JOURNAL OF FOOD SCIENCE, Issue 1 2008
C.A. Wright
ABSTRACT:, In general beer has not been portrayed as part of a balanced diet. However, red wine has been promoted as a beneficial part of a nutritious diet. The evidence is that beer is at least the equal of wine from a nutritional perspective and in countering ailments such as coronary heart disease. This study used surveys to compare beer and wine consumers' perceptions of alcoholic and nonalcoholic beverages. The consumers ranked 7 beverages based upon perceived healthfulness both before and after they were exposed to nutritional information about the beverages. The ranked data were analyzed using analysis of variance. The variance due to the 3-way interaction of place of recruitment, beverage, and ranking was found to be significant at P < 0.05. There was no significant difference between genders. Overall, consumers of alcoholic beverages perceived red wine to be more healthful than the other 6 beverages, including beer and white wine. The perceived healthfulness of a beverage does not appear to be the main factor driving the choice of beverage. Nutritional information does impact consumers' perceptions of the healthfulness of beverages. Consumers who are predominately beer drinkers were more heavily influenced by nutritional information than consumers who were predominately wine drinkers. [source]

MicroRNA Expression Profile in Lieber-DeCarli Diet-Induced Alcoholic and Methionine Choline Deficient Diet-Induced Nonalcoholic Steatohepatitis Models in Mice

ALCOHOLISM, Issue 10 2009
Angela Dolganiuc
Background:, Alcoholic and nonalcoholic steatohepatitis are leading causes of liver diseases worldwide. While of different etiology, these share common pathophysiological mechanisms and feature abnormal fat metabolism, inflammation and fibrosis. MicroRNAs (miRNA) are highly conserved noncoding RNAs that control gene expression at the post-transcriptional level either via the degradation of target mRNAs or the inhibition of translation. Each miRNA controls the expression of multiple targets; miRNAs have been linked to regulation of lipid metabolism and inflammation. Methods:, We fed Lieber-DeCarli alcohol or methionine-choline-deficient (MCD) diets to C57Bl6 and analyzed livers for histopathology, cytokines by ELISA, alanine aminotransferase (ALT) by biochemical assay, and microRNA profile by microarray. Results:, Both Lieber-DeCarli and MCD diets lead to development of liver steatosis, liver injury, indicated by increased ALT, and elevated levels of serum TNF,, suggesting that animal models portray the pathophysiological features of alcoholic and nonalcoholic fatty liver, respectively. We identified that Lieber-deCarli diet up-regulated 1% and down-regulated 1% of known miRNA; MCD diet up-regulated 3% and down-regulated 1% of known miRNA, compared to controls. Of miRNAs that changed expression levels, 5 miRNAs were common in alcoholic and nonalcoholic fatty livers: the expression of both miR-705 and miR-1224 was increased after Lieber-DeCarli or MCD diet feeding. In contrast, miR-182, miR-183, and miR-199a-3p were down-regulated in Lieber-deCarli feeding, while MCD diet lead to their up-regulation, compared to corresponding controls. Conclusions:, Our findings indicate etiology-specific changes in miRNA expression profile during steatohepatitis models, which opens new avenues for research in the pathophysiology of alcoholic and nonalcoholic fatty liver disease. [source]

Imaging of Language-Related Brain Regions in Detoxified Alcoholics

ALCOHOLISM, Issue 6 2009
Sandra Chanraud-Guillermo
Background:, Neuroimaging studies showed clear evidence of alcoholism-related damage to the frontal lobes and cerebellum. Although these regions have been involved in language processing, language skills are relatively spared in alcoholics. Here, we aimed at identifying neural substrates associated with the preserved mechanisms of language processing in alcoholics. We hypothesized that alcoholics would show a different pattern of neural activity compared with the controls. Methods:, Alcoholic and nonalcoholic subjects performed an auditory language task while receiving a functional magnetic resonance imaging (fMRI) scan in a 1.5 T magnet. This task has been previously shown to solicit the comprehension processing in healthy controls, with reliable fMRI response in the left frontal and temporal/parietal lobes. Results:, Behavioral results showed comparable performance (error rates, response time) between the alcoholics and the matched controls. However, analysis of the functional data revealed that the alcoholics exhibited greater fMRI response in the left middle frontal gyrus (pars triangularis), the right superior frontal gyrus, and the cerebellar vermis relative to the controls. Conclusions:, These findings suggest that frontocerebellar neural activity, supporting the comprehension processing of the auditory language task, may require compensatory mechanisms in alcoholics in order to maintain the same level of performance as the controls. [source]

Predictors of 16-Year Mortality Among Individuals Initiating Help-Seeking for an Alcoholic Use Disorder

ALCOHOLISM, Issue 10 2006
Christine Timko
Background and Methods: We examined rates and predictors of mortality in individuals (47% women) who had just initiated help-seeking for their alcohol use disorders (AUDs) at the start of the study (n=628) and were followed for 16 years. Results: For both women and men, the observed-to-expected mortality ratio (1.4) was lower than rates found in samples of treated individuals with AUDs, suggesting that those initiating help-seeking careers have better chances of long-term survival. Of the individuals for whom cause of death was known, 68% died of alcohol-related causes. Men were more likely to die than were women. When gender was controlled, individuals who were older and unmarried and had more alcohol dependence symptoms at baseline were more likely to die over the 16-year period. When these baseline characteristics were controlled, better drinking outcomes at 1 year were associated with a lower likelihood of subsequent death. The combination of a shorter duration of inpatient/residential care and better drinking outcomes at 1 year was related to a lower probability of death, as was the combination of a longer duration of outpatient care or Alcoholics Anonymous attendance and better drinking outcomes at 1 year. Conclusions: Efforts should be made to help providers identify individuals who are not responding positively to inpatient or residential treatment and intervene to motivate participation in continuing outpatient care and community 12-step self-help groups to reduce the likelihood of a chronic and fatal AUD course. [source]

