, Eric P

2012-09-01

Stressful experiences can result in elevated alcohol drinking, as exemplified in many individuals with post-traumatic stress disorder. However, how stress history, rather than acute stressors, influences alcohol intake remains uncertain. To model the protracted effects of past stress, male Wistar rats were subjected to light-cued footshock (stress history) or light cues alone (control) prior to acquisition of alcohol self-administration (1-hour sessions, fixed ratio 1-3, 100 µl of 10% v/v alcohol as reinforcer). Stress history did not alter mean alcohol intake during acquisition of self-administration, but it increased preference for the alcohol-paired lever over the inactive lever. Following an extinction period, rats with a history of stress exposure and low baseline alcohol intake showed a twofold elevation in alcohol self-administration, as compared with low-drinking rats with no stress history. Similar effects were not seen in rats self-administering 0.1% sucrose. Analysis of mRNA levels of phosphodiesterase 10A (PDE10A), a dual-specificity cyclic adenosine monophosphate and cyclic guanosine monophosphate hydrolyzing enzyme, showed that stress history increased Pde10a mRNA levels in the basolateral amygdala and, in low-drinking rats, the prelimbic prefrontal cortex (plPFC). Pde10a mRNA levels in the plPFC correlated directly with greater alcohol self-administration during the relapse-like phase, and greater BLA Pde10a mRNA levels correlated with increased ethanol preference after acquisition. The data demonstrate that stress history sensitizes otherwise low alcohol drinkers to consume more alcohol in a relapse-like situation and identify stress-induced neuroadaptations in amygdala and prefrontal cortical Pde10a expression as changes that may drive heightened alcohol intake and preference in susceptible individuals. © 2012 The Authors. Addiction Biology © 2012 Society for the Study of Addiction.

Alcohol and the risk of myocardial infarction.

Science.gov (United States)

Flesch, M; Rosenkranz, S; Erdmann, E; Böhm, M

2001-04-01

Epidemiological studies have repeatedly demonstrated a beneficial effect of moderate alcohol consumption on the incidence of coronary heart disease, myocardial infarction and overall mortality. The latter increases with excessive alcohol consumption. Although most epidemiological studies demonstrate a beneficial effect of alcohol consumption independent from the specific kind of alcoholic beverage, there is increasing evidence that wine and in particular red wine might contain pharmacological substances, which prevent atherosclerosis and myocardial infarction independent from the wine ethanol. Pathophysiological mechanisms mediating these beneficial effects include effects of wine phenols and tannins on LDL-cholesterol oxidation status, thrombocyte aggregation, endothelial function and smooth muscle cell proliferation. Identification and characterization of the pharmacologically active substances might provide the stage for the development of new substances to be used in the prevention of coronary artery disease and myocardial infarction.

Efficacy of intrahepatic absolute alcohol in unrespectable hepatocellular carcinoma

International Nuclear Information System (INIS)

Farooqi, J.I.; Hameed, K.; Khan, I.U.; Shah, S.

2001-01-01

To determine efficacy of intrahepatic absolute alcohol injection in researchable hepatocellular carcinoma. A randomized, controlled, experimental and interventional clinical trial. Gastroenterology Department, PGMI, Hayatabad Medical Complex, Peshawar during the period from June, 1998 to June, 2000. Thirty patients were treated by percutaneous, intrahepatic absolute alcohol injection sin repeated sessions, 33 patients were not given or treated with alcohol to serve as control. Both the groups were comparable for age, sex and other baseline characteristics. Absolute alcohol therapy significantly improved quality of life of patients, reduced the tumor size and mortality as well as showed significantly better results regarding survival (P< 0.05) than the patients of control group. We conclude that absolute alcohol is a beneficial and safe palliative treatment measure in advanced hepatocellular carcinoma (HCC). (author)

Lipid metabolism abnormalities in alcohol-treated rabbits: a morphometric and haematologic study comparing high and low alcohol doses.

Science.gov (United States)

Ikemura, Satoshi; Yamamoto, Takuaki; Motomura, Goro; Iwasaki, Kenyu; Yamaguchi, Ryosuke; Zhao, Garida; Iwamoto, Yukihide

2011-08-01

The pathogenesis of alcohol-induced osteonecrosis remains unclear. The purpose of the present study was to evaluate the morphological changes in bone marrow fat cells and the changes in the serum lipid levels in alcohol-treated rabbits. Fifteen rabbits were randomly assigned into three groups: Four rabbits intragastrically received low-dose alcohol (LDA) (15 ml/kg per day) containing 15% ethanol for 4 weeks, five rabbits received high-dose alcohol (HDA) (30 ml/kg per day) for 4 weeks and six rabbits received physiologic saline for 4 weeks as a control group. Six weeks after the initial alcohol administration, all rabbits were sacrificed. The mean size of the bone marrow fat cells in rabbits treated with HDA was significantly larger than that in the control group (P = 0.0001). Haematologically, the levels of triglycerides and free fatty acids in the rabbits treated with both low-dose and HDA were significantly higher than those in the control group (P = 0.001 for both comparisons). The results of this study are that there are lipid metabolism abnormalities, both morphologically and haematologically, after alcohol administration. Also these findings were more apparent in rabbits treated with HDA than those treated with LDA. © 2011 The Authors. International Journal of Experimental Pathology © 2011 International Journal of Experimental Pathology.

Fragrance material review on benzyl alcohol.

Science.gov (United States)

Scognamiglio, J; Jones, L; Vitale, D; Letizia, C S; Api, A M

2012-09-01

A toxicologic and dermatologic review of benzyl alcohol when used as a fragrance ingredient is presented. Benzyl alcohol is a member of the fragrance structural group Aryl Alkyl Alcohols and is a primary alcohol. The AAAs are a structurally diverse class of fragrance ingredients that includes primary, secondary, and tertiary alkyl alcohols covalently bonded to an aryl (Ar) group, which may be either a substituted or unsubstituted benzene ring. The common structural element for the AAA fragrance ingredients is an alcohol group -C-(R1)(R2)OH and generically the AAA fragrances can be represented as an Ar-C-(R1)(R2)OH or Ar-Alkyl-C-(R1)(R2)OH group. This review contains a detailed summary of all available toxicology and dermatology papers related to this individual fragrance ingredient and is not intended as a stand-alone document. Available data for benzyl alcohol were evaluated then summarized and includes physical properties, acute toxicity, skin irritation, mucous membrane (eye) irritation, skin sensitization, elicitation, phototoxicity, photoallergy, toxicokinetics, repeated dose, reproductive toxicity, genotoxicity, and carcinogenicity data. A safety assessment of the entire Aryl Alkyl Alcohols will be published simultaneously with this document; please refer to Belsito et al. (2012) for an overall assessment of the safe use of this material and all Aryl Alkyl Alcohols in fragrances. Copyright © 2011 Elsevier Ltd. All rights reserved.

Effects of dexamphetamine with and without alcohol on simulated driving

NARCIS (Netherlands)

Simons, M.; Martens, M.H.; Ramaekers, J.; Krul, A.; Klöpping-Ketelaars, I.; Skopp, G.

2012-01-01

Rationale In party circuits dexamphetamine is frequently used in combination with alcohol. It is hypothesized that co-administration of dexamphetamine to alcohol might reduce the sedative effects of alcohol, but may potentiate risk-taking behaviour. Objectives The study was aimed at assessing the

Effects of dexamphetamine with and without alcohol on simulated driving

NARCIS (Netherlands)

Simons, R.; Martens, Marieke Hendrikje; Ramaekers, J.; Krul, A.; Klöpping-Ketelaars, I.; Skopp, G.

2012-01-01

Rationale: In party circuits dexamphetamine is frequently used in combination with alcohol. It is hypothesized that co-administration of dexamphetamine to alcohol might reduce the sedative effects of alcohol, but may potentiate risk-taking behaviour. Objectives: The study was aimed at assessing the

Drug and alcohol testing results 2009 annual report

Science.gov (United States)

2013-11-01

This is the 15th annual report of the results of the Federal Transit Administrations (FTA) Drug and Alcohol Testing Program. This report summarizes the reporting requirements for calendar year 2009, the requirements of the overall drug and alcohol...

Drug and alcohol testing results 2007 annual report

Science.gov (United States)

2009-05-01

This is the 13th annual report of the results of the Federal Transit Administrations (FTA) Drug and Alcohol Testing Program. This report summarizes the reporting requirements for calendar year 2007, the requirements of the overall drug and alcohol...

College Alcohol Policy and Student Drinking-while-Driving: A Multilevel Model

Science.gov (United States)

Liu, Jing

2012-01-01

Alcohol prohibition and legal or administrative sanctions have been implemented in attempts to curb alcohol drinking and drinking-while-driving in the general population as well as among college students. This dissertation study examines the impact of college alcohol prohibition and policy enforcement on students' alcohol drinking and…

Childhood experiences and repeated suicidal behavior

DEFF Research Database (Denmark)

Krarup, Gertrud; Nielsen, Bent; Rask, P

1991-01-01

The aim of this study was to elucidate the influence of various events in childhood on suicidal behavior in adult age. For this purpose, 99 patients admitted to the Department of Psychiatry of Odense University Hospital after making a suicide attempt were followed for 5 years, to register repeated...... that the psychological climate of the home may be more important than the rupture of early home life. It is noteworthy that the group of repeaters, as against the first-evers, could be characterized by personality disorders and abuse, especially of alcohol: disorders known to be precipitated by a discordant childhood....... It is commonly agreed that the experience in childhood of suicidal behavior among family members or other persons in the close environment is of importance in future suicidal risk. The results of this study indicate that the predictive value of this factor mainly applies to attempts with no fatal outcome...

31 CFR 8.62 - Administrative Law Judge.

Science.gov (United States)

2010-07-01

... 31 Money and Finance: Treasury 1 2010-07-01 2010-07-01 false Administrative Law Judge. 8.62... BUREAU OF ALCOHOL, TOBACCO AND FIREARMS Disciplinary Proceedings § 8.62 Administrative Law Judge. (a) Appointment. An Administrative Law Judge, appointed as provided by 5 U.S.C. 3105, shall conduct proceedings...

Drug and alcohol testing results 2006 annual report.

Science.gov (United States)

2008-08-01

This is the 12th annual report of the results of the Federal Transit Administration's (FTA) Drug and Alcohol Testing Program. This report summarizes the reporting requirements for calendar year 2006, the requirements of the overall drug and alcohol t...

Alcohol intake, wine consumption and the development of depression: the PREDIMED study

Science.gov (United States)

2013-01-01

Background Alcoholic beverages are widely consumed. Depression, the most prevalent mental disorder worldwide, has been related to alcohol intake. We aimed to prospectively assess the association between alcohol intake and incident depression using repeated measurements of alcohol intake. Methods We followed-up 5,505 high-risk men and women (55 to 80 y) of the PREDIMED Trial for up to seven years. Participants were initially free of depression or a history of depression, and did not have any history of alcohol-related problems. A 137-item validated food frequency questionnaire administered by a dietician was repeated annually to assess alcohol intake. Participants were classified as incident cases of depression when they reported a new clinical diagnosis of depression, and/or initiated the use of antidepressant drugs. Cox regression analyses were fitted over 23,655 person-years. Results Moderate alcohol intake within the range of 5 to 15 g/day was significantly associated with lower risk of incident depression (hazard ratio (HR) and 95% confidence interval (95% CI) = 0.72 (0.53 to 0.98) versus abstainers). Specifically, wine consumption in the range of two to seven drinks/week was significantly associated with lower rates of depression (HR (95% CI) = 0.68 (0.47 to 0.98)). Conclusions Moderate consumption of wine may reduce the incidence of depression, while heavy drinkers seem to be at higher risk. PMID:23988010

The effect of prior alcohol consumption on the ataxic response to alcohol in high-alcohol preferring mice.

Science.gov (United States)

Fritz, Brandon M; Boehm, Stephen L

2014-12-01

We have previously shown that ethanol-naïve high-alcohol preferring (HAP) mice, genetically predisposed to consume large quantities of alcohol, exhibited heightened sensitivity and more rapid acute functional tolerance (AFT) to alcohol-induced ataxia compared to low-alcohol preferring mice. The goal of the present study was to evaluate the effect of prior alcohol self-administration on these responses in HAP mice. Naïve male and female adult HAP mice from the second replicate of selection (HAP2) underwent 18 days of 24-h, 2-bottle choice drinking for 10% ethanol vs. water, or water only. After 18 days of fluid access, mice were tested for ataxic sensitivity and rapid AFT following a 1.75 g/kg injection of ethanol on a static dowel apparatus in Experiment 1. In Experiment 2, a separate group of mice was tested for more protracted AFT development using a dual-injection approach where a second, larger (2.0 g/kg) injection of ethanol was given following the initial recovery of performance on the task. HAP2 mice that had prior access to alcohol exhibited a blunted ataxic response to the acute alcohol challenge, but this pre-exposure did not alter rapid within-session AFT capacity in Experiment 1 or more protracted AFT capacity in Experiment 2. These findings suggest that the typically observed increase in alcohol consumption in these mice may be influenced by ataxic functional tolerance development, but is not mediated by a greater capacity for ethanol exposure to positively influence within-session ataxic tolerance. Copyright © 2014 Elsevier Inc. All rights reserved.

[Development of a prediabetic state under chronic alcohol intoxication].

Science.gov (United States)

Voĭtenko, V V; Konopel'niuk, V V; Savchuk, O M; Ostapchenko, L I

2013-01-01

We investigated the changes in key parameters of carbohydrate and lipid metabolism, which correspond to the clinical picture that accompanies the development of prediabetic condition on the background of chronic alcohol intoxication. From the analysis of glycemic curves obtained during the insulin-glucose test, a speed of glucose uptake by peripheral tissues increased at the 1st day (1.5 fold) and the third day (1.3 fold) of administration of alcohol solution. At the later periods, at 7 and 11 days of ethanol administration, a decreased rate of glucose uptake in animals with chronic alcohol intoxication was detected. We also detected an increased content of serotonin in the blood serum and a decreased (1.2 fold) serotonin content in rat brain during the whole period of development of chronic alcohol intoxication.

Oral repeated-dose systemic and reproductive toxicity of 6:2 fluorotelomer alcohol in mice

Directory of Open Access Journals (Sweden)

Pushkor Mukerji

2015-01-01

Full Text Available 6:2 fluorotelomer alcohol (6:2 FTOH was evaluated for potential systemic repeated-dose and reproductive toxicity in mice. 6:2 FTOH was administered by oral gavage to CD-1 mice as a suspension in 0.5% aqueous methylcellulose with 0.1% Tween-80 at dosages of 1, 5, 25, or 100 mg/kg/day. The no-observed-adverse-effect level (NOAEL for systemic toxicity was 25 mg/kg/day (males and 5 mg/kg/day (females, based on effects at higher doses on mortality, clinical observations, body weight, nutritional parameters, hematology (red and white blood cell, clinical chemistry (liver-related, liver weights, and histopathology (liver, teeth, reproductive tract, and mammary gland. However, 6:2 FTOH was not a selective reproductive toxicant. The NOAEL for reproductive toxicity was >100 mg/kg/day; no effects on reproductive outcome were observed at any dosage. The NOAEL for viability and growth of the offspring was 25 mg/kg/day, based on clinical signs of delayed maturation in pups, and reductions in pup survival and pup body weight during lactation at 100 mg/kg/day. While the severity of the effects was generally greater in mice than previously reported in CD rats, the overall NOAELs were identical in both species, 5 mg/kg/day for systemic toxicity and 25 mg/kg/day for offspring viability/growth. 6:2 FTOH was not a selective reproductive toxicant in either species; no effects on reproductive outcome occurred at any dose level, and any effects observed in offspring occurred at dose levels that induced mortality and severe toxicity in maternal animals.

Acute alcohol effects on explicit and implicit motivation to drink alcohol in socially drinking adolescents.

Science.gov (United States)

Jünger, Elisabeth; Javadi, Amir-Homayoun; Wiers, Corinde E; Sommer, Christian; Garbusow, Maria; Bernhardt, Nadine; Kuitunen-Paul, Sören; Smolka, Michael N; Zimmermann, Ulrich S

2017-07-01

Alcohol-related cues can evoke explicit and implicit motivation to drink alcohol. Concerning the links between explicit and implicit motivation, there are mixed findings. Therefore, we investigated both concepts in 51 healthy 18- to 19-year-old males, who are less affected by neuropsychological deficits in decision-making that are attributed to previous alcohol exposure than older participants. In a randomized crossover design, adolescents were infused with either alcohol or placebo. Self-ratings of alcohol desire, thirst, well-being and alcohol effects comprised our explicit measures of motivation. To measure implicit motivation, we used money and drink stimuli in a Pavlovian conditioning (Pc) task and an Approach-Avoidance Task (AAT). Alcohol administration increased explicit motivation to drink alcohol, reduced Pc choices of alcoholic drink-conditioned stimuli, but had no effect on the AAT. This combination of results might be explained by differences between goal-directed and habitual behavior or a temporary reduction in rewarding outcome expectancies. Further, there was no association between our measures of motivation to drink alcohol, indicating that both self-reported motivation to drink and implicit approach tendencies may independently contribute to adolescents' actual alcohol intake. Correlations between Alcohol Use Disorders Identification Test (AUDIT) scores and our measures of motivation to drink alcohol suggest that interventions should target high-risk adolescents after alcohol intake. Clinical trials: Project 4: Acute Effects of Alcohol on Learning and Habitization in Healthy Young Adults (LeAD_P4); NCT01858818; https://clinicaltrials.gov/ct2/show/NCT01858818.

21 CFR 173.250 - Methyl alcohol residues.

Science.gov (United States)

2010-04-01

... 21 Food and Drugs 3 2010-04-01 2009-04-01 true Methyl alcohol residues. 173.250 Section 173.250 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) FOOD.... Methyl alcohol may be present in the following foods under the conditions specified: (a) In spice...

Immunological changes in the intestines and skin after senna administration.

Science.gov (United States)

Yamate, Yurika; Hiramoto, Keiichi; Yokoyama, Satoshi; Ooi, Kazuya

2015-06-01

It has been reported that chronic sennoside use is associated with the development of melanosis coli, colonic adenoma, and/or carcinomas. In this study, we investigated the immunological changes in the colon and skin after the administration of senna. In this study, we investigated the colon and epidermis of C57/BL6j mice after a single administration of 10 mg/kg of senna [Cassia angustifolia (Caesalpiniaceae); 3, 6, 12, and 24 h after administration] and after repeated once per week administrations (on days 3, 5, 7, 14, and 21 of administration). The LD50 and ED50 of senna used in this experiment were 165 mg/kg and 13 g/kg, respectively. We demonstrated that the DOPA-positive cells in the colon increased at 12 h after single administration and were further increased from at 5-28 d after repeated administration. We also studied the physiological changes of the small intestine using the charcoal meal test. We found that there was a tendency for peristalsis to be inhibited after repeated senna administration. In the epidermis, we investigated the number of Langerhans cells, because they are important immune cells of the skin. The number of these cells decreased, especially after repeated administration. The present findings suggested that it is necessary to pay attention to not only the intestine but also the skin, during long-term senna treatment.

Final report of the safety assessment of Alcohol Denat., including SD Alcohol 3-A, SD Alcohol 30, SD Alcohol 39, SD Alcohol 39-B, SD Alcohol 39-C, SD Alcohol 40, SD Alcohol 40-B, and SD Alcohol 40-C, and the denaturants, Quassin, Brucine Sulfate/Brucine, and Denatonium Benzoate.

Science.gov (United States)

2008-01-01

animals that died, respiratory arrest was the cause. The acute i.p. LD(50) for 15 ml/kg of Brucine base was 62.0 mg/kg, with central nervous system depression prior to the onset of convulsions, just as with oral Brucine. The acute intravenous (i.v.) LD(50) was 12.0 mg/kg. Brucine was nonmutagenic in an Ames assay at levels up to 6666 mu g/plate, with and without metabolic activation. In a repeat-insult patch test, for a hair care product containing 47% SD Alcohol 40 (95%), it was reported that Brucine Sulfate may be considered a nonprimary irritant and a nonprimary sensitizer. Three different sunscreen products (35% SD Alcohol 40-B, 72.4% SD Alcohol 40, and 74.5% SD Alcohol 40) did not show any signs of photoallergy in human subjects. Also, these three formulas did not exhibit any evidence of phototoxicity in humans. Denatonium Benzoate is a bitter substance detectable at a concentration of 10 ppb, discernibly bitter at 50 ppb, and unpleasantly bitter at 10 ppm. The distribution of topically applied lidocaine, a topical anesthetic chemically related to Denatonium Benzoate demonstrated that virtually no lidocaine appears in the plasma, suggesting that the larger Denatonium Benzoate molecule also would have little or no systemic exposure. Denatonium Benzoate (0.1%) did not show adverse effects in 10 rats in an acute inhalation toxicity test and 0.005% to 0.05% was nonirritating to ocular mucosa in 6 albino rabbits. The acute oral LD(50) for the male rats was 640 mg/kg and for females, 584 mg/kg. The LD(50) for the male rabbits was 508 mg/kg and for the female rabbits, 640 mg/kg. In two chronic toxicity studies, Denatonium Benzoate was administered (by gavage) at 1.6, 8, and 16 mg/kg/day, one using cynomologus monkeys and the other rats, resulted in no compound-related toxicity. The toxicity of SD Alcohols has also been tested, with implications for the particular denaturant used. An irritation test of 55.65% SD Alcohol 40-B denatured with Denatonium Benzoate using rabbits

Alcohol Use During Pregnancy or Breastfeeding: A National Survey in France.

Science.gov (United States)

Dumas, Agnès; Toutain, Stéphanie; Simmat-Durand, Laurence

2017-07-01

Adverse effects are associated with alcohol drinking during pregnancy and breastfeeding. Data are lacking on the size of the population at risk and on the characteristics of women engaging in risky behaviors such as daily consumption or repeated binge drinking. A cross-sectional survey was carried out by telephone among a nationally representative sample of pregnant and postpartum women. Frequency of alcohol use and binge drinking was retrospectively measured according to distinct time periods. Multivariable regression models were used to identify the characteristics of women reporting risk-taking behaviors. A total of 3,603 women participated. Daily consumption was reported by 0.1% of pregnant women and by 0.4% of breastfeeding women. In early pregnancy, 8.0% of women reported binge drinking (≥1 episode) and 1.2% reported repeated binge drinking (≥3 episodes). Binge drinking was estimated at 1.1% in late pregnancy and at 6.8% during breastfeeding. Characteristics of drinkers varied across these different drinking patterns and subpopulations. Moderate drinking during pregnancy and breastfeeding was associated with higher educational level. Smoking increased with increased frequency of alcohol use. Repeated binge drinking in early pregnancy was associated with late recognition of the pregnancy, while binge drinking in late pregnancy was associated with smoking. Daily alcohol use during pregnancy or breastfeeding was limited, while binge drinking in early pregnancy was reported by a large proportion of women. Demographic and socioeconomic characteristics of drinkers varied across drinking patterns.

Risk of sensitization in healthy adults following repeated administration of rdESAT-6 skin test reagent by the Mantoux injection technique

DEFF Research Database (Denmark)

Lillebaek, Troels; Bergstedt, Winnie; Tingskov, Pernille N

2009-01-01

1 open clinical trial was to assess the sensitization risk and safety of repeated administration of rdESAT-6 reagent in 31 healthy adult volunteers. Three groups of volunteers received two fixed doses of 0.1 microg rdESAT-6 28, 56 or 112 days apart, respectively. After the second injection...... of 31 (3%) volunteers showed a positive skin reaction (sensitization) upon a second injection of rdESAT-6 after 28days and an increased IFN-gamma response to ESAT-6. For 7 (23%) of the volunteers, local adverse reactions related to the product were registered, but all reactions were mild and predictable...

The Leu72Met Polymorphism of the Prepro-ghrelin Gene is Associated With Alcohol Consumption and Subjective Responses to Alcohol: Preliminary Findings.

Science.gov (United States)

Suchankova, Petra; Yan, Jia; Schwandt, Melanie L; Stangl, Bethany L; Jerlhag, Elisabet; Engel, Jörgen A; Hodgkinson, Colin A; Ramchandani, Vijay A; Leggio, Lorenzo

2017-07-01

The orexigenic peptide ghrelin may enhance the incentive value of food-, drug- and alcohol-related rewards. Consistent with preclinical findings, human studies indicate a role of ghrelin in alcohol use disorders (AUD). In the present study an a priori hypothesis-driven analysis was conducted to investigate whether a Leu72Met missense polymorphism (rs696217) in the prepro-ghrelin gene (GHRL), is associated with AUD, alcohol consumption and subjective responses to alcohol. Association analysis was performed using the National Institute on Alcohol Abuse and Alcoholism (NIAAA) clinical sample, comprising AUD individuals and controls (N = 1127). Then, a post-hoc analysis using data from a human laboratory study of intravenous alcohol self-administration (IV-ASA, N = 144) was performed to investigate the association of this SNP with subjective responses following a fixed dose of alcohol (priming phase) and alcohol self-administration (ad libitum phase). The case-control study revealed a trend association (N = 1127, OR = 0.665, CI = 0.44-1.01, P = 0.056) between AUD diagnosis and Leu72Met. In AUD subjects, the SNP was associated with significantly lower average drinks per day (n = 567, β = -2.49, 95% CI = -4.34 to -0.64, P = 0.008) and significantly fewer heavy drinking days (n = 567, β = -12.00, 95% CI = -19.10 to -4.89, P polymorphism in the prepro-ghrelin gene, is associated with alcohol use disorder, alcohol consumption and subjective responses to alcohol. Although preliminary, results suggest that the Leu72Leu genotype may lead to increased risk of alcohol use disorder possibly via mechanisms involving a lower response to alcohol. Medical Council on Alcohol and Oxford University Press 2017. This work is written by (a) US Government employee(s) and is in the public domain in the US.

The influence of age and repeated LPS administration on body temperature and the relation with interleukin-6 and IgM antibodies in broiler chickens

OpenAIRE

De Boever , Sandra; Beyaert , Rudi; Vandemaele , Fréderic; Baert , Kris; Duchateau , Luc; Goddeeris , Bruno; De Backer , Patrick; Croubels , Siska

2008-01-01

Abstract Our objective was to create a standardized and reproducible inflammation model in chickens in order to study the pharmacodynamics of several anti-pyretic and anti-inflammatory drugs. We studied the influence of age and repeated lipopolysaccharide (LPS) administration on body temperature and the correlation of this with concentrations of interleukin 6 (IL-6) and IgM antibodies against LPS in plasma of chickens. Three and five week old broilers were injected intravenously...

Effects of catecholamine agonists and antagonists on alcohol uptake in rats with different stages of experimental alcoholism

Energy Technology Data Exchange (ETDEWEB)

Burov, Yu V; Varov, A I

1985-02-01

The effects of various catecholamine agonists and antagonists on 15% ethanol ingestion by outbred albino rats were studied in relation to the stage of experimental alcoholism. In animals with stage I and II alcoholism, alcohol intake was most profoundly inhibited by administration of alpha-adrenoblockers (AA), klofelin, and alpha-methyl-DOPA (AMD), while L-DOPA and cocaine stimulated a significant increase in ethanol ingestion. In stage III alcoholism, both AA and L-DOPA depressed alcohol intake, while AMD and haloperidol had a stimulatory effect. It appears, therefore, that different neurochemical mechanisms are involved in alcohol dependence in different stages of experimental alcoholism in the rat. Furthermore, it seems evident that alpha-adrenergic receptors have a key function in maintaining alcohol dependence. In well-established physical dependence, the importance of the noradrenergic system seems to diminish and dopaminergic mechanisms appear to become predominant. Consequently, in the initial stages of alcoholism, agents which depress the noradrenergic system seem indicated, while at the stage of physical dependence agents which normalize noradrenergic mechanisms and depress dopaminergic mechanisms should be considered. 13 references.

Fragrance material review on α-methylbenzyl alcohol.

Science.gov (United States)

Scognamiglio, J; Jones, L; Letizia, C S; Api, A M

2012-09-01

A toxicologic and dermatologic review of α-methylbenzyl alcohol when used as a fragrance ingredient is presented. α-Methylbenzyl alcohol is a member of the fragrance structural group Aryl Alkyl Alcohols and is a secondary alcohol. The AAAs are a structurally diverse class of fragrance ingredients that includes primary, secondary, and tertiary alkyl alcohols covalently bonded to an aryl (Ar) group, which may be either a substituted or unsubstituted benzene ring. The common structural element for the AAA fragrance ingredients is an alcohol group -C-(R1)(R2)OH and generically the AAA fragrances can be represented as an Ar-C-(R1)(R2)OH or Ar-Alkyl-C-(R1)(R2)OH group. This review contains a detailed summary of all available toxicology and dermatology papers that are related to this individual fragrance ingredient and is not intended as a stand-alone document. Available data for α-methylbenzyl alcohol were evaluated then summarized and includes physical properties, acute toxicity, skin irritation, mucous membrane (eye) irritation, skin sensitization, toxicokinetics, repeated dose, genotoxicity, and carcinogenicity data. A safety assessment of the entire Aryl Alkyl Alcohols will be published simultaneously with this document; please refer to Belsito et al. (2012) for an overall assessment of the safe use of this material and all Aryl Alkyl Alcohols in fragrances. Copyright © 2011 Elsevier Ltd. All rights reserved.

Fragrance material review on α-isobutylphenethyl alcohol.

Science.gov (United States)

Scognamiglio, J; Jones, L; Letizia, C S; Api, A M

2012-09-01

A toxicologic and dermatologic review of α-isobutylphenethyl alcohol when used as a fragrance ingredient is presented. α-Isobutylphenethyl alcohol is a member of the fragrance structural group Aryl Alkyl Alcohols and is a secondary alcohol. The AAAs are a structurally diverse class of fragrance ingredients that includes primary, secondary, and tertiary alkyl alcohols covalently bonded to an aryl (Ar) group, which may be either a substituted or unsubstituted benzene ring. The common structural element for the AAA fragrance ingredients is an alcohol group -C-(R1)(R2)OH and generically the AAA fragrances can be represented as an Ar-C-(R1)(R2)OH or Ar-Alkyl-C-(R1)(R2)OH group. This review contains a detailed summary of all available toxicology and dermatology papers that are related to this individual fragrance ingredient and is not intended as a stand-alone document. Available data for α-isobutylphenethyl alcohol were evaluated then summarized and includes physical properties, skin sensitization, and repeated dose data. A safety assessment of the entire Aryl Alkyl Alcohols will be published simultaneously with this document; please refer to Belsito et al. (2012) for an overall assessment of the safe use of this material and all Aryl Alkyl Alcohols in fragrances. Copyright © 2011 Elsevier Ltd. All rights reserved.

The role of neuroimmune signaling in alcoholism.

Science.gov (United States)

Crews, Fulton T; Lawrimore, Colleen J; Walter, T Jordan; Coleman, Leon G

2017-08-01

Alcohol consumption and stress increase brain levels of known innate immune signaling molecules. Microglia, the innate immune cells of the brain, and neurons respond to alcohol, signaling through Toll-like receptors (TLRs), high-mobility group box 1 (HMGB1), miRNAs, pro-inflammatory cytokines and their associated receptors involved in signaling between microglia, other glia and neurons. Repeated cycles of alcohol and stress cause a progressive, persistent induction of HMGB1, miRNA and TLR receptors in brain that appear to underlie the progressive and persistent loss of behavioral control, increased impulsivity and anxiety, as well as craving, coupled with increasing ventral striatal responses that promote reward seeking behavior and increase risk of developing alcohol use disorders. Studies employing anti-oxidant, anti-inflammatory, anti-depressant, and innate immune antagonists further link innate immune gene expression to addiction-like behaviors. Innate immune molecules are novel targets for addiction and affective disorders therapies. This article is part of the Special Issue entitled "Alcoholism". Copyright © 2017 Elsevier Ltd. All rights reserved.

Effects of dexamphetamine with and without alcohol on simulated driving.

Science.gov (United States)

Simons, Ries; Martens, Marieke; Ramaekers, Jan; Krul, Arno; Klöpping-Ketelaars, Ineke; Skopp, Gisela

2012-08-01

In party circuits dexamphetamine is frequently used in combination with alcohol. It is hypothesized that co-administration of dexamphetamine to alcohol might reduce the sedative effects of alcohol, but may potentiate risk-taking behaviour. The study was aimed at assessing the effects of alcohol, dexamphetamine and the combination of both on simulated driving and cognitive performance. Eighteen subjects participated in a randomized, crossover, placebo-controlled study employing four conditions: 10 mg dexamphetamine, 0.8 g/kg alcohol, 10 mg dexamphetamine + 0.8 g/kg alcohol, and placebo. Fundamental driving skills and risk-taking behaviour were assessed in a driving simulator. Subjects also completed vigilance and divided attention tasks, and subjective ratings. Mean BAC levels during simulated driving were between 0.91‰ and 0.64‰. Subjects using alcohol showed a significantly larger mean standard deviation of lateral position and shorter accepted gap time and distance. Use of alcohol or dexamphetamine + alcohol was associated with a higher frequency of red light running and collisions than the dexamphetamine or placebo conditions. Performance of vigilance and divided attention tasks was significantly impaired in the alcohol condition and, to a lesser degree, in the dexamphetamine + alcohol condition. Single doses of 0.8 g/kg alcohol increased risk-taking behaviours and impaired tracking, attention and reaction time during a 3-h period after drinking when BACs declined from 0.9 to 0.2 mg/ml. The stimulatory effects of co-administration of dexamphetamine 10 mg were not sufficient to overcome the impairing effects of alcohol on skills related to driving.

Altered performance in a rat gambling task after acute and repeated alcohol exposure

NARCIS (Netherlands)

Spoelder, Marcia; Lesscher, Heidi M B; Hesseling, Peter; Baars, Annemarie M; Lozeman-van T Klooster, José G; Mijnsbergen, Rob; Vanderschuren, Louk J M J

2015-01-01

RATIONALE: A bidirectional relationship between alcohol use disorder (AUD) and deficits in impulse control and decision making has been suggested. However, the mechanisms by which neurocognitive impairments predispose to, or result from AUD remain incompletely understood. OBJECTIVES: The aim of this

Repeated exposure of adult rats to transient oxidative stress induces various long-lasting alterations in cognitive and behavioral functions.

Directory of Open Access Journals (Sweden)

Yoshio Iguchi

Full Text Available Exposure of neonates to oxidative stress may increase the risk of psychiatric disorders such as schizophrenia in adulthood. However, the effects of moderate oxidative stress on the adult brain are not completely understood. To address this issue, we systemically administrated 2-cyclohexen-1-one (CHX to adult rats to transiently reduce glutathione levels. Repeated administration of CHX did not affect the acquisition or motivation of an appetitive instrumental behavior (lever pressing rewarded by a food outcome under a progressive ratio schedule. In addition, response discrimination and reversal learning were not affected. However, acute CHX administration blunted the sensitivity of the instrumental performance to outcome devaluation, and this effect was prolonged in rats with a history of repeated CHX exposure, representing pro-depression-like phenotypes. On the other hand, repeated CHX administration reduced immobility in forced swimming tests and blunted acute cocaine-induced behaviors, implicating antidepressant-like effects. Multivariate analyses segregated a characteristic group of behavioral variables influenced by repeated CHX administration. Taken together, these findings suggest that repeated administration of CHX to adult rats did not cause a specific mental disorder, but it induced long-term alterations in behavioral and cognitive functions, possibly related to specific neural correlates.

Sigma-1 Receptor Mediates Acquisition of Alcohol Drinking and Seeking behavior in Alcohol-Preferring Rats

Science.gov (United States)

Blasio, Angelo; Valenza, Marta; Iyer, Malliga R.; Rice, Kenner C.; Steardo, Luca; Hayashi, T.; Cottone, Pietro; Sabino, Valentina

2015-01-01

Sigma-1 receptor (Sig-1R) has been proposed as a novel therapeutic target for drug and alcohol addiction. We have shown previously that Sig-1R agonists facilitate the reinforcing effects of ethanol and induce binge-like drinking, while Sig-1R antagonists block excessive drinking in both genetic and environmental models of alcoholism, without affecting intake in outbred non-dependent rats. Even though significant progress has been made in understanding the function of Sig-1Rs in alcohol reinforcement, its role in the early and late stage of alcohol addiction remains unclear. Administration of the selective Sig-1R antagonist BD-1063 dramatically reduced the acquisition of alcohol drinking behavior as well as the preference for alcohol in genetically selected TSRI Sardinian alcohol preferring (Scr:sP) rats; the treatment had no effect on total fluid intake, food intake or body weight gain, proving selectivity of action. Furthermore, BD-1063 dose-dependently decreased alcohol-seeking behavior in rats trained under a second-order schedule of reinforcement, in which responding is maintained by contingent presentation of a conditioned reinforcer. Finally, an innate elevation in Sig-1R protein levels was found in the nucleus accumbens of alcohol-preferring Scr:sP rats, compared to outbred Wistar rats, alteration which was normalized by chronic, voluntary alcohol drinking. Taken together these findings demonstrate that Sig-1R blockade reduces the propensity to both acquire alcohol drinking and to seek alcohol, and point to the nucleus accumbens as a potential key region for the effects observed. Our data suggest that Sig-1R antagonists may have therapeutic potential in multiple stages of alcohol addiction. PMID:25848705

Alcohol's actions on neuronal nicotinic acetylcholine receptors.

Science.gov (United States)

Davis, Tiffany J; de Fiebre, Christopher M

2006-01-01

Although it has been known for many years that alcoholism and tobacco addiction often co-occur, relatively little information is available on the biological factors that regulate the co-use and abuse of nicotine and alcohol. In the brain, nicotine acts at several different types of receptors collectively known as nicotinic acetylcholine receptors (nAChRs). Alcohol also acts on at least some of these receptors, enhancing the function of some nAChR subtypes and inhibiting the activity of others. Chronic alcohol and nicotine administration also lead to changes in the numbers of nAChRs. Natural variations (i.e., polymorphisms) in the genes encoding different nAChR subunits may be associated with individual differences in the sensitivity to some of alcohol's and nicotine's effects. Finally, at least one subtype of nAChR may help protect cells against alcohol-induced neurotoxicity.

Epidermal Growth Factor Improves Intestinal Integrity and Survival in Murine Sepsis Following Chronic Alcohol Ingestion.

Science.gov (United States)

Klingensmith, Nathan J; Yoseph, Benyam P; Liang, Zhe; Lyons, John D; Burd, Eileen M; Margoles, Lindsay M; Koval, Michael; Ford, Mandy L; Coopersmith, Craig M

2017-02-01

Epidermal growth factor (EGF) is a cytoprotective protein that improves survival in preclinical models of sepsis through its beneficial effects on intestinal integrity. Alcohol use disorder worsens intestinal integrity and is associated with increased morbidity and mortality in critical illness. We sought to determine whether chronic alcohol ingestion alters the host response to systemic administration of EGF in sepsis. Six-week-old FVB/N mice were randomized to receive 20% alcohol or water for 12 weeks. All mice then underwent cecal ligation and puncture to induce polymicrobial sepsis. Mice were then randomized to receive either intraperitoneal injection of EGF (150 μg/kg/day) or normal saline. Water-fed mice given EGF had decreased 7-day mortality compared with water-fed mice (18% vs. 55%). Alcohol-fed mice given EGF also had decreased 7-day mortality compared with alcohol-fed mice (48% vs. 79%). Notably, while systemic EGF improved absolute survival to a similar degree in both water-fed and alcohol-fed mice, mortality was significantly higher in alcohol+EGF mice compared with water+EGF mice. Compared with water-fed septic mice, alcohol-fed septic mice had worsened intestinal integrity with intestinal hyperpermeability, increased intestinal epithelial apoptosis, decreased proliferation and shorter villus length. Systemic administration of EGF to septic alcohol-fed mice decreased intestinal permeability compared with septic alcohol-fed mice given vehicle, with increased levels of the tight junction mediators claudin-5 and JAM-A. Systemic administration of EGF to septic alcohol-fed mice also decreased intestinal apoptosis with an improvement in the Bax/Bcl-2 ratio. EGF also improved both crypt proliferation and villus length in septic alcohol-fed mice. EGF administration resulted in lower levels of both pro- and anti-inflammatory cytokines monocyte chemoattractant protein-1, tumor necrosis factor, and interleukin 10 in alcohol-fed mice. EGF is therefore

Repeated administration of fresh garlic increases memory retention in rats.

