Hot off the presses! Mar 01 Alcohol Alcohol

The Mar 01 issue of the Alcohol Alcohol is now up on Pubget (About Alcohol Alcohol): if you're at a subscribing institution, just click the link in the latest link at the home page. (Note you'll only be able to get all the PDFs in the issue if your institution subscribes to Pubget.)

Latest Articles Include:

• Special Issue on Alcohol and Brain Damage
  Chick J de Witte P - Alcohol Alcohol 44(2):105 (2009)
  
• Introduction to This Issue: The Seven Ages of Man ... (or Woman)
  Marshall EJ Guerrini I Thomson AD - Alcohol Alcohol 44(2):106-107 (2009)
  
• Foetal Alcohol Spectrum Disorders and Alterations in Brain and Behaviour
  Guerri C Bazinet A Riley EP - Alcohol Alcohol 44(2):108-114 (2009)
  The term Foetal Alcohol Spectrum Disorders (FASD)' refers to the range of disabilities that may result from prenatal alcohol exposure. This article reviews the effects of ethanol on the developing brain and its long-term structural and neurobehavioural consequences. Brain imaging, neurobehavioural and experimental studies demonstrate the devastating consequences of prenatal alcohol exposure on the developing central nervous system (CNS), identifying specific brain regions affected, the range of severity of effects and mechanisms involved. In particular, neuroimaging studies have demonstrated overall and regional volumetric and surface area reductions, abnormalities in the shape of particular brain regions, and reduced and increased densities for white and grey matter, respectively. Neurobehaviourally, FASD consists of a continuum of long-lasting deficits affecting multiple aspects of cognition and behaviour. Experimental studies have also provided evidence of the vuln! erability of the CNS to the teratogenic effects of ethanol and have provided new insight on the influence of risk factors in the type and severity of observed brain abnormalities. Finally, the potential molecular mechanisms that underlie the neuroteratological effects of alcohol are discussed, with particular emphasis on the role of glial cells in long-term neurodevelopmental liabilities.
• Mechanisms of Neurodegeneration and Regeneration in Alcoholism
  Crews FT Nixon K - Alcohol Alcohol 44(2):115-127 (2009)
  Aims: This is a review of preclinical studies covering alcohol-induced brain neuronal death and loss of neurogenesis as well as abstinence-induced brain cell genesis, e.g. brain regeneration. Efforts are made to relate preclinical studies to human studies. Methods: The studies described are preclinical rat experiments using a 4-day binge ethanol treatment known to induce physical dependence to ethanol. Neurodegeneration and cognitive deficits following binge treatment mimic the mild degeneration and cognitive deficits found in humans. Various histological methods are used to follow brain regional degeneration and regeneration. Results: Alcohol-induced degeneration occurs due to neuronal death during alcohol intoxication. Neuronal death is related to increases in oxidative stress in brain that coincide with the induction of proinflammatory cytokines and oxidative enzymes that insult brain. Degeneration is associated with increased NF-{kappa}B proinflammatory transcripti! on and decreased CREB transcription. Corticolimbic brain regions are most sensitive to binge-induced degeneration and induce relearning deficits. Drugs that block oxidative stress and NF-{kappa}B transcription or increase CREB transcription block binge-induced neurodegeneration, inhibition of neurogenesis and proinflammatory enzyme induction. Regeneration of brain occurs during abstinence following binge ethanol treatment. Bursts of proliferating cells occur across multiple brain regions, with many new microglia across brain after months of abstinence and many new neurons in neurogenic hippocampal dentate gyrus. Brain regeneration may be important to sustain abstinence in humans. Conclusions: Alcohol-induced neurodegeneration occurs primarily during intoxication and is related to increased oxidative stress and proinflammatory proteins that are neurotoxic. Abstinence after binge ethanol intoxication results in brain cell genesis that could contribute to the return of brain f! unction and structure found in abstinent humans.
• Biochemical and Neurotransmitter Changes Implicated in Alcohol-Induced Brain Damage in Chronic or 'Binge Drinking' Alcohol Abuse
  Ward RJ Lallemand F de Witte P - Alcohol Alcohol 44(2):128-135 (2009)
  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 ([~]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.