Bedside Detection of Urine ,-Hydroxybutyrate in Diagnosing Metabolic Acidosis

ACADEMIC EMERGENCY MEDICINE, Issue 8 2008
Silas W. Smith MD
Abstract Objectives:, While critically important, the rapid identification of the etiology of metabolic acidosis (MA) may be labor-intensive and time-consuming. Alcoholic, starvation, and severe diabetic ketoacidosis (AKA, SKA, and DKA, respectively) may produce ,-hydroxybutyrate (BOHB) in marked excess of acetone (ACET) and acetoacetate (AcAc). Unfortunately, current urine dipstick technology poorly detects ACET and cannot measure BOHB. The inability to detect BOHB might delay therapy for ketoacidoses or provoke unnecessary evaluation or empiric treatment of other causes of MA, such as toxic alcohol poisoning. The authors tested the previous assertion that commonly available hydrogen peroxide (H2O2) would improve BOHB detection. The effectiveness of alkalinization and use of a silver nitrate (AgNO3) catalyst was also assessed. Methods:, Control and urine test specimens containing from 0.5 to 800 mmol/L ACET, AcAc, and BOHB were prepared. Urine specimens were oxidized with H2O2 (3%) 1:9 (H2O2:urine), alkalinized with potassium hydroxide (KOH; 10%), exposed to AgNO3 sticks, or altered with a combination of these methods in a random fashion. Three emergency physicians (EPs) blinded to the preparation technique evaluated urine dipsticks (Multistix, Bayer Corp.) placed in the specimens for "ketones." Results:, Multistix detected AcAc appropriately; ACET was detected only at high concentrations of ,600 mmol/L. Multistix failed to measure BOHB at all concentrations tested. H2O2 improved urinary BOHB detection, although not to clinically relevant levels (40 mmol/L). Alkalinization and AgNO3 sticks did not improve BOHB detection beyond this threshold. Conclusions:, Addition of H2O2 (3%), alkalinization, or AgNO3 sticks did not improve clinically meaningful urine BOHB detection. Clinicians should use direct methods to detect BOHB when suspected. [source]

Rats bred for high alcohol drinking are more sensitive to delayed and probabilistic outcomes

GENES, BRAIN AND BEHAVIOR, Issue 7 2008
C. J. Wilhelm
Alcoholics and heavy drinkers score higher on measures of impulsivity than nonalcoholics and light drinkers. This may be because of factors that predate drug exposure (e.g. genetics). This study examined the role of genetics by comparing impulsivity measures in ethanol-naive rats selectively bred based on their high [high alcohol drinking (HAD)] or low [low alcohol drinking (LAD)] consumption of ethanol. Replicates 1 and 2 of the HAD and LAD rats, developed by the University of Indiana Alcohol Research Center, completed two different discounting tasks. Delay discounting examines sensitivity to rewards that are delayed in time and is commonly used to assess ,choice' impulsivity. Probability discounting examines sensitivity to the uncertain delivery of rewards and has been used to assess risk taking and risk assessment. High alcohol drinking rats discounted delayed and probabilistic rewards more steeply than LAD rats. Discount rates associated with probabilistic and delayed rewards were weakly correlated, while bias was strongly correlated with discount rate in both delay and probability discounting. The results suggest that selective breeding for high alcohol consumption selects for animals that are more sensitive to delayed and probabilistic outcomes. Sensitivity to delayed or probabilistic outcomes may be predictive of future drinking in genetically predisposed individuals. [source]

ERP and RT Delays in Long-Term Abstinent Alcoholics in Processing of Emotional Facial Expressions During Gender and Emotion Categorization Tasks

ALCOHOLISM, Issue 7 2010
George Fein
Background:, There is considerable evidence that alcoholics differ from nonalcoholics in the processing of stimuli that have emotional content. The current study examines those differences that are present in multi-year abstinent individuals. Methods:, We compared reaction time (RT), accuracy, and Event Related Potentials (ERP) measures in long-term abstinent alcoholics (LTAA, n = 52) with that in age- and gender-comparable nonalcoholic controls (NAC, n = 47). Subjects were presented with male and female faces exhibiting happy, neutral, or sad facial expressions and were instructed to identify the picture gender in 1 task and the emotion being expressed in a subsequent task. Results:, LTAA had slower RTs than NAC when instructed to identify emotion, while RT was comparable when identifying gender. There were no differences between groups on task accuracy. P160 latency was increased in LTAA for both tasks compared to NAC, though P160 amplitude did not differ between groups. The P160 effect was about 5 × as large as the RT effect and was statistically independent of the RT effect, while the RT effect was no longer present after removing variance because of the P160 effect. Conclusions:, Our data demonstrate slower early processing of emotional facial stimuli in alcoholics that is unresolved by long-term abstinence and is most sensitively indexed by delayed P160 latency in LTAA. [source]

Sensation Seeking in Long-Term Abstinent Alcoholics, Treatment-Naïve Active Alcoholics, and Nonalcoholic Controls

ALCOHOLISM, Issue 6 2010
George Fein
Background:, Elevated sensation seeking is associated with the development of alcohol dependence; however, it has not been studied in long-term abstinent alcoholics. In the current study, we examine sensation seeking in middle-aged long-term abstinent alcoholics (LTAA) and in younger actively drinking treatment-naïve alcoholics (TxN). Methods:, A modified version of the Sensation Seeking Scale (SSS) was administered to 52 middle-aged LTAA (average age = 46.6 years) and 86 younger TxN (average age = 31.2 years), each study with its own age and gender comparable nonalcoholic controls (NAC). The SSS was modified to remove items specifically associated with alcohol or drug use. The associations between the SSS and alcohol use and deviance proneness were examined. Results:, The 2 NAC samples did not differ on the SSS, allowing the 2 NAC samples to be combined into a single control group (NAC = 118), and the LTAA and TxN samples to be directly compared without concern for cohort effects. LTAA did not differ from NAC on the SSS; however, the TxN group had higher SSS scores compared with NAC on all subscales except Boredom Susceptibility. Sensation seeking was comparably associated with lower socialization in each group. Conclusions:, The results suggest that either sensation seeking normalizes with long-term abstinence or that relatively normal levels of sensation seeking predict the ability to achieve long-term abstinence. In either case, the results have important implications for our understanding of long-term abstinence. [source]

NeoHepatocytes From Alcoholics and Controls Express Hepatocyte Markers and Display Reduced Fibrogenic TGF-,/Smad3 Signaling: Advantage for Cell Transplantation?

