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Alcoholic Subjects (alcoholic + subject)

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Medical Sciences	100%

Selected Abstracts

Frontal White Matter and Cingulum Diffusion Tensor Imaging Deficits in Alcoholism

ALCOHOLISM, Issue 6 2008
Gordon J. Harris
Background:, Alcoholism-related deficits in cognition and emotion point toward frontal and limbic dysfunction, particularly in the right hemisphere. Prefrontal and anterior cingulate cortices are involved in cognitive and emotional functions and play critical roles in the oversight of the limbic reward system. In the present study, we examined the integrity of white matter tracts that are critical to frontal and limbic connectivity. Methods:, Diffusion tensor magnetic resonance imaging (DT-MRI) was used to assess functional anisotropy (FA), a measure of white matter integrity, in 15 abstinent long-term chronic alcoholic and 15 demographically equivalent control men. Voxel-based and region-based analyses of group FA differences were applied to these scans. Results:, Alcoholic subjects had diminished frontal lobe FA in the right superior longitudinal fascicles II and III, orbitofrontal cortex white matter, and cingulum bundle, but not in corresponding left hemisphere regions. These right frontal and cingulum white matter regional FA measures provided 97% correct group discrimination. Working Memory scores positively correlated with superior longitudinal fascicle III FA measures in control subjects only. Conclusions:, The findings demonstrate white matter microstructure deficits in abstinent alcoholic men in several right hemisphere tracts connecting prefrontal and limbic systems. These white matter deficits may contribute to underlying dysfunction in memory, emotion, and reward response in alcoholism. [source]

Factors Affecting %CDT Status at Entry Into a Multisite Clinical Treatment Trial: Experience from the COMBINE Study

ALCOHOLISM, Issue 11 2006
Raymond F. Anton
Background: Carbohydrate-deficient transferrin (CDT) occurs as a higher percentage of normal transferrin (%CDT) in heavy drinkers. %CDT is used as a marker of both alcohol use disorder severity and treatment outcome both clinically and in treatment trials. Nevertheless, little is known about the parameters that predict which patients are %CDT positives at treatment entry. These parameters might include level of drinking, days of abstinence before testing, and severity of alcohol dependence before evaluation. Methods: %CDT levels were collected before randomization from participants of the COMBINE Study, a large federally sponsored multisite clinical trial evaluating medications and behavioral therapies in alcohol-dependent outpatients. %CDT (assayed in a central laboratory) was available in 1,193 individuals for whom drinking history in the 30 days before testing and measures of alcoholism severity were documented. The effects of drinking history and alcohol severity were evaluated for prediction of a %CDT-positive test status. Results: Less percent days abstinent (PDA) and more drinks per drinking day (DDD) were predictive of higher rates of %CDT-positive patients (maximum 67%). Up to 14 days of continuous abstinence before testing did not appear to significantly affect %CDT status. Rates of %CDT positives remained reasonably steady up to about 40% PDA. Years of drinking at dependence levels had an unexpected negative impact on %CDT-positive rates while previous treatment had a small but positive impact of %CDT-positive rates. ADS and DrInC scores had no predictive value over and above recent drinking amounts on %CDT status. Conclusions: %CDT is more likely to be positive in those who have more days of drinking and to a lesser degree in those who drink more per drinking day. It can remain positive even in those alcoholic subjects who stop drinking many days before testing. Alcoholic subjects with more treatment experiences appear to have a marginally higher %CDT-positive rate. [source]

Craving: what can be done to bring the insights of neuroscience, behavioral science and clinical science into synchrony

