bluuebunny/crossref_metadata_2025 huggingface dataset:
A Comparison of Substance Use and Injury Among Mexican American Emergency Room Patients in the United States and Mexicans in Mexico
Authors: Cherpitel Cheryl J. , Borges Guilherme
Published: April 2006

Background: Emergency room (ER) studies have found differences in the association of alcohol with injury (intentional and unintentional) across cultures. These differences may be due to differences in drinking patterns across cultures. Few comparative data have been reported on associations of alcohol and injury between Mexican American ER patients and ER patients living in Mexico, and general population studies suggest that Mexican Americans may adopt more frequent heavy drinking patterns after migrating to the United States.

Methods: A comparative analysis of drinking, drug use, and injury was performed in probability samples of 550 ER patients from Santa Clara County (San Jose, CA) and 1417 ER patients in Pachuca (Hidalgo), Mexico.

Results: Both injured and uninjured (i.e., medical conditions) patients in Pachuca were less likely to report heavy drinking, drug use, drunkenness, or alcohol‐related problems compared with those in Santa Clara. Those scoring high on level of acculturation in Santa Clara were more likely to report both drinking and drug use before the event, and heavy drinking, drug use, and consequences related to drinking in the last year compared with those scoring lower. Those scoring low on acculturation were similar on substance use variables to those in the Pachuca sample.

Conclusions: Findings suggest that alcohol's association with injury may not just reflect typical drinking patterns in a culture. Among Mexican Americans, this association my vary by acculturation, and those migrating to the United States may be at increased risk for alcohol‐related injury as their drinking patterns undergo change to those of the dominant culture. The ER, in this context, may take on increasing importance as a site for health services providers to implement intervention and prevention services for alcohol‐related consequences in this ethnic group.
Interferon α and Alcohol Augment Nuclear Regulatory Factor‐κB Activation in HepG2 Cells, and Interferon α Increases Pro‐Inflammatory Cytokine Production
Authors: Szabo Gyongyi , Catalano Donna , Bellerose Gary , Mandrekar Pranoti
Published: April 2006

Background: The mechanisms for decreased therapeutic response to IFNα in chronic hepatitis C patients with alcohol are unknown. We investigated the hypothesis that IFNα and alcohol regulate cells both in the liver parenchyma and the immune system.

Methods: We used the hepatocellular carcinoma cells (HepG2) to determine if IFNα (500–10,000 U/ml) or ethanol (25–100 mM) modulates NF‐kB activation alone or in combination with TNFα (0.1–20 μg/ml) as determined in electromobility gel shift assays. IkB levels were evaluated in the cytoplasmic extracts by western blot. Monocytes from normal donors were activated with LPS (1 μg/ml) in combination with IFNα or ethanol overnight and TNFα, IL‐6, and IL‐12 were measured in the supernatants.

Results: In HepG2 cells, both IFNα and acute alcohol treatment induced NF‐κB activation and augmented TNFα‐induced NF‐κB binding. Pretreatment of HepG2 cells with IFNα resulted in the highest levels of NF‐κB activation in response to TNFα or TNFα plus ethanol stimulation. Supershift experiments confirmed that the NF‐κB dimer induced by TNFα and its combination with IFNα or ethanol contains RelA (p65) and involves rapid degradation of IκBα. Experiments using the proteasome inhibitor, MG132, revealed that augmentation of NF‐κB by ethanol and IFNα is mediated via the proteasome pathway. We show that in normal monocytes, IFNα augments LPS‐induced production of the inflammatory cytokines TNFα, IL‐6, and IL‐12 (p < 0.06) without further modulation by acute alcohol treatment.

Conclusions: These results suggest that IFNα can increase HepG2 cell sensitivity to TNFα and ethanol‐mediated activation. Augmentation of monocyte inflammatory cytokines, particularly of IL‐12 production, by IFNα could be a key element of the antiviral response in chronic HCV. These results support the hypothesis that the therapeutic benefits of IFNα likely involve activation of both immune and parenchymal cells in the liver.
Increased Serum IgE in Alcoholics: Relationship With Th1/Th2 Cytokine Production by Stimulated Blood Mononuclear Cells
Authors: Domínguez‐Santalla M. J. , Vidal C. , Viñuela J. , Pérez L. F. , González‐Quintela A.
Published: April 2006

Background: Increased serum immunoglobulin (Ig) E values are frequently found in alcoholics. Cytokines produced by T‐helper‐2 (Th2) lymphocytes are required for IgE synthesis. Chronic alcoholism is associated with altered cytokine balance. This study analyzed the relationship between Th1 and Th2 cytokine production by stimulated peripheral blood mononuclear cells (PBMCs) and serum IgE levels, both in atopic and nonatopic alcoholics.