• The Neuropathology of Alcohol-Related Brain Damage
  Harper C - Alcohol Alcohol 44(2):136-140 (2009)
  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.
• Update of Cell Damage Mechanisms in Thiamine Deficiency: Focus on Oxidative Stress, Excitotoxicity and Inflammation
  Hazell AS Butterworth RF - Alcohol Alcohol 44(2):141-147 (2009)
  Thiamine deficiency (TD) is a well-established model of Wernicke's encephalopathy. Although the neurologic dysfunction and brain damage resulting from the biochemical consequences of TD is well characterized, the mechanism(s) that lead to the selective histological lesions characteristic of this disorder remain a mystery. Over the course of many years, various structural and functional changes have been identified that could lead to cell death in this disorder. However, despite a concerted effort to explain the consequences of TD in terms of these changes, our understanding of the pathophysiology of this disorder remains unclear. This review will focus on three of these processes, i.e. oxidative stress, glutamate-mediated excitotoxicity and inflammation and their role in selective vulnerability in TD. Since TD inhibits oxidative metabolism, a feature of many neurodegenerative disease states, it represents a model system with which to explore pathological mechanisms inh! erent in such maladies, with the potential to yield new insights into their possible treatment and prevention.
• The Korsakoff Syndrome: Clinical Aspects, Psychology and Treatment
  Kopelman MD Thomson AD Guerrini I Marshall EJ - Alcohol Alcohol 44(2):148-154 (2009)
  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 n! ew 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.
• Neuroimaging of the Wernicke-Korsakoff Syndrome
  Sullivan EV Pfefferbaum A - Alcohol Alcohol 44(2):155-165 (2009)
  Aim: Presented is the neuroradiological signature of acute Wernicke's encephalopathy (WE), derived from different types of magnetic resonance imaging (MRI) sequences. WE results from thiamine depletion, and its most typical antecedent is chronic alcohol dependence. Brain regions observed with in vivo MRI affected in acute WE include the mammillary bodies, periaqueductal and periventricular gray matter, collicular bodies and thalamus. These affected areas are usually edematous and are best visualized and quantified with MRI sequences that highlight such tissue. Following the acute WE phase and resolution of edema and inflammation of affected brain tissue, WE, if not adequately treated with thiamine repletion, can herald Korsakoff's syndrome (KS), with its symptomatic hallmark of global amnesia, that is, the inability to commit newly encountered (episodic) information to memory for later recall or recognition. Methods: Neuropathology of KS detectable with MRI has a diffe! rent neuroradiological signature from the acute stage and can be observed as tissue shrinkage or atrophy of selective brain structures, including the mammillary bodies and thalamus and ventricular expansion, probably indicative of atrophy of surrounding gray matter nuclei. Quantification of these and additional gray matter structures known to underlie global amnesia reveal substantial bilateral volume deficits in the hippocampus, in addition to the mammillary bodies and thalamus, and modest deficits in the medial septum/diagonal band of Broca. The infratentorium is also affected, exhibiting volume deficits in cerebellar hemispheres, anterior superior vermis and pons, contributing to ataxia of gait and stance. Results: Consideration of WKS structural brain changes in the context of the neuropathology of non-WKS alcoholism revealed a graded pattern of volume deficits, from mild in non-WKS alcoholics to moderate or severe in WKS, in the mammillary bodies, hippocampus, thalamus! , cerebellum and pons. The development and resolution of brain! structures affected in acute, chronic and treated WE was verified in longitudinal MRI study of rats that modeled of the interaction of extensive alcohol consumption and thiamine depletion and repletion. Conclusions: Thus, neuroradiological examination with MRI is valuable in the diagnosis of acute WE and enables in vivo tracking of the progression of the brain pathology of WE from the acute pathological phase to resolution with thiamine treatment or to progression to KS without treatment. Further, in vivo MRI facilitates translational studies to model antecedent conditions contributing to the development, sequelae and treatment of WE.
• Molecular Genetics of Alcohol-Related Brain Damage
  Guerrini I Thomson AD Gurling HM - Alcohol Alcohol 44(2):166-170 (2009)
  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 sugge! st 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.