ADDICTION, Issue 8s2 2000
Roger E. Meyer
Alcohol self-administration behavior is the common thread that is necessary to bring the insights of neuroscience, behavioral science and clinical science into synchrony around the concept of craving. Animal models should address the molecular and cellular changes that take place in behaviorally relevant brain regions of rats consequent to chronic self-administration of ethanol. Animal models can focus on the biology of the anticipatory state in alcohol preferring/consuming rats, as well as studies of the effects of possible medications on this state in the animal model, on actual alcohol consuming behavior, and on the residual effects of chronic alcohol on the non-human mammalian brain. In human studies of craving, cue-reactivity in the absence of the opportunity to drink alcohol does not have the same salience as cue-reactivity in which drinking is possible. Moreover, actual drinking behavior serves to validate self-reports of craving. Studies of limited alcohol self-administration in the laboratory are an essential element in screening new medications for the treatment of alcoholism. Studies to date suggest no adverse reaction to the participation of alcoholic subjects in limited alcohol self-administration studies, but the research community should continue to monitor carefully the outcomes of alcohol-dependent subjects who participate in this type of research, and efforts should always be made to encourage these subjects to enter active treatment. In outpatient clinical trials of new treatments for alcoholism, the assessment of craving should include queries regarding symptoms and signs of protracted abstinence such as sleep disturbances, as well as questions regarding situational craving. Field observations of alcoholics in their favorite drinking environments would contribute greatly to our understanding of the real-world phenomenology of craving. [source]

QT Interval Dispersion and Cardiac Sympathovagal Balance Shift in Rats With Acute Ethanol Withdrawal

ALCOHOLISM, Issue 2 2010
Seiko Shirafuji
Background:, Dysregulation of autonomic nervous system function and impaired homogeneity of myocardial repolarization are 2 important mechanisms for the genesis of ventricular arrhythmias in nonalcoholic subjects. Our previous study suggested that acute ethanol withdrawal promoted the shift of cardiac sympathovagal balance toward sympathetic predominance and reduced the vagal tone, which were related to a higher incidence of ventricular arrhythmia and related death. However, the homogeneity of myocardial repolarization and its relation with the cardiac sympathovagal balance are unknown, especially in alcoholic subjects. The aim of the present study was to clarify these points. Methods:, Male Wistar rats were treated with a continuous ethanol liquid diet for 49 days, and then subjected to 1-day withdrawal and 1-day withdrawal with 7-day carvedilol (can block the sympathetic nervous system completely via ,1, ,2, and , adrenergic receptors) pretreatment. The cardiac sympathovagal balance and homogeneity of myocardial repolarization were evaluated based on the heart rate variability (HRV) and QT interval dispersion (QTd: dynamic changes in QT interval duration). Results:, The increase in QTd was observed only in rats at 1-day withdrawal, but not in nonalcoholic, continuous ethanol intake, and 1-day withdrawal with 7-day carvedilol pretreatment rats. At 1-day withdrawal, the low-frequency power/high-frequency power (LF/HF) ratio in HRV was elevated and correlated with the QTd. The increased QTd and elevated LF/HF ratio were normalized by the 7-day carvedilol pretreatment in rats at 1-day ethanol withdrawal. Conclusions:, In rats with an abrupt termination of the chronic continuous ethanol intake, the homogeneity of myocardial repolarization impaired and correlated with the cardiac sympathovagal balance. Carvedilol pretreatment is associated with a reduction in both the QTd and LF/HF ratio, raising the possibility that the cardiac sympathovagal balance shift may be responsible for the impaired homogeneity of myocardial repolarization, and that ,-blocker pretreatment may decrease the mortality risk during alcoholic withdrawal. [source]

Alcohol Stimulates Activation of Snail, Epidermal Growth Factor Receptor Signaling, and Biomarkers of Epithelial,Mesenchymal Transition in Colon and Breast Cancer Cells

