bluuebunny/crossref_metadata_2025_split huggingface dataset:
Drinks of the Father: Father's Maximum Number of Drinks Consumed Predicts Externalizing Disorders, Substance Use, and Substance Use Disorders in Preadolescent and Adolescent Offspring
Authors: Malone Stephen M. , Iacono William G. , McGue Matt 
Published: April 2006

Background The maximum number of drinks consumed in 24 hr seems to be an interesting phenotype related to alcoholism. The goal of the present study was to determine in an epidemiologic sample whether this measure of drinking history in fathers predicted externalizing behavioral disorders, substance use, and substance abuse in preadolescent and adolescent offspring and whether any such associations would be independent of paternal alcohol dependence diagnoses.Methods Subjects were male and female twins from both age cohorts of the Minnesota Twin Family Study, a population‐based longitudinal study, and were approximately 11 or 17 years of age, respectively, upon study enrollment. In both age cohorts, diagnoses of conduct disorder, oppositional defiant disorder, and attention‐deficit/hyperactivity disorder served as outcome measures. In addition, measures of lifetime substance use and of the presence of symptoms of substance abuse were derived for the 11‐year‐old cohort when subjects were approximately 14 years old and diagnoses of substance abuse were derived for the older cohort at age 17. An extension of logistic regression using generalized estimating equations served to assess whether paternal maximum alcohol consumption predicted filial outcome measures.Results Paternal maximum alcohol consumption was consistently associated with conduct disorder, substance use, and substance abuse or dependence in male and female offspring. These associations were not mediated by a primary effect of paternal alcoholism.Conclusions Paternal maximum alcohol consumption was uniquely associated with those offspring characteristics most reliably found in adolescent children of alcoholic parents. This phenotype might supplement DSM diagnoses of alcohol dependence to reduce the number of false positives in genetic research.
Effects of Chronic Hepatic Dysfunction on Pulmonary Glutathione Homeostasis
Authors: Foreman Marilyn G. , Hoor Terri Ten , Brown Lou Ann S. , Moss Marc 
Published: April 2006

Background The development of acute respiratory distress syndrome (ARDS) in patients with pre‐existing cirrhosis of the liver is associated with very high mortality. One possible cause may be alteration of pulmonary antioxidant capacity as a result of chronic hepatic dysfunction. Glutathione (GSH) is the most substantial nonprotein thiol in living organisms and likely plays a key role in neutralizing the oxidants and reactive oxygen species that are increased in ARDS. The lung is unable to synthesize GSH and is dependent on the liver. During periods of oxidant stress, individuals may exhibit relative deficiencies of GSH. With cirrhosis, the end result of chronic alcohol ingestion, this deficiency is more profound.Methods Sixteen stable subjects with cirrhosis primarily due to alcohol consumption and 15 healthy controls underwent bronchoscopy and bronchoalveolar lavage with concurrent measurement of GSH in the plasma and the alveolar epithelial lining fluid (ELF).Results For standardizing for saline dilution of the epithelial lining fluid as a result of bronchoalveolar lavage, GSH values are expressed in relation to immunoglobulin A (IgA). GSH in the ELF was profoundly reduced in the cirrhotic group [12.5 μg of GSH per μg of IgA (5.3–16.9 μg)] compared with the control group [64.0 μg of GSH per μg of IgA (55.1–242.5 μg);p < 0.001]. The ratio of oxidized GSH to total GSH in the ELF was also significantly increased in the cirrhotic group [9.2% (5.1–16.4%) vs. 3.4% (1.7–5.7%);p < 0.003]Conclusions Despite a total reduction in GSH concentrations in the alveolar epithelial lining fluid of individuals with cirrhosis, the amount of oxidized GSH is increased. There is increased utilization of GSH despite the low supply in stable individuals with cirrhosis during steady state. These perturbations in GSH homeostasis in the alveolar epithelial lining fluid may be a factor in the poor outcomes seen in these individuals with ARDS.
Alcohol Unmasks Simian Immunodeficiency Virus‐Induced Cognitive Impairments in Rhesus Monkeys
Authors: Winsauer Peter J. , Moerschbaecher Joseph M. , Brauner Ian N. , Purcell Jeanette E. , Lancaster Jack R. , Bagby Gregory J. , Nelson Steve 
Published: April 2006

