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Alcohol Treatment (alcohol + treatment)
Selected AbstractsGender Differences in Alcohol Treatment: An Analysis of Outcome From the COMBINE StudyALCOHOLISM, Issue 10 2010Shelly F. Greenfield Background:, Relatively few studies have examined gender differences in the effectiveness of specific behavioral or pharmacologic treatment of alcohol dependence. The aim of this study is to assess whether there were gender differences in treatment outcomes for specific behavioral and medication treatments singly or in combination by conducting a secondary analysis of public access data from the national, multisite NIAAA-sponsored COMBINE study. Methods:, The COMBINE study investigated alcohol treatment among 8 groups of patients (378 women, 848 men) who received medical management (MM) with 16 weeks of placebo, naltrexone (100 mg/day), acamprosate (3 g/day), or their combination with or without a specialist-delivered combined behavioral intervention. We examined efficacy measures separately for men and women, followed by an overall analysis that included gender and its interaction with treatment condition in the analyses. These analyses were performed to confirm whether the findings reported in the parent trial were also relevant to women, and to more closely examine secondary outcome variables that were not analyzed previously for gender effects. Results:, Compared to men, women reported a later age of onset of alcohol dependence by approximately 3 years, were significantly less likely to have had previous alcohol treatment, and drank fewer drinks per drinking day. Otherwise, there were no baseline gender differences in drinking measures. Outcome analyses of 2 primary (percent days abstinent and time to first heavy drinking day) and 2 secondary (good clinical response and percent heavy drinking days) drinking measures yielded the same overall pattern in each gender as that observed in the parent COMBINE study report. That is, only the naltrexone by behavioral intervention interaction reached or approached significance in women as well as in men. There was a naltrexone main effect that was significant in both men and women in reduction in alcohol craving scores with naltrexone-treated subjects reporting lower craving than placebo-treated subjects. Conclusions:, This gender-focused analysis found that alcohol-dependent women responded to naltrexone with COMBINE's Medical Management, similar to the alcohol-dependent men, on a wide range of outcome measures. These results suggest that clinicians can feel comfortable prescribing naltrexone for alcohol dependence in both men and women. In this study, it is also notable that fewer women than men reported receiving any alcohol treatment prior to entry into the COMBINE study. Of note, women tend to go to primary health care more frequently than to specialty substance abuse programs for treatment, and so the benefit we confirm for women of the naltrexone and MM combination has practical implications for treating alcohol-dependent women. [source] The effectiveness of brief alcohol interventions in primary care settings: A systematic reviewDRUG AND ALCOHOL REVIEW, Issue 3 2009EILEEN F. S. KANER Abstract Issues. Numerous studies have reported that brief interventions delivered in primary care are effective in reducing excessive drinking. However, much of this work has been criticised for being clinically unrepresentative. This review aimed to assess the effectiveness of brief interventions in primary care and determine if outcomes differ between efficacy and effectiveness trials. Approach. A pre-specified search strategy was used to search all relevant electronic databases up to 2006. We also hand-searched the reference lists of key articles and reviews. We included randomised controlled trials (RCT) involving patients in primary care who were not seeking alcohol treatment and who received brief intervention. Two authors independently abstracted data and assessed trial quality. Random effects meta-analyses, subgroup and sensitivity analyses and meta-regression were conducted. Key Findings. The primary meta-analysis included 22 RCT and evaluated outcomes in over 5800 patients. At 1 year follow up, patients receiving brief intervention had a significant reduction in alcohol consumption compared with controls [mean difference: ,38 g week,1, 95%CI (confidence interval): ,54 to ,23], although there was substantial heterogeneity between trials (I2 = 57%). Subgroup analysis confirmed the benefit of brief intervention in men but not in women. Extended intervention was associated with a non-significantly increased reduction in alcohol consumption compared with brief intervention. There was no significant difference in effect sizes for efficacy and effectiveness trials. Conclusions. Brief interventions can reduce alcohol consumption in men, with benefit at a year after intervention, but they are unproven in women for whom there is insufficient research data. Longer counselling has little additional effect over brief intervention. The lack of differences in outcomes between efficacy and effectiveness trials suggests that the current literature is relevant to routine primary care. [Kaner EFS, Dickinson HO, Beyer F, Pienaar E, Schlesinger C, Campbell F, Saunders JB, Burnand B, Heather N. The effectiveness of brief alcohol interventions in primary care settings: A systematic review. Drug Alcohol Rev 2009;28:301,323] [source] Should symptom frequency be factored into scalar measures of alcohol use disorder severity?ADDICTION, Issue 9 2010Deborah A. Dawson ABSTRACT Aims To evaluate whether weighting counts of alcohol use disorder (AUD) criteria or symptoms by their frequency of occurrence improves their association with correlates of AUD. Design and participants Data were collected in personal interviews with a representative sample of US adults interviewed in 1991,92. Analyses were conducted among past-year drinkers (12+ drinks, n = 18 352) and individuals with past-year DSM-IV AUD (n = 2770). Measurements Thirty-one symptom item indicators, whose frequency of occurrence was measured in eight categories, were used to create unweighted and frequency-weighted counts of DSM-IV past-year AUD symptoms and criteria. Correlates included density of familial alcoholism and past-year volume of ethanol intake, frequency of intoxication and utilization of alcohol treatment. Findings Although the AUD correlates were associated strongly and positively with the frequency of AUD symptom occurrence, weighting for symptom frequency did not strengthen their association consistently with AUD severity scores. Improved performance of the weighted scores was observed primarily among AUD correlates linked closely with the frequency of heavy drinking and among individuals with AUD. Criterion counts were correlated nearly as strongly as symptom counts with the AUD correlates. Conclusions Frequency weighting may add somewhat to the validity of AUD severity measures, especially those that are intended for use among individuals with AUD, e.g. in clinical settings. For studying the etiology and course of AUD in the