• Proteomics Approach in the Study of the Pathophysiology of Alcohol-Related Brain Damage
  Matsumoto I - Alcohol Alcohol 44(2):171-176 (2009)
  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 dorsolate! ral 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 dat! a did not show any evidence of "direct" alcohol effects to ind! uce 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.
• Biomarkers in Alcohol Misuse: Their Role in the Prevention and Detection of Thiamine Deficiency
  Mancinelli R Ceccanti M - Alcohol Alcohol 44(2):177-182 (2009)
  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.
• Alcohol Withdrawal and Prolonged Hospital Stay in a Patient with Neuroimaging Abnormalities: A Case Report
  Gupta M - Alcohol Alcohol 44(2):183-184 (2009)
  A hospital stay of 30 days was required in a 47-year-old woman with alcohol withdrawal. Magnetic resonance imaging (MRI) findings revealed a focal brain stem lesion and multiple focal supracortical abnormalities. Could asymptomatic neuroimaging abnormalities predict risk of complicated alcohol withdrawal? Future clinical observations and longitudinal studies may wish to address this potential risk factor.
• In vitro Neurogenesis from Neural Progenitor Cells Isolated from the Hippocampus Region of the Brain of Adult Rats Exposed to Ethanol during Early Development through Their Alcohol-Drinking Mothers
  Singh AK Gupta S Jiang Y Younus M Ramzan M - Alcohol Alcohol 44(2):185-198 (2009)
  Aims: This study was aimed to determine whether ethanol exposure during early development altered neurogenesis in the brain of adult rats. Methods: Pregnant rats were given either ethanol-mixed or mannose-mixed (for control) rodent liquid diet ad libitum. Ethanol drinking continued during pregnancy and nursing. After weaning, the pups (ACo: pups from control mothers, AEo: pups from ethanol exposed mothers) received normal diet and water ad libitum for 11 weeks. Then the rats were anesthetized, their brains were collected and the hippocampal samples were processed for isolation of neural progenitor cells (NPCs). ACo NPCs and AEo NPCs were sequentially grown in media containing different growth factors that induced proliferation and differentiation. Results and Conclusions: Neuronal maturation was significantly delayed in ethanol-exposed rats. ACo NPCs, up to day 7 of culture, exhibited high {beta}-catenin-probe binding, an increase in Ca2+ when exposed to {gamma}-amino ! butyric acid (GABA) and lack of response to glutamate (Glu) exposure. {beta}-Catenin-probe binding and the stimulatory effects of GABA declined thereafter. ACo NPCs, at culture day 29, exhibited high {beta}-catenin-probe binding, lack of response to GABA and elevated Glu-induced increase in Ca2+i. Cultures of AEo NPCs showed an amplified stimulatory effects of GABA, attenuated stimulatory effects of Glu and attenuated the delayed (culture day 29) increase in the expression of Wnt proteins and {beta}-catenin-probe binding. This suggests a significant alteration in neurogenesis and synapse formation in adult rats exposed to ethanol at early development through their alcohol-drinking mothers.
• Biomarkers of Liver Status in Heavy Drinkers, Moderate Drinkers and Abstainers
  Alatalo P Koivisto H Puukka K Hietala J Anttila P Bloigu R Niemelä O - Alcohol Alcohol 44(2):199-203 (2009)
  Aims: Although a wide variety of biomarkers reflecting liver status are known to be influenced by excessive ethanol consumption, the dose-response relationships between ethanol intake and marker changes have remained less understood. Methods: Serum gamma-glutamyltransferase (GGT), aspartate aminotransferase (AST), alanine aminotransferase (ALT) activities, and ferritin and albumin protein concentrations were compared in a large population of heavy drinkers (105 men, 28 women), moderate drinkers (781 men, 723 women) and abstainers (252 men, 433 women), who were devoid of apparent liver disease. Results: In heavy drinkers, serum GGT, AST, ALT, ferritin and albumin were all significantly higher than in moderate drinkers or abstainers (P < 0.001 for all comparisons). The highest incidences of elevated values were found for GGT (62%) followed by AST (53%), ALT (39%), ferritin (34%) and albumin (20%). Serum GGT (P < 0.001), ALT (P < 0.01) and ferritin (P < 0.05) in moderate ! drinkers were also higher than the levels observed in abstainers. When the study population was further divided into subgroups according to gender, significant differences between moderate drinkers and abstainers in GGT and ALT were noted in men whereas not in women. Conclusions: The data demonstrate that biomarkers of alcohol abuse and liver function may respond to even rather low levels of ethanol intake in a gender-dependent manner, which should be implicated in studies on the early-phase interactions of ethanol and the liver and in the definition of normal ranges for such biomarkers.