Background Alcohol and human immunodeficiency virus (HIV) produce similar neuropathological profiles, including loss of neurons in the frontal cortex. Additionally, HIV‐positive patients with a history of alcohol abuse have greater neurologic deficits, and chronic alcohol abuse produces electrophysiological deficits earlier in the HIV disease process. Few studies, preclinical or clinical, have examined whether alcohol administration exacerbates the neuropsychological deficits in subjects with lentiviruses such as HIV.Methods To examine the combined effects of alcohol and immunodeficiency viruses (IVs) on neuropsychological functioning, four groups of young adult rhesus monkeys trained to respond under two complex behavioral tasks were administered ethanol 4 days per week via an intragastric catheter for 3 months and then infected with simian immunodeficiency virus (SIV). Behavioral testing after SIV inoculation was conducted in each group (−ethanol [EtOH]/−SIV, −EtOH/+SIV, +EtOH/−SIV, and +EtOH/+SIV) on days when alcohol was not administered to avoid a direct confound and on several occasions when ethanol or sucrose was administered as a probe of the effect of alcohol alone and the effect of caloric supplementation on the food‐maintained tasks, respectively.Results During the days of the week when ethanol was not administered, little or no disruption was observed in either response rate or the percentage of errors (accuracy) across the different treatment groups. In contrast, behavioral testing during alcohol administration revealed that subjects in the various treatment groups had different susceptibilities to ethanol administration. As expected, a two‐way ANOVA (ethanol condition, SIV condition) indicated there were significant main effects of ethanol on both response rate and percent errors in both behavioral tasks, but it also indicated there was a significant interaction between ethanol administration and SIV infection on the accuracy of responding in the acquisition (learning) task. In addition, the main effect of SIV on percent errors was in the performance task.Conclusions The fact that alcohol administration in SIV‐infected monkeys produced greater behavioral deficits than either alcohol or SIV alone further strengthens the supposition that IVs adversely affect neural substrates involved in cognition and that the adverse effects of many central nervous system drugs may be enhanced in IV‐infected individuals.
Muscle Antioxidant Status in Chronic Alcoholism
Authors: Fernández‐Solà Joaquim , García Gloria , Elena Montserrat , Tobías Esther , Sacanella Emilio , Estruch Ramón , Nicolás José‐María 
Published: April 2006

Background Chronic myopathy due to excessive ethanol intake is one of the most frequent causes of acquired skeletal myopathy in developed countries. Its pathogenesis is multi‐factorial, only partially clarified, and antioxidant imbalance has been suggested to influence its development, being a type II glucolytic, fast‐twitch fiber subset more sensitive to this effect.Methods We assessed superoxide dismutase, glutathione peroxidase, and glutathione reductase enzyme activities as well as the total antioxidant status capacity in muscle samples obtained from 41 chronic alcoholic males and 12 age‐matched controls. Alcoholic skeletal myopathy was defined according to standard histologic criteria. We evaluated the influence of ethanol consumption, caloric and protein nutritional status, and the presence of skeletal myopathy with the tissue activities of these antioxidant enzymes.Results Chronic alcoholics showed a 16% reduction in glutathione peroxidase and a 13% increase of superoxide dismutase in the skeletal muscle, compared with controls (p < 0.05, both). Muscle antioxidant changes in chronic alcoholics were not related to the presence of skeletal myopathy, parameters of alcohol consumption, or conventional nutritional parameters.Conclusions Antioxidant muscle enzyme activities are partially disturbed in chronic alcoholism, although not related to the presence of myopathy, amount of ethanol consumed, or the nutritional status of the patients. Further studies should assess other aspects not included in the present study such as muscle site‐specific changes in antioxidant status/oxidative damage, specific fiber‐type sensitivity to alcohol, and type and quantity of antioxidant content of the diet or in the alcohol beverages.
Alcohol Potentiates HIV‐1 Infection of Human Blood Mononuclear Phagocytes
Authors: Wang Xu , Douglas Steven D. , Metzger David S. , Guo Chang‐Jiang , Li Yuan , O'Brien Charles P. , Song Li , Davis‐Vogal Annet , Ho Wen‐Zhe 
Published: April 2006