general population, an equally effective and less time-consuming alternative to obtaining symptom frequency may be the use of unweighted criterion counts accompanied by independent measures of frequency of heavy drinking. [source] Ethnic differences in drinking outcomes following a brief alcohol intervention in the trauma care settingADDICTION, Issue 1 2010Craig A. Field ABSTRACT Background Evidence suggests that brief interventions in the trauma care setting reduce drinking, subsequent injury and driving under the influence (DUI) arrest. However, evidence on the effectiveness of these interventions in ethnic minority groups is lacking. The current study evaluates the efficacy of brief intervention among whites, blacks and Hispanics in the United States. Methods We conducted a two-group parallel randomized trial comparing brief motivational intervention (BMI) and treatment as usual with assessment (TAU+) to evaluate treatment differences in drinking patterns by ethnicity. Patients were recruited from a level 1 urban trauma center over a 2-year period. The study included 1493 trauma patients, including 668 whites, 288 blacks and 537 Hispanics. Hierarchical linear modeling was used to evaluate ethnic differences in drinking outcomes including volume per week, maximum amount consumed in 1 day, percentage days abstinent and percentage days heavy drinking at 6- and 12-month follow-up. Analyses controlled for age, gender, employment status, marital status, prior alcohol treatment, type of injury and injury severity. Special emphasis was given to potential ethnic differences by testing the interaction between ethnicity and BMI. Results At 6- and 12-month follow-up, BMI significantly reduced maximum amount consumed in 1 day (P < 0.001; P < 0.001, respectively) and percentage days heavy drinking (P < 0.05; P < 0.05, respectively) among Hispanics. Hispanics in the BMI group also reduced average volume per week at 12-month follow-up (,2 = 6.8, df = 1, P < 0.01). In addition, Hispanics in TAU+ reduced maximum amount consumed at 6- and 12-month follow-up (P < 0.001; P < 0.001) and volume per week at 12-month follow-up (P < 0.001). Whites and blacks in both BMI and TAU+ reduced volume per week and percentage days heavy drinking at 12-month follow-up (P < 0.001; P < 0.01, respectively) and decreased maximum amount at 6- (P < 0.001) and 12-month follow-up (P < 0.001). All three ethnic groups In both BMI and TAU+ reduced volume per week at 6-month follow-up (P < 0.001) and percentage days abstinent at 6- (P < 0.001) and 12-month follow-up (P < 0.001). Conclusions All three ethnic groups evidenced reductions in drinking at 6- and 12-month follow-up independent of treatment assignment. Among Hispanics, BMI reduced alcohol intake significantly as measured by average volume per week, percentage days heavy drinking and maximum amount consumed in 1 day. [source] Smoking cessation during alcohol treatment: a randomized trial of combination nicotine patch plus nicotine gumADDICTION, Issue 9 2009Ned L. Cooney ABSTRACT Aims The primary aim was to compare the efficacy of smoking cessation treatment using a combination of active nicotine patch plus active nicotine gum versus therapy consisting of active nicotine patch plus placebo gum in a sample of alcohol-dependent tobacco smokers in an early phase of out-patient alcohol treatment. A secondary aim was to determine whether or not there were any carry-over effects of combination nicotine replacement on drinking outcomes. Design Small-scale randomized double-blind placebo-controlled clinical trial with 1-year smoking and drinking outcome assessment. Setting Two out-patient substance abuse clinics provided a treatment platform of behavioral alcohol and smoking treatment delivered in 3 months of weekly sessions followed by three monthly booster sessions. Participants Participants were 96 men and women with a diagnosis of alcohol abuse or dependence and smoking 15 or more cigarettes per day. Intervention All participants received open-label transdermal nicotine patches and were randomized to receive either 2 mg nicotine gum or placebo gum under double-blind conditions. Findings Analysis of 1-year follow-up data revealed that patients receiving nicotine patch plus active gum had better smoking outcomes than those receiving patch plus placebo gum on measures of time to smoking relapse and prolonged abstinence at 12 months. Alcohol outcomes were not significantly different across medication conditions. Conclusions Results of this study were consistent with results of larger trials of smokers without alcohol problems, showing that combination therapy (nicotine patch plus gum) is more effective than monotherapy (nicotine patch) for smoking cessation. [source] Alcohol tolerance and nicotine cross-tolerance in adolescent miceADDICTION BIOLOGY, Issue 2 2001Marcelo F. Lopez The present experiment was designed to evaluate the development of tolerance to alcohol and cross-tolerance to nicotine in adolescent mice. C57BL/6J mice (30,40 days old) were injected IP with alcohol (2.5 g/kg) for 4 consecutive days. A control group received four saline injections. On the test day, all subjects received an alcohol injection. Tolerance to alcohol's hypothermic effect was observed. Mice (male and female) exposed to alcohol for the 4 previous days showed less hypothermic response to an alcohol challenge than animals injected for 4 days with saline and then challenged with alcohol. Tolerance to alcohol's motor incoordinating effects and differences in blood alcohol concentrations were not observed. Thirty days following alcohol treatment, the same mice received a single nicotine injection (1 mg/kg) to assess cross-tolerance. Nicotine's effect on locomotor activity (open field test) and rectal temperature varied as a function of prior adolescent alcohol exposure and gender. Specifically, female mice who had been exposed to alcohol administrations were more resistant to nicotine's effect on locomotion and temperature than saline-treated animals. In summary, these data demonstrate that adolescent mice develop tolerance to some, but not all, alcohol-induced responses, and that female mice are cross-tolerant to nicotine's effects on temperature and activity. [source] Protective effects of cysteine, methionine and vitamin C on the stomach in chronically alcohol treated ratsJOURNAL OF APPLIED TOXICOLOGY, Issue 5 2008Ramazan Amanvermez Abstract A chronic intake of high dose alcohol may cause oxidative stress and inflammation in the stomach. It is hypothesized that cysteine-methionine and vitamin C may neutralize harmful compounds while potentiating the antioxidant capacity of the cell or tissue. The experimental animals were fed regular diets and were maintained for 90 days in the control group, the alcoholic group, which was given 2.5 g of 50% ethanol kg,1 body wt. administered intragastrically every other day, or the alcoholic with antioxidant supplement group, to whom 2.5 g of 50% ethanol kg,1 body wt. + a solution that contained 200 mg vitamin C, 100 mg cysteine and 100 mg methionine was administered intragastrically every other day. After the treatments, the