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CORK Bibliography: Alcohol. Chronic Effects

98 citations. January 2008 to present

Prepared: June 2009

Al-Housseini AM; Sivanandam TM; Bradbury EL; Tannenberg RK; Dodd PR; Gu Q. Upregulation of beta-catenin levels in superior frontal cortex of chronic alcoholics. (review). Alcoholism: Clinical and Experimental Research 32(6): 1080-1090, 2008. (106 refs.)

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 alpha-, beta-, and delta-catenins, their upstream activators cadherin-3 (type I cadherin) and cadherin-5 (type II cadherin), and 5 cytoplasmic regulators c-Src, CK1 epsilon, GSK-3 beta, PP2A-C alpha, and APC, as well as the nuclear complex partner of beta-catenin CBP and 2 downstream genes Myc and cyclin D1. ILK, G(alpha 1), G(beta 1), and G(beta 2), which are activity regulators of GSK-3 beta, were also analyzed. Results: Both alpha- and beta-catenin showed significantly increased levels, while delta-catenin did not change significantly, in chronic alcoholics. In addition, the level of the beta-catenin downstream gene product Myc was significantly increased. Average levels of the catenin regulators c-Src, CK1 epsilon, 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 alpha- and beta-catenin levels, which in turn increase downstream gene expressions such as Myc that is controlled by beta-catenin signaling. This study showed that the beta-catenin signal transduction pathway was upregulated by chronic alcohol abuse, and prompts further investigation of mechanisms underlying the upregulation of alpha- and beta-catenins in alcoholism, which may have considerable pathogenic and therapeutic relevance.

Auguet T; Vidal F; Lopez-Dupla M; Broch M; Gutierrez C; Olona M et al. A study on the TNF-alpha system in Caucasian Spanish patients with alcoholic liver disease. Drug and Alcohol Dependence 92(1/3): 91-99, 2008. (56 refs.)

Background: Tumor necrosis factor-alpha (TNF-alpha) is thought to be a critical driving force of inflammatory damage in alcoholic liver disease (ALD). We aimed to establish whether there is a correlation between plasma levels of the soluble TNF-alpha receptors 1 and 2 (sTNFR1 and sTNFR2) and the severity of liver damage in patients with ALD. We also aimed to elucidate whether functionally active polymorphisms in the promoter region of the TNF-alpha gene modulate the development of ALD. Design: We studied 614 Spaniards. Of these, 278 were alcoholics (103 without liver histologic abnormalities, 89 with non-cirrhotic liver disease and 86 with cirrhosis) and 336 were non-alcoholics (115 healthy controls, 114 with non-alcoholic non-cirrhotic liver disease and 107 with cirrhosis unrelated to alcohol). Plasma levels of sTNFR1 and sTNFR2 were determined by ELISA and results were expressed in ng/mL and subsequently converted in log(10). TNF-alpha gene promoter region polymorphisms at the positions -238, -308 and -863 were assessed by restriction fragment length polymorphisms (RFLPs) on white cell DNA. Differences in plasma sTNFR1 and sTNFR2 levels between groups were compared with the one-way and two-factor analysis of variance test, and Student's t-test. Genotype distribution and allele frequencies in the different groups were compared using the chi(2) test or Fisher's exact test. Results: sTNFR1 and sTNFR2 plasma levels were significantly higher in patients with cirrhosis than in those with non-cirrhotic liver disease (p < 0.001) and individuals without liver disease (p < 0.001), both in the alcoholic and the non-alcoholic group. Among cirrhotics, sTNFR1 and sTNFR2 levels had a significant positive correlation with the severity of the liver disease, graded with the Child-Pugh's score (P = 0.003 and p < 0.001, respectively). TNF-alpha genotype distribution and allele frequencies of the three loci assessed were similar in the groups studied, hence no particular genotype or haplotype could be linked to ALD. Conclusions: The TNF-alpha system is activated in patients with cirrhosis of the liver irrespective of aetiology. TNF-alpha polymorphisms at positions -238, -308 and -863 are not linked to ALD.

Badaoui A; De Saeger C; Duchemin J; Gihousse D; de Timary P; Starkel P. Alcohol dependence is associated with reduced plasma and fundic ghrelin levels. European Journal of Clinical Investigation 38(6): 397-403, 2008. (27 refs.)

Background Conflicting data concerning the involvement of ghrelin in the pathophysiology of alcohol dependence have been reported. The aim of this study is to investigate how chronic alcohol ingestion influences plasma ghrelin levels and whether potential changes observed in plasma relate to modifications in ghrelin production in the stomach where this peptide is primarily synthesized. Materials and methods Fifty-one consecutive alcoholics admitted for alcohol withdrawal were prospectively enrolled and compared to a control group of 32 healthy volunteers matched for age, sex, height and weight. All subjects underwent fasting plasma ghrelin determination. Twenty-seven randomly selected alcoholics and 17 controls underwent gastroscopy for fundic and duodenal biopsies. Tissues were fixed for histology or frozen in liquid nitrogen for ghrelin protein and mRNA determinations by a radioimmunoassay and quantitative polymerase chain reaction, respectively. Alcohol consumption was normalized to body weight (BW) or body mass index (BMI) given the influence of BW and volume distribution on alcohol levels. Results Plasma and fundic ghrelin protein levels were significantly decreased in alcoholics. Fundic but not plasma ghrelin protein levels inversely correlated with alcohol consumption normalized to BW or BMI. Ghrelin mRNA levels in fundic biopsies were similar in alcoholics and controls. No significant differences in duodenal ghrelin protein and mRNA levels were found between both groups. Conclusions Alcoholism was associated with decreased plasma ghrelin levels partly due to reduced ghrelin production in the stomach. Alcohol affected ghrelin production on the post-transcriptional level in the fundus, whereas duodenal ghrelin secretion did not respond in a similar manner to alcohol intake.

Borsutzky S; Fujiwara E; Brand M; Markowitsch HJ. Confabulations in alcoholic Korsakoff patients. Neuropsychologia 46(13): 3133-3143, 2008. (95 refs.)

Besides forgetting, memory is also prone to distortions, errors and illusions. Confabulation is one type of memory distortion that may occur in cases of brain damage. Although confabulations are described anecdotally in patients with alcoholic Korsakoff syndrome (KS), there are few systematic investigations of the presence and nature of these types of false memories in KS. Moreover, it is unclear whether KS patients' confabulations evenly affect all types of memories, or whether certain memory domains are more susceptible. Our study attempted to clarify two questions: first, whether confabulations are a critical feature of the cognitive impairment associated with long-term KS in a large sample of patients (N=42). Second, we investigated which memory domain is most likely affected by confabulations in KS. To elicit confabulations, we used a Confabulation Interview containing questions from different memory domains. We found that KS patients overall confabulated more compared to a group of healthy subjects. Furthermore, we found that patients confabulated most within the episodic/autobiographical memory domain. Our results imply that besides pronounced memory deficits typically associated with KS, confabulation can also be regarded as a clinical feature of the disease. The preponderance of episodic confabulation obtained here by using a standardized test, confirms anecdotic reports that KS patients confabulate in everyday life mainly with respect to their personal past and present. Thus, for a detailed description of the memory profile of KS patients, the screening of confabulation tendencies may be a useful supplementary clinical tool.

Brokate B; Bernsdorff K; Braamhorst W; Eling P; Hildebrandt H. Object alternation in alcohol dependent patients without amnesic syndrome. Zeischrift fur Neuropsychologie 18(1): 33-40, 2008. (54 refs.)

Several studies indicate that the frontal cortex is sensitive to the toxic effects of alcohol. Recent studies of our group revealed all impairment of alcohol dependent subjects in object alternation. One major problem of these studies is that they all used object alternation embedded in a spatial presentation and with two spatially arranged response buttons: a left and a right hand response key. The deficit in alternation tasks may be due to problems in processing these spatial features. We investigated 24 detoxified alcohol dependent patients, who were in a long term treatment program, and 28 control subjects matched for intelligence and age. using a new object alternation paradigm avoiding confounding of spatial effects. The results indicate that object alternation is impaired in long term alcohol dependent patients without amnesic syndrome, even when no differential spatial response is afforded. We suggest that internal control on a cognitive level, as well as oil a behavioral level, may be a fundamental problem in addiction and might be related to ventromedial and orbitofrontal dysfunction.

Brust JCM. A 74-year-old man with memory loss and neuropathy who enjoys alcoholic beverages. Journal of the American Medical Association 299(9): 1046-1054, 2008. (103 refs.)

Adverse effects of alcohol on the peripheral and central nervous system can be direct ( ie, neurotoxicity) or indirect (eg, nutritional deficiency). Using the case of Mr E, an older, moderate to heavy drinker experiencing memory difficulty, the diagnostic considerations, which include mild cognitive impairment, early Alzheimer dementia, Wernicke-Korsakoff syndrome, and "alcoholic dementia," are discussed. These disorders are not mutually exclusive, and in a patient with either mild cognitive impairment or dementia, the contributory role of alcohol can be difficult to determine. In fact, epidemiological studies suggest that mild to moderate intake of alcohol actually reduces the risk of developing mild cognitive impairment or dementia, including Alzheimer dementia. Appropriate management includes measures to reduce alcohol dependence (eg, behavioral or pharmacological therapy) and to delay progression of the cognitive impairment (eg, engaging in healthy behaviors such as cognitive leisure activities).

Burnham EL; Halkar R; Burks M; Moss M. The effects of alcohol abuse on pulmonary alveolar-capillary barrier function in humans. Alcohol and Alcoholism 44(1): 8-12, 2009. (29 refs.)

Aims: Alcohol abuse is associated with the development of the acute respiratory distress syndrome, a disorder characterized by abnormal alveolar-capillary permeability. We hypothesized that individuals with a history of alcohol abuse would have clinical evidence of abnormal alveolar-capillary permeability even in the absence of symptoms. This could contribute to their propensity for the development of this disorder. Methods: Thirty-three subjects with a history of alcohol abuse, but no other medical problems, and 13 age- and smoking-matched controls inhaled Tc-99m-DTPA (technetium-labeled diethylenetriamine penta-acetate; an isotope used to measure lung permeability) for a 3-min period, and washout of this isotope was measured for a 90-min period. The rate at which it was cleared from the lungs was assessed and compared between subjects and controls. Results: The half-life of Tc-99m-DTPA in the lungs of subjects with alcohol abuse was significantly shorter than that observed in matched controls, even when correcting for the effects of concomitant tobacco use. When the half-life of the isotope for smoking alcohol-abusing subjects and smoking controls were compared separately, there was a trend for the alcohol-abusing subjects to have a shorter half-life of the isotope present in the lungs. This was also true when non-smokers were compared. Conclusions: These observations provide further evidence that alcohol abuse affects the normal permeability of the alveolar-capillary barrier and thereby may contribute to the development of the acute respiratory distress syndrome in individuals with alcohol abuse.

Buttari B; Profumo E; Mancinelli R; Incani UC; Tosti ME; Attilia ML et al. Chronic and acute alcohol exposure prevents monocyte-deried dendritic cells from differentiating and maturing. International Journal of Immunopathology and Pharmacology 21(4): 929-939, 2008. (30 refs.)

Increasing evidence suggests that alcohol abuse may be linked to adverse immunomodulatory effects on immune responses. Our study was undertaken to clarify the immunological consequences of chronic and acute alcohol exposure on differentiation and maturation of human dendritic cells (DCs). Using immunochemical and cytofluorimetric analysis we determined the phenotype and functions of monocyte-derived DCs from alcoholics and healthy subjects and analyzed their ability to respond to lipopolysaccharide (LPS) in the presence or absence of ethanol (EtOH) exposure. Our results showed that alcoholics' monocytes differentiated to immature DCs with altered phenotype and functions (alciDCs). Alc-iDCs showed fewer CD1a(+) cells, weaker CD86 expression and higher HLA-DR expression associated with lower endocytosis and allostimulatory functions than iDCs from healthy subjects (control-iDCs). Despite these impairments, alc-iDCs produced TNF-alpha and IL-6 in large amounts. LPS stimulation failed to induce full phenotypical and functional alc-iDC maturation. In vitro acute EtOH exposure also prevented alc-iDCs and control-iDCs from maturing in response to LPS. T-cell priming experiments showed that EtOH treatment prevented LPS-stimulated control-iDCs from priming and polarizing naive allogeneic T cells into Th1 cells, thus favouring a predominant Th2 environment. Collectively, our results provide evidence that chronic and acute alcohol exposure prevents DCs from differentiating and maturing in response to a microbial stimulus.

Choo EK; McElroy S. Spontaneous bowel evisceration in a patient with alcoholic cirrhosis and an umbilical hernia. Journal of Emergency Medicine 34(1): 41-43, 2008. (15 refs.)

We present a case of spontaneous intestinal evisceration through an umbilical hernia in a patient with alcoholic cirrhosis and long-standing ascites. Hernia rupture is an unusual and potentially life-threatening event in patients with tense ascites. Patients should be managed on an individual basis, balancing aggressive medical stabilization with the need for prompt surgical repair.

Cooreman S; De Doncker M; Van Hee P; Uyttenbroeck W; Dits H; Neels H. A case of fatal alcoholic ketoacidosis. Imuno-Analyse & Biolgic Specialisee 23(2): 116-118, 2008. (16 refs.)

Alcoholic ketoacidosis is an acid-base disturbance which is often observed in chronic alcoholic patients when drinking is ceased after a period of excessive alcohol intake. Dehydration and little food intake are frequently present in these patients. It is very important for the treatment of alcoholic ketoacidosis that a distinction with diabetic ketoacidosos is made. The authors present a case of alcoholic ketoacidosis that ended fatally, probably due to pathophysiological conditions induced by tong-term alcohol abuse.

Crews FT. Alcohol-related neurodegeneration and recovery mechanisms from animal models. Alcohol Research & Health 31(4): 377-388, 2008. (51 refs.)

Human studies have found alcoholics to have a smaller brain size than moderate drinkers; however, these studies are complicated by many uncontrollable factors, including timing and amount of alcohol use. Animal experiments, which can control many factors, have established that alcohol can cause damage to brain cells (i.e., neurons), which results in their loss of structure or function (i.e., neurodegeneration) in multiple brain regions, similar to the damage found in human alcoholics. In addition, animal studies indicate that inhibition of the creation of neurons (i.e., neurogenesis) and other brain-cell genesis contributes to alcoholic neurodegeneration. Animal studies also suggest that neurodegeneration changes cognition, contributing to alcohol use disorders. Risk factors such as adolescent age and genetic predisposition toward alcohol consumption worsen neurodegeneration. Mild impairment of executive functions similar to that found in humans occurs in animals following binge alcohol treatment. Thus, animal studies suggest that heavy alcohol use contributes to neurodegeneration and the progressive loss of control over drinking. Despite the negative consequences of heavy drinking, there is hope of recovery with abstinence, which in animal models can result in neural stem-cell proliferation and the formation of new neurons and other brain cells, indicative of brain growth.

Public Domain

Danel T; Cottencin O; Tisserand L; Touitou Y. Inversion of melatonin circadian rhythm in chronic alcoholic patients during withdrawal: Preliminary study on seven patients. Alcohol and Alcoholism 44(1): 42-45, 2009. (21 refs.)

Aims: The inversion of melatonin circadian rhythm secretion in some alcoholics during both intake and acute withdrawal has been widely reported. In the same way, what happens to this inversion when these patients are in long-term withdrawal is not known. To document this abnormality in alcoholics after withdrawal we investigated melatonin secretion observed during chronic alcoholization and after withdrawal. Methods: We measured the urinary 6-sulfatoxymelatonin (6SM) (6SM/creatinine ratio), main metabolite of the hormone, in two fractions, one diurnal and the other nocturnal, in seven alcohol-dependent patients presenting with this abnormality during alcoholization at two times: in acute withdrawal phase (under benzodiazepines) and 15 days after beginning of withdrawal (free of any psychotropic treatment). Results: Our results show that this reversed rhythm of melatonin secretion as seen by the diurnal excretion of 6SM (6SM/creatinine ratio) persists during acute withdrawal in more than half of the patients and is still present 15 days after withdrawal in three patients. Conclusion: It is remarkable that the inversion of the melatonin rhythms gets corrected in four out of seven patients after withdrawal. But, the circadian disorganization of melatonin secretion in three patients could underline a desynchronization in some alcoholic patients and may indicate more widespread circadian temporal structure disturbances in these patients.