Science.gov (United States)

Haider, Saida; Naz, Nosheen; Khaliq, Saima; Perveen, Tahira; Haleem, Darakhshan J

2008-12-01

Garlic (Allium sativum) is regarded as both a food and a medicinal herb. Increasing attention has focused on the biological functions and health benefits of garlic as a potentially major dietary component. Chronic garlic administration has been shown to enhance memory function. Evidence also shows that garlic administration in rats affects brain serotonin (5-hydroxytryptamine [5-HT]) levels. 5-HT, a neurotransmitter involved in a number of physiological functions, is also known to enhance cognitive performance. The present study was designed to investigate the probable neurochemical mechanism responsible for the enhancement of memory following garlic administration. Sixteen adult locally bred male albino Wistar rats were divided into control (n = 8) and test (n = 8) groups. The test group was orally administered 250 mg/kg fresh garlic homogenate (FGH), while control animals received an equal amount of water daily for 21 days. Estimation of plasma free and total tryptophan (TRP) and whole brain TRP, 5-HT, and 5-hydroxyindole acetic acid (5-HIAA) was determined by high-performance liquid chromatography with electrochemical detection. For assessment of memory, a step-through passive avoidance paradigm (electric shock avoidance) was used. The results showed that the levels of plasma free TRP significantly increased (P < .01) and plasma total TRP significantly decreased (P < .01) in garlic-treated rats. Brain TRP, 5-HT, and 5-HIAA levels were also significantly increased following garlic administration. A significant improvement in memory function was exhibited by garlic-treated rats in the passive avoidance test. Increased brain 5-HT levels were associated with improved cognitive performance. The present results, therefore, demonstrate that the memory-enhancing effect of garlic may be associated with increased brain 5-HT metabolism in rats. The results further support the use of garlic as a food supplement for the enhancement of memory.

Hyperactivity, Learning Disabilities, and Alcohol.

Science.gov (United States)

Gold, Sandra; Sherry, Lee

1984-01-01

A review of research on the effects of alcohol consumption by pregnant women supports the U.S. Food and Drug Administration's warning about the possible negative effects (learning disabilities, hyperactivity, short attention span, and emotional liability) of children. (Author/CL)

Validity and reproducibility of a self-administered semi-quantitative food-frequency questionnaire for estimating usual daily fat, fibre, alcohol, caffeine and theobromine intakes among Belgian post-menopausal women.

Science.gov (United States)

Bolca, Selin; Huybrechts, Inge; Verschraegen, Mia; De Henauw, Stefaan; Van de Wiele, Tom

2009-01-01

A novel food-frequency questionnaire (FFQ) was developed and validated to assess the usual daily fat, saturated, mono-unsaturated and poly-unsaturated fatty acid, fibre, alcohol, caffeine, and theobromine intakes among Belgian post-menopausal women participating in dietary intervention trials with phyto-oestrogens. The relative validity of the FFQ was estimated by comparison with 7 day (d) estimated diet records (EDR, n 64) and its reproducibility was evaluated by repeated administrations 6 weeks apart (n 79). Although the questionnaire underestimated significantly all intakes compared to the 7 d EDR, it had a good ranking ability (r 0.47-0.94; weighted kappa 0.25-0.66) and it could reliably distinguish extreme intakes for all the estimated nutrients, except for saturated fatty acids. Furthermore, the correlation between repeated administrations was high (r 0.71-0.87) with a maximal misclassification of 7% (weighted kappa 0.33-0.80). In conclusion, these results compare favourably with those reported by others and indicate that the FFQ is a satisfactorily reliable and valid instrument for ranking individuals within this study population.

Validation of coding algorithms for the identification of patients hospitalized for alcoholic hepatitis using administrative data.

Science.gov (United States)

Pang, Jack X Q; Ross, Erin; Borman, Meredith A; Zimmer, Scott; Kaplan, Gilaad G; Heitman, Steven J; Swain, Mark G; Burak, Kelly W; Quan, Hude; Myers, Robert P

2015-09-11

Epidemiologic studies of alcoholic hepatitis (AH) have been hindered by the lack of a validated International Classification of Disease (ICD) coding algorithm for use with administrative data. Our objective was to validate coding algorithms for AH using a hospitalization database. The Hospital Discharge Abstract Database (DAD) was used to identify consecutive adults (≥18 years) hospitalized in the Calgary region with a diagnosis code for AH (ICD-10, K70.1) between 01/2008 and 08/2012. Medical records were reviewed to confirm the diagnosis of AH, defined as a history of heavy alcohol consumption, elevated AST and/or ALT (34 μmol/L, and elevated INR. Subgroup analyses were performed according to the diagnosis field in which the code was recorded (primary vs. secondary) and AH severity. Algorithms that incorporated ICD-10 codes for cirrhosis and its complications were also examined. Of 228 potential AH cases, 122 patients had confirmed AH, corresponding to a positive predictive value (PPV) of 54% (95% CI 47-60%). PPV improved when AH was the primary versus a secondary diagnosis (67% vs. 21%; P codes for ascites (PPV 75%; 95% CI 63-86%), cirrhosis (PPV 60%; 47-73%), and gastrointestinal hemorrhage (PPV 62%; 51-73%) had improved performance, however, the prevalence of these diagnoses in confirmed AH cases was low (29-39%). In conclusion the low PPV of the diagnosis code for AH suggests that caution is necessary if this hospitalization database is used in large-scale epidemiologic studies of this condition.

Alcohol-flavoured tobacco products.

Science.gov (United States)

Jackler, Robert K; VanWinkle, Callie K; Bumanlag, Isabela M; Ramamurthi, Divya

2018-05-01

In 2009, the Food and Drug Administration (FDA) banned characterising flavours in cigarettes (except for menthol) due to their appeal to teen starter smokers. In August 2016, the agency deemed all tobacco products to be under its authority and a more comprehensive flavour ban is under consideration. To determine the scope and scale of alcohol-flavoured tobacco products among cigars & cigarillos, hookahs and electronic cigarettes (e-cigarettes). Alcohol-flavoured tobacco products were identified by online search of tobacco purveyors' product lines and via Google search cross-referencing the various tobacco product types versus a list of alcoholic beverage flavours (eg, wine, beer, appletini, margarita). 48 types of alcohol-flavoured tobacco products marketed by 409 tobacco brands were identified. Alcohol flavours included mixed drinks (n=25), spirits (11), liqueurs (7) and wine/beer (5). Sweet and fruity tropical mixed drink flavours were marketed by the most brands: piña colada (96), mojito (66) and margarita (50). Wine flavours were common with 104 brands. Among the tobacco product categories, brands offering alcohol-flavoured e-cigarettes (280) were most numerous, but alcohol-flavoured products were also marketed by cigars & cigarillos (88) and hookah brands (41). Brands by major tobacco companies (eg, Philip Morris, Imperial Tobacco) were well represented among alcohol-flavoured cigars & cigarillos with five companies offering a total of 17 brands. The widespread availability of alcohol-flavoured tobacco products illustrates the need to regulate characterising flavours on all tobacco products. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Effects of repeated administration of chemotherapeutic agents tamoxifen, methotrexate, and 5-fluorouracil on the acquisition and retention of a learned response in mice

Science.gov (United States)

Foley, John J.; Clark-Vetri, Rachel; Raffa, Robert B.

2011-01-01

Rationale A number of cancer chemotherapeutic agents have been associated with a loss of memory in breast cancer patients although little is known of the causality of this effect. Objectives To assess the potential cognitive effects of repeated exposure to chemotherapeutic agents, we administered the selective estrogen receptor modulator tamoxifen or the antimetabolite chemotherapy, methotrexate, and 5-fluorouracil, alone and in combination to mice and tested them in a learning and memory assay. Methods Swiss-Webster male mice were injected with saline, 32 mg/kg tamoxifen, 3.2 or 32 mg/kg methotrexate, 75 mg/kg 5-fluorouracil, 3.2 or 32 mg/kg methotrexate in combination with 75 mg/kg 5-fluorouracil once per week for 3 weeks. On days 23 and 24, mice were tested for acquisition and retention of a nose-poke response in a learning procedure called autoshaping. In addition, the acute effects of tamoxifen were assessed in additional mice in a similar procedure. Results The chemotherapeutic agents alone and in combination reduced body weight relative to saline treatment over the course of 4 weeks. Repeated treatment with tamoxifen produced both acquisition and retention effects relative to the saline-treated group although acute tamoxifen was without effect except at a behaviorally toxic dose. Repeated treatment with methotrexate in combination with 5-fluorouracil produced effects on retention, but the magnitude of these changes depended on the methotrexate dose. Conclusions These data demonstrate that repeated administration of tamoxifen or certain combination of methotrexate and 5-fluorouracil may produce deficits in the acquisition or retention of learned responses which suggest potential strategies for prevention or remediation might be considered in vulnerable patient populations. PMID:21537942

Ketogenic Diet suppresses Alcohol Withdrawal Syndrome in Rats

DEFF Research Database (Denmark)

Dencker, Ditte; Molander, Anna; Thomsen, Morgane

2018-01-01

, we investigated the potential therapeutic benefit of a ketogenic diet in managing alcohol withdrawal symptoms during detoxification. METHODS: Male Sprague Dawley rats fed either ketogenic or regular diets were administered ethanol or water orally, twice daily for 6 days while the diet conditions were...... maintained. Abstinence symptoms were rated 6, 24, 48, and 72 hours after the last alcohol administration. RESULTS: Maintenance on a ketogenic diet caused a significant decrease in the alcohol withdrawal symptoms 'rigidity' and 'irritability'. CONCLUSION: Our preclinical pilot study suggests that a ketogenic...... diet may be a novel approach for treating alcohol withdrawal symptoms in humans. This article is protected by copyright. All rights reserved....

Utilization of a Sobering Center for Acute Alcohol Intoxication.

Science.gov (United States)

Smith-Bernardin, Shannon; Carrico, Adam; Max, Wendy; Chapman, Susan

2017-09-01

The objective was to describe the population utilizing a sobering center for public alcohol intoxication and compare between single-visit users, repeat users, and high users. We conducted a secondary analysis of 1,271 adults cared for in a sobering center from July 2014 to June 2015. We divided the population into three groups-single use (one visit), repeat users (two to five visits), and high (six or more) users-and evaluated demographics, lifetime health diagnoses utilizing the Elixhauser Comorbidity Index, rates of public service utilization including ambulance and emergency department, and related costs. The population was primarily male, middle-aged, and ethnically diverse. Compared to single-visit users (n = 869), repeat (n = 287) and high users (n = 115) were older, were more likely to be currently homeless, and had spent more time homeless. Repeat and high users had significantly higher rates of hypertension, liver disease, diabetes, depression, psychoses, and drug abuse diagnoses compared to single-visit users. In addition to sobering visits, utilization of ambulance and ED and related costs were significantly greater for the high users compared to repeat and single-visit users. From an overall heterogeneous population, more frequent utilizers of the sobering center, both high and repeat users compared to low users, had significantly greater prevalence of chronic disorders, service utilization, and homelessness. Findings indicate that a sobering center can have a prominent role in the care for those with acute alcohol intoxication, particularly those individuals with chronic public intoxication who are likewise homeless. Further longitudinal research could offer important insights as to the population served over time, investigating changes in utilization and efforts toward health and housing stabilization. © 2017 by the Society for Academic Emergency Medicine.

Binge Alcohol Exposure Transiently Changes the Endocannabinoid System: A Potential Target to Prevent Alcohol-Induced Neurodegeneration

Directory of Open Access Journals (Sweden)

Daniel J. Liput

2017-11-01

Full Text Available Excessive alcohol consumption leads to neurodegeneration, which contributes to cognitive decline that is associated with alcohol use disorders (AUDs. The endocannabinoid system has been implicated in the development of AUDs, but little is known about how the neurotoxic effects of alcohol impact the endocannabinoid system. Therefore, the current study investigated the effects of neurotoxic, binge-like alcohol exposure on components of the endocannabinoid system and related N-acylethanolamines (NAEs, and then evaluated the efficacy of fatty acid amide hydrolase (FAAH inhibition on attenuating alcohol-induced neurodegeneration. Male rats were administered alcohol according to a binge model, which resulted in a transient decrease in [3H]-CP-55,940 binding in the entorhinal cortex and hippocampus following two days, but not four days, of treatment. Furthermore, binge alcohol treatment did not change the tissue content of the three NAEs quantified, including the endocannabinoid and anandamide. In a separate study, the FAAH inhibitor, URB597 was administered to rats during alcohol treatment and neuroprotection was assessed by FluoroJade B (FJB staining. The administration of URB597 during binge treatment did not significantly reduce FJB+ cells in the entorhinal cortex or hippocampus, however, a follow up “target engagement” study found that NAE augmentation by URB597 was impaired in alcohol intoxicated rats. Thus, potential alcohol induced alterations in URB597 pharmacodynamics may have contributed to the lack of neuroprotection by FAAH inhibition.

Protective Effect of Hericium erinaceus on Alcohol Induced Hepatotoxicity in Mice.

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Hao, Lijun; Xie, Yuxi; Wu, Guikai; Cheng, Aibin; Liu, Xiaogang; Zheng, Rongjuan; Huo, Hong; Zhang, Junwei

2015-01-01

We investigated the effects of Hericium erinaceus (HEM) on liver injury induced by acute alcohol administration in mice. Mice received ethanol (5 g/kg BW) by gavage every 12 hrs for a total of 3 doses. HEM (200 mg/kg BW) was gavage before ethanol administration. Subsequent serum alanine aminotransferase (ALT) level, aspartate aminotransaminase (AST) level, Maleic dialdehyde (MDA) level, hepatic total antioxidant status (TAOS), and activated nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) were determined by ELISA and immunohistochemistry, respectively. HEM administration markedly (P < 0.05) decreased serum ALT, AST, and MDA levels. The hepatic histopathological observations showed that HEM had a relatively significant role in mice model, which had alcoholic liver damage. In conclusion, we observed that HEM (200 mg/kg BW) supplementation could restrain the hepatic damage caused by acute alcohol exposure.

Protective Effect of Hericium erinaceus on Alcohol Induced Hepatotoxicity in Mice

Directory of Open Access Journals (Sweden)

Lijun Hao

2015-01-01

Full Text Available We investigated the effects of Hericium erinaceus (HEM on liver injury induced by acute alcohol administration in mice. Mice received ethanol (5 g/kg BW by gavage every 12 hrs for a total of 3 doses. HEM (200 mg/kg BW was gavage before ethanol administration. Subsequent serum alanine aminotransferase (ALT level, aspartate aminotransaminase (AST level, Maleic dialdehyde (MDA level, hepatic total antioxidant status (TAOS, and activated nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB were determined by ELISA and immunohistochemistry, respectively. HEM administration markedly (P<0.05 decreased serum ALT, AST, and MDA levels. The hepatic histopathological observations showed that HEM had a relatively significant role in mice model, which had alcoholic liver damage. In conclusion, we observed that HEM (200 mg/kg BW supplementation could restrain the hepatic damage caused by acute alcohol exposure.

Ketogenic Diet Suppresses Alcohol Withdrawal Syndrome in Rats.

Science.gov (United States)

Dencker, Ditte; Molander, Anna; Thomsen, Morgane; Schlumberger, Chantal; Wortwein, Gitta; Weikop, Pia; Benveniste, Helene; Volkow, Nora D; Fink-Jensen, Anders

2018-02-01

Alcohol use disorder is underdiagnosed and undertreated, and up to 50% of alcohol-abstinent patients diagnosed with alcohol dependence relapse within the first year of treatment. Current treatments for the maintenance of alcohol abstinence in patients with alcohol use disorder have limited efficacy, and there is an urgent need for novel treatment strategies. Decreased cerebral glucose metabolism and increased brain uptake of acetate were recently reported in heavy drinkers, relative to controls. Given the switch of metabolic fuel from glucose to acetate in the alcohol-dependent brain, we investigated the potential therapeutic benefit of a ketogenic diet in managing alcohol withdrawal symptoms during detoxification. Male Sprague Dawley rats fed either ketogenic or regular diet were administered ethanol or water orally, twice daily for 6 days while the diet conditions were maintained. Abstinence symptoms were rated 6, 24, 48, and 72 hours after the last alcohol administration. Maintenance on a ketogenic diet caused a significant decrease in the alcohol withdrawal symptoms' "rigidity" and "irritability." Our preclinical pilot study suggests that a ketogenic diet may be a novel approach for treating alcohol withdrawal symptoms in humans. Copyright © 2017 by the Research Society on Alcoholism.

Ethanol affects acylated and total ghrelin levels in peripheral blood of alcohol-dependent rats.

Science.gov (United States)

Szulc, Michal; Mikolajczak, Przemyslaw L; Geppert, Bogna; Wachowiak, Roman; Dyr, Wanda; Bobkiewicz-Kozlowska, Teresa

2013-07-01

There is a hypothesis that ghrelin could take part in the central effects of alcohol as well as function as a peripheral indicator of the changes which occur during long-term alcohol consumption. The aim of this study was to determine a correlation between alcohol concentration and acylated and total form of ghrelin after a single administration of alcohol (intraperitoneal, i.p.) (experiment 1) and prolonged ethanol consumption (experiment 2). The study was performed using Wistar alcohol preferring (PR) and non-preferring (NP) rats and rats from inbred line (Warsaw High Preferring, WHP; Warsaw Low Preferring, WLP). It was found that ghrelin in ethanol-naive WHP animals showed a significantly lower level when compared with the ethanol-naive WLP or Wistar rats. After acute ethanol administration in doses of 1.0; 2.0 and 4.0 g/kg, i.p., the simple (WHP) or inverse (WLP and Wistar) relationship between alcohol concentration and both form of ghrelin levels in plasma were found. Chronic alcohol intake in all groups of rats led to decrease of acylated ghrelin concentration. PR and WHP rats, after chronic alcohol drinking, had lower levels of both form of ghrelin in comparison with NP and WLP rats, respectively, and the observed differences in ghrelin levels were in inverse relationship with their alcohol intake. In conclusion, it is suggested that there is a strong relationship between alcohol administration or intake, ethanol concentration in blood and both active and total ghrelin level in the experimental animals, and that ghrelin plasma concentration can be a marker of alcohol drinking predisposition. © 2013 The Authors, Addiction Biology © 2013 Society for the Study of Addiction.

Differential Susceptibility: The Genetic Moderation of Peer Pressure on Alcohol Use.

Science.gov (United States)

Griffin, Amanda M; Cleveland, H Harrington; Schlomer, Gabriel L; Vandenbergh, David J; Feinberg, Mark E

2015-10-01

Although peer pressure can influence adolescents' alcohol use, individual susceptibility to these pressures varies across individuals. The dopamine receptor D4 gene (DRD4) is a potential candidate gene that may influence adolescents' susceptibility to their peer environment due to the role dopamine plays in reward sensation during social interaction. We hypothesized that DRD4 genotype status would moderate the impact of 7th-grade antisocial peer pressure on 12th-grade lifetime alcohol use (n = 414; 58.7% female; 92.8% White). The results revealed significant main effects for antisocial peer pressure, but no main effects for DRD4 genotype on lifetime alcohol use. Adolescent DRD4 genotype moderated the association between peer pressure and lifetime alcohol use. For individuals who carried at least one copy of the DRD4 7-repeat allele (7+), antisocial peer pressure was associated with increased lifetime alcohol use. These findings indicate that genetic sensitivity to peer pressure confers increased alcohol use in late adolescence.

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

Science.gov (United States)

Rejitha, S; Prathibha, P; Indira, M

2012-10-01

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

Alcoholic Pancreatitis: Pathogenesis, Incidence and Treatment with Special Reference to the Associated Pain

Directory of Open Access Journals (Sweden)

Antonio M. Morselli-Labate

2009-11-01

Full Text Available Alcoholic pancreatitis continues to stir up controversy. One of the most debated points is whether from onset it is a chronic disease or whether it progresses to a chronic form after repeated episodes of acute pancreatitis. Histological studies on patients with alcoholic pancreatitis have shown that the disease is chronic from onset and that alcoholic acute pancreatitis occurs in a pancreas already damaged by chronic lesions. Genetic factors may also play a role in the pathogenesis of alcoholic disease. The incidence of chronic alcoholic pancreatitis seems to have decreased in the last twenty years. Finally, recent therapeutic studies which have shown medical or surgical approaches capable of reducing the pain episodes in chronic pancreatitis patients will be described.

Acute Alcohol Effects on Narrative Recall and Contextual Memory: An Examination of Fragmentary Blackouts

OpenAIRE

Wetherill, Reagan R.; Fromme, Kim

2011-01-01

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, no alcohol) administration procedures and neuropsychological assessments measured narrative recall and context...

Ups and downs of alcohol use among first-year college students: Number of drinks, heavy drinking, and stumble and pass out drinking days.

Science.gov (United States)

Maggs, Jennifer L; Williams, Lela Rankin; Lee, Christine M

2011-03-01

Given the dynamic fluctuating nature of alcohol use among emerging adults (Del Boca, Darkes, Greenbaum, & Goldman, 2004), patterns of alcohol use were modeled across 70 days in an intensive repeated-measures diary design. Two hundred first-year college students provided 10 weekly reports of their daily alcohol consumption via computer-assisted telephone interviews. Multi-level models demonstrated large within-person variability across days in drinks consumed, binge drinking, and days exceeding self-reported limits for stumbling around and passing out; these outcome variables were predicted by weekdays vs. weekend days (within-person) and gender, age of drinking initiation, fraternity/sorority membership, and alcohol motivations (between-persons). Repeated measurement of alternate indicators of alcohol use permits the examination of novel and important questions about alcohol use and abuse particularly in young adult and other erratically drinking populations. Copyright © 2010 Elsevier Ltd. All rights reserved.

Early initiation of alcohol consumption by adolescents in reconstructed families may be explained by parenting style

OpenAIRE

Iakunchykova, Olena P

2011-01-01

BACKGROUND. Literature about risk factors of alcohol use points at the association between alcohol use and parenting style. This study investigates the relationship between family structure of adolescents in Ukraine and their initiation of alcohol use with parenting style as a mediating variable. METHODS: Pooled data from the repeated cross-sectional nationally representative survey of classes in Ukrainian secondary schools with target group of all 15-16 year old students, held in 1999, 2003,...

Cabergoline decreases alcohol drinking and seeking behaviors via glial cell line-derived neurotrophic factor.

Science.gov (United States)

Carnicella, Sebastien; Ahmadiantehrani, Somayeh; He, Dao-Yao; Nielsen, Carsten K; Bartlett, Selena E; Janak, Patricia H; Ron, Dorit

2009-07-15

Cabergoline is an ergotamine derivative that increases the expression of glial cell line-derived neurotrophic factor (GDNF) in vitro. We recently showed that GDNF in the ventral tegmental area (VTA) reduces the motivation to consume alcohol. We therefore set out to determine whether cabergoline administration decreases alcohol-drinking and -seeking behaviors via GDNF. Reverse transcription polymerase chain reaction (RT-PCR) and Enzyme-Linked ImmunoSorbent Assay (ELISA) were used to measure GDNF levels. Western blot analysis was used for phosphorylation experiments. Operant self-administration in rats and a two-bottle choice procedure in mice were used to assess alcohol-drinking behaviors. Instrumental performance tested during extinction was used to measure alcohol-seeking behavior. The [35S]GTPgammaS binding assay was used to assess the expression and function of the dopamine D2 receptor (D2R). We found that treatment of the dopaminergic-like cell line SH-SY5Y with cabergoline and systemic administration of cabergoline in rats resulted in an increase in GDNF level and in the activation of the GDNF pathway. Cabergoline treatment decreased alcohol-drinking and -seeking behaviors including relapse, and its action to reduce alcohol consumption was localized to the VTA. Finally, the increase in GDNF expression and the decrease in alcohol consumption by cabergoline were abolished in GDNF heterozygous knockout mice. Together, these findings suggest that cabergoline-mediated upregulation of the GDNF pathway attenuates alcohol-drinking behaviors and relapse. Alcohol abuse and addiction are devastating and costly problems worldwide. This study puts forward the possibility that cabergoline might be an effective treatment for these disorders.

Testing a new alcohol-free hand sanitizer to combat infection.

Science.gov (United States)

Dyer, D L; Gerenraich, K B; Wadhams, P S

1998-08-01

Universal precautions require that perioperative health care personnel wash their hand before and after all patient contact. Time constraints, however, can make adhering to universal precautions, including proper hand washing, difficult. Some perioperative health care workers, therefore, routinely use rise-free hand sanitizers to supplement normal hand washing. This study evaluated immediate and persistent antimicrobial effectiveness of two alcohol--containing hand sanitizers and a novel surfactant, allantoin, benzalkonium chloride (SAB) hand sanitizer using a federally approved effectiveness protocol. Results indicate that all three products were equally effective after a single application. After repeated use, the alcohol-containing sanitizers did not meet federal performance standards, and the alcohol-free sanitizer did. These properties and others illustrated in this article indicate that the nonflammable, alcohol-free SAB hand sanitizer is the most favorable of the rise-free hand sanitizer formulas for normal hand washing.

Study I: effects of 0.06% and 0.10% blood alcohol concentration on human postural control.

Science.gov (United States)

Modig, F; Patel, M; Magnusson, M; Fransson, P A

2012-03-01

Alcohol intoxication causes many accidental falls presented at emergency departments, with the injury severity often related to level of blood alcohol concentration (BAC). One way to evaluate the decline in postural control and the fall risk is to assess standing stability when challenged. The study objective was to comprehensively investigate alcohol-related impairments on postural control and adaptive motor learning at specific BAC levels. Effects of alcohol intoxication at 0.06% and 0.10% BAC were examined with posturography when unperturbed or perturbed by calf vibration. Twenty-five participants (mean age 25.1 years) were investigated standing with either eyes open or closed. Our results revealed several significant findings: (1) stability declined much faster from alcohol intoxication between 0.06% and 0.10% BAC (60-140%) compared with between 0.0% and 0.06% BAC (30%); (2) sustained exposure to repeated balance perturbations augmented the alcohol-related destabilization; (3) there were stronger effects of alcohol intoxication on stability in lateral direction than in anteroposterior direction; and (4) there was a gradual degradation of postural control particularly in lateral direction when the balance perturbations were repeated at 0.06% and 0.10% BAC, indicating adaptation deficits when intoxicated. To summarize, alcohol has profound deteriorating effects on human postural control, which are dose dependent, time dependent and direction specific. The maximal effects of alcohol intoxication on physiological performance might not be evident initially, but may be revealed first when under sustained sensory-motor challenges. Copyright © 2011 Elsevier B.V. All rights reserved.

75 FR 3153 - Drug and Alcohol Testing Program; Correction

Science.gov (United States)

2010-01-20

... definition of prohibited drugs. In Sec. Sec. 120.103 and 120.211, we omitted the reference to Sec. 135.1 from.... FAA-2008-0937; Amendment No. 120-0A, 135-117A] RIN 2120-AJ37 Drug and Alcohol Testing Program... Aviation Administration (FAA) is correcting its drug and alcohol testing regulations published on May 14...

Cue-induced alcohol-seeking behaviour is reduced by disrupting the reconsolidation of alcohol-related memories.

Science.gov (United States)

von der Goltz, Christoph; Vengeliene, Valentina; Bilbao, Ainhoa; Perreau-Lenz, Stephanie; Pawlak, Cornelius R; Kiefer, Falk; Spanagel, Rainer

2009-08-01

In humans, the retrieval of memories associated with an alcohol-related experience frequently evokes alcohol-seeking behaviour. The reconsolidation hypothesis states that a consolidated memory could again become labile and susceptible to disruption after memory retrieval. The aim of our study was to examine whether retrieval of alcohol-related memories undergoes a reconsolidation process. For this purpose, male Wistar rats were trained to self-administer ethanol in the presence of specific conditioned stimuli. Thereafter, animals were left undisturbed in their home cages for the following 21 days. Memory retrieval was performed in a single 5-min exposure to all alcohol-associated stimuli. The protein synthesis inhibitor anisomycin, the non-competitive N-methyl-D: -aspartate (NMDA) receptor antagonist MK-801 and acamprosate, a clinically used drug known to reduce a hyper-glutamatergic state, were given immediately after retrieval of alcohol-related memories. The impact of drug treatment on cue-induced alcohol-seeking behaviour was measured on the following day and 7 days later. Administration of both anisomycin and MK-801 reduced cue-induced alcohol-seeking behaviour, showing that memory reconsolidation was disrupted by these compounds. However, acamprosate had no effect on the reconsolidation process, suggesting that this process is not dependent on a hyper-glutamatergic state but is more related to protein synthesis and NMDA receptor activity. Pharmacological disruption of reconsolidation of alcohol-associated memories can be achieved by the use of NMDA antagonists and protein synthesis inhibitors and may thus provide a potential new therapeutic strategy for the prevention of relapse in alcohol addiction.

Repeated administration of mazindol reduces spontaneous pain-related behaviors without modifying bone density and microarchitecture in a mouse model of complete Freund’s adjuvant-induced knee arthritis

Directory of Open Access Journals (Sweden)

Robledo-González LE

2017-07-01

Full Text Available LE Robledo-González,1 A Martínez-Martínez,1 VM Vargas-Muñoz,1 RI Acosta-González,2 R Plancarte-Sánchez,3 M Anaya-Reyes,4 C Fernández del Valle-Laisequilla,5 JG Reyes-García,6 JM Jiménez-Andrade1 1Laboratorio de Farmacología, 2Departamento de Análisis Clínicos, Unidad Académica Multidisciplinaria Reynosa-Aztlán, UAT, Reynosa, Tamaulipas, Mexico; 3Departamento de Anestesiología, Terapia Intensiva y Clínica del Dolor, Instituto Nacional de Cancerología, Mexico City, Mexico; 4Investigación Clínica y Farmacovigilancia, 5Investigación Clínica y Farmacovigilancia, Productos Medix, S.A. de C.V., Mexico City, Mexico; 6Sección de Estudios de Posgrado e Investigación, Escuela Superior de Medicina, Instituto Politécnico Nacional, Mexico City, Mexico Background: The role of dopaminergic system in the development of rheumatoid arthritis-related pain, a major symptom in this disease, has not been explored. Therefore, the antinociceptive effect of mazindol, a dopamine uptake inhibitor, was evaluated in a model of complete Freund’s adjuvant (CFA-induced arthritis. Furthermore, as studies have shown that the dopaminergic system regulates bone metabolism, the effect of mazindol on bone mass and microarchitecture was determined.Methods: Adult ICR male mice received intra-articular injections of either CFA or saline into the right knee joint every week. Spontaneous pain-like behaviors (flinching and guarding and locomotor activity were assessed at day 26 post-first CFA, following which, a single intraperitoneally (i.p. administered dose of mazindol was given (1, 3 and 10 mg/kg. Then, the antinociceptive effect of a repeated administration of 3 mg/kg mazindol (daily, i.p.; day 15–day 26 was evaluated. Additionally, at day 26, the participation of D1-like, D2-like or opioid receptors in the antinociceptive effect of mazindol was evaluated. The effect of mazindol on bone density and microarchitecture was evaluated by micro

Social outcomes associated with alcohol-related diagnoses: a population-based analysis using linked administrative data

Directory of Open Access Journals (Sweden)

Nathan Nickel

2017-04-01

Receiving an alcohol-related diagnosis is associated with subsequent increased use of social services and contacts with the justice system. Upstream efforts to reduce alcohol-related diagnoses may result in reduced use of social services and justice contacts.

49 CFR 655.49 - Refusal to submit to a drug or alcohol test.

Science.gov (United States)

2010-10-01

... 49 Transportation 7 2010-10-01 2010-10-01 false Refusal to submit to a drug or alcohol test. 655... TRANSIT ADMINISTRATION, DEPARTMENT OF TRANSPORTATION PREVENTION OF ALCOHOL MISUSE AND PROHIBITED DRUG USE IN TRANSIT OPERATIONS Types of Testing § 655.49 Refusal to submit to a drug or alcohol test. (a) Each...

Controlled and implicit processes in evaluative conditioning on implicit and explicit attitudes toward alcohol and intentions to drink

NARCIS (Netherlands)

Zerhouni, O.; Bègue, L.; Comiran, F.; Wiers, R.W.

Since implicit attitudes (i.e. evaluations occurring outside of complete awareness) are highly predictive of alcohol consumption, we tested an evaluative learning procedure based on repeated pairing to a critical stimulus (i.e. alcohol, the CS) with a valenced stimulus (the US) in order to modify

Neonates' responses to repeated exposure to a still face.

Science.gov (United States)

Nagy, Emese; Pilling, Karen; Watt, Rachel; Pal, Attila; Orvos, Hajnalka

2017-01-01

The main aims of the study were to examine whether human neonates' responses to communication disturbance modelled by the still-face paradigm were stable and whether their responses were affected by their previous experience with the still-face paradigm. The still face procedure, as a laboratory model of interpersonal stress, was administered repeatedly, twice, to 84 neonates (0 to 4 day olds), with a delay of an average of 1.25 day. Frame-by-frame analysis of the frequency and duration of gaze, distressed face, crying, sleeping and sucking behaviours showed that the procedure was stressful to them both times, that is, the still face effect was stable after repeated administration and newborns consistently responded to such nonverbal violation of communication. They averted their gaze, showed distress and cried more during the still-face phase in both the first and the second administration. They also showed a carry-over effect in that they continued to avert their gaze and displayed increased distress and crying in the first reunion period, but their gaze behaviour changed with experience, in the second administration. While in the first administration the babies continued averting their gaze even after the stressful still-face phase was over, this carry-over effect disappeared in the second administration, and the babies significantly increased their gaze following the still-face phase. After excluding explanations of fatigue, habituation and random effects, a self-other regulatory model is discussed as a possible explanation for this pattern.

Isoflavonoid compounds extracted from Pueraria lobata suppress alcohol preference in a pharmacogenetic rat model of alcoholism.

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Lin, R C; Guthrie, S; Xie, C Y; Mai, K; Lee, D Y; Lumeng, L; Li, T K

1996-06-01

The extract from an edible vine, Pueraria lobata, has long been used in China to lessen alcohol intoxication. We have previously shown that daidzin, one of the major components from this plant extract, is efficacious in lowering blood alcohol levels and shortens sleep time induced by alcohol ingestion. This study was conducted to test the antidipsotropic effect of daidzin and two other major isoflavonoids, daidzein and puerarin, from Pueraria lobata administered by the oral route. An alcohol-preferring rat model, the selectively-bred P line of rats, was used for the study. All three isoflavonoid compounds were effective in suppressing voluntary alcohol consumption by the P rats. When given orally to P rats at a dose of 100 mg/kg/day, daidzein, daidzin, and puerarin decreased ethanol intake by 75%, 50%, and 40%, respectively. The decrease in alcohol consumption was accompanied by an increase in water intake, so that the total fluid volume consumed daily remained unchanged. The effects of these isoflavonoid compounds on alcohol and water intake were reversible. Suppression of alcohol consumption was evident after 1 day of administration and became maximal after 2 days. Similarly, alcohol preference returned to baseline levels 2 days after discontinuation of the isoflavonoids. Rats receiving the herbal extracts ate the same amounts of food as control animals, and they gained weight normally during the experiments. When administered orally, none of these compounds affected the activities of liver alcohol dehydrogenase and aldehyde dehydrogenase. Therefore, the reversal of alcohol preference produced by these compounds may be mediated via the CNS. Data demonstrate that isoflavonoid compounds extracted from Pueraria lobata is effective in suppressing the appetite for alcohol when taken orally, raising the possibility that other constituents of edible plants may exert similar and more potent actions.

Clinical evaluation of the hypoxic cytotoxin tirapazamine (SR-4233): phase I experience with repeated dose administration during fractionated irradiation

International Nuclear Information System (INIS)

Hancock, Steven L.; Spencer, Sharon; Mariscal, Carol; Wooten, Ann; Wheeler, Richard; Brown, J. Martin; Fisher, Cheryl; Roemeling, Reinhard von

1996-01-01

Purpose: Regions of chronic or transient hypoxia are common in many human tumors and are thought to limit tumor cell killing and tumor control with conventional irradiation and some chemotherapeutic agents. Tirapazamine (3-amino-1,2,4-benzotriazine-1,4-di-N-oxide) forms a cytotoxic free radical during reductive metabolism in regions of hypoxia. In well oxygenated regions, the tirapazamine radical reacts with molecular oxygen to form the inactive parent drug. This results in markedly greater toxicity for hypoxic cells than for the well oxygenated cells that comprise most normal tissues. Tirapazamine increased the anti-tumor effects of single dose or fractionated irradiation or cis-platin chemotherapy in murine tumors,in vivo . This study evaluated the ability to repeat the administration of Tirapazamine during courses of fractionated irradiation in humans after an earlier phase I trial established a maximum tolerated dose of 390 mg per square meter of body surface area (mg/m 2 ) when given as a single dose with radiotherapy. Materials and Methods: Between December 1993 and August 1995 22 patients with locally advanced or metastatic tumors of varying histology, normal renal, hepatic, and hematologic functions, and Karnofsky performance status ≥ 60 received repeated doses of Tirapazamine during a planned, 6 weeks course of standardly fractionated radiotherapy. After anti-emetic treatment with ondansetron (32 mg) and dexamethasone (16 mg), Tirapazamine was administered during a 2 hour intravenous infusion that ended from 30 to 90 minutes before a radiation treatment. Patients were monitored for acute toxicity during the course of treatment and for a minimum of one month after radiotherapy. Results: The study was initiated with three, biweekly doses of Tirapazamine at 330 mg/m 2 . Four of 7 patients who initiated treatment at this dose refused the second (1 patient) or third dose of Tirapazamine (3 patients). Two of the three patients who received three doses

Surrogate alcohol containing methanol, social deprivation and public health in Novosibirsk, Russia.

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Neufeld, Maria; Lachenmeier, Dirk; Hausler, Thomas; Rehm, Jürgen

2016-11-01

Surrogate alcohol, i.e. alcohol not intended or not officially intended for human consumption, continues to play an important role in alcohol consumption in Russia, especially for people with alcohol dependence. Among the different types of surrogate alcohol, there are windshield washer antifreeze liquids; these products are the cheapest kinds of non-beverage alcohol available and thus likely to be used by the most deprived and marginalised groups such as homeless people with alcohol dependence. Although it is well known, that non-beverage alcohol is used for consumption by various groups in Russia, and although there are laws to prohibit the use of methanol as part of windshield washer antifreeze liquids for the very reason that such products could be used as surrogate alcohol, we detected products in retail sale which were a mix of water and methanol only. Methanol poses serious health threats including blindness and death, and there had been repeated methanol deaths from surrogate alcohol in Russia over the last years. If law-enforcement does not change for surrogate products, we can expect more methanol-resulting deaths in the most deprived and marginalized groups of people with alcohol dependence in Russia. In addition, ingredients with questionable safety profiles such as formic acid should also be prohibited in non-beverage alcohol products that are likely to be consumed as surrogate alcohol. Copyright © 2016. Published by Elsevier B.V.

Exposure to the taste of alcohol elicits activation of the mesocorticolimbic neurocircuitry.

Science.gov (United States)

Filbey, Francesca M; Claus, Eric; Audette, Amy R; Niculescu, Michelle; Banich, Marie T; Tanabe, Jody; Du, Yiping P; Hutchison, Kent E

2008-05-01

A growing number of imaging studies suggest that alcohol cues, mainly visual, elicit activation in mesocorticolimbic structures. Such findings are consistent with the growing recognition that these structures play an important role in the attribution of incentive salience and the pathophysiology of addiction. The present study investigated whether the presentation of alcohol taste cues can activate brain regions putatively involved in the acquisition and expression of incentive salience. Using functional magnetic resonance imaging, we recorded BOLD activity while delivering alcoholic tastes to 37 heavy drinking but otherwise healthy volunteers. The results yielded a pattern of BOLD activity in mesocorticolimbic structures (ie prefrontal cortex, striatum, ventral tegmental area/substantia nigra) relative to an appetitive control. Further analyses suggested strong connectivity between these structures during cue-elicited urge and demonstrated significant positive correlations with a measure of alcohol use problems (ie the Alcohol Use Disorders Identification Test). Thus, repeated exposure to the taste alcohol in the scanner elicits activation in mesocorticolimbic structures, and this activation is related to measures of urge and severity of alcohol problems.

Repeated intermittent administration of psychomotor stimulant drugs alters the acquisition of Pavlovian approach behavior in rats: differential effects of cocaine, d-amphetamine and 3,4- methylenedioxymethamphetamine ("Ecstasy").