Methods: Twenty‐five patients admitted to the hospital with alcohol withdrawal syndrome were included in the study. Five were classified as atopic and 20 as nonatopic by means of skin‐prick tests. Interleukin‐4 (IL‐4), IL‐10, IL‐12, IL‐13, and interferon γ were measured in the supernatants of 48‐hr cultures of PBMCs stimulated with phytohemagglutinin. Total serum IgE was measured by chemiluminescent enzyme immunoassay. Results were compared with those of 15 healthy controls (seven atopics and eight nonatopics).

Results: Total serum IgE concentrations were higher in alcoholics than in controls, in both atopic and nonatopic subjects. The ratio of IL‐4 to interferon γ production by phytohemagglutinin‐stimulated PBMCs (as an approach to Th2/Th1 balance) was significantly lower in alcoholics than in healthy controls, both in the atopic and in the nonatopic group. No difference was observed regarding IL‐10, IL‐12, and IL‐13 production between alcoholics and controls. No correlation was demonstrated between cytokine production and total serum IgE levels in any group.

Conclusions: Increased total serum IgE is observed in alcoholics together with a paradoxically low ratio of Th2 to Th1 cytokine production by phytohemagglutinin‐stimulated PBMCs. These findings are independent of the atopic status of patients.
Effects of Abstinence From Alcohol on the Broad Phospholipid Signal in Human Brain: An In Vivo 31P Magnetic Resonance Spectroscopy Study
Authors: Estilaei M. R. , Matson G. B. , Payne G. S. , Leach M. O. , Fein G. , Meyerhoff D. J.
Published: April 2006

Background: In vivo phosphorus magnetic resonance spectroscopy (31P MRS) at a magnetic field strength of 1.5 T allows measurement of fairly mobile membrane phospholipids in the human brain. We previously showed that subjects who are heavy drinkers had a smaller signal and a shorter transverse relaxation time (T2) of white matter phospholipids than light drinkers, which suggested lower concentrations and molecular mobility of phospholipids in heavy drinkers. The purpose of the present study was to measure if such chronic alcohol‐induced white matter tissue changes are persistent in long‐term abstinent alcoholics.

Methods: Fourteen abstinent alcoholics (mean age 45 years, seven men and seven women) were studied by localized 31P MRS in the centrum semiovale and were compared with 13 male, alcohol‐dependent, heavy drinkers and 23 nondependent light drinkers (17 men, 6 women) of similar age. Methods for measurements of the broad membrane phospholipid signal and its relaxation time were described previously.

Results: Phospholipid concentrations and relaxation times in alcoholics abstinent for an average of 31 months were not significantly different from those measured in light drinkers. The contribution of fast and slowly relaxing signal components to the broad phospholipid signal, however, was still different in abstinent alcoholics compared with light drinkers. No effects of sex or of family history of alcoholism were noted on any of our spectroscopic measures within the light‐drinking or abstinent groups.

Conclusions: Most of our results suggest at least partial recovery of chronic alcohol‐induced white matter phospholipid damage with long‐term abstinence. They offer myelination changes and/or dendritic rearborization as a possible mechanism for the commonly observed white matter volume gain with prolonged abstinence. But the results also suggest a persistent abnormality in the nature and/or physical properties of white matter phospholipids in long‐term abstinent alcoholics.
Early Alteration in Leukocyte Populations and Th1/Th2 Function in Ethanol‐Consuming Mice
Authors: Starkenburg Shawn , Munroe Melissa E. , Waltenbaugh Carl
Published: April 2006

Background: Chronic alcohol consumption polarizes the immune response away from Th1‐mediated cell‐mediated immunity. In the present report we investigate the first onset of alteration in immune parameters during ethanol consumption in terms of changes in splenic leukocyte cellularity and surface phenotype as well as alterations in Th1 and Th2 function.