ALCOHOLISM, Issue 4 2010
Sabrina Ehnert
Background:, Liver transplantation is the only definitive treatment for end stage liver disease. Donor organ scarcity raises a growing interest in new therapeutic options. Recently, we have shown that injection of monocyte-derived NeoHepatocytes can increase survival in rats with extended liver resection. In order to apply this technology in humans with chronic liver diseases in an autologous setting, we generated NeoHepatocytes from patients with alcoholic liver disease and healthy controls and compared those to human hepatocytes. Methods:, We generated NeoHepatocytes from alcoholics with Child A and B cirrhosis and healthy controls. Hepatocytes marker expression and transforming growth factor (TGF)-, signaling was investigated by RT-PCR, Western blot, immunofluorescent staining, and adenoviral reporter assays. Glucose and urea was measured photometrically. Phase I and II enzyme activities were measured using fluorogenic substrates. Neutral lipids were visualized by Oil Red O staining. Results:, There was no significant difference in generation and yield of NeoHepatocytes from alcoholics and controls. Hepatocyte markers, e.g., cytokeratin18 and alcohol dehydrogenase 1, increased significantly throughout differentiation. Glucose and urea production did not differ between alcoholics and controls and was comparable to human hepatocytes. During differentiation, phase I and II enzyme activities increased, however remained significantly lower than in human hepatocytes. Fat accumulation was induced by treatment with insulin, TGF-, and ethanol only in differentiated cells and hepatocytes. TGF-, signaling, via Smad transcription factors, critically required for progression of chronic liver disease, was comparable among the investigated cell types, merely expression of Smad1 and -3 was reduced (,30 and ,60%) in monocytes, programmable cells of monocytic origin, and NeoHepatocytes. Subsequently, expression of TGF-, regulated pro-fibrogenic genes, e.g., connective tissue growth factor and fibronectin was reduced. Conclusions:, Generation of NeoHepatocytes from alcoholics, displaying several features of human hepatocytes, offers new perspectives for cell therapeutic approaches, as cells can be obtained repeatedly in a noninvasive manner. Furthermore, the autologous setting reduces the need for immunosuppressants, which may support recovery of patients which are declined for liver transplantation. [source]

Mechanisms of Postural Control in Alcoholic Men and Women: Biomechanical Analysis of Musculoskeletal Coordination During Quiet Standing

ALCOHOLISM, Issue 3 2010
Edith V. Sullivan
Background:, Excessive sway during quiet standing is a common sequela of chronic alcoholism even with prolonged sobriety. Whether alcoholic men and women who have remained abstinent from alcohol for weeks to months differ from each other in the degree of residual postural instability and biomechanical control mechanisms has not been directly tested. Method:, We used a force platform to characterize center-of-pressure biomechanical features of postural sway, with and without stabilizing conditions from touch, vision, and stance, in 34 alcoholic men, 15 alcoholic women, 22 control men, and 29 control women. Groups were matched in age (49.4 years), general intelligence, socioeconomic status, and handedness. Each alcoholic group was sober for an average of 75 days. Results:, Analysis of postural sway when using all 3 stabilizing conditions versus none revealed diagnosis and sex differences in ability to balance. Alcoholics had significantly longer sway paths, especially in the anterior,posterior direction, than controls when maintaining erect posture without balance aids. With stabilizing conditions the sway paths of all groups shortened significantly, especially those of alcoholic men, who demonstrated a 3.1-fold improvement in sway path difference between the easiest and most challenging conditions; the remaining 3 groups, each showed a ,2.4-fold improvement. Application of a mechanical model to partition sway paths into open-loop and closed-loop postural control systems revealed that the sway paths of the alcoholic men but not alcoholic women were characterized by greater short-term (open-loop) diffusion coefficients without aids, often associated with muscle stiffening response. With stabilizing factors, all 4 groups showed similar long-term (closed loop) postural control. Correlations between cognitive abilities and closed-loop sway indices were more robust in alcoholic men than alcoholic women. Conclusions:, Reduction in sway and closed-loop activity during quiet standing with stabilizing factors shows some differential expression in men and women with histories of alcohol dependence. Nonetheless, enduring deficits in postural instability of both alcoholic men and alcoholic women suggest persisting liability for falling. [source]

Greater Activation in Left Hemisphere Language-Related Regions During Simple Judgment Tasks Among Substance-Dependent Patients in Treatment for Alcoholism

ALCOHOLISM, Issue 2 2010
Jodi M. Gilman
Background:, Alcoholism is often associated with impaired emotional control. Alcoholics have also been found to have deficits in frontal lobe executive functions. Recent functional imaging studies have suggested that alcoholics show greater activation than nonalcoholics in circuits involving frontal lobes, as well as more posterior brain regions, when engaged in executive-type tasks. In this study, we compared brain activations of alcohol-dependent patients and healthy nonalcoholics while they performed 2 simple judgment tasks designed to activate frontal circuits involved in a basic form of decision making. Participants completed 1 judgment task that required an emotional judgment and 1 task that did not, which enabled us to study whether alcoholics had greater brain activation while performing executive tasks, and to determine if emotional tasks elicited even greater activation than nonemotional tasks. Methods:, We performed functional magnetic resonance imaging scans while alcoholic patients and nonalcoholic controls viewed pictures from the International Affective Picture System. In 3 separate runs, participants viewed the images without making a judgment, determined whether the images were indoor or outdoor scenes, or decided if they liked or disliked the images. Results:, There was little difference in brain activation between alcoholics and controls when no judgment was required. When participants made judgments about either the location or whether they liked or disliked an image, however, we observed significantly increased activation in frontal, limbic, and temporal regions in the patients relative to the controls. Increases were particularly robust in the frontal lobe and in areas of the brain associated with language. When we compared the emotional to the nonemotional judgment, the alcoholics, but not the controls, showed greater activation in the ventral mesial frontal cortex. Conclusions:, Alcoholic patients appear to use brain language areas more than nonalcoholics while making judgments about the setting or liking of emotionally arousing visual images. This increased activation may reflect a compensatory recruitment of brain regions to perform simple decision-making tasks. [source]