ALCOHOLISM, Issue 1 2010
Christopher B. Forsyth
Background:, Alcohol consumption is associated with the risk of progressive cancers including colon and breast cancer. The mechanisms for the alcohol-induced aggressive behavior of these epithelial cancer cells have not been fully identified. Epithelial,mesenchymal transition (EMT) is a developmental program recently shown to play a role in cancer progression and metastases. We hypothesized that alcohol might promote cancer progression by inducing EMT in cancer cells and tested this hypothesis by assessing alcohol-stimulated changes in phenotypic markers of EMT as well as the EMT transcription factor Snail and its related cell signaling. Methods:, Colon and breast cancer cell lines and a normal intestinal epithelial cell line were tested as well as colonic mucosal biopsy samples from alcoholic subjects. Cells were treated with alcohol and assessed for EMT-related changes using immunofluorescent microscopy, western blotting, reporter assays, RT-PCR, and knockdown of Snail with siRNA. Results:, We show alcohol upregulated the signature EMT phenotypic marker vimentin as well as matrix metalloprotease (MMP)-2, MMP-7, and MMP-9 and cell migration in colon and breast cancer cells,all characteristics of EMT. Alcohol also stimulated nuclear localization of Snail phosphorylated at Ser246, transcription from a Snail reporter plasmid, and Snail mRNA expression by RT-PCR. Snail siRNA knockdown prevented alcohol-stimulated vimentin expression. In vivo, Snail expression was significantly elevated in colonic mucosal biopsies from alcoholics. Also, we found alcohol stimulated activation of epidermal growth factor receptor (EGFR) signaling and an EGFR inhibitor blocked alcohol-induced cell migration and Snail mRNA expression. Conclusions:, Collectively, our data support a novel mechanism for alcohol promoting cancer progression through stimulating the EMT program in cancer cells via an EGFR-Snail mediated pathway. This study reveals new pathways for alcohol-mediated promotion of cancer that could be targeted for therapy or prevention of alcohol-related cancers. [source]

Genuine Episodic Memory Deficits and Executive Dysfunctions in Alcoholic Subjects Early in Abstinence

ALCOHOLISM, Issue 7 2007
Anne 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]

Serum Free Sialic Acid as a Marker of Alcohol Abuse

ALCOHOLISM, Issue 6 2007
Lech Chrostek
Background: Previous studies have shown that serum total sialic acid (TSA) concentration significantly increases during alcohol abuse. Chronic ethanol consumption impairs glycosylation of many proteins. The increased desialylation rate of serum glycoproteins is one of the effects of alcohol abuse. The aim of this study was to investigate the diagnostic value of free sialic acid (FSA) as a marker of alcohol abuse. Methods: We determined serum FSA concentrations in the group of 156 alcoholic subjects and 35 healthy control subjects by means of a modification of the thiobarbituric acid method. The alcoholic group was divided into subgroups according to their history of abuse. Results: The FSA concentration was significantly higher in alcoholic subjects than in healthy controls. The subjects who consumed alcohol for longer than a week showed significantly higher FSA level than those who consumed alcohol for a shorter period. The serum FSA concentration was significantly higher in alcoholic subjects with elevated markers of liver dysfunction. The diagnostic accuracy of FSA was high, although it did not differ from TSA, and was limited by its low sensitivity. Conclusions: This study shows that FSA concentration in the sera of alcoholic subjects is increased. The low diagnostic sensitivity is accompanied by high specificity, however the accuracy is high and similar to the accuracy of TSA. Free sialic acid does not seem to be a better marker of alcohol abuse than TSA and current markers. [source]

Effect of Episodic and Working Memory Impairments on Semantic and Cognitive Procedural Learning at Alcohol Treatment Entry