Methods: BALB/c and C57BL/6 mice were fed ethanol‐containing liquid diets, were pair‐fed an isocaloric liquid control diet, or were fed solid diet and water ad libitum for up to 12 days. At intervals during the feeding period, splenic leukocytes were assessed for phenotypic markers by flow cytometry and for their ability to support antigen‐induced interferon‐γ (IFNγ) production in a coculture system. Mice were bled at intervals throughout the feeding period, and serum immunoglobin E (IgE) and alcohol levels were determined.

Results: Data show that phenotypic and functional alterations occur within the first few days of alcohol consumption. Both liquid diets affect splenic cellularity, and by dietary day 5, ethanol‐containing liquid diets further reduce B and NK cell numbers. The decline in B cells is accompanied by a concomitant decline in the amount of major histocompatibility complex class II expressed on this population. Functional alteration in Th1‐mediated IFNγ production occurred in the population fed ethanol‐containing liquid diets by dietary day 5. Th2 function, as indicated by systemic serum IgE levels in these unimmunized mice, is increased by dietary day 6 to 8 and correlated with significant blood alcohol levels.

Conclusions: Ethanol consumption by mice causes a rapid decrease in splenic cellularity accompanied by a decrease in Th1 function and a rapid increase in systemic IgE levels.
Effect of Ethanol on Polyunsaturated Fatty Acid Biosynthesis in Hepatocytes From Spontaneously Hypertensive Rats
Authors: Narce Michel , Poisson Jean‐Pierre , Bellenger Jérôme , Bellenger Sandrine
Published: April 2006

Background: Polyunsaturated fatty acids (PUFA) play a major role in membrane structures that are modified during alcoholism. PUFA are also precursors of second messengers—eicosanoids—involved in the regulation of blood pressure. Alcohol has been related to hypertension and to alterations in liver PUFA metabolism. We investigated the effects of ethanol on PUFA biogenesis in hepatocytes of Wistar Kyoto (WKY) rats and Spontaneously Hypertensive Rats (SHR). The effects of a diet enriched with n‐3 PUFA, which is known to modulate hypertension, were also studied.

Methods: Isolated hepatocytes from male normotensive Wistar Kyoto (WKY) rats and SHR were incubated for 60 min in the presence of labeled linoleic acid and DGLA, which are precursors of the limiting desaturation steps of PUFA biosynthesis, into a medium containing different concentrations of ethanol. Hepatocytes from SHR that were fed a diet supplemented with n‐3 PUFA were incubated with the same precursors.

Results: First, the hepatic biogenesis of PUFA is dependent on the level of ethanol in the incubation medium. Second, Δ5 desaturase was more sensitive than Δ6 desaturase to changes in alcohol concentration. Third, in SHR, a tremendous decrease of arachidonic acid biosynthesis was evidenced in alcohol‐intoxicated hepatocytes; the effect was reinforced when ethanol concentration was high, mainly for Δ5 desaturase. Fourth, in the presence of ethanol, the biogenesis of PUFA was altered in isolated hepatocytes from SHR that were fed the diet supplemented with n‐3 PUFA, particularly via an inhibition of Δ5 desaturation.

Conclusions: Our study showed that hepatocyte PUFA biogenesis is dependent on ethanol concentration. Ethanol strongly inhibits the synthesis of PUFA in hepatocytes from SHR, which can explain the deficit of prostaglandin precursors observed in cardiovascular diseases linked to ethanol intoxication. n‐3 PUFA supplemented diet reinforces the inhibition of arachidonic acid synthesis, likely by a substrate competition toward Δ5 desaturation. This in vitro approach provides a better understanding of the effects of ethanol on fatty acid metabolism in relation to hypertension.
Increased Ethanol Self‐Administration in δ‐Opioid Receptor Knockout Mice
Authors: Roberts Amanda J. , Gold Lisa H. , Polis Ilham , McDonald Jeffrey S. , Filliol Dominique , Kieffer Brigitte L. , Koob George F.
Published: April 2006

Background: The role of the δ‐opioid receptor in ethanol drinking has remained unclear despite the use of traditional pharmacological and correlational approaches. The results of several studies suggest that pharmacological blockade of these receptors results in decreases in ethanol drinking behavior, but an approximately equal number of reports have failed to observe an effect of δ‐receptor antagonism on ethanol drinking. It is clear that alternative approaches to understanding opioid‐receptor involvement in ethanol drinking are needed.