• Impact of Body Weight on the Relationship between Alcohol Intake and Blood Pressure
  Wakabayashi I - Alcohol Alcohol 44(2):204-210 (2009)
  Aims: The reduction of habitual alcohol drinking is recommended for the prevention of hypertension. Daily or weekly alcohol consumption, which is used for evaluation of the effects of alcohol drinking on blood pressure, is usually not corrected by body weight. In this study, the influence of body weight on the relationship between alcohol intake and blood pressure was investigated.Methods: The subjects (27,005 healthy men at ages of 35-54 years) were divided into four groups by average daily ethanol intake [non-, light (<15 g per day), moderate ([≥]15 and <30 g per day) and heavy ([≥]30 g per day) drinkers]. The subjects were also divided into four quartile groups by body weight.Results: Alcohol intake and the percentage of drinkers were not different in the four quartile groups of body weight. In the first and second quartiles of body weight, systolic and diastolic blood pressures were significantly higher in moderate and heavy drinkers than in non-drinkers, whi! le systolic and diastolic blood pressures in the fourth quartile of body weight were significantly higher in heavy drinkers than in non-drinkers but were not significantly different in moderate drinkers and non-drinkers. The differences in systolic or diastolic blood pressure between non-drinkers and moderate drinkers and between non-drinkers and heavy drinkers became greater as body weight decreased. These results were not altered when age and smoking history were adjusted.Conclusions: The results suggest that body weight modifies the relationship between alcohol consumption and blood pressure and thus should be taken into account when effects of alcohol on blood pressure are considered.
• Is Cortisol Involved in the Alcohol-Related Fat Mass Impairment? A Longitudinal Clinical Study
  Leggio L Malandrino N Ferrulli A Cardone S Miceli A Gasbarrini G Capristo E Addolorato G - Alcohol Alcohol 44(2):211-215 (2009)
  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--reflected by higher cortisol levels--was 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.
• Reported Beverage Consumed and Alcohol-Related Diseases among Male Hospital Inpatients with Problem Drinking
  Coder B Freyer-Adam J Lau K Riedel J Rumpf HJ Meyer C John U Hapke U - Alcohol Alcohol 44(2):216-221 (2009)
  Aims: The aim of this study was to examine if problem drinkers have varying risks of having alcohol-related diseases according to their reported beverage consumed. Methods: In a cross-sectional study all consecutive inpatients aged 18- 64 years from four general hospitals of one catchment area were systematically screened for alcohol use. A total of 1011 men with problem drinking were used for this study. Routine treatment diagnoses for all participants were provided by hospital physicians and were classified into three categories according to their alcohol-attributable fractions (AAF; AAF = 0; AAF < 1; AAF = 1). Results: According to their reported beverage consumed, 53.0% of the participants were identified as exclusively beer drinkers, 14.1% exclusively spirits drinkers, 26.0% mixed beer and spirits drinkers and 6.9% individuals drinking wine exclusively or in combination with one or two other beverages (mixed wine drinkers). Compared to spirits drinkers and control! ling for possible confounders (i.e. alcohol-associated characteristics, demographic variables), multinomial regressions revealed that beer drinkers, mixed beer and spirits drinkers, and mixed wine drinkers had lower odds of having diseases with AAF = 1 than spirits drinkers (e.g. for AAF = 1: beer versus spirits drinkers: OR = 0.42, CI: 0.25-0.72). Beer drinkers and mixed wine drinkers also had lower odds of having diseases with AAF < 1 than spirits drinkers (e.g. mixed wine versus spirits drinkers: OR = 0.36, CI: 0.18-0.72). Conclusions: These data suggest an association between the reported beverage consumed and alcohol-related diseases. Among hospitalized problem drinkers, spirits drinkers had the greatest risk of having diseases with AAF < 1 and with AAF = 1.