stomach was taken for pathological and biochemical analysis. The stomach of the alcoholic group rats had higher scores of pathological findings compared with the control group, whereas the scores of the antioxidant-supplemented group were lower than the alcoholic group. In addition, the oxidized protein and lipid content in the stomachs of the alcoholic group were significantly higher than the control, but antioxidant supplementation lowered the amount of oxidation in the antioxidant supplemented group. The amount of stomach glutathione in the alcoholic group was higher than that of the control and antioxidant-supplemented groups. Interestingly, the level of total thiol in the stomach tissue of rats with antioxidant supplement was statistically higher than that of the control and alcoholic groups. In conclusion, the scores of the pathological findings in the stomach of rats with the antioxidant supplement were lower than the chronic alcohol-treated rats, albeit the amount of total thiol was increased in this group. Moreover, chronic alcohol treatment led to an increase in the level of lipid and protein oxidation in the stomach tissue of rats. A simultaneous intake of ascorbate/l -cys/l -met along with ethanol attenuated the amount of oxidation which suggested that cysteine-methionine and vitamin C could play a protective role in the stomach against oxidative damage resulting from chronic alcohol ingestion. Copyright © 2007 John Wiley & Sons, Ltd. [source] Gender Differences in Alcohol Treatment: An Analysis of Outcome From the COMBINE StudyALCOHOLISM, Issue 10 2010Shelly F. Greenfield Background:, Relatively few studies have examined gender differences in the effectiveness of specific behavioral or pharmacologic treatment of alcohol dependence. The aim of this study is to assess whether there were gender differences in treatment outcomes for specific behavioral and medication treatments singly or in combination by conducting a secondary analysis of public access data from the national, multisite NIAAA-sponsored COMBINE study. Methods:, The COMBINE study investigated alcohol treatment among 8 groups of patients (378 women, 848 men) who received medical management (MM) with 16 weeks of placebo, naltrexone (100 mg/day), acamprosate (3 g/day), or their combination with or without a specialist-delivered combined behavioral intervention. We examined efficacy measures separately for men and women, followed by an overall analysis that included gender and its interaction with treatment condition in the analyses. These analyses were performed to confirm whether the findings reported in the parent trial were also relevant to women, and to more closely examine secondary outcome variables that were not analyzed previously for gender effects. Results:, Compared to men, women reported a later age of onset of alcohol dependence by approximately 3 years, were significantly less likely to have had previous alcohol treatment, and drank fewer drinks per drinking day. Otherwise, there were no baseline gender differences in drinking measures. Outcome analyses of 2 primary (percent days abstinent and time to first heavy drinking day) and 2 secondary (good clinical response and percent heavy drinking days) drinking measures yielded the same overall pattern in each gender as that observed in the parent COMBINE study report. That is, only the naltrexone by behavioral intervention interaction reached or approached significance in women as well as in men. There was a naltrexone main effect that was significant in both men and women in reduction in alcohol craving scores with naltrexone-treated subjects reporting lower craving than placebo-treated subjects. Conclusions:, This gender-focused analysis found that alcohol-dependent women responded to naltrexone with COMBINE's Medical Management, similar to the alcohol-dependent men, on a wide range of outcome measures. These results suggest that clinicians can feel comfortable prescribing naltrexone for alcohol dependence in both men and women. In this study, it is also notable that fewer women than men reported receiving any alcohol treatment prior to entry into the COMBINE study. Of note, women tend to go to primary health care more frequently than to specialty substance abuse programs for treatment, and so the benefit we confirm for women of the naltrexone and MM combination has practical implications for treating alcohol-dependent women. [source] Future Prospects for Biomarkers of Alcohol Consumption and Alcohol-Induced DisordersALCOHOLISM, Issue 6 2010Willard M. Freeman The lack of reliable measures of alcohol intake is a major obstacle to the diagnosis, treatment, and research of alcohol abuse and alcoholism. Successful development of a biomarker that allows for accurate assessment of alcohol intake and drinking patterns would not only be a major advance in clinical care but also a valuable research tool. A number of advances have been made in testing the validity of proposed biomarkers as well as in identifying potential new biomarkers through systems biology approaches. This commentary will examine the definition of a biomarker of heavy drinking, the types of potential biomarkers, the steps in biomarker development, the current state of biomarker development, and critical obstacles for the field. The challenges in developing biomarkers for alcohol treatment and research are similar to those found in other fields. However, the alcohol research field must reach a competitive level of rigor and organization. We recommend that NIAAA consider taking a leadership role in organizing investigators in the field and providing a common set of clinical specimens for biomarker validation studies. [source] Intestinal Dysbiosis: A Possible Mechanism of Alcohol-Induced Endotoxemia and Alcoholic Steatohepatitis in RatsALCOHOLISM, Issue 10 2009Ece Mutlu Background:, Clinical and animal data indicate that gut-derived endotoxin and other luminal bacterial products are necessary cofactors for development of alcoholic liver disease (ALD). Although gut leakiness is clearly an important cause of endotoxemia in ALD, it cannot fully explain endotoxemia in all ALD subjects and thus other factors may be involved. One possible factor is a change in gut microbiota composition (dysbiosis). Thus, the aim of our study was to interrogate the gut bacterial microbiota in alcohol-fed rats to see if chronic alcohol consumption affects gut bacteria composition. Method:, Male Sprague,Dawley rats were given either alcohol or dextrose intragastrically by gavage twice daily for up to 10 weeks. A subgroup of rats was also given either a probiotic (lactobacillus GG) or a prebiotic (oats) by gavage. Ileal and colonic mucosal-attached microbiota composition were interrogated by Length Heterogeneity PCR (LH-PCR) fingerprinting. Results:, Bacterial microbiota composition in alcohol-fed rats is not different from dextrose-fed rats at weeks 4 and 6. Mucosa-associated microbiota composition in the colon is altered at 10 weeks of daily alcohol gavage. Both LGG and oats prevented alcohol-induced dysbiosis up to 10 weeks of alcohol treatment. Conclusion:, Daily alcohol consumption