Methods: In this study, ethanol drinking was examined in δ‐opioid receptor knockout (KO) mice by using first a two‐bottle–choice test, then an operant self‐administration paradigm and a second two‐bottle–choice test, in that order. In addition, because KO mice were previously shown to display enhanced anxiety‐like behavior relative to wild‐type (WT) mice, the effect of ethanol self‐administration on anxiety‐like responses was determined.

Results: δ KO mice initially showed no evidence of a preference for ethanol in the first two‐bottle–choice drinking test; however, after an experience of operant self‐administration of ethanol, a preference for ethanol developed in the second two‐bottle–choice test. KO mice also showed a preference for ethanol over water and self‐administered more ethanol than WT mice in the operant self‐administration paradigm. The ethanol self‐administered in this procedure was sufficient to reverse the innate anxiety‐like response observed in this strain.

Conclusions: δ KO mice showed a greater preference for ethanol and consumed more ethanol than their WT counterparts, suggesting that a decrease in δ‐receptor activity is associated with increased ethanol‐drinking behavior. It is hypothesized that δ receptors may influence ethanol self‐administration at least partly through an effect of these receptors on anxiety‐like behavior.
Health Problems in Adolescents With Alcohol Use Disorders: Self‐Report, Liver Injury, and Physical Examination Findings and Correlates
Authors: Clark Duncan B. , Lynch Kevin G. , Donovan John E. , Block Geoffrey D.
Published: April 2006

Background: Although adolescent alcohol consumption has been found to be positively correlated with self‐reported health problems, few studies have examined other health indicators. This study compared adolescents with alcohol use disorders (AUDs) and a community reference group on self‐reported health problems, serum liver enzymes, and physical examination findings. The relevance of negative emotionality to understanding these health problems was also investigated.

Methods: The subjects were adolescents with AUDs recruited from clinical programs and classified as having DSM‐IV alcohol dependence (n= 71) or alcohol abuse (n= 57) and reference adolescents without AUDs recruited from community sources (n= 131). The assessment of health status included self‐reported health problems in 15 areas; serum liver enzyme assays, including γ‐glutamyl transpeptidase, alanine aminotransferase, and aspartate aminotransferase; and physical examination findings. Negative emotionality was determined by systematically combining scores from the Hamilton Anxiety Rating Scale, the Beck Depression Inventory, the Child Behavior Checklist, and the Multidimensional Personality Questionnaire.

Results: Adolescent AUDs were associated with more self‐reported health problems, higher γ‐glutamyl transpeptidase and alanine aminotransferase levels, and more physical examination abnormalities. Negative emotionality was highly correlated with self‐reported health problems, mediated the relationship between AUDs and self‐reported health problems, and was not correlated with serum liver enzyme levels or physical examination abnormalities.

Conclusions: These results indicated that AUDs during adolescence were associated with health problems, including modest but demonstrable liver injury. Self‐reported health problems were probably best understood, in this context, as a negative emotionality manifestation.
Alcohol Impairs Protein Synthesis and Degradation in Cultured Skeletal Muscle Cells
Authors: Hong‐Brown Ly Q. , Frost Robert A. , Lang Charles H.
Published: April 2006

Background: Acute and chronic alcohol intoxication decreases skeletal muscle protein synthesis under in vivo conditions. We investigated whether ethanol (EtOH) and its major metabolites, acetaldehyde and acetate, can directly modulate protein balance under in vitro conditions.

Methods: Human myocytes were incubated with different doses of EtOH for varying periods of time (i.e., 4–72 hr). Alternatively, cells were incubated with acetaldehyde, acetate, insulin, insulin‐like growth factor‐I (IGF‐I), or with a combination of EtOH plus insulin or IGF‐I. Rates of protein synthesis or degradation were determined by 35S‐methionine/cysteine incorporation into or release from cellular protein.

Results: A significant, 15% to 20%, decrease in basal protein synthesis was observed after 24 hr, but not at earlier time points, in response to 80 mM EtOH. Incubation of myocytes for 72 hr decreased synthesis in cells incubated with EtOH ranging between 60 and 120 mM. The ability of IGF‐I or insulin to stimulate protein synthesis was impaired by 30% and 60%, respectively, in cells incubated with 80 mM EtOH for 72 hr. Exposure of cells to 200 μM acetaldehyde or 5 mM Na‐acetate also decreased basal protein synthesis. In contrast, neither EtOH, acetaldehyde, nor acetate altered the basal rate of protein degradation. However, EtOH completely impaired the ability of insulin and IGF‐I to inhibit proteolysis. Finally, EtOH did not impair IGF‐I receptor autophosphorylation, but inhibited the ability of insulin to phosphorylate its own receptor. EtOH also did not alter the number of insulin or IGF‐I receptors or the formation of insulin/IGF‐I hybrid receptors.