Science.gov (United States)

Taylor, J R; Jentsch, J D

2001-07-15

Psychomotor stimulant drugs can produce long-lasting changes in neurochemistry and behavior after multiple doses. In particular, neuroadaptations within corticolimbic brain structures that mediate incentive learning and motivated behavior have been demonstrated after chronic exposure to cocaine, d-amphetamine, and 3,4-methylenedioxymethamphetamine (MDMA). As stimulus-reward learning is likely relevant to addictive behavior (i.e., augmented conditioned reward and stimulus control of behavior), we have investigated whether prior repeated administration of psychomotor stimulant drugs (of abuse, including cocaine, d-amphetamine, or MDMA, would affect the acquisition of Pavlovian approach behavior. Water-deprived rats were tested for the acquisition of Pavlovian approach behavior after 5 days treatment with cocaine (15-20 mg/kg once or twice daily), d-amphetamine (2.5 mg/kg once or twice daily), or MDMA (2.5 mg/kg twice daily) followed by a 7-day, drug-free period. Prior repeated treatment with cocaine or d-amphetamine produced a significant enhancement of acquisition of Pavlovian approach behavior, indicating accelerated stimulus-reward learning, whereas MDMA administration produced increased inappropriate responding, indicating impulsivity. Abnormal drug-induced approach behavior was found to persist throughout the testing period. These studies demonstrate that psychomotor stimulant-induced sensitization can produce long-term alterations in stimulus-reward learning and impulse control that may contribute to the compulsive drug taking that typifies addiction.

Receptionist input to quality and safety in repeat prescribing in UK general practice: ethnographic case study.

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Swinglehurst, Deborah; Greenhalgh, Trisha; Russell, Jill; Myall, Michelle

2011-11-03

To describe, explore, and compare organisational routines for repeat prescribing in general practice to identify contributors and barriers to safety and quality. Ethnographic case study. Four urban UK general practices with diverse organisational characteristics using electronic patient records that supported semi-automation of repeat prescribing. 395 hours of ethnographic observation of staff (25 doctors, 16 nurses, 4 healthcare assistants, 6 managers, and 56 reception or administrative staff), and 28 documents and other artefacts relating to repeat prescribing locally and nationally. Potential threats to patient safety and characteristics of good practice. Observation of how doctors, receptionists, and other administrative staff contributed to, and collaborated on, the repeat prescribing routine. Analysis included mapping prescribing routines, building a rich description of organisational practices, and drawing these together through narrative synthesis. This was informed by a sociological model of how organisational routines shape and are shaped by information and communications technologies. Results Repeat prescribing was a complex, technology-supported social practice requiring collaboration between clinical and administrative staff, with important implications for patient safety. More than half of requests for repeat prescriptions were classed as "exceptions" by receptionists (most commonly because the drug, dose, or timing differed from what was on the electronic repeat list). They managed these exceptions by making situated judgments that enabled them (sometimes but not always) to bridge the gap between the idealised assumptions about tasks, roles, and interactions that were built into the electronic patient record and formal protocols, and the actual repeat prescribing routine as it played out in practice. This work was creative and demanded both explicit and tacit knowledge. Clinicians were often unaware of this input and it did not feature in policy

Meta-Analysis Reveals Significant Association of the 3'-UTR VNTR in SLC6A3 with Alcohol Dependence.

Science.gov (United States)

Ma, Yunlong; Fan, Rongli; Li, Ming D

2016-07-01

Although many studies have analyzed the association of 3'-untranslated region variable-number tandem repeat (VNTR) polymorphism in SLC6A3 with alcohol dependence (AD), the results remain controversial. This study aimed to determine whether this variant indeed has any genetic effect on AD by integrating 17 reported studies with 5,929 participants included. The A9-dominant genetic model that considers A9-repeat and non-A9 repeat as 2 genotypes and compared their frequencies in alcoholics with that in controls was adopted. Considering the potential influence of ethnicity, differences in diagnostic criteria of AD, and alcoholic subgroups, stratified meta-analyses were conducted. There existed no evidence for the presence of heterogeneity among the studied samples, indicating the results under the fixed-effects model are acceptable. We found a significant association of VNTR A9 genotypes with AD in all ethnic populations (pooled odds ratio [OR] 1.12; 95% confidence interval [CI] 1.00, 1.25; p = 0.045) and the Caucasian population (pooled OR 1.15; 95% CI 1.01, 1.31; p = 0.036). We also found VNTR A9 genotypes to be significantly associated with alcoholism as defined by the DSM-IV criteria (pooled OR 1.18; 95% CI 1.03, 1.36; p = 0.02). Further, we found a significant association between VNTR A9 genotypes and alcoholism associated with alcohol withdrawal seizure or delirium tremens (pooled OR 1.55; 95% CI 1.24, 1.92; p = 1.0 × 10(-4) ). In all these meta-analyses, no evidence of publication bias was detected. We concluded that the VNTR polymorphism has an important role in the etiology of AD, and individuals with at least 1 A9 allele are more likely to be dependent on alcohol than persons carrying the non-A9 allele. Copyright © 2016 by the Research Society on Alcoholism.

Scope and mechanism in palladium-catalyzed isomerizations of highly substituted allylic, homoallylic, and alkenyl alcohols.

Science.gov (United States)

Larionov, Evgeny; Lin, Luqing; Guénée, Laure; Mazet, Clément

2014-12-03

Herein we report the palladium-catalyzed isomerization of highly substituted allylic alcohols and alkenyl alcohols by means of a single catalytic system. The operationally simple reaction protocol is applicable to a broad range of substrates and displays a wide functional group tolerance, and the products are usually isolated in high chemical yield. Experimental and computational mechanistic investigations provide complementary and converging evidence for a chain-walking process consisting of repeated migratory insertion/β-H elimination sequences. Interestingly, the catalyst does not dissociate from the substrate in the isomerization of allylic alcohols, whereas it disengages during the isomerization of alkenyl alcohols when additional substituents are present on the alkyl chain.

Validity and Reproducibility of a Self-Administered Semi-Quantitative Food-Frequency Questionnaire for Estimating Usual Daily Fat, Fibre, Alcohol, Caffeine and Theobromine Intakes among Belgian Post-Menopausal Women

Directory of Open Access Journals (Sweden)

Selin Bolca

2009-01-01

Full Text Available A novel food-frequency questionnaire (FFQ was developed and validated to assess the usual daily fat, saturated, mono-unsaturated and poly-unsaturated fatty acid, fibre, alcohol, caffeine, and theobromine intakes among Belgian post-menopausal women participating in dietary intervention trials with phyto-oestrogens. The relative validity of the FFQ was estimated by comparison with 7 day (d estimated diet records (EDR, n 64 and its reproducibility was evaluated by repeated administrations 6 weeks apart (n 79. Although the questionnaire underestimated significantly all intakes compared to the 7 d EDR, it had a good ranking ability (r 0.47-0.94; weighted κ 0.25-0.66 and it could reliably distinguish extreme intakes for all the estimated nutrients, except for saturated fatty acids. Furthermore, the correlation between repeated administrations was high (r 0.71-0.87 with a maximal misclassification of 7% (weighted κ 0.33-0.80. In conclusion, these results compare favourably with those reported by others and indicate that the FFQ is a satisfactorily reliable and valid instrument for ranking individuals within this study population.

The effects of hypoglycemic and alcoholic coma on the blood-brain barrier permeability

Science.gov (United States)

Yorulmaz, Hatice; Seker, Fatma Burcu; Oztas, Baria

2011-01-01

In this investigation, the effects of hypoglycemic coma and alcoholic coma on the blood-brain barrier (BBB) permeability have been compared. Female adult Wistar albino rats weighing 180-230 g were divided into three groups: Control group (n=8), Alcoholic Coma Group (n=18), and Hypoglycemic Coma group (n=12). The animals went into coma approximately 3-4 hours after insulin administration and 3-5 minutes after alcohol administration. Evans blue (4mL/kg) was injected intravenously as BBB tracer. It was observed that the alcoholic coma did not significantly increase the BBB permeability in any of the brain regions when compared to control group. Changes in BBB permeability were significantly increased by the hypoglycemic coma in comparison to the control group values (pcoma have different effects on the BBB permeability depending on the energy metabolism. PMID:21619558

Alcoholism and Alcohol Abuse

Science.gov (United States)

... their drinking causes distress and harm. It includes alcoholism and alcohol abuse. Alcoholism, or alcohol dependence, is a disease that causes ... the liver, brain, and other organs. Drinking during pregnancy can harm your baby. Alcohol also increases the ...

Acute alcohol effects on facial expressions of emotions in social drinkers: a systematic review

Science.gov (United States)

Capito, Eva Susanne; Lautenbacher, Stefan; Horn-Hofmann, Claudia

2017-01-01

Background As known from everyday experience and experimental research, alcohol modulates emotions. Particularly regarding social interaction, the effects of alcohol on the facial expression of emotion might be of relevance. However, these effects have not been systematically studied. We performed a systematic review on acute alcohol effects on social drinkers’ facial expressions of induced positive and negative emotions. Materials and methods With a predefined algorithm, we searched three electronic databases (PubMed, PsycInfo, and Web of Science) for studies conducted on social drinkers that used acute alcohol administration, emotion induction, and standardized methods to record facial expressions. We excluded those studies that failed common quality standards, and finally selected 13 investigations for this review. Results Overall, alcohol exerted effects on facial expressions of emotions in social drinkers. These effects were not generally disinhibiting, but varied depending on the valence of emotion and on social interaction. Being consumed within social groups, alcohol mostly influenced facial expressions of emotions in a socially desirable way, thus underscoring the view of alcohol as social lubricant. However, methodical differences regarding alcohol administration between the studies complicated comparability. Conclusion Our review highlighted the relevance of emotional valence and social-context factors for acute alcohol effects on social drinkers’ facial expressions of emotions. Future research should investigate how these alcohol effects influence the development of problematic drinking behavior in social drinkers. PMID:29255375

Histamine H3 receptor: A novel therapeutic target in alcohol dependence?

Directory of Open Access Journals (Sweden)

Pertti ePanula

2012-05-01

Full Text Available The brain histaminergic system is one of the diffuse modulatory neurotransmitter systems which regulate neuronal activity in many brain areas. Studies on both rats and mice indicate that histamine H3 receptor antagonists decrease alcohol drinking in several models, like operant alcohol administration and drinking in the dark paradigm. Alcohol-induced place preference is also affected by these drugs. Moreover, mice lacking H3R do not drink alcohol like their wild type littermates, and they do not show alcohol-induced place preference. Although the mechanisms of these behaviors are still being investigated, we propose that H3R antagonists are promising candidates for use in human alcoholics, as these drugs are already tested for treatment of other disorders like narcolepsy and sleep disorders.

Neonates’ responses to repeated exposure to a still face

Science.gov (United States)

Pilling, Karen; Watt, Rachel; Pal, Attila; Orvos, Hajnalka

2017-01-01

Aim The main aims of the study were to examine whether human neonates’ responses to communication disturbance modelled by the still-face paradigm were stable and whether their responses were affected by their previous experience with the still-face paradigm. Methods The still face procedure, as a laboratory model of interpersonal stress, was administered repeatedly, twice, to 84 neonates (0 to 4 day olds), with a delay of an average of 1.25 day. Results Frame-by-frame analysis of the frequency and duration of gaze, distressed face, crying, sleeping and sucking behaviours showed that the procedure was stressful to them both times, that is, the still face effect was stable after repeated administration and newborns consistently responded to such nonverbal violation of communication. They averted their gaze, showed distress and cried more during the still-face phase in both the first and the second administration. They also showed a carry-over effect in that they continued to avert their gaze and displayed increased distress and crying in the first reunion period, but their gaze behaviour changed with experience, in the second administration. While in the first administration the babies continued averting their gaze even after the stressful still-face phase was over, this carry-over effect disappeared in the second administration, and the babies significantly increased their gaze following the still-face phase. Conclusion After excluding explanations of fatigue, habituation and random effects, a self-other regulatory model is discussed as a possible explanation for this pattern. PMID:28771555

Possibility as monosaccharide laxative of rare sugar alcohols.

Science.gov (United States)

Oosaka, Kazumasa

2009-05-01

Allitol, D-talitol and L-iditol are sugar alcohols that are rare in nature. Due to their previous rarity, little is known about the laxative effects of these rare sugar alcohols. Therefore, reliable data on the laxative effect that these sugar alcohols cause in experimental animals could help to evaluate the effectiveness of new monosaccharide laxative drugs. To investigate the laxative effect of rare sugar alcohols, the study was designed to observe the diarrhea that occurred after oral administration of these sugar alcohols in mice. Moreover, to investigate the influence on intestinal function of rare sugar alcohols, the study was designed to examine small intestine transit and the luminal water content. Results indicated that rare sugar alcohols have a laxative effect in mice. Diarrhea started at a dose of 4.95 g/kg of rare sugar alcohols. There was a statistically significant laxative effect for D-talitol and L-iditol at a dose of 9.9 g/kg as compared to vehicle. Moreover, rare sugar alcohols significantly increased the small intestinal transit and the luminal water content of the small intestine and cecum in mice as compared to each vehicle. Overall, L-iditol greatly changes the function of intestine. In conclusion, rare sugar alcohols increase water content in small intestine and accelerate small intestine transit. These results support laxative effect of rare sugar alcohols. Therefore, rare sugar alcohols may be useful as monosaccharide laxatives and may be used to treat constipation.

Adolescent alcohol exposure and persistence of adolescent-typical phenotypes into adulthood: a mini-review

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Spear, Linda Patia; Swartzwelder, H. Scott

2014-01-01

Alcohol use is typically initiated during adolescence, which, along with young adulthood, is a vulnerable period for the onset of high-risk drinking and alcohol abuse. Given across-species commonalities in certain fundamental neurobehavioral characteristics of adolescence, studies in laboratory animals such as the rat have proved useful to assess persisting consequences of repeated alcohol exposure. Despite limited research to date, reports of long-lasting effects of adolescent ethanol exposure are emerging, along with certain common themes. One repeated finding is that adolescent exposure to ethanol sometimes results in the persistence of adolescent-typical phenotypes into adulthood. Instances of adolescent -like persistence have been seen in terms of baseline behavioral, cognitive, electrophysiological and neuroanatomical characteristics, along with the retention of adolescent-typical sensitivities to acute ethanol challenge. These effects are generally not observed after comparable ethanol exposure in adulthood. Persistence of adolescent-typical phenotypes is not always evident, and may be related to regionally-specific ethanol influences on the interplay between CNS excitation and inhibition critical for the timing of neuroplasticity. PMID:24813805

Effects of Repeated Administration of Pilocarpine and Isoproterenol on Aquaporin-5 Expression in Rat Salivary Glands

International Nuclear Information System (INIS)

Susa, Taketo; Sawai, Nobuhiko; Aoki, Takeo; Iizuka-Kogo, Akiko; Kogo, Hiroshi; Negishi, Akihide; Yokoo, Satoshi; Takata, Kuniaki; Matsuzaki, Toshiyuki

2013-01-01

Aquaporins are water channel proteins which enable rapid water movement across the plasma membrane. Aquaporin-5 (AQP5) is the major aquaporin and is expressed on the apical membrane of salivary gland acinar cells. We examined the effects of repeated administration of pilocarpine, a clinically useful stimulant for salivary fluid secretion, and isoproterenol (IPR), a stimulant for salivary protein secretion, on the abundance of AQP5 protein in rat salivary glands by immunofluorescence microscopy and semi-quantitative immunoblotting. Unexpectedly AQP5 was decreased in pilocarpine-administered salivary glands, in which fluid secretion must be highly stimulated, implying that AQP5 might not be required for fluid secretion at least in pilocarpine-administered state. The abundance of AQP5, on the other hand, was found to be significantly increased in IPR-administered submandibular and parotid glands. To address the possible mechanism of the elevation of AQP5 abundance in IPR-administered animals, changes of AQP5 level in fasting animals, in which the exocytotic events are reduced, were examined. AQP5 was found to be decreased in fasting animals as expected. These results suggested that the elevation of cAMP and/or frequent exocytotic events could increase AQP5 protein. AQP5 expression seems to be easily changed by salivary stimulants, although these changes do not always reflect the ability in salivary fluid secretion

Effects of administration of sertraline, clozapine, amitriptyline and ...

African Journals Online (AJOL)

Dr Gatsing

imipramine on brain serotonin, liver enzymes and blood chemistry of rabbit. O. A. T. EBUEHI ... The chronic administration of sertraline, clozapine, amitriptyline and imipramine on brain serotonin, liver ..... and Alcohol consumption affect human.

Effect of alcohol dose on deliberate self-harm in men and women.

Science.gov (United States)

Berman, Mitchell E; Fanning, Jennifer R; Guillot, Casey R; Marsic, Angelika; Bullock, Joshua; Nadorff, Michael R; McCloskey, Michael S

2017-09-01

Nonexperimental survey and field research support the notion that alcohol use may be associated with deliberate self-harm (DSH) across the spectrum of lethality, from nonsuicidal self-injury (NSSI) through suicide. Nonexperimental studies, however, provide limited information about potential causal relationships between alcohol consumption and DSH. Two previous experiments showed that a relatively high-dose of alcohol increases the likelihood of engaging in DSH in men, with DSH defined by the self-administration of a "painful" shock (the self-aggression paradigm [SAP]; Berman & Walley, 2003; McCloskey & Berman, 2003). In this study, we examined whether (a) lower doses of alcohol also elicit DSH, (b) this effect occurs for women as well as men, and (c) individual differences in past nonsuicidal self-injury (NSSI) moderate alcohol's effects on DSH. Nonalcohol dependent men and women (N = 210) were assigned either to .00%, .05%, .075%, or .100% blood alcohol concentration (BAC) drink conditions and completed a self-rating scale of NSSI (the Deliberate Self-Harm Inventory [DSHI]; Gratz, 2001). As in previous SAP studies, DSH was operationalized by shock setting behavior during a competitive reaction time (RT) game. Overall, a greater proportion of participants in the .075% and .100% (but not .050%) alcohol conditions self-selected a "painful" shock to administer compared to participants in the placebo condition. NSSI predicted self-administration of painful shocks, but did not moderate the alcohol effect. Results provide experimental evidence to support the notion that interventions for self-harm should include processes to monitor and limit alcohol intake. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

Extensive neuroadaptive changes in cortical gene-transcript expressions of the glutamate system in response to repeated intermittent MDMA administration in adolescent rats

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Malki Rana

2008-04-01

Full Text Available Abstract Background Many studies have focused on the implication of the serotonin and dopamine systems in neuroadaptive responses to the recreational drug 3,4-methylenedioxy-metamphetamine (MDMA. Less attention has been given to the major excitatory neurotransmitter glutamate known to be implicated in schizophrenia and drug addiction. The aim of the present study was to investigate the effect of repeated intermittent MDMA administration upon gene-transcript expression of the glutamate transporters (EAAT1, EAAT2-1, EAAT2-2, the glutamate receptor subunits of AMPA (GluR1, GluR2, GluR3, the glutamate receptor subunits of NMDA (NR1, NR2A and NR2B, as well as metabotropic glutamate receptors (mGluR1, mGluR2, mGluR3, mGluR5 in six different brain regions. Adolescent male Sprague Dawley rats received MDMA at the doses of 3 × 1 and 3 × 5 mg/kg/day, or 3× vehicle 3 hours apart, every 7th day for 4 weeks. The gene-transcript levels were assessed using real-time PCR validated with a range of housekeeping genes. Results The findings showed pronounced enhancements in gene-transcript expression of GluR2, mGluR1, mGluR5, NR1, NR2A, NR2B, EAAT1, and EAAT2-2 in the cortex at bregma +1.6. In the caudate putamen, mRNA levels of GluR3, NR2A, and NR2B receptor subunits were significantly increased. In contrast, the gene-transcript expression of GluR1 was reduced in the hippocampus. In the hypothalamus, there was a significant increase of GluR1, GluR3, mGluR1, and mGluR3 gene-transcript expressions. Conclusion Repeated intermittent MDMA administration induces neuroadaptive changes in gene-transcript expressions of glutamatergic NMDA and AMPA receptor subunits, metabotropic receptors and transporters in regions of the brain regulating reward-related associative learning, cognition, and memory and neuro-endocrine functions.

Federalizing Medical Campaigns against Alcoholism and Drug Abuse

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Metlay, Grischa

2013-01-01

Context The formation of the National Institute on Alcohol Abuse and Alcoholism (NIAAA) and the Special Action Office for Drug Abuse Prevention (SAODAP) in the early 1970s dramatically expanded scientific and medical efforts to control alcoholism and drug abuse in the United States. Methods Drawing on a variety of primary, secondary, and archival sources, this article describes the creation and early years of these agencies. Findings I show that while the agencies appeared at roughly the same time, their creation involved separate sets of issues and actors. In addition, I show that SAODAP received more money and resources, even though advocates for alcoholics mobilized a stronger lobbying campaign. Conclusions Two factors explain this discrepancy in money and resources: (1) alcoholism was framed as a public health problem, whereas drug abuse was drawn into broader debates about crime and social decline; and (2) alcohol programs relied on congressional support, whereas drug programs found champions at high levels of the Nixon administration. These political and cultural factors help explain why current programs for illegal drugs receive more federal support, despite alcohol's greater public health burden. PMID:23488713

Federalizing medical campaigns against alcoholism and drug abuse.

Science.gov (United States)

Metlay, Grischa

2013-03-01

The formation of the National Institute on Alcohol Abuse and Alcoholism (NIAAA) and the Special Action Office for Drug Abuse Prevention (SAODAP) in the early 1970s dramatically expanded scientific and medical efforts to control alcoholism and drug abuse in the United States. Drawing on a variety of primary, secondary, and archival sources, this article describes the creation and early years of these agencies. I show that while the agencies appeared at roughly the same time, their creation involved separate sets of issues and actors. In addition, I show that SAODAP received more money and resources, even though advocates for alcoholics mobilized a stronger lobbying campaign. Two factors explain this discrepancy in money and resources: (1) alcoholism was framed as a public health problem, whereas drug abuse was drawn into broader debates about crime and social decline; and (2) alcohol programs relied on congressional support, whereas drug programs found champions at high levels of the Nixon administration. These political and cultural factors help explain why current programs for illegal drugs receive more federal support, despite alcohol's greater public health burden. © 2013 Milbank Memorial Fund.

Alcohol detection using carbon nanotubes acoustic and optical sensors

Science.gov (United States)

Penza, M.; Cassano, G.; Aversa, P.; Antolini, F.; Cusano, A.; Cutolo, A.; Giordano, M.; Nicolais, L.

2004-09-01

We demonstrate the integration of single-walled carbon nanotubes (SWCNTs) onto quartz crystal microbalance (QCM) and standard silica optical fiber (SOF) sensor for alcohol detection at room temperature. Different transducing mechanisms have been used in order to outline the sensing properties of this class of nanomaterials, in particular the attention has been focused on two key parameters in sensing applications: mass and refractive index changes due to gas absorption. Here, Langmuir-Blodgett (LB) films consisting of tangled bundles of SWCNTs without surfactant molecules have been successfully transferred onto QCM and SOF. Mass-sensitive 10MHz QCM SWCNTs sensor exhibited a resonant frequency decreasing upon tested alcohols exposure; also the normalized optoelectronic signal (λ=1310nm) of the refractive index-sensitive SOF SWCNTs sensor was found to decrease upon alcohols ambient. Highly sensitive, repeatable and reversible responses of the QCM and SOF SWCNTs sensors indicate that the detection, at room temperature, in a wide mmHg vapor pressures range of alcohols and potentially other volatile organic compounds is feasible.

21 CFR 173.240 - Isopropyl alcohol.

Science.gov (United States)

2010-04-01

... 21 Food and Drugs 3 2010-04-01 2009-04-01 true Isopropyl alcohol. 173.240 Section 173.240 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) FOOD FOR HUMAN CONSUMPTION (CONTINUED) SECONDARY DIRECT FOOD ADDITIVES PERMITTED IN FOOD FOR HUMAN CONSUMPTION Solvents...

Repeated administration of alpha7 nicotinic acetylcholine receptor (nAChR) agonists, but not positive allosteric modulators, increases alpha7 nAChR levels in the brain

DEFF Research Database (Denmark)

Christensen, Ditte Z; Mikkelsen, Jens D; Hansen, Henrik H

2010-01-01

AChR binding sites in several brain regions, particularly in the prefrontal cortex. The alpha7 nAChR agonists SSR180711 and PNU-282987 also increase [(125)I]-BTX binding, suggesting that this is a general consequence of alpha7 nAChR agonism. Interestingly, the alpha7 nAChR positive allosteric modulators PNU......The alpha7 nicotinic acetylcholine receptor (nAChR) is an important target for treatment of cognitive deficits in schizophrenia and Alzheimer's disease. However, the receptor desensitizes rapidly in vitro, which has led to concern regarding its applicability as a clinically relevant drug target....... Here we investigate the effects of repeated agonism on alpha7 nAChR receptor levels and responsiveness in vivo in rats. Using [(125)I]-alpha-bungarotoxin (BTX) autoradiography we show that acute or repeated administration with the selective alpha7 nAChR agonist A-582941 increases the number of alpha7 n...

Increased ethane exhalation, an in vivo index of lipid peroxidation, in alcohol-abusers.

Science.gov (United States)

Lettéron, P; Duchatelle, V; Berson, A; Fromenty, B; Fisch, C; Degott, C; Benhamou, J P; Pessayre, D

1993-01-01

Ethane exhalation was measured in 42 control subjects, 52 patients with various non-alcoholic liver diseases, and 89 alcohol abusers who had been admitted to hospital for alcohol withdrawal and assessment of liver disease (six with normal liver tests, 10 with steatosis with or without fibrosis, six with alcoholic hepatitis, 29 with cirrhosis, 34 with both cirrhosis and alcoholic hepatitis, and four with both cirrhosis and a hepatocellular carcinoma). Ethane exhalation was similar in control subjects and in patients with non-alcoholic liver diseases, but was five times higher in alcohol abusers. Ethane exhalation in alcohol abusers was significantly, but very weakly, correlated with the daily ethanol intake before hospital admission, and the histological score for steatosis, but not with the inflammation or alcoholic hepatitis scores. Ethane exhalation was inversely correlated with the duration of abstinence before the test. In nine alcoholic patients, the exhalation of ethane was measured repeatedly, and showed slow improvement during abstinence. Ethane exhalation was significantly but weakly correlated with the Pugh's score in patients with alcoholic cirrhosis. It is concluded that the mean ethane exhalation is increased in alcohol abusers. One of the possible mechanisms may be the presence of oxidizable fat in the liver. The weak correlation with the Pugh's score is consistent with the contribution of many other factors in the progression to severe liver disease. PMID:8472992

The current situation of treatment systems for alcoholism in Korea.

Science.gov (United States)

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.

Neuromodulation Therapies for Alcohol Addiction: A Literature Review.

Science.gov (United States)

Azevedo, Celeste A; Mammis, Antonios

2018-02-01

The goal of this review is to explore alternative neurological therapies in the treatment of alcohol use disorder; including transcranial direct current stimulation (tDCS), transcranial magnetic stimulation, deep brain stimulation (DBS), electroconvulsive therapy (ECT), and the off-label use of the GABA B receptor agonist baclofen. A comprehensive literature search was conducted through EBSCOhost regarding the neurological therapies in the treatment of alcoholism discussed in this paper. To date, few studies have been conducted on the subject, sample sizes are consistently small, and long-term abstinence appears a common problem. tDCS has shown to temporarily reduce alcohol cravings but with a high number of long-term relapses, 50-70%. DBS and TMS, similarly, fail to overcome high relapse rates. In one DBS study, for example, only two of five patients achieved prolonged abstinence. ECT seems to avoid such problems, but only a single case study exists to date. As such, no solid conclusions can be made regarding its success in alcohol addiction treatment. Baclofen, however, implicated in studies with comparatively larger patient samples and higher efficacy rates, presents with great promise, particularly in patients with more severe forms of AUD. In one of the largest observational studies to date (100 subjects) 92% of patients reported craving suppression and long-term relapse rates were low. The side-effects of oral baclofen (i.e., somnolence, insomnia, dizziness, paresthesia, etc.) though, pose a principle limitation to its administration in alcohol addiction. Based on current information in the literature, the authors advocate that, following more extensive research on oral baclofen and its indications in the treatment of alcohol addiction, intrathecal administration be the next logical therapeutic option to be explored. In particular, those patients with severe AUD, requiring high doses of the medication, may benefit, as it eliminates the systemic side effects

Residential environments, alcohol advertising, and initiation and continuation of alcohol consumption among adolescents in urban Taiwan: A prospective multilevel study.

Science.gov (United States)

Chen, Yen-Tyng; Cooper, Hannah L F; Windle, Michael; Haardörfer, Regine; Crawford, Natalie D; Chen, Wei J; Chen, Chuan-Yu

2016-12-01

Research indicates that place characteristics and the media environment are important contextual determinants of underage drinking behaviors in Western countries, but it is unknown whether these exposures influence adolescent alcohol consumption outside Western contexts, including in Asia׳s emerging global alcohol markets. Guided by the social ecological framework, we prospectively investigated the influences of place characteristics and alcohol advertising on initiation and continuation of alcohol consumption among adolescents in Taipei, Taiwan. Data on individual-level characteristics, including alcohol use behaviors and perceived exposure to alcohol advertising, were obtained from two waves of a longitudinal school-based study through a stratified probability sampling method in 2010 (Grade 7/Grade 8, aged 13-14 years old) and 2011-2012 (Grade 9, aged 15 years old) from 1795 adolescents residing in 22 of 41 districts in Taipei. Data on district-level characteristics were drawn from administrative sources and Google Street View virtual audit to describe districts where adolescents lived at baseline. Hierarchical generalized linear models tested hypotheses about the associations of place characteristics and perceived alcohol advertising with underage drinking, with stratification by baseline lifetime alcohol consumption. Among alcohol-naïve adolescents, lower district-level economic disadvantage, a higher proportion of betel nut kiosks (a relatively unregulated alcohol source) compared to off-premises alcohol outlets, and exposure to television-based alcohol advertising predicted increased likelihood of alcohol initiation at one-year follow-up. Among alcohol-experienced adolescents, greater spatial access to off-premises alcohol outlets, and lower access to metro rapid transportation (MRT) and to temples were found to predict a subsequent increased likelihood of continued alcohol use. Parental drinking moderated the relationship between district-level violent

21 CFR 184.1293 - Ethyl alcohol.

Science.gov (United States)

2010-04-01

... 21 Food and Drugs 3 2010-04-01 2009-04-01 true Ethyl alcohol. 184.1293 Section 184.1293 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) FOOD FOR HUMAN CONSUMPTION (CONTINUED) DIRECT FOOD SUBSTANCES AFFIRMED AS GENERALLY RECOGNIZED AS SAFE Listing of Specific...

Effect of a Short-Term and Long-Term Melatonin Administration on Mammary Carcinogenesis in Female Sprague-Dawley Rats Influenced by Repeated Psychoemotional Stress

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M. Kassayová

2007-01-01

Full Text Available The aim of this study was to evaluate the effect of melatonin (MEL on N-methyl-N-nitrosourea (NMU-induced mammary carcinogenesis in female Sprague-Dawley rats exposed to repeated psychoemotional stress - immobilization in boxes. NMU was applied intraperitoneally in two doses each of 50 mg/kg b.w. between 40 - 50 postnatal days. Melatonin was administered in drinking water at a concentration of 4 μg/ml daily from 15:00 h to 8:00 h. The application was initiated 5 days prior to the fi rst NMU dose and lasted 15 days, i.e. during the promotion phase of tumour development, or long-term until the end of the experiment (week 20. Immobilization (2 h per day began on the third day after the second carcinogen application and lasted for 7 consecutive days. Short-term MEL administration to immobilized animals increased incidence by 22%, decreased tumour frequency per animal by 26% and reduced tumour volume gain (by 21% when compared to the immobilized group without MEL application. Decreased frequency per animal by 28% and more than a 40% decrease in tumour volume gain and cumulative volume were the most pronounced changes in the animals drinking MEL until the end of the experiment. Long-term MEL administration reduced the number and size of mammary tumours more markedly than its short-term administration. Melatonin decreased certain attributes of mammary carcinogenesis in female rats influenced by psychoemotional stress.

Extraction of low-temperature tar by various alcohols

Energy Technology Data Exchange (ETDEWEB)

Hara, N; Osawa, M; Azuma, H

1948-01-01

MeOH was the most effective of the alcohols tested (MeOH to pentanol) in extracting acid components from low-temperature tar. The optimum concentrations of MeOH were 70 to 80% for 1 extraction and 70 to 75% for repeated or continuous extractions when the solvent-tar ratio was 1:1. By 2 to 3 extractions neutral oil could be separated in about 90% yield including > 3% acidic oil.

Portion, package or tableware size for changing selection and consumption of food, alcohol and tobacco

OpenAIRE

Hollands, Gareth J; Shemilt, Ian; Marteau, Theresa M; Jebb, Susan A; Lewis, Hannah B; Wei, Yinghui; Higgins, Julian Pt; Ogilvie, David

2015-01-01

Background Overeating and harmful alcohol and tobacco use have been linked to the aetiology of various non-communicable diseases, which are among the leading global causes of morbidity and premature mortality. As people are repeatedly exposed to varying sizes and shapes of food, alcohol and tobacco products in environments such as shops, restaurants, bars and homes, this has stimulated public health policy interest in product size and shape as potential targets for intervention. Objectives 1)...

A randomized, double-masked, placebo-controlled crossover trial on the effects of L-ornithine on salivary cortisol and feelings of fatigue of flushers the morning after alcohol consumption

Directory of Open Access Journals (Sweden)

Kokubo Takeshi

2013-02-01

Full Text Available Abstract Background Residual alcohol effects on physiological and psychological symptoms are commonly experienced the morning after alcohol consumption. The purpose of this study was to assess the effects of L-ornithine on subjective feelings and salivary stress markers the morning after alcohol consumption and to investigate whether L-ornithine acutely accelerates ethanol metabolism. Methods This study had a randomized, placebo-controlled, double-masked crossover design. Subjects were all healthy Japanese adults with the ‘flusher’ phenotype for alcohol tolerance. In experiment 1, 11 subjects drank 0.4 g/kg body weight alcohol 1.5 h before their usual bedtime. Half an hour after drinking, they ingested either a placebo or 400 mg ornithine. The next morning on awakening, subjects completed a questionnaire containing a visual analog scale (VAS, the Oguri-Shirakawa-Azumi sleep inventory MA version (OSA-MA, and a profile of mood states (POMS and collected a saliva sample for measurement of salivary stress markers (cortisol, secretory immunoglobulin A, and α-amylase. In experiment 2, placebo or 400 mg ornithine were administrated to 16 subjects both before and after drinking, and the feeling of drunkenness, breath ethanol concentration and one-leg standing time were repeatedly investigated until 180 min after alcohol consumption. Results There were significant decreases in “awareness”, “feeling of fatigue” and “lassitude” VAS scores and in “anger-hostility” and “confusion” POMS scores and a significant increase in “sleep length” in the OSA-MA test. Salivary cortisol concentrations on awakening were reduced after ornithine supplementation. There were no differences between ornithine and placebo in any of the subjective or physiological parameters of acute alcohol metabolism. Conclusions Taking 400 mg ornithine after alcohol consumption improved various negative feelings and decreased the salivary stress marker cortisol the

Refeeding syndrome is uncommon in alcoholics admitted to a hospital detoxification unit.

Science.gov (United States)

Manning, S; Gilmour, M; Weatherall, M; Robinson, G M

2014-05-01

The refeeding syndrome is increasingly recognised. It is a serious change in electrolytes when nutrition is reintroduced to malnourished patients. Alcohol dependence is a risk factor for the refeeding syndrome. We report a prospective cohort study of 36 alcoholics hospitalised for withdrawal management. We found no evidence of refeeding syndrome in any patient after 3 days of hospitalisation, despite hypomagnesaemia, a risk factor for the refeeding syndrome being prevalent (44% of subjects). Low thiamine levels were infrequent affecting 3/29 (10%). We recommend that in alcoholics admitted for managed withdrawal, risk of refeeding syndrome appears to be low, and routine testing of repeat electrolytes appears unnecessary. © 2014 The Authors; Internal Medicine Journal © 2014 Royal Australasian College of Physicians.

Drug and Alcohol Testing Results 2008 Annual Report

Science.gov (United States)

2010-09-01

This is the 14th annual report of the results of the Federal Transit Administration's (FTA) Drug and Alcohol Testing : Program. This report summarizes the reporting requirements for calendar year 2008, the requirements of the overall : drug and alcoh...

Residential environments, alcohol advertising, and initiation and continuation of alcohol consumption among adolescents in urban Taiwan: A prospective multilevel study

Directory of Open Access Journals (Sweden)

Yen-Tyng Chen

2016-12-01

Full Text Available Background: Research indicates that place characteristics and the media environment are important contextual determinants of underage drinking behaviors in Western countries, but it is unknown whether these exposures influence adolescent alcohol consumption outside Western contexts, including in Asia׳s emerging global alcohol markets. Guided by the social ecological framework, we prospectively investigated the influences of place characteristics and alcohol advertising on initiation and continuation of alcohol consumption among adolescents in Taipei, Taiwan. Methods: Data on individual-level characteristics, including alcohol use behaviors and perceived exposure to alcohol advertising, were obtained from two waves of a longitudinal school-based study through a stratified probability sampling method in 2010 (Grade 7/Grade 8, aged 13-14 years old and 2011-2012 (Grade 9, aged 15 years old from 1795 adolescents residing in 22 of 41 districts in Taipei. Data on district-level characteristics were drawn from administrative sources and Google Street View virtual audit to describe districts where adolescents lived at baseline. Hierarchical generalized linear models tested hypotheses about the associations of place characteristics and perceived alcohol advertising with underage drinking, with stratification by baseline lifetime alcohol consumption. Results: Among alcohol-naïve adolescents, lower district-level economic disadvantage, a higher proportion of betel nut kiosks (a relatively unregulated alcohol source compared to off-premises alcohol outlets, and exposure to television-based alcohol advertising predicted increased likelihood of alcohol initiation at one-year follow-up. Among alcohol-experienced adolescents, greater spatial access to off-premises alcohol outlets, and lower access to metro rapid transportation (MRT and to temples were found to predict a subsequent increased likelihood of continued alcohol use. Parental drinking moderated the

Correlates of major depressive disorder with and without comorbid alcohol use disorder nationally in the veterans health administration.

Science.gov (United States)

Yoon, Gihyun; Petrakis, Ismene L; Rosenheck, Robert A

2015-08-01

This study assesses medical and psychiatric comorbidities, service utilization, and psychotropic medication prescriptions in veterans with comorbid major depressive disorder (MDD) and alcohol use disorder (AUD) relative to veterans with MDD alone. Using cross-sectional administrative data (fiscal year [FY]2012: October 1, 2011-September 30, 2012) from the Veterans Health Administration (VHA), we identified veterans with a diagnosis of current (12-month) MDD nationally (N = 309,374), 18.8% of whom were also diagnosed with current (12-month) AUD. Veterans with both MDD and AUD were compared to those with MDD alone on sociodemographic characteristics, current (12-month) medical and psychiatric disorders, service utilization, and psychotropic prescriptions. We then used logistic regression analyses to calculate odds ratio and 95% confidence interval of characteristics that were independently different between the groups. Dually diagnosed veterans with MDD and AUD, relative to veterans with MDD alone, had a greater number of comorbid health conditions, such as liver disease, drug use disorders, and bipolar disorder as well as greater likelihood of homelessness and higher service utilization. Dually diagnosed veterans with MDD and AUD had more frequent medical and psychiatric comorbidities and more frequently had been homeless. These data suggest the importance of assessing the presence of comorbid medical/psychiatric disorders and potential homelessness in order to provide appropriately comprehensive treatment to dually diagnosed veterans with MDD and AUD and indicate a need to develop more effective treatments for combined disorders. © American Academy of Addiction Psychiatry.

Ras pathway activation in gliomas: a strategic target for intranasal administration of perillyl alcohol

International Nuclear Information System (INIS)

Fonseca, C. O.; Linden, R.; Futuro, D.; Gattass, C.R.; Quirico-Santos, T.