Background Acute and chronic alcohol abuse impairs various functions of the immune system and thus has been implicated as a cofactor in HIV infection. The mechanisms by which alcohol affects the function of human immune cells that are the targets for HIV are unknown.Methods Human blood monocyte‐derived macrophages (MDM) were incubated with or without alcohol (10–40 mM) for 24 hr and then infected with HIV for 24 hr. Culture supernatants were harvested for HIV reverse transcription assay. HIV entry receptor (CCR5, CD4, and CXCR4) expression was determined by reverse transcription‐polymerase chain reaction and flow cytometry assays. β‐Chemokines were analyzed using enzyme‐linked immunosorbent assay. Different HIV strains (Bal, SF‐162, 89.6, and UG024) were used for infection experiments. In addition, ADA (macrophage‐tropic strain) and murine leukemia virus envelope‐pseudotyped HIV infection was carried out.Results Although alcohol had little effect on HIV T‐lymphocyte‐tropic strain infection, it significantly enhanced HIV R5 strain infection in MDM. The enhancing effect of alcohol on the HIV R5 strain was further evidenced by the observation that the R5 (ADA) strain envelope‐pseudotyped HIV infection is markedly increased by alcohol, whereas murine leukemia virus envelope‐pseudotyped HIV infection was not affected. Alcohol significantly up‐regulated CCR5 receptor expression and inhibited the endogenous production of β‐chemokines by MDM.Conclusion Alcohol, through the down‐regulation of β‐chemokine production and the up‐regulation of CCR5 receptor expression, enhances HIV R5 strain infection of MDM and may have an important role as a cofactor in the progression of HIV disease.
Early‐Onset Alcoholism With Conduct Disorder: Go/No Go Learning Deficits, Working Memory Capacity, and Personality
Authors: Finn Peter R. , Mazas Carlos A. , Justus Alicia N. , Steinmetz Joseph 
Published: April 2006

Background: Two studies were conducted to investigate the disinhibitory mechanisms that (1) discriminate early‐onset alcoholism (EOA) with conduct disorder (CD; antisocial EOA) from a nonantisocial subtype of EOA and (2) are associated with novelty‐seeking and low harm avoidance.Methods: Young adults with antisocial EOA (n= 96), with nonantisocial EOA (without CD;n= 80), with CD alone (n= 50), and controls (n= 125) were given two go/no go tasks (one with monetary loss and the other with shock punishment), the Digit Span test (working memory capacity), and personality measures of harm avoidance, novelty‐seeking/impulsivity, excitement‐seeking, and negative affectivity.Results: Study 1 revealed that antisocial EOA subjects had poor behavioral inhibition compared with nonantisocial EOAs and controls on both go/no go tasks and with the CD‐alone group on the monetary‐loss task. Low Digit Span scores accentuated poor inhibition in antisocial EOAs on the monetary loss, but not the shock task. EOA with low Digit Span was associated with higher hit rates on the shock task. Study 2 revealed that antisocial EOAs had high novelty‐seeking/impulsivity and low harm avoidance compared with both nonantisocial EOAs and controls. Low harm avoidance was associated with poor inhibition with shock punishment, and this association was mediated by CD. For subjects with low Digit Span scores, novelty‐seeking/impulsivity was associated with poor inhibition to monetary‐loss punishment and higher hit rates to shock punishment.Conclusions: The results suggest two disinhibitory mechanisms that distinguish antisocial from nonantisocial EOA: an increased sensitivity to reward in nonaversive contexts associated with novelty‐seeking/impulsivity and a decreased sensitivity to punishment in aversive contexts associated with low harm avoidance. Results also suggest that EOA and novelty‐seeking/impulsivity are associated with a greater response to rewards in those with low working memory capacity.
Chronic Ethanol Consumption Increases Plasma Leptin Levels and Alters Leptin Receptors in the Hypothalamus and the Perigonadal Fat of C57BL/6 Mice
Authors: Obradovic Tanja , Meadows Gary G. 
Published: April 2006