for 10 weeks alters colonic mucosa-associated bacterial microbiota composition in rats. Our data showed, for the first time, that daily alcohol consumption can affect colonic microbiome composition and suggest that dysbiosis may be an important mechanism of alcohol-induced endotoxemia. Further studies are needed to determine how dysbiotic microbiota contributes to development of ALD and whether therapeutic interventions targeted towards dysbiotic microbiota can prevent complications of alcoholism like ALD. [source] Adverse Drinking-Related Consequences Among Lower Income, Racial, and Ethnic Minority Drinkers: Cross-Sectional ResultsALCOHOLISM, Issue 4 2009Anna-Marie Vilamovska Objective:, To examine factors associated with adverse consequences of alcohol consumption among a community sample of drinkers in a low-income, racial, and ethnic minority community. Methods:, A sample of 329 drinkers was recruited from 17 randomly selected off-sell alcohol outlets in South Los Angeles. Respondents were interviewed by trained research personnel on their demographic characteristics, income, drinking patterns and preferences, and alcohol-related adverse consequences (using the Drinkers Inventory of Consequences,DrInC), among other items. We developed logistic regression models predicting high scores on DrInC total score and subscales (impulse control, interpersonal, intrapersonal, physical, and social responsibility). Results:, In this sample, we found drinking patterns,bingeing, drinking outdoors, drinking in the morning,to be significantly associated with total DrInC scores and some subscales. Malt liquor beverage (MLB) use was significantly associated with total DrInC score and interpersonal and social responsibility subscales. Previous alcohol treatment predicted all but 1 DrInC subscale and total score. Conclusions:, A diverse array of factors predicted high DrInC total and subscale scores. More research on the association between MLB use and consequences is required. In addition, studies with community samples are likely to further enrich our understanding of the interactions between drinking patterns and preferences, settings, and negative consequences. [source] Effects of the Glucocorticoid Antagonist, Mifepristone, on the Consequences of Withdrawal From Long Term Alcohol ConsumptionALCOHOLISM, Issue 12 2008Catherine Jacquot Background:, Studies were carried out to test the hypothesis that administration of a glucocorticoid Type II receptor antagonist, mifepristone (RU38486), just prior to withdrawal from chronic alcohol treatment, would prevent the consequences of the alcohol consumption and withdrawal in mice. Materials and Methods:, The effects of administration of a single intraperitoneal dose of mifepristone were examined on alcohol withdrawal hyperexcitability. Memory deficits during the abstinence phase were measured using repeat exposure to the elevated plus maze, the object recognition test, and the odor habituation/discrimination test. Neurotoxicity in the hippocampus and prefrontal cortex was examined using NeuN staining. Results:, Mifepristone reduced, though did not prevent, the behavioral hyperexcitability seen in TO strain mice during the acute phase of alcohol withdrawal (4 hours to 8 hours after cessation of alcohol consumption) following chronic alcohol treatment via liquid diet. There were no alterations in anxiety-related behavior in these mice at 1 week into withdrawal, as measured using the elevated plus maze. However, changes in behavior during a second exposure to the elevated plus maze 1 week later were significantly reduced by the administration of mifepristone prior to withdrawal, indicating a reduction in the memory deficits caused by the chronic alcohol treatment and withdrawal. The object recognition test and the odor habituation and discrimination test were then used to measure memory deficits in more detail, at between 1 and 2 weeks after alcohol withdrawal in C57/BL10 strain mice given alcohol chronically via the drinking fluid. A single dose of mifepristone given at the time of alcohol withdrawal significantly reduced the memory deficits in both tests. NeuN staining showed no evidence of neuronal loss in either prefrontal cortex or hippocampus after withdrawal from chronic alcohol treatment. Conclusions:, The results suggest mifepristone may be of value in the treatment of alcoholics to reduce their cognitive deficits. [source] Temporal Vulnerability of Fetal Cerebellar Purkinje Cells to Chronic Binge Alcohol Exposure: Ovine ModelALCOHOLISM, Issue 10 2007Jayanth Ramadoss Background: Human magnetic resonance imaging (MRI) and autopsy studies reveal abnormal cerebellar development in children who had been exposed to alcohol prenatally, independent of the exposure period. Animal studies conducted utilizing the rat model similarly demonstrate a broad period of vulnerability, albeit the third trimester-equivalent of human brain development is reported to be the most vulnerable period, and the first trimester-equivalent exposure produces cerebellar Purkinje cell loss only at high doses of alcohol. However, in the rat model, all 3 trimester-equivalents do not occur prenatally, requiring the assumption that intrauterine environment, placenta, maternal interactions, and parturition do not play an important role in mediating the damage. In this study, we utilized the ovine model, where all 3 trimester-equivalents occur in utero, to determine the critical window of vulnerability of fetal cerebellar Purkinje cells. Methods: Four groups of pregnant sheep were used: first trimester-equivalent pair-fed saline control group, first trimester-equivalent alcohol group (1.75 g/kg), third trimester-equivalent pair-fed saline control group, and third trimester-equivalent alcohol group (1.75 g/kg). The alcohol exposure regimen was designed to mimic a human binge pattern. Alcohol was administered intravenously on 3 consecutive days beginning on day 4 and day 109 of gestation in the first and third trimester-equivalent groups, respectively, and the alcohol treatment was followed by a 4-day inter-treatment interval when the animals were not exposed to alcohol. Such treatment episodes were replicated until gestational day 41 and 132 in the first and third trimester-equivalent groups, respectively. All fetal brains were harvested on day 133 and processed for stereological cerebellar Purkinje cell counting. Results: Significant deficits were found in the fetal cerebellar Purkinje cell number and density in the first and third trimester-equivalent alcohol exposed fetuses compared with those in the saline controls. However, there was no difference between the first and third trimester-equivalent alcohol administered groups. When comparing the present findings to those from a previous study where the duration of alcohol exposure was all 3 trimester-equivalents of gestation, we did not detect a difference in fetal cerebellar Purkinje cell number. Conclusions: We conclude that the fetal cerebellar Purkinje cells are sensitive to alcohol exposure at any time during gestation and that women who engage in binge drinking during the first trimester are at