Demirhan O; Tastemir D. Cytogenetic effects of ethanol on chronic alcohol users. Alcohol and Alcoholism 43(2): 127-136, 2008. (52 refs.)

Aim: Alcoholism is a significant public health problem that is also associated with a complex genetic trait. Fragile sites (FS) are potentially informative endpoints for the study of clinical disorders. We aimed to find chromosomal damages in chronic alcohol users for the purpose of finding the correlation between alcohol and chromosomal anomalies. Methods: The potential roles/effects of ethanol on chromosome(s) were assessed in this study by investigating its cytotoxic effects in lymphocyte cultures from chronic alcoholics and controls. Results: Alcoholics revealed a significantly higher frequency of FS and chromosomal aberrations (CA), and the FS clusters in specific chromosomal regions: 1q12, 1q21, 1q32, 2p13, 2q21, 2q31, 3p14, 3p25, 3q21, 4q21, 4q31, 5q31, 6p21, 7q22, 7q32, 9q13, 9q22, 10q22, 11q23, and 12q13. We also observed a significantly greater number of numerical and structural CA in alcoholics. The most frequent exchange types were deletions and polymorphic variations. CA could be due to the cumulative effect of both alcohol and smoking. The loci 1q12, 3p25, 4q31, 6p21, and 12q13 were not reported previously in alcoholics and may be hot spots for alcoholism. The overall FS frequencies were not statistically different between smoker and non-smoker controls, but smoking significantly increased the expression of 1p36, 3q21, and 5p15 sites. These sites have important clinical significance. Conclusions: Chronic alcohol abuse and the smoking habit can lead to chromosome damages that are especially influential on oncogenic regions, which may persist for a long time, and constitute a relevant factor of risk for the development of neoplasias.

Durazzo TC; Rothlind JC; Gazdzinski S; Meyerhoff DJ. The relationships of sociodemographic factors, medical, psychiatric, and substance-misuse co-morbidities to neurocognition in short-term abstinent alcohol-dependent individuals. (review). Alcohol 42(6): 439-449, 2008. (118 refs.)

Co-morbidities that commonly accompany those afflicted with an alcohol use disorder (AUD) may promote variability in the pattern and magnitude of neurocognitive abnormalities demonstrated. The goal of this study was to investigate the influence of several common co-morbid medical conditions (primarily hypertension and hepatitis Q, psychiatric (primarily unipolar mood and anxiety disorders), and substance use (primarily psychostimulant and cannabis) disorders, and chronic cigarette smoking on the neurocognitive functioning in short-term abstinent, treatment-seeking individuals with AUD. Seventy-five alcohol -dependent participants (ALC; 51 +/- 9 years of age; three females) completed comprehensive neurocognitive testing after approximately I month of abstinence. Multivariate multiple linear regression evaluated the relationships among neurocognitive variables and medical conditions, psychiatric, and substance-use disorders, controlling for sociodemographic factors. Sixty-four percent of ALC had at least one medical, psychiatric, or substance-abuse co-morbidity (excluding smoking). Smoking status (smoker or nonsmoker) and age were significant independent predictors of cognitive efficiency, general intelligence, postural stability, processing speed, and visuospatial memory after age-normed adjustment and control for estimated premorbid verbal intelligence, education, alcohol consumption, and medical, psychiatric, and substance-misuse co-morbidities. Results indicated that chronic smoking accounted for a significant portion of the variance in the neurocognitive performance of this middle-aged AUD cohort. The age-related findings for ALC suggest that alcohol dependence, per se, was associated with diminished neurocognitive functioning with increasing age. The study of participants who demonstrate common co-morbidities observed in AUD is necessary to fully understand how AUD, as a clinical syndrome, affects neurocognition, brain neurobiology, and their changes with extended abstinence.

El-Serag HB; Lagergren J. Alcohol drinking and the risk of Barrett's esophagus and esophageal Adenocarcinoma. (editorial). Gatroenterology 136(4): 1155-1157, 2009. (13 refs.)

Fan AZ; Russell M; Stranges S; Dorn J; Trevisan M. Association of lifetime alcohol drinking trajectories with cardiometabolic risk. Journal of Clinical Endocrinology and Metabolism 93(1): 154-161, 2008. (31 refs.)

Context and Objective: Alcohol intakes may vary considerably over a drinker's lifetime. This study was designed to examine whether lifetime drinking trajectories are associated with cardiovascular risk factors that are used to define the metabolic syndrome (MetS). Design, Setting, Participants, and Outcomes: This is a population-based cross-sectional study. Participants were ever-regular drinkers (n = 2818) selected from healthy controls for the Western New York Health Study (1996-2001) in which lifetime lifestyle was ascertained retrospectively. Prevalence of the MetS and its individual components, including obesity, high triglycerides, low high-density lipoprotein cholesterol, elevated blood pressure, and high fasting glucose, were the main outcomes. Results: Trajectory analyses were based on estimates of total kilograms of ethanol for each age decade between 10 and 59 yr. Two groups of drinkers with distinct lifetime drinking trajectories were obtained, an early peak and a stable trajectory group. Compared with stable trajectory drinkers, early-peak drinkers were 10 yr younger on average, had earlier onset of regular drinking, drank heavily in late adolescence and early adulthood tapering off in middle age, averaged more drinks per drinking day in lifetime, and were more likely to abstain when interviewed. After controlling for age, sex, and other potential confounders, early-peak trajectories were modestly associated with high odds of the MetS [1.31; 95% confidence interval (CI) 1.00, 1.71] overall, low high-density lipoprotein cholesterol (1.62; 95% CI 1.27, 2.08), abdominal obesity(1.48; 95% CI 1.23, 1.78), and overweight (1.32; 95% CI 1.10, 1.60). Conclusion: Early initiation of alcohol drinking and heavy drinking in adolescence and early adulthood may be associated with an adverse cardiometabolic profile.

Feeney GFX; Connor JP. Wernicke-Korsakoff syndrome (WKS) in Australia: No room for complacency. Drug and Alcohol Review 27(4): 388-392, 2008. (28 refs.)

Australia has made a substantial contribution to the recognition and treatment of the Wernicke-Korsakoff syndrome (WKS). Much of this occurred over a generation ago, and vigilance in identifying this condition needs to be sustained. More recently, treatment protocols have been developed by the Royal College of Physicians (London). These provide guidelines on when and how to treat both patients at risk and those with acute Wernicke's encephalopathy (WE). It is not known how widespread these recommendations have been applied in Australia. We highlight these current treatment guidelines and illustrate management issues with two case reports. A decline in treatment practices in the United Kingdom prompted the development of these guidelines. Current treatment practices in Australia have not been reported. All alcohol and drug workers need to be reminded regularly of this condition and the need for prompt recognition and treatment.

Fein G; Shimotsu R; Di Sclafani V; Barakos J; Harper C. Increased white matter signal hyperintensities in long-term abstinent alcoholics compared with nonalcoholic controls. Alcoholism: Clinical and Experimental Research 33(1): 70-78, 2009. (74 refs.)

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). 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. 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. 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.

Ferdinandis TGHC; De Silva HJ. Illicit alcohol consumption and neuropathy: A preliminary study in Sri Lanka. Alcohol and Alcoholism 43(2): 171-173, 2008. (15 refs.)

Aims: To compare the effects on peripheral and autonomic nerve functions of Sri Lankan illicitly distilled alcohol consumption versus legal spirit consumption. Methods: Peripheral nerve conduction and autonomic nerve functions were assessed in 40 healthy control subjects and two groups of chronic heavy drinkers: 41 illicit spirit drinkers and 17 legal spirit drinkers. Results: Lower-limb motor and sensory nerve conduction parameters were affected in both groups of alcoholics. When compared with controls, in illicit spirit drinkers the mean heart rate indexes of all parasympathetic tests were lower while in legal spirit drinkers the heart rate response to standing was affected. There were no differences in the results of the above tests when the two groups of heavy drinkers were compared. Conclusions: Though chronic alcoholism results in peripheral and autonomic nerve damage, the damage caused by consumption of illicitly distilled spirit is not worse than the damage caused by consumption of legal spirits.

Fillmore KM; Chikritzhs T; Stockwell T; Bostrom A; Pascal R. Alcohol use and prostate cancer: A meta-analysis. (review). Molecular Nutrition & Food Research 53(2): 240-255, 2009. (64 refs.)

Past reviews have concluded that there is no association between alcohol use and prostate cancer incidence. We performed a meta-analysis of existing epidemiological studies finding, in contrast, evidence to suggest that prostate incidence is positively linearly associated with heavier alcohol use. This finding was largely due to the contribution of population case-control studies and those measuring men recruited before age 60. No relationship between alcohol consumption and prostate cancer was found for cohort and hospital case-control studies. Analyses of design effects modestly suggests that population case-control studies were probably better suited to identify potential alcohol-prostate cancer relationships due to the close temporal proximity of the measurement of level of alcohol consumption to diagnosis. Future efforts should be made to exclude all ill subjects from control groups/baseline samples in addition to accounting for changes in consumption with advancing age and the onset of illness. The alcohol-prostate cancer association remained significant despite controlling for the degree to which studies endeavored to eliminate false negatives from their control groups.

Finn PR; Rickert ME; Miller MA; Lucas J; Bogg T; Bobova L et al. Reduced cognitive ability in alcohol dependence: Examining the role of covarying externalizing psychopathology. Journal of Abnormal Psychology 118(1): 100-116, 2009. (76 refs.)

Reduced executive cognitive ability is associated with alcohol dependence (AD) and other comorbid externalizing disorders. Working memory capacity, short-term memory, conditional associative learning, and intelligence were assessed in a sample (N = 477) with variation in lifetime histories of externalizing problems (conduct disorder, adult antisocial behavior, substance problems); this included a subsample (n = 285) with a Diagnostic and Statistical Manual of Mental Disorders (4th ed.; American Psychiatric Association, 1994) diagnosis of AD. Individuals with both AD and a history of childhood conduct disorder (CCD) scored lower on cognitive measures compared to those with AD and no history of CCD. Structural equation models showed that reduced ability in all cognitive domains was predicted by a latent externalizing factor reflecting covariation among lifetime problems with alcohol, drugs, childhood conduct, and adult antisocial behavior and was not uniquely related to any one problem. Further, for those with AD, the externalizing factor was associated with reductions in all the domains of cognitive ability. The results suggest that the reduced executive cognitive ability observed in AD individuals is partly accounted for by a general latent externalizing factor rather than alcohol-related problems per se.

Fitzpatrick LE; Jackson M; Crowe SF. The relationship between alcoholic cerebellar degeneration and cognitive and emotional functioning. Neuroscience and Biobehavioral Reviews 32(3): 466-485, 2008. (274 refs.)

Although it is now widely acknowledged that the cerebellum contributes to the modulation of higher-order cognitive and emotional functions, this relationship has not been extensively explored in perhaps the largest group of individuals with cerebellar damage, chronic alcoholics. Localised damage to the cerebellum has been associated with a specific constellation of deficits and has been termed the cerebellar cognitive affective syndrome' (CCAS) [Schmahmann, J.D., Sherman, J.C., 1998. The cerebellar cognitive affective syndrome. Brain 121, 561-579]. The CCAS describes a profile of impairments, including deficits in executive functioning and visuospatial skills, language disruption and altered personality and affective behaviour. It is conceivable that the CCAS may also develop in a subgroup of alcoholics with alcoholic cerebellar degeneration and may in part account for a proportion of the cognitive and affective deficits commonly observed with the condition. While evidence has emerged supporting such a relationship, methodological limitations and the lack of theoretically driven investigation of the contribution of cerebellar dysfunction to cognitive and emotional functioning in chronic alcoholics, preclude definitive conclusions being drawn.

Garcia-Gomez MD; Gonzalez JO; del Barrio AG; Garcia NA. Rhabdomyolysis and drug abuse in a patient with bulimia nervosa. International Journal of Eating Disorders 42(1): 93-95, 2009. (11 refs.)

Objective: Eating disorders, particularly bulimia nervosa, have long been associated with alcohol and illicit drug abuse. impulsivity has been linked to substance abuse, but there are other explanations for this association. This comorbidity could be very harmful, even deadly, because Of the medical consequences of drug abuse. Method: This article reports on the case of a 23-year-old woman with bulimia nervosa, severe alcohol and illicit drug abuse, and impulsive behavior who developed rhabdomyolysis. One of the reasons for her drug addiction was the effect of these substances in appetite suppression. Results: The patient successfully recovered after medical and psychological treatment. Conclusion: This article presents the case of a patient with bulimia nervosa and a serious medical complication of illicit drug abuse. It is important to be aware of the increased risk of morbidity and mortality for this patient group.

Gazdzinski S; Durazzo TC; Weiner MW; Meyerhoff DJ. Are treated alcoholics representative of the entire population with alcohol use disorders? A magnetic resonance study of brain injury. Alcohol 42(2): 67-76, 2008. (67 refs.)

Almost all we know about neurobiological brain injury in alcohol use disorders has been derived from convenience samples of treated alcoholics. Recent research has demonstrated more comorbid conditions, poorer psychosocial functioning, and higher dependence levels in treated alcoholics than in their treatment-naive counterparts. Thus, it is not clear whether neuroimaging results from convenience samples of treated alcoholics can be generalized to the entire population with alcohol use disorders. We compared 35 treated alcoholics at I week of abstinence (ALC) and 32 treatment-naive heavy drinkers (HD) on regional brain volumes and metabolite concentrations obtained by in vivo magnetic resonance at 1.5 Tesla to evaluate for potential group differences. Then, we evaluated whether comorbid cigarette smoking and common demographic and clinical variables mediated any existing neurobiological group differences. ALC demonstrated smaller lobar gray matter volumes and thalami than HD, exacerbated by chronic smoking. Furthermore, concentrations of N-acetyl-aspartate (an accepted marker of neuronal viability), choline-containing metabolites (involved in membrane turnover), and myo-inositol (a putative marker of glial cells and osmolyte) were lower in multiple brain regions of ALC compared to HD. The lower N-acetyl-aspartate concentrations in white matter of ALC versus HD were explained by average number of drinks per month over the year preceding study. However, the other group differences were not explained by common drinking, demographic, and clinical variables (used as covariates at the same time) or by excluding participants with comorbid mood disorders. Taken together, this suggests that the degree of brain atrophy, as well as neuronal and membrane injury in clinical samples of alcoholics cannot be generalized to the much larger population with alcohol use disorders that does not seek treatment.

Glass JM; Buu A; Adams KM; Nigg JT; Puttler LI; Jester JM et al. Effects of alcoholism severity and smoking on executive neurocognitive function. Addiction 104(1): 38-48, 2009. (49 refs.)

Aims: Neurocognitive deficits in chronic alcoholic men are well documented. Impairments include memory, visual-spatial processing, problem solving and executive function. The cause of impairment could include direct effects of alcohol toxicity, pre-existing cognitive deficits that predispose towards substance abuse, comorbid psychiatric disorders and abuse of substances other than alcohol. Cigarette smoking occurs at higher rates in alcoholism and has been linked to poor cognitive performance, yet the effects of smoking on cognitive function in alcoholism are often ignored. We examined whether chronic alcoholism and chronic smoking have effects on executive function. Methods: Alcoholism and smoking were examined in a community-recruited sample of alcoholic and non-alcoholic men (n = 240) using standard neuropsychological and reaction-time measures of executive function. Alcoholism was measured as the average level of alcoholism diagnoses across the study duration (12 years). Smoking was measured in pack-years. Results: Both alcoholism and smoking were correlated negatively with a composite executive function score. For component measures, alcoholism was correlated negatively with a broad range of measures, whereas smoking was correlated negatively with measures that emphasize response speed. In regression analyses, both smoking and alcoholism were significant predictors of executive function composite. However, when IQ is included in the regression analyses, alcoholism severity is no longer significant. Conclusions: Both smoking and alcoholism were related to executive function. However, the effect of alcoholism was not independent of IQ, suggesting a generalized effect, perhaps affecting a wide range of cognitive abilities of which executive function is a component. On the other hand, the effect of smoking on measures relying on response speed were independent of IQ, suggesting a more specific processing speed deficit associated with chronic smoking.