Background: Leptin, a protein secreted from adipocytes, and leptin receptors, expressed in the hypothalamus and fat tissue, regulate energy balance and adiposity. Leptin receptors exist as several forms that are delineated by the length of their cytoplasmic domains. Only the longest form is physiologically active through stimulation of the signal transducers and activators of transcription (STAT) second messenger system. Previous studies demonstrated that chronic ethanol consumption increases body adiposity and circulating leptin levels. This study examined the effect of chronic alcohol intake on the expression of leptin receptors and associated STAT second messengers in the hypothalamus and fat tissue.Methods: Female C57BL/6 mice were given water or 20% w/v ethanol and Purina 5001 laboratory chow ad libitum for 2 or 5 weeks. Plasma leptin levels were determined by radioimmunoassay and body adiposity was evaluated by measuring the amount of perigonadal fat. Expression of leptin receptors as well as STAT molecules in whole‐cell lysates of the hypothalamus and the perigonadal fat were assayed by Western blot analysis.Results: Plasma leptin and perigonadal fat were increased after 5 weeks. The overall expression of leptin receptors was increased while the expression of the physiologically active long form of leptin receptor was decreased in the hypothalamus and the perigonadal fat of ethanol‐consuming mice. Ethanol consumption also decreased hypothalamic expression of STAT3, a protein associated with leptin receptor activation in this region of the brain. In contrast, STAT1, a protein associated with leptin receptor activation in adipose tissue, was significantly elevated in the perigonadal fat of ethanol‐consuming mice.Conclusions: Chronic ethanol consumption increases the circulating level of leptin, and this is accompanied by altered expression of leptin‐sensing molecules in the hypothalamus and peripheral adipose tissue. These results suggest that chronic ethanol intake affects metabolism by altering the leptin system that regulates energy balance.
CDT, GGT, and AST As Markers of Alcohol Use: The WHO/ISBRA Collaborative Project
Authors: Conigrave Katherine M. , Degenhardt Louisa J. , Whitfield John B. , Saunders John B. , Helander Anders , Tabakoff Boris ,   on behalf of the WHO/ISBRA Study Group
Published: April 2006

Background: Estimates of the performance of carbohydrate deficient transferrin (CDT) and gamma glutamyltransferase (GGT) as markers of alcohol consumption have varied widely. Studies have differed in design and subject characteristics. The WHO/ISBRA Collaborative Study allows assessment and comparison of CDT, GGT, and aspartate aminotransferase (AST) as markers of drinking in a large, well‐characterized, multicenter sample.Methods: A total of 1863 subjects were recruited from five countries (Australia, Brazil, Canada, Finland, and Japan). Recruitment was stratified by alcohol use, age, and sex. Demographic characteristics, alcohol consumption, and presence of ICD‐10 dependence were recorded using an interview schedule based on the AUDADIS. CDT was assayed using CDTect™ and GGT and AST by standard methods. Statistical techniques included receiver operating characteristic (ROC) analysis. Multiple regression was used to measure the impact of factors other than alcohol on test performance.Results: CDT and GGT had comparable performance on ROC analysis, with AST performing slightly less well. CDT was a slightly but significantly better marker of high‐risk consumption in men. All were more effective for detection of high‐risk rather than intermediate‐risk drinking. CDT and GGT levels were influenced by body mass index, sex, age, and smoking status.Conclusions: CDT was little better than GGT in detecting high‐ or intermediate‐risk alcohol consumption in this large, multicenter, predominantly community‐based sample. As the two tests are relatively independent of each other, their combination is likely to provide better performance than either test alone. Test interpretation should take account sex, age, and body mass index.
Metadoxine in Acute Alcohol Intoxication: A Double‐Blind, Randomized, Placebo‐Controlled Study
Authors: Shpilenya Leonid S. , Muzychenko Alexander P. , Gasbarrini Giovanni , Addolorato Giovanni 
Published: April 2006