a high risk of giving birth to children with cerebellar damage even if drinking ceases after the first trimester. Our findings also support the hypothesis that only a certain population of Purkinje cells are vulnerable to alcohol-induced depletion irrespective of the timing or duration of alcohol exposure. [source] Genuine Episodic Memory Deficits and Executive Dysfunctions in Alcoholic Subjects Early in AbstinenceALCOHOLISM, Issue 7 2007Anne Lise Pitel Background: Chronic alcoholism is known to impair episodic memory function, but the specific nature of this impairment is still unclear. Moreover, it has never been established whether episodic memory deficit in alcoholism is an intrinsic memory deficit or whether it has an executive origin. Thus, the objectives are to specify which episodic memory processes are impaired early in abstinence from alcohol and to determine whether they should be regarded as genuine memory deficits or rather as the indirect consequences of executive impairments. Methods: Forty recently detoxified alcoholic inpatients at alcohol entry treatment and 55 group-matched controls underwent a neuropsychological assessment of episodic memory and executive functions. The episodic memory evaluation consisted of 3 tasks complementing each other designed to measure the different episodic memory components (learning, storage, encoding and retrieval, contextual memory, and autonoetic consciousness) and 5 executive tasks testing capacities of organization, inhibition, flexibility, updating, and integration. Results: Compared with control subjects, alcoholic patients presented impaired learning abilities, encoding processes, retrieval processes, contextual memory and autonoetic consciousness. However, there was no difference between the 2 groups regarding the storage capacities assessed by the rate of forgetting. Concerning executive functions, alcoholic subjects displayed deficits in each executive task used. Nevertheless, stepwise regression analyses showed that only performances on fluency tasks were significantly predictive of some of the episodic memory disorders (learning abilities for 40%, encoding processes for 20%, temporal memory for 21%, and state of consciousness associated with memories for 26%) in the alcoholic group. Discussion: At alcohol treatment entry, alcoholic patients present genuine episodic memory deficits that cannot be regarded solely as the consequences of executive dysfunctions. These results are in accordance with neuroimaging findings showing hippocampal atrophy. Moreover, given the involvement of episodic memory and executive functions in alcohol treatment, these data could have clinical implications. [source] Effects of Alcohol Consumption on Iron Metabolism in Mice with Hemochromatosis MutationsALCOHOLISM, Issue 1 2007Jonathan M. Flanagan Background: Alcoholic liver disease is associated with increased hepatic iron accumulation. The liver-derived peptide hepcidin is the central regulator of iron homeostasis and recent animal studies have demonstrated that exposure to alcohol reduces hepcidin expression. This down-regulation of hepcidin in vivo implies that disturbed iron sensing may contribute to the hepatosiderosis seen in alcoholic liver disease. Alcohol intake is also a major factor in expression of the hemochromatosis phenotype in patients homozygous for the C282Y mutation of the HFE gene. Methods: To assess the effect of alcohol in mice with iron overload, alcohol was administered to mice with disrupted Hfe and IL-6 genes and Tfr2 mutant mice and their respective 129x1/SvJ, C57BL/6J, and AKR/J wild-type congenic strains. Iron absorption, serum iron levels, and hepcidin expression levels were then measured in these mice compared with water-treated control mice. Results: Alcohol was shown to have a strain-specific effect in 129x1/SvJ mice, with treated 129x1/SvJ mice showing a significant increase in iron absorption, serum iron levels, and a corresponding decrease in hepcidin expression. C57BL/6J and AKR/J strain mice showed no effect from alcohol treatment. 129x1/SvJ mice heterozygous or homozygous for the Hfe knockout had a diminished response to alcohol. All 3 strains were shown to have high blood alcohol levels. Conclusions: The effect of alcohol on iron homeostasis is dependent on the genetic background in mice. In an alcohol-susceptible strain, mutation of the Hfe gene diminished the response of the measured iron indices to alcohol treatment. This indicates that either maximal suppression of hepcidin levels had already occurred as a result of the Hfe mutation or that Hfe was a component of the pathway utilized by EtOH in suppressing hepcidin production and increasing iron absorption. [source] Moderate Alcohol Intake in Humans Attenuates Monocyte Inflammatory Responses: Inhibition of Nuclear Regulatory Factor Kappa B and Induction of Interleukin 10ALCOHOLISM, Issue 1 2006Pranoti Mandrekar Background: In contrast to the deleterious effects of chronic excessive alcohol consumption on the liver and cardiovascular system, modest alcohol intake, such as 1 to 2 drinks per day, has benefits on cardiovascular mortality. Little is known about the length of time or the amounts of alcohol consumed that may cause alterations in inflammatory cells such as monocytes that are crucial to atherosclerotic vascular disease. Here, we determine in vivo effects of acute alcohol consumption on inflammatory cytokine production and nuclear regulatory factor ,B (NF- ,B) binding in human monocytes. Methods: Human blood monocytes were isolated by plastic adherence before and after acute alcohol consumption (2 ml vodka/kg body weight). Lipopolysaccharide (LPS)- and superantigen-induced tumor necrosis factor , (TNF ,), interleukin (IL)-1,, and IL-10 production were then determined in monocytes by ELISA. Nuclear regulatory factor- ,B activity of monocytes before and after alcohol consumption was estimated by electromobility shift assay and promoter-driven reporter activity. I,B, was determined by Western blotting in the cytoplasmic extracts. Results: Eighteen hours after moderate alcohol consumption, we found a significant reduction in monocyte production of inflammatory mediators, TNF- , and IL-1,, in response to LPS or staphylococcal enterotoxin B stimulation. Acute alcohol consumption inhibited LPS-induced DNA binding of the p65/p50 NF- ,B in monocytes that regulates the expression of both the TNF- , and the IL-1, genes. Consistent with this, acute alcohol treatment (25 mM) significantly reduced LPS-induced activation of an NF- ,B-driven reporter gene suggesting inhibition of this proinflammatory signaling pathway. Further, LPS-induced I,B, degradation was not affected by acute alcohol consumption indicating an I,B, -independent mechanism, as observed earlier in the in vitro acute alcohol studies. In contrast, monocyte production of the anti-inflammatory cytokine, IL-10, was augmented by acute alcohol intake. Conclusions: Our findings suggest that acute alcohol consumption has dual anti-inflammatory effects that involve augmentation of IL-10 and attenuation of monocyte inflammatory responses involving inhibition of NF- ,B. These