2008-01-01

Targeted therapy directed at specific molecular alterations is already creating a shift in the treatment of cancer patients. Malignant gliomas commonly overexpress the oncogenes EGFR and PDGFR and contain mutations and deletions of the tumor suppressor genes PTEN and TP53. Some of these alterations lead to activation of the P13K/Akt and Ras/MAPK pathways, which provide targets for therapy. Perillyl alcohol (POH), the isoprenoid of greatest clinical interest, was initially considered to inhibit farnesyl protein transferase. Follow-up studies revealed that POH suppresses the synthesis of small G proteins, including Ras. Intranasal delivery allows drugs that do not cross the blood-brain barrier to enter the central nervous system. Moreover, it eliminates the need for systemic delivery, thereby reducing unwanted systemic side effects. Applying this method, a phase I/II clinical trial of POH was performed in patients with relapsed malignant gliomas after standard treatment: surgery, radiotherapy, and chemotherapy. POH was administrated in a concentration of 0.3% volume/volume (55 mg) four times daily in an interrupted administration schedule. The objective was to evaluate toxicity and progression-free survival (PFS) after six months of treatment. The cohort consisted of 37 patients, including 29 with glioblastoma multiforme (GBM), 5 with grade III astrocytoma (AA), and 3 with anaplastic oligodendroglioma (AO). Neurological examination and suitable image analysis (computed tomography (CT), magnetic resonance imaging (MRI)) established disease progression. Complete response was defined as neurological stability or improvement of conditions, disappearance of CT/MRI tumor image, and corticosteroid withdraw; partial response (PR) as .50% reduction of CT/MRI tumor image, neurological stability, or improvement of conditions and corticosteroid requirement; progressive course (PC) as .25% increase in CT/MRI tumor image or the appearance of a new lesion; and stable disease as a

Evaluation of Ashwagandha in alcohol withdrawal syndrome

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Ruby B

2012-10-01

Full Text Available Objective: To evaluate the effect of Ashwagandha (ASW in attenuation of alcohol withdrawal in ethanol withdrawal mice model. Methods: Alcohol dependence was induced in mice by the oral, once-daily administration of 10% v/v ethanol (2 g/kg for one week. Once the animals were withdrawn from alcohol, the efficacy of ASW (200mg/kg and 500mg/kg in comparison with diazepam (1 mg/kg in the attenuation of withdrawal was studied using, pentylenetetrazole (PTZ kindling test for seizure threshold, forced swim test (FST for depression and locomotor activity (LCA in open field test (OFT. 6 hours after the last ethanol administration, seizure threshold was measured in all the groups by administering the convulsant drug, PTZ with a subconvulsive dose of 30 mg/kg i.p. In FST, mice were forced to swim and the total duration of immobility (seconds was measured during the last 4 min of a single 6-min test session. In OFT, number of crossings of the lines marked on the floor was recorded for a period of 5 min. Results: Compared to ethanol group, ASW (500 mg/Kg has suppressed the PTZ kindling seizures in ethanol withdrawal animals [0% convulsion], FST has shown decreased immobility time and OFT has exhibited increase in the number of line crossing activity by mice which may be the consequence of anxiolytic activity of ASW similar to that of diazepam. Conclusions: The present study provides satisfactory evidence to use ASW as a safe and reliable alternative to diazepam in alcohol withdrawal conditions.

Beverage Alcohol Choice Among University Students: Perception, Consumption and Preferences

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Claudia Liana SALANTA

2017-05-01

Full Text Available This paper aims to analyze and compare the beverage alcohol choice among university students. The study was carried out on a total of 1069 students (men and women from University of Agricultural Sciences and Veterinary Medicine Cluj-Napoca, Romania. A general questionnaire assessed alcoholic beverage consumption, perception and preference. The main reasons associated with alcohol consumption were relaxation and socialization followed by taste and flavour. The most respondents are attracted by flavor and aroma of the favourite beverage. The participants in the study were not heavy social drinkers (only 1.7 % of participants consume alcohol every day. Beer and wine, were the alcoholic beverages ranked in the top of preferences. Our findings can provide information for educators and policymakers in Romania to implement target-orientated interventions against alcohol abuse at universities. The results of this study may also add evidence to university administrators and public health educators elsewhere dealing with students from Romania.

Alcoholism and alcohol drinking habits predicted from alcohol dehydrogenase genes

DEFF Research Database (Denmark)

Tolstrup, J.S.; Nordestgaard, Børge; Rasmussen, S.

2008-01-01

Alcohol is degraded primarily by alcohol dehydrogenase (ADH) wherein genetic variation that affects the rate of alcohol degradation is found in ADH1B and ADH1C. It is biologically plausible that these variations may be associated with alcohol drinking habits and alcoholism. By genotyping 9080 whi...

Repeated cocaine administration results in supersensitivity of striatal D-2 dopamine autoreceptors to pergolide

International Nuclear Information System (INIS)

Dwoskin, L.P.; Peris, J.; Yasuda, R.P.; Philpott, K.; Zahniser, N.R.

1988-01-01

Groups of rats administered cocaine-HCl (10 mg/kg, i.p.) or saline either acutely or once daily for 8 or 14 days were killed 24 hrs after the last dose. In striatal slices prelabelled with [ 3 H]DA, modulation of [ 3 H]-overflow by pergolide was used to measure D-2 autoreceptor activity. Compared to the contemporaneous control group pergolide produced a greater inhibition only in striatal slices from rats treated repeatedly with cocaine. In radioligand binding studies using striatal membranes from control rats, pergolide had a 500-fold greater affinity for the D-2, as opposed to the D-1, dopamine (DA) receptor subtype. These results indicate that repeated treatment with cocaine produces supersensitive striatal D-2 release-modulating autoreceptors consistent with a compensatory change to diminish the effect of elevated synaptic concentrations of DA produced by cocaine. In contrast, supersensitivity of D-2 receptors was not detected in [ 3 H]spiperone binding assays. 31 references, 2 figures, 1 table

78 FR 77196 - Random Drug and Alcohol Testing Percentage Rates of Covered Aviation Employees for the Period of...

Science.gov (United States)

2013-12-20

... DEPARTMENT OF TRANSPORTATION Federal Aviation Administration Random Drug and Alcohol Testing... the minimum random drug and alcohol testing percentage rates for the period January 1, 2014, through... Federal Regulations Title 14, section 120.109(b) (for drug testing), and 120.217(c) (for alcohol testing...

Safety level of Levofloxacin following repeated oral adminstration in White Leg Horn layer birds

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Jatin H. Patel

2009-08-01

Full Text Available Levofloxacin is a fluorinated quinolone which has broad-spectrum antibacterial activity at low plasma/tissue concentration. The present study was designed to investigate safety of levofloxacin (10 mg/kg after repeated oral administration at 12 hours interval for 14 days in layer birds (30-35 weeks old and weighing between 1.5-2.0 kg and to determine tissue concentration of the drug following oral administration (10 mg/kg for 5 days. Drug concentration in tissue was determined using High Performance Liquid Chromatography (HPLC. Repeated oral administration of levofloxacin in layer birds was found safe based on evaluation of haematological (Hb, PCV, TLC and DLC, blood biochemical (AST, ALT, AKP, ACP, LDH, BUN, Serum total protein, Serum albumin, Serum Creatinine, Blood glucose and Total bilirubin and histopathology of liver, kidney and joint cartilage. Levofloxacin could not be detected in body tissues (liver and skeletal muscle at 12 hours after the last administration. [Vet. World 2009; 2(4.000: 137-139

Breaking the 'detox-loop' for alcoholics with social detoxification.

Science.gov (United States)

Richman, A; Neumann, B

1984-01-01

A significant number of alcoholics do not respond to detoxification as a step on the way to rehabilitation. Instead, they periodically 'dry out' and subsequently return to alcohol abuse. They do not accept the responsibilities inherent in the sick role (cooperation in order to improve status of health by entering and continuing treatment), although they do accept the privileges (care, shelter and asylum). Repeated detoxifications (within medical and non-medical settings) of persons who do not commit themselves to entering rehabilitation, are of minimum benefit to the patient and absorb resources which could be better used by those more amendable to treatment. An appropriate level of care--social detoxification--should be provided for ' detox - loopers '. Such a model can focus on the alcoholic's social welfare needs. Social detoxification provides both respite and basic care. The door to ongoing rehabilitation through professional services, as well as self-help groups, can remain open, without being the main objective of the centre.

Alcohol-related and mental health care for patients with unhealthy alcohol use and posttraumatic stress disorder in a National Veterans Affairs cohort.

Science.gov (United States)

Chen, Jessica A; Owens, Mandy D; Browne, Kendall C; Williams, Emily C

2018-02-01

Unhealthy alcohol use and posttraumatic stress disorder (PTSD) frequently co-occur. Patients with both conditions have poorer functioning and worse treatment adherence compared to those with either condition alone. Therefore, it is possible that PTSD, when co-occurring with unhealthy alcohol use, may influence receipt of evidence-based alcohol-related care and mental health care. We evaluated receipt of interventions for unhealthy alcohol use and receipt of mental health follow-up care among patients screening positive for unhealthy alcohol use with and without PTSD in a national sample from the Veterans Health Administration (VA). National clinical and administrative data from VA's electronic medical record were used to identify all patients who screened positive for unhealthy alcohol use (AUDIT-C score≥5) between 10/1/09-5/30/13. Unadjusted and adjusted Poisson regression models were fit to estimate the relative rate and prevalence of receipt of: brief interventions (advice to reduce or abstain from drinking≤14days after positive screening), specialty addictions treatment for alcohol use disorder (AUD; documented visit≤365days after positive screening), pharmacotherapy for AUD (filled prescription≤365days after positive screening), and mental health care ≤14days after positive screening for patients with and without PTSD (documented with ICD-9 CM codes). In secondary analyses, we tested effect modification by both severity of unhealthy alcohol use and age. Among 830,825 patients who screened positive for unhealthy alcohol use, 140,388 (16.9%) had documented PTSD. Of the full sample, 71.6% received brief interventions, 10.3% received specialty AUD treatment, 3.1% received pharmacotherapy for AUD, and 24.0% received mental health care. PTSD was associated with increased likelihood of receiving all types of care. Adjusted relative rates were 1.04 (95% CI 1.03-1.05) for brief interventions, 1.06 (1.05-1.08) for specialty AUD treatment, 1.35 (1.31-1.39) for

Drunk decisions: Alcohol shifts choice from habitual towards goal-directed control in adolescent intermediate-risk drinkers.

Science.gov (United States)

Obst, Elisabeth; Schad, Daniel J; Huys, Quentin Jm; Sebold, Miriam; Nebe, Stephan; Sommer, Christian; Smolka, Michael N; Zimmermann, Ulrich S

2018-05-01

Studies in humans and animals suggest a shift from goal-directed to habitual decision-making in addiction. We therefore tested whether acute alcohol administration reduces goal-directed and promotes habitual decision-making, and whether these effects are moderated by self-reported drinking problems. Fifty-three socially drinking males completed the two-step task in a randomised crossover design while receiving an intravenous infusion of ethanol (blood alcohol level=80 mg%), or placebo. To minimise potential bias by long-standing heavy drinking and subsequent neuropsychological impairment, we tested 18- to 19-year-old adolescents. Alcohol administration consistently reduced habitual, model-free decisions, while its effects on goal-directed, model-based behaviour varied as a function of drinking problems measured with the Alcohol Use Disorders Identification Test. While adolescents with low risk for drinking problems (scoring towards goal-directed decision-making, such that alcohol possibly even improved their performance. We assume that alcohol disrupted basic cognitive functions underlying habitual and goal-directed decisions in low-risk drinkers, thereby enhancing hasty choices. Further, we speculate that intermediate-risk drinkers benefited from alcohol as a negative reinforcer that reduced unpleasant emotional states, possibly displaying a novel risk factor for drinking in adolescence.

Treatment of infected bulla with alcohol sclerosis combined with percutaneous catheter drainage: a preliminary report

International Nuclear Information System (INIS)

Han, Young Min; Lee, Jeong Min; Kim, Chong Soo; Chung, Gyung Ho; Rhee, Yang Keen; Lee, Yong Chul; Sohn, Myung Hee; Choi, Ki Chul

1995-01-01

To evaluate effectiveness of alcohol sclerosis combined with percutaneous catheter drainage (PCD) for treatment of infected bulla. Infected bulla in four consecutive patients were treated. In all patients, percutaneous catheter drainage of the bulla was performed. Instillation of sterile alcohol (99% ethanol) was carried out into the cavity of the bulla. Alcohol was left in the cavity for approximately 30 minutes in each session. Alcohol instillation was repeated according to the size of bulla. Patients were subsequently followed up with serial chest radiographs and CT scans. All patients showed significant improvement both clinically and radiologically. Disappearance of the bulla and reexpansion of surrounding lung parenchyma was observed in two patients and partial resolution (80% reduction in size) was seen in another two patients. Complications included mild chest pain during instillation of alcohol in all patients and delayed radiating shoulder pain in one patient. We provisionally conclude that intracavitary alcohol instillation combined with PCD is effective in the treatment of the infected bulla

Relaxin-3 receptor (RXFP3 signalling mediates stress-related alcohol preference in mice.

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Andrew W Walker

Full Text Available Stressful life events are causally linked with alcohol use disorders (AUDs, providing support for a hypothesis that alcohol consumption is aimed at stress reduction. We have previously shown that expression of relaxin-3 mRNA in rat brain correlates with alcohol intake and that central antagonism of relaxin-3 receptors (RXFP3 prevents stress-induced reinstatement of alcohol-seeking. Therefore the objectives of these studies were to investigate the impact of Rxfp3 gene deletion in C57BL/6J mice on baseline and stress-related alcohol consumption. Male wild-type (WT and Rxfp3 knockout (KO (C57/B6JRXFP3TM1/DGen littermate mice were tested for baseline saccharin and alcohol consumption and preference over water in a continuous access two-bottle free-choice paradigm. Another cohort of mice was subjected to repeated restraint followed by swim stress to examine stress-related alcohol preference. Hepatic alcohol and aldehyde dehydrogenase activity was assessed in mice following chronic alcohol intake and in naive controls. WT and Rxfp3 KO mice had similar baseline saccharin and alcohol preference, and hepatic alcohol processing. However, Rxfp3 KO mice displayed a stress-induced reduction in alcohol preference that was not observed in WT littermates. Notably, this phenotype, once established, persisted for at least six weeks after cessation of stress exposure. These findings suggest that in mice, relaxin-3/RXFP3 signalling is involved in maintaining high alcohol preference during and after stress, but does not appear to strongly regulate the primary reinforcing effects of alcohol.

Impaired recovery of brain muscarinic receptor sites following an adaptive down-regulation induced by repeated administration of diisopropyl fluorophosphate in aged rats

International Nuclear Information System (INIS)

Pintor, A.; Fortuna, S.; De Angelis, S.; Michalek, H.

1990-01-01

Potential age-related differences in the recovery rate of brain cholinesterase activity (ChE) and muscarinic acetylcholine receptor binding sites (mAChRs) following reduction induced by repeated treatment with diisopropyl fluorophosphate (DFP) were evaluated in Sprague-Dawley rats. Male 3- and 24-month old rats were s.c. injected with DFP on alternate days for 2 weeks and killed 48 hr and 7, 14, 21, 28 and 35 days after the last treatment. In the hippocampus and striatum, but not in the cerebral cortex, of control rats there as a significant age-related decline of ChE activity and maximal density of 3H-QNB binding sites (Bmax). The repeated administration of DFP during the first week caused a syndrome of cholinergic stimulation both in aged and young rats. The syndrome was more pronounced, in terms of intensity and duration in aged than in young animals resulting in 40 and 12% mortality, respectively; during the second week the syndrome attenuated in the two age-groups. The percentage inhibition of brain ChE at the end of DFP treatment did not differ between young and surviving aged rats. The down-regulation of mACRs was present in the three brain regions of both young and age rats (from 20 to 40%). Factorial analysis of variance showed significant differences for age, recovery rate, and significant interaction between age and recovery rate, both for ChE and mAChRs in young rats the three brain areas

Impaired recovery of brain muscarinic receptor sites following an adaptive down-regulation induced by repeated administration of diisopropyl fluorophosphate in aged rats

Energy Technology Data Exchange (ETDEWEB)

Pintor, A.; Fortuna, S.; De Angelis, S.; Michalek, H. (Istituto Superiore di Sanita, Rome (Italy))

1990-01-01

Potential age-related differences in the recovery rate of brain cholinesterase activity (ChE) and muscarinic acetylcholine receptor binding sites (mAChRs) following reduction induced by repeated treatment with diisopropyl fluorophosphate (DFP) were evaluated in Sprague-Dawley rats. Male 3- and 24-month old rats were s.c. injected with DFP on alternate days for 2 weeks and killed 48 hr and 7, 14, 21, 28 and 35 days after the last treatment. In the hippocampus and striatum, but not in the cerebral cortex, of control rats there as a significant age-related decline of ChE activity and maximal density of 3H-QNB binding sites (Bmax). The repeated administration of DFP during the first week caused a syndrome of cholinergic stimulation both in aged and young rats. The syndrome was more pronounced, in terms of intensity and duration in aged than in young animals resulting in 40 and 12% mortality, respectively; during the second week the syndrome attenuated in the two age-groups. The percentage inhibition of brain ChE at the end of DFP treatment did not differ between young and surviving aged rats. The down-regulation of mACRs was present in the three brain regions of both young and age rats (from 20 to 40%). Factorial analysis of variance showed significant differences for age, recovery rate, and significant interaction between age and recovery rate, both for ChE and mAChRs in young rats the three brain areas.

The Relationship between Assessment and Alcohol Treatment.

Science.gov (United States)

Maisto, Stephen A.; Nirenberg, Ted D.

The matching hypothesis, presented in this study, predicts that designing treatment according to patient characteristics leads to better outcomes. A study was conducted to collect data on current practices of patient-treatment matching in alcohol treatment. A questionnaire was completed by 70 directors of Veterans Administration inpatient alcohol…

Fenofibrate--a lipid-lowering drug--reduces voluntary alcohol drinking in rats.

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Karahanian, Eduardo; Quintanilla, Maria Elena; Fernandez, Katia; Israel, Yedy

2014-11-01

The administration of disulfiram raises blood acetaldehyde levels when ethanol is ingested, leading to an aversion to alcohol. This study was aimed at assessing the effect of fenofibrate on voluntary ethanol ingestion in rats. Fenofibrate reduces blood triglyceride levels by increasing fatty acid oxidation by liver peroxisomes, along with an increase in the activity of catalase, which can oxidize ethanol to acetaldehyde. UChB drinker rats were allowed to consume alcohol 10% v/v freely for 60 days, until consumption stabilized at around 7 g ethanol/kg/24 h. About 1-1.2 g ethanol/kg of this intake is consumed in the first 2 h of darkness of the circadian cycle. Fenofibrate subsequently administered (50 mg/kg/day by mouth [p.o.]) for 14 days led to a 60-70% (p intake was determined within the first 2 h of darkness, the reduction was 85-90% (p chronically allowed access to ethanol and subsequently treated with fenofibrate, would a) increase liver catalase activity, and b) increase blood acetaldehyde levels after a 24-h ethanol deprivation and the subsequent administration of 1 g ethanol/kg. The oral administration of 1 g ethanol/kg produced a rapid increase in blood (arterial) acetaldehyde in fenofibrate-treated animals versus controls also administered 1 g/kg ethanol (70 μM vs. 7 μM; p alcohol dehydrogenase and aldehyde dehydrogenase) remained unchanged. No liver damage was induced, as measured by serum glutamic-pyruvic transaminase (GPT) activity. The effect of fenofibrate in reducing alcohol intake was fully reversible. Overall, in rats allowed chronic ethanol intake, by mouth (p.o.), fenofibrate administration increased liver catalase activity and reduced voluntary ethanol intake. The administration of 1 g ethanol/kg (p.o.) to these animals increased blood acetaldehyde levels in fenofibrate-treated animals, suggesting the possible basis for the reduction in ethanol intake. Copyright © 2014 Elsevier Inc. All rights reserved.

75 FR 76069 - Random Drug and Alcohol Testing Percentage Rates of Covered Aviation Employees for the Period of...

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2010-12-07

... DEPARTMENT OF TRANSPORTATION Federal Aviation Administration Random Drug and Alcohol Testing... minimum random drug and alcohol testing percentage rates for the period January 1, 2011, through December... Regulations Title 14, section 120.109(b) (for drug testing), and 120.217(c) (for alcohol testing). Issued in...

77 FR 71669 - Random Drug and Alcohol Testing Percentage Rates of Covered Aviation Employees for the Period of...

Science.gov (United States)

2012-12-03

... DEPARTMENT OF TRANSPORTATION Federal Aviation Administration Random Drug and Alcohol Testing... the minimum random drug and alcohol testing percentage rates for the period January 1, 2013, through... Regulations Title 14, Sec. Sec. 120.109(b) (for drug testing), and 120.217(c) (for alcohol testing). Issued in...

76 FR 74843 - Random Drug and Alcohol Testing Percentage Rates of Covered Aviation Employees for the Period of...

Science.gov (United States)

2011-12-01

... DEPARTMENT OF TRANSPORTATION Federal Aviation Administration Random Drug and Alcohol Testing... the minimum random drug and alcohol testing percentage rates for the period January 1, 2012, through... Regulations Title 14, Sec. 120.109(b) (for drug testing), and 120.217(c) (for alcohol testing). Issued in...

A moderate dose of alcohol does not influence experience of social ostracism in hazardous drinkers

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Joseph OL Buckingham

2016-04-01

Full Text Available Anecdotal and correlational evidence suggests a relationship between social ostracism and alcohol dependence. Furthermore, a recent fMRI investigation found differences in the neural correlates associated with ostracism in people with alcohol dependence compared to healthy controls. We predicted that acutely administered alcohol would reduce the negative effects of social ostracism. Alcohol (0.4g/kg or matched placebo was administered to a sample of 32 hazardous drinkers over two sessions in a randomized, double-blind, cross-over design. In each session, participants were exposed to an ostracism event via the computerized ball passing game, Cyberball. In order to quantify the effects of ostracism, the fundamental needs questionnaire was completed twice on each testing session; immediately after (i social inclusion and (ii social exclusion. Ostracism caused robust changes to scores on the fundamental needs questionnaire, in line with previous literature. Alcohol administration did not influence the effects of simulated social ostracism, which was supported by a Bayesian analysis. Exploratory analyses revealed a negative relationship between age and ostracism induced fundamental needs threat across both sessions. In conclusion, a moderate dose of alcohol did not influence experience of simulated social ostracism in hazardous drinkers. Further research is needed to establish the effects of alcohol administration on social ostracism using different doses and populations of alcohol users.

Applications of virtual reality in individuals with alcohol misuse: A systematic review.

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Ghiţă, Alexandra; Gutiérrez-Maldonado, José

2018-06-01

Alcohol use and misuse have been intensively studied, due to their negative consequences in the general population. Evidence-based literature emphasizes that alcohol craving plays a crucial role in the development and maintenance of alcohol-drinking patterns. Many individuals develop Alcohol Use Disorders (AUD); significantly, after treatment many also experience relapses, in which alcohol craving has been repeatedly implicated. Cue-exposure therapy (CET) has been widely used in the treatment of alcohol misuse, but the results are inconsistent. Virtual reality (VR) can add effectiveness to cue-exposure techniques by providing multiple variables and inputs that enable personalized alcohol use assessment and treatment. The aim of this review was to examine the applications of virtual reality in individuals who misuse alcohol. We conducted an exhaustive literature search of the Web of Science, Scopus, Embase, Google Scholar, and PsycInfo databases, using as search items terms such as "alcohol" and its derivates, and virtual reality. We identified 13 studies on alcohol craving that implemented virtual reality as an assessment or treatment tool. The studies that incorporate VR present clear limitations. First, no clinical trials were conducted to explore the efficacy of the VR as a treatment tool; nor were there any studies of the generalization of craving responses in the real world, or of the long-term effects of VR treatment. Despite these limitations, the studies included showed consistent results as regards eliciting and reducing alcohol craving. We suggest that VR shows promise as a tool for the assessment and treatment of craving among individuals with alcohol misuse. Further studies implementing VR in the field of alcohol consumption are now required. Copyright © 2018 Elsevier Ltd. All rights reserved.

Results from the 2013 drug and alcohol testing survey.

Science.gov (United States)

2015-12-01

This report summarizes the results of the 2013 Federal Motor Carrier Safety Administration (FMCSA) Drug and Alcohol Testing Survey. This annual survey measures the percentage of drivers with commercial drivers licenses (CDLs) that test positive fo...

Results from the 2008 Drug and Alcohol Testing Survey

Science.gov (United States)

2010-01-01

This report summarizes the results of the 2008 Federal Motor Carrier Safety Administration Drug and Alcohol Testing Survey. This annual survey measures the percentage of drivers with commercial drivers licenses who test positive for controlled sub...

Moderate alcohol consumption after a mental stressor attenuates the endocrine stress response.

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Schrieks, I C; Joosten, M M; Klöpping-Ketelaars, W A A; Witkamp, R F; Hendriks, H F J

2016-12-01

Alcohol is often consumed to reduce tension and improve mood when exposed to stressful situations. Previous studies showed that moderate alcohol consumption may reduce stress when alcohol is consumed prior to a stressor, but data on the effect of alcohol consumption after a mental stressor is limited. Therefore, our objective was to study whether moderate alcohol consumption immediately after a mental stressor attenuates the stress response. Twenty-four healthy men (age 21-40 y, BMI 18-27 kg/m 2 ) participated in a placebo-controlled trial. They randomly consumed 2 cans (660 mL, ∼26 g alcohol) of beer or alcohol-free beer immediately after a mental stressor (Stroop task and Trier Social Stress Test). Physiological and immunological stress response was measured by monitoring heart rate and repeated measures of the hypothalamic-pituitary-adrenal axis (HPA-axis), white blood cells and a set of cytokines. After a mental stressor, cortisol and adrenocorticotropic hormone (ACTH) concentrations were 100% and 176% more reduced at 60 min (P = 0.012 and P = 0.001, respectively) and 92% and 60% more reduced at 90 min (P stress recovery period after beer consumption than after alcohol-free beer consumption (P stress response as reflected by decreasing plasma ACTH and cortisol. Copyright © 2016 Elsevier Inc. All rights reserved.

Successful repeat transcatheter ablation of a mediastinal parathyroid adenoma 6 years after alcohol embolization

International Nuclear Information System (INIS)

Cook, Gary J. R.; Fogelman, Ignac; Reidy, John F.

1997-01-01

Recurrent hyperparathyroidism is rare following transcatheter ablation of mediastinal parathyroid adenomas. When it occurs it is usually early and resistant to further attempts at ablation. We present a patient with primary hyperparathyroidism in whom two surgical attempts at cure had been unsuccessful. Subsequently, a mediastinal adenoma was demonstrated angiographically and embolized with absolute alcohol. Hyperparathyroidism recurred 6 years later and the mediastinal adenoma was subsequently successfully ablated a second time by angiographic embolization with ionic contrast medium

An Examination of Problems and Solutions Related to the Chronic "Revolving Door" Alcohol Abuser. DHSS Planning Guideline #1, Task Assignment #1.11. Long-Term Support, Chronic Alcoholism and Other Drug Abuse.

Science.gov (United States)

Vick, John W.; Houden, Dorothy

This report contains recommendations of a Wisconsin Task Assignment Steering Committee created to explore solutions to some significant problems facing adult chronic "revolving-detox-door" alcohol abusers (CRA's), persons with repeated admissions for detoxification services; and to examine the system that serves and funds them. This…

Pharmacokinetics/Pharmacodynamics findings after repeated administration of ARTESUNATE thermostable suppositories (RECTOCAPS) in Vietnamese patients with uncomplicated malaria.

Science.gov (United States)

Benakis, A; Binh, Tran Quang; Keundjian, A; Scheiwe, M W

2006-01-01

technique with electrochemical detector was used for quantification of ART and DHART. From the blood concentration values of ART and DHART, the following observation can be derived: the onset of action is observed within the first half hours, therapeutic levels of the drug obtained (89 microg/ml ART compared to 84 microg/ml DHART). The DHART levels are somewhat higher than those of ART (a peak concentration after 6 h starting medication of 151 microg/ml ART as compared to 276 microg/ml DHART). The variations as a function of frequency of DHART uptake are much less marked than those observed for ART. Another finding is that after the administration, some sort of a plateau of DHART and ART is built up, lasting at least from 9 to 12 hours with DHART level of about 190 microg/ml and ART of 90 microg/ml. In the case of single-dose administration, the levels of both compounds were below the detection threshold after three hours. With regard to the parasite counts, although there were inter-individual variations, it should be noted that after 48 hours a high proportion of the patients (8 out of 12) was completely clear of parasites. Similar results were observed with regard to the body temperature (7 out of 12 returned to normal temperature 36 hours after starting the therapy). The findings of the study support the RECTOCAPS application principle resulting in effectiveness both for the velocity of drug uptake as well as for the height of plasma levels. Repeated administration of ART can extend the duration of therapeutic plasma levels of the drug.

Impulsive and reflective processes related to alcohol use in young adolescents

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Sara ePieters

2014-05-01

Full Text Available Background: Dual process models suggest that the development of addictive behaviors is the result of interplay between impulsive and reflective processes, modulated by boundary conditions such as individual or situational factors. Empirical support for this model has been repeatedly demonstrated in adult samples (for a meta-analysis see Rooke, Hine, & Thorsteinsson, 2008. The purpose of this study was to test these processes as they relate to emerging alcohol use in adolescents. Specifically, the interactive effects of several measures of impulsive and reflective processes and working memory capacity are examined as predictors of changes in alcohol use among adolescents. It was expected that measures of reflective processes would better predict changes in alcohol use than measures of impulsive processes. Moreover, it was anticipated that working memory capacity would moderate the relation between alcohol-specific impulsive and reflective processes and changes in adolescent alcohol use. Methods: The sample consisted of 427 adolescents (47.7% male between 12 and 16 years of age (M = 13.96, SD = .78 who reported drinking alcohol at least once. Four measures of impulsive processes were included. Attentional bias for alcohol was assessed with a Visual Probe Test; approach bias toward alcohol was assessed with a Stimulus Response Compatibility Test (SRC; and memory associations with alcohol were assessed with an Implicit Association Test (IAT and a Word Association Test (WAT. Two measures of reflective measures were included: positive and negative expectancies. Working memory capacity was measured using a Self-Ordered Pointing Task (SOPT.Results: Results showed that positive expectancies predicted changes in alcohol use, but this effect was qualified by an interaction with IAT scores. Moreover, SRC scores predicted changes in alcohol use only when negative expectancies were low. Attentional bias and word association scores did not predict changes in

Effects of low doses of alcohol on declarative memory in humans

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José Arturo Bríñez-Horta

2011-09-01

Full Text Available This study assessed the effect of low doses of alcohol on two elements of explicit or declarative memory, in 16 participants, 8 women and 8 men, with The Weschler Memory Scale III Text Test. A factorial 2 * 4 counterbalanced with repeated measures design was used. There were no statistically significant differences by gender, but there were differences among doses, specially 0.150 g / Kg., which reduced episodic and semantic retrieval, between 43.9 and 62.9 % of effect strength, in intermediate term memory. These results provided evidence that alcohol in low doses has a more pronounced effect in semantic, rather than episodic memory, in the middle term

21 CFR 573.880 - Normal propyl alcohol.

Science.gov (United States)

2010-04-01

... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Normal propyl alcohol. 573.880 Section 573.880 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS FOOD ADDITIVES PERMITTED IN FEED AND DRINKING WATER OF ANIMALS Food...

Changes in undergraduates' marijuana, heavy alcohol and cigarette use following legalization of recreational marijuana use in Oregon.

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Kerr, David C R; Bae, Harold; Phibbs, Sandi; Kern, Adam C

2017-11-01

Recreational marijuana legalization (RML) went into effect in Oregon in July 2015. RML is expected to influence marijuana use by adolescents and young adults in particular, and by those with a propensity for substance use. We sought to quantify changes in rates of marijuana use among college students in Oregon from pre- to post-RML relative to college students in other states across the same time period. Repeated cross-sectional survey data from the 2012-16 administrations of the Healthy Minds Study. Seven 4-year universities in the United States. There were 10 924 undergraduate participants. One large public Oregon university participated in 2014 and 2016 (n = 588 and 1115, respectively); six universities in US states where recreational marijuana use was illegal participated both in 2016 and at least once between 2012 and 2015. Self-reported marijuana use in the past 30 days (yes/no) was regressed on time (pre/post 2015), exposure to RML (i.e. Oregon students in 2016) and covariates using mixed-effects logistic regression. Moderation of RML effects by recent heavy alcohol use was examined. Rates of marijuana use increased from pre- to post-2015 at six of the seven universities, a trend that was significant overall. Increases in rates of marijuana use were significantly greater in Oregon than in comparison institutions, but only among students reporting recent heavy alcohol use. Rates of Oregon college students' marijuana use increased (relative to that of students in other states) following recreational marijuana legislation in 2015, but only for those who reported recent heavy use of alcohol. Such alcohol misuse may be a proxy for vulnerabilities to substance use or lack of prohibitions (e.g. cultural) against it. © 2017 Society for the Study of Addiction.

The Effects of Mothers' Protective Parenting and Alcohol Use on Emerging Adults' Alcohol Use: Testing Indirect Effects Through Prototype Favorability Among African American Youth.

Science.gov (United States)

Cleveland, Michael J; Turrisi, Rob; Gibbons, Frederick X; Gerrard, Meg; Marzell, Miesha

2018-06-07

We examined how mothers' protective parenting and alcohol use influenced changes in offspring's heavy drinking among a sample of African American youth. The conceptual model also tested indirect effects of mothers' behaviors, through changes in the youths' social images (i.e., prototypes) of heavy drinkers, derived from the prototype willingness (PW) model. Participants were 686 emerging adults (55% female) from the Family and Community Health Study (FACHS), an ongoing prospective study of African American families. Three waves of FACHS data were used as follows: T3 during 10th grade (M age = 16.3 years), T4 shortly after high school (M age = 19.4 years), and T5 3 years later (M age = 22.1 years). Mothers' self-reports of protective parenting and alcohol use were assessed at T4. Two separate path models tested the study hypotheses. The first model specified direct and indirect effects of mothers' protective parenting and alcohol use. The second model added interaction terms between the protective parenting behaviors and mothers' alcohol use. The analyses were first conducted using the full sample and then repeated separately for female and male participants. Maternal alcohol use had a positive and direct effect on offspring's alcohol use. Mothers' endorsement of alcohol-related rules inhibited normative increases in the favorability of the offspring's social image of heavy drinkers (prototype) while her warmth was positively related to these increases. Maternal alcohol use amplified the positive association between mothers' warmth and the daughters' increased drinking. For sons, maternal alcohol use increased the positive association between alcohol-related rules and increased prototype favorability. Results indicated clear gender differences in how mothers' behaviors influence her offspring's alcohol use during the transition to emerging adulthood. Interventions that target culturally specific risk and protective factors within the family environment are

Effects of BCL oral administation and herbal acupuncture at BL18, BL19 on Liver function changes induced by Alcohol in the mice

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Sa-Hyun Park

2002-02-01

Full Text Available This dissertation was designed to evaluate the effect of BCL(refinded Bambusae Caulis in Liqua-men oral administration and herbal acupuncture on alcohol metabolism and liver function. For this study. mice were damaged by a large quantity of alcohol and received treatment of either BCL 1 mg/kg in oral or BCL 250㎍/kg in herbal acupuncture-BL18 . BL19 bilateral. and then such parameters as GOT. GPT. catalase and superoxide dismustase(CuZn-SOD, Mn-SOD were measured. The results of the experiments were summarized as follows. 1. Compared with control group, the proper degree of alcohol in serum was not significantly differ from oral administration group and herbal acupuncture group. 2. Compared with control group. the activity of GOT in serum was significantly reduced both oral administration and herbal acupuncture group. 3. Compared with control group. the activity of GPT in serum was significantly reduced both oral administration and herbal acupuncture group. 4. The activity of catalase in liver cell tissue, compared with control group. was not sigificantly affected either by oral administration and herbal acupuncture group. 5. The activity of CuZn-SOD in liver cell tissue was not significantly change in herbal acupuncture and oral administration group. The activity of Mn-SOD was significantly increased in oral administration group. while it was not the case in acupuncture group. In conclusion. we consider that BCL oral administration and herbal acupuncture is highly effetive in recovering alcohol metabolism and liver disfunction induced by alcohol.

Alcohol abuse management in primary care: an e-learning course.

Science.gov (United States)

Pereira, Celina Andrade; Wen, Chao Lung; Tavares, Hermano

2015-03-01

The mental health knowledge gap challenges public health. The Alcohol Abuse Management in Primary Care (AAMPC) is an e-learning course designed to cover alcohol-related problems from the primary care perspective. The goal of this study was to verify if the AAMPC was able to enhance healthcare professionals' alcohol-related problems knowledge. One hundred subscriptions for the AAMPC were offered through the federal telehealth program. The course was instructor-led and had nine weekly classes, delivered synchronously or asynchronously, at the students' convenience, using a varied array of learning tools. At the beginning, students took a test that provided a positive score, related to critical knowledge for clinical management, and a negative score, related to misconceptions about alcohol-related problems. The test was repeated 2 months after course completion. Thirty-three students completed the course. The positive score improved significantly (pE-learning was highly appreciated as a learning tool, especially by students with the least frequency of Internet use. Nonetheless, it worked better for those previously familiar with e-courses. The AAMPC e-course provided effective knowledge transmission and retention. Complementary strategies to reduce misconceptions about alcohol-related problems must be developed for the training of primary care staff.

Short-term effects of repeated olfactory administration of homeopathic sulphur or pulsatilla on electroencephalographic alpha power in healthy young adults.

Science.gov (United States)

Bell, Iris R; Brooks, Audrey J; Howerter, Amy; Jackson, Nicholas; Schwartz, Gary E

2011-10-01

Homeopathic pathogenetic trials usually rely on symptom self report measures. Adding objective biomarkers could enhance detection of subtle initial remedy effects. The present feasibility study examined electroencephalographic (EEG) effects of repeated olfactory administration of two polycrest remedies. College student volunteers (ages 18-30, both sexes) from an introductory psychology course were screened for good health and relatively elevated Sulphur or Pulsatilla symptom scores on the Homeopathic Constitutional Type Questionnaire (CTQ). Subjects underwent a series of 3 once-weekly double-blind sessions during which they repeatedly sniffed the remedy matched to their CTQ type and solvent controls. Each remedy was given in a 6c, 12c, and 30c potency, one potency per week, in randomly assigned order. Solvent controls included both plain distilled water and a water-ethanol (95%) solution. All sniff test solutions were further diluted just prior to laboratory sessions (0.5 ml test solution in 150 ml distilled water). Within a session, remedies and control solvents were administered via 2-s sniffs (8 sniffs of each of 4 different succussion levels for the potency in randomized order). Primary outcome variable was relative EEG power (alpha 1 8-10 Hz; alpha 2 10-12 Hz) averaged over 19 electrode sites, including all succussions for a given potency. Mixed-effect models revealed significant main effects for remedy type (Sulphur >Pulsatilla) in both alpha bands, controlling for gender, baseline resting EEG alpha, and solvent control responses. Additional analyses showed significant nonlinear interactions between dilution and time (weekly session) in alpha 2 for both remedies and alpha 1 for Sulphur. EEG alpha offers an objective biomarker of remedy effects for future studies and potential method for distinguishing time-dependent effects of specific remedies and remedy potencies from one another. Copyright © 2011 The Faculty of Homeopathy. Published by Elsevier Ltd

Does alcohol affect memory for emotional and non-emotional experiences in different ways?

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Knowles, S K Z; Duka, T

2004-03-01

Alcohol has been shown to have both impairing and facilitating effects on memory, depending on the sequencing of learning and ingestion of the drug. Its effects on memory for emotional material, however, have not been shown reliably. The current experiment sought to investigate the effects of alcohol on later recall of emotional and neutral events experienced before and after alcohol drinking. Using an incidental-learning paradigm, alcohol (0.65 g/kg) or placebo was administered in a double-blind randomized design to 34 participants, between two learning phases in which they viewed and rated positive, negative and neutral images. The drug's effects on memory were assessed in a surprise test of free recall. In addition, impact of alcohol on ratings of mood states, and of valence and arousal that the pictures evoked, was examined. Alcohol facilitated memory for material seen before, and impaired memory for material seen after, its administration. Furthermore, under alcohol, emotional images in the first set were more recalled over neutral than in the second set, indicating a higher retrograde facilitation for emotional than for neutral material. Alcohol improved positive mood states but had no effect on negative mood states. Evaluation of pictures with regard to valence showed an increase of the ratings for the positive and neutral images after alcohol and a decrease after placebo. No drug effects were found for arousal ratings. Whether a picture was likely to be remembered or not (tested only for set 2) was dependent on the intensity of the arousal but not of the valence that the picture evoked in the participants. Pictures that were rated high in arousal were also remembered better, and this effect was irrespective of alcohol or placebo ingestion. These data have shown that alcohol elicits retrograde facilitation and anterograde impairment for emotional materials. Furthermore, these data demonstrate that alcohol selectively facilitates memories for emotional events

Quantifying the global contribution of alcohol consumption to cardiomyopathy.