Gonzalez-Reimers E; Garcia-Valdecasas-Campelo E; Santolaria-Fernandez F; Sanchez-Perez MJ; Rodriguez-Rodriguez E; Gomez-Rodriguez MA et al. Prognostic value of nutritional status in alcoholics, assessed by double-energy X-ray absorptiometry. Alcohol and Alcoholism 43(3): 314-319, 2008. (22 refs.)

Objectives: This study was performed in order to assess nutritional status of 77 alcoholic patients. Methods: Patients underwent a total body double-energy X-ray absorptiometry (DEXA) analysis, with estimation of lean and fat mass at different parts of the body. Results: Lean mass, but not fat mass, was significantly reduced among alcoholics, compared to 31 age-matched controls, especially at right arm, legs, and total body. Lean mass at both arms was significantly related to liver function parameters (albumin, prothrombin activity, bilirubin) and, inversely, with ethanol consumption. The 24 patients who died during a follow-up period of 88 months showed less lean mass at both arms, trunk, and left leg, and also less fat at the left arm, than survivors. When right and left arm lean mass were classified in quartiles, Kaplan-Meier curves showed significant differences between dead and survivors. Left arm lean mass was the parameter which was independently related to mortality when encephalopathy was not included in a stepwise Cox regression analysis, but was displaced by this last parameter when it was also introduced in the analysis. Conclusion: lean mass is reduced in alcoholics, is related to liver function derangement and ethanol consumption, and is related to mortality.

Goral J; Karavitis J; Kovacs EJ. Exposure-dependent effects of ethanol on the innate immune system. (review). Alcohol 42(4): 237-247, 2008. (138 refs.)

Extensive evidence indicates that ethanol (alcohol) has immunomodulatory properties. Many of its effects on innate immune response are dose dependent, with acute or moderate use associated with attenuated inflammatory responses, and heavy ethanol consumption linked with augmentation of inflammation. Ethanol may modify innate immunity via functional alterations of the cells of the innate immune system. Mounting evidence indicates that ethanol can diversely affect antigen recognition and intracellular signaling events, which include activation of mitogen activated protein kinases, and NF kappa B, mediated by Toll-like receptors, leading to altered inflammatory responses. The mechanism(s) underlying these changes may involve dose-dependent effects of ethanol on the fluidity of cell membrane, resulting in interference with the timely assembly or disassembly of lipid rafts. Ethanol could also modify cell activation by specific interactions with cell membrane molecules.

Guerrini I; Thomson AD; Gurling HM. Molecular genetics of alcohol-related brain damage. Alcohol and Alcoholism 44(2): 166-170, 2009. (43 refs.)

Aims: In the scientific literature it has been repeatedly hypothesized that there is a heritable susceptibility to thiamine deficiency comparable to other hereditary metabolic disorders. The aim of this paper is to review the most recent knowledge on the genetic susceptibility to the development of alcohol-related Wernicke-Korsakoff syndrome (WKS). Methods: A literature review was carried out looking at the molecular genetics studies performed in alcohol-dependent patients affected by WKS. Results: A genetic component in the pathogenesis of WKS has been postulated since the late seventies. Since then, very few genetic studies have been carried out on candidate genes such as thiamine-dependent enzymes, alcohol-metabolizing enzymes and GABA receptors. The findings are controversial and not conclusive. Several authors reported the important role of the thiamine transporters in the pathogenesis of the thiamine deficiency disorders. Our findings on SLC19A2 and SLC19A3 suggest a potential role of these two genes in the pathophysiology of alcohol-related thiamine deficiency but further studies need to be carried out. Conclusions: The WKS may be a very complex, multifactorial disorder where the interaction of multiple genes and environment plays an important role in the pathogenesis. However, it is still plausible that megaphenic gene effects are responsible for WKS susceptibility and the thiamine transport genes are good candidates for having such a role. Further genetic studies are definitely needed to investigate the association with candidate genes or linkage with hot spot areas.

Guo QM; Zakhari S. Commentary: Systems biology and its relevance to alcohol research. (editorial). Alcohol Research & Health 31(1): 5-10, 2008. (14 refs.)

Systems biology, a new scientific discipline, aims to study the behavior of a biological organization or process in order to understand the function of a dynamic system. This commentary will put into perspective topics discussed in this issue of Alcohol Research & Health, provide insight into why alcohol-induced disorders exemplify the kinds of conditions for which a systems biological approach would be fruitful, and discuss the opportunities and challenges facing alcohol researchers.

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Gupta S; Warner J. Alcohol-related dementia: A 21st-century silent epidemic? (editorial). British Journal of Psychiatry 193(5): 351-353, 2008. (20 refs.)

Evidence suggests a J-shaped relationship between alcohol consumption and cognitive impairment and other health indicators, with low levels of consumption having better outcomes than abstention or moderate to heavy drinking. Most research to date has focused on the protective effects of drinking small amounts of alcohol. As alcohol consumption is escalating rapidly in many countries, the current cohort of young and middle-aged people may face an upsurge of alcohol-related dementia. The dangers of heavy drinking and its effect on cognition require further attention.

Harper C. The neuropathology of alcohol-related brain damage. Alcohol and Alcoholism 44(2): 136-140, 2009. (87 refs.)

Excessive alcohol use can cause structural and functional abnormalities of the brain and this has significant health, social and economic implications for most countries in the world. Even heavy social drinkers who have no specific neurological or hepatic problems show signs of regional brain damage and cognitive dysfunction. Changes are more severe and other brain regions are damaged in patients who have additional vitamin B1 (thiamine) deficiency (Wernicke-Korsakoff syndrome). Quantitative studies and improvements in neuroimaging have contributed significantly to the documentation of these changes but mechanisms underlying the damage are not understood. A human brain bank targeting alcohol cases has been established in Sydney, Australia, and tissues can be used for structural and molecular studies and to test hypotheses developed from animal models and in vivo studies. The recognition of potentially reversible changes and preventative medical approaches are important public health issues.

Harris GJ; Jaffin SK; Hodge SM; Kennedy D; Caviness VS; Marinkovic K et al. Frontal white matter and cingulum diffusion tensor imaging deficits in alcoholism. (review). Alcoholism: Clinical and Experimental Research 32(6): 1001-1013, 2008. (107 refs.)

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.

Hiller-Sturmhofel S; Sobin J; Mayfield RD. Proteomic approaches for studying alcoholism and alcohol-induced organ damage. Alcohol Research & Health 31(1): 36-48, 2008. (36 refs.)

Proteomics research is concerned with the analysis of all proteins found in an organism, tissue, cell type, or cellular structure. The shotgun proteomic approach, which involves two-dimensional gel electrophoresis or liquid chromatography combined with mass spectrometry (MS), is used to identify novel proteins affected by alcohol. More targeted analyses study protein-protein interactions using such techniques as the yeast two-hybrid system, affinity chromatography, or immunoprecipitation. Finally, proteomic strategies can be combined with genomic research findings using computer analyses (i.e., in silico). All of these approaches have been used in the alcohol field. These studies have identified proteins in various brain regions whose expression is affected by alcohol. Other investigators have used proteomic approaches to identify proteins that could serve as potential biomarkers of alcohol use. Finally, interaction proteomic analyses have begun to identify proteins involved in several nerve signaling networks in the brain, which then can serve as targets for further studies on alcohol's effects. Future proteomic studies likely will shed more light on the mechanisms underlying alcohol's actions on the body.

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Hipolito L; Sanchez-Catalan MJ; Polache A; Granero L. Induction of brain CYP2E1 changes the effects of ethanol on dopamine release in nucleus accumbens shell. Drug and Alcohol Dependence 100(1-2): 83-90, 2009. (61 refs.)

CYP2E1 is an important enzyme involved in the brain metabolism of ethanol that can be induced by chronic consumption of alcohol. Recent works have highlighted the importance of this system in the context of the behavioural effects of ethanol. Unfortunately, the underlying neurochemical events for these behavioural changes, has not been yet explored. In this work, we have started this exploration by analyzing the possible changes in the neurochemical response of the mesolimbic system to ethanol after pharmacological induction of brain CYP2E1. We have used the clopamine extracellular levels in nucleus accumbens (NAc) core and shell, measured by means of microdialysis in vivo, as an index of the effects of ethanol. Acetone 1% in the tap water was used to induce brain CYP2E1. Efficacy of the induction protocol was assessed by immunoblotting. Intravenous administration of 1.5 g/kg of ethanol in control rats provoked a significant increase of the dopamine levels in both the core (up to 127% of baseline) and the shell (up to 122% of baseline) of the NAc. However, the same dose of ethanol in acetone-treated rats only increased the dopamine extracellular levels in the core (up to 142% of baseline) whereas dopamine levels in the shell subregion remain unaltered relative to baseline. The results of this study indicate that induction of CYP2E1 changes the response of the mesolimbic system to ethanol in a region-dependent manner. Two hypotheses are postulated to explain the observed effects.

Hitzemann R; Oberbeck D. Stategies to study the neuroscience of alcoholism: Introduction. (editorial). Alcohol Research & Health 31(3): 231-232, 2008. (0 refs.)

Johansson S; Ekstrom TJ; Marinova Z; Okvist A; Sheedy D; Garrick T. Dysregulation of cell death machinery in the prefrontal cortex of human alcoholics. International Journal of Neuropsychopharmacology 12(1): 109-115, 2009. (21 refs.)

In human alcoholics, the cell density is decreased in the prefrontal cortex (PFC) and other brain areas. This may be due to persistent activation of cell death pathways. To address this hypothesis, we examined the status of cell death machinery in the dorsolateral PFC in alcoholics. Protein and mRNA expression levels of several key pro- and anti-apoptotic genes were compared in post-mortem samples of 14 male human alcoholics and 14 male controls. The findings do not support the hypothesis. On the contrary, they show that several components of intrinsic apoptotic pathway are decreased in alcoholics. No differences were evident in the motor cortex, which is less damaged in alcoholics and was analysed for comparison. Thus, cell death mechanisms may be dysregulated by inhibition of intrinsic apoptotic pathway in the PFC in human alcoholics. This inhibition may reflect molecular adaptations that counteract alcohol neurotoxicity in cells that survive after many years of alcohol exposure and withdrawal.

Kapasova Z; Szumlinski KK. Strain differences in alcohol-induced neurochemical plasticity: A role for accumbens glutamate in alcohol intake. Alcoholism: Clinical and Experimental Research 32(4): 617-631, 2008. (90 refs.)

Background: Repeated alcohol administration alters nucleus accumbens (NAC) basal glutamate content and sensitizes the capacity of alcohol to increase NAC extracellular glutamate levels. However, the relevance of alcohol-induced changes in NAC glutamate for alcohol drinking behavior is under-investigated. Methods: To examine the relationship between genetic variance in alcohol consumption and alcohol-induced neuroadaptations within the NAC, in vivo microdialysis was conducted in the alcohol-preferring C57BL/6J (B6) and alcohol-avoiding DBA2/J (D2) mouse strains on injections 1 and 8 of repeated alcohol treatment (8 x 2 g/kg, IP). To confirm an active role for NAC glutamate in regulating alcohol drinking behavior, the glutamate reuptake inhibitor DL-threo-beta-benzyloxyaspartic acid (TBOA) (300 mu M) and the Group 2 metabotropic glutamate autoreceptor agonist (2R,4R)-4-aminopyrrolidine-2,4-dicarboxylate (APDC) (50 mu M) were infused into the NAC of B6 and D2 mice prior to alcohol consumption in a 4 bottle-choice test. Results: While strain differences were not apparent for NAC basal levels of dopamine, serotonin or gamma-amino butyric acid (GABA), repeated alcohol treatment elevated NAC basal glutamate content only in B6 mice. Strain differences in both the acute and the sensitized neurochemical responses to 2 g/kg alcohol were observed for all neurotransmitters examined. While the alcohol-induced rise in NAC dopamine and glutamate levels sensitized in B6 mice, a sensitization was not observed in D2 animals. Moreover, B6 mice exhibited a sensitized serotonin and GABA response to alcohol followed repeated treatment, whereas neither tolerance nor sensitization was observed in D2 animals. An intra-NAC APDC infusion reduced alcohol intake in both B6 and D2 mice by approximately 50%. In contrast, TBOA infusion elevated alcohol intake selectively in B6 mice. Conclusions: These data indicate an active role for NAC glutamate in regulating alcohol consumption in mice and support the hypothesis that predisposition to high alcohol intake involves genetic factors that facilitate alcohol-induced adaptations in glutamate release within the NAC.

Karkoulias K; Tsitsaras H; Patouchas D; Sampsonas F; Likouras D; Kaparianos A et al. The alcoholic lung disease: Historical background and clinical features. (review). Medicina (Lithuania) 44(9): 651-664, 2008. (87 refs.)

The purpose of this review article is to prove the damage that alcohol causes to the respiratory system. We will make a brief review of alcohols history in the course of the centuries till nowadays. The problem of addiction to alcohol (alcoholism) will be examined for several countries. Alcohol's metabolism is another topic to he discussed parallel to its pharmacological action. In addition, alcohol's impact on the respiratory system varies from damaging the mucociliary system to the regulation of breathing and from the sleep apnea syndrome to diffusion disorders. "Alcoholic lung disease" constitutes a syndrome despite the, fact that the damage of the lung due to concurrent smoking and drug use is often indistinguishable.

Kavitha G; Reddy VD; Paramahamsa M; Akhtar PM; Varadacharyulu NC. Role of nitric oxide in alcohol-induced changes in lipid profile of moderate and heavy alcoholics. Alcohol 42(1): 47-53, 2008. (59 refs.)

Biochemical changes in plasma and red cell membrane in moderate and heavy alcoholics were investigated to compare them with teetotalers in the present study. Significant changes in lipid, lipoprotein profile, and lipid peroxidation were evident from the study suggesting the cardioprotective effect in moderate alcoholics, and adverse changes leading to cardiovascular risk in heavy alcoholics. Both nitrite and nitrate levels in plasma of moderate alcoholics increased significantly when compared with teetotalers and the increase is more pronounced in heavy alcoholics. The results of the present study showed no significant difference in osmotic hemolysis in red cells from moderate and heavy alcoholics incubated with NaCl at concentrations ranging from 0.1% to 0.9%. Further, the study showed a possible relationship of nitric oxide (NO) with changes in plasma lipid profile. To sum up, these changes in both moderate and heavy alcoholics clearly indicated the involvement of NO in rendering tolerance to alcohol-induced effects and also in modulation of alcohol effects.

Kershaw CD; Guidot DM. Alcoholic lung disease. Alcohol Research & Health 31(1): 66-75, 2008. (74 refs.)

In addition to its well-known association with lung infection (i.e., pneumonia), alcohol abuse now is recognized as an independent factor that increases by three- to four-fold the incidence of the acute respiratory distress syndrome, a severe form of acute lung injury with a mortality rate of 40 to 50 percent. This translates to tens of thousands of excess deaths in the United States each year from alcohol-mediated lung injury, which is comparable to scarring of the liver (i.e., cirrhosis) in terms of alcohol-related mortality. Experimental and clinical studies are shedding light on the basic mechanisms by which alcohol abuse predisposes some people to both acute lung injury and pneumonia. At the same time, novel therapeutic targets could be utilized in treating these uniquely vulnerable people. However, there have been no systems biological approaches to the study of the alcoholic lung to date. This is in part because the association between alcohol abuse and acute lung injury was made relatively recently and remains largely unrecognized, even by lung researchers. in parallel, efforts to study complex diseases such as acute lung injury and pneumonia using a genomics and/or proteomics approach, which involves the study of an organism's genes andlor proteins, still are in their infancy. However, the alcoholic lung represents a clear example of environment-host interactions that should be well suited for such applications.

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Kokavec A. Is decreased appetite for food a physiological consequence of alcohol consumption? Appitite 51(2): 233-243, 2008. (0 refs.)