mechanisms may contribute to the beneficial effects of moderate alcohol use on atherosclerosis. [source] Increased Lipopolysaccharide Sensitivity in Alcoholic Fatty Livers Is Independent of Leptin Deficiency and Toll-Like Receptor 4 (TLR4) or TLR2 mRNA ExpressionALCOHOLISM, Issue 6 2005Laszlo Romics Jr Background: Both alcoholic (AFL) and nonalcoholic (NAFL) fatty livers show increased sensitivity to endotoxin-induced injury. Lipopolysaccharide (LPS) is recognized by toll-like receptor 4 (TLR4), whereas lipopeptide triggers TLR2 to induce common downstream activation of nuclear factor (NF)-,B and pro-inflammatory pathways that are activated in AFL and NAFL. Methods: Serum alanine aminotransferase (ALT), tumor necrosis factor (TNF)-,, and interleukin (IL)-6 levels; hepatic NF-,B activity; and expression of TLR2, TLR4, inducible nitric oxide synthase (iNOS), and heme oxygenase (HO)-1 mRNAs were investigated in lean and leptin-deficient ob/ob mice after LPS challenge in combination with acute or chronic alcohol feeding. Results: Increased LPS sensitivity in AFL and NAFL was characterized by elevated serum TNF-, and IL-6 induction. However, there was no difference in TLR2 and TLR4 mRNA levels between lean and ob/ob livers at baseline and after acute or chronic alcohol treatment. LPS increased TLR2, but not TLR4, mRNA levels in all groups. Chronic alcohol feeding and LPS increased serum ALT and TNF-, levels in lean but not in ob/ob mice compared with pair-fed controls. Hepatic NF-,B activation was increased in both ob/ob and lean mice after chronic alcohol feeding compared with pair-fed controls. Expression of iNOS, an inducer of oxidative stress, and HO-1, a cytoprotective protein, were higher in ob/ob compared with lean mice after chronic alcohol feeding. However, LPS-induced HO-1, but not iNOS, expression was attenuated in ob/ob compared with lean mice. Conclusion: These results imply that the increased sensitivity of AFL to LPS occurs without up-regulation of TLR2 or TLR4 genes and may be related to an imbalance of pro-inflammatory/oxidative and cytoprotective mechanisms. [source] Assessing Drinking Outcomes in Alcohol Treatment Efficacy Studies: Selecting a Yardstick of SuccessALCOHOLISM, Issue 10 2003Linda Carter Sobell Background: Although the number of alcohol treatment efficacy trials has mushroomed, there is no consensus on how best to measure outcomes. To advance the goal of establishing cross-trial consistency in measuring outcomes in clinical efficacy studies, the National Institute on Alcohol Abuse and Alcoholism convened a panel of experts and charged them with exploring, debating, and, ultimately, selecting a "sentinel" or "optimal" outcome measure to be used in future alcohol treatment studies. The goal of this article, one in a series of several presented at the National Institute on Alcohol Abuse and Alcoholism conference, is to discuss (1) the rationale underlying selection of an optimal outcome measure, (2) the necessary characteristics of an optimal outcome measure, (3) the utility of selecting an optimal measure, and (4) which drinking assessment methods could be used to collect data to portray the optimal outcome measure. Methods: At a minimum, the criteria for an "optimal" measure include that it be psychometrically sound. In addition, it should have considerable currency in the field, thereby increasing its prospects for adoption. The measure should also be consistent with the concepts of greatest interest and relevance to the field (e.g., directly reflect the fundamental goal of alcohol treatment). In light of these highly desired features, percent of days heavy drinking was chosen at the conference as a practical and relevant measure of alcohol treatment outcome. Conclusions: Percent of days heavy drinking should be the optimal measure of alcohol treatment outcome. Currently, daily drinking estimation methods are the most useful for gathering data that can reflect the optimal measure. In addition, data gathered by daily drinking estimation methods can be used to study a variety of other outcome variables of interest to clinical researchers. [source] Additive Inhibition of Dendritic Cell Allostimulatory Capacity by Alcohol and Hepatitis C Is Not Restored by DC Maturation and Involves Abnormal IL-10 and IL-2 InductionALCOHOLISM, Issue 6 2003Angela Dolganiuc Background: Excessive alcohol use results in impaired immunity, and it is associated with increased incidence and progression of chronic hepatitis C virus (HCV) infection. Here we investigated the effects of HCV infection and alcohol on myeloid dendritic cells (DC) that are critical in antiviral immunity. Methods: Immature and mature DCs were generated from monocytes of chronic HCV infected patients (HCV-DC) and controls (N-DC) with IL-4 plus granulocyte-macrophage colony stimulating factor (GM-CSF) in the presence or absence of alcohol (25 mM). DC allostimulatory capacity was tested in mixed lymphocyte reaction (MLR) and cytokine production by ELISA. Results: Allostimulatory capacity of HCV-DCs was reduced compared to N-DCs and it was further inhibited by alcohol treatment (p < 0.01). MLR was also decreased with alcohol-treated N-DCs. DC phenotypic markers and apoptosis were comparable between HCV-DCs and N-DCs irrespective of alcohol treatment. However, HCV-DCs and alcohol-treated N-DCs exhibited elevated IL-10 and reduced IL-12 production. Reduced MLR with HCV-DCs and its further inhibition by alcohol coexisted with decreasing IL-2 levels (p < 0.017). DC maturation partially improved but failed to fully restore the reduced allostimulatory function of either alcohol-treated or alcohol-naïve HCV-DCs (p < 0.018). Conclusions: Alcohol and HCV independently and together inhibit DC allostimulatory capacity, increase IL-10, reduce IL-12 and IL-2 production that cannot be normalized by DC maturation. HCV and alcohol interact to modulate innate and adaptive immune responses via dendritic cells. [source] Acute Alcohol Inhibits the Induction of Nuclear Regulatory Factor ,B Activation Through CD14/Toll-Like Receptor 4, Interleukin-1, and Tumor Necrosis Factor Receptors: A Common Mechanism Independent of Inhibitory ,B, Degradation?ALCOHOLISM, Issue 11 2002Pranoti Mandrekar Background Nuclear translocation and DNA binding of the nuclear factor ,B (NF-,B) is an early event in inflammatory cell activation in response to stimulation with bacterial components or cytokines. Cell activation via different receptors culminates in a common pathway leading to NF-,B activation and proinflammatory cytokine induction. We have previously shown that acute alcohol inhibits NF-,B activation by lipopolysaccharide (LPS) in human monocytes. Here we investigated whether acute alcohol treatment of human monocytes also inhibits NF-,B when induced through activation of the interleukin (IL)-1 or tumor necrosis factor (TNF) receptors. Methods Human peripheral blood monocytes were treated with LPS, TNF,, and IL-1, in the presence or absence of 25mM alcohol for 1 hr. NF-,B activation was determined by electrophoretic mobility shift assays using nuclear extracts. Inhibitory ,B, (I,B,) was estimated by Western