Science.gov (United States)

Manthey, Jakob; Imtiaz, Sameer; Neufeld, Maria; Rylett, Margaret; Rehm, Jürgen

2017-05-25

The global impact of alcohol consumption on deaths due to cardiomyopathy (CM) has not been quantified to date, even though CM contains a subcategory for alcoholic CM with an effect of heavy drinking over time as the postulated underlying causal mechanism. In this feasibility study, a model to estimate the alcohol-attributable fraction (AAF) of CM deaths based on alcohol exposure measures is proposed. A two-step model was developed based on aggregate-level data from 95 countries, including the most populous (data from 2013 or last available year). First, the crude mortality rate of alcoholic CM per 1,000,000 adults was predicted using a negative binomial regression based on prevalence of alcohol use disorders (AUD) and adult alcohol per capita consumption (APC) (n = 52 countries). Second, the proportion of alcoholic CM among all CM deaths (i.e., AAF) was predicted using a fractional response probit regression with alcoholic CM crude mortality rate (from Step 1), AUD prevalence, APC per drinker, and Global Burden of Disease region as predictions. Additional models repeated these steps by sex and for the wider Global Burden of Disease study definition of CM. There were strong correlations (>0.9) between the crude mortality rate of alcoholic CM and the AAFs, supporting the modeling strategy. In the first step, the population-weighted mean crude mortality rate was estimated at 8.4 alcoholic CM deaths per 1,000,000 (95% CI: 7.4-9.3). In the second step, the global AAFs were estimated at 6.9% (95% CI: 5.4-8.4%). Sex-specific figures suggested a lower AAF among females (2.9%, 95% CI: 2.3-3.4%) as compared to males (8.9%, 95% CI: 7.0-10.7%). Larger deviations between observed and predicted AAFs were found in Eastern Europe and Central Asia. The model proposed promises to fill the gap to include AAFs for CM into comparative risk assessments in the future. These predictions likely will be underestimates because of the stigma involved in all fully alcohol

Predictors for repeat self-harm and suicide among older people within 12 months of a self-harm presentation.

Science.gov (United States)

Cheung, Gary; Foster, Gisele; de Beer, Wayne; Gee, Susan; Hawkes, Tracey; Rimkeit, Sally; Tan, Yu Mwee; Merry, Sally; Sundram, Frederick

2017-08-01

A past history of self-harm is a significant risk factor for suicide in older people. The aims of this study are to (i) characterize older people who present with self-harm to emergency departments (EDs); and (ii) determine the predictors for repeat self-harm and suicide. Demographic and clinical data were retrospectively collected on older people (age 65+ years), who presented to seven EDs in New Zealand following an episode of self-harm between 1st July 2010 and 30th June 2013. In addition, 12-month follow-up information on repeat self-harm and suicide was collected. The sample included 339 older people (55.2% female) with an age range of 65-96 years (mean age = 75.0; SD = 7.6). Overdose (68.7%) was the most common method of self-harm. 76.4% of the self-harm cases were classified as suicide attempts. Perceived physical illness (47.8%) and family discord (34.5%) were the most common stressors. 12.7% of older people repeated self-harm and 2.1% died by suicide within 12 months. Older people who had a positive blood alcohol reading (OR = 3.87, 95% Cl = 1.35-11.12, p = 0.012) and were already with mental health services at the index self-harm (OR = 2.73, 95% Cl = 1.20-6.25, p = 0.047) were more likely to repeat self-harm/suicide within 12 months. Older people who self-harm are at very high risk of repeat self-harm and suicide. Screening and assessment for alcohol use disorders should be routinely performed following a self-harm presentation, along with providing structured psychological treatment as an adjunct to pharmacological treatment for depression and interventions to improve the person's resilience resources.

AN EXPERIMENTAL STUDY REGARDING THE BIOLOGICAL EFFECTS OF MINERAL WATER FROM SPRING 3 IN BĂILE TUŞNAD ON SOME ORGANS AFTER ETHYL ALCOHOL ADMINISTRATION

Directory of Open Access Journals (Sweden)

Gabriela Dogaru

2016-02-01

Full Text Available Hepatobiliary and renal disorders are currently on the increase, being favored by increasing environmental pollution, alcohol consumption and synthesis drugs. Mineral water from spring 3 in Băile Tuşnad, with a total mineralization of 3351.0 mg/l, is recommended in chronic liver, gallbladder, pancreas diseases, kidney diseases and stones. This study aimed to assess potential changes in the liver, kidney, pancreas and stomach following ethyl alcohol administration in rats, as well as to monitor anatomopathological differences between animals that drank tap water and those that drank Tușnad mineral water, after cessation of ethyl alcohol administration. The study was carried out on 25 white Wistar rats over a period of 100 days. The animals were divided into 3 groups: group I, negative control group – 5 animals; group II, positive control group – 6 animals; group III, experimental group – 14 animals. The animals of group I received tap water (50-75 ml/day/animal throughout the experiment, and those of groups II and III were administered ethyl alcohol 12% (12-15 ml/day/animal during the first 70 days. During the last 30 days of the experiment, the animals of group II received tap water (50-75 ml/day/animal, and those of group III were administered Tuşnad mineral water (50-75 ml/day/animal. On experimental day 70, 5 animals were euthanized (2 of group I, 1 of group II and 2 of group III, and on day 100, the rest of 20 animals were euthanized. Fragments in the form of 4 mm thick slices from the liver, kidneys, pancreas and stomach of the euthanized animals were collected for histological investigations. The only changes detectable by optical microscopy were present in the liver. The rest of the studied organs did not show lesion aspects detectable by optical microscopy. The structural changes found in the liver were represented by mild to moderate fibrosis around the centrilobular venule in about 50% of the lobules. In the outer third of

Commercial Ethyl Glucuronide (EtG) and Ethyl Sulfate (EtS) Testing is Not Vulnerable to Incidental Alcohol Exposure in Pregnant Women.

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Ondersma, Steven J; Beatty, Jessica R; Rosano, Thomas G; Strickler, Ronald C; Graham, Amy E; Sokol, Robert J

2016-01-02

Ethyl Glucoronide (EtG) and Ethyl Sulfate (EtS) have shown promise as biomarkers for alcohol and may be sensitive enough for use with pregnant women in whom even low-level alcohol use is important. However, there have been reports of over-sensitivity of EtG and EtS to incidental exposure to sources such as alcohol-based hand sanitizer. Further, few studies have evaluated these biomarkers among pregnant women, in whom the dynamics of these metabolites may differ. This study evaluated whether commercial EtG-EtS testing was vulnerable to high levels of environmental exposure to alcohol in pregnant women. Two separate samples of five nurses-one pregnant and the other postpartum, all of whom reported high levels of alcohol-based hand sanitizer use-provided urine samples before and 4-8 hours after rinsing with alcohol-based mouthwash and using hand sanitizer. The five pregnant nurses provided urine samples before, during, and after an 8-hour nursing shift, during which they repeatedly cleansed with alcohol-based hand sanitizer (mean 33.8 uses). The five postpartum nurses used hand sanitizer repeatedly between baseline and follow-up urine samples. No urine samples were positive for EtG-EtS at baseline or follow-up, despite use of mouthwash and-in the pregnant sample-heavy use of hand sanitizer (mean of 33.8 uses) throughout the 8-hour shift. Current, commercially available EtG-EtS testing does not appear vulnerable to even heavy exposure to incidental sources of alcohol among pregnant and postpartum women.

Effect of alcohol consumption on the liver detoxication capacity as measured by [13C]methacetin- and [methyl-13C]methionine-breath tests.

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Wutzke, Klaus D; Forberger, Anke; Wigger, Marianne

2008-06-01

The aim of this study was to investigate the hepatic microsomal and mitochondrial functions by using the 13CO2-breath test in healthy subjects either before or after the consumption of red wine. Fourteen adults received [13C]methacetin and [methyl-13C]methionine together with a standardised dinner. Expired air samples were taken over 6 h. After a wash-out period, the subjects consumed 0.4 ml ethanol/kg/day together with dinner over a 10-day period. Thereafter, 13C-tracer administration was repeated under identical conditions. The 13CO2-enrichments were measured by isotope ratio mass spectrometry. The mean cumulative percentage 13C-dose recovery (CPDR) after administration of [13C]methacetin and [methyl-13C]methionine either without or with red wine consumption amounted to 38.2+/-6.3 vs. 36.3+/-6.7% (p=0.363) and 9.5+/-3.3 vs. 8.8+/-2.5% (p=0.47), respectively. Moderate alcohol consumption does not induce significant short-term changes of the microsomal and the mitochondrial functions of the human liver in healthy subjects.

The Reinforcing Properties of Ethanol are Quantitatively Enhanced in Adulthood by Peri-Adolescent Ethanol, but not Saccharin, Consumption in Female Alcohol-Preferring (P) Rats

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Toalston, Jamie E.; Deehan, Gerald A.; Hauser, Sheketha R.; Engleman, Eric A.; Bell, Richard L.; Murphy, James M.; McBride, William J.; Rodd, Zachary A.

2015-01-01

Alcohol drinking during adolescence is associated in adulthood with heavier alcohol drinking and an increased rate of alcohol dependence. Past research in our laboratory has indicated that peri-adolescent ethanol consumption can enhance the acquisition and reduce the rate of extinction of ethanol self-administration in adulthood. Caveats of the past research include reinforcer specificity, increased oral consumption during peri-adolescence, and a lack of quantitative assessment of the reinforcing properties of ethanol. The current experiments were designed to determine the effects of peri-adolescent ethanol or saccharin drinking on acquisition and extinction of oral ethanol self-administration and ethanol seeking, and to quantitatively assess the reinforcing properties of ethanol (progressive ratio). Ethanol or saccharin access by alcohol-preferring (P) rats occurred during postnatal day (PND) 30–60. Animals began operant self-administration of ethanol or saccharin after PND 85. After 10 weeks of daily operant self-administration, rats were tested in a progressive ratio paradigm. Two weeks later, self-administration was extinguished in all rats. Peri-adolescent ethanol consumption specifically enhanced the acquisition of ethanol self-administration, reduced the rate of extinction for ethanol self-administration, and quantitatively increased the reinforcing properties of ethanol during adulthood. Peri-adolescent saccharin consumption was without effect. The data indicate that ethanol consumption during peri-adolescence results in neuroadaptations that may specifically enhance the reinforcing properties of ethanol during adulthood. This increase in the reinforcing properties of ethanol could be a part of biological sequelae that are the basis for the effects of adolescent alcohol consumption on the increase in the rate of alcoholism during adulthood. PMID:26074425

Stimulant and motivational effects of alcohol: lessons from rodent and primate models.

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Brabant, Christian; Guarnieri, Douglas J; Quertemont, Etienne

2014-07-01

In several animal species including humans, the acute administration of low doses of alcohol increases motor activity. Different theories have postulated that alcohol-induced hyperactivity is causally related to alcoholism. Moreover, a common biological mechanism in the mesolimbic dopamine system has been proposed to mediate the stimulant and motivational effects of alcohol. Numerous studies have examined whether alcohol-induced hyperactivity is related to alcoholism using a great variety of animal models and several animal species. However, there is no review that has summarized this extensive literature. In this article, we present the various experimental models that have been used to study the relationship between the stimulant and motivational effects of alcohol in rodents and primates. Furthermore, we discuss whether the theories hypothesizing a causal link between alcohol-induced hyperactivity and alcoholism are supported by published results. The reviewed findings indicate that animal species that are stimulated by alcohol also exhibit alcohol preference. Additionally, the role of dopamine in alcohol-induced hyperactivity is well established since blocking dopaminergic activity suppresses the stimulant effects of alcohol. However, dopamine transmission plays a much more complex function in the motivational properties of alcohol and the neuronal mechanisms involved in alcohol stimulation and reward are distinct. Overall, the current review provides mixed support for theories suggesting that the stimulant effects of alcohol are related to alcoholism and highlights the importance of animal models as a way to gain insight into alcoholism. Copyright © 2014 Elsevier Inc. All rights reserved.

Prevention of fetal demise and growth restriction in a mouse model of fetal alcohol syndrome.

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Spong, C Y; Abebe, D T; Gozes, I; Brenneman, D E; Hill, J M

2001-05-01

Two peptides [NAPVSIPQ (NAP) and SALLRSIPA (ADNF-9)], that are associated with novel glial proteins regulated by vasoactive intestinal peptide, are shown now to provide protective intervention in a model of fetal alcohol syndrome. Fetal demise and growth restrictions were produced after intraperitoneal injection of ethanol to pregnant mice during midgestation (E8). Death and growth abnormalities elicited by alcohol treatment during development are believed to be associated, in part, with severe oxidative damage. NAP and ADNF-9 have been shown to exhibit antioxidative and antiapoptotic actions in vitro. Pretreatment with an equimolar combination of the peptides prevented the alcohol-induced fetal death and growth abnormalities. Pretreatment with NAP alone resulted in a significant decrease in alcohol-associated fetal death; whereas ADNF-9 alone had no detectable effect on fetal survival after alcohol exposure, indicating a pharmacological distinction between the peptides. Biochemical assessment of the fetuses indicated that the combination peptide treatment prevented the alcohol-induced decreases in reduced glutathione. Peptide efficacy was evident with either 30-min pretreatment or with 1-h post-alcohol administration. Bioavailability studies with [(3)H]NAPVSIPQ indicated that 39% of the total radioactivity comigrated with intact peptide in the fetus 60 min after administration. These studies demonstrate that fetal death and growth restriction associated with prenatal alcohol exposure were prevented by combinatorial peptide treatment and suggest that this therapeutic strategy be explored in other models/diseases associated with oxidative stress.

White Matter Integrity Pre- and Post Marijuana and Alcohol Initiation in Adolescence

Directory of Open Access Journals (Sweden)

Lindsay M. Squeglia

2013-03-01

Full Text Available Characterizing the effects of alcohol and marijuana use on adolescent brain development is important for understanding potential alterations in neurodevelopment. Several cross sectional studies have identified group differences in white matter integrity after initiation of heavy alcohol and marijuana use, however none have explored white matter trajectories in adolescents pre- and post initiation of use, particularly for marijuana users. This study followed 16 adolescents with minimal alcohol and marijuana use at ages 16–18 over three years. At follow-up, teens were 19–22 years old; half of the participants initiated heavy alcohol use and half initiated heavy alcohol and marijuana use. Repeated-measures ANOVA revealed 20 clusters in association and projection fibers tracts (p < 0.01 in which a group by time interaction was found. Most consistently, white matter integrity (i.e., fractional anisotropy decreased for those who initiated both heavy alcohol and marijuana use over the follow-up interval. No effect of time or change in white matter integrity was seen for those who initiated alcohol use only in the majority of clusters. In most regions, at the baseline time point, teens who would later initiate both alcohol and marijuana use demonstrated white matter integrity greater than or equal to teens that initiated alcohol use only. Findings suggest poorer tissue integrity associated with combined initiation of heavy alcohol and marijuana use in late adolescence. While pre-existing differences may also be related to likelihood of substance use, the present data suggest an effect on tissue integrity for these teens transitioning to combined alcohol and marijuana use in later adolescence.

Effects of acute alcohol consumption on measures of simulated driving: A systematic review and meta-analysis.

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Irwin, Christopher; Iudakhina, Elizaveta; Desbrow, Ben; McCartney, Danielle

2017-05-01

Driving simulators are used in a wide range of research settings to help develop an understanding of driver behavior in complex environments. Acute alcohol impairment is an important research topic for traffic safety and a large number of studies have indicated levels of simulated driving impairment imposed by alcohol across a range of performance outcome variables. The aim of the present study was to examine the impact of acute alcohol consumption on simulated driving performance by conducting a systematic review and meta-analysis of the available evidence. The online databases PubMed (MEDLINE), Web of Science (via Thomas Reuters) and Scopus were searched to identify studies that measured simulated car driving performance under control ('no alcohol' or 'placebo alcohol' ingestion) and intervention (acute alcohol ingestion) conditions, using repeated-measures experimental designs. Primary research outcomes were standard deviation of lane position (SDLP) and standard deviation of speed (SDSP); (total number of lane crossings (LC) and average speed (Speed) were secondary research outcomes). Meta-analytic procedures were used to quantify the effect of acute alcohol consumption on vehicle control, and to determine the influence of methodological variables (i.e. the duration of the simulated driving task, the limb of the BAC curve (ascending vs. descending) and the type of driving simulator employed (i.e. car vs. PC-based)) on the magnitude of the performance change due to alcohol consumption. 423 records were screened, and 50 repeated-measures trials (n=962 participants, 62% male) derived from 17 original publications were reviewed. 37 trials (n=721 participants) used a 'placebo alcohol' comparator to determine the effect of alcohol consumption on SDLP (32/37) and SDSP (22/37). Alcohol consumption significantly increased SDLP by 4.0±0.5cm (95% CI: 3.0, 5.1) and SDSP by 0.38±0.10km⋅h -1 (95% CI: 0.19, 0.57). Regression analyses indicate BAC (p=0.004) and driving

Patterns of alcohol use and consequences among empirically derived sexual minority subgroups.

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Talley, Amelia E; Sher, Kenneth J; Steinley, Douglas; Wood, Phillip K; Littlefield, Andrew K

2012-03-01

The current study develops an empirically determined classification of sexual orientation developmental patterns based on participants' annual reports of self-identifications, sexual attractions, and sexual behaviors during the first 4 years of college. A secondary aim of the current work was to examine trajectories of alcohol involvement among identified subgroups. Data were drawn from a subsample of a longitudinal study of incoming first-time college students at a large, public university (n = 2,068). Longitudinal latent class analysis was used to classify sexual minority participants into empirically derived subgroups based on three self-reported facets of sexual orientation. Multivariate repeated-measures analyses were conducted to examine how trajectories of alcohol involvement varied by sexual orientation class membership. Four unique subclasses of sexual orientation developmental patterns were identified for males and females: one consistently exclusively heterosexual group and three sexual minority groups. Despite generally similar alcohol use patterns among subclasses, certain sexual minority subgroups reported elevated levels of alcohol-related negative consequences and maladaptive motivations for use throughout college compared with their exclusively heterosexual counterparts. Elevations in coping and conformity motivations for alcohol use were seen among those subgroups that also evidenced heightened negative alcohol-related consequences. Implications and limitations of the current work are discussed.

The alcohol industry lobby and Hong Kong's zero wine and beer tax policy.

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Yoon, Sungwon; Lam, Tai-Hing

2012-08-30

Whereas taxation on alcohol is becoming an increasingly common practice in many countries as part of overall public health measures, the Hong Kong Special Administrative Region Government is bucking the trend and lowered its duties on wine and beer by 50 percent in 2007. In 2008, Hong Kong removed all duties on alcohol except for spirits. The aim of this paper is to examine the case of Hong Kong with its history of changes in alcohol taxation to explore the factors that have driven such an unprecedented policy evolution. The research is based on an analysis of primary documents. Searches of official government documents, alcohol-related industry materials and other media reports on alcohol taxation for the period from 2000 to 2008 were systematically carried out using key terms such as "alcohol tax" and "alcohol industry". Relevant documents (97) were indexed by date and topic to undertake a chronological and thematic analysis using Nvivo8 software. Our analysis demonstrates that whereas the city's changing financial circumstances and the Hong Kong Special Administrative Region Government's strong propensity towards economic liberalism had, in part, contributed to such dramatic transformation, the alcohol industry's lobbying tactics and influence were clearly the main drivers of the policy decision. The alcohol industry's lobbying tactics were two-fold. The first was to forge a coalition encompassing a range of catering and trade industries related to alcohol as well as industry-friendly lawmakers so that these like-minded actors could find common ground in pursuing changes to the taxation policy. The second was to deliberately promote a blend of ideas to garner support from the general public and to influence the perception of key policy makers. Our findings suggest that the success of aggressive industry lobbying coupled with the absence of robust public health advocacy was the main driving force behind the unparalleled abolition of wine and beer duties in Hong

Final report of the addendum to the safety assessment of n-butyl alcohol as used in cosmetics.

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McLain, Valerie C

2008-01-01

n-Butyl Alcohol is a primary aliphatic alcohol historically used as a solvent in nail care cosmetic products, but new concentration of use data indicate that it also is being used at low concentrations in eye makeup, personal hygiene, and shaving cosmetic products. n-Butyl Alcohol has been generally recognized as safe for use as a flavoring substance in food and appears on the 1982 Food and Drug Administration (FDA) list of inactive ingredients for approved prescription drug products. n-Butyl Alcohol can be absorbed through the skin, lungs, and gastrointestinal tract. n-Butyl Alcohol may be formed by hydrolysis of butyl acetate in the blood, but is rapidly oxidized. The single oral dose LD(50) of n-Butyl Alcohol for rats was 0.79 to 4.36 g/kg. The dermal LD(50) for rabbits was 4.2 g/kg. Inhalation toxicity studies in humans demonstrate sensory irritation of the upper respiratory tract, but only at levels above 3000 mg/m(3). Animal studies demonstrate intoxication, restlessness, ataxia, prostration, and narcosis. Exposures of rats to levels up to 4000 ppm failed to produce hearing defects. High concentrations of n-Butyl Alcohol vapors can be fatal. Ocular irritation was observed for n-Butyl alcohol at 0.005 ml of a 40% solution. The behavioral no-effect dose for n-Butyl Alcohol injected subcutaneously (s.c.) was 120 mg/kg. Fetotoxicity has been demonstrated, but only at maternally toxic levels (1000 mg/kg). No significant behavioral or neurochemical effects were seen in offspring following either maternal or paternal exposure to 3000 or 6000 ppm. n-Butyl Alcohol was not mutagenic in Ames tests, did not induce sister-chromatid exchange or chromosome breakage in chick embryos or Chinese hamster ovary cells, did not induce micronuclei formation in V79 Chinese hamster cells, did not have any chromosome-damaging effects in a mouse micronucleus test, and did not impair chromosome distribution in the course of mitosis. Clinical testing of n-Butyl Alcohol for

Beer self-administration provokes lateralized nucleus accumbens dopamine release in male heavy drinkers.

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Oberlin, Brandon G; Dzemidzic, Mario; Tran, Stella M; Soeurt, Christina M; O'Connor, Sean J; Yoder, Karmen K; Kareken, David A

2015-03-01

Although striatal dopamine (DA) is important in alcohol abuse, the nature of DA release during actual alcohol drinking is unclear, since drinking includes self-administration of both conditioned flavor stimuli (CS) of the alcoholic beverage and subsequent intoxication, the unconditioned stimulus (US). Here, we used a novel self-administration analog to distinguish nucleus accumbens (NAcc) DA responses specific to the CS and US. Right-handed male heavy drinkers (n = 26) received three positron emission tomography (PET) scans with the D2/D3 radioligand [(11)C]raclopride (RAC) and performed a pseudo self-administration task that separately administered a flavor CS of either a habitually consumed beer or the appetitive control Gatorade®, concomitant with the US of ethanol intoxication (0.06 g/dL intravenous (IV) administration) or IV saline. Scan conditions were Gatorade flavor + saline (Gat&Sal), Gatorade flavor + ethanol (Gat&Eth), and beer flavor + ethanol (Beer&Eth). Ethanol (US) reduced RAC binding (inferring DA release) in the left (L) NAcc [Gat&Sal > Gat&Eth]. Beer flavor (CS) increased DA in the right (R) NAcc [Gat&Eth > Beer&Eth]. The combination of beer flavor and ethanol (CS + US), [Gat&Sal > Beer&Eth], induced DA release in bilateral NAcc. Self-reported intoxication during scanning correlated with L NAcc DA release. Relative to saline, infusion of ethanol increased alcoholic drink wanting. Our findings suggest lateralized DA function in the NAcc, with L NAcc DA release most reflecting intoxication, R NAcc DA release most reflecting the flavor CS, and the conjoint CS + US producing a bilateral NAcc response.

Curcumin confers neuroprotection against alcohol-induced hippocampal neurodegeneration via CREB-BDNF pathway in rats.

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Motaghinejad, Majid; Motevalian, Manijeh; Fatima, Sulail; Hashemi, Hajar; Gholami, Mina

2017-03-01

Alcohol abuse causes severe damage to the brain neurons. Studies have reported the neuroprotective effects of curcumin against alcohol-induced neurodegeneration. However, the precise mechanism of action remains unclear. Seventy rats were equally divided into 7 groups (10 rats per group). Group 1 received normal saline (0.7ml/rat) and group 2 received alcohol (2g/kg/day) for 21days. Groups 3, 4, 5 and 6 concurrently received alcohol (2g/kg/day) and curcumin (10, 20, 40 and 60mg/kg, respectively) for 21days. Animals in group 7 self- administered alcohol for 21days. Group 8 treated with curcumin (60mg/kg, i.p.) alone for 21days. Open Field Test (OFT) was used to investigate motor activity in rats. Hippocampal oxidative, antioxidative and inflammatory factors were evaluated. Furthermore, brain cyclic adenosine monophosphate (cAMP) response element binding protein (CREB) and brain derived neurotrophic factor (BDNF) levels were studied at gene level by reverse transcriptase polymerase chain reaction (RT-PCR). In addition, protein expression for BDNF, CREB, phosphorylated CREB (CREB-P), Bax and Bcl-2 was determined by western blotting. Voluntary and involuntary administration of alcohol altered motor activity in OFT, and curcumin treatment inhibited this alcohol-induced motor disturbance. Also, alcohol administration augmented lipid peroxidation, mitochondrial oxidized glutathione (GSSG), interleukin-1 beta (IL-1β), tumor necrosis factor-alpha (TNF-α) and Bax levels in isolated hippocampal tissues. Furthermore, alcohol-induced significant reduction were observed in reduced form of glutathione (GSH), superoxide dismutase (SOD), glutathione peroxidase (GPx) and glutathione reductase (GR) activities and CREB, BDNF and Bcl-2 levels. Also curcumin alone did not change the behavior and biochemical and molecular parameters. Curcumin can act as a neuroprotective agent against neurodegenerative effects of alcohol abuse, probably via activation of CREB-BDNF signaling pathway

Parental alcohol use, alcohol-related problems, and alcohol-specific attitudes, alcohol-specific communication, and adolescent excessive alcohol use and alcohol-related problems: An indirect path model

NARCIS (Netherlands)

Mares, S.H.W.; Vorst, H. van der; Engels, R.C.M.E.; Lichtwarck-Aschoff, A.

2011-01-01

Alcohol-specific parent-child communication has often been studied in relation to regular alcohol use of adolescents. However, it might be as important to focus on adolescent problematic alcohol use. In addition, the way parents communicate with their children about alcohol might depend on their own

Adolescent binge-pattern alcohol exposure alters genome-wide DNA methylation patterns in the hypothalamus of alcohol-naïve male offspring.

Science.gov (United States)

Asimes, AnnaDorothea; Torcaso, Audrey; Pinceti, Elena; Kim, Chun K; Zeleznik-Le, Nancy J; Pak, Toni R

2017-05-01

Teenage binge drinking is a major health concern in the United States, with 21% of teenagers reporting binge-pattern drinking behavior in the previous 30 days. Recently, our lab showed that alcohol-naïve offspring of rats exposed to alcohol during adolescence exhibited altered gene expression profiles in the hypothalamus, a brain region involved in stress regulation. We employed Enhanced Reduced Representation Bisulfite Sequencing as an unbiased approach to test the hypothesis that parental exposure to binge-pattern alcohol during adolescence alters DNA methylation profiles in their alcohol-naïve offspring. Wistar rats were administered a repeated binge-ethanol exposure paradigm during early (postnatal day (PND) 37-44) and late (PND 67-74) adolescent development. Animals were mated 24 h after the last ethanol dose and subsequent offspring were produced. Analysis of male PND7 offspring revealed that offspring of alcohol-exposed parents exhibited differential DNA methylation patterns in the hypothalamus. The differentially methylated cytosines (DMCs) were distinct between offspring depending on which parent was exposed to ethanol. Moreover, novel DMCs were observed when both parents were exposed to ethanol and many DMCs from single parent ethanol exposure were not recapitulated with dual parent exposure. We also measured mRNA expression of several differentially methylated genes and some, but not all, showed correlative changes in expression. Importantly, methylation was not a direct predictor of expression levels, underscoring the complexity of transcriptional regulation. Overall, we demonstrate that adolescent binge ethanol exposure causes altered genome-wide DNA methylation patterns in the hypothalamus of alcohol-naïve offspring. Copyright © 2016 Elsevier Inc. All rights reserved.

Repeated ketamine administration alters N-methyl-d-aspartic acid receptor subunit gene expression: Implication of genetic vulnerability for ketamine abuse and ketamine psychosis in humans

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Lipsky, Robert H

2015-01-01

For more than 40 years following its approval by the Food and Drug Administration (FDA) as an anesthetic, ketamine, a non-competitive N-methyl-d-aspartic acid (NMDA) receptor antagonist, has been used as a tool of psychiatric research. As a psychedelic drug, ketamine induces psychotic symptoms, cognitive impairment, and mood elevation, which resemble some symptoms of schizophrenia. Recreational use of ketamine has been increasing in recent years. However, little is known of the underlying molecular mechanisms responsible for ketamine-associated psychosis. Recent animal studies have shown that repeated ketamine administration significantly increases NMDA receptor subunit gene expression, in particular subunit 1 (NR1 or GluN1) levels. This results in neurodegeneration, supporting a potential mechanism where up-regulation of NMDA receptors could produce cognitive deficits in chronic ketamine abuse patients. In other studies, NMDA receptor gene variants are associated with addictive behavior. Here, we focus on the roles of NMDA receptor gene subunits in ketamine abuse and ketamine psychosis and propose that full sequencing of NMDA receptor genes may help explain individual vulnerability to ketamine abuse and ketamine-associated psychosis. PMID:25245072

Repeated ketamine administration alters N-methyl-D-aspartic acid receptor subunit gene expression: implication of genetic vulnerability for ketamine abuse and ketamine psychosis in humans.

Science.gov (United States)

Xu, Ke; Lipsky, Robert H

2015-02-01

For more than 40 years following its approval by the Food and Drug Administration (FDA) as an anesthetic, ketamine, a non-competitive N-methyl-D-aspartic acid (NMDA) receptor antagonist, has been used as a tool of psychiatric research. As a psychedelic drug, ketamine induces psychotic symptoms, cognitive impairment, and mood elevation, which resemble some symptoms of schizophrenia. Recreational use of ketamine has been increasing in recent years. However, little is known of the underlying molecular mechanisms responsible for ketamine-associated psychosis. Recent animal studies have shown that repeated ketamine administration significantly increases NMDA receptor subunit gene expression, in particular subunit 1 (NR1 or GluN1) levels. This results in neurodegeneration, supporting a potential mechanism where up-regulation of NMDA receptors could produce cognitive deficits in chronic ketamine abuse patients. In other studies, NMDA receptor gene variants are associated with addictive behavior. Here, we focus on the roles of NMDA receptor gene subunits in ketamine abuse and ketamine psychosis and propose that full sequencing of NMDA receptor genes may help explain individual vulnerability to ketamine abuse and ketamine-associated psychosis. © 2014 by the Society for Experimental Biology and Medicine.

[Alcohol consumption before and during pregnancy in Argentina: prevalence and risk factors].

Science.gov (United States)

López, Mariana B; Filippetti, Vanessa Arán; Cremonte, Mariana

2015-05-01

Describe alcohol consumption by Argentine women before and during pregnancy and identify the factors associated with consumption- and pregnancy-related changes. Cross-sectional observational study. Women were interviewed after giving birth and receiving care at two perinatal health care centers in Santa Fe, Argentina. Sociodemographic information, data on their alcohol use, and other information were obtained from the participants. A descriptive analysis of consumption prevalence rates was made and the factors associated with patterns of alcohol use were identified by means of repeated measure analysis. Of the 614 participants, 75.2% had had at least one alcoholic drink (standard unit) during pregnancy and 83.3% had done so in the previous year; 15.1% admitted having at least one episode of binge drinking (five or more drinks) during pregnancy and 27.6% in the year prior to pregnancy. Only 30.6% of the women said they had made any change in consumption during the previous year; of those, 55.6% reduced their consumption and 41.8% stopped drinking. Women who consumed the most alcohol before and during pregnancy reported higher consumption by their partners, smoked, and had more permissive attitudes about alcohol use during pregnancy. A specific prevention plan is required in Argentina to reduce alcohol use in pregnant women, adjusted to local patterns of use, with interventions that include couples, and focused on the youngest women, those who use tobacco, and those who have more permissive attitudes about alcohol use.

Brain reactivity to alcohol and cannabis marketing during sobriety and intoxication.

Science.gov (United States)

de Sousa Fernandes Perna, Elizabeth B; Theunissen, Eef L; Kuypers, Kim P C; Evers, Elisabeth A; Stiers, Peter; Toennes, Stefan W; Witteman, Jurriaan; van Dalen, Wim; Ramaekers, Johannes G

2017-05-01

Drugs of abuse stimulate striatal dopamine release and activate reward pathways. This study examined the impact of alcohol and cannabis marketing on the reward circuit in alcohol and cannabis users while sober and intoxicated. It was predicted that alcohol and cannabis marketing would increase striatal activation when sober and that reward sensitivity would be less during alcohol and cannabis intoxication. Heavy alcohol (n = 20) and regular cannabis users (n = 21) participated in a mixed factorial study involving administration of alcohol and placebo in the alcohol group and cannabis and placebo in the cannabis group. Non-drug users (n = 20) served as between group reference. Brain activation after exposure to alcohol and cannabis marketing movies was measured using functional magnetic resonance imaging and compared between groups while sober and compared with placebo while intoxicated. Implicit alcohol and cannabis cognitions were assessed by means of a single-category implicit association test. Alcohol and cannabis marketing significantly increased striatal BOLD activation across all groups while sober. Striatal activation however decreased during intoxication with alcohol and cannabis. Implicit associations with cannabis marketing cues were significantly more positive in alcohol and cannabis users as compared with non-drug using controls. Public advertising of alcohol or cannabis use elicits striatal activation in the brain's reward circuit. Reduction of marketing would reduce brain exposure to reward cues that motivate substance use. Conversely, elevated dopamine levels protect against the reinforcing potential of marketing. © 2016 Society for the Study of Addiction.

The reinforcing properties of ethanol are quantitatively enhanced in adulthood by peri-adolescent ethanol, but not saccharin, consumption in female alcohol-preferring (P) rats.

Science.gov (United States)

Toalston, Jamie E; Deehan, Gerald A; Hauser, Sheketha R; Engleman, Eric A; Bell, Richard L; Murphy, James M; McBride, William J; Rodd, Zachary A

2015-08-01

Alcohol drinking during adolescence is associated in adulthood with heavier alcohol drinking and an increased rate of alcohol dependence. Past research in our laboratory has indicated that peri-adolescent ethanol consumption can enhance the acquisition and reduce the rate of extinction of ethanol self-administration in adulthood. Caveats of the past research include reinforcer specificity, increased oral consumption during peri-adolescence, and a lack of quantitative assessment of the reinforcing properties of ethanol. The current experiments were designed to determine the effects of peri-adolescent ethanol or saccharin drinking on acquisition and extinction of oral ethanol self-administration and ethanol seeking, and to quantitatively assess the reinforcing properties of ethanol (progressive ratio). Ethanol or saccharin access by alcohol-preferring (P) rats occurred during postnatal day (PND) 30-60. Animals began operant self-administration of ethanol or saccharin after PND 85. After 10 weeks of daily operant self-administration, rats were tested in a progressive ratio paradigm. Two weeks later, self-administration was extinguished in all rats. Peri-adolescent ethanol consumption specifically enhanced the acquisition of ethanol self-administration, reduced the rate of extinction for ethanol self-administration, and quantitatively increased the reinforcing properties of ethanol during adulthood. Peri-adolescent saccharin consumption was without effect. The data indicate that ethanol consumption during peri-adolescence results in neuroadaptations that may specifically enhance the reinforcing properties of ethanol during adulthood. This increase in the reinforcing properties of ethanol could be a part of biological sequelae that are the basis for the effects of adolescent alcohol consumption on the increase in the rate of alcoholism during adulthood. Published by Elsevier Inc.

Acute alcohol impairs conditioning of a behavioural reward-seeking response and inhibitory control processes--implications for addictive disorders.

Science.gov (United States)

Loeber, Sabine; Duka, Theodora

2009-12-01

To investigate whether acute alcohol would affect performance of a conditioned behavioural response to obtain a reward outcome and impair performance in a task measuring inhibitory control to provide new knowledge of how the acute effects of alcohol might contribute to the transition from alcohol use to dependence. A randomized controlled between-subjects design was employed. The laboratory of experimental psychology at the University of Sussex. Thirty-two light to moderate social drinkers recruited from the undergraduate and postgraduate population. After the administration of alcohol (0.8 g/kg) or placebo participants underwent an instrumental reward-seeking procedure, with abstract stimuli serving as S+ (always predicting a win of 10 pence) and S- (always predicting a loss of 10 pence). In addition, a Stop Signal task was administered before and after the administration of alcohol. Participants of the alcohol group performed the behavioural response to obtain the reward outcome more often than placebo subjects in trials associated with loss of money. This finding was observed, although alcohol was not affecting explicit knowledge of stimulus-response outcome contingencies and acquisition of conditioned attentional and emotional responses. In addition, alcohol increased Stop Signal reaction time indicating disinhibiting effects of alcohol, and this was associated positively with response probability to the S-. These results demonstrate that alcohol is affecting inhibitory control of behavioural responses to external signals even when associated with punishment, contributing in this way to the transition from alcohol use to dependence.

Adolescent alcohol use in the Netherlands : the role of ethnicity, ethnic intermarriage, and ethnic school composition

NARCIS (Netherlands)

Tubergen, F.A. van; Poortman, A.-R.

2010-01-01

Objective. To examine the association between ethnicity, ethnic intermarriage, ethnic composition of schools and adolescent alcohol use. Design. Data were derived from the National Survey of Students in the Netherlands, a repeated, nationally representative, cross-sectional study of students aged

Impact of alcohol on male reproductive hormones, oxidative stress and semen parameters in Sprague–Dawley rats

Directory of Open Access Journals (Sweden)

A.A. Oremosu

2015-06-01

Conclusion: Acute and chronic administration of alcohol depletes testosterone levels, increases oxidative stress and decreases semen parameters. This impact of alcohol on testosterone levels is mediated by direct testicular toxicity and by altering the hormone feedback system in the pituitary gland and the hypothalamus.

The Great Recession and employee alcohol use: a U.S. population study.

Science.gov (United States)

Frone, Michael R

2016-03-01

This is the first study to examine broadly the overall net change in U.S. population estimates of alcohol use related to a recession--The Great Recession--among individuals who remain employed. The alcohol variables included drinker status, usual frequency and quantity of alcohol use, frequency of heavy drinking and intoxication, as well as contextual assessments of the frequency and quantity of alcohol use during the workday and after work. The moderating influence of gender, race, and age also was explored. Data for this repeated cross-sectional study were obtained from 2 national telephone surveys of U.S. workers. The first survey occurred prior to the Great Recession (2002-2003; N = 2,501), whereas the second survey occurred during and after the official end of the Great Recession (2008-2011; N = 2,581). The results revealed that the recession was related to a higher proportion of drinkers among middle-aged employees, but not among young employees. Gender and race did not moderate the relation of the recession to drinker status. Among drinkers, the recession was not related to usual alcohol use (frequency and quantity), but was positively related to the frequency of heavy drinking and intoxication. Further, the recession had a differential relation to the contextual alcohol measures. It was negatively related to the frequency and quantity of workday alcohol use, but was positively related to the frequency and quantity of afterwork alcohol use. Among drinkers, gender, race, and age did not moderate the relation of the recession to alcohol use. (c) 2016 APA, all rights reserved).

How can repeat drunk drivers be influenced to change? Analysis of the association between drunk driving and DUI recidivists' attitudes and beliefs.

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Greenberg, Michael D; Morral, Andrew R; Jain, Arvind K

2004-07-01

Public policy interventions designed to deter or prevent drunk driving depend, in part, on modifying beliefs concerning the riskiness, social acceptability and immorality of driving under the influence of alcohol. The current study examines the association of these beliefs with the incidence of alcohol-impaired driving. Interviews were conducted with 273 people with multiple driving under the influence (DUI) offenses. Data included self-reported frequency of driving after drinking in the past year, as well as measures of moral and prescriptive beliefs concerning alcohol-impaired driving (internal behavioral controls), perceived risks of criminal punishment and accidents associated with alcohol-impaired driving (external behavioral controls) and perceived peer group attitudes toward alcohol-impaired driving (social controls). Logit regression modeling showed significant, unique protective associations with behavioral control items in each category. Behavioral controls may protect against alcohol-impaired driving behavior even in a high-risk sample of repeat DUI offenders. Policy interventions designed to curtail drunk driving might seek to enhance these sorts of behavioral controls among DUI offenders.