Despite the overwhelming evidence linking alcohol to the development of disease, the contribution of alcohol toxicity to ill health remains controversial. One of the major problems facing researchers is the fact that alcoholic beverages, which contribute little to the nutritional requirements of the body, are often substituted for food and nutritional deficiency alone can promote cell damage. Long-term alcohol intake can decrease the total amount of food consumed when food is freely available and the alcoholic individual is often held accountable for their irregular eating behaviour. Assessment of meal composition has highlighted that appetite for food-containing carbohydrate (in particular) is altered in moderate-heavy drinkers but at present there is insufficient biochemical evidence to confirm or deny this observation. The biochemical processes associated with appetite are many and it would be impossible to address all of these events in a single paper. Therefore, the aim of this review will be to focus on one of the major biochemical markers of appetite for carbohydrate in order to put forward the suggestion that a decreased appetite for food could be a physiological consequence of consuming some forms of alcohol.

Kopelman MD; Thomson AD; Guerrini I; Marshall EJ. The Korsakoff Syndrome: Clinical aspects, psychology and treatment. Alcohol and Alcoholism 44(2): 148-154, 2009. (74 refs.)

Aims: The Korsakoff syndrome is a preventable memory disorder that usually emerges (although not always) in the aftermath of an episode of Wernicke's encephalopathy. The present paper reviews the clinical and scientific literature on this disorder. Methods: A systematic review of the clinical and scientific literature on Wernicke's encephalopathy and the alcoholic Korsakoff syndrome. Results: The Korsakoff syndrome is most commonly associated with chronic alcohol misuse, and some heavy drinkers may have a genetic predisposition to developing the syndrome. The characteristic neuropathology includes neuronal loss, micro-haemorrhages and gliosis in the paraventricular and peri-aqueductal grey matter. Lesions in the mammillary bodies, the mammillo-thalamic tract and the anterior thalamus may be more important to memory dysfunction than lesions in the medial dorsal nucleus of the thalamus. Episodic memory is severely affected in the Korsakoff syndrome, and the learning of new semantic memories is variably affected. 'Implicit' aspects of memory are preserved. These patients are often first encountered in general hospital settings where they can occupy acute medical beds for lengthy periods. Abstinence is the cornerstone of any rehabilitation programme. Korsakoff patients are capable of new learning, particularly if they live in a calm and well-structured environment and if new information is cued. There are few long-term follow-up studies, but these patients are reported to have a normal life expectancy if they remain abstinent from alcohol. Conclusions: Although we now have substantial knowledge about the nature of this disorder, scientific questions (e.g. regarding the underlying genetics) remain. More particularly, there is a dearth of appropriate long-term care facilities for these patients, given that empirical research has shown that good practice has beneficial effects.

Kristiansen L; Gronbaek M; Becker U; Tolstrup JS. Risk of pancreatitis according to alcohol drinking habits: A population- based cohort study. American Journal of Epidemiology 168(8): 932-937, 2008. (21 refs.)

The association between alcohol intake and pancreatitis has been examined previously in case-control studies, mostly consisting of men. The significance of beverage type and drinking pattern is unknown. The objective of this study was to assess the association between amount, type, and frequency of alcohol intake and risk of pancreatitis. For this purpose, the authors used data on 17,905 men and women who participated in the Copenhagen City Heart Study in 1976-1978, 1981-1983, 1991-1994, and 2001-2003 in Copenhagen, Denmark. Alcohol intake and covariates were assessed by questionnaire. Information on pancreatitis was obtained from national registers. A high alcohol intake was associated with a higher risk of pancreatitis. Hazard ratios associated with drinking 1-6, 7-13, 14-20, 21-34, 35-48, and > 48 drinks/week were 1.1 (95% confidence interval (CI): 0.8, 1.6), 1.2 (95% CI: 0.8, 1.8), 1.3 (95% CI: 0.8, 2.1), 1.3 (95% CI: 0.7, 2.2), 2.6 (95% CI: 1.4, 4.8), and 3.0 (95% CI: 1.6, 5.7), respectively, compared with 0 drinks/week (P-trend < 0.001). Associations were similar for men and women. Drinking frequency did not seem to be independently associated with pancreatitis.

Kubo A; Levin TR; Block G; Rumore GJ; Quesenberry CP; Buffler P et al. Alcohol types and sociodemographic characteristics as risk factors for Barrett's esophagus. Gastroenterology 136(3): 806-815, 2009. (46 refs.)

Background & Aims: Little is known about the effects of alcohol use and sociodemographics on the risk of Barrett's esophagus, a precursor to esophageal adenocarcinoma. We evaluated the association between alcohol use, alcohol type, sociodemographic profiles, other lifestyle factors, and the risk of Barrett's esophagus. Methods: With the use of a case-control study within the Kaiser Permanente Northern California membership, patients with a new diagnosis of Barrett's esophagus (n = 320) diagnosed between 2002 and 2005 were matched to persons with gastroesophageal reflux disease (GERD; n = 316) and to population controls (n 317). We collected information using validated questionnaires during direct in-person interviews. Analyses used multivariate unconditional logistic regression. Results: Total alcohol use was not Significantly associated with the risk of Barrett's esophagus, although stratification by beverage type showed an inverse association for wine drinkers compared with nondrinkers (>= 7 drinks of wine per week vs none: odds ratio, 0.44; 95% confidence interval, 0.20-0.99; multivariate analysis). Among population controls, those who preferred wine were more likely to have college degrees and regularly take vitamin supplements than those who preferred beer or liquor, although adjustment for these factors or GERD symptoms did not eliminate the inverse association between wine consumption and Barrett's esophagus. Education status was significantly inversely associated with the risk of Barrett's esophagus. Conclusions: There are associations between alcohol types, socioeconomic status, and the risk of Barrett's esophagus. Although choice of alcoholic beverages was associated with several factors, multiple adjustments (including for GERD) did no eliminate the association between alcohol and Barrett's esophagus. Further research to evaluate the associations among socioeconomic status, GERD, and Barrett's esophagus is warranted.

Lau A; von Dossow V; Sander M; MacGuill M; Lanzke N; Spies C. Alcohol use disorder and perioperative immune dysfunction. (review). Anesthesia and Analgesia 108(3): 916-920, 2009. (48 refs.)

The anesthesiological sequelae of long-term alcohol abuse include a three to fivefold increased risk of postoperative infection, prolonged intensive care unit stays and longer hospital stays. The cause of the higher infection rates is an altered immune response in long-term alcoholic patients. Preoperatively, the T helper cells 1 to T helper cells 2 ratio is depressed in long-term alcoholic patients and remains suppressed after surgery. The lower preoperative T helper cells 1 to T helper cells 2 ratio is predictive of later onset of infections. Postoperatively, the cytotoxic lymphocyte (Tc1/Tc2) ratio is decreased in long-term alcoholic patients and remains depressed for 5 days. The interleukin (IL)-6/IL-10 ratio and the lipopolysaccharide-stimulated interferon gamma/IL-10 ratio in whole blood cells are decreased after surgery in long-term alcoholic patients. Depressed Tc1/Tc2, IL-6/IL-10 and lipopolysaccharide-stimulated interferon gamma/IL-10 ratios in the postoperative period are predictive of subsequent postoperative infections. Perioperative interventions should aim to minimize dysregulation of the immune system.

Leggio L; Ferrulli A; Cardone S; Malandrino N; Mirijello A; D'Angelo C et al. Relationship between the hypothalamic-pituitary-thyroid axis and alcohol craving in alcohol-dependent patients: A longitudinal study. Alcoholism: Clinical and Experimental Research 32(12): 2047-2053, 2008. (55 refs.)

A relationship between some hypothalamic-pituitary-related hormones and craving for alcohol has been suggested, leading to hypothesize a role of some hormones in the neurobiology of alcohol dependence. Investigating this association in alcohol-dependent (AD) patients was the aim of this preliminary and exploratory study. Cortisol, adrenocorticotropic hormone, prolactin, thyroid-stimulating hormone (TSH), free T3, free T4, growth hormone, follicle-stimulating hormone, luteinizing hormone as well as administering the Obsessive-Compulsive Drinking Scale (OCDS) and Penn Alcohol Craving Scale (PACS) were assessed at baseline and after 12 weeks in 25 current AD patients. Patients were treated with baclofen (10 mg t.i.d.) for these 12 weeks. Sixteen patients remained totally abstinent for 12 weeks. At baseline, a significant inverse correlation was found between TSH and PACS (r = -0.46; p = 0.022) and OCDS scores (r = -0.53; p = 0.007). A significant direct correlation was found between free T3 and OCDS score (r = 0.44; p = 0.026). In the 16 abstinent patients, craving scores were significantly decreased at 12 weeks (p < 0.01). At 12 weeks, no significant correlation was found between TSH and craving, but free T3 remained directly correlated with OCDS score (r = 0.60; p = 0.013). A relationship between alcohol craving and free T3 and TSH was demonstrated in AD patients, suggesting the potential involvement of the hypothalamic-pituitary-thyroid axis in the neurobiology of alcohol craving.

Leggio L; Malandrino N; Ferrulli A; Cardone S; Miceli A; Gasbarrini G et al. Is cortisol involved in the alcohol-related fat mass impairment ? A longitudinal clinical study. Alcohol and Alcoholism 44(2): 211-215, 2009. (43 refs.)

Aims: Subjects with chronic alcohol abuse can present several metabolic and nutritional alterations. The hypothalamic-pituitary-adrenal (HPA) axis may play a role in these nutritional and metabolic disorders. The goal of this study was to investigate if there is any relationship between HP-hormones and metabolic and nutritional parameters in alcoholic subjects. Methods: Sixteen alcoholics were considered before and after 3 months of total alcohol abstinence. HP-related hormones were determined. Nutritional and metabolic parameters were assessed by dual-energy X-ray absorptiometry (DXA) and indirect calorimetry. Results: At baseline, a significant negative correlation was found between fat mass (FM) and cortisol (r = -0.54, P = 0.03). During abstinence, a significant increase of both body mass index (BMI) (P < 0.0001) and FM (P < 0.0001) was found at 12 weeks compared to baseline. A significant decrease of both plasma cortisol (P = 0.044) and aldosterone (P = 0.023) was found at 12 weeks compared to baseline. At 12 weeks, the significant correlation between cortisol and FM disappeared. Conclusions: A higher HPA-axis activation-025EFreflected by higher cortisol levels-025EFwas associated with a lower FM in alcoholics. Conversely, during total abstinence a reduced HPA-axis activity can play a role in the parallel nutritional recovery. The present results suggest a role of the HPA axis throughout cortisol both in the etiology of the alcohol-related nutritional alterations and in their recovery after a period of total alcohol abstinence.

Lovinger DM. Communication networks in the brain neurons, receptors, neurotransmitters, and alcohol. (review). Alcohol Research & Health 31(3): 196-214, 2008. (141 refs.)

Nerve cells (i.e., neurons) communicate via a combination of electrical and chemical signals. Within the neuron, electrical signals driven by charged particles allow rapid conduction from one end of the cell to the other. Communication between neurons occurs at tiny gaps called synapses, where specialized parts of the two cells (i.e., the presynaptic and postsynaptic neurons) come within nanometers of one another to allow for chemical transmission. The presynaptic neuron releases a chemical (i.e., a neuro transmitter) that is received by the postsynaptic neuron's specialized proteins called neurotransmitter receptors. The neurotransmitter molecules bind to the receptor proteins and alter postsynaptic neuronal function. Two types of neurotransmitter receptors exist-ligand-gated ion channels, which permit rapid ion flow directly across the outer cell membrane, and G-protein-coupled receptors, which set into motion chemical signaling events within the cell. Hundreds of molecules are known to act as neuro transmitters in the brain. Neuronal development and function also are affected by peptides known as neurotrophins and by steroid hormones, This article reviews the chemical nature, neuronal actions, receptor subtypes, and therapeutic roles of several transmitters, neurotrophins, and hormones. It focuses on neurotransmitters with important roles in acute and chronic alcohol effects on the brain, such as those that contribute to intoxication, tolerance, dependence, and neurotoxicity, as well as maintained alcohol drinking and addiction.

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Makris N; Oscar-Berman M; Jaffin SK; Hodge SM; Kennedy DN; Caviness VS et al. Decreased volume of the brain reward system in alcoholism. (review). Biological Psychiatry 64(3): 192-202, 2008. (109 refs.)

Background: Reinforcement of behavioral responses involves a complex cerebral circuit engaging specific neuronal networks that are modulated by cortical oversight systems affiliated with emotion, memory, judgment, and decision making (collectively referred to in this study as the "extended reward and oversight system" or "reward network"). We examined whether reward-network brain volumes are reduced in alcoholics and how volumes of subcomponents within this system are correlated with memory and drinking history. Methods: Morphometric analysis was performed on magnetic resonance brain scans in 21 abstinent long-term chronic alcoholic men and 21 healthy control men, group-matched on age, verbal IQ, and education. We derived volumes of total brain and volumes of cortical and subcortical reward-related structures including the dorsolateral-prefrontal, orbitofrontal, cingulate cortices, and the insula, as well as the amygdala, hippocampus, nucleus accumbens septi (NAc), and ventral diencephalon. Results: Morphometric analyses of reward-related regions revealed decreased total reward-network volume in alcoholic subjects. Volume reduction was most pronounced in right dorsolateral-prefrontal cortex, right anterior insula, and right NAc, as well as left amygdala. In alcoholics, NAc and anterior insula volumes increased with length of abstinence, and total reward-network and amygdala volumes correlated positively with memory scores. Conclusions: The observation of decreased reward-network volume suggests that alcoholism is associated with alterations in this neural reward system. These structural reward system deficits and their correlation with memory scores elucidate underlying structural-functional relationships between alcoholism and emotional and cognitive processes.

Malik P; Gasser RW; Kemmler G; Moncayo R; Finkenstedt G; Kurz M et al. Low bone mineral density and impaired bone metabolism in young alcoholic patients without liver cirrhosis: A cross-sectional study. Alcoholism: Clinical and Experimental Research 33(2): 375-381, 2009. (31 refs.)

Osteoporosis is regularly mentioned as a consequence of alcoholism. Ethanol's direct effect on bone-modeling cells as well as alcoholism-related "life-style factors" such as malnutrition, lack of exercise, hormonal changes, and liver cirrhosis are discussed as potential causative factors. In a cross-sectional study, we have examined 57 noncirrhotic alcoholic patients (37 male, 20 female) aged 27 to 50 years. Patients suffering from comorbid somatic diseases and with co-medication known to have an influence on bone mineral density (e.g., glucocorticoids, heparin, anticonvulsant agents, oral contraceptives) were excluded. We determined bone mineral density (BMD) by dual x-ray absorptiometry (DXA) in the lumbar spine (L1-L4) and the proximal right femur (femoral neck, total hip) as well as parameters of bone metabolism. In males but not females, BMD was significantly reduced in the lumbar region, as well as in the proximal femur (femoral neck, total hip). Nine male patients (24.3% of men) and 1 female patient (5% of women) had low BMD (defined as Z-score <= -2.0). As expected, there was a positive correlation between body mass index (BMI) and BMD. Alcohol-related factors (e.g., duration of abuse, consumed amount of alcohol per day) as well as smoking were not associated with a significant effect on BMD. All of the 20 women examined showed elevated estradiol levels, which may have served as a protective factor. In this study, 75.7% of the men and 90% of the women had vitamin D insufficiency or deficiency (plasma levels of 25-hydroxy-vitamin D < 30 ng/ml). Our study indicates that younger alcoholic patients without other diseases may suffer from an increased risk to develop low BMD and a disturbance of vitamin D metabolism. Nutritional factors or less exposure to sunlight may play an important role in bone loss in young alcoholic patients. BMD measurement and assessment of bone metabolism should be considered in all patients with chronic alcoholism.

Mancinelli R; Ceccanti M. Biomarkers in alcohol misuse: Their role in the prevention and detection of thiamine deficiency. Alcohol and Alcoholism 44(2): 177-182, 2009. (65 refs.)