The Interaction of Reward Genes With Environmental Factors in Contribution to Alcoholism in Mexican Americans

ALCOHOLISM, Issue 12 2009
Yanlei Du
Background:, Alcoholism is a polygenic disorder resulting from reward deficiency; polymorphisms in reward genes including serotonin transporter (5-HTT)-linked polymorphic region (5-HTTLPR), A118G in opioid receptor mu1 (OPRM1), and ,141C Insertion/Deletion (Ins/Del) in dopamine receptor D2 (DRD2) as well as environmental factors (education and marital status) might affect the risk of alcoholism. Objective of the current study was to examine the main and interacting effect of these 3 polymorphisms and 2 environmental factors in contribution to alcoholism in Mexican Americans. Methods:, Genotyping of 5-HTTLPR, OPRM1 A118G, and DRD2-141C Ins/Del was performed in 365 alcoholics and 338 nonalcoholic controls of Mexican Americans who were gender- and age-matched. Alcoholics were stratified according to tertiles of MAXDRINKS, which denotes the largest number of drinks consumed in one 24-hour period. Data analysis was done in the entire data set and in each alcoholic stratum. Multinomial logistic regression was conducted to explore the main effect of 3 polymorphisms and 2 environmental factors (education and marital status); classification tree, generalized multifactor dimensionality reduction (GMDR) analysis, and polymorphism interaction analysis version 2.0 (PIA 2) program were used to study factor interaction. Results:, Main effect of education, OPRM1, and DRD2 was detected in alcoholic stratum of moderate and/or largest MAXDRINKS with education ,12 years, OPRM1 118 A/A, and DRD2 ,141C Ins/Ins being risk factors. Classification tree analysis, GMDR analysis, and PIA 2 program all supported education*OPRM1 interaction in alcoholics of largest MAXDRINKS with education ,12 years coupled with OPRM1 A/A being a high risk factor; dendrogram showed synergistic interaction between these 2 factors; dosage-effect response was also observed for education*OPRM1 interaction. No definite effect of marital status and 5-HTTLPR in pathogenesis of alcoholism was observed. Conclusions:, Our results suggest main effect of education background, OPRM1 A118G, and DRD2 ,141C Ins/Del as well as education*OPRM1 interaction in contribution to moderate and/or severe alcoholism in Mexican Americans. Functional relevance of these findings still needs to be explored. [source]

Ethical Considerations for Administering Alcohol or Alcohol Cues to Treatment-Seeking Alcoholics in a Research Setting: Can the Benefits to Society Outweigh the Risks to the Individual?

ALCOHOLISM, Issue 9 2009
A commentary in the context of the National Advisory Council on Alcohol Abuse, Alcoholism, Recommended Council Guidelines on Ethyl Alcohol Administration in Human Experimentation (2005)
First page of article [source]

Imaging of Language-Related Brain Regions in Detoxified Alcoholics

Association Between Personality Traits and ALDH2 Polymorphism in Japanese Male Alcoholics

ALCOHOLISM, Issue 5 2009
Mitsuru Kimura
Background:, Alcoholics who have developed alcoholism despite a strong negative risk factor, that is, the inactive form of aldehyde dehydrogenase-2 (ALDH2), are considered advantageous for studying predisposing factors for alcoholism. This study aimed to compare personality profiles and clinical characteristics between alcoholics with active and inactive ALDH2. Methods:, Subjects were 460 male Japanese alcoholics hospitalized in Kurihama Alcoholism Center. All patients underwent Cloninger's Tridimensional Personality Questionnaire and semi-structured interviews 4 to 8 weeks after admission to obtain data on personalities and clinical characteristics. ALDH2 genotypes were determined by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. Sixty-six patients had the inactive form of ALDH2 (ALDH2*1/2*2) and 394 had the active form (ALDH2*1/2*1). Results:, Alcoholics with inactive ALDH2 had significantly higher novelty-seeking (NS) and lower harm-avoidance (HA) scores compared with those with active ALDH2. The inactive ALDH2 group experienced delirium tremens significantly less frequently than the active ALDH2 group. Conclusions:, These results suggest that high NS and low HA scores in alcoholics with inactive ALDH2 are associated with an increased risk for developing alcoholism, despite a low enzymatic ability to eliminate toxic acetaldehyde in these subjects. A study of alcoholics with inactive ALDH2 is useful for detecting environmental or personality factors related to alcoholism. [source]

Influence of Antisocial and Psychopathic Traits on Decision-Making Biases in Alcoholics

ALCOHOLISM, Issue 5 2009
Robert Miranda Jr
Background:, Although decision-making processes have become a principal target of study among addiction researchers, few studies have specifically examined decision-making among individuals with alcohol dependence (AD) and findings to date are mixed. The present study examined the relationship between AD and decision-making, and tested whether different facets of antisocial and psychopathic traits explain this association. Methods:, Participants were men with AD (n = 22), AD and comorbid antisocial personality disorder (AD + ASPD; n = 17), or a history of recreational alcohol use, but no current or lifetime symptoms of a substance use disorder, conduct disorder, or ASPD (n = 21). Decision-making was tested using the Iowa Gambling Task (IGT). Results:, Across groups, participants reported similar levels of awareness of the contingencies of the task, but the AD groups with and without ASPD had poorer IGT performance compared with controls (p < 0.05). A block-by-block analysis revealed that while AD had slow but steady improvement across the task, AD + ASPD exhibited initial improvement followed by a significant decrease in advantageous decision-making during the last 20 trials (p < 0.05). This was further confirmed via evidence that impulsive/antisocial personality traits but not psychopathic traits mediated poor IGT performance beyond ASPD diagnosis. Conclusions:, Alcohol-dependent males favored risky choices regardless of whether they met criteria for ASPD. However, decision-making deficits were more pronounced among those with ASPD, and personality traits characterized by impulsive and antisocial tendencies mediated the relationship between AD and decision-making. [source]

Global,Local Interference is Related to Callosal Compromise in Alcoholism: A Behavior-DTI Association Study