blotting in cytoplasmic extracts. Chinese hamster ovary cells expressing human CD14 were treated with LPS in the presence or absence of alcohol to study NF-,B and I,B, regulation. Results Our results indicate that acute alcohol inhibits IL-1,- and TNF,-induced NF-,B activation. We further show in CD14/toll-like receptor 4,expressing Chinese hamster ovary cells the specificity of alcohol-mediated inhibition of NF-,B via the toll-like receptor 4/CD14 receptors. Inhibition of NF-,B by acute alcohol was concomitant with decreased levels of the I,B, molecule in the cytoplasm of LPS, IL-1, and TNF,-activated monocytes. Conclusions These data suggest a unique, I,B,-independent pathway for the inhibition of NF-,B activation by acute alcohol in monocytes. Universal inhibition of NF-,B by acute alcohol via these various receptor systems suggests a target for the effects of alcohol in the NF-,B activation cascade that is downstream from I,B, degradation. Further, these results demonstrate that acute alcohol is a potent inhibitor of NF-,B activation by mediators of early (LPS) or late (IL-1, TNF,) stages of inflammation in monocytes. [source] Platelet Adenylyl Cyclase Activity as a Trait Marker of Alcohol DependenceALCOHOLISM, Issue 6 2000John A. Menninger Background: There is compelling evidence that genetic factors play a major role in the development of alcohol dependence. Platelet adenylyl cyclase (AC) activity has been proposed as a biochemical marker for differentiating alcohol-dependent and nondependent subjects, but the sensitivity and specificity of this marker have not been ascertained. The objective of this study was to determine the sensitivity and specificity of platelet AC activity in identifying alcohol-dependent subjects and to ascertain the effect of medical/psychiatric variables, drinking and smoking history, and age and body weight on AC activity. Methods: The cross-sectional study was conducted from 1995 to 1998. Participants were 210 Australian White men who were community volunteers and alcohol treatment inpatients in Sydney, Australia. There were 41 nondrinkers, 140 drinkers, and 29 men who were entering alcohol treatment. The main outcome measure was platelet AC activity. Classification variables were plasma ethanol, ,-glutamyltransferase, aspartate aminotransferase, serum carbohydrate-deficient transferrin (CDT), and urinary5-hydroxytryptophol/5-hydroxyindoleacetic acid (5-HTOL/5-HIAA) levels, and World Health Organization/International Society for Biomedical Research on Alcoholism Interview Schedule variables, which included alcohol use and dependence criteria. Results: Among subjects who reported abstinence for at least 4 days, both cesium fluoride (CsF)- and forskolin-stimulated platelet AC activities were significantly lower in those with a lifetime history of alcohol dependence compared with those with no such history (p < 0.005 and p < 0.05, respectively). The sensitivity and specificity of CsF-stimulated AC activity to discriminate individuals with a lifetime history of alcohol dependence were 75% and 79%, respectively. Similar values for sensitivity and specificity for CsF-stimulated AC activity were calculated when discriminating current alcohol dependence in the subjects in our sample. Irrespective of the history of alcohol dependence, persons who had consumed alcohol recently (within the last 3,4 days) showed significantly higher mean basal, CsF-stimulated, and forskolin-stimulated AC activity (p < 0.001), as did those who had elevated 5-HTOL/5-HIAA ratios or CDT levels, indicative of recent (heavy) drinking. The "normalization" of platelet AC activity to baseline levels after an individual stops drinking may be related to the generation of new platelets during the abstinence period. Conduct disorder and antisocial personality disorder were not associated with low AC activity, but low forskolin-stimulated AC activity was associated with major depression. Conclusions: We found that CsF- and forskolin-stimulated platelet AC activity discriminates between subjects with and without alcohol dependence in a population of subjects who had not consumed significant quantities of ethanol recently. Recent alcohol consumption is a confounding variable that can alter the measured levels of AC activity. Forskolin-stimulated platelet AC activity also may be influenced by a history of major depression. [source] Metronidazole Increases Intracolonic but Not Peripheral Blood Acetaldehyde in Chronic Ethanol-Treated RatsALCOHOLISM, Issue 4 2000Jyrki Tillonen Background: Metronidazole leads to the overgrowth of aerobic flora in the large intestine by reducing the number of anaerobes. According to our previous studies, this shift may increase intracolonic bacterial acetaldehyde formation if ethanol is present. Metronidazole is also reported to cause disulfiram-like effects after alcohol intake, although the mechanism behind this is obscure. Therefore, the aim was to study the effect of long-term metronidazole and alcohol treatment on intracolonic acetaldehyde levels and to explore the possible role of intestinal bacteria in the metronidazole related disulfiram-like reaction. Methods: A total of 32 rats were divided into four groups: controls (n= 6), controls receiving metronidazole (n= 6), ethanol group (n= 10), and ethanol and metronidazole group (n= 10). All rats were pair-fed with the liquid diet for 6-weeks, whereafter blood and intracolonic acetaldehyde levels and liver and colonic mucosal alcohol (ADH) and aldehyde dehydrogenase (ALDH) activities were analyzed. Results: The rats receiving ethanol and metronidazole had five times higher intracolonic acetaldehyde levels than the rats receiving only ethanol (431.4 ± 163.5 ,M vs. 84.7 ± 14.4 ,M, p= 0.0035). In contrast, blood acetaldehyde levels were equal. Cecal cultures showed the increased growth of Enterobacteriaceae in the metronidazole groups. Metronidazole had no inhibitory effect on hepatic or colonic mucosal ADH and ALDH activities. Conclusions: The increase in intracolonic acetaldehyde after metronidazole treatment is probably due to the replacement of intestinal anaerobes by ADH-containing aerobes. Unlike disulfiram, metronidazole neither inhibits liver ALDH nor increases blood acetaldehyde. Thus, our findings suggested that the mechanism behind metronidazole related disulfiram-like reaction might be located in the gut flora instead of the liver. [source] Need for Medical and Psychosocial Services Among Injection Drug Users: A Comparative Study of Needle Exchange and Methadone MaintenanceTHE AMERICAN JOURNAL ON ADDICTIONS, Issue 4 2002Michael D. Stein M.D. This study compares the prevalence of perceived and unmet needs of HIV-negative injection drug users (IDUs) not receiving drug treatment (n = 251) and those recruited from a methadone maintenance program (n = 312) in 1998. We studied self-reported needs for six community services: medical, mental health, housing, income assistance, alcohol treatment, and drug treatment. Respondents reported the highest levels of need for mental health and housing services. Ninety-four percent of out-of-treatment IDUs reported having at least one need