In Western countries alcohol misuse is the most frequent cause of thiamine (vitamin B1) deficiency (TD) and consequent neuro-impairment. Studies have demonstrated that between 30 and 80% of alcoholics are thiamine deficient, and this puts them at risk of developing the Wernicke-Korsakoff (WK) syndrome. The relative roles of alcohol and TD in causing brain damage remain controversial and it is important to try to determine the role played by each factor. Animal studies support an additive effect of alcohol exposure and TD, and indicate the potential for interaction between alcohol and TD in human alcohol-related brain damage. Early diagnosis of alcohol-related TD is therefore an important aspect of effective intervention and treatment. Alcohol biomarkers provide a direct and indirect way of estimating the amount of alcohol being consumed, the duration of ingestion and the harmful effects that long-term alcohol use has on body functions. Appropriate use of these markers is very helpful when considering a diagnosis of alcohol-related TD.

Marshall EJ; Guerrini I; Thomson AD. Introduction to this issue: The seven ages of man ... (or woman) (editorial). Alcohol and Alcoholism 44(2): 106-107, 2009. (7 refs.)

Alcohol affects the brain throughtout life, from the results of prental alcohol exposure, through the binge pattern of drinking the occurs in adolescents, as well as being manifest in the presence of Wernicke-Korsakof's that results from extended heavy alcohol use. This special issue presents the latest views on alcohol-related brain damage that document the advances that have been made and give us considerable optimism for future understanding and prevention of this condition. The public should be given information about how alcohol affects the brain, so that they can make up their mind about how to drink. What is required is the political will and medical determination to educate all members of the medical and allied professions who are likely to be responsible for individuals with alcohol-related brain damage. Much has been achieved over the last 40 years in highlighting and treating the effects of alcohol on the liver. In many ways, alcohol-related brain damage is more fundamental and its effects on society more profound. It is time that equal efforts were made to protect what makes us who we are, and so allow us to �play (our) part� at every stage in our lives.

Mathurin P; Deltenre P. Effect of binge drinking on the liver: An alarming public health issue? Gut 58(5): 613-617, 2009. (55 refs.)

Alcohol consumers show strong variations in demographic characteristics, alcohol intake, frequency, duration and profile of consumption. Individuals consuming up to two drinks per day (men) or one drink per day (women) are defined as moderate drinkers and do not have an increased risk compared to abstainers. Conversely, a high-risk pattern, defined as daily consumption above those limits, or binge drinking episodes, cause health, personal and social problems. This definition separates chronic drinkers from binge drinkers, as their drinking patterns are different. Binge drinking implies "drinking too much too fast". well-known consequences of binge drinking include unintentional injuries, interpersonal violence, fetal alcohol syndrome, child neglect, loss of productivity, suicide, sexually transmitted diseases and unintended pregnancy. This review compiles experimental, clinical and epidemiological data on the binge drinking phenomenon. Binge drinking is a major public heath issue that can no longer be considered simply a momentary risk factor of behavioural concerns, but must now be viewed in light of long-term consequences, such as alcohol-induced liver disease. Binge drinking has a deleterious effect on the liver exacerbated by repeated episodes. The drastic increase in liver cirrhosis and mortality rates in the UK is particularly alarming. The binge phenomenon is now spreading throughout young populations in almost all Western countries. Studies specifically focusing on the risk threshold for development of alcohol cirrhosis in binge drinkers are warranted.

Matsumoto I. Proteomics approach in the study of the pathophysiology of alcohol-related brain damage. Alcohol and Alcoholism 44(2): 171-176, 2009. (81 refs.)

Aims: Chronic, excessive drinking of alcohol can induce brain damage in the regions important for neurocognitive function. Some of the damage are permanent while some are appearantly reversible. It is our aim to understand the molecular mechanisms underlying alcohol-induced and/or related brain damage, particularly of that observed in 'medically uncomplicated' (without heptatic cirrhosis or Wernicke-Korsakoff Syndrome [WKS]) alcoholics. Methods: A high-throughput proteomics technology has been applied to several 'alcohol-sensitive' brain regions from uncomplicated and hepatic cirrhosis-complicated alcoholics to understand the mechanisms of alcohol-related brain damage at the level of protein expression. Results: It was clearly demonstrated that each brain region reacts in significantly different manner to chronic alcohol ingestion. Appearant abnormalities in vitamin B1 (thiamine)-related biochemical pathways were observed in several brain regions, such as the dorsolateral prefrontal cortex, genu (a frontal part of the corpus callosum) and cerebellar vermis in uncomplicated alcoholics, suggesting that the reduction of this important nutritional component might be associated with brain damage even without the signs of WKS. In addition, in the two different subregions of the corpus callosum (genu and splenium [a posterior part of the corpus callosum]) and the cerebellar vermis, significant differences in protein expression profiles between uncomplicated and complicated alcoholics with hepatic cirrhosis were identified, suggesting that hepatic factors such as ammonia have significant additive influences on brain protein expression, which might lead to the structural changes and/or damage in these brain regions. Furthermore, in the hippocampus, significant change of the level of glutamine synthetase expression was observed, suggesting once again the importance of ammonia as a cause of brain damage in this region. Conclusions: Although our data did not show any evidence of "direct" alcohol effects to induce the alteration of protein expression in association with brain damage, high-throughput neuroproteomics approaches are proven to have a potential to dissect the mechanisms of complex brain disorders.

Maurage P; Campanella S; Philippot P; Vermeulen N; Constant E; Luminet O et al. Electrophysiological correlates of the disrupted processing of anger in alcoholism. International Journal of Psychopathology 70(1): 50-62, 2008. (74 refs.)

Objective: Recent studies have shown that alcoholism is characterized by a deficit in the processing of emotional facial expressions (EFE), and that this deficit could be "emotion specific". The present study explored the hypothesis that there is a specific deficit for the EFE of anger compared to another negative emotion (disgust). Moreover, on the basis of event-related potentials (ERPs), this study aimed at determining the locus of this deficit in the information-processing stream. Methods: Fifteen patients suffering from alcoholism and fifteen matched healthy controls took part in the study, which used a "modified emotional" oddball paradigm. ERPs were recorded in response to repetitions of a particular facial expression (i.e. anger) and in response to two deviant (rare) stimuli obtained by a morphing procedure, one depicting the same emotion as the frequent stimulus, the other depicting a different emotion (i.e. disgust). The participants' task was to press a key as soon as they spotted the deviant stimulus. Results: Behavioural data showed an absence of categorical perception effect for anger (but not for disgust) stimuli among alcoholic patients. Moreover, electrophysiological data revealed that alcoholism is associated with an impaired processing of anger at the attentional level (N2b/P3a complex), extending to the decisional level (P3b). Conclusion: This study demonstrated disturbed processing of anger in alcoholism, at behavioural and electrophysiological levels. These preliminary results strengthen the proposition of a specific deficit for anger, and localize its possible origin to the attentional level (N2b/P3a complex) of the information processing stream. The clinical implications of these results are discussed.

Maurage P; Campanella S; Philippot P; Martin S; de Timary P. Face processing in chronic alcoholism: A specific deficit for emotional features. Alcoholism: Clinical and Experimental Research 32(4): 600-606, 2008. (39 refs.)

Background: It is well established that chronic alcoholism is associated with a deficit in the decoding of emotional facial expression (EFE). Nevertheless, it is still unclear whether this deficit is specifically for emotions or due to a more general impairment in visual or facial processing. This study was designed to clarify this issue using multiple control tasks and the subtraction method. Methods: Eighteen patients suffering from chronic alcoholism and 18 matched healthy control subjects were asked to perform several tasks evaluating (1) Basic visuo-spatial and facial identity processing; (2) Simple reaction times; (3) Complex facial features identification (namely age, emotion, gender, and race). Accuracy and reaction times were recorded. Results: Alcoholic patients had a preserved performance for visuo-spatial and facial identity processing, but their performance was impaired for visuo-motor abilities and for the detection of complex facial aspects. More importantly, the subtraction method showed that alcoholism is associated with a specific EFE decoding deficit, still present when visuo-motor slowing down is controlled for. Conclusion: These results offer a post hoc confirmation of earlier data showing an EFE decoding deficit in alcoholism by strongly suggesting a specificity of this deficit for emotions. This may have implications for clinical situations, where emotional impairments are frequently observed among alcoholic subjects.

Mehlig K; Skoog I; Guo X; Schutze M; Gustafson D; Waern M et al. Alcoholic beverages and incidence of dementia: 34-year follow-up of the prospective population study of women in Goteborg. American Journal of Epidemiology 167(6): 684-691, 2008. (35 refs.)

The objective of this study was to assess the association between different types of alcoholic beverages and 34-year incidence of dementia. Among a random sample of 1,462 women aged 38-60 years and living in Goteborg, Sweden, in 1968-1969, 164 cases of dementia were diagnosed by 2002. At baseline as well as in 1974-1975, 1980-1981, and 1992-1993, the frequency of alcohol intake, as well as other lifestyle and health factors, was recorded and related to dementia with Cox proportional hazard regression, by use of both baseline and updated covariates. Wine was protective for dementia (hazard ratio (HR) = 0.6, 95% confidence interval (CI): 0.4, 0.8) in the updated model, and the association was strongest among women who consumed wine only (HR = 0.3, 95% CI: 0.1, 0.8). After stratification by smoking, the protective association of wine was stronger among smokers. In contrast, consumption of spirits at baseline was associated with slightly increased risk of dementia (HR = 1.5, 95% CI: 1.0, 2.2). Results show that wine and spirits displayed opposing associations with dementia. Because a protective effect was not seen for the other beverages, at least part of the association for wine may be explained by components other than ethanol.

Mertens JR; Flisher AJ; Satre DD; Weisner M. The role of medical conditions and primary care services in 5-year substance use outcomes among chemical dependency treatment patients. Drug and Alcohol Dependence 98(1/2): 45-53, 2008. (54 refs.)

Introduction: Health problems are prevalent in chemical dependency (CD) treatment populations, and often precede reductions in substance use among untreated populations. Few studies have examined whether medical problems predict better long-term outcomes in treated individuals, or how primary care utilization and CD/primary care service integration affects long-term outcomes among those with health problems. Method: In a sample of 598 CD patients in a private health plan, logistic regression models examined whether substance abuse-related medical conditions (SAMCs), integrated medical and CD care, and on-going primary care predicted remission of CD problems at 5 years. Results: Those with SAMCs were no more likely than others to be remitted at 5 years except among young adults and those with medical, but not psychiatric SAMCs. Higher levels of medical problem severity at intake and receiving integrated CD and primary care in the index treatment episode predicted remission in the full sample and among those with SAMCs. Among those with SAMCs, individuals with ongoing medical care - 2-10 primary care visits - in the 5 years following intake were more likely to be remitted at 5 years than those with fewer visits. Conclusions: This study highlights the potentially important role of medical services in the long-term treatment of CD disorders. CD treatment may benefit from a disease management approach similar to that recommended for other chronic medical problems: specialty care when the condition is severe followed by services in primary care when the condition is stabilized.

Molina PE; Lang CH; McNurlan M; Bagby GJ; Nelson S. Chronic alcohol accentuates simian acquired immunodeficiency syndrome-associated wasting. Alcoholism: Clinical and Experimental Research 32(1): 138-147, 2008. (57 refs.)

Background: Survival following human immunodeficiency virus (HIV) infection has improved significantly following the advent of highly active antiretroviral therapy. A large percentage of HIV-infected patients consume and abuse alcohol. Erosion of lean body mass is an important contributing factor to patient morbidity and mortality, and is a common feature of both chronic alcohol (ALC) consumption and acquired immunodeficiency syndrome (AIDS). We hypothesized that alcohol-induced loss in lean body mass is likely to exacerbate the AIDS wasting syndrome, particularly at the terminal stage of AIDS (SAIDS). Methods: This study examined the impact of chronic, intra-gastric ALC (5 h/d x 4 d/wk; blood alcohol levels = 55 mM to 60 mM) administration on body composition and muscle mass in simian immunodeficiency virus (SIV)-infected male Rhesus macaques in contrast to SIV-infected isocaloric (22 kcal/kg/d) sucrose (SUC)-infused control animals at the terminal stage of SIV infection. Results: At terminal stage, ALC/SIV+ animals had significantly lower body weight, body mass index, and limb muscle area than SUC/SIV+ animals. Both ALC/SIV+ and SUC/SIV+ animals had suppressed expression of insulin-like growth factor-I and increased expression of the ubiquitin ligase muscle-specific RING finger-1 mRNA. ALC increased mRNA expression of atrogin-1 (pre-SIV and at SAIDS) and tumor necrosis factor (TNF)-alpha (SAIDS). These changes were not associated with significant differences in fractional rates of muscle protein synthesis or in overall survival rate. These data show that chronic ALC exacerbated the loss of muscle mass at terminal SAIDS. Conclusion: Our findings suggest the involvement of TNF-alpha and increased muscle proteolysis via atrogin-1 for the greater erosion of lean body mass at terminal SAIDS in ALC-treated Rhesus macaques.

Ness KJ; Fan J; Wilke WW; Coleman RA; Cook RT; Schlueter AJ. Chronic ethanol consumption decreases murine langerhans cell numbers and delays migration of langerhans cells as well as dermal dendritic cells. Alcoholism: Clinical and Experimental Research 32(4): 657-668, 2008. (42 refs.)

Background: Chronic alcoholics experience increased incidence and severity of infections, the mechanism of which is incompletely understood. Dendritic cells (DC) migrate from peripheral locations to lymph nodes (LN) to initiate adaptive immunity against infection. Little is known about how chronic alcohol exposure affects skin DC numbers or migration. Methods: Mice received 20% EtOH in the drinking water for up to 35 weeks. Baseline Langerhans cell (LC) and dermal DC (dDC) numbers were enumerated by immunofluorescence (IF). LC repopulation after inflammation was determined following congenic bone marrow (BM) transplant and ultraviolet (UV) irradiation. Net LC loss from epidermis was determined by IF following TNF-alpha or CpG stimulation. LC and dDC migration into LN was assessed by flow cytometry following epicutaneous FITC administration. Results: Chronic EtOH consumption caused a baseline reduction in LC but not dDC numbers. The deficit was not corrected following transplantation with non-EtOH-exposed BM and UV irradiation, supporting the hypothesis that the defect is intrinsic to the skin environment rather than LC precursors. Net loss of LC from epidermis following inflammation was greatly reduced in EtOH-fed mice versus controls. Ethanol consumption for at least 4 weeks led to delayed LC migration into LN, and consumption for at least 8 weeks led to delayed dDC migration into LN following epicutaneous FITC application. Conclusions: Chronic EtOH consumption causes decreased density of epidermal LC, which likely results in decreased epidermal immunosurveillance. It also results in altered migratory responsiveness and delayed LC and dDC migration into LN, which likely delays activation of adaptive immunity. Decreased LC density at baseline appears to be the result of an alteration in the skin environment rather than an intrinsic LC defect. These findings provide novel mechanisms to at least partially explain why chronic alcoholics are more susceptible to infections, especially those following skin penetration.

Noel X; Billieux J; Van der Linden M; Dan B; Hanak C; de Bournonville S et al. Impaired inhibition of proactive interference in abstinent individuals with alcoholism. Journal of Clinical and Experimental Neuropsychology 31(1): 57-64, 2009. (39 refs.)

Cognitive impairment has been associated with higher risk of alcoholism and relapse. Recent theoretical refinements have separated inhibition of dominant response and inhibition of proactive interference. We assessed the latter using a directed-forgetting procedure in 38 recently detoxified individuals with alcoholism and in 26 controls. On this task, memory performance of letter trigrams was compared when presented alone, followed by a second trigram to be recalled, then a second trigram to be forgotten (directed-forgetting condition). Individuals with alcoholism recalled more letters to be forgotten and performed worse than controls in the directed-forgetting condition, which significantly correlated with the duration of alcoholism.

Otis JS; Mitchell PO; Kershaw CD; Joshi PC; Guidot DM. Na,K-ATPase expression is increased in the lungs of alcohol-fed rats. Alcoholism: Clinical and Experimental Research 32(4): 699-705, 2008. (42 refs.)