ALCOHOLISM, Issue 3 2009
Eva M. Müller-Oehring
Background:, Visuospatial ability is a multifactorial process commonly impaired in chronic alcoholism. Identification of which features of visuospatial processing are affected and which are spared in alcoholism, however, has not been clearly determined. We used a global,local paradigm to assess component processes of visuospatial ability and MR diffusion tensor imaging (DTI) to examine whether alcoholism-related microstructural degradation of the corpus callosum contributes to disruption of selective lateralized visuospatial and attention processes. Methods:, A hierarchical letter paradigm was devised, where large global letters were composed of small local letters. The task required identification of target letters among distractors presented at global, local, both, or neither level. Attention was either selectively directed to global or local levels or divided between levels. Participants were 18 detoxified chronic alcoholics and 22 age-matched healthy controls. DTI provided quantitative assessment of the integrity of corpus callosal white matter microstructure. Results:, Alcoholics generally had longer reaction times than controls but obtained similar accuracy scores. Both groups processed local targets faster than global targets and showed interference from targets at the unattended level. Alcoholics exhibited moderate compromise in selectively attending to the global level when the global stimuli were composed of local targets. Such local interference was less with longer abstinence. Callosal microstructural integrity compromise predicted degree of interference from stimulus incongruency in the alcoholic group. This relationship was not observed for lateral or third ventricular volumes, which are measures of nonspecific cortical volume deficits. Conclusion:, Global,local feature perception was generally spared in abstinent chronic alcoholics, but impairments were observed when directing attention to global features and when global and local information interfered at stimulus or response levels. Furthermore, the interference-callosal integrity relationship in alcoholics indicates that compromised visuospatial functions include those requiring bilateral integration of information. [source]

Changes in the Episodic Memory and Executive Functions of Abstinent and Relapsed Alcoholics Over a 6-Month Period

ALCOHOLISM, Issue 3 2009
Anne Lise Pitel
Background:, It is still unclear whether episodic memory and executive functions capacities can return to normal in abstinent patients over a 6-month period. Furthermore, the role of interim drinking in cognitive recovery is still not well known. Finally, further research is required to specify the predictive value of cognitive abilities at initial testing in the treatment outcome (abstinence or relapse). The aims of the present study were therefore to measure changes in episodic memory and executive functions over a 6-month period in abstinent and relapsed alcoholics and to ascertain whether neuropsychological results at treatment entry can predict treatment outcome at follow-up. Methods:, Fifty-four alcoholic patients and 54 matched control subjects performed baseline neuropsychological tasks assessing episodic memory, executive functions, the slave systems of working memory and attentional abilities. At the follow-up session (i.e., 6 months later), episodic memory and 3 executive functions (inhibition, flexibility, and updating) were re-examined in the alcoholic patients. Results:, Results showed that over the 6-month interval, the abstainers' episodic memory and executive performances had returned to normal, whereas the relapsers performed lower than before in the flexibility task. Episodic memory and executive functions recovery was correlated, in abstainers, with drinking history and age respectively. Finally, there was no significant difference regarding neuropsychological scores at baseline between abstainers and relapsers. Discussion:, Over the 6-month interval, abstainers normalized episodic memory and executive performances whereas relapsers obtained executive results which were more severely impaired, emphasizing the influence of interim drinking on cognitive changes. Episodic memory, executive functions, the slave systems of working memory and attentional abilities did not appear to be reliable predictors of treatment outcome over a 6-month interval. [source]

Alcohol Functionally Upregulates Toll-Like Receptor 2 in Airway Epithelial Cells

ALCOHOLISM, Issue 3 2009
Kristina L. Bailey
Background:, Alcoholics are known to have more severe airway diseases of the lung, such as bronchitis. Little is known about why this phenomenon is observed. We hypothesized that alcohol may modulate Toll-like receptor 2 (TLR2), which regulates inflammation caused by gram-positive bacteria. Methods:, Airway epithelial cells [primary bronchial epithelial cells (NHBE) and 16HBE 14o-] were exposed to 0 to 100 mM alcohol for 0 to 24 hours. Real time PCR was used to quantify TLR2 mRNA. Protein levels of TLR2 were determined using Western blots and fluorescence activated cell sorting (FACS) on cells exposed to 0, 50, and 100 mM alcohol. Finally, cells were "primed" with alcohol, stimulated with a TLR2 agonist (peptidoglycan), and interleukin 8 (IL-8) release was measured. Results:, Alcohol, at biologically relevant concentrations (25 to 100 mM), caused a 2 to 3-fold time- and concentration-dependent increase in TLR2 mRNA in normal human bronchial epithelial cells and 16HBE 14o- cells. Western blots for TLR2 revealed a qualitative increase in TLR2 protein in cells exposed to 100 mM alcohol. FACS showed that TLR2 was quantitatively increased on the surface of airway epithelial cells that were exposed to alcohol. Airway cells that were primed with alcohol produced nearly twice as much IL-8 in response to 40 ng of peptidoglycan than naive cells. Conclusions:, Alcohol upregulates TLR2 message and protein in the airway epithelium. This leads to exaggerated inflammation in response to environmental stimuli that would normally be well tolerated in airway epithelial cells. This may be a partial explanation of why alcoholics have more severe airway disease than nonalcoholics. [source]

Alterations in Brain Serotonin Synthesis in Male Alcoholics Measured Using Positron Emission Tomography

ALCOHOLISM, Issue 2 2009
Masami Nishikawa
Background:, A consistent association between low endogenous 5HT function and high alcohol preference has been observed, and a number of serotonergic manipulations (uptake blockers, agonists) alter alcohol consumption in animals and humans. Studies have also shown an inverse relationship between alcohol use and cerebrospinal fluid levels of serotonin metabolites, suggesting that chronic alcohol consumption produces alterations in serotonin synthesis or release. Methods:, The objective of the study was to characterize regional brain serotonin synthesis in nondepressed chronic alcoholics at treatment entry in comparison to normal nonalcoholic controls using PET and the tracer ,-[11C]-methyl- l -tryptophan. Results:, Comparisons of the alcoholics and controls by SPM found that there were significant differences in the rate of serotonin synthesis between groups. Serotonin synthesis was significantly lower among alcoholics in Brodmann Area (BA) 9, 10, and 32. However, serotonin synthesis among the alcoholics group was significantly higher than controls at BA19 in the occipital lobe and around the transverse temporal convolution in the left superior temporal gyrus (BA41). In addition, there were correlations between regional serotonin synthesis and a quantity-frequency measure of alcohol consumption. Regions showing a significant negative correlation with QF included the bilateral rectus gyri (BA11) in the orbitofrontal area, the bilateral medial frontal area (BA6), and the right amygdala. Conclusions:, Current alcoholism is associated with serotonergic abnormalities in brain regions that are known to be involved in planning, judgment, self-control, and emotional regulation. [source]