Conclusions: We have demonstrated that EtOH can directly inhibit muscle protein synthesis under in vitro conditions. Neither EtOH nor its metabolites altered basal protein degradation, although EtOH did compromise the ability of both insulin and IGF‐I to slow proteolysis. This impairment seems to be mediated by different defects in signal transduction.
Moderate Alcohol During Pregnancy: Learning and Behavior in Adolescent Rhesus Monkeys
Authors: Schneider Mary L. , Moore Colleen F. , Kraemer Gary W.
Published: April 2006

Background: Although high‐dose prenatal alcohol exposure is related to cognitive and behavioral impairments in children and adolescents with fetal alcohol syndrome, there is relatively little research on the effects of moderate drinking during pregnancy. We examined learning, memory, and behavior in adolescent rhesus monkeys prenatally exposed to moderate levels of alcohol, psychological stress, or both alcohol and stress.

Methods: Forty adolescent rhesus monkey subjects were derived from four groups of female rhesus monkeys that (1) consumed alcohol throughout gestation; (2) experienced prenatal stress; (3) experienced prenatal stress and alcohol consumption; or (4) control group (no alcohol, no stress). The subjects were assessed for number of trials required to reach 90% criterion of correct responses on nonmatching‐to‐sample task (NMS), followed by trials with delays of 30, 60, or 120 sec. Ratings of behavior during testing were made after each session.

Results: Subjects exposed to moderate prenatal alcohol required significantly more trials to reach criterion on the acquisition phase of the NMS task but had no difficulty with delays. Prenatally stressed monkeys showed lower response inhibition or less behavioral restraint, whereas prenatal alcohol plus stress monkeys showed higher activity level and stereotypies compared with controls. High scores on neonatal measures of orientation (attending to novel stimuli) and motor maturity and low scores on irritability, activity, stereotypies, and impulsivity during acquisition were correlated with fewer trials to criterion on acquisition of NMS.

Conclusions: NMS trials required to reach criterion and behavior during testing are sensitive to moderate‐level prenatal alcohol exposure in monkeys. The most adverse behavioral outcomes (hyperactivity and stereotypies) were associated with prenatal alcohol plus stress, raising concerns that environmental stress might provide the context within which fetal alcohol exposure could promote adverse behavioral outcomes. These effects occurred in the absence of either facial deformities or retarded physical growth.
Nonalcoholic Fatty Liver Disease: Implications for Alcoholic Liver Disease Pathogenesis
Authors: Diehl Anna Mae
Published: April 2006

This article represents the proceedings of a symposium at the 2000 ISBRA Meeting in Yokohama, Japan. The presentation was Nonalcoholic fatty liver disease: Implications for alcoholic liver disease pathogenesis, by Anna Mae Diehl.
Ethanol and Lipid Metabolic Signaling
Authors: Shukla Shivendra D. , Sun Grace Y. , Gibson Wood W. , Savolainen Markku J. , Alling Christer , Hoek Jan B.
Published: April 2006

This article represents the proceedings of a symposium at the 2000 ISBRA Meeting in Yokohama, Japan. The chairs were Shivendra D. Shukla and Grace Y. Sun. The presentations were (1) Metabolic turnover of ethanol into cellular lipids and platelet activating factor, by Shivendra D. Shukla; (2) Ethanol action on the phospholipase A2 signaling pathways in astrocytes, by Grace Y. Sun; (3) Mechanisms of ethanol‐induced perturbation of lipoprotein cholesterol transport, by W. Gibson Wood; (4) Transfer of an abnormal ethanol‐induced phospholipid, phosphatidylethanol, between lipoproteins, by Markku J. Savolainen; (5) Phospholipase‐d‐mediated formation of phosphatidylethanol, by Christer Alling; and (6) Changes in phosphoinositide signaling after chronic ethanol treatment, by Jan B. Hoek.
Sex Difference in Alcohol‐Related Organ Injury
Authors: Sato Nobuhiro , Lindros Kai O. , Baraona Enrique , Ikejima Kenichi , Mezey Esteban , Järveläinen Harri A. , Ramchandani Vijay A.
Published: April 2006