Background: Alcohol abuse independently increases the risk of developing the acute respiratory distress syndrome (ARDS), a disease characterized by diffuse alveolar epithelial damage, lung edema, and consequent severe hypoxemia. Chronic alcohol abuse increases alveolar epithelial permeability both in vitro and in vivo, in part due to altered tight junction formation. However, both alcohol-fed animals and otherwise healthy alcoholic humans do not have pulmonary edema at baseline, even though their lungs are highly susceptible to acute edematous injury in response to inflammatory stresses. This suggests that active fluid transport by the alveolar epithelium is preserved or even augmented in the alcoholic lung. Chronic alcohol ingestion increases expression of apical sodium channels in the alveolar epithelium; however, its effects on the Na,K-ATPase complex that drives sodium and fluid transport out of the alveolar space have not been examined. Methods: Age- and gender-matched Sprague-Dawley rats were fed the Lieber-DeCarli liquid diet containing either alcohol or an isocaloric substitution (control diet) for 6 weeks. Gene and protein expression of lung Na,K-ATPase alpha 1, alpha 2, and beta 1 subunits were quantified via real-time PCR and immunobiological analyses, respectively. Alcohol-induced, Na,K-ATPase-dependent epithelial barrier dysfunction was determined by calculating lung tissue wet:dry ratios following an ex vivo buffer-perfused challenge for 2 hours in the presence of ouabain (10(-4) M), a Na,K-ATPase inhibitor. Results: Chronic alcohol ingestion significantly increased gene and protein expression of each Na,K-ATPase subunit in rat lungs. Immunohistochemical analyses of the alcoholic lung also revealed that protein expression of the Na,K-ATPase alpha 1 subunit was increased throughout the alveolar epithelium. Additionally, lungs isolated from alcohol-fed rats developed more edema than comparably treated lungs from control-fed rats, as reflected by increased lung tissue wet:dry ratios. Conclusions: These findings indicate that chronic alcohol ingestion, which is known to increase alveolar epithelial paracellular permeability, actually increases the expression of Na,K-ATPase in the lung as a compensatory mechanism. This provides a potential explanation as to why the otherwise healthy alcoholic does not have evidence of pulmonary edema at baseline.

Pandeya N; Williams G; Green AC; Webb PM; Whiteman DC. Alcohol consumption and the risks of adenocarcinoma and squamous cell carcinoma of the esophagus. Gastroenterology 136(4): 1215-1224, 2009. (34 refs.)

Background and Aim: Alcohol has been declared a carcinogen for cancers of the esophagus, although the evidence relates largely to the squamous subtype. Evidence for an effect on adenocarcinomas is scant and inconsistent. Methods: We compared nationwide samples of patients with esophageal adenocarcinoma (EAC) (n = 365) or esophagogastric junction adenocarcinoma (EGJAC) (n = 426) or esophageal squamous cell carcinoma (ESCC) (n = 303) with controls sampled from a population register (n = 1580). We used generalized additive models to assess nonlinear effects of self-reported alcohol intake on cancer risk, and calculated odds ratios (ORs) and 95% confidence intervals (CIs) using multivariate logistic and piecewise regression. Results: We observed no association between average weekly alcohol intake and EAC or EGJAC risk. For ESCC, the relationship with alcohol was nonlinear. At intakes of less than 170 g/wk there was no significant association; at greater than this level, there was a significant linear effect (OR, 1.03; 95% CI, 1.02-1.05 per 10 g alcohol/wk). For ESCC, but not EAC or EGJAC, a statistically significant multiplicative interaction between smoking and alcohol was observed (P = .02). In analyses by beverage type, ESCC risks, but not EAC or EGJAC, increased linearly with beer intake (OR, 1.05; 95% CI, 1.04-1.07). Those who drank modest levels of wine (< 50-90 g/wk) or port or spirits (< 10-20 g/wk) had significantly lower risks of all 3 cancers than nondrinkers; higher intakes were associated with increased risks of ESCC only. Conclusions: Alcohol intake above the recommended US dietary guidelines significantly increases the risk of ESCC, but not EAC or EGJAC. Smoking modifies the effect of alcohol intake on ESCC risk.

Pfefferbaum A; Rosenbloom M; Rohlfing T; Sullivan EV. Degradation of association and projection white matter systems in alcoholism detected with quantitative fiber tracking. Biological Psychiatry 65(8): 680-690, 2009. (87 refs.)

Background: Excessive alcohol use can cause macrostructural tissue shrinkage with regional preference for frontal systems. The extent and locus of alcoholism's effect on white matter microstructure is less known. Methods: Quantitative fiber tracking derived from diffusion tensor imaging (DTI) assessed the integrity of samples of 11 major white matter bundles in 87 alcoholics (59 men, 28 women) and 88 healthy control subjects (42 men, 46 women). Fiber integrity was expressed as fractional anisotropy (FA) and apparent diffusion coefficient (ADC), quantified separately for longitudinal diffusivity (lambda L), a putative index of axonal integrity, and transverse diffusivity (lambda L), a putative index of myelin integrity. Results: Alcoholism affected FA and diffusivity, particularly lambda T, of several fiber bundles. Frontal and superior sites (frontal forceps, internal and external capsules, fornix, and superior cingulate and longitudinal fasciculi) showed greatest abnormalities in alcoholics relative to control subjects. More posterior and inferior bundles were relatively spared. Lifetime alcohol consumption correlated with regional DTI measures in alcoholic men but not women. When matched for alcohol exposure, alcoholic women showed more DTI signs of white matter degradation than alcoholic men in several fiber bundles. Among all alcoholics, poorer performance on speeded tests correlated with DTI signs of regional white matter degradation. Conclusions: This survey of multiple brain fiber systems revealed a differential pattern of alcoholism's effect on regional FA and diffusivity with functional consequences attributable in part to compromised fiber microstructure with prominence in signs of myelin degradation. Sex-based differences suggest that women are at enhanced risk for alcoholism-related degradation in selective white matter systems.

Pitel AL; Beaunieux H; Witkowski T; Vabret F; de la Sayette V; Viader F et al. Episodic and working memory deficits in alcoholic Korsakoff patients: The continuity theory revisited. Alcoholism: Clinical and Experimental Research 32(7): 1229-1241, 2008. (89 refs.)

Background: The exact nature of episodic and working memory impairments in alcoholic Korsakoff patients (KS) remains unclear, as does the specificity of these neuropsychological deficits compared with those of non-Korsakoff alcoholics (AL). The goals of the present study were therefore to (1) specify the nature of episodic and working memory impairments in KS, (2) determine the specificity of the KS neuropsychological profile compared with the AL profile, and (3) observe the distribution of individual performances within the 2 patient groups. Methods: We investigated episodic memory (encoding and retrieval abilities, contextual memory and state of consciousness associated with memories), the slave systems of working memory (phonological loop, visuospatial sketchpad and episodic buffer) and executive functions (inhibition, flexibility, updating and integration abilities) in 14 strictly selected KS, 40 AL and 55 control subjects (CS). Results: Compared with CS, KS displayed impairments of episodic memory encoding and retrieval, contextual memory, recollection, the slave systems of working memory and executive functions. Although episodic memory was more severely impaired in KS than in AL, the single specificity of the KS profile was a disproportionately large encoding deficit. Apart from organizational and updating abilities, the slave systems of working memory and inhibition, flexibility and integration abilities were impaired to the same extent in both alcoholic groups. However, some KS were unable to complete the most difficult executive tasks. There was only a partial overlap of individual performances by KS and AL for episodic memory and a total mixture of the 2 groups for working memory. Conclusions: Korsakoff's syndrome encompasses impairments of the different episodic and working memory components. AL and KS displayed similar profiles of episodic and working memory deficits, in accordance with neuroimaging investigations showing similar patterns of brain damage in both alcoholic groups.

Pitel AL; Beaunieux H; Guillery-Girard B; Witkowski T; de la Sayette V; Viader F et al. How do Korsakoff patients learn new concepts? Neuropsychologia 47(3): 879-886, 2009. (51 refs.)

The goal of the present investigation was to assess semantic learning in Korsakoff patients (KS), compared with uncomplicated alcoholics (AL) and control subjects (CS), taking the nature of the information to-be-learned and the episodic memory profiles of the three groups into account. Ten new complex concepts, each illustrated by a photo and composed of a label, a category and three features, were taught to 13 KS, 23 AL and 45 CS. When examined independently of the main experimental task, the two patients' groups presented episodic memory, working memory and executive impairments but episodic memory was more severely impaired in KS. Both AL and KS exhibited label learning deficits but KS were more severely impaired than AL The episodic memory results were the main factor accounting for label learning performance when the three groups were pooled together. When examined within each group, the correlation was significant in CS and AL but not in KS. Only KS exhibited impaired category and feature learning results. Episodic memory did not account for category and feature learning performance. New label learning may be equivalent to that of proper names, requiring the involvement of episodic memory notably to arbitrarily associate a meaningless word with a specific identity. However, when episodic memory is severely impaired like in KS, an alternative neocortical learning route, bypassing episodic memory, may be invoked. Category and feature seem to be acquired independently of episodic memory. The specific impairment in category and feature learning in KS may therefore reflect a genuine deficit of semantic memory in Korsakoff's syndrome.

Poikolainen K; Alho H. Magnesium treatment in alcoholics: A randomized clinical trial. Substance Abuse Treatment, Prevention, and Policy 3(e-article 1), 2008. (17 refs.)

Background: Magnesium (Mg) deficiency is common among alcoholics. Earlier research suggests that Mg treatment may help to normalize elevated enzyme activities and some other clinically relevant parameters among alcoholics but the evidence is weak. Methods: The effect of Mg was studied in a randomized, parallel group, double blind trial. The patients were first treated for alcohol withdrawal symptoms and then received for 8 weeks either 500 mg of Mg divided into two tablets or matching placebo. Measurements were made at the beginning and in the end of the Mg treatment period. The primary outcome was serum gamma-glutamyltransferase (S-GGT) activity; secondary outcomes included aspartate-aminotransferase (S-AST) and alanine-aminotransferase (S-ALT) activity. Results:The number of randomized patients (completers) was 64 (27) in the treatment and 54 (31) in the control group. In intention-to-treat-analyses and in most analyses of study completers, there were no significant differences between the Mg-treated and placebo groups in the outcome variables. When baseline serum Mg level, coffee intake, and the number of unused Mg tablets were controlled for in a multivariate regression model, after-treatment serum Mg levels were found to be higher among the Mg-treated group than in the placebo group (t-test 3.334, df=53, p=0.002). After controlling for age, body weight, baseline alcohol intake, subsequent change in alcohol intake and baseline S-AST, the after-treatment S-AST levels were found to be lower among the Mg-treated group than in the placebo group (t-test 2.061, df=49, p=0.045). Conclusions: Mg treatment may speed up the S-AST decrease in compliant patients. This might decrease the risk of death from alcoholic liver disease. Correction. After publication of our work (Poikolainen et al; Substance Abuse Treatment, Prevention, and Policy 2008, 3:1), we noticed that the magnesium (Mg) content of the trial tablets was inadvertently given as 250 mg. The correct content was 200 mg. Thus the first sentence under the subtitle "Intervention" should read: The patients received orally for 8 weeks either a daily dose of 400 mg of Mg tablets divided in two tablets (200 mg each) or matching placebo tablets.

Rehm J. Commentary. Alcohol poisoning in Russia: implications for monitoring and comparative risk factor assessment. (editorial). International Journal of Epidemiology 38(1): 154-155, 2009. (13 refs.)

Richardson HN; Lee SY; O'Dell LE; Koob GF; Rivier CL. Alcohol self-administration acutely stimulates the hypothalamic-pituitary-adrenal axis, but alcohol dependence leads to a dampened neuroendocrine state. European Journal of Neuroscience 28(8): 1641-1653, 2008. (77 refs.)

Clinical studies link disruption of the neuroendocrine stress system with alcoholism, but remaining unknown is whether functional differences in the hypothalamic-pituitary-adrenal (HPA) axis precede alcohol abuse and dependence or result from chronic exposure to this drug. Using an operant self-administration animal model of alcohol dependence and serial blood sampling, we show that long-term exposure to alcohol causes significant impairment of HPA function in adult male Wistar rats. Acute alcohol (voluntary self-administration or experimenter-administered) stimulated the release of corticosterone and its upstream regulator, adrenocorticotropic hormone, but chronic exposure sufficient to produce dependence led to a dampened neuroendocrine state. HPA responses to alcohol were most robust in 'low-responding' non-dependent animals (averaging < 0.2 mg/kg/session), intermediate in non-dependent animals (averaging similar to 0.4 mg/kg/session), and most blunted in dependent animals (averaging similar to 1.0 mg/kg/session) following several weeks of daily 30-min self-administration sessions, suggesting that neuroendocrine tolerance can be initiated prior to dependence and relates to the amount of alcohol consumed. Decreased expression of corticotropin-releasing factor (CRF) mRNA expression in the paraventricular nucleus of the hypothalamus and reduced sensitivity of the pituitary to CRF may contribute to, but do not completely explain, neuroendocrine tolerance. The present results, combined with previous studies, suggest that multiple adaptations to stress regulatory systems may be brought about by excessive drinking, including a compromised hormonal response and a sensitized brain stress response that together contribute to dependence.

Rosenbloom MJ; Pfefferbaum A. Magnetic resonance imaging of the living brain: Evidence for brain degeneration among alcoholics and recovery with abstinence. (review). Alcohol Research & Health 31(4): 362-376, 2008. (110 refs.)

Magnetic resonance imaging (MRI) provides a safe, noninvasive method to examine the brain's macrostructure, microstructure, and some aspects of how the living brain functions. MRI is capable of detecting abnormalities that can occur with alcoholism as well as changes that can occur with sobriety and relapse. The brain pathology associated with chronic excessive alcohol consumption is well documented with imaging of the living body (i.e., in vivo imaging). Consistent findings include shrinkage of the frontal cortex,(1) underlying white matter, and cerebellum and expansion of the ventricles. Some of these changes are reversible with abstinence, but some appear to be enduring. Research showing correlations between brain structure and quantitative neuropsychological testing demonstrates the functional consequences of the pathology. In addition, functional imaging studies provide evidence that the brain compensates for cognitive deficits. The myriad concomitants of alcoholism, the antecedents, and the consumption patterns each may influence the observed brain changes associated with alcoholism, which tend to be more deleterious with increasing age. The multifaceted nature of alcoholism presents unique challenges and opportunities to understand the mechanisms underlying alcoholism-induced neuropathology and its recovery. Longitudinal MRI studies of animal models of alcoholism, however, can address questions about the development and course of alcohol dependence and the scope and limits of in vivo degeneration and recovery of brain structure and concomitant function that may not be readily addressed in clinical studies.

Public Domain

Scully C; Bagan JV; Eveson JW; Barnard N; Turner FM. Sialosis: 35 cases of persistent parotid swelling from two countries. British Journal of Oral & Maxillofacial Surgery 46(6): 468-472, 2008. (25 refs.)

Diffuse, non-inflammatory, non-neoplastic enlargement of the major salivary glands (sialosis) is uncommon and has various systemic causes. This paper examines 35 patients whose persistent swelling of the parotid was diagnosed as sialosis, and shows that diabetes mellitus and alcoholism are the most common causes.

Shibuya N; La Fontaine J; Frania SJ. Alcohol-induced neuroarthropathy in the foot: A case series and review of literature. Journal of Foot & Ankle Surgery 47(2): 118-124, 2008. (28 refs.)

Charcot arthropathy, also known as neuroarthropathy, is most commonly associated with diabetes mellitus, despite a variety of other etiologies. A limited number of case reports have been published on neuroarthropathies caused by other forms of neuropathy, including alcoholic peripheral neuropathy. We report 4 cases of neuroarthropathy associated with chronic alcoholism in nondiabetic individuals. Conservative management similar to that afforded diabetic patients was successfully employed in these cases. A review of the clinical presentation and the pathology of alcoholic neuropathy is included in this report.

Singer MV; Pfutzer RH; Kiefer F. Striving for abstinence in alcoholic pancreatitis: Act of humanity, economic necessity, or flogging a dead horse after all? (ediorial). Gastroenterology 136(3): 757-760, 2009. (19 refs.)

Song HJ; Kim HJ; Choi NK; Hahn S; Cho YJ; Park BJ. Gender differences in gastric cancer incidence in elderly former drinkers. Alcohol 42(5): 363-368, 2008. (19 refs.)