Background: At present there are only intriguing and preliminary clinical results regarding the efficacy of metadoxine (pyridoxol L‐2‐pyrrolidone‐5‐carboxylate) in acute alcohol intoxication. The present study was planned with the aim of investigating the effectiveness of metadoxine in the management of patients affected by acute ethanol intoxication.Methods: A double‐blind, randomized, multicenter, placebo‐controlled trial was carried out on 58 patients of both sexes with acute ethanol intoxication. Patients were treated with a single dose of 900‐mg intravenous metadoxine (n= 29) or with placebo (n= 29). Patients were clinically and biochemically evaluated at 0.5, 1, 2, 3, 6, 9, and 12 hr after treatment.Results: Treatment with metadoxine significantly decreased the half‐life of ethanol in blood (from 6.70 ± 1.84 to 5.41 ± 1.99 hr;p < 0.013) and showed a faster rate of ethanol elimination. The effects on ethanol half‐life in blood were accompanied by a faster onset of recovery from intoxication, defined as the time of the transition of blood ethanol levels to the immediately lower range defined by intoxication categories (in g/liter: 0 to 0.5, absent; 0.51 to 1.0, mild; 1.1 to 2.5, moderate; >2.5, severe). Thus the median time to onset of recovery was 0.95 hr with metadoxine and 2.34 hr with placebo (p= 0.013). The effects of treatment on blood alcohol levels were paralleled by a significant decrease in the rating of the toxic clinical symptomatology. At 2 hr the improvement of toxic symptoms (in percent of maximum possible) was 68 ± 28 vs. 44 ± 27% in controls (p < 0.002).Conclusions: In patients with acute ethanol intoxication metadoxine accelerated the elimination of ethanol from blood, which led to faster recovery from intoxication, and improved the behavioral toxic symptomatology. Metadoxine could be helpful in the management of acute ethanol intoxication.
Altered Emotion‐Modulated Startle in Young Adults With a Family History of Alcoholism
Authors: Miranda Robert , Meyerson Lori A. , Buchanan Tony W. , Lovallo William R. 
Published: April 2006

Background: Alcoholism risk may be accompanied by poor regulation of emotions, signaling altered central nervous system processes. This study used the emotion‐modulated startle paradigm to test the hypothesis that young adults with a positive paternal history of alcoholism (FH+), relative to family‐history‐negative persons (FH−), have altered emotional reactivity to environmental cues.Methods: We tested 30 FH+ and 30 FH−, 15 males and 15 females in each group. Participants completed self‐report instruments and interviews and had eye blink electromyograms (EMG) measured to acoustic startle probes while viewing color photographs rated as affectively pleasant, neutral, and unpleasant.Results: FH− had the expected linear increase in startle magnitude, with eye blink EMG gaining in strength (F= 18, p < 0.0002) from pleasant to neutral to unpleasant slides. In contrast, FH+ did not show EMG potentiation to the unpleasant slides and therefore lacked the same linear trend (F < 1, p > 0.4). Notably, FH groups rated the emotional valence and arousal of the photographs in similar ways. Self‐reported negative affect partly accounted for the lack of startle potentiation in FH+, suggesting that startle modulation differences between the groups may be associated with underlying psychological characteristics.Conclusions: These findings implicate altered limbic outputs to the startle pathway in FH+ despite normal conscious evaluation of emotional arousal and pleasantness of the slides. This method may provide a useful paradigm for testing processing of emotionally relevant stimuli in relation to risk for alcohol use disorders.
Comparison of 3190 Alcohol‐Dependent Individuals With and Without Suicide Attempts
Authors: Preuss U. W. , Schuckit M. A. , Smith T. L. , Danko G. P. , Buckman K. , Bierut L. , Bucholz K. K. , Hesselbrock M. N. , Hesselbrock V. M. , Reich T. 
Published: April 2006

Introduction: Suicidal behaviors are often seen in alcohol‐dependent individuals. The aim of this study is to identify and confirm risk factors for suicide attempts in a large, family‐based sample of alcoholics.Methods: Semistructured, detailed interviews were administered to 3190 alcohol‐dependent individuals as part of the Collaborative Study on the Genetics of Alcoholism (COGA). Information about suicidal behavior, socioeconomic characteristics, psychiatric comorbidity, substance use disorders, and characteristics of alcohol dependence were obtained from alcohol‐dependent probands, controls, and their relatives.Results: As determined by both univariate comparison and multivariate logistic regression analysis, alcohol‐dependent individuals with a history of suicide attempts were found to have a significantly more severe course of alcohol dependence and a higher prevalence of both independent and substance‐induced psychiatric disorders and other substance dependence. First‐degree relatives of subjects with suicide attempts showed a significantly higher rate of suicide attempts even after controlling for additional relevant diagnoses.Conclusion: These results support the hypothesis that alcohol‐dependent individuals with a history of suicide attempts are more severely impaired. Screening and subsequent treatment of alcohol use disorder, psychiatric comorbidity, and substance use disorders among alcoholics may be crucial in preventing suicide attempts and completions.