This article represents the proceedings of a symposium at the 2000 ISBRA Meeting in Yokohama, Japan. The chairs were Nobuhiro Sato and Kai O. Lindros. The presentations were (1) Sex differences in ethanol pharmacokinetics, by E. Baraona; (2) Estrogen regulates the sensitivity to endotoxin in hepatic Kupffer cells, by K. Ikejima; (3) Sex difference in alcohol‐related organ injury, by E. Mezey; (4) Aggravated ethanol‐induced liver injury in female rats: Protection by the antiestrogen toremifene, by Harri A. Järveläinen; and (5) Alcohol metabolism in Asian subjects: Sex differences and flushing response, by V. A. Ramchandani.
Alcohol Biomarkers: Clinical Significance and Biochemical Basis
Authors: Lakshman Raj , Tsutsumi Mikihiro , Ghosh P. , Takase S. , Anni H. , Nikolaeva O. , Israel Y. , Anton R. F. , Lesch O. M. , Helender A. , Eriksson G. , Jeppson J‐O. , Marmillot P. , Rao M. N.
Published: April 2006

This article represents the proceedings of a symposium at the 2000 ISBRA Meeting in Yokohama, Japan. The chairs were Raj Lakshman and Mikihiro Tsutsumi. The presentations were (1) Sialic acid index of apolipoprotein J: A new marker for chronic alcohol consumption, by P. Ghosh and M. R. Lakshman; (2) Microheterogeneity of serum glycoproteins in alcoholics, by M. Tsutsumi and S. Takase; (3) Probing protein‐ethanol adducts with combinatorial peptide libraries displayed by filamentous phage, by H. Anni, O. Nikolaeva, and Y. Israel Y; (4) Carbohydrate‐deficient transferrin as a marker for heavy alcohol use: What have we learned; Where do we go from here, by R. F. Anton; (5) Sensitivity and specificity of carbohydrate‐deficient transferrin in drinking experiments and different patient groups, by O. M. Lesch; (6), Transferrin variants interfere with the measurement of carbohydrate‐deficient transferrin, by A. Helender, G. Eriksson, and J‐O. Jeppson; and (7) Chronic ethanol on protein trafficking in liver, by P. Marmillot, M. N. Rao, and M. R. Lakshman.
Ethanol and Gene Expression in Brain
Authors: Matsumoto Izuru , Wilce Peter A. , Buckley Tracey , Dodd Peter , Puzke Jorg , Spanagel Rainer , Zieglgansberger Walther , Wolf Gerald , Leng Shuangying , Rommelspacher Hans , Finckh Ulrich , Schmidt Lutz G.
Published: April 2006

This article represents the proceedings of a symposium at the 2000 ISBRA Meeting in Yokohama, Japan. The chairs were Izuru Matusmoto and Peter A. Wilce. The presentations were (1) GABA receptor subunit expression in the human alcoholic brain, by Tracey Buckley and Peter Dodd; (2) NMDAR gene expression during ethanol addiction, by Jorg Puzke, Rainer Spanagel, Walther Zieglgansberger, and Gerald Wolf; (3) Differentially expressed gene in the nucleus accumbens from ethanol‐administered rat, by Shuangying Leng; (4) Expression of a novel gene in the alcoholic brain, by Peter A. Wilce; and (5) Investigations of haplotypes of the dopamine D2‐receptor gene in alcoholics, by Hans Rommelspacher, Ulrich Finckh, and Lutz G. Schmidt.
Core Heritable Personality Characteristics and Relapse in Alcoholics
Authors: Janowsky David S. , Fawcett Jan , Meszaros Kurt , Verheul Roel
Published: April 2006

This article represents the proceedings of a symposium at the 2000 ISBRA Meeting in Yokohama, Japan. The chairs were David S. Janowsky and Jan Fawcett. The presentations were (1) The tridimensional personality questionnaire: Predictor of relapse in detoxified alcoholics, by Kurt Meszaros; (2) Novelty seeking predicts clinical trial attrition in alcoholics, by Jan Fawcett; (3) Personality and alcohol/substance use disorder patient relapse and attendance at self‐help group meetings, by David S. Janowsky; and (4) A three‐pathway psychobiological model for craving for alcohol, by Roel Verheul.
Functional Relevance of Human ADH Polymorphism
Authors: Eriksson C. J. Peter , Fukunaga Tatsushige , Sarkola Taisto , Chen Wei J. , Chen C. C. , Ju J. M. , Cheng Andrew T. A. , Yamamoto Hidetaka , Kohlenberg‐Müller Kathrin , Kimura Mitsuru , Murayama Masanobu , Matsushita Sachio , Kashima Haruo , Higuchi Susumu , Carr Lucinda , Viljoen D. , Brooke L. , Stewart T. , Foroud T. , Su J. , Li Ting‐Kai , Whitfield John B.
Published: April 2006