Although numerous studies have been done on gastric cancer and alcohol consumption, results from these studies are inconsistent. We conducted a population-based, prospective cohort study to establish a relationship between alcohol and gastric cancer according to gender. The cohort consisted of elderly (> 64 years of age) subjects at the baseline of 1993-1998. Baseline information was surveyed using a self-administered questionnaire. Gastric cancers were identified by the National Cancer Registry. Cox proportional hazards models were used to calculate relative risks with 95% confidence intervals. A follow up of 116,997.1 person-years of the 13,396 subjects revealed 151 newly diagnosed gastric cancers (80 men and 71 women). The risk of gastric cancer was higher by a factor of three among female former drinkers (adjusted relative risk 2.85 [95% confidence interval 1.11-7.32]) compared to current and nondrinkers. Female former drinkers showed greater alcohol consumption than current drinkers (36.5 g/week vs. 16.4 g/week; P <.0001) and a longer duration of alcohol consumption than did current drinkers (24.5 years vs. 18.46 years; P <.0001). Female subjects with more than 110 g of weekly alcohol consumption had an increased risk of developing gastric cancer (adjusted relative risk 2.23 [95% confidence interval 0.79-6.29]), although the result was statistically insignificant. No relationship was observed for male subjects. The relationship between alcohol and gastric cancer differs according to gender. Alcohol consumption may increase the risk of gastric cancer in women, and the risk elevation may persist for several years after drinking ceases.

Soyka M. Prevalence of delirium tremens. (letter). American Journal on Addictions 17(5): 452, 2008. (7 refs.)

Sprah L; Novak T. Neurocognitive assessment of alcohol inpatients during recovery from alcoholism. Zdravinski Vestnik-Slovenia Medical Journal 77(Supplement 2): 1175-1184, 2008. (71 refs.)

Objective: The aim of study was a neuropsychological evaluation of cognitive, emotional and motivational functioning of abstinent alcohol inpatients. Background: Alcohol dependence is characterized by a neuropsychological profile of extensive impairment in executive functions, visuospatial abilities, sociocognitive, emotional and motivational dysfunctions. A growing body of research evidence suggests that alcoholism-related structural and functional brain changes may underlay abovementioned deficits. Nevertheless, certain alcohol-related impairments are reversible with abstinence. Several studies indicated that with prolonged abstinence functional improvement in memory, visuospatial abilities, and attention occur within 3 to 4 weeks of abstinence accompanied by at least partial reversal of brain shrinkage and some recovery of metabolic functions in the frontal lobes and cerebellum, as well as with increased cortical grey matter volume. Methods: 33 male abstinent alcohol inpatients (average abstinence: 8 weeks) and 36 healthy controls were tested on the following domains: attention (classical vs. emotional Stroop Task), working memory (spatial vs. verbal), visuospatial abilities (Benton Face Recognition Task, Line Orientation Test), emotionality (Ekman Emotional Recognition Task, Test of Emotional Styles, Beck Depression Inventory) and motivation (Behavioural Inhibition/Activation Scale). Results: Alcohol abstainers compared to healthy controls showed impaired attention, more depressive symptoms and overactive activation behavioural system, whereas the working memory and visuospatial tasks did not reveal significant differences between groups. A specific neuropsychological profile has been found among alcohol abstainers with suicidal history where lower emotion recognition ability and attention difficulties with emotional stimuli have been recorded. Conclusions: Our study demonstrated that some alcohol-related cognitive, emotional and motivational deficits can also persist to certain extent after several weeks of sobriety. Especially alcohol abstainers with suicidal history revealed a specific neuropsychological profile in this regard. Employed neurocognitive assessment proved as useful approach for clinical evaluation of alcohol abstainers functioning, since cognitive deficits have been also hypothesized to affect the efficacy of alcoholism treatment.

Stephens DN; Duka T. Cognitive and emotional consequences of binge drinking: Role of amygdala and prefrontal cortex. Philosophical Transactions of the Royal Society of London. Series B. Biological Sciences 363(1507): 3169-3179, 2008. (88 refs.)

Binge drinking is an increasingly recognized problem within the UK. We have studied the relationship of binge drinking to cognitive and emotional functioning in young adults, and have found evidence for increased impulsivity, impairments in spatial working memory and impaired emotional learning. Since in human studies it is difficult to understand whether such behavioural changes predate or are a consequence of binge drinking, we have also studied parallel behaviours in a rodent model, in which rats are exposed to intermittent episodes of alcohol consumption and withdrawal. In this model, and in parallel with our findings in human binge drinkers, and alcoholic patients who have undergone multiple episodes of detoxification, we have found evidence for impairments in aversive conditioning as well as increased impulsivity. These behavioural changes are accompanied by facilitated excitatory neurotransmission and reduced plasticity (long-term potentiation (LTP)) in amygdala and hippocampus. The impaired LTP is accompanied by both impaired associative learning and inappropriate generalization of previously learned associations to irrelevant stimuli. We propose that repeated episodes of withdrawal from alcohol induce aberrant neuronal plasticity that results in altered cognitive and emotional competences.

Sullivan EV; Zahr NM. Neuroinflammation as a neurotoxic mechanism in alcoholism: Commentary on "Increased MCP-1 and microglia in various regions of human alcoholic brain" (editorial). Experimental Neurology 213(1): 10-17, 2008

Takougang I; Ngogang J; Sihom F; Ntep M; Kamgno J; Eyamba A et al. Does alcohol consumption increase the risk of severe adverse events to ivermectin treatment? African Journal of Pharmacy and Pharmacology 2(4): 77-82, 2008. (22 refs.)

The present investigation is a case-control study designed to assess the level of association between alcohol consumption and the occurrence of severe adverse reaction (SAE) following ivermectin consumption. [Note: Ivermectin is a medication to deal with worms that cause river blindness] Thirty-six (36) cases of SAE occurred in the health districts of Bankim, Nanga Eboko, Obala, Okola and Sa'a. Case and control (43) individuals were submitted to a questionnaire related to their alcohol consumption 24 before and 24 to 48 h following ivermectin intake. An in-depth interview of siblings and local health worker was conducted to assess alcohol consumption around Mectizan intake. The degree of alcohol use was assessed using the level of serum transaminases and the alcohol use disorder identification test (AUDIT). The alcoholic beverages of the study communities were conventional such as beer, whisky, or locally made. Locally produced beverages included "arki" ("Odontol", "Hah", ...) and palm wine. The bark, sap or fruit of plants adjuvant are known to contain alkaloids and tannins which are potent neurotropic substances. The likelihood of developing SAE among cases and controls did not differ significantly with history of consumption of alcoholic beverages. Nor did it differ for other indicators of chronic alcohol consumption.

Tanev KS; Roether M; Yang C. Alcohol dementia and thermal dysregulation: A case report and review of the literature. (review). American Journal of Alzheimers Disease and Other Dementias 23(6): 563-570, 2008. (27 refs.)

Wernicke's encephalopathy and Korsakoff's psychosis in alcoholics are thought to be due to thiamine deficiency. When the process goes untreated, patients may develop alcohol-induced persisting dementia. We review the literature on thermal dysregulation and the place of thiamine treatment in Wernicke's encephalopathy, Korsakoff's psychosis, and alcohol-induced persisting dementia. We describe a patient with alcohol-induced persisting dementia who showed thermal dysregulation which responded to parenteral but not oral thiamine. Subsequently, he developed aspiration pneumonia with associated fever reaction and expired. We describe the neuroimaging findings-diffuse cortical atrophy, ventricular dilatation, atrophy of the corpus callosum, hypothalamus, and medulla, and a probable arachnoid cyst in the left temporal tip. We conclude that thermal dysregulation was likely related to dysfunction of temperature regulatory brain centers, that thermal dysregulation was stabilized with parenteral but not oral thiamine, and that parenteral thiamine may have a role even in chronic cases of alcohol-induced persisting dementia.

Thoma P; Johann K; Wahner A; Juckel G; Daum I. Recollective experience in alcohol dependence: A laboratory study. Addiction 103(12): 1969-1978, 2008. (65 refs.)

Alcohol dependence has been linked to dysfunction of fronto-temporo-striatal circuits which mediate memory and executive function. The present study aimed to explore the specificity of recognition memory changes in alcohol dependence. Twenty hospitalized alcohol-dependent detoxified patients and 20 healthy control subjects completed a verbal list discrimination task. Hits and false alarm rates were analysed. Additionally, both the dual process signal detection model (DPSD) and the process dissociation procedure (PDP) were used to derive estimates of the contribution of recollection and familiarity processes to the recognition memory performance in patients and controls. Alcohol-dependent patients showed intact hit rates, but increased false alarm rates and an impaired ability to remember the learning context. Both the DPSD model and PDP estimates yielded significantly reduced recollection estimates in the alcohol-dependent compared to control subjects. Whether or not familiarity was impaired, depended upon the sensitivity of the estimation procedure. Taken together, the result pattern suggests a significant impairment in recollection and mild familiarity changes in recently detoxified, predominantly male, alcohol-dependent subjects.

Thomson AD; Cook CCH; Guerrini I; Sheedy D; Harper C; Marshall EJ. Wernickes encephalopathy: 'Plus ca change, plus c'est la meme chose'. Alcohol and Alcoholism 43(2): 180-186, 2008. (40 refs.)

Aims: To develop clinical guidelines to identify individuals who misuse alcohol and are at risk of developing Wernickes Encephalopathy (WE). Method: Non-systematic literature review of studies which includes a careful clinical record of the development of signs and symptoms of thiamine deficiency and in which the diagnosis of WE has been confirmed at autopsy. Results: The review of the clinical findings in cases of WE, diagnosed at autopsy, shows a consistent pattern of signs and symptoms. The pattern appears to be similar regardless of whether the thiamine deficiency is related to nutritional problems alone or associated with alcohol misuse. Conclusions: The assessment of the degree of thiamine deficiency and the diagnosis of WE remain a clinical evaluation, and guidelines are suggested to help the clinician. Since neurotoxicity due to the metabolism of excessive alcohol in patients with chronic and severe alcohol dependence may be an important factor in determining long-term outcome of treatment, this must form part of the overall evaluation.

Thomson AD; Cook CCH; Guerrini I; Sheedy D; Harper C; Marshall EJ. Wernicke's encephalopathy revisited. (review). Alcohol and Alcoholism 43(2): 174-179, 2008. (16 refs.)

Aims: A translation into English of the case history section of Carl Wernickes original manuscript of 1881, with a discussion on its relevance for clinicians today. Methods: A copy of Carl Wernickes original German text was obtained by one of the authors (CCHC) and translated into English from the old German by a professional translator. Results: The translation was subsequently agreed by native German speaking referees, and minor changes made. Conclusions: The authors studied the translation in detail and concluded that Wernickes description had stood the test of time. The diagnosis of Wernickes Encephalopathy remains a clinical one.

Uekermann J; Daum I. Social cognition in alcoholism: A link to prefrontal cortex dysfunction? (review). Addiction 103(5): 726-735, 2008. (129 refs.)

Aims: Alcoholism is associated with a range of cognitive deficits. These deficits might be explained by the 'frontal lobe hypothesis' which suggests a specific vulnerability of the prefrontal cortex (PFC) to the neurotoxic effects of alcohol. Social cognition is thought to be processed in the PFC, but so far only few studies have addressed the issue of social cognition deficits in alcoholism. This review aims to evaluate the deficits in social cognition in alcoholic patients. In addition an outline for future perspectives is given. Methods Medline and Psyclit searches were performed for a 30-year period (1977-2007). Results: Alcoholism is associated clearly with social cognition impairments which include emotional face and prosody perception problems, theory of mind deficits and humour processing difficulties. Conclusions: In summary, the social cognition impairments are consistent with the frontal lobe hypothesis of alcoholism. Future studies should focus on (i) the delineation of the basic cognitive processes which underlie social cognition deficits; and (ii) their relevance as predictors of treatment outcome in alcoholism.

Underwood MD; Mann JJ; Huang YY; Arango V. Family history of alcoholism is associated with lower 5-HT2A receptor binding in the prefrontal cortex. Alcoholism: Clinical and Experimental Research 32(4): 593-599, 2008. (51 refs.)

Background: 5-Hydroxytryptophan (5-HT2A) receptor involvement in alcoholism is suggested by less 5-HT2A binding in alcohol preferring rats, association of a 5-HT2A receptor gene polymorphism with alcohol dependence and reduced alcohol intake with 5-HT2A antagonists. We sought to determine postmortem whether 5-HT2A receptors are altered in the prefrontal cortex (PFC) of alcoholics. Methods: Brain tissue from 25 alcoholics and 19 controls was collected at autopsy. Diagnosis of DSM-IV alcoholism/abuse and other psychiatric disorders and the determination of family history of alcoholism were made by psychological autopsy. Specific binding to 5-HT2A (H-3-ketanserin) receptors in the PFC was measured by quantitative autoradiography. Results: 5-HT2A binding decreased with age [Brodmann areas (BA) 9, 46 gyrus; r = -0.381, -0.334, p < 0.05]. No differences in receptor binding between alcoholics and controls were detected in the gyrus or sulcus of any PFC area examined. Cases (controls or alcoholics) with a family history of alcoholism (n = 23) had less 5-HT2A binding throughout PFC than subjects without (n = 21) a family history of alcoholism (p < 0.05). 5-HT2A receptor binding in alcoholics without a family history of alcoholism (n = 7) did not differ from controls without a family history of alcoholism (n = 14). There was no association between alcoholism or alcohol rating and genotype. There was an association between genotype and the total amount of H-3-ketanserin binding in BA46 with the TT genotype having more binding (TT > TC approximate to CC). Conclusions: Lower 5-HT2A receptor binding in the PFC of cases with a family history of alcoholism suggests a genetic predisposition to alcoholism. Alcohol abuse by itself did not have a significant effect on PFC 5-HT2A binding and as 5-HT2A binding in alcoholics is not different from controls and antagonists may be therapeutic, fewer receptors may result in downstream developmental effects on the brain resulting in a predisposition to alcoholism.

Vanlemmens C; Di Martino V; Milan C; Messner M; Minello A; Duvoux C et al. Immediate listing for liver transplantation versus standard care for Child-Pugh stage B alcoholic cirrhosis: A randomized trial. Annals of Internal Medicine 150(3): 153+, 2009. (30 refs.)

Background: Liver transplantation improves survival of patients with end-stage (Child-Pugh stage C) alcoholic cirrhosis, but its benefit for patients with stage B disease is uncertain. Objective: To compare the outcomes of patients with Child-Pugh stage B alcoholic cirrhosis who are immediately listed for liver transplantation with those of patients assigned to standard treatment with delay of transplantation until progression to stage C disease. Design: Randomized, controlled trial. Setting: 13 liver transplantation programs in France. Patients: 120 patients with Child-Pugh stage B alcoholic cirrhosis and no viral hepatitis, cancer, or contraindication to transplantation. Interventions: Patients were randomly assigned to immediate listing for liver transplantation (60 patients) or standard care (60 patients). Measurements: Overall and cancer-free survival over 5 years. Results: Sixty-eight percent of patients assigned to immediate listing for liver transplantation and 25% of those assigned to standard care received a liver transplant. All-cause death and cirrhosis-related death did not statistically differ between the 2 groups: 5-year survival was 58% (95% CI, 43% to 70%) for those assigned to immediate listing versus 69% (CI, 54% to 80%) for those assigned to standard care. In multivariate analysis, independent predictors of long-term survival were absence of ongoing alcohol consumption (hazard ratio, 7.604 [ CI, 2.395 to 24.154]), recovery from Child-Pugh stage C (hazard ratio, 7.633 [ CI, 2.392 to 24.390]), and baseline Child-Pugh score less than 8 (hazard ratio, 2.664 [ CI, 1.052 to 6.746]). Immediate listing for transplantation was associated with an increased risk for extrahepatic cancer: The 5-year cancer-free survival rate was 63% (CI, 43% to 77%) for patients who were immediately listed and 94% (CI, 81% to 98%) for those who received standard care. Limitation: Restriction of the study sample to alcoholic patients may limit the generalizability of results to other settings. Conclusion: Immediate listing for liver transplantation did not show a survival benefit compared with standard care for Child-Pugh stage B alcoholic cirrhosis. In addition, immediate listing for transplantation increased the risk for extrahepatic cancer.