The Combined Effects of Alcohol, Caffeine and Expectancies on Subjective Experience, Impulsivity and Risk-Taking

Science.gov (United States)

Heinz, Adrienne J.; de Wit, Harriet; Lilje, Todd C.; Kassel, Jon D.

2013-01-01

Caffeinated alcoholic beverage (CAB) consumption is a rapidly growing phenomenon among young adults and is associated with a variety of health-risk behaviors. The current study examined whether either caffeinated alcohol or the expectation of receiving caffeinated alcohol altered affective, cognitive and behavioral outcomes hypothesized to contribute to risk behavior. Young adult social drinkers (N=146) participated in a single session where they received alcohol (peak Breath Alcohol Content = .088 g/dL, SD = .019; equivalent to about 4 standard drinks) and were randomly assigned to one of four further conditions 1) no caffeine, no caffeine expectancy, 2) caffeine and caffeine expectancy, 3) no caffeine but caffeine expectancy, 4) caffeine but no caffeine expectancy. Participants’ habitual CAB consumption was positively correlated with measures of impulsivity and risky behavior, independently of study drugs. Administration of caffeine (mean dose = 220 mg, SD = 38; equivalent to about 2.75 Red Bulls) in the study reduced subjective ratings of intoxication and reversed the decrease in desire to continue drinking, regardless of expectancy. Caffeine also reduced the effect of alcohol on inhibitory reaction time (faster incorrect responses). Participants not expecting caffeine were less attentive after alcohol, whereas participants expecting caffeine were not, regardless of caffeine administration. Alcohol decreased response accuracy in all participants except those who both expected and received caffeine. Findings suggest that CABs may elevate risk for continued drinking by reducing perceived intoxication, and by maintaining the desire to continue drinking. Simply expecting to consume caffeine may reduce the effects of alcohol on inattention, and either expecting or consuming caffeine may protect against other alcohol-related performance decrements. Caffeine, when combined with alcohol, has both beneficial and detrimental effects on mechanisms known to contribute to

Repeatability and Reproducibility of Fibre-Based Nanogenerator Synthesized by Electrospinning Machine

International Nuclear Information System (INIS)

Suyitno; Huda, Sholiehul; Arifin, Zainal; Hadi, Syamsul; Lambang, Raymundus Lullus

2014-01-01

Zinc oxide fibres-based nanogenerators synthesized easily by electrospinning machine are promising to harvest electricity from mechanical energy. However, the repeatability and reproducibility were two major factors needed to be investigated to minimize product failure and to determine the feasibility of mass production of nanogenerators. The green fibres of zinc oxide were produced by electrospinning machine of zinc acetate and polyvinyl alcohol solution at a flow rate of 4 μL/min followed by sintering at temperature 550°C with heating rate 240°C/h. Each 10 nanogenerators was tested by three trained operators with three times of repetition at compressive load 0.5 kg. The nanogenerators revealed the maximum output voltage ranging from 203 to 217 mV. The value of repeatability and reproducibility of nanogenerators was approximately 24.29% showing that nanogenerators were still acceptable to be mass-produced. The relatively low reproducibility was mainly due to the operators, so that the checklist needed to be made easier and simpler for all the variables affecting to the quality of the fibres. Reducing the value of the repeatability and reproducibility is interesting to study further by creating a rotating collector so that the thickness and orientation of fibres can be arranged better

Alcoholics' selective attention to alcohol stimuli: automated processing?

Science.gov (United States)

Stormark, K M; Laberg, J C; Nordby, H; Hugdahl, K

2000-01-01

This study investigated alcoholics' selective attention to alcohol words in a version of the Stroop color-naming task. Alcoholic subjects (n = 23) and nonalcoholic control subjects (n = 23) identified the color of Stroop versions of alcohol, emotional, neutral and color words. Manual reaction times (RTs), skin conductance responses (SCRs) and heart rate (HR) were recorded. Alcoholics showed overall longer RTs than controls while both groups were slower in responding to the incongruent color words than to the other words. Alcoholics showed longer RTs to both alcohol (1522.7 milliseconds [ms]) and emotional words (1523.7 ms) than to neutral words (1450.8 ms) which suggests that the content of these words interfered with the ability to attend to the color of the words. There was also a negative correlation (r = -.41) between RT and response accuracy to alcohol words for the alcoholics, reflecting that the longer time the alcoholics used to respond to the color of the alcohol words, the more incorrect their responses were. The alcoholics also showed significantly greater SCRs to alcohol words (0.16 microSiemens) than to any of the other words (ranging from 0.04-0.08 microSiemens), probably reflecting the emotional significance of the alcohol words. Finally, the alcoholics evidenced smaller HR acceleration to alcohol (1.9 delta bpm) compared to neutral (2.8 delta bpm), which could be related to difficulties alcoholics experience in terminating their attention to the alcohol words. These findings indicate that it is difficult for alcoholics to regulate their attention to alcohol stimuli, suggesting that alcoholics' processing of alcohol information is automated.

Prior alcohol use enhances vulnerability to compulsive cocaine self-administration by promoting degradation of HDAC4 and HDAC5

OpenAIRE

Griffin, Edmund A.; Melas, Philippe A.; Zhou, Royce; Li, Yang; Mercado, Peter; Kempadoo, Kimberly A.; Stephenson, Stacy; Colnaghi, Luca; Taylor, Kathleen; Hu, Mei-Chen; Kandel, Eric R.; Kandel, Denise B.

2017-01-01

Addiction to cocaine is commonly preceded by experiences with legal or decriminalized drugs, such as alcohol, nicotine, and marijuana. The biological mechanisms by which these gateway drugs contribute to cocaine addiction are only beginning to be understood. We report that in the rat, prior alcohol consumption results in enhanced addiction-like behavior to cocaine, including continued cocaine use despite aversive consequences. Conversely, prior cocaine use has no effect on alcohol preference....

Repeated lipopolysaccharide administration produces tolerance to anorexia and fever but not to inhibition of thirst in rat.

Science.gov (United States)

Nava, F; Carta, G

2000-11-01

In 24 h water and food deprived rats, a single lipopolysaccharide treatment (0.25, 0.50 and 1 mg/kg, i.p.) induced inhibition of thirst and hunger as well as fever. Moreover, the same treatment increased serum cytokines, plasma nitrite/nitrate and corticosterone and urinary prostaglandin levels. In another group of 24 h water and food deprived rats, a repeated lipopolysaccharide treatment (0.25, 0. 50 and 1 mg/kg, i.p.), given at 0, 2, 6, 12 and 24 h, induced tolerance to inhibition of food intake and fever, but not to antidipsogenic effect. Moreover, the same repeated treatment stopped the increase in serum cytokines, plasma corticosterone and urinary prostaglandin concentrations and failed to reduce plasma nitrite/nitrate levels. This data, together with the evidence that a pretreatment with N(G)-nitro-L-arginine methyl ester hydrochloride (L-NAME) (5 and 10 microg per rat) reverses the antidipsogenic effects in lipopolysaccharide tolerant rats, suggests that the persistent reduction of water intake after a repeated lipopolysaccharide treatment is due to the antidipsogenic action of nitric oxide in the brain.

Performance of optical biosensor using alcohol oxidase enzyme for formaldehyde detection

Science.gov (United States)

Sari, A. P.; Rachim, A.; Nurlely, Fauzia, V.

2017-07-01

The recent issue in the world is the long exposure of formaldehyde which is can increase the risk of human health, therefore, that is very important to develop a device and method that can be optimized to detect the formaldehyde elements accurately, have a long lifetime and can be fabricated and produced in large quantities. A new and simple prepared optical biosensor for detection of formaldehyde in aqueous solutions using alcohol oxidase (AOX) enzyme was successfully fabricated. The poly-n-butyl acrylic-co-N-acryloxysuccinimide (nBA-NAS) membranes containing chromoionophore ETH5294 were used for immobilization of alcohol oxidase enzyme (AOX). Biosensor response was based on the colour change of chromoionophore as a result of enzymatic oxidation of formaldehyde and correlated with the detection concentration of formaldehyde. The performance of biosensor parameters were measured through the optical absorption value using UV-Vis spectrophotometer including the repeatability, reproducibility, selectivity and lifetime. The results showed that the prepared biosensor has good repeatability (RSD = 1.9 %) and good reproducibility (RSD = 2.1 %). The biosensor was selective formaldehyde with no disturbance by methanol, ethanol, and acetaldehyde, and also stable before 49 days and decrease by 41.77 % after 49 days.

Brain GABA and Glutamate Concentrations Following Chronic Gabapentin Administration: A Convenience Sample Studied During Early Abstinence From Alcohol

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Dieter J. Meyerhoff

2018-03-01

Full Text Available Gabapentin (GBP, a GABA analog that may also affect glutamate (Glu production, can normalize GABA and Glu tone during early abstinence from alcohol, effectively treating withdrawal symptoms and facilitating recovery. Using in vivo magnetic resonance spectroscopy, we tested the degree to which daily GBP alters regional brain GABA and Glu levels in short-term abstinent alcohol-dependent individuals. Regional metabolite levels were compared between 13 recently abstinent alcohol-dependent individuals who had received daily GBP for at least 1 week (GBP+ and 25 matched alcohol-dependent individuals who had not received GBP (GBP−. Magnetic resonance spectra from up to five different brain regions were analyzed to yield absolute GABA and Glu concentrations. GABA and Glu concentrations in the parieto-occipital cortex were not different between GBP− and GBP+. Glu levels in anterior cingulate cortex, dorsolateral prefrontal cortex, and basal ganglia did not differ between GBP− and GBP+. However, in a subgroup of individuals matched on age, sex, and abstinence duration, GBP+ had markedly lower Glu in the frontal white matter (WM than GBP−, comparable to concentrations found in light/non-drinking controls. Furthermore, lower frontal WM Glu in GBP+ correlated with a higher daily GBP dose. Daily GBP treatment at an average of 1,600 mg/day for at least 1 week was not associated with altered cortical GABA and Glu concentrations during short-term abstinence from alcohol, but with lower Glu in frontal WM. GBP for the treatment of alcohol dependence may work through reducing Glu in WM rather than increasing cortical GABA.

Toxicological characteristics of petroleum products repeated exposure

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V.M. Rubin

2015-03-01

Full Text Available Abstract. The ability of petroleum products to initiate cumulative effects was assessed in experimental intragastric admission to male albino rats for one month. The analysis of skin-resorptive effects was performed using "test-tube" method on the skin of rats’ tails. It has been established that petroleum products can penetrate the intact skin and, with repeated admission, cause a general toxic effect. There were reductions bodyweights, the negative effect on the function of the kidneys and liver, changes of hematological parameters, as well as activation of the antioksidatnoy system. Repeated intragastric administration does not lead to the death of the animals testifying to the lack of accumulation capacity for petroleum products at the level of functional mortal effects, the cumulation coefficient being > 5.1. Negative impact on urinary function and hepatobiliary system, changes in hematological parameters and activation of the «lipid peroxidation – antioksidant defense» were observed.

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

Science.gov (United States)

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. Copyright © 2011 Elsevier Ltd. All rights reserved.

Lack of association of the serotonin transporter gene promoter region polymorphism, 5-HTTLPR, including rs25531 with cigarette smoking and alcohol consumption

DEFF Research Database (Denmark)

Rasmussen, Henrik; Bagger, Yu; Tanko, Laszlo B

2009-01-01

We addressed the question whether 5-HTTLPR, a variable number of tandem repeats located in the 5' end of the serotonin transporter gene, is associated with smoking or alcohol consumption. Samples of DNA from 1,365 elderly women with a mean age of 69.2 years were genotyped for this polymorphism...... using a procedure, which allowed the simultaneous determination of variation in the number of repeat units and single nucleotide changes, including the A > G variation at rs25531 for discrimination between the L(A) and L(G) alleles. Qualitative and quantitative information on the women's current...... and previous consumption of cigarettes and alcohol were obtained using a questionnaire. Genotypes were classified according to allele size, that is, S and L with 14 and 16 repeat units, respectively, and on a functional basis by amalgamation of the L(G) and S alleles. Data were subjected to regression analyses...

Enzymes extracted from apple peels have activity in reducing higher alcohols in Chinese liquors.

Science.gov (United States)

Han, Qi'an; Shi, Junling; Zhu, Jing; Lv, Hongliang; Du, Shuangkui

2014-10-01

As the unavoidable byproducts of alcoholic fermentation, higher alcohols are unhealthy compounds widespread in alcoholic drinks. To investigate the activity of apple crude enzymes toward higher alcohols in liquors, five kinds of apple peels, namely, Fuji, Gala, Golden Delicious, Red Star, and Jonagold, were chosen to prepare enzymes, and three kinds of Chinese liquors, namely, Xifeng (containing 45% ethanol), Taibai (containing 50% ethanol), and Erguotou (containing 56% ethanol), were tested. Enzymes were prepared in the forms of liquid solution, powder, and immobilized enzymes using sodium alginate (SA) and chitosan. The treatment was carried out at 37 °C for 1 h. The relative amounts of different alcohols (including ethanol, 1-propanol, isobutanol, 1-butanol, isoamylol, and 1-hexanol) were measured using gas chromatography (GC). Conditions for preparing SA-immobilized Fuji enzymes (SA-IEP) were optimized, and the obtained SA-IEP (containing 0.3 g of enzyme) was continuously used to treat Xifeng liquor eight times, 20 mL per time. Significant degradation rates (DRs) of higher alcohols were observed at different degrees, and it also showed enzyme specificity according to the apple varieties and enzyme preparations. After five repeated treatments, the DRs of the optimized Fuji SA-IEP remained 70% for 1-hexanol and >15% for other higher alcohols.

Employed women with alcohol problems who seek help from employee assistance programs. Description and comparisons.

Science.gov (United States)

Blum, T C; Roman, P M; Harwood, E M

1995-01-01

After a brief description of employee assistance programs (EAP), we present data collected from 6,400 employees from 84 worksites who used the services of EAPs, a portion of whom were assessed by the EAP as having alcohol-related problems and/or received scores on the Alcohol Dependence Scale (ADS) indicative of a potential alcohol-related problem. In addition, data were collected at intake from the EAP administrators, and employment status of the employee clients was assessed 18 to 24 months later. These data indicate that EAPs are effective in sustaining the employment of most women with alcohol-related problems who seek services from EAPs and that EAPs' goal of early intervention is especially realized among women with alcohol problems. Other conclusions include: women with alcohol problems do not enter EAPs through routes that are strikingly different from those of men; many of the gender differences that are revealed are associated with job status differences; employed women with alcohol problems are detached from nuclear families, with markedly low rates of current marriage; even when married, spouses are less likely to play a role in the referral of women with alcohol problems than the spouses of the men; and, there is no clear indication that women are the target of any form of discrimination in the process of EAP utilization. However, women are considerably more likely to have less adequate insurance coverage, according to the EAP administrators' assessment reported at client intake, than their male counterparts, leading to treatment choices that may be less than appropriate.

Comparison of Student Self-Reported and Administrative Data regarding Intercession into Alcohol Misuse among College Freshmen Dormitory Residents

Science.gov (United States)

Novik, Melinda G.; Boekeloo, Bradley O.

2013-01-01

Intercession into collegiate alcohol misuse by the Department of Resident Life (DRL) in freshmen dormitories at one large Mid-Atlantic, diverse, public university was examined. Freshmen dormitory resident drinkers (n = 357), 71% of whom reported alcohol misuse, were surveyed. Student self-report and DRL documentation, respectively, revealed that…

Alcohol Alert

Science.gov (United States)

... of Alcohol Consumption Alcohol's Effects on the Body Alcohol Use Disorder Fetal Alcohol Exposure Support & Treatment Alcohol Policy Special ... 466 KB] No. 81: Exploring Treatment Options for Alcohol Use Disorders [ PDF - 539K] No. 80: Alcohol and HIV/AIDS: ...

Dose- and time-dependent changes in tissue levels of tetrabromobisphenol A (TBBPA and its sulfate and glucuronide conjugates following repeated administration to female Wistar Han Rats

Directory of Open Access Journals (Sweden)

S.J. Borghoff

Full Text Available Tetrabromobisphenol A (TBBPA, a nongenotoxic flame retardant, causes uterine tumors in female rats. A proposed mode of action (MoA for these tumors involves an increase in the bioavailability of estradiol as a result of TBBPA inhibiting estrogen sulfotransferases (ES, the enzymes responsible for inactivating and enhancing the elimination of estradiol. The objective of this study was to evaluate the effect of dose and repeated administration of TBBPA on the level of TBBPA, TBBPA-glucuronide (GA and TBBPA-sulfate (S conjugates in plasma, liver and uterus of female Wistar Han rats administered TBBPA (50, 100, 250, 500 or 1000 mg/kg for 28 consecutive days. In accordance with this objective, TBBPA sulfation was used as a surrogate for evaluating the potential for estradiol sulfation to be limited at high dose levels of TBBPA. Blood samples were collected at 4 and 8 h post-dosing on study day 7, 14, and 28, while liver and uterus were collected at the same time points following 28 days of dosing. Tissue samples were analyzed for TBBPA, TBBPA-GA and TBBPA-S by LC–MS/MS. A dose-related increase in the concentration of all three analytes occurred in plasma (day 7, 14, and 28 as well as liver and uterus tissue (day 28 at both 4 and 8 h post dose. The plasma concentration of TBBPA-GA and TBBPA-S was higher in animals dosed for 28 days compared to those dosed for 7 or 14 days showing an increase in systemic circulation of these conjugates with repeated administration. The balance of these conjugates was also different in tissues with TBBPA-S > TBBPA-GA at high doses in the liver and TBBPA-GA > TBBPA-S in both plasma and uterus. In all three tissues the ratio of TBBPA-S/TBBPA-GA showed a decreasing trend with dose, suggesting that at high TBBPA dose levels sulfation of TBBPA becomes limited. This effect was most apparent in the liver and plasma at 28 days of administration. Together these data show that administration of high doses of TBBPA

Maryland Alcohol Sales Tax and Sexually Transmitted Infections: A Natural Experiment.

Science.gov (United States)

Staras, Stephanie A S; Livingston, Melvin D; Wagenaar, Alexander C

2016-03-01

Sexually transmitted infections are common causes of morbidity and mortality, including infertility and certain types of cancer. Alcohol tax increases may decrease sexually transmitted infection rates overall and differentially across population subgroups by decreasing alcohol consumption in general and prior to sex, thus decreasing sexual risk taking and sexually transmitted infection acquisition. This study investigated the effects of a Maryland increase in alcohol beverage sales tax on statewide gonorrhea and chlamydia rates overall and within age, gender, and race/ethnicity subpopulations. This study used an interrupted time series design, including multiple cross-state comparisons, to examine the effects of the 2011 alcohol tax increase in Maryland on chlamydia and gonorrhea cases reported to the U.S. National Notifiable Disease Surveillance System for January 2003 to December 2012 (N=120 repeated monthly observations, analyzed in 2015). Effects were assessed with Box-Jenkins autoregressive moving average models with structural parameters. After the alcohol-specific sales tax increase, gonorrhea rates decreased 24% (95% CI=11%, 37%), resulting in 1,600 fewer statewide gonorrhea cases annually. Cohen's d indicated a substantial effect of the tax increase on gonorrhea rates (range across control group models, -1.25 to -1.42). The study did not find evidence of an effect on chlamydia or differential effects across age, race/ethnicity, or gender subgroups. Results strengthen the evidence from prior studies of alcohol taxes influencing gonorrhea rates and extend health prevention effects from alcohol excise to sales taxes. Alcohol tax increases may be an efficient strategy for reducing sexually transmitted infections. Copyright © 2016 American Journal of Preventive Medicine. Published by Elsevier Inc. All rights reserved.

Effect of long-term intraperitoneal zinc administration on liver glycogen levels in diabetic rats subjected to acute forced swimming.

Science.gov (United States)

Bicer, Mursel; Gunay, Mehmet; Akil, Mustafa; Avunduk, Mustafa Cihat; Mogulkoc, Rasim; Baltaci, Abdulkerim Kasim

2011-03-01

This study aims to examine the effect of zinc administration on liver glycogen levels of rats in which diabetes was induced with streptozotocin and which were subjected to acute swimming exercise. The study was conducted on 80 adult Sprague-Dawley male rats, which were equally allocated to eight groups: group 1, general control; group 2, zinc-administrated control; group 3, zinc-administrated diabetic control; group 4, swimming control; group 5, zinc-administrated swimming; group 6, zinc-administrated diabetic swimming; group 7, diabetic swimming; group 8, diabetic control group. In order to induce diabetes, animals were injected with 40 mg/kg intraperitoneal (ip) streptozotocin. The injections were repeated in the same dose after 24 h. Animals which had blood glucose at or above 300 mg/dl 6 days after the last injections were accepted as diabetic. Zinc was administrated ip for 4 weeks as 6 mg/kg/day per rat. Hepatic tissue samples taken from the animals at the end of the study were fixed in 95% ethyl alcohol. Cross sections of 5 µm thickness, taken by the help of a microtome from the tissue samples buried in paraffin, were placed on a microscope slide and stained with periodic acid-Schiff and evaluated by light microscope. All microscopic images were transferred to a PC and assessed with the help of Clemex PE3.5 image analysis software. The lowest liver glycogen levels in the study were obtained in groups 3, 4, 6, 7, and 8. Liver glycogen levels in group 5 were higher than groups 3, 4, 6, 7, and 8, but lower than groups 1 and 2 (p swimming exercise were restored by zinc administration and that diabetes induced in rats prevented the protective effect of zinc.

Fucoidan from Fucus vesiculosus Protects against Alcohol-Induced Liver Damage by Modulating Inflammatory Mediators in Mice and HepG2 Cells

Directory of Open Access Journals (Sweden)

Jung Dae Lim

2015-02-01

Full Text Available Fucoidan is an l-fucose-enriched sulfated polysaccharide isolated from brown algae and marine invertebrates. In this study, we investigated the protective effect of fucoidan from Fucus vesiculosus on alcohol-induced murine liver damage. Liver injury was induced by oral administration of 25% alcohol with or without fucoidan (30 mg/kg or 60 mg/kg for seven days. Alcohol administration increased serum aspartate aminotransferase and alanine aminotransferase levels, but these increases were suppressed by the treatment of fucoidan. Transforming growth factor beta 1 (TGF-β1, a liver fibrosis-inducing factor, was highly expressed in the alcohol-fed group and human hepatoma HepG2 cell; however, the increase in TGF-β1 expression was reduced following fucoidan administration. Treatment with fucoidan was also found to significantly reduce the production of inflammation-promoting cyclooygenase-2 and nitric oxide, while markedly increasing the expression of the hepatoprotective enzyme, hemeoxygenase-1, on murine liver and HepG2 cells. Taken together, the antifibrotic and anti-inflammatory effects of fucoidan on alcohol-induced liver damage may provide valuable insights into developing new therapeutics or interventions.

Modulation of the effects of alcohol on driving-related psychomotor skills by chronic exposure to cannabis.

Science.gov (United States)

Wright, A; Terry, P

2002-03-01

Many previous studies have reported that alcohol and cannabis produce additive psychomotor effects in acute combination, but few have explicitly tested whether chronic exposure to cannabis, in the absence of acute administration, alters the effects of alcohol on psychomotor performance. To test whether long-term cannabis use modulates the effects of alcohol on psychomotor skills and self-reported mood and sensation. Regular cannabis users (minimum: daily use for at least 3 years) and infrequent users (maximum: once-monthly use for at most 3 years) were matched for sex, age, alcohol intake and other drug use (14 participants in each group). Participants received alcohol (females 0.35 g/kg; males 0.45 g/kg) and placebo drinks. By urinalysis, only regular users tested positive for metabolites of Delta(9)-tetrahydrocannabinol; breath alcohol levels were similar between groups. Participants were tested on a computerised tracking task that has been used to screen drugs for adverse effects on driving. The task involved tracking a moving target on a computer screen while simultaneously responding to occasional presentations of stimuli in the periphery of the screen. Tracking accuracy was similar for both groups after placebo, but alcohol caused a significant deterioration in performance among infrequent cannabis users relative to regular users. These changes were mirrored by significant changes in self-reported scores for dizziness, measured by visual analogue scales. Alcohol slowed reaction times, but not differentially between groups. For psychomotor skills relevant to driving, chronic cannabis use (in the absence of acute administration) does not potentiate the effects of alcohol. In fact, the superior tracking accuracy of regular users relative to infrequent users after alcohol, and their lower scores for dizziness, suggest that chronic cannabis use may instead confer cross-tolerance to specific effects of alcohol on behaviour.

Relationship between pathological gambling, alcoholism and drug addiction.

Science.gov (United States)

Baldo, V; Cristofoletti, M; Majori, S; Cibin, M; Peron, C; Dal Zotto, A; Zampieri, N; Saia, M; Trivello, R

2006-01-01

The aim of this survey was to evaluate the distribution of pathological gamblers treated in an alcohol or drug addiction treatment program run by the Italian National Health Service providing assistance to alcohol and drug abusers in Venice (North east Italy) from September 1 to December 31, 2001. Each drug- or alcohol-dependent patient retained for treatment for at least one month was administrated an anonymous precoded questionnaire to collect personal and socio-demographic features. The South Oaks Gambling Screen (SOGS) was used to measure pathological gambling and the Symptom Checklist-90-Revised (SCL-90-R) to measure psychological distress levels and psychiatric symptoms. Among the 113 enrolled subjects we found a greater prevalence of pathological gamblers among drug users than among alcoholics and drug abusers were younger than alcoholics; moreover, there was a prevalence of single status, low schooling, and a low-medium income despite full-time occupation. Only pathological gamblers revealed a significant positive correlation with a family history of gambling and reached positive scores (>1.5) for some likely psychiatric symptoms. Abuse disorders and pathological gambling are frequently associated with multidependence personality traits. Preventing substance abuse may reduce the pathological gambling rates and better results can be obtained with educational campaigns beginning earlier in life.

Is proximity to alcohol outlets associated with alcohol consumption and alcohol-related harm in Denmark?

DEFF Research Database (Denmark)

Kedir, Abdu; Berg-Beckhoff, Gabriele; Stock, Christiane

2018-01-01

Background: This study examined the associations between distance from residence to the nearest alcohol outlet with alcohol consumption as well as with alcohol-related harm. Methods: Data on alcohol consumption, alcohol-related harm and sociodemographics were obtained from the 2011 Danish Drug...... and Alcohol Survey (n=5133) with respondents aged 15–79 years. The information on distances from residence to the nearest alcohol outlets was obtained from Statistics Denmark. Multiple logistic and linear regressions were used to examine the association between distances to outlets and alcohol consumption...... whereas alcohol-related harm was analysed using negative binomial regression. Results: Among women it was found that those living closer to alcohol outlets were more likely to report alcohol-related harm (p

Is proximity to alcohol outlets associated with alcohol consumption and alcohol-related harm in Denmark?

DEFF Research Database (Denmark)

Seid, Abdu K.; Berg-Beckhoff, Gabriele; Stock, Christiane

2018-01-01

Background: This study examined the associations between distance from residence to the nearest alcohol outlet with alcohol consumption as well as with alcohol-related harm. Methods: Data on alcohol consumption, alcohol-related harm and sociodemographics were obtained from the 2011 Danish Drug...... and Alcohol Survey (n = 5133) with respondents aged 15–79 years. The information on distances from residence to the nearest alcohol outlets was obtained from Statistics Denmark. Multiple logistic and linear regressions were used to examine the association between distances to outlets and alcohol consumption...... whereas alcohol-related harm was analysed using negative binomial regression. Results: Among women it was found that those living closer to alcohol outlets were more likely to report alcohol-related harm (p

Development and validation of the alcohol Expectancy Questionnaire Short Form (EQ-SF).

Science.gov (United States)

Mezquita, Laura; Camacho, Laura; Suso-Ribera, Carlos; Ortet, Generós; Ibáñez, Manuel I

2018-01-15

Alcohol expectancies are proximal variables to alcohol use and misuse. In recent decades, different measures have been developed to assess this construct. One of the most frequently used and recommended instruments is the Expectancy Questionnaire (EQ; Leigh y Stacy, 1993). Our aim is to develop a short version of the EQ (EQ-SF) for suitable use in time-limited administrations. Two samples, adolescents (N = 514, 57.20% females) and adults (N = 548, 61.50% females), completed the EQ together with alcohol-use measures. Different item selection strategies were applied to select the 24 items. The EQ-SF structure was explored using confirmatory factor analysis, and measurement invariance was tested running a multi-group analysis comparing groups by sex and age. Reliability was tested using Cronbach's alpha and omega coefficients. Concurrent validity was investigated with regression analyses. The EQ-SF showed acceptable between-groups measurement invariance. Alphas and omegas ranged from .77 to .93. Positive expectancies predicted both alcohol use and alcohol-related problems. Negative expectancies predicted alcohol-related problems. Sex and age moderated these associations. Males with high positive alcohol expectancies showed higher alcohol consumption than females, while adults with high negative alcohol expectancies showed greater alcohol-related problems than adolescents. Different evidence on the validity and reliability of the EQ-SF suggest that it is a suitable instrument to assess alcohol expectancies in the Spanish population.

Haemopoiesis-enhancing effects of repeatedly administered carboxymethylglucan in mice exposed to fractionated irradiation

International Nuclear Information System (INIS)

Hofer, M.; Pospisil, M.; Pipalova, I.; Hola, J.

1995-01-01

Carboxymethylglucan (CMG), a water-soluble glucan derivative, enhanced the number of granulocytes in the peripheral blood as well as other indices of haemopoietic recovery (total cellularity and the number of granulocyte-macrophage progenitor cells in femoral marrow, spleen weight) investigated after fractionated gamma-irradiation of mice (five doses of 2 Gy each, or three, four and five doses of 3 Gy each given at 24 hours' intervals). An increased liver weight and a more pronounced anaemia found in the CMG-treated mice suggested that also inflammatory side effects were evoked by repeated CMG administration. On the other hand, the development of tolerance, i.e., a decreased effectiveness of CMG treatment on repeated administration did not seem to play a major role under the experimental conditions studied because the protective effects of CMG increased with the increasing number of CMG injections. (author) 2 figs., 16 refs

Global alcohol policy and the alcohol industry.

Science.gov (United States)

Anderson, Peter

2009-05-01

The WHO is preparing its global strategy on alcohol, and, in so doing, has been asked to consult with the alcohol industry on ways it could contribute in reducing the harm done by alcohol. This review asks which is more effective in reducing harm: the regulatory approaches that the industry does not favour; or the educational approaches that it does favour. The current literature overwhelmingly finds that regulatory approaches (including those that manage the price, availability, and marketing of alcohol) reduce the risk of and the experience of alcohol-related harm, whereas educational approaches (including school-based education and public education campaigns) do not, with industry-funded education actually increasing the risk of harm. The alcohol industry should not be involved in making alcohol policy. Its involvement in implementing policy should be restricted to its role as a producer, distributor, and marketer of alcohol. In particular, the alcohol industry should not be involved in educational programmes, as such involvement could actually lead to an increase in harm.

Fetal Alcohol Spectrum Disorders (FASDs): Alcohol Use Quiz

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... Links to Other Websites About Us More CDC Alcohol Topics CDC Alcohol Portal Excessive Alcohol Use Binge ... of alcohol screening and counseling for all women Alcohol Use Quiz Recommend on Facebook Tweet Share Compartir ...

Results from the 2012 drug and alcohol testing survey : [analysis brief].

Science.gov (United States)

2014-12-01

This report summarizes the results of the 2012 Federal Motor Carrier Safety Administration (FMCSA) Drug and Alcohol Testing Survey. This annual survey measures the percentage of drivers with commercial drivers licenses (CDLs) who test positive for...

Results from the 2015 Drug and Alcohol Testing Survey : analysis brief.

Science.gov (United States)

2017-06-01

This report summarizes the results of the 2015 Federal Motor Carrier Safety Administration (FMCSA) Drug and Alcohol Testing Survey. This annual survey measures the percentage of commercial drivers license (CDL) drivers who test positive for contro...

Results from the 2014 drug and alcohol testing survey : analysis brief.

Science.gov (United States)

2016-10-01

This report summarizes the results of the 2014 Federal Motor Carrier Safety Administration (FMCSA) Drug and Alcohol Testing Survey. This annual survey measures the percentage of commercial drivers license (CDL) drivers who test positive for contro...

Results from the 2016 Drug and Alcohol Testing Survey : Analysis Brief

Science.gov (United States)

2018-01-01

This report summarizes the results of the 2016 Federal Motor Carrier Safety Administration (FMCSA) Drug and Alcohol Testing Survey. This annual survey measures the percentage of commercial drivers license (CDL) drivers who test positive for contro...

Congenital Splenic Cyst Treated with Percutaneous Sclerosis Using Alcohol

International Nuclear Information System (INIS)

Anon, Ramon; Guijarro, Jorge; Amoros, Cirilo; Gil, Joaquin; Bosca, Marta M.; Palmero, Julio; Benages, Adolfo

2006-01-01

We report a case of successful percutaneous treatment of a congenital splenic cyst using alcohol as the sclerosing agent. A 14-year-old female adolescent presented with a nonsymptomatic cystic mass located in the spleen that was believed to be congenital. After ultrasonography, a drainage catheter was placed in the cavity. About 250 ml of serous liquid was extracted and sent for microbiologic and pathologic studies to rule out an infectious or malignant origin. Immediately afterwards, complete drainage and local sclerotherapy with alcohol was performed. This therapy was repeated 8 days later, after having observed 60 ml of fluid in the drainage bag. One year after treatment the cyst has practically disappeared. We believe that treatment of splenic cyst with percutaneous puncture, ethanolization, and drainage is a valid option and it does not rule out surgery if the conservative treatment fails

Physio-pathological effects of alcohol on the cardiovascular system: its role in hypertension and cardiovascular disease.

Science.gov (United States)

Kawano, Yuhei

2010-03-01

Alcohol has complex effects on the cardiovascular system. The purpose of this article is to review physio-pathological effects of alcohol on cardiovascular and related systems and to describe its role in hypertension and cardiovascular disease. The relationship between alcohol and hypertension is well known, and a reduction in the alcohol intake is widely recommended in the management of hypertension. Moreover, alcohol has both pressor and depressor actions. The latter actions are clear in Oriental subjects, especially in those who show alcohol flush because of the genetic variation in aldehyde dehydrogenase activity. Repeated alcohol intake in the evening causes an elevation in daytime and a reduction in nighttime blood pressure (BP), with little change in the average 24-h BP in Japanese men. Thus, the hypertensive effect of alcohol seems to be overestimated by the measurement of casual BP during the day. Heavy alcohol intake seems to increase the risk of several cardiovascular diseases, such as hemorrhagic stroke, arrhythmia and heart failure. On the other hand, alcohol may act to prevent atherosclerosis and to decrease the risk of ischemic heart disease, mainly by increasing HDL cholesterol and inhibiting thrombus formation. A J- or U-shaped relationship has been observed between the level of alcohol intake and risk of cardiovascular mortality and total mortality. It is reasonable to reduce the alcohol intake to less than 30 ml per day for men and 15 ml per day for women in the management of hypertension. As a small amount of alcohol seems to be beneficial, abstinence from alcohol is not recommended to prevent cardiovascular disease.

Extraversion and the Rewarding Effects of Alcohol in a Social Context

Science.gov (United States)

Fairbairn, Catharine E.; Sayette, Michael A.; Wright, Aidan G. C.; Levine, John M.; Cohn, Jeffrey F.; Creswell, Kasey G.

2015-01-01

The personality trait of extraversion has been linked to problematic drinking patterns. Researchers have long hypothesized that such associations are attributable to increased alcohol-reward sensitivity among extraverted individuals, and surveys suggest that individuals high in extraversion gain greater mood enhancement from alcohol than those low in extraversion. Surprisingly, however, alcohol administration studies have not found individuals high in extraversion to experience enhanced mood following alcohol consumption. Of note, prior studies have examined extraverted participants—individuals who self-identify as being highly social—consuming alcohol in isolation. In the present research, we used a group drinking paradigm to examine whether individuals high in extraversion gained greater reward from alcohol than did those low in extraversion and, further, whether a particular social mechanism (partners’ Duchenne smiling) might underlie alcohol reward sensitivity among extraverted individuals. Social drinkers (n = 720) consumed a moderate dose of alcohol, placebo, or control beverage in groups of three over the course of 36-min. This social interaction was video-recorded, and Duchenne smiling was coded using the Facial Action Coding System. Results indicated that participants high in extraversion reported significantly more mood enhancement from alcohol than did those low in extraversion. Further, mediated moderation analyses focusing on Duchenne smiling of group members indicated that social processes fully and uniquely accounted for alcohol reward-sensitivity among individuals high in extraversion. Results provide initial experimental evidence that individuals high in extraversion experience increased mood-enhancement from alcohol and further highlight the importance of considering social processes in the etiology of Alcohol Use Disorder. PMID:25844684

Extraversion and the Rewarding Effects of Alcohol in a Social Context.

Science.gov (United States)

Fairbairn, Catharine E; Sayette, Michael A; Wright, Aidan G C; Levine, John M; Cohn, Jeffrey F; Creswell, Kasey G

2015-08-01

The personality trait of extraversion has been linked to problematic drinking patterns. Researchers have long hypothesized that such associations are attributable to increased alcohol-reward sensitivity among extraverted individuals, and surveys suggest that individuals high in extraversion gain greater mood enhancement from alcohol than those low in extraversion. Surprisingly, however, alcohol administration studies have not found individuals high in extraversion to experience enhanced mood following alcohol consumption. Of note, prior studies have examined extraverted participants-individuals who self-identify as being highly social-consuming alcohol in isolation. In the present research, we used a group drinking paradigm to examine whether individuals high in extraversion gained greater reward from alcohol than did those low in extraversion and, further, whether a particular social mechanism (partners’ Duchenne smiling) might underlie alcohol reward sensitivity among extraverted individuals. Social drinkers (n 720) consumed a moderate dose of alcohol, placebo, or control beverage in groups of 3 over the course of 36 min. This social interaction was video-recorded, and Duchenne smiling was coded using the Facial Action Coding System. Results indicated that participants high in extraversion reported significantly more mood enhancement from alcohol than did those low in extraversion. Further, mediated moderation analyses focusing on Duchenne smiling of group members indicated that social processes fully and uniquely accounted for alcohol reward-sensitivity among individuals high in extraversion. Results provide initial experimental evidence that individuals high in extraversion experience increased mood-enhancement from alcohol and further highlight the importance of considering social processes in the etiology of alcohol use disorder. (c) 2015 APA, all rights reserved).

Male clients' behaviours with and perspectives about their last male escort encounter: comparing repeat versus first-time hires.

Science.gov (United States)

Wolff, Margaret M; Grov, Christian; Smith, Michael D; Koken, Juline A; Parsons, Jeffrey T

2014-01-01

Research on men who have sex with men suggests that condomless anal intercourse occurs more frequently in established sexual relationships. While comparable data regarding male-for-male escorting is unavailable, research implies that many clients seek emotional as well as physical connections with the men they hire. In 2012, 495 male clients, recruited via daddysreviews.com completed an online survey about their last hiring experience. Most participants were from the USA (85.7%), the UK and Canada (3.2% each). In total, 75% of encounters involved an escort hired for the first time; 25% were with a previously hired escort ('repeat encounter'). The client's age, lifetime number of escorts hired and number hired in the past year were positively associated with the last encounter being a repeat encounter. Cuddling, sharing a meal, drinking alcohol, taking a walk, watching a show and shopping were also positively associated with repeat encounters. Conversely, none of the sexual behaviours were significantly associated with repeat encounters. Repeat encounters were significantly more likely to include non-sexual behaviours alongside sexual activities, but no more likely to involve condomless anal intercourse. Moreover, clients' knowledge of escorts' HIV status was not significantly associated with engaging in condomless anal intercourse with repeat encounters.

A critical role of lateral hypothalamus in context-induced relapse to alcohol seeking after punishment-imposed abstinence.