Increased White Matter Signal Hyperintensities in Long-Term Abstinent Alcoholics Compared with Nonalcoholic Controls

ALCOHOLISM, Issue 1 2009
George Fein
Background:, The harmful effects of alcohol dependence on brain structure and function have been well documented, with many resolving with sufficient abstinence. White matter signal hyperintensities (WMSH) are thought to most likely be consequences secondary to the vascular (i.e., hypertension and atherosclerosis) effects of AD. We hypothesized that such effects would persist into long-term abstinence, and evaluated them in middle-aged long-term abstinent alcoholics (LTAA) compared with age and gender comparable nonalcoholic controls (NAC). Methods:, Ninety-seven participants (51 LTAA and 46 NAC) underwent cognitive, psychiatric, and structural brain magnetic resonance image evaluations. WMSH were identified and labeled as deep or periventricular by an automated algorithm developed in-house. WMSH volumes were compared between groups, and the associations of WMSH measures with demographic, alcohol use, psychiatric, and cognitive measures were examined within group. Results:, Long-term abstinent alcoholics had more WMSH than NAC. There was a significant group by age interaction, with WMSH increasing with age in LTAA, but not in NAC. Within LTAA, WMSH load was independently positively associated with alcohol burden and with age. No associations were evident between WMSH volumes and abstinence duration, family drinking history, years of education, or psychiatric or cognitive variables. Conclusion:, The magnitude of alcohol abuse was related to increased WMSH volume. The presence of an age effect in the LTAA but not the controls indicates a synergistic effect wherein alcohol advances the onset of aging-related WMSH formation. The increased WMSH load did not appear to have any significant clinical correlates, indicating that the white matter lesions in our sample may not have been severe enough to manifest as cognitive deficits. A limitation of the study is that we did not have data on the presence or severity of lifetime or current indices of vascular risk factors such as hypertension, smoking, or diabetes. [source]

Upregulation of ,-Catenin Levels in Superior Frontal Cortex of Chronic Alcoholics

ALCOHOLISM, Issue 6 2008
Ali M. Al-Housseini
Background:, Chronic and excessive alcohol misuse results in neuroadaptive changes in the brain. The complex nature of behavioral, psychological, emotional, and neuropathological characteristics associated with alcoholism is likely a reflection of the network of proteins that are affected by alcohol-induced gene expression patterns in specific brain regions. At the molecular level, however, knowledge remains limited regarding alterations in protein expression levels affected by chronic alcohol abuse. Thus, novel techniques that allow a comprehensive assessment of this complexity will enable the simultaneous assessment of changes across a group of proteins in the relevant neural circuitry. Methods:, A proteomics analysis was performed using antibody microarrays to determine differential protein levels in superior frontal cortices between chronic alcoholics and age- and gender-matched control subjects. Seventeen proteins related to the catenin signaling pathway were analyzed, including ,-, ,-, and ,-catenins, their upstream activators cadherin-3 (type I cadherin) and cadherin-5 (type II cadherin), and 5 cytoplasmic regulators c-Src, CK1,, GSK-3,, PP2A-C,, and APC, as well as the nuclear complex partner of ,-catenin CBP and 2 downstream genes Myc and cyclin D1. ILK, G,1, G,1, and G,2, which are activity regulators of GSK-3,, were also analyzed. Results:, Both ,- and ,-catenin showed significantly increased levels, while ,-catenin did not change significantly, in chronic alcoholics. In addition, the level of the ,-catenin downstream gene product Myc was significantly increased. Average levels of the catenin regulators c-Src, CK1,, and APC were also increased in chronic alcoholics, but the changes were not statistically significant. Conclusion:, Chronic and excessive alcohol consumption leads to an upregulation of ,- and ,-catenin levels, which in turn increase downstream gene expressions such as Myc that is controlled by ,-catenin signaling. This study showed that the ,-catenin signal transduction pathway was upregulated by chronic alcohol abuse, and prompts further investigation of mechanisms underlying the upregulation of ,- and ,-catenins in alcoholism, which may have considerable pathogenic and therapeutic relevance. [source]

Blunted Rostral Anterior Cingulate Response During a Simplified Decoding Task of Negative Emotional Facial Expressions in Alcoholic Patients

ALCOHOLISM, Issue 9 2007
Jasmin B. Salloum
Background:, Alcoholism is characterized by deficits in emotional functioning as well as by deficits in cognitive functioning. However, most brain imaging research on alcoholism has focused on cognition rather than emotion. Method:, We used an event-related functional magnetic imaging approach to examine alcoholics' brain blood oxygenation level dependent (BOLD) response to evaluation of emotional stimuli and to compare their response to that of nonalcoholic controls. The task used was a simplified variant of a facial emotion-decoding task in which subjects determined the intensity level of a target emotion displayed as a facial expression. Facial expressions of happy, sad, anger, disgust, and fear were used as stimuli. Results:, Alcoholics and controls did not differ in accurately identifying the intensity level on the simple emotional decoding task but there were significant differences in their BOLD response during evaluation of facial emotion. In general, alcoholics showed less brain activation than nonalcoholic controls. The greatest differences in activation were during decoding of facial expressions of fear and disgust during which alcoholics had significantly less activation than controls in the affective division of the anterior cingulate cortex (ACC). Alcoholics also had significantly less activation than controls in the affective division of the ACC, while viewing sad faces. Only to facial expressions of anger did the alcoholics show significant activation in the affective ACC and in this case, their BOLD response did not significantly differ from that of the controls. Conclusion:, Alcoholics show a deficit in the function of the affective division of the ACC during evaluation of negative facial emotions that can serve as cues for flight or avoidance. This deficit may underlie some of the behavioral dysfunction in alcoholism. [source]

Increased Interleukin-10 and Cortisol in Long-term Alcoholics after Cardiopulmonary Bypass: A Hint to the Increased Postoperative Infection Rate?