ALCOHOLISM, Issue 2 2007
Anne Lise Pitel
Background: Chronic alcoholism is known to impair the functioning of episodic and working memory, which may consequently reduce the ability to learn complex novel information. Nevertheless, semantic and cognitive procedural learning have not been properly explored at alcohol treatment entry, despite its potential clinical relevance. The goal of the present study was therefore to determine whether alcoholic patients, immediately after the weaning phase, are cognitively able to acquire complex new knowledge, given their episodic and working memory deficits. Methods: Twenty alcoholic inpatients with episodic memory and working memory deficits at alcohol treatment entry and a control group of 20 healthy subjects underwent a protocol of semantic acquisition and cognitive procedural learning. The semantic learning task consisted of the acquisition of 10 novel concepts, while subjects were administered the Tower of Toronto task to measure cognitive procedural learning. Results: Analyses showed that although alcoholic subjects were able to acquire the category and features of the semantic concepts, albeit slowly, they presented impaired label learning. In the control group, executive functions and episodic memory predicted semantic learning in the first and second halves of the protocol, respectively. In addition to the cognitive processes involved in the learning strategies invoked by controls, alcoholic subjects seem to attempt to compensate for their impaired cognitive functions, invoking capacities of short-term passive storage. Regarding cognitive procedural learning, although the patients eventually achieved the same results as the controls, they failed to automate the procedure. Contrary to the control group, the alcoholic groups' learning performance was predicted by controlled cognitive functions throughout the protocol. Conclusion: At alcohol treatment entry, alcoholic patients with neuropsychological deficits have difficulty acquiring novel semantic and cognitive procedural knowledge. Compared with controls, they seem to use more costly learning strategies, which are nonetheless less efficient. These learning disabilities need to be considered when treatment requiring the acquisition of complex novel information is envisaged. [source]

Glutamate Decarboxylase Genes and Alcoholism in Han Taiwanese Men

ALCOHOLISM, Issue 11 2006
El-Wui Loh
Objective: Glutamate decarboxylase (GAD), the rate-limiting enzyme in the synthesis of , -aminobutyric acid (GABA), may be involved in the development of alcoholism. This study examined the possible roles of the genes that code for 2 forms of GAD (GAD1 and GAD2) in the development of alcoholism. Method: An association study was conducted among 140 male alcoholic subjects meeting the DSM-III-R criteria for alcohol dependence and 146 controls recruited from the Han Taiwanese in community and clinical settings. Psychiatric assessment of drinking conditions was conducted using a Chinese version of the Schedules for Clinical Assessment in Neuropsychiatry. The SHEsis and Haploview programs were used in statistical analyses. Results: Nine single-nucleotide polymorphisms (SNPs) at the GAD1 gene were valid for further statistics. Between alcoholic subjects and controls, significant differences were found in genotype distributions of SNP1 (p=0.000), SNP2 (p=0.015), SNP4 (p=0.015), SNP5 (p=0.031), SNP6 (p=0.012), and SNP8 (p=0.004) and in allele distributions of SNP1 (p=0.001), SNP2 (p=0.009), and SNP8 (p=0.009). Permutation tests of SNP1, SNP2, and SNP8 demonstrated significant differences in allele frequencies but not in 2 major haplotype blocks. Three valid SNPs at the GAD2 gene demonstrated no associations with alcoholism. Further permutation tests in the only 1 haplotype block or individual SNPs demonstrated no significant differences. Conclusions: This is the first report indicating a possible significant role of the GAD1 gene in the development of alcohol dependence and/or the course of alcohol withdrawal and outcome of alcoholism. [source]

Factors Affecting %CDT Status at Entry Into a Multisite Clinical Treatment Trial: Experience from the COMBINE Study

Effects of Chronic Alcohol Abuse on Alveolar Epithelial Barrier Function and Glutathione Homeostasis

ALCOHOLISM, Issue 7 2003
Ellen L. Burnham
Background: An association between the development and severity of the acute respiratory distress syndrome has been described in individuals who abuse alcohol chronically, possibly through a mechanism involving the deficiency of pulmonary glutathione. In a rodent model of chronic alcohol abuse, this antioxidant contributes to the maintenance of alveolar-capillary membrane integrity. We postulated that humans who chronically abuse alcohol will have similar alterations in alveolar-capillary barrier function. Methods: Bronchoalveolar lavage was performed in 18 healthy chronic alcoholics and 18 control subjects; total protein and glutathione concentrations were measured within the epithelial lining fluid. To examine possible protracted effects of alcohol abuse, a subset of 11 chronic alcoholic subjects underwent a second bronchoalveolar lavage after a week of abstinence. Results: Chronic alcoholic subjects had significantly elevated protein concentrations compared with controls (8.64 ,g protein/ng immunoglobulin A vs. 5.91 ,g protein/ng immunoglobulin A, p= 0.01). After a week of abstinence, no significant increase in either the glutathione levels or normalization of the protein concentrations in the epithelial lining fluid was demonstrable. Conclusions: Increased protein levels in the epithelial lining fluid of individuals who abuse alcohol chronically may signify abnormal alveolar epithelial barrier function that does not appear to readily reverse after a period of abstinence. [source]