Science.gov (United States)

Marchant, Nathan J; Rabei, Rana; Kaganovsky, Konstantin; Caprioli, Daniele; Bossert, Jennifer M; Bonci, Antonello; Shaham, Yavin

2014-05-28

In human alcoholics, abstinence is often self-imposed, despite alcohol availability, because of the negative consequences of excessive use. During abstinence, relapse is often triggered by exposure to contexts associated with alcohol use. We recently developed a rat model that captures some features of this human condition: exposure to the alcohol self-administration environment (context A), after punishment-imposed suppression of alcohol self-administration in a different environment (context B), provoked renewal of alcohol seeking in alcohol-preferring P rats. The mechanisms underlying context-induced renewal of alcohol seeking after punishment-imposed abstinence are unknown. Here, we studied the role of the lateral hypothalamus (LH) and its forebrain projections in this effect. We first determined the effect of context-induced renewal of alcohol seeking on Fos (a neuronal activity marker) expression in LH. We next determined the effect of LH reversible inactivation by GABAA + GABAB receptor agonists (muscimol + baclofen) on this effect. Finally, we determined neuronal activation in brain areas projecting to LH during context-induced renewal tests by measuring double labeling of the retrograde tracer cholera toxin subunit B (CTb; injected in LH) with Fos. Context-induced renewal of alcohol seeking after punishment-imposed abstinence was associated with increased Fos expression in LH. Additionally, renewal was blocked by muscimol + baclofen injections into LH. Finally, double-labeling analysis of CTb + Fos showed that context-induced renewal of alcohol seeking after punishment-imposed abstinence was associated with selective activation of accumbens shell neurons projecting to LH. The results demonstrate an important role of LH in renewal of alcohol seeking after punishment-imposed abstinence and suggest a role of accumbens shell projections to LH in this form of relapse. Copyright © 2014 the authors 0270-6474/14/347447-11$15.00/0.

Internet Alcohol Marketing and Underage Alcohol Use.

Science.gov (United States)

McClure, Auden C; Tanski, Susanne E; Li, Zhigang; Jackson, Kristina; Morgenstern, Matthis; Li, Zhongze; Sargent, James D

2016-02-01

Internet alcohol marketing is not well studied despite its prevalence and potential accessibility and attractiveness to youth. The objective was to examine longitudinal associations between self-reported engagement with Internet alcohol marketing and alcohol use transitions in youth. A US sample of 2012 youths aged 15 to 20 was surveyed in 2011. An Internet alcohol marketing receptivity score was developed, based on number of positive responses to seeing alcohol advertising on the Internet, visiting alcohol brand Web sites, being an online alcohol brand fan, and cued recall of alcohol brand home page images. We assessed the association between baseline marketing receptivity and both ever drinking and binge drinking (≥6 drinks per occasion) at 1-year follow-up with multiple logistic regression, controlling for baseline drinking status, Internet use, sociodemographics, personality characteristics, and peer or parent drinking. At baseline, ever-drinking and binge-drinking prevalence was 55% and 27%, respectively. Many (59%) reported seeing Internet alcohol advertising, but few reported going to an alcohol Web site (6%) or being an online fan (3%). Higher Internet use, sensation seeking, having family or peers who drank, and past alcohol use were associated with Internet alcohol marketing receptivity, and a score of 1 or 2 was independently associated with greater adjusted odds of initiating binge drinking (odds ratio 1.77; 95% confidence interval, 1.13-2.78 and odds ratio 2.15; 95% confidence interval, 1.06-4.37 respectively) but not with initiation of ever drinking. Although high levels of engagement with Internet alcohol marketing were uncommon, most underage youths reported seeing it, and we found a prospective association between receptivity to this type of alcohol marketing and future problem drinking, making additional research and ongoing surveillance important. Copyright © 2016 by the American Academy of Pediatrics.

Internet Alcohol Marketing and Underage Alcohol Use

Science.gov (United States)

McClure, Auden C.; Tanski, Susanne E.; Li, Zhigang; Jackson, Kristina; Morgenstern, Matthis; Li, Zhongze; Sargent, James D.

2016-01-01

BACKGROUND AND OBJECTIVE Internet alcohol marketing is not well studied despite its prevalence and potential accessibility and attractiveness to youth. The objective was to examine longitudinal associations between self-reported engagement with Internet alcohol marketing and alcohol use transitions in youth. METHODS A US sample of 2012 youths aged 15 to 20 was surveyed in 2011. An Internet alcohol marketing receptivity score was developed, based on number of positive responses to seeing alcohol advertising on the Internet, visiting alcohol brand Web sites, being an online alcohol brand fan, and cued recall of alcohol brand home page images. We assessed the association between baseline marketing receptivity and both ever drinking and binge drinking (≥6 drinks per occasion) at 1-year follow-up with multiple logistic regression, controlling for baseline drinking status, Internet use, sociodemographics, personality characteristics, and peer or parent drinking. RESULTS At baseline, ever-drinking and binge-drinking prevalence was 55% and 27%, respectively. Many (59%) reported seeing Internet alcohol advertising, but few reported going to an alcohol Web site (6%) or being an online fan (3%). Higher Internet use, sensation seeking, having family or peers who drank, and past alcohol use were associated with Internet alcohol marketing receptivity, and a score of 1 or 2 was independently associated with greater adjusted odds of initiating binge drinking (odds ratio 1.77; 95% confidence interval, 1.13–2.78 and odds ratio 2.15; 95% confidence interval, 1.06–4.37 respectively) but not with initiation of ever drinking. CONCLUSIONS Although high levels of engagement with Internet alcohol marketing were uncommon, most underage youths reported seeing it, and we found a prospective association between receptivity to this type of alcohol marketing and future problem drinking, making additional research and ongoing surveillance important. PMID:26738886

Testosterone Administration Moderates Effect of Social Environment on Trust in Women Depending on Second-to-Fourth Digit Ratio.

Science.gov (United States)

Buskens, Vincent; Raub, Werner; van Miltenburg, Nynke; Montoya, Estrella R; van Honk, Jack

2016-06-10

Animal research has established that effects of hormones on social behaviour depend on characteristics of both individual and environment. Insight from research on humans into this interdependence is limited, though. Specifically, hardly any prior testosterone experiments in humans scrutinized the interdependency of testosterone with the social environment. Nonetheless, recent testosterone administration studies in humans repeatedly show that a proxy for individuals' prenatal testosterone-to-estradiol ratio, second-to-fourth digit-ratio (2D:4D ratio), influences effects of testosterone administration on human social behaviour. Here, we systematically vary the characteristics of the social environment and show that, depending on prenatal sex hormone priming, testosterone administration in women moderates the effect of the social environment on trust. We use the economic trust game and compare one-shot games modelling trust problems in relations between strangers with repeated games modelling trust problems in ongoing relations between partners. As expected, subjects are more trustful in repeated than in one-shot games. In subjects prenatally relatively highly primed by testosterone, however, this effect disappears after testosterone administration. We argue that impairments in cognitive empathy may reduce the repeated game effect on trust after testosterone administration in subjects with relatively high prenatal testosterone exposure and propose a neurobiological explanation for this effect.

21 CFR 584.200 - Ethyl alcohol containing ethyl acetate.

Science.gov (United States)

2010-04-01

... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Ethyl alcohol containing ethyl acetate. 584.200 Section 584.200 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS FOOD SUBSTANCES AFFIRMED AS GENERALLY RECOGNIZED AS...

Further evidence for GHB naturally occurring in common non-alcoholic beverages.

Science.gov (United States)

Elliott, Simon P; Fais, Paolo

2017-08-01

GHB has been implicated in many cases of suspected surreptitious administration with the purpose of increasing victim vulnerability to sexual assault. Low amounts of endogenous (or naturally occurring) GHB, which do not reach pharmacologically active levels, have been detected in alcoholic and non-alcoholic beverages. Due to the continued requirement to obtain data on the presence of endogenous GHB in various beverage types, GHB concentrations were measured in a series of non-alcoholic beverages. Tonic water and lemon flavoured tonic water beverages were analysed at 0, 24 and 96h after the bottle opening using gas chromatography coupled to tandem mass spectrometry (GC-MS/MS) on an Agilent 6890/7000C Triple Quadrupole. GHB was detected in all beverages at very low amounts ranging from 89 to 145ng/mL (0.089-0.145mg/L) and did not demonstrate a general trend of variation for concentration along the tested time span (96h). The presented data provide additional evidence for the endogenous nature of GHB in non-alcoholic beverages at very low concentrations, which are many orders of magnitude lower than those described to produce any pharmacological effect on the subject. However, when considering a case of alleged drug-facilitated sexual assault, a low level of GHB detected in a drink may be related both to a surreptitiously GHB administration with subsequent dilution for concealment or to the presence of endogenous GHB. On this basis, a comprehensive analysis of all the available information, including circumstantial data demonstrating possible attempts to conceal GHB administration and an assessment of levels of endogenous GHB in the suspected beverage type, is of the utmost importance for a proper interpretation of the toxicological results. Copyright © 2017 Elsevier B.V. All rights reserved.

A multimodal investigation of contextual effects on alcohol's emotional rewards.

Science.gov (United States)

Fairbairn, Catharine E; Bresin, Konrad; Kang, Dahyeon; Rosen, I Gary; Ariss, Talia; Luczak, Susan E; Barnett, Nancy P; Eckland, Nathaniel S

2018-05-01

Regular alcohol consumption in unfamiliar social settings has been linked to problematic drinking. A large body of indirect evidence has accumulated to suggest that alcohol's rewarding emotional effects-both negative-mood relieving and positive-mood enhancing-will be magnified when alcohol is consumed within unfamiliar versus familiar social contexts. But empirical research has never directly examined links between contextual familiarity and alcohol reward. In the current study, we mobilized novel ambulatory technology to examine the effect of social familiarity on alcohol reward in everyday drinking contexts while also examining how alcohol reward observed in these field contexts corresponds to reward observed in the laboratory. Heavy social drinking participants (N = 48, 50% male) engaged in an intensive week of ambulatory assessment. Participants wore transdermal alcohol sensors while they reported on their mood and took photographs of their social contexts in response to random prompts. Participants also attended 2 laboratory beverage-administration sessions, during which their emotional responses were assessed and transdermal sensors were calibrated to estimate breathalyzer readings (eBrACs). Results indicated a significant interaction between social familiarity and alcohol episode in everyday drinking settings, with alcohol enhancing mood to a greater extent in relatively unfamiliar versus familiar social contexts. Findings also indicated that drinking in relatively unfamiliar social settings was associated with higher eBrACs. Finally, results indicated a correspondence between some mood effects of alcohol experienced inside and outside the laboratory. This study presents a novel methodology for examining alcohol reward and indicates social familiarity as a promising direction for research seeking to explain problematic drinking. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

Differences in neurocognitive functioning associated with alcohol consumption in a multiethnic rural cohort: A Project FRONTIER study.

Science.gov (United States)

Lambert, Matthew Edward

2016-01-01

The current study assessed if a neuroprotective effect on cognition from mild alcohol consumption occurs in multiethnic rural communities and if effect differences occur due to gender or ethnicity. Participants were drawn from Project FRONTIER (Facing Rural Obstacles to healthcare Now Through Intervention, Education & Research), a community-based participatory research study assessing aging in a rural, West Texas, multiethnic cohort of participants aged 40 years and older. Alcohol consumption patterns were determined from Alcohol Use Disorders Identification Test responses. Cognitive measures included the Repeatable Battery for the Assessment of Neuropsychological Status. Because few participants had greater than a mild alcohol consumption pattern, only abstinent participants and those with mild consumption were compared (N = 1,004 1st observation; N = 256 2nd observation). Multivariate analysis of covariance revealed main effects for alcohol consumption pattern, gender, and ethnicity. Attention was most affected by alcohol consumption pattern followed by verbal memory. Mild alcohol consumption was associated with better performance in these areas. Gender and ethnicity had broad effects on cognitive abilities but inconsistent attention effects. Overall, mild alcohol consumption was associated with better attentional and other abilities compared with abstinence in a rural multiethnic sample. These findings are consistent with previous research and suggest ethnicity and gender are uninvolved in any alcohol neuroprotective effects.

Increased expression of protein kinase A inhibitor alpha (PKI-alpha) and decreased PKA-regulated genes in chronic intermittent alcohol exposure.

Science.gov (United States)

Repunte-Canonigo, Vez; Lutjens, Robert; van der Stap, Lena D; Sanna, Pietro Paolo

2007-03-23

Intermittent models of alcohol exposure that mimic human patterns of alcohol consumption produce profound physiological and biochemical changes and induce rapid increases in alcohol self-administration. We used high-density oligonucleotide microarrays to investigate gene expression changes during chronic intermittent alcohol exposure in three brain regions that receive mesocorticolimbic dopaminergic projections and that are believed to be involved in alcohol's reinforcing actions: the medial prefrontal cortex, the nucleus accumbens and the amygdala. An independent replication of the experiment was used for RT-PCR validation of the microarray results. The protein kinase A inhibitor alpha (PKI-alpha, Pkia), a member of the endogenous PKI family implicated in reducing nuclear PKA activity, was found to be increased in all three regions tested. Conversely, we observed a downregulation of the expression of several PKA-regulated transcripts in one or more of the brain regions studied, including the activity and neurotransmitter-regulated early gene (Ania) - 1, -3, -7, -8, the transcription factors Egr1 and NGFI-B (Nr4a1) and the neuropeptide NPY. Reduced expression of PKA-regulated genes in mesocorticolimbic projection areas may have motivational significance in the rapid increase in alcohol self-administration induced by intermittent alcohol exposure.

Subjective aggression during alcohol and cannabis intoxication before and after aggression exposure.

Science.gov (United States)

De Sousa Fernandes Perna, E B; Theunissen, E L; Kuypers, K P C; Toennes, S W; Ramaekers, J G

2016-09-01

Alcohol and cannabis use have been implicated in aggression. Alcohol consumption is known to facilitate aggression, whereas a causal link between cannabis and aggression has not been clearly demonstrated. This study investigated the acute effects of alcohol and cannabis on subjective aggression in alcohol and cannabis users, respectively, following aggression exposure. Drug-free controls served as a reference. It was hypothesized that aggression exposure would increase subjective aggression in alcohol users during alcohol intoxication, whereas it was expected to decrease subjective aggression in cannabis users during cannabis intoxication. Heavy alcohol (n = 20) and regular cannabis users (n = 21), and controls (n = 20) were included in a mixed factorial study. Alcohol and cannabis users received single doses of alcohol and placebo or cannabis and placebo, respectively. Subjective aggression was assessed before and after aggression exposure consisting of administrations of the point-subtraction aggression paradigm (PSAP) and the single category implicit association test (SC-IAT). Testosterone and cortisol levels in response to alcohol/cannabis treatment and aggression exposure were recorded as secondary outcome measures. Subjective aggression significantly increased following aggression exposure in all groups while being sober. Alcohol intoxication increased subjective aggression whereas cannabis decreased the subjective aggression following aggression exposure. Aggressive responses during the PSAP increased following alcohol and decreased following cannabis relative to placebo. Changes in aggressive feeling or response were not correlated to the neuroendocrine response to treatments. It is concluded that alcohol facilitates feelings of aggression whereas cannabis diminishes aggressive feelings in heavy alcohol and regular cannabis users, respectively.

Inhibitory Effects of Pretreatment with Radon on Acute Alcohol-Induced Hepatopathy in Mice

Directory of Open Access Journals (Sweden)

Teruaki Toyota

2012-01-01

Full Text Available 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/m3 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.

Postprocedural pain in shoulder arthrography: differences between using preservative-free normal saline and normal saline with benzyl alcohol as an intraarticular contrast diluent.

Science.gov (United States)

Storey, Troy F; Gilbride, George; Clifford, Kelly

2014-11-01

The purpose of this study was to prospectively evaluate the effect of benzyl alcohol, a common preservative in normal saline, on postprocedural pain after intraarticular injection for direct shoulder MR arthrography. From April 2011 through January 2013, 138 patients underwent direct shoulder MR arthrography. Using the Wong-Baker Faces Pain Scale, patients were asked to report their shoulder pain level immediately before and immediately after the procedure and then were contacted by telephone 6, 24, and 48 hours after the procedure. Fourteen patients did not receive the prescribed amount of contrast agent for diagnostic reasons or did not complete follow-up. Sixty-two patients received an intraarticular solution including preservative-free normal saline (control group) and 62 patients received an intraarticular solution including normal saline with 0.9% benzyl alcohol as a contrast diluent (test group). Patients were randomized as to which intraarticular diluent they received. Fluoroscopic and MR images were reviewed for extracapsular contrast agent administration or extravasation, full-thickness rotator cuff tears, and adhesive capsulitis. The effect of preservative versus control on pain level was estimated with multiple regression, which included time after procedure as the covariate and accounted for repeated measures over patients. Pain scale scores were significantly (p = 0.0382) higher (0.79 units; 95% CI, 0.034-1.154) with benzyl alcohol preservative compared with control (saline). In both study arms, the pain scale scores decreased slightly after the procedure, increased by roughly 1 unit over baseline for the test group and 0.3 unit over baseline for the control group by 6 hours after the procedure, were 0.50 unit over baseline for the test group and 0.12 unit over baseline for the control group at 24 hours, then fell to be slightly greater than baseline at 48 hours with benzyl alcohol and slightly less than baseline without benzyl alcohol. These trends

Role of cannabinoidergic mechanisms in ethanol self-administration and ethanol seeking in rat adult offspring following perinatal exposure to Δ9-tetrahydrocannabinol

International Nuclear Information System (INIS)

Economidou, Daina; Mattioli, Laura; Ubaldi, Massimo; Lourdusamy, Anbarasu; Soverchia, Laura; Hardiman, Gary; Campolongo, Patrizia; Cuomo, Vincenzo; Ciccocioppo, Roberto

2007-01-01

The present study evaluated the consequences of perinatal Δ 9 -tetrahydrocannabinol (Δ 9 -THC) treatment (5 mg/kg/day by gavage), either alone or combined with ethanol (3% v/v as the only fluid available), on ethanol self-administration and alcohol-seeking behavior in rat adult offspring. Furthermore, the effect of the selective cannabinoid CB 1 receptor antagonist, SR-141716A, on ethanol self-administration and on reinstatement of ethanol-seeking behavior induced either by stress or conditioned drug-paired cues was evaluated in adult offspring of rats exposed to the same perinatal treatment. Lastly, microarray experiments were conducted to evaluate if perinatal treatment with Δ 9 -tetrahydrocannabinol, ethanol or their combination causes long-term changes in brain gene expression profile in rats. The results of microarray data analysis showed that 139, 112 and 170 genes were differentially expressed in the EtOH, Δ 9 -THC, or EtOH + Δ 9 -THC group, respectively. No differences in alcohol self-administration and alcohol seeking were observed between rat groups. Intraperitoneal (IP) administration of SR-141716A (0.3-3.0 mg/kg) significantly reduced lever pressing for ethanol and blocked conditioned reinstatement of alcohol seeking. At the same doses SR-141716A failed to block foot-shock stress-induced reinstatement of alcohol seeking. The results reveal that perinatal exposure to Δ 9 -THC ethanol or their combination results in evident changes in gene expression patterns. However, these treatments do not significantly affect vulnerability to ethanol abuse in adult offspring. On the other hand, the results obtained with SR-141716A emphasize that endocannabinoid mechanisms play a major role in ethanol self-administration, as well as in the reinstatement of ethanol-seeking behavior induced by conditioned cues, supporting the idea that cannabinoid CB 1 receptor antagonists may represent interesting agents for the pharmacotherapy of alcoholism

Effects of consuming alcohol mixed with energy drinks versus consuming alcohol only on overall alcohol consumption and negative alcohol-related consequences

Directory of Open Access Journals (Sweden)

de Haan L

2012-11-01

Full Text Available Lydia de Haan,1 Hein A de Haan,2,3 Job van der Palen,4,5 Berend Olivier,1 Joris C Verster11Utrecht University, Utrecht Institute for Pharmaceutical Sciences, Division of Pharmacology, Utrecht, 2Tactus Addiction Treatment, Deventer, 3Nijmegen Institute for Scientist-Practitioners in Addiction, Nijmegen, 4Medical School Twente, Medisch Spectrum Twente, Enschede, 5Department of Research Methodology, Measurement, and Data Analysis, University of Twente, Enschede, The NetherlandsBackground: The aim of this study was to examine differences in alcohol consumption and its consequences when consumed alone and when mixed with energy drinks.Methods: A survey was conducted among Dutch students at Utrecht University and the College of Utrecht. We collected data on alcohol consumption and alcohol-related consequences of alcohol consumed alone and/or alcohol mixed with energy drinks (AMED. The data were analyzed using a retrospective within-subject design, comparing occasions when subjects consumed AMED with those when they consumed alcohol only in the past 30 days.Results: A representative sample of 6002 students completed the survey, including 1239 who consumed AMED. Compared with consuming alcohol only, when consuming AMED, students consumed significantly fewer alcoholic drinks on an average drinking day (6.0 versus 5.4, respectively, and reported significantly fewer drinking days in the previous month (9.2 versus 1.4, significantly fewer days being drunk (1.9 versus 0.5, and significantly fewer occasions of consuming more than four (female/five (male alcoholic drinks (4.7 versus 0.9. The maximum number of mixed alcoholic drinks (4.5 in the previous month was significantly lower when compared with occasions when they consumed alcohol only (10.7. Accordingly, the mean duration of a drinking session was significantly shorter when mixing alcoholic drinks (4.0 versus 6.0 hours. Finally, when consuming AMED, significantly fewer alcohol-related consequences were

El consumo de alcohol en personal administrativo y de servicios de una universidad del Ecuador O consumo de álcool em pessoal administrativo e de serviço de uma universidade do Equador Alcohol consumption in administrative and service personnel in an Ecuadorian university

Directory of Open Access Journals (Sweden)

Carmita María Bravo Ortiz

2010-06-01

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

Effect of alcohol and kolanut interaction on biochemical indices of ...

African Journals Online (AJOL)

The status of neuronal gene expression was monitored through assessment of these parameters. The results showed that alcohol-kolanut co-administration decreased brain total protein, DNA, RNA levels and protein/RNA ratios, and inhibited gene expression. These effects, in turn, inhibited DNA transcription, MRNA ...

Human pharmacology of 3,4-methylenedioxymethamphetamine (MDMA, ecstasy) after repeated doses taken 4 h apart Human pharmacology of MDMA after repeated doses taken 4 h apart.

Science.gov (United States)

Farré, Magí; Tomillero, Angels; Pérez-Mañá, Clara; Yubero, Samanta; Papaseit, Esther; Roset, Pere-Nolasc; Pujadas, Mitona; Torrens, Marta; Camí, Jordi; de la Torre, Rafael

2015-10-01

3,4-Methylenedioxymethamphetamine (MDMA, ecstasy) is a popular psychostimulant, frequently associated with multiple administrations over a short period of time. Repeated administration of MDMA in experimental settings induces tolerance and metabolic inhibition. The aim is to determine the acute pharmacological effects and pharmacokinetics resulting from two consecutive 100mg doses of MDMA separated by 4h. Ten male volunteers participated in a randomized, double-blind, crossover, placebo-controlled trial. The four conditions were placebo plus placebo, placebo plus MDMA, MDMA plus placebo, and MDMA plus MDMA. Outcome variables included pharmacological effects and pharmacokinetic parameters. After a second dose of MDMA, most effects were similar to those after a single dose, despite a doubling of MDMA concentrations (except for systolic blood pressure and reaction time). After repeated MDMA administration, a 2-fold increase was observed in MDMA plasma concentrations. For a simple dose accumulation MDMA and MDA concentrations were higher (+23.1% Cmax and +17.1% AUC for MDMA and +14.2% Cmax and +10.3% AUC for MDA) and HMMA and HMA concentrations lower (-43.3% Cmax and -39.9% AUC for HMMA and -33.2% Cmax and -35.1% AUC for HMA) than expected, probably related to MDMA metabolic autoinhibition. Although MDMA concentrations doubled after the second dose, most pharmacological effects were similar or slightly higher in comparison to the single administration, except for systolic blood pressure and reaction time which were greater than predicted. The pharmacokinetic-effects relationship suggests that when MDMA is administered at a 4h interval there exists a phenomenon of acute tolerance to its effects. Copyright © 2015 Elsevier B.V. and ECNP. All rights reserved.

Perspectives on the neuroscience of alcohol from the National Institute on Alcohol Abuse and Alcoholism.

Science.gov (United States)

Reilly, Matthew T; Noronha, Antonio; Warren, Kenneth

2014-01-01

Mounting evidence over the last 40 years clearly indicates that alcoholism (alcohol dependence) is a disorder of the brain. The National Institute on Alcohol Abuse and Alcoholism (NIAAA) has taken significant steps to advance research into the neuroscience of alcohol. The Division of Neuroscience and Behavior (DNB) was formed within NIAAA in 2002 to oversee, fund, and direct all research areas that examine the effects of alcohol on the brain, the genetic underpinnings of alcohol dependence, the neuroadaptations resulting from excessive alcohol consumption, advanced behavioral models of the various stages of the addiction cycle, and preclinical medications development. This research portfolio has produced important discoveries in the etiology, treatment, and prevention of alcohol abuse and dependence. Several of these salient discoveries are highlighted and future areas of neuroscience research on alcohol are presented. © 2014 Elsevier B.V. All rights reserved.

An ultrastructural analysis of the effects of ethanol self-administration on the hypothalamic paraventricular nucleus in rhesus macaques

Directory of Open Access Journals (Sweden)

Vanessa Anne Jimenez

2015-07-01

Full Text Available A bidirectional relationship between stress and alcohol exists whereby stressful events are comorbid with problematic alcohol use and prolonged alcohol exposure results in adaptations of the physiological stress response. Endocrine response to stress is initiated in the hypothalamic paraventricular nucleus (PVN with the synthesis and release of corticotropin-releasing hormone (CRH and arginine-vasopressin (AVP. Alterations in CRH and AVP following long-term alcohol exposure in rodents is well demonstrated, however little is known about the response to alcohol in primates or the mechanisms of adaptation. We hypothesized that long-term alcohol self-administration in nonhuman primates would lead to ultrastructural changes in the PVN underlying adaptation to chronic alcohol. Double-label immunogold electron microscopy was used to measure presynaptic GABA and glutamate density within synaptic terminals contacting CRH- and AVP-immunoreactive dendrites. Additionally, pituitary-adrenal hormones (ACTH, cortisol, DHEA-s and aldosterone under two conditions (low and mild stress were compared before and after self-administration. All hormones were elevated in response to the mild stressor independent of alcohol consumption. The presynaptic glutamate density in recurrent (i.e., intra-hypothalamic CRH terminals was highly related to alcohol intake, and may be a permissive factor in increased drinking due to stress. Conversely, glutamate density within recurrent AVP terminals showed a trend-level increase following alcohol, but was not related to average daily consumption. Glutamate density in non-recurrent AVP terminals was related to aldosterone under the low stress condition while GABAergic density in this terminal population was related to water consumption. The results reveal distinct populations of presynaptic terminals whose glutamatergic or GABAergic density were uniquely related to water and alcohol consumption and circulating hormones.

Alcohol-specific parenting, adolescent alcohol use and the mediating effect of adolescent alcohol-related cognitions

NARCIS (Netherlands)

Mares, S.H.W.; Lichtwarck-Aschoff, A.; Engels, R.C.M.E.

2013-01-01

Objectives : Previous research indicated that alcohol-specific parenting is an important precursor of adolescent alcohol use, but failed to define the underlying mechanism. Based on social cognitive theory, alcohol-related cognitions such as alcohol refusal self-efficacy and alcohol-related

Heavy episodic drinking and alcohol-related injuries: An open cohort study among college students.

Science.gov (United States)

Caamaño-Isorna, Francisco; Moure-Rodríguez, Lucía; Doallo, Sonia; Corral, Montserrat; Rodriguez Holguín, Socorro; Cadaveira, Fernando

2017-03-01

The objective of this study is to assess the effects of Heavy Episodic Drinking (HED) on the incidence of alcohol-related injuries among university students in Spain, taking sex into consideration. We carried out an open cohort study among college students in Spain (992 women and 371 men). HED and alcohol-related injuries were measured by question 3rd and 9th of Alcohol Use Disorders Identification Test to every participant at the ages of 18, 20, 22, 24 and 27. For data analysis we used a Multilevel Logistic Regression for repeated measures adjusting for alcohol and cannabis use. The incidence rate of alcohol-related injuries was 0.028year -1 for females and 0.036year -1 for males. The multivariate analysis showed that among females a high frequency of HED and use of cannabis are risk factors for alcohol-related injuries (Odds Ratio [OR]=2.64 and OR=3.68), while being more than 23 is a protective factor (OR=0.34). For males, bivariate analysis also showed HED like risk factor (OR=4.69 and OR=2.51). Finally, the population attributable fraction for HED among females was 37.12%. HED leads to an increase of alcohol-related injuries in both sexes and being over 23 years old acts as a protective factor among women. Our results suggest that about one third of alcohol-related injuries among women could be avoided by removing HED. Copyright © 2016 Elsevier Ltd. All rights reserved.

Repeated administration of phytocannabinoid Δ(9)-THC or synthetic cannabinoids JWH-018 and JWH-073 induces tolerance to hypothermia but not locomotor suppression in mice, and reduces CB1 receptor expression and function in a brain region-specific manner.

Science.gov (United States)

Tai, S; Hyatt, W S; Gu, C; Franks, L N; Vasiljevik, T; Brents, L K; Prather, P L; Fantegrossi, W E

2015-12-01

These studies probed the relationship between intrinsic efficacy and tolerance/cross-tolerance between ∆(9)-THC and synthetic cannabinoid drugs of abuse (SCBs) by examining in vivo effects and cellular changes concomitant with their repeated administration in mice. Dose-effect relationships for hypothermic effects were determined in order to confirm that SCBs JWH-018 and JWH-073 are higher efficacy agonists than ∆(9)-THC in mice. Separate groups of mice were treated with saline, sub-maximal hypothermic doses of JWH-018 or JWH-073 (3.0mg/kg or 10.0mg/kg, respectively) or a maximally hypothermic dose of 30.0mg/kg ∆(9)-THC once per day for 5 consecutive days while core temperature and locomotor activity were monitored via biotelemetry. Repeated administration of all drugs resulted in tolerance to hypothermic effects, but not locomotor effects, and this tolerance was still evident 14 days after the last drug administration. Further studies treated mice with 30.0mg/kg ∆(9)-THC once per day for 4 days, then tested with SCBs on day 5. Mice with a ∆(9)-THC history were cross-tolerant to both SCBs, and this cross-tolerance also persisted 14 days after testing. Select brain regions from chronically treated mice were examined for changes in CB1 receptor expression and function. Expression and function of hypothalamic CB1Rs were reduced in mice receiving chronic drugs, but cortical CB1R expression and function were not altered. Collectively, these data demonstrate that repeated ∆(9)-THC, JWH-018 and JWH-073 can induce long-lasting tolerance to some in vivo effects, which is likely mediated by region-specific downregulation and desensitization of CB1Rs. Copyright © 2015 Elsevier Ltd. All rights reserved.

Effect of alcohol and paracetamol on aspect of the hematology of ...

African Journals Online (AJOL)

WBC) and lymphocyte counts as well as serum cholesterol level were used to access the effects of administration of alcohol and paracetamol to albino rats. Fifteen male albino rats weighing between 75 – 160 grams were grouped into five and ...

Alcohol-attributable and alcohol-preventable mortality in Denmark

DEFF Research Database (Denmark)

Eliasen, Marie; Becker, Ulrik; Grønbæk, Morten

2014-01-01

The aim of the study was to quantify alcohol-attributable and -preventable mortality, totally and stratified on alcohol consumption in Denmark 2010, and to estimate alcohol-related mortality assuming different scenarios of changes in alcohol distribution in the population. We estimated alcohol......-attributable and -preventable fractions based on relative risks of conditions causally associated with alcohol from meta-analyses and information on alcohol consumption in Denmark obtained from 14,458 participants in the Danish National Health Survey 2010 and corrected for adult per capita consumption. Cause-specific mortality...... data were obtained from the Danish Register of Causes of Death. In total, 1,373 deaths among women (5.0 % of all deaths) and 2,522 deaths among men (9.5 % of all deaths) were attributable to alcohol, while an estimated number of 765 (2.8 %) and 583 (2.2 %) deaths were prevented by alcohol...

Protective Effect of Hericium erinaceus on Alcohol Induced Hepatotoxicity in Mice

OpenAIRE

Hao, Lijun; Xie, Yuxi; Wu, Guikai; Cheng, Aibin; Liu, Xiaogang; Zheng, Rongjuan; Huo, Hong; Zhang, Junwei

2015-01-01

We investigated the effects of Hericium erinaceus (HEM) on liver injury induced by acute alcohol administration in mice. Mice received ethanol (5?g/kg?BW) by gavage every 12?hrs for a total of 3 doses. HEM (200?mg/kg?BW) was gavage before ethanol administration. Subsequent serum alanine aminotransferase (ALT) level, aspartate aminotransaminase (AST) level, Maleic dialdehyde (MDA) level, hepatic total antioxidant status (TAOS), and activated nuclear factor kappa-light-chain-enhancer of activat...

Effect of Low Dose Lead (Pb) Administration on Tail Immersion Test ...

African Journals Online (AJOL)

olayemitoyin

Effect of Low Dose Lead (Pb) Administration on Tail ... Acute and sub-acute effects of lead are caused by relatively large ... As such, the brain is the organ most studied in lead toxicity. ..... inflammatory Properties of Hydro-alcohol Extract of.

Effectiveness of a nonrinse, alcohol-free antiseptic hand wash.

Science.gov (United States)

Moadab, A; Rupley, K F; Wadhams, P

2001-06-01

This study evaluated the efficacy of a novel surfactant, allantoin, and benzalkonium chloride hand sanitizer using the US Food and Drug Administration's method for testing antiseptic hand washes that podiatric physicians and other health-care personnel use. The alcohol-free product, HandClens, was compared with an alcohol-based product, Purell. Independent researchers from the California College of Podiatric Medicine conducted the study using 40 volunteer students from the class of 2001. The results show that HandClens outperformed Purell and met the regulatory requirements for a hand sanitizer. Purell failed as an antimicrobial hand wash and was less effective than a control soap used in the study.

The alcohol industry lobby and Hong Kong’s zero wine and beer tax policy

Directory of Open Access Journals (Sweden)

Yoon Sungwon

2012-08-01

Full Text Available Abstract Background Whereas taxation on alcohol is becoming an increasingly common practice in many countries as part of overall public health measures, the Hong Kong Special Administrative Region Government is bucking the trend and lowered its duties on wine and beer by 50 percent in 2007. In 2008, Hong Kong removed all duties on alcohol except for spirits. The aim of this paper is to examine the case of Hong Kong with its history of changes in alcohol taxation to explore the factors that have driven such an unprecedented policy evolution. Methods The research is based on an analysis of primary documents. Searches of official government documents, alcohol-related industry materials and other media reports on alcohol taxation for the period from 2000 to 2008 were systematically carried out using key terms such as “alcohol tax” and “alcohol industry”. Relevant documents (97 were indexed by date and topic to undertake a chronological and thematic analysis using Nvivo8 software. Results Our analysis demonstrates that whereas the city’s changing financial circumstances and the Hong Kong Special Administrative Region Government’s strong propensity towards economic liberalism had, in part, contributed to such dramatic transformation, the alcohol industry’s lobbying tactics and influence were clearly the main drivers of the policy decision. The alcohol industry’s lobbying tactics were two-fold. The first was to forge a coalition encompassing a range of catering and trade industries related to alcohol as well as industry-friendly lawmakers so that these like-minded actors could find common ground in pursuing changes to the taxation policy. The second was to deliberately promote a blend of ideas to garner support from the general public and to influence the perception of key policy makers. Conclusions Our findings suggest that the success of aggressive industry lobbying coupled with the absence of robust public health advocacy was the

The alcohol industry lobby and Hong Kong’s zero wine and beer tax policy

Science.gov (United States)

2012-01-01

Background Whereas taxation on alcohol is becoming an increasingly common practice in many countries as part of overall public health measures, the Hong Kong Special Administrative Region Government is bucking the trend and lowered its duties on wine and beer by 50 percent in 2007. In 2008, Hong Kong removed all duties on alcohol except for spirits. The aim of this paper is to examine the case of Hong Kong with its history of changes in alcohol taxation to explore the factors that have driven such an unprecedented policy evolution. Methods The research is based on an analysis of primary documents. Searches of official government documents, alcohol-related industry materials and other media reports on alcohol taxation for the period from 2000 to 2008 were systematically carried out using key terms such as “alcohol tax” and “alcohol industry”. Relevant documents (97) were indexed by date and topic to undertake a chronological and thematic analysis using Nvivo8 software. Results Our analysis demonstrates that whereas the city’s changing financial circumstances and the Hong Kong Special Administrative Region Government’s strong propensity towards economic liberalism had, in part, contributed to such dramatic transformation, the alcohol industry’s lobbying tactics and influence were clearly the main drivers of the policy decision. The alcohol industry’s lobbying tactics were two-fold. The first was to forge a coalition encompassing a range of catering and trade industries related to alcohol as well as industry-friendly lawmakers so that these like-minded actors could find common ground in pursuing changes to the taxation policy. The second was to deliberately promote a blend of ideas to garner support from the general public and to influence the perception of key policy makers. Conclusions Our findings suggest that the success of aggressive industry lobbying coupled with the absence of robust public health advocacy was the main driving force behind the

Targeted intervention: Computational approaches to elucidate and predict relapse in alcoholism.

Science.gov (United States)

Heinz, Andreas; Deserno, Lorenz; Zimmermann, Ulrich S; Smolka, Michael N; Beck, Anne; Schlagenhauf, Florian

2017-05-01

Alcohol use disorder (AUD) and addiction in general is characterized by failures of choice resulting in repeated drug intake despite severe negative consequences. Behavioral change is hard to accomplish and relapse after detoxification is common and can be promoted by consumption of small amounts of alcohol as well as exposure to alcohol-associated cues or stress. While those environmental factors contributing to relapse have long been identified, the underlying psychological and neurobiological mechanism on which those factors act are to date incompletely understood. Based on the reinforcing effects of drugs of abuse, animal experiments showed that drug, cue and stress exposure affect Pavlovian and instrumental learning processes, which can increase salience of drug cues and promote habitual drug intake. In humans, computational approaches can help to quantify changes in key learning mechanisms during the development and maintenance of alcohol dependence, e.g. by using sequential decision making in combination with computational modeling to elucidate individual differences in model-free versus more complex, model-based learning strategies and their neurobiological correlates such as prediction error signaling in fronto-striatal circuits. Computational models can also help to explain how alcohol-associated cues trigger relapse: mechanisms such as Pavlovian-to-Instrumental Transfer can quantify to which degree Pavlovian conditioned stimuli can facilitate approach behavior including alcohol seeking and intake. By using generative models of behavioral and neural data, computational approaches can help to quantify individual differences in psychophysiological mechanisms that underlie the development and maintenance of AUD and thus promote targeted intervention. Copyright © 2016 Elsevier Inc. All rights reserved.

[Alcohol].

Science.gov (United States)

Zima, T

1996-07-14

Alcohol is one of the most widely used addictive substances. It can be assumed that everybody encounters alcohol--ethanol in various forms and concentrations in the course of their lives. A global and social problem of our civilization is alcohol consumption which has a rising trend. Since 1989 the consumption of alcoholic beverages is rising and the mean annual consumption of concentrated ethanol per head is cea 10 litres. In ethanol abuse the organism is damaged not only by ethanol alone but in particular by substances formed during its metabolism. Its detailed knowledge is essential for the knowledge and investigations of the metabolic and toxic effect of ethanol on the organism. Ingested alcohol is in 90-98% eliminated from the organism by three known metabolic pathways: 1-alcohol dehydrogenase, 2-the microsomal ethanol oxidizing system and 3-catalase. Alcohol is a frequent important risk factor of serious "diseases of civilization" such as IHD, hypertension, osteoporosis, neoplastic diseases. Cirrhosis of the liver and chronic pancreatitis are the well known diseases associated with alcohol ingestion and also their most frequent cause. It is impossible to list all organs and diseases which develop as a result of alcohol consumption. It is important to realize that regular and "relatively" small amounts in the long run damage the organism and may be even fatal.