ALCOHOLISM, Issue 9 2005
Michael Sander
Background: Previous studies have shown that 20% of all patients admitted to the hospital abuse alcohol and have increased morbidity after surgery. Long-term alcoholic patients are shown to suffer from immune alterations, which might be critical for adequate postoperative performance. Cardiac surgery with cardiopulmonary bypass (CPB) also leads to pronounced immune alteration, which might be linked with patients' ability to combat infections. Therefore, the aim of our study was to investigate the perioperative levels of TNF-alpha, interleukin-6, interleukin-10, and cortisol in long-term alcoholic and nonalcoholic patients undergoing cardiac surgery to elucidate a possible association with postoperative infections. Methods: Forty-four patients undergoing elective cardiac surgery were included in this prospective study. Long-term alcoholic patients (n= 10) were defined as having a daily ethanol consumption of at least 60 g and fulfilling the Diagnostic and Statistical Manual of Mental Disorders for alcohol abuse. The nonalcoholic patients (n= 34) were defined as drinking less than 20 g ethanol per day. Blood samples were obtained to analyze the immune status upon admission to hospital, the morning before surgery and on admission to the ICU, the morning of days one and three after surgery. Results: Basic characteristics of patients did not differ between groups. Long-term alcoholics had a fourfold increase in postsurgery infection rate and prolonged need for ICU treatment and mechanical ventilation. Postoperative levels of interleukin-10 and cortisol were significantly increased in long-term alcoholic patients compared with nonalcoholic patients. These observations were in line with postoperative interleukin-10 being predictive for postoperative infectious complications. Conclusions: The increased infection rate in long-term alcoholics strengthens the urgent need for interventional approaches providing modulation of the perioperative immune and HPA response in these high-risk patients to counteract their postoperative immune suppression. [source]

The Pathophysiology of ,Brain Shrinkage' in Alcoholics , Structural and Molecular Changes and Clinical Implications

ALCOHOLISM, Issue 6 2005
Clive Harper
This article represents a symposium of the 2004 ISBRA Congress held in Mannheim. The presentations were: Review of the neuropathological and neurochemical changes seen in alcohol-related ,brain shrinkage' by Clive Harper; In Vivo Detection of Macrostructural and Microstructural Markers of Brain Integrity in Human Alcoholism and a Rodent Model of Alcoholism by Adolf Pfefferbaum, Elfar Adalsteinsson and Edith Sullivan; Gene and Protein Changes in the Brains of Alcoholics with ,Brain Shrinkage' by Joanne Lewohl and Peter Dodd; Cross sectional and longitudinal MR spectroscopy studies of chronic adult alcoholics by Michael Taylor; Brain Atrophy Associated with Impairment on a Simulated Gambling Task in Long-Term Abstinent Alcoholics by George Fein and Bennett Landman. [source]

Smoke Exposure Exacerbates an Ethanol-Induced Defect in Mucociliary Clearance of Streptococcus pneumoniae

ALCOHOLISM, Issue 5 2005
Elizabeth A. Vander Top
Background: Alcoholics and smokers are particularly susceptible to pulmonary infections caused by Streptococcus pneumoniae, the pneumococcus. Infection begins when pneumococci colonizing the nasopharynx are aspirated into the lower respiratory tract. The major host defense against this movement is the mucociliary clearance apparatus. Both cigarette smoke and ethanol (EtOH) exposure alter ciliary beating and protein kinase activity in the respiratory mucosa in vitro, but their effects on bacterial clearance in the intact animal have not been determined. Methods: Male Sprague Dawley rats were exposed twice daily for 12 weeks to either the smoke generated from 30 cigarettes (smoke,exposed) or room air (sham,exposed). For the last five weeks of smoke exposure, the rats were fed Lieber-DeCarli liquid diets containing 0%, 16%, 26%, or 36% EtOH calories. The rats then were infected intranasally with S. pneumoniae, and movement of the organisms into the lower respiratory tract was quantified by plate counts of the tracheas and lungs 4 hr later. Ciliary beat frequency (CBF) analysis was performed on tracheal ring explants from each animal before and after stimulation with the ,-agonist isoproterenol, and tracheal epithelial cell protein kinase C (PKC) activity was measured. Results: Ingestion of any of the EtOH-containing diets resulted in a dose-dependent increase in movement of S. pneumoniae into the rats' lungs. This EtOH-induced defect was augmented further by concurrent smoke exposure, although smoke exposure alone had little effect on S. pneumoniae movement. Smoke, but not EtOH exposure, activated tracheal epithelial cell PKC. Increased movement of organisms into lungs correlated with a decrease in CBF and loss of the ciliary response to isoproterenol. Conclusion: EtOH ingestion in our model facilitated movement of S. pneumoniae into rats' lungs, a phenomenon exacerbated by concurrent smoke exposure. Furthermore, the organism's movement into the lungs correlated with a blunting of the rats' ciliary response to an established stimulus. Defects in mucociliary clearance thus may be one cause of the increased risk of pneumococcal infections in people who abuse alcohol, particularly if they also smoke. [source]

Psychiatric Comorbidity in Treatment-Seeking Alcoholics: The Role of Childhood Trauma and Perceived Parental Dysfunction