compared to 62% of methadone clients (p < .001). Across all reported service needs, at least 69% of respondents in both cohorts reported their needs were unmet. While HIV-infected drug users receive assistance through the Ryan White CARE Act, these findings suggest that seronegative drug users may benefit from similar community service programs. [source] Diverging trends in alcohol consumption and alcohol-related harm in VictoriaAUSTRALIAN AND NEW ZEALAND JOURNAL OF PUBLIC HEALTH, Issue 4 2010Michael Livingston Abstract Objective: To examine recent trends in alcohol-related harm and risky drinking in Victoria, Australia. Methods: The study compiled eight measures of alcohol-related harm from published and unpublished sources, covering data relating to health, crime, alcohol treatment and traffic crashes for the financial years 1999/2000 to 2007/08. In addition, published estimates of short and long-term risky drinking from three-sets of surveys between 2001 and 2007 were examined. Results: Six of the eight harm indicators substantially increased, while only alcohol-related mortality and single-vehicle night-time crashes remained relatively stable. In particular, rates of emergency presentations for intoxication and alcohol-related ambulance attendances increased dramatically. Contrastingly, survey-derived estimates of the rate of risky-drinking among Victorians were stable over the time-period examined. Conclusions: Evidence across the data examined suggests significant increases in alcohol-related harm taking place during a period of relatively stable alcohol consumption levels. This disparity may be accounted for by changing drinking patterns among small, high-risk, subgroups of the population. Implications: The sharply increasing rates of alcohol-related harm among Victorians suggest that changes to alcohol policies focusing on improving public health are necessary. [source] Young people who attend specialist alcohol treatment: who are they and do they need special treatment?AUSTRALIAN AND NEW ZEALAND JOURNAL OF PUBLIC HEALTH, Issue 4 2008Devon Indig Abstract Objective: Patterns of drinking in adolescence and young adulthood may have major short term impacts and influences on later drinking, yet little is known about the characteristics of young people who seek help for alcohol problems. Here we examine the characteristics of treatment episodes for adolescents and young adults who present to specialist alcohol treatment in New South Wales (NSW). Methods: The NSW Minimum Data Set for Alcohol and Other Drug Treatment Services was examined for all alcohol-related treatment episodes (N=21,012) reported between July 2004 and June 2005. We compared treatment episodes for adolescents aged 12-19 years, young adults aged 20-29 years and clients aged 30 years or more for their demographics, drug use and service delivery characteristics. Results: Clients aged under 30 years were significantly more likely to be referred into specialist treatment by a police, court or criminal justice diversion program compared with older clients (adolescent: OR=3.7, 95%CI: 3.1-4.4; young adult: OR=2.2, 95%CI: 1.9-2.4). Concern about cannabis use was significantly higher among younger clients (adolescents: OR=2.8 95%CI: 2.3-3.3; young adults: OR=2.1, 95%CI: 2.0-2.4) than those aged 30 years or more. Younger clients were also more likely to be of Indigenous origin or seen in a rural setting. Conclusions: Adolescent and young adult alcohol treatment clients include a higher proportion of clients who are Indigenous, legally coerced, and who have concerns with polydrug use. Service providers should seek to tailor their treatment programs to better meet these unique needs and to better attract young people into voluntary treatment. [source] How applicable is the general adaptation syndrome to the unicellular Tetrahymena?CELL BIOCHEMISTRY AND FUNCTION, Issue 1 2009György Csaba Abstract Hormone receptors, hormones and signal transduction pathways characteristic of higher vertebrates can be observed also in the unicellular Tetrahymena. Previous work showed that stress conditions (starvation, high temperature, high salt concentration, formaldehyde or alcohol treatment) elevated the intracellular level of four hormones (ACTH, endorphin, serotonin and T3). Here, the effect of other stressors (CuSO4 poisoning, tryptophan hydroxylase inhibitor parachlorphenylalanine (PCPA) treatment) on the same and other hormones (epinephrine, insulin, histamine) was studied, using immunocytochemistry and flow cytometric analysis. It was found, that each effect increased the intracellular hormone contents, but some hormones (histamine, T3) were less reactive. Insulin,which is a life-saving factor for Tetrahymena,itself provoked elevation of hormone amounts in association with a stressor, further increased the level of hormones. It was concluded that the ancestor of Selye's General Adaptation Syndrome (GAS) can be found already at unicellular level, and this possibly has a life saving function. Copyright © 2008 John Wiley & Sons, Ltd. [source] Randomized controlled trial of cognitive,behavioural therapy for coexisting depression and alcohol problems: short-term outcomeADDICTION, Issue 1 2010Amanda L. Baker ABSTRACT Aims Alcohol use disorders and depression co-occur frequently and are associated with poorer outcomes than when either condition occurs alone. The present study (Depression and Alcohol Integrated and Single-focused Interventions; DAISI) aimed to compare the effectiveness of brief intervention, single-focused and integrated psychological interventions for treatment of coexisting depression and alcohol use problems. Methods Participants (n = 284) with current depressive symptoms and hazardous alcohol use were assessed and randomly allocated to one of four individually delivered interventions: (i) a brief intervention only (single 90-minute session) with an integrated focus on depression and alcohol, or followed by a further nine 1-hour sessions with (ii) an alcohol focus; (iii) a depression focus; or (iv) an integrated focus. Follow-up assessments occurred 18 weeks after baseline. Results Compared with the brief intervention, 10 sessions were associated with greater reductions in average drinks per week, average drinking days per week and maximum consumption on 1 day. No difference in duration of treatment was found for depression outcomes. Compared with single-focused interventions, integrated treatment was associated with a greater reduction in drinking days and level of depression. For men, the alcohol-focused rather than depression-focused intervention was associated with a greater reduction in average drinks per day and drinks per week and an increased level of general functioning. Women showed greater improvements on each of these variables when they received depression-focused rather than alcohol-focused treatment. Conclusions Integrated treatment may be superior to single-focused treatment for coexisting depression and alcohol problems, at least in the short term. Gender differences between single-focused depression and alcohol treatments warrant further study. [source] | ||||||||||||||||