Vargas R; Lang CH. Alcohol accelerates loss of muscle and impairs recovery of muscle mass resulting from disuse atrophy. Alcoholism: Clinical and Experimental Research 32(1): 128-137, 2008. (52 refs.)

Background: Muscle disuse atrophy is observed in patients recovering from trauma and there is an increased risk and severity of injury in patients abusing alcohol (EtOH). However, the interaction of EtOH and disuse on muscle protein balance has not been examined. Therefore, the present study addressed the hypothesis that EtOH accelerates the disuse atrophy and/or impairs the accretion of muscle protein during muscle recovery. Methods: To address this aim, disuse atrophy was induced in rats by 3 days of unilateral hindlimb immobilization (casting), using the contralateral leg as control, with EtOH or saline being orally gavaged twice, each day during this period. In a separate study, EtOH-treated rats received Velcade to inhibit proteasomal degradation. Finally, in the last study, rats had 1 limb casted for 5 days, the cast removed, and EtOH or saline gavaged twice daily during a 5-day recovery period. Muscle protein metabolism was assessed using surrogate markers of protein synthesis [i.e., phosphorylation of 4E-binding protein 1 (BP1) and S6 kinase 1 (S6K1)] and protein degradation (i.e., mRNA content of the ubiquitin E3 ligases atrogin-1 and MuRF1). Results: Ethanol alone did not decrease muscle weight in the uncasted muscle. However, the loss of mass of immobilized muscle from EtOH-gavaged rats was 80% greater than in the animals not receiving EtOH. This atrophic response was not associated with a change in Akt, 4E-BP1 or S6K1 phosphorylation among groups. In contrast, immobilization alone increased both atrogin-1 and MuRF1 mRNA, and EtOH further increased their expression in immobilized muscle. The proteasome inhibitor Velcade attenuated atrophy produced by EtOH + disuse. When administered during the recovery period, EtOH prevented the normal accretion of muscle mass. This EtOH effect was associated with increased atrogin-1 mRNA, a reduction in 4E-BP1 and S6 phosphorylation, and an increased AMP-activated kinase phosphorylation. Conclusions: Based on the changes in these surrogate markers, our data suggest that EtOH accelerates disuse atrophy by stimulating ubiquitin-mediated proteolysis, and blunts repletion of muscle protein during recovery from disuse by increasing proteolysis and decreasing protein synthesis.

Verbaten MN. Chronic effects of low to moderate alcohol consumption on structural and functional properties of the brain: Beneficial or not? (review). Human Psychopharmacology: Clinical and Experimental 24(3): 199-205, 2009. (36 refs.)

Objective: Some studies suggest that the effects of low to moderate drinking (about 1-3 standard glasses of alcohol per day) on the brain and cognitive rerformance are positive. In the present study this hypothesis is investigated. Methods For this purpose studies on the effects of low to moderate drinking on brain structure (Magnetic Resonance Induction (MRI) studies) and on cognitive performance were analysed and discussed Results In MRI studies, a linear negative effect of alcohol consumption on brain volume was found. Furthermore, a linear decrease in grey matter concurring with a linear increase in white matter volumes as a function of number of drinks was reported in males, but not in females. Only in elderly low to moderate drinkers (aged > 65 years) there appeared to be an U-shaped relationship between alcohol consumption and white matter integrity (grade) on the one hand and cognition on the other hand. Conclusions The changes reported in brain shrinkage, grey matter and white matter volume, as a result of low to moderate alcohol consumption sooner offer support for the contention that such drinking decreases brain health than for its beneficial effect. An exception might hold for elderly light and moderate drinkers where less white matter damage was found than in abstainers concurring with better cognitive performance. However, methodological problems impose limits on this conclusion.

Verrill C; Markham H; Templeton A; Carr NJ; Sheron N. Alcohol-related cirrhosis: Early abstinence is a key factor in prognosis, even in the most severe cases. Addiction 104(5): 768-774, 2009. (92 refs.)

Aims: To determine the effect of pathological severity of cirrhosis on survival in patients with alcohol-related cirrhosis. Design Liver biopsies from 100 patients were scored for Laennec score of severity of cirrhosis, and medical notes were reviewed to determine various clinical factors, including drinking status. Up-to-date mortality data were obtained using the National Health Service Strategic Tracing Service. Setting Southampton General Hospital between 1 January 1995 and 31 December 2000. Participants A total of 100 consecutive patients with biopsy proven alcohol-induced liver cirrhosis. Measurements Laennec score of severity of cirrhosis and mortality. Findings Most surprisingly, the severity of cirrhosis on biopsy had little impact on survival; indeed, early death was more likely in patients with the least severe cirrhosis. Abstinence from alcohol at 1 month after diagnosis of cirrhosis was the more important factor determining survival with a 7-year survival of 72% for the abstinent patients versus 44% for the patients continuing to drink. Conclusions It is never too late to stop drinking, even with the most severe degrees of cirrhosis on biopsy. Early drinking status is the most important factor determining long-term survival in alcohol-related cirrhosis.

Wakabayashi I. Influence of gender on the association of alcohol drinking with blood pressure. American Journal of Hypertension 21(12): 1310-1317, 2008. (39 refs.)

BACKGROUND: The purpose of this study was to determine whether gender influences the association of alcohol drinking with blood pressure. METHODS: The subjects (43,810 healthy men and women at ages of 35-54 years) were divided into five groups by average daily ethanol intake (non-, very light (<10 g per day), light (>= 10 g and <20 g per day), moderate (>= 20g and <30g per day), and heavy (>= 30g per day) drinkers). The means of each variable after adjustment for age, body weight, and history of smoking were compared among the groups. RESULTS: Systolic blood pressure of men was significantly higher in moderate and heavy drinkers than in nondrinkers, and systolic blood pressure of women was significantly higher in heavy drinkers but not in moderate drinkers than in nondrinkers. Diastolic blood pressure of men and women was significantly higher in light, moderate and heavy drinkers than in nondrinkers. The differences in systolic and diastolic blood pressure between drinkers and nondrinkers were greater in men than in women. Both in men and women, serum HDL cholesterol was significantly higher in all four drinker groups than in the nondrinker group, and the difference between drinkers and nondrinkers was greater in women than in men. The above findings were not altered when age-and alcohol intake-matched groups of subjects were used. CONCLUSIONS: The results suggest that blood pressure is more prone to be elevated by alcohol drinking in men than in women.

Waldrop AE; Back SE; Sensenig A; Brady KT. Sleep disturbances associated with posttraumatic stress disorder and alcohol dependence. Addictive Behaviors 33(2): 328-335, 2008. (18 refs.)

Sleep disturbances commonly appear in the context of both posttraumatic stress disorder (PTSD) and alcohol disorders. Sleep symptoms typically reported among clinical populations include delayed sleep onset, poor sleep continuity, early morning awakening, and disturbed sleep architecture. The aim of the present study was to examine multiple forms of sleep disturbances among individuals with comorbid PTSD and alcohol dependence, PTSD only, alcohol dependence only, and a control group. Both PTSD and alcohol dependence diagnoses were associated with multiple forms of sleep disturbance, but comorbidity of the two disorders did not appear to increase the risk over and above either single disorder for reporting any of the sleep difficulties examined. As PTSD symptom severity increased, so did sleep latency, mid-sleep wakening, and early morning wakening. However, contrary to our hypothesis, no significant direct relationship between severity of alcohol use and sleep disturbances was revealed. These findings suggest a need for thorough assessment of sleep symptoms in patients presenting with PTSD or alcohol dependence.

Ward RJ; Lallemand F; de Witte P. Biochemical and neurotransmitter changes implicated in alcohol-induced brain damage in chronic or 'binge drinking' alcohol abuse. Alcohol and Alcoholism 44(2): 128-135, 2009. (73 refs.)

The brain damage, which occurs after either chronic alcoholization or binge drinking regimes, shows distinct biochemical and neurotransmitter differences. An excessive amount of glutamate is released into specific brain regions during binge drinking (in excess of 4- to 5-fold of the normal basal concentration) that is not evident during periods of excessive alcohol consumption in chronic alcohol abusers. Increases in glutamate release are only observed during the initial stages of withdrawal from chronic alcoholism (similar to 2- to 3-fold) due to alterations in the sensitivities of the NMDA receptors. Such changes in either density or sensitivity of these receptors are reported to be unaltered by binge drinking. When such excesses of glutamate are released in these two different models of alcohol abuse, a wide range of biochemical changes occur, mediated in part by increased fluxes of calcium ions and/or activation of various G-protein-associated signalling pathways. Cellular studies of alveolar macrophages isolated from these two animal models of alcohol abuse showed enhanced (binge drinking) or reduced (chronic alcoholization) lipopolysaccharide (LPS)-stimulated NO release. Such studies could suggest that neuroadaptation occurs with the development of tolerance to alcohol's effects in both neurotransmitter function and cellular processes during chronic alcoholization that delay the occurrence of brain damage. In contrast, 'binge drinking' induces immediate and toxic effects and there is no evidence of an increased preference for alcohol as seen after withdrawal from chronic alcoholization.

Wilhelm J; Frieling H; Hillemacher T; Degner D; Kornhuber J; Bleich S et al. Hippocampal volume loss in patients with alcoholism is influenced by the consumed type of alcoholic beverage. Alcohol and Alcoholism 43(3): 296-299, 2008. (31 refs.)

Aims: The individual extent of structural brain tissue changes in patients with alcohol dependence is influenced by genetic factors, gender, age and possibly a dose/duration-effect. Aim of the present study was to investigate different types of alcoholic beverages with regard to hippocampal volume loss in patients suffering from alcoholism. Methods: We included 52 patients with alcohol dependence and divided them according to their preferred type of beverage consumption (beer, wine, and spirits). Hippocampal volumes were determined using volumetric high-resolution MR imaging. Results: There was a significant difference in hippocampal volumes between patients consuming different beverages (ANOVA: F = 7.454; df = 2; P = 0.0015) with the smallest volumes in the wine group, followed by the spirits group. Furthermore, patients with a preferred spirits consumption showed significantly higher plasma homocysteine levels (ANOVA: F = 3.39; df = 2; P = 0.042). Linear regression analyses revealed an association of homocysteine and hippocampal volume only in the group of patients preferring spirits (R-2 = 0.364; P = 0.008). Conclusions: Homocysteine-mediated excitotoxicity may be an important pathophysiological mechanism in ethanol-related brain damage, particularly in patients consuming wine and spirits. The extent of brain atrophy in beer consuming patients seems to be more moderate.

Williams R. The pervading influence of alcoholic liver disease in hepatology. (review). Alcohol and Alcoholism 43(4): 393-397, 2008. (36 refs.)

Rising levels of alcohol consumption in the UK are leading to substantial increases in morbidity and mortality from liver disease. Drinking is starting at an earlier age with binging an increasing common pattern, and women are overtaking men in the consumption. Manifestations of liver damage range from fatty liver to end-stage cirrhosis, but it is the increasing number of cases presenting with an acute alcoholic hepatitis (AAH) that are the cause for greatest concern. Development of well-validated prognostic scoring systems (Maddrey Modified Discriminant Function, Glasgow Alcohol Score) makes it possible to select those patients with AAH who are most likely to respond to corticosteroids. The results of early pilot studies of a number of anti-TNF agents are encouraging and with infliximab, reduction in portal pressure has been demonstrated to be consequent on controlling inflammatory processes in the liver. For those deteriorating to the stage of liver failure, artificial liver support with MARS is of value in correcting major pathophysiological disturbances and as a bridge to liver transplantation, the results of which both for end-stage alcoholic cirrhosis and for AAH-of which there is limited experience, are excellent. Even as the stringent regulatory measures needed to control rising alcohol consumption are introduced by government, the burden of liver disease in the UK will remain high for years to come.

Wobrock T; Falkai P; Schneider-Axmann T; Frommann N; Wolwer W; Gaebel W. Effects of abstinence on brain morphology in alcoholism. European Archives of Psychiatry and Clinical Neuroscience 259(3): 143-150, 2009. (37 refs.)

Chronic alcohol abuse leads to morphological changes of the brain. We investigated if these volumetric changes are reversible after a period of abstinence. For this reason 41 male and 15 female alcohol patients underwent MRI-scanning after in-patient detoxification (baseline) entering alcoholism treatment programs, and between 6 and 9 months later (follow-up), in a phase of convalescence. Additionally, 29 male and 16 female control subjects were examined. The MRI-scans were delineated and the resulting regions of interest, volumes of lateral ventricles and prefrontal lobes were expressed relatively to total brain volume. Compared to control subjects alcohol patients showed bilaterally decreased prefrontal lobes (11% reduction) and increased lateral ventricles (up to 42% enlargement). The extent of the ventricular increase was depending on patient's additional psychiatric diagnosis, showing smaller lateral ventricles in patients with additional personality disorder. While at follow-up the size of prefrontal lobes remained unchanged, volumes of the lateral ventricles decreased (5-6% reduction) in alcohol patients with abstinence and improved drinking behavior, especially in patients that underwent only one detoxification. The extent of the ventricular enlargement correlated with the elevation of alcohol related laboratory measures (mean corpuscular volume, gamma-glutamyl transpeptidase). In conclusion this study confirms the hypothesis that alcoholism causes brain damages that are partially reversible. It should be analyzed in further studies with larger sample sizes, if complete brain regeneration is possible maintaining abstinence over a longer period.

Yin RX; Pan SL; Chen H; Yang HJ; Wu H; Chen YM et al. Diet, alcohol consumption, and serum lipid levels of the middle-aged and elderly in the Guangxi Bai Ku Yao and Han populations. Alcohol 42(3): 219-229, 2008. (66 refs.)

Bai Ku Yao is an isolated subgroup of the Yao minority in China. The special customs and cultures including their clothings, intraethnic marriages, corn wine and rum intakes are still completely conserved to the present day. Little is known about the association of diet and alcohol consumption with serum lipid levels in this population. The aim of this study was to compare the differences in diet, alcohol consumption, and serum lipid levels of the middle-aged and elderly between the Guangxi Bai Ku Yao and Han populations. A total of 485 subjects of Bai Ku Yao and 501 participants of Han Chinese aged 40 and over were surveyed by a stratified randomized cluster sampling. Information on dietary intake and alcohol consumption was collected by standard questionnaires. Serum lipid levels were measured. Education level, height, weight, body mass index, waist circumference, blood pressure, hypertension, and total energy, fat, protein, dietary cholesterol, and salt intakes were lower in Bai Ku Yao than in Han (P < .05-.001), whereas physical activity level, carbohydrate, vegetal protein, and total dietary fiber intakes were higher in Bai Ku Yao than in Han (P <.001 for all). Serum total cholesterol, high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), apolipoprotein (Apo) A1, and Apo B levels were lower in Bai Ku Yao than in Han (P <.001 for all). The levels of triglyceride, HDL-C, Apo A1, and the ratio of Apo A1 to Apo B in Bai Ku Yao were higher, but the levels of LDL-C and Apo B were lower in drinkers than in nondrinkers. The levels of triglyceride, HDLC, LDL-C, Apo A1, Apo B, and the ratio of Apo A1 to Apo B in Bai Ku Yao were also influenced by the amount of alcohol consumed (P <.05-.001). High-density lipoprotein cholesterol levels in Han were higher and LDL-C levels were lower in drinkers than in nondrinkers (P <.01 for each). Serum total cholesterol, HDL-C, and LDL-C levels in Han were also associated with the amount of alcohol consumed (P <.05-.001). The differences in the lipid levels between the two ethnic groups may partially attribute to the differences in dietary habits and alcohol consumption.

Yoon B; Shim YS; Chung SW. Central pontine and extrapontine myelinolysis after alcohol withdrawal. Alcohol and Alcoholism 43(6): 647-649, 2008. (12 refs.)

Central pontine myelinolysis (CPM) and extrapontine myelinolysis (EPM) are well-recognized syndromes that are related to various conditions such as rapid correction of hyponatremia and chronic alcoholism. We report a very case of a patient with dysarthria, dysphagia and psychiatric symptoms including abnormal behavior starting after alcohol withdrawal, with radiological evidence of CPM and EPM. There was little improvement in the dysarthria or psychiatric symptoms in the first month.