Genetic Repeat Polymorphism in the Regulating Region of CYP2E1: Frequency and Relationship With Enzymatic Activity in Alcoholics

ALCOHOLISM, Issue 6 2001
E. Plee-Gautier
Background: Differences in the regulatory region of the CYP2E1 gene could be responsible for the interindividual variation in the cytochrome P-450 2E1 (CYP2E1) involved in ethanol oxidation. Recently, a polymorphic repeat sequence in the human gene was described between ,2178 and ,1945 base pairs. Its frequency seemed to vary among different ethnic populations, and it was suspected to be related to an increased inducibility to further ethanol intake. In the study reported here, the frequency of this polymorphism was investigated in a white French population. Its relationship with the previously described Pst I/Rsa I or Dra I CYP2E1 polymorphisms, alcoholism, alcoholic liver disease, and inducibility of CYP2E1 by ethanol was examined. Methods: The polymorphic region was characterized by polymerase chain reaction in 103 controls, 148 alcoholic subjects without liver diseases, and 98 others with liver cirrhosis. By using in vivo chlorzoxazone (CHZ) metabolism, CYP2E1 phenotype was assessed in 36 non,ethanol-induced subjects (17 controls and 19 withdrawn alcoholics) and in 14 ethanol-induced subjects (10 controls after ingestion of 0.8 g/kg ethanol and four alcoholics with 100 g of daily intake). This phenotype was expressed as the 6-hydroxy CHZ/CHZ ratio. Results: The rare allele frequency was found to be 1.58% in whites (n= 349). Neither significant association with alcoholism or alcoholic liver diseases, nor relationship with the Pst I/Rsa I polymorphism, was observed. But the Dra I polymorphism was more frequent among the heterozygous subjects when compared with wild-type homozygous ones (p < 0.05). The CYP2E1 phenotype was similar in wild-type homozygotes and in heterozygotes at the constitutive level, as well as after induction with ethanol. Conclusions: Our data suggest that CYP2E1 repeat polymorphism does not seem to constitute a major factor for interindividual differences in CYP2E1 expression and susceptibility to alcohol-related disorders in whites. [source]

Alcohol And Endothelial Function: A Brief Review

CLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY, Issue 12 2001
IB Puddey
SUMMARY 1. In spite of the dose-related effects of alcohol consumption to increase blood pressure, regular light to moderate alcohol intake appears to confer protection against both coronary artery disease and ischaemic stroke. In contrast, heavy alcohol consumption increases the risk of coronary artery disease and the risk of both haemorrhagic and ischaemic stroke. 2. Effects of alcohol consumption on endothelial cell function may be relevant to these disparate effects on cardiovascular outcomes. In in vitro animal studies, low doses of alcohol have been demonstrated to increase release of nitric oxide and augment endothelium-mediated vasodilatation, whereas higher doses impair endothelium-dependent relaxation responses. In contrast, chronic administration of alcohol to rats has generally been associated with tolerance to the acute inhibitory effects of alcohol on endothelium-mediated vasodilatation and may even result in augmentation of such responses. 3. The few human studies to date that have examined the effects of alcohol on endothelial function have focused on postischaemic flow-mediated dilation of the brachial artery (FMD). Although blunted FMD responses have been reported in alcoholic subjects, acute administration of alcohol or short-term interventions to reduce alcohol intake have had no effect to either improve or impair FMD. 4. Further studies in humans assessing acute and longer term dose-related effects of alcohol on endothelial function in both conduit and resistance vessels will be necessary if the relevance of the findings from in vitro and in vivo animal studies are to be understood in the context of the complex interrelationships of alcohol with cardiovascular disease. [source]