ALCOHOLISM, Issue 3 2004
Willie Langeland
Abstract: Background: This study among treatment-seeking alcoholics examined the relationship between childhood abuse (sexual abuse only [CSA], physical abuse only [CPA], or dual abuse [CDA]) and the presence of comorbid affective disorders, anxiety disorders, and suicide attempts, controlling for the potential confounding effects of other childhood adversities (early parental loss, witnessing domestic violence, parental alcoholism, and/or dysfunction) and adult assault histories. Method: We assessed 155 (33 females, 122 males) treatment-seeking alcoholics using the European Addiction Severity Index, the Structured Trauma Interview, and the Composite International Diagnostic Interview. Results: The severity of childhood abuse was associated with posttraumatic stress disorder (PTSD) and suicide attempts in females and with PTSD, social phobia, agoraphobia, and dysthymia in males. Among men, multiple logistic regression models showed that CPA and CDA were not independently associated with any of the examined comorbid disorders or with suicide attempts. However, CSA independently predicted comorbid social phobia, agoraphobia, and PTSD. For the presence of comorbid affective disorders (mainly major depression) and suicide attempts, maternal dysfunctioning was particularly important. CSA also independently contributed to the number of comorbid diagnoses. For females, small sample size precluded the use of multivariate analyses. Conclusion: Childhood abuse is an important factor in understanding clinical impairment in treated alcoholics, especially regarding comorbid phobic anxiety disorders, PTSD, and suicidality. These findings underline the importance of routine assessment of childhood trauma and possible trauma-related disorders in individuals presenting to alcohol treatment services. More studies with bigger samples sizes of female alcohol-dependent patients are needed. [source]

Mismatch Negativity: No Difference Between Controls and Abstinent Alcoholics

ALCOHOLISM, Issue 1 2004
George Fein
Abstract: Background: A number of studies have examined the amplitude of the mismatch negativity (MMN) evoked potential as a measure of a brain inhibitory deficit in alcoholics or those at risk for alcoholism. The current study examined MMN in alcoholics abstinent an average of 6.7 years (with a minimum of six months abstinence) compared to controls. This study examined the association of MMN with alcoholism family history density, with indices of the presence and severity of externalizing disorders (a risk-factor for alcoholism), and with alcohol use variables. Methods: Electroencephalograms were gathered on 76 subjects (38 controls, 38 abstinent alcoholics) during a nonattending mismatch negativity experiment. Measures of alcoholism family history density, disinhibited personality traits, and antisocial symptoms served as measures of risk-factors known to be associated with a genetic liability to alcoholism. Alcohol use variables were used as measures of alcoholism severity. Results: There were no differences in MMN amplitude or latency between controls and abstinent alcoholics. There also were no significant associations between MMN measures and the measures of risk for alcoholism or with the severity of alcohol use or duration of abstinence. Conclusions: The results suggest that MMN is neither affected in chronic alcoholics nor associated with alcoholism vulnerability, and thus does not reflect a trait marker of alcoholism or alcoholism risk. The current results do not address effects on MMN of acute alcohol ingestion or withdrawal from alcohol. [source]

Leptin and Cellular and Innate Immunity in Abstinent Alcoholics and Controls

ALCOHOLISM, Issue 11 2003
Sarosh J. Motivala
Background: Basic studies indicate that in vitro and in vivo doses of leptin modulate cellular immune responses. Given evidence that concentrations of leptin are altered in alcoholics who also show immune abnormalities, this study examined the relationships between circulating levels of leptin and markers of cellular and innate immunity. Methods: Circulating levels of leptin, natural killer cell (NK) activity, interleukin-2 (IL-2),stimulated NK activity, and concanavalin A,stimulated production of IL-2, IL-6, IL-10, and IL-12 were compared between abstinent DSM-IV alcohol-dependent men (n= 27) and age- and gender-matched controls (n= 34). Results: As compared with controls, alcoholics showed lower NK activity (p < 0.01) and a trend for lower levels of leptin (p= 0.055). In the total sample, leptin predicted NK activity (,= 0.33; p < 0.05) after controlling for the confounding influence of body mass index, alcohol intake, and smoking. Leptin was not correlated with any of the cytokine measures. To examine whether the effects of leptin were mediated by its direct action on NK, additional studies examined in vitro effects of leptin on NK activity in healthy volunteers (n= 10); leptin doses (0.1, 1, and 10 nM) yielded levels of NK activity comparable to those with media alone. Conclusions: These data show that circulating levels of leptin are associated with NK activity in humans and suggest that abnormal in vivo concentrations of leptin may contribute to the declines of NK activity in alcoholics who are at risk for infectious diseases. [source]

Longitudinal Brain Metabolic Characterization of Chronic Alcoholics With Proton Magnetic Resonance Spectroscopy

ALCOHOLISM, Issue 9 2002
Mitchell H. Parks
Background Proton magnetic resonance spectroscopy may elucidate the molecular underpinnings of alcoholism-associated brain shrinkage and the progression of alcohol dependence. Methods Using proton magnetic resonance spectroscopy, we determined absolute concentrations of N -acetylaspartate (NAA), creatine/phosphocreatine (Cr), and choline (Cho)-containing compounds and myo -inositol (mI) in the anterior superior cerebellar vermis and frontal lobe white matter in 31 alcoholics and 12 normal controls. All patients were examined within 3 to 5 days of their last drink. Patients who did not relapse were again studied after 3 weeks and 3 months of abstinence by using an on-line repositioning technique that allows reliable localization of volumes of interest (VOIs). Results At 3 to 5 days after the last drink, frontal white matter metabolite concentrations were not significantly different from those of normal controls, whereas brain tissue in the VOI was reduced. Cerebellar [NAA] and [Cho] and brain and cerebellar volumes were decreased, but [Cr], [mI], and VOI brain tissue volume were not significantly different. Eight patients relapsed before 3 weeks (ER), 12 relapsed between 3 weeks and 3 months (LR), and 11 did not relapse (NR) during 3 months. Cerebellar [NAA] was reduced only in ER patients, despite the fact that ER patients drank for significantly fewer years and earlier in life than LR or NR patients. After 3 months, in the 11 continuously abstinent patients, cerebellar [NAA] and brain and cerebellar volumes increased; cerebellar [Cho], [Cr], and [mI] and VOI brain tissue did not change significantly. Conclusions Decreased [NAA] and [Cho] in cerebellar vermis indicate a unique sensitivity to alcohol-induced brain injury. Cerebellar [NAA] increased with abstinence, but reduced [Cho] persisted beyond 3 months. Further studies are needed to determine whether low cerebellar [NAA] is a risk factor for, or consequence of, malignant, early-onset alcoholism. [source]