Quantification and Assessment of the Chemical Form of Residual Gadolinium in the Brain After Repeated Administration of Gadolinium-Based Contrast Agents

Science.gov (United States)

Frenzel, Thomas; Apte, Chirag; Jost, Gregor; Schöckel, Laura; Lohrke, Jessica; Pietsch, Hubertus

2017-01-01

Objective Multiple clinical and preclinical studies have reported a signal intensity increase and the presence of gadolinium (Gd) in the brain after repeated administration of Gd-based contrast agents (GBCAs). This bioanalytical study in rat brain tissue was initiated to investigate whether the residual Gd is present as intact GBCA or in other chemical forms by using tissue fractionation and chromatography. Materials and Methods Rats were divided randomly in 6 groups of 10 animals each. They received 10 daily injections of 2.5 mmol/kg bodyweight of 1 of 5 different GBCAs: linear GBCAs such as gadodiamide (Omniscan; GE Healthcare), gadopentetate dimeglumine (Gd-DTPA, Magnevist; Bayer), or gadobenate dimeglumine (Multihance; Bracco) and macrocyclic GBCAs such as gadobutrol (Gadovist; Bayer) and gadoterate meglumine (Gd-DOTA, Dotarem; Guerbet) or saline. On days 3 and 24 after the last injection (p.i.), 5 randomly chosen animals of each group were killed by exsanguination, and their brains were excised and divided into cerebrum, pons, and cerebellum. The brain sections were homogenized by sonication in ice-cold buffer at pH 7.4. Soluble and insoluble fractions were separated by centrifugation, and the soluble fractions were further separated by gel permeation chromatography (GPC). The Gd concentration in all tissue fractions and in the GPC eluate was measured by inductively coupled plasma–mass spectrometry. In a recovery control experiment, all GBCAs were spiked to blank brain tissue and more than 94% recovery of Gd in the tissue fractions was demonstrated. Results Only traces of the administered Gd were found in the rat brain tissue on day 3 and day 24 p.i. In the animals treated with macrocyclic GBCAs, Gd was found only in the soluble brain fraction and was present solely as low molecular weight molecules, most likely the intact GBCA. In the animals treated with linear GBCAs Gd was found to a large extent in the insoluble tissue fraction. The Gd concentration in

The lack of influence of food and local alcoholic brew on the blood level of Mectizan(®) (ivermectin).

Science.gov (United States)

Homeida, Mamoun M; Malcolm, Stephen B; ElTayeb, A Z; Eversole, Rob R; Elassad, Asma S; Geary, Timothy G; Ali, Magdi M; Mackenzie, Charles D

2013-08-01

There is concern that extraneous factors, such as food and drink, may alter the pharmacodynamics of Mectizan(®) (ivermectin) in patients receiving this important anti-parasitic drug, and thus might put such individuals in danger of serious adverse events. The effects of a common local alcohol-containing beverage and a local food on plasma levels of ivermectin were studied in Sudanese volunteers after administration of the standard dose used in mass drug administration programs for onchocerciasis and filariasis. Plasma levels of ivermectin at various time points (0-48h) after administration of ivermectin were ascertained by HPLC assay in ten volunteers given 150μgkg(-1) ivermectin together with either a local sorghum-based food ('assida'), or a locally brewed alcoholic beverage ('arangi' made from sorghum grain) or in those who were fasting. Maximum mean (±SD) plasma levels of ivermectin (67±49ngml(-1)) were reached within 2h in fasting patients, and had dropped to 26±20ngml(-1) after 30h. The coadministration of local food or alcoholic beverage did not cause an increase in ivermectin plasma levels above those observed in people who were fasting. However, at 2h after ivermectin administration, patients given alcohol had significantly lower plasma ivermectin levels than fed patients or fasting patients. There were no significant differences among treatments for AUC0-30, Cmax, or tmax, and so the coadministration of local food or alcoholic beverage did not cause any change in pharmacokinetic parameters of ivermectin in the plasma in comparison with fasting. None of the measured levels of plasma ivermectin were greater than those reported in previous studies with this compound. These findings do not support the hypothesis that acute intake of alcohol is an important factor in the development of the serious adverse reactions that can occur during the treatment of loaisis patients with ivermectin (Mectizan(®)). Copyright © 2013 Elsevier B.V. All rights reserved.

Alcohol

Science.gov (United States)

... because that's how many accidents occur. What Is Alcoholism? What can be confusing about alcohol is that ... develop a problem with it. Sometimes, that's called alcoholism (say: al-kuh-HOL - ism) or being an ...

Alcohol

Science.gov (United States)

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 ...

Glutathione depletion in tissues after administration of buthionine sulphoximine

International Nuclear Information System (INIS)

Minchinton, A.I.; Rojas, A.; Smith, A.; Soranson, J.A.; Shrieve, D.C.; Jones, N.R.; Bremner, J.C.

1984-01-01

Buthionine sulphoximine (BSO) an inhibitor of glutathione (GSH) biosynthesis, was administered to mice in single and repeated doses. The resultant pattern of GSH depletion was studied in liver, kidney, skeletal muscle and three types of murine tumor. Liver and kidney exhibited a rapid depletion of GSH. Muscle was depleted to a similar level, but at a slower rate after a single dose. All three tumors required repeated administration of BSO over several days to obtain a similar degree of depletion to that shown in the other tissues

Geocoding routinely collected administrative data to measure access to alcohol outlets in Wales

Directory of Open Access Journals (Sweden)

Richard Fry

2017-04-01

All authorities were able to provide an actual or approximate license issue date, allowing us to summarise the number of outlets annually. Several authorities were unable to provide precise outlet closure dates, so the date of the last interaction with the outlet was used to generate an approximate end date. One-half of the unitary authorities were able to provide the On/Off sales status of outlets, and 9 were able to provide opening hours. From these data we were able to geocode 53% (range 28% to 72% by local authority using GIS, the remaining 47% were matched using Google products to verify and extract a precise geographic location. Conclusions The collation and processing of retrospective alcohol outlet data was successfully completed to enable the building of a longitudinal exposure dataset. There was considerable variation between the unitary authorities in the quality of address data, and data related to the availability of alcohol, for example opening hours. The lack of address structure required us to devise a manual address matching process to capture the addresses that could not be geocoded. To aid future data linkage based evaluations to provide policy evidence in a timely manner, local government datasets should use standardised data fields, including addresses and Point-of-Capture address verification.

Lactobacillus rhamnosus CCFM1107 treatment ameliorates alcohol-induced liver injury in a mouse model of chronic alcohol feeding.

Science.gov (United States)

Tian, Fengwei; Chi, Feifei; Wang, Gang; Liu, Xiaoming; Zhang, Qiuxiang; Chen, Yongquan; Zhang, Hao; Chen, Wei

2015-12-01

Lactobacillus rhamnosus CCFM1107 was screened for high antioxidative activity from 55 lactobacilli. The present study attempted to explore the protective properties of L. rhamnosus CCFM1107 in alcoholic liver injury. A mouse model was induced by orally feeding alcohol when simultaneously treated with L. rhamnosus CCFM1107, the drug Hu-Gan- Pian (HGP), L. rhamnosus GG (LGG), and L. plantarum CCFM1112 for 3 months. Biochemical analysis was performed for both serum and liver homogenate. Detailed intestinal flora and histological analyses were also carried out. Our results indicated that the administration of L. rhamnosus CCFM1107 significantly inhibited the increase in the levels of serum aminotransferase and endotoxin, as well as the levels of triglyceride (TG) and cholesterol (CHO) in the serum and in the liver. Glutathione (GSH), glutathione peroxidase (GSH-Px) and superoxide dismutase (SOD) were elevated while the levels of malondialdehyde (MDA) were decreased. The enteric dysbiosis caused by alcohol was restored by increasing the numbers of both lactobacilli and bifidobacteria and decreasing the numbers of both enterococci and enterobacter. Histological analysis confirmed the protective effect of L. rhamnosus CCFM1107. Compared with the other lactobacilli and to the drug Hu-Gan-Pian, there is a high chance that L. rhamnosus CCFM1107 provides protective effects on alcoholic liver injury by reducing oxidative stress and restoring the intestinal flora.

Pharmacokinetics of repeated oral administration of tramadol hydrochloride in Hispaniolan Amazon parrots (Amazona ventralis).

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Souza, Marcy J; Gerhardt, Lillian; Cox, Sherry

2013-07-01

To determine the pharmacokinetics of tramadol hydrochloride (30 mg/kg) following twice-daily oral administration in Hispaniolan Amazon parrots (Amazona ventralis). 9 healthy adult Hispaniolan Amazon parrots. Tramadol hydrochloride was administered to each parrot at a dosage of 30 mg/kg, PO, every 12 hours for 5 days. Blood samples were collected just prior to dose 2 on the first day of administration (day 1) and 5 minutes before and 10, 20, 30, 60, 90, 180, 360, and 720 minutes after the morning dose was given on day 5. Plasma was harvested from blood samples and analyzed by high-performance liquid chromatography. Degree of sedation was evaluated in each parrot throughout the study. No changes in the parrots' behavior were observed. Twelve hours after the first dose was administered, mean ± SD concentrations of tramadol and its only active metabolite M1 (O-desmethyltramadol) were 53 ± 57 ng/mL and 6 ± 6 ng/mL, respectively. At steady state following 4.5 days of twice-daily administration, the mean half-lives for plasma tramadol and M1 concentrations were 2.92 ± 0.78 hours and 2.14 ± 0.07 hours, respectively. On day 5 of tramadol administration, plasma concentrations remained in the therapeutic range for approximately 6 hours. Other tramadol metabolites (M2, M4, and M5) were also present. On the basis of these results and modeling of the data, tramadol at a dosage of 30 mg/kg, PO, will likely need to be administered every 6 to 8 hours to maintain therapeutic plasma concentrations in Hispaniolan Amazon parrots.

Studies on reversibility of cerebral atrophy in alcoholics by computed tomography

International Nuclear Information System (INIS)

Nakamura, Kiyoshi; Kikuchi, Yoshito; Sanga, Kenji; Nakamura, Kazuyoshi; Kawamura, Toshiaki; Domon, Yuji; Mitamura, Akira; Hayashi, Yu; Ogata, Motoyo.

1987-01-01

Only sparse data exist concerning objectively quantified reversibility of cerebral atrophy (CA) in alcoholics by computed tomography (CT). This study explored reversible CA changes from measurements of the area seen on repeated CT scans, which were acquired over a period of 6 - 191 weeks in 44 alcoholics. In the group of abstinent alcoholics, significant recovery of CA was observed in all 6 regions of interest (ROI) at the second CT scan, as compared with that at the first CT scan. Measurements obtained from CT revealed aggravation of CA in the bilateral anterior horns, right cella media, and frontal subarachnoid space in the group with drinking alcoholics. The rate of recovery was significantly higher with the interval between the first and second CT scans and the duration of abstinence being longer. For the frontal area, it tended to be better when the degree of CA was severer at the first CT scan. There was no significant correlation between the rate of recovery and age or the duration of drinking habit in any of the ROIs. The beginning of CA recovery after abstinence is likely to depend on the brain sites; The cella media seemed to be the first to recover from CA. (Namekawa, K.)

Alcohol, microbiome, life style influence alcohol and non-alcoholic organ damage.

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Neuman, Manuela G; French, Samuel W; Zakhari, Samir; Malnick, Stephen; Seitz, Helmut K; Cohen, Lawrence B; Salaspuro, Mikko; Voinea-Griffin, Andreea; Barasch, Andrei; Kirpich, Irina A; Thomes, Paul G; Schrum, Laura W; Donohue, Terrence M; Kharbanda, Kusum K; Cruz, Marcus; Opris, Mihai

2017-02-01

This paper is based upon the "8th Charles Lieber's Satellite Symposium" organized by Manuela G. Neuman at the Research Society on Alcoholism Annual Meeting, on June 25, 2016 at New Orleans, Louisiana, USA. The integrative symposium investigated different aspects of alcohol-induced liver disease (ALD) as well as non-alcohol-induced liver disease (NAFLD) and possible repair. We revealed the basic aspects of alcohol metabolism that may be responsible for the development of liver disease as well as the factors that determine the amount, frequency and which type of alcohol misuse leads to liver and gastrointestinal diseases. We aimed to (1) describe the immuno-pathology of ALD, (2) examine the role of genetics in the development of alcoholic hepatitis (ASH) and NAFLD, (3) propose diagnostic markers of ASH and non-alcoholic steatohepatitis (NASH), (4) examine age and ethnic differences as well as analyze the validity of some models, (5) develop common research tools and biomarkers to study alcohol-induced effects, 6) examine the role of alcohol in oral health and colon and gastrointestinal cancer and (7) focus on factors that aggravate the severity of organ-damage. The present review includes pre-clinical, translational and clinical research that characterizes ALD and NAFLD. Strong clinical and experimental evidence lead to recognition of the key toxic role of alcohol in the pathogenesis of ALD with simple fatty infiltrations and chronic alcoholic hepatitis with hepatic fibrosis or cirrhosis. These latter stages may also be associated with a number of cellular and histological changes, including the presence of Mallory's hyaline, megamitochondria, or perivenular and perisinusoidal fibrosis. Genetic polymorphisms of ethanol metabolizing enzymes and cytochrome p450 (CYP) 2E1 activation may change the severity of ASH and NASH. Other risk factors such as its co-morbidities with chronic viral hepatitis in the presence or absence of human deficiency virus were discussed

Accelerated blood clearance phenomenon upon cross-administration of PEGylated nanocarriers in beagle dogs

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Wang CL

2015-05-01

Full Text Available Chunling Wang,1 Xiaobo Cheng,2 Yuqing Su,1 Ying Pei,3 Yanzhi Song,1 Jiao Jiao,1 Zhenjun Huang,1 Yanfei Ma,1 Yinming Dong,1 Ying Yao,1 Jingjing Fan,1 Han Ta,1 Xinrong Liu,1 Hui Xu,1 Yihui Deng1 1College of Pharmacy, Shenyang Pharmaceutical University, Shenyang, People’s Republic of China; 2Deli Wei Biological Technology Co, Ltd, Beijing, People’s Republic of China; 3Shenyang Women’s and Children’s Hospital, Shenyang, People’s Republic of China Abstract: The cross-administration of nanocarriers modified by poly(ethylene glycol (PEG, named PEGylated nanocarriers, a type of combination therapy, is becoming an increasingly important method of long-term drug delivery, to decrease side effects, avoid multidrug resistance, and increase therapeutic efficacy. However, repeated injections of PEGylated nanocarriers induces the accelerated blood clearance (ABC phenomenon, prevents long circulation, and can cause adverse effects owing to alterations in the biodistribution of the drug. Although the nature of the ABC phenomenon that is induced by repeated injections of PEGylated nanocarriers has already been studied in detail, there are few reports on the immune response elicited by the cross-administration of PEGylated nanocarriers. In this study, we investigated the ABC phenomenon induced by the intravenous cross-administration of various PEGylated nanocarriers, including PEGylated liposomes (PL, PEG micelles (PM, PEGylated solid lipid nanoparticles (PSLN, and PEGylated emulsions (PE, in beagle dogs. The results indicated that the magnitude of the immune response elicited by the cross-administration was in the following order (from the strongest to the weakest: PL, PE, PSLN, PM. It is specifically PEG in the brush structure that elicits a significant immune response, in both the induction phase and the effectuation phase. Furthermore, the present study suggests that there is a considerable difference between the effect of repeated injections and

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

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Yuan Wang

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

Experimental psychopathology paradigms for alcohol use disorders: Applications for translational research.

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Bujarski, Spencer; Ray, Lara A

2016-11-01

In spite of high prevalence and disease burden, scientific consensus on the etiology and treatment of Alcohol Use Disorder (AUD) has yet to be reached. The development and utilization of experimental psychopathology paradigms in the human laboratory represents a cornerstone of AUD research. In this review, we describe and critically evaluate the major experimental psychopathology paradigms developed for AUD, with an emphasis on their implications, strengths, weaknesses, and methodological considerations. Specifically we review alcohol administration, self-administration, cue-reactivity, and stress-reactivity paradigms. We also provide an introduction to the application of experimental psychopathology methods to translational research including genetics, neuroimaging, pharmacological and behavioral treatment development, and translational science. Through refining and manipulating key phenotypes of interest, these experimental paradigms have the potential to elucidate AUD etiological factors, improve the efficiency of treatment developments, and refine treatment targets thus advancing precision medicine. Copyright © 2016 Elsevier Ltd. All rights reserved.

Cellular Composition of the Spleen and Changes in Splenic Lysosomes in the Dynamics of Dyslipidemia in Mice Caused by Repeated Administration of Poloxamer 407.

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Goncharova, N V; Shurlygina, A V; Mel'nikova, E V; Karmatskikh, O L; Avrorov, P A; Loktev, K V; Korolenko, T A

2015-11-01

We studied the effect of dyslipidemia induced by poloxamer 407 (300 mg/kg twice a week for 30 days) on cellular composition of the spleen and splenocyte lysosomes in mice. Changes in blood lipid profile included elevated concentrations of total cholesterol, aterogenic LDL, and triglycerides most pronounced in 24 h after the last poloxamer 407 injection; gradual normalization of lipid profile was observed in 4 days (except triglycerides) and 10 days. The most pronounced changes in the spleen (increase in organ weight and number of cells, inhibition in apoptosis, and reduced accumulation of vital dye acridine orange in lysosomes) were detected on day 4; on day 10, the indices returned to normal. Cathepsin D activity in the spleen also increased at these terms. The relationship between changes in the cellular composition of the spleen and dynamics of serum lipid profile in mice in dyslipidemia caused by repeated administrations of relatively low doses of poloxamer 407 is discussed.

Receptivity to alcohol marketing predicts initiation of alcohol use.

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Henriksen, Lisa; Feighery, Ellen C; Schleicher, Nina C; Fortmann, Stephen P

2008-01-01

This longitudinal study examined the influence of alcohol advertising and promotions on the initiation of alcohol use. A measure of receptivity to alcohol marketing was developed from research about tobacco marketing. Recall and recognition of alcohol brand names were also examined. Data were obtained from in-class surveys of sixth, seventh, and eighth graders at baseline and 12-month follow-up. Participants who were classified as never drinkers at baseline (n = 1,080) comprised the analysis sample. Logistic regression models examined the association of advertising receptivity at baseline with any alcohol use and current drinking at follow-up, adjusting for multiple risk factors, including peer alcohol use, school performance, risk taking, and demographics. At baseline, 29% of never drinkers either owned or wanted to use an alcohol branded promotional item (high receptivity), 12% students named the brand of their favorite alcohol ad (moderate receptivity), and 59% were not receptive to alcohol marketing. Approximately 29% of adolescents reported any alcohol use at follow-up; 13% reported drinking at least 1 or 2 days in the past month. Never drinkers who reported high receptivity to alcohol marketing at baseline were 77% more likely to initiate drinking by follow-up than those were not receptive. Smaller increases in the odds of alcohol use at follow-up were associated with better recall and recognition of alcohol brand names at baseline. Alcohol advertising and promotions are associated with the uptake of drinking. Prevention programs may reduce adolescents' receptivity to alcohol marketing by limiting their exposure to alcohol ads and promotions and by increasing their skepticism about the sponsors' marketing tactics.

Intranasal Oxytocin Selectively Modulates Social Perception, Craving, and Approach Behavior in Subjects With Alcohol Use Disorder.

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Mitchell, Jennifer M; Arcuni, Peter A; Weinstein, Dawn; Woolley, Josh D

2016-01-01

A pharmacotherapy that both improves social abilities and promotes abstinence may be particularly helpful for the treatment of alcohol use disorder. Recent clinical and preclinical evidence suggests that oxytocin has prosocial and antiaddiction effects. We performed a pilot, laboratory-based, preclinical trial of oxytocin in subjects with alcohol abuse (as per Diagnostic and Statistical Manual of Mental Disorders, 4 Edition criteria) to evaluate therapeutic potential and assess tolerability. Social perceptual ability, cue-induced craving, and approach bias for alcohol and appetitive imagery were quantified after intranasal oxytocin and placebo administration to 32 nontreatment-seeking individuals with alcohol abuse in a double-blind, crossover study. Because attachment style can moderate the effects of oxytocin, we also explored whether attachment style moderated oxytocin's effects on our behavioral measures. Oxytocin significantly improved recognition of easier items on a social perception task, but had no significant group-level effect on cue-induced craving. However, oxytocin effects on craving were moderated by attachment anxiety, with oxytocin reducing craving in more anxiously attached individuals and increasing craving in less anxiously attached individuals. Subjects did not display an approach bias to alcohol images on the placebo day, preventing meaningful analysis of this measure. Subjects did display an approach bias to appetitive images on the placebo day, which was significantly reduced by oxytocin administration. No adverse reactions were observed. Intranasal oxytocin has potential to improve social perception, reduce cue-induced alcohol cravings, and reduce appetitive approach bias in subjects with alcohol abuse, and can be safely tolerated in this population. The effects of oxytocin are complex, however, and require further investigation.

Drinking water to reduce alcohol craving? A randomized controlled study on the impact of ghrelin in mediating the effects of forced water intake in alcohol addiction.

Science.gov (United States)

Koopmann, Anne; Lippmann, Katharina; Schuster, Rilana; Reinhard, Iris; Bach, Patrick; Weil, Georg; Rietschel, Marcella; Witt, Stephanie H; Wiedemann, Klaus; Kiefer, Falk

2017-11-01

Recent data suggest that ghrelin is involved in the pathophysiology of alcohol use disorders, affecting alcohol self-administration and craving. Gastric ghrelin secretion is reduced by stomach distension. We now tested the hypothesis whether the clinically well-known effects of high-volume water intake on craving reduction in alcoholism is mediated by acute changes in ghrelin secretion. In this randomized human laboratory study, we included 23 alcohol-dependent male inpatient subjects who underwent alcohol cue exposure. Participants of the intervention group drank 1000ml of mineral water within 10min directly thereafter, compared to the participants of the control group who did not. Craving and plasma concentrations of acetylated ghrelin were measured ten times during the 120min following the alcohol cue exposure session. In the intervention group, a significant decrease in acetylated ghrelin in plasma compared to the control group was observed. This decrease was correlated to a reduction in patients' subjective level of craving. In the control group, no decrease of acetylated ghrelin in plasma and no association between alcohol craving and changes in plasma concentrations of acetylated ghrelin were observed. Our results present new evidence that the modulation in the ghrelin system by oral water intake mediates the effects of volume intake with craving reduction in alcohol use disorders. Hence, in addition to pharmacological interventions with ghrelin antagonists, the reduction of physiological ghrelin secretion might be a target for future interventions in the treatment of alcohol craving. Copyright © 2017 Elsevier Ltd. All rights reserved.

The economic impact of alcohol abuse and alcoholism.

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Burke, T R

1988-01-01

The economic effects of alcohol abuse are as damaging to the nation as the health effects, affecting the family, the community, and persons of all ages. Underaged drinking is interfering with children's development, affecting the nation's ability to respond to economic challenge in the future. The college aged may be the most difficult to educate about alcohol abuse because of drinking patterns established at an early age and susceptibility to advertising inducements. Health care costs for families with an alcoholic member are twice those for families without one, and up to half of all emergency room admissions are alcohol related. Fetal alcohol syndrome is one of the top three known causes of birth defects, and is totally preventable. Alcohol abuse and alcoholism are estimated to have cost the nation $117 billion in 1983, while nonalcoholic drug abuse that year cost $60 billion. Costs of alcohol abuse are expected to be $136 billion a year by 1990, mostly from lost productivity and employment. Between 6 and 7 million workers are alcoholic, with an undetermined loss of productivity, profits, and competitiveness of American business. Alcohol abuse contributes to the high health care costs of the elderly beneficiaries of Federal health financing programs. Heavily affected minorities include blacks, Hispanics, and Native Americans. Society tends to treat the medical and social consequences of alcohol abuse, rather than its causes. Although our experience with the consequences of alcohol abuse is greater than that for any other drug, public concern for its prevention and treatment is less than for other major illnesses or abuse of other drugs. Alcohol abuse is a problem being given high priority within the Department in an effort to create a national agenda on the issue and to try to impart a greater sense of urgency about the problems. Ways are being explored to integrate alcoholism activities into more Departmental programs. Employee assistance programs for alcohol

Changes in alcohol drinking and subsequent sickness absence.

Science.gov (United States)

Salonsalmi, Aino; Rahkonen, Ossi; Lahelma, Eero; Laaksonen, Mikko

2015-06-01

The aim was to examine whether changes in alcohol drinking are associated with sickness absence. Repeated postal questionnaires on alcohol drinking were conducted among employees of the City of Helsinki in 2000-2 and 2007 to assess changes in drinking habits between these two time points. Data on the number of self-certified and medically confirmed sickness absences were derived from the employer's register. Sickness absences were followed from 2007 until the end of 2010 among employees participating in both questionnaire surveys. The study includes 3252 female and 682 male employees 40-60 years old at baseline. Poisson regression was used in the data analysis and population attributable fractions (PAFs) were calculated. Alcohol drinking was associated especially with self-certified sickness absence. Rate ratios (RRs) and 95% confidence intervals (CIs) for increasing weekly average drinking were 1.38, 1.18-1.62 among women and 1.58, 1.18-2.12 among men. Also stable problem drinking (for women 1.39, 1.26-1.54, for men 1.44, 1.10-1.87) and among women stable heavy drinking (1.53, 1.20-1.94) increased self-certified sickness absence. There were associations between alcohol drinking and medically confirmed sickness absence but these were mainly explained by health and health behaviours. Also, a decrease in weekly average drinking was associated with sickness absence among women whereas among men former problem drinking increased sickness absence. According to the PAF values, problem drinking had a stronger contribution to sickness absence than weekly average drinking. Alcohol drinking is particularly associated with self-certified sickness absence. Reducing adverse drinking habits is likely to prevent sickness absence. © 2015 the Nordic Societies of Public Health.

Alcohol

International Nuclear Information System (INIS)

Navarro Junior, L.

1988-01-01

The alcohol production as a secondary energy source, the participation of the alcohol in Brazilian national economic and social aspects are presented. Statistical data of alcohol demand compared with petroleum by-products and electricity are also included. (author)

Chronic voluntary alcohol consumption results in tolerance to sedative/hypnotic and hypothermic effects of alcohol in hybrid mice

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Ozburn, Angela Renee; Harris, R. Adron; Blednov, Yuri A.

2013-01-01

The continuous two bottle choice test is the most common measure of alcohol consumption but there is remarkably little information about the development of tolerance or dependence with this procedure. We showed that C57BL/6JxFVB/NJ and FVB/NJxC57BL/6J F1 hybrid mice demonstrate greater preference for and consumption of alcohol than either parental strain. In order to test the ability of this genetic model of high alcohol consumption to produce neuroadaptation, we examined development of alcohol tolerance and dependence after chronic self-administration using a continuous access two-bottle choice paradigm. Ethanol-experienced mice stably consumed about 16–18 g/kg/day of ethanol. Ethanol-induced withdrawal severity was assessed (after 59 days of drinking) by scoring handling-induced convulsions; withdrawal severity was minimal and did not differ between ethanol-experienced and -naïve mice. After 71 days of drinking, the rate of ethanol clearance was similar for ethanol-experienced and -naïve mice. After 77 days of drinking, ethanol-induced loss of righting reflex (LORR) was tested daily for 5 days. Ethanol-experienced mice had a shorter duration of LORR. For both ethanol-experienced and -naïve mice, blood ethanol concentrations taken at gain of righting reflex were greater on day 5 than on day 1, indicative of tolerance. After 98 days of drinking, ethanol-induced hypothermia was assessed daily for 3 days. Both ethanol-experienced and –naïve mice developed rapid and chronic tolerance to ethanol-induced hypothermia, with significant group differences on the first day of testing. In summary, chronic, high levels of alcohol consumption in F1 hybrid mice produced rapid and chronic tolerance to both the sedative/hypnotic and hypothermic effects of ethanol; additionally, a small degree of metabolic tolerance developed. The development of tolerance supports the validity of using this model of high alcohol consumption in genetic studies of alcoholism. PMID:23313769

Development of country-wide strategies to reduce the alcohol abuse

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Ali Nikfarjam

2014-01-01

Full Text Available Background: Evidence shows that in Iran alcohol abuse rate may be of concern, especially among the youth. The mental and social health and addiction Department of the Ministry of Health and Medical Education has designed a plan to prevent, treat, and rehabilitate the patients abusing alcohol in a time period of 2011-2015. Methods: In a 6-month period, three guiding committees of experts in the field of alcohol abuse reviewed the literature. The meetings of the steering committee were held in order to collect the comments of the policy-makers in recognition of the problem, orientation, and administration procedures for the suggested strategies. The first input was discussed in the committee meeting. In the orientation phase, intervention strategies were suggested whose base was the evaluation of the previous international guidelines. In the final phase, the suggested strategies and challenges and their possible solutions were criticized. Finally, using these strategies, appropriate interventions were defined. Results: Preventing alcohol supply, school- and community-based prevention efforts, monitoring and vigilance were defined as primary prevention. While secondary and tertiary prevention are defined to be the treating and rehabilitating services for the alcohol abusers. Conclusions: We hope by using this strategy we will be able to control alcohol abuse in our country. The first step to reach this aim is done by breaking the taboo of giving alcohol-related information and news using media and educational programs especially to the young population.

Harry Potter and the Underage Drinkers: Can We Use This to Talk to Teens about Alcohol?

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Welsh, Christopher

2007-01-01

Underage drinking continues to be a major problem in America. Approximately 20% of all alcohol consumed in the United States is consumed by minors with 44% of 8th graders and 77% of 12th graders reporting that they have tried alcohol at least once. The National Highway Traffic Safety Administration reported that, in 2003, as many as 3,657 drivers,…

Alcohol Use and Alcohol-Related Seizures in Patients With Epilepsy

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Michael Hamerle

2018-06-01

Full Text Available Purpose: This study aimed to assess alcohol consumption and the occurrence of alcohol-related seizures in patients with epilepsy within the last 12 months.Methods: In an epilepsy outpatient clinic, a standardized questionnaire was used to collect data retrospectively from consecutive adult epilepsy patients who had been suffering from the disease for at least 1 year. Logistic regression analyses were performed to identify independent predictors.Results: A total of 310 patients with epilepsy were included. Of these, 204 subjects (65.8% consumed alcohol within the last 12 months. Independent predictors for alcohol use were antiepileptic drug monotherapy (OR 1.901 and physicians' advice that a light alcohol intake is harmless (OR 4.102. Seizure worsening related to alcohol consumption was reported by 37 of the 204 patients (18.1% who had used alcohol. All 37 subjects had consumed large quantities of alcohol prior to the occurrence of alcohol-related seizures regardless of their usual alcohol-drinking behavior. The amount of alcohol intake prior to alcohol-related seizures was at least 7 standard drinks, which is equivalent to 1.4 L of beer or 0.7 L of wine. In 95% of cases, alcohol-related seizures occurred within 12 h after cessation of alcohol intake. Independent predictors for alcohol-related seizures were generalized genetic epilepsy (OR 5.792 and chronic heavier alcohol use (OR 8.955.Conclusions: Two-thirds of interviewed subjects had consumed alcohol within the last 12 months. This finding may be an underestimate due to patients' self-reporting and recall error. In all cases, the occurrence of alcohol related-seizures was associated with timely consumption of considerably large amounts of alcohol. Thus, a responsible alcohol intake seems to be safe for most patients with epilepsy. However, subjects with epilepsy and especially those with generalized genetic epilepsy should be made aware of an increased risk for seizures related to heavy

The impact of stressful life events on excessive alcohol consumption in the French population: findings from the GAZEL cohort study.

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Tamers, Sara L; Okechukwu, Cassandra; Bohl, Alex A; Guéguen, Alice; Goldberg, Marcel; Zins, Marie

2014-01-01

Major life changes may play a causative role in health through lifestyle factors, such as alcohol. The objective was to examine the impact of stressful life events on heavy alcohol consumption among French adults. Trajectories of excessive alcohol consumption in 20,625 employees of the French national gas and electricity company for up to 5 years before and 5 years after an event, with annual measurements from 1992. We used repeated measures analysis of time series data indexed to events, employing generalized estimating equations. For women, excessive alcohol use increased before important purchase (p = 0.021), children leaving home (pdivorce, widowhood, and death of loved one (all pchildren leaving home and retirement, where we observed an increase (all pdivorce and increased after (all pimpact alcohol intake temporarily while others have longer-term implications. Research should disentangle women's and men's distinct perceptions of events over time.

Alcohol drinking pattern and risk of alcoholic liver cirrhosis

DEFF Research Database (Denmark)

Askgaard, Gro; Grønbæk, Morten; Kjær, Mette S

2015-01-01

BACKGROUND & AIMS: Alcohol is the main contributing factor of alcoholic cirrhosis, but less is known about the significance of drinking pattern. METHODS: We investigated the risk of alcoholic cirrhosis among 55,917 participants (aged 50-64years) in the Danish Cancer, Diet, and Health study (1993......-2011). Baseline information on alcohol intake, drinking pattern, and confounders was obtained from a questionnaire. Follow-up information came from national registers. We calculated hazard ratios (HRs) for alcoholic cirrhosis in relation to drinking frequency, lifetime alcohol amount, and beverage type. RESULTS......: We observed 257 and 85 incident cases of alcoholic cirrhosis among men and women, respectively, none among lifetime abstainers. In men, HR for alcoholic cirrhosis among daily drinkers was 3.65 (95% CI: 2.39; 5.55) compared to drinking 2-4days/week. Alcohol amount in recent age periods (40-49 and 50...

Early experience and sex interact to influence limbic-hypothalamic-pituitary-adrenal-axis function after acute alcohol administration in rhesus macaques (Macaca mulatta).

Science.gov (United States)

Barr, C S; Newman, T K; Lindell, S; Becker, M L; Shannon, C; Champoux, M; Suomi, S J; Higley, J D

2004-07-01

Studies in rodents demonstrate sex differences in neuroendocrine stress axis activity after treatment with alcohol. In abstinent alcoholics, atypical depressives, and individuals with posttraumatic stress disorder, limbic-hypothalamic-pituitary-adrenal (LHPA)-axis activity is often blunted; among females in these patient populations, however, resistance to glucocorticoid feedback and increased pituitary reactivity is observed. Early parental loss is a major life stressor and is a risk factor for both affective disturbances and LHPA-axis abnormalities later in life. We wanted to determine whether sex and early life parental absence would interact to influence alcohol-induced alterations in LHPA-axis activity after exposure to ethanol in macaques. Animals were reared with their mothers in social groups (MR, n = 94) or without adults in peer-only groups (PR, n = 79). At 5 years of age, they received an intravenous infusion of alcohol (2-2.2 g/kg), and the effects of alcohol, sex, and rearing condition on ACTH and cortisol levels were analyzed by ANOVA. Peer-reared females had higher ACTH levels than did PR males, MR females, and MR males after alcohol infusion. Alcohol-induced cortisol levels were not affected by sex and rearing condition. These findings suggest that there are sex differences in glucocorticoid negative feedback, pituitary responsivity, or release of ACTH secretagogues among individuals exposed to early life stress and emphasize the importance of considering sex effects when studying LHPA-axis dysregulation in alcoholism and other stress-related neuropsychiatric disorders.

[Genetic variations in alcohol dehydrogenase, drinking habits and alcoholism

DEFF Research Database (Denmark)

Tolstrup, J.S.; Rasmussen, S.; Tybjaerg-Hansen, A.

2008-01-01

Alcohol is degraded primarily by alcohol dehydrogenase (ADH), and genetic variation that affects the rate of alcohol degradation is found in ADH1B and ADH1C. By genotyping 9,080 white men and women from the general population, we found that men and women with ADH1B slow versus fast alcohol...... degradation drank approximately 30% more alcohol per week and had a higher risk of everyday and heavy drinking, and of alcoholism. Individuals with ADH1C slow versus fast alcohol degradation had a higher risk of heavy drinking Udgivelsesdato: 2008/8/25...

Acute Alcohol Consumption, Alcohol Outlets, and Gun Suicide

Science.gov (United States)

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

Increased alcohol use over the past 20 years among the oldest old in Sweden

Directory of Open Access Journals (Sweden)

Kelfve Susanne

2014-06-01

Full Text Available AIMS - Increased alcohol consumption among old people, reported in many countries, will likely present a major challenge to public health and policy in the future. In Sweden, current knowledge about old people’s alcohol consumption is incomplete because of limited historical data and a dearth of nationally representative studies. We describe the frequency of alcohol consumption among the oldest old in Sweden over a 20-year period by sex, age, education, living situation, mobility and Activities of Daily Living. METHODS - We used repeated cross-sectional survey data from the Swedish Panel Study of Living Conditions of the Oldest Old (SWEOLD, conducted in 1992, 2002 and 2011. The samples were nationally representative of the Swedish population aged 77+, with response rates of 95.4%, 84.4% and 86.2% (total n=2007. Self-reported consumption frequency was measured with the question “How often do you drink alcoholic beverages, such as wine, beer or spirits?” RESULTS - Frequency of alcohol consumption increased among the oldest old from 1992 to 2011. The proportion reporting no or less-than-monthly alcohol consumption decreased, whereas the proportion reporting weekly consumption increased. This was true for men, women and most age and educational groups. The period change in consumption frequency was not explained by changes in demographic factors, living situation or functional capacity during the study period. CONCLUSIONS - Alcohol use increased among the oldest old in Sweden during the 20-year study period. More liberal attitudes toward alcohol could contribute to the increased use. The increase in weekly alcohol consumers suggests an increase in the number of older risk consumers.

Exposure to alcohol advertisements and teenage alcohol-related problems.

Science.gov (United States)

Grenard, Jerry L; Dent, Clyde W; Stacy, Alan W

2013-02-01

This study used prospective data to test the hypothesis that exposure to alcohol advertising contributes to an increase in underage drinking and that an increase in underage drinking then leads to problems associated with drinking alcohol. A total of 3890 students were surveyed once per year across 4 years from the 7th through the 10th grades. Assessments included several measures of exposure to alcohol advertising, alcohol use, problems related to alcohol use, and a range of covariates, such as age, drinking by peers, drinking by close adults, playing sports, general TV watching, acculturation, parents' jobs, and parents' education. Structural equation modeling of alcohol consumption showed that exposure to alcohol ads and/or liking of those ads in seventh grade were predictive of the latent growth factors for alcohol use (past 30 days and past 6 months) after controlling for covariates. In addition, there was a significant total effect for boys and a significant mediated effect for girls of exposure to alcohol ads and liking of those ads in 7th grade through latent growth factors for alcohol use on alcohol-related problems in 10th grade. Younger adolescents appear to be susceptible to the persuasive messages contained in alcohol commercials broadcast on TV, which sometimes results in a positive affective reaction to the ads. Alcohol ad exposure and the affective reaction to those ads influence some youth to drink more and experience drinking-related problems later in adolescence.

Exposure to Alcohol Advertisements and Teenage Alcohol-Related Problems

Science.gov (United States)

Dent, Clyde W.; Stacy, Alan W.

2013-01-01

OBJECTIVE: This study used prospective data to test the hypothesis that exposure to alcohol advertising contributes to an increase in underage drinking and that an increase in underage drinking then leads to problems associated with drinking alcohol. METHODS: A total of 3890 students were surveyed once per year across 4 years from the 7th through the 10th grades. Assessments included several measures of exposure to alcohol advertising, alcohol use, problems related to alcohol use, and a range of covariates, such as age, drinking by peers, drinking by close adults, playing sports, general TV watching, acculturation, parents’ jobs, and parents’ education. RESULTS: Structural equation modeling of alcohol consumption showed that exposure to alcohol ads and/or liking of those ads in seventh grade were predictive of the latent growth factors for alcohol use (past 30 days and past 6 months) after controlling for covariates. In addition, there was a significant total effect for boys and a significant mediated effect for girls of exposure to alcohol ads and liking of those ads in 7th grade through latent growth factors for alcohol use on alcohol-related problems in 10th grade. CONCLUSIONS: Younger adolescents appear to be susceptible to the persuasive messages contained in alcohol commercials broadcast on TV, which sometimes results in a positive affective reaction to the ads. Alcohol ad exposure and the affective reaction to those ads influence some youth to drink more and experience drinking-related problems later in adolescence. PMID:23359585

Effect of alcohol consumption on the liver detoxication capacity as measured by [13C2]aminopyrine and L-[1-13C]phenylalanine breath tests.

Science.gov (United States)

Wutzke, Klaus D; Wigger, Marianne

2009-09-01

The aim of this study was to investigate the hepatic microsomal and cytosolic functions by using the 13CO2 breath test in healthy subjects either before or after consumption of red wine. Twelve adults received [13C2]aminopyrine and L-[1-13C]phenylalanine together with a standardised dinner. Expired air samples were taken over 6 h. After a wash-out period, the subjects consumed 0.4 ml ethanol per kg per day together with dinner over a 7.5-day period on average. Thereafter, 13C-tracer administration was repeated under identical conditions. The 13CO2 enrichments were measured by isotope ratio mass spectrometry. The mean cumulative percentage 13C-dose recovery after administration of [13C2]aminopyrine and L-[1-13C]phenylalanine either without or with red wine consumption amounted to 17.0+/-4.4 vs. 14.7+/-3.1% (p=0.170) and 14.0+/-2.8 vs. 11.5+/-3.9% (p=0.084), respectively. Moderate alcohol consumption does not induce significant short-term changes of the microsomal and the cytosolic function of the human liver in healthy subjects.

Repeating and non-repeating fast radio bursts from binary neutron star mergers