This article represents the proceedings of a symposium at the 2000 ISBRA Meeting in Yokohama, Japan. The chairs were C. J. Peter Eriksson and Tatsushige Fukunaga. The presentations were (1) 4‐Methylpyrazole as a tool in the investigation of the role of ADH in the actions of alcohol in humans, by Taisto Sarkola and C. J. Peter Eriksson; (2) ADH2 polymorphism and flushing in Asian populations, by Wei J. Chen, C. C. Chen, J. M. Ju, and Andrew T. A. Cheng; (3) Role of ADH3 genotypes in the acute effects of alcohol in a Finnish population, by Hidetaka Yamamoto, Kathrin Kohlenberg‐Müller, and C. J. Peter Eriksson; (4) Clinical characteristics and disease course of alcoholics with different ADH2 genotypes, by Mitsuru Kimura, Masanobu Murayama, Sachio Matsushita, Haruo Kashima, and Susumu Higuchi; (5) ADH2 polymorphism, alcohol drinking, and birth defects, by Lucinda Carr, D. Viljoen, L. Brooke, T. Stewart, T. Foroud, J. Su, and Ting‐Kai Li; and (6) ADH genotypes and alcohol use in Europeans, by John B. Whitfield.
Perioperative Morbidity and Mortality in Chronic Alcoholic Patients
Authors: Spies Claudia , Tønnesen Hanne , Andreasson Sven , Helander Anders , Conigrave Kate
Published: April 2006

This article represents the proceedings of a symposium at the 2000 ISBRA Meeting in Yokohama, Japan. The chairs were Claudia Spies and Hanne Tønnesen. The presentations were (1) Relevance of alcohol misuse in surgical patients, by Hanne Tønnesen; (2) Diagnosis of alcohol abuse and alcohol dependence, by Sven Andreasson; (3) Diagnosis of acute alcohol misuse, by Anders Helander; (4) Preoperative intervention for excessive alcohol consumption, by Kate Conigrave; and (5) Prevention and treatment of perioperative complications in chronic alcoholics, by Claudia Spies.
How Is the Liver Primed or Sensitized for Alcoholic Liver Disease?
Authors: Tsukamoto Hidekazu , Takei Yoshiyuki , McClain Craig J. , Joshi‐Barve S. , Hill D. , Schmidt J. , Deaciuc I. , Barve S. , Colell Anna , Garcia‐Ruiz Carmen , Kaplowitz Neil , Fernandez‐Checa Jose C. , Yokoyama Hirokazu , Okamura Yukishige , Nakamura Yuji , Ishii Hiromasa , Chawla Rajendar K. , Barve S. , Joshi‐Barve S. , Watson W. , Nelson W. , Lin Min , Ohata Mitsuru , Motomura Kenta , Enomoto N. , Ikejima K. , Kitamura T. , Oide H. , Hirose M. , Bradford B. U. , Rivera C. A. , Kono H. , Peter S. , Yamashina S. , Konno A. , Ishikawa M. , Shimizu H. , Sato N. , Thurman R.
Published: April 2006

This article represents the proceedings of a symposium at the 2000 ISBRA Meeting in Yokohama, Japan. The chairs were Hidekazu Tsukamoto and Yoshiyuki Takei. The presentations were (1) Tribute to Professor Rajendar K. Chawla, by Craig J. McClain; (2) Dysregulated TNF signaling in alcoholic liver disease, by Craig J. McClain, S. Joshi‐Barve, D. Hill, J Schmidt, I. Deaciuc, and S. Barve; (3) The role of mitochondria in ethanol‐mediated sensitization of the liver, by Anna Colell, Carmen Garcia‐Ruiz, Neil Kaplowitz, and Jose C. Fernandez‐Checa; (4) A peroxisome proliferator (bezafibrate) can prevent superoxide anion release into hepatic sinusoid after acute ethanol administration, by Hirokazu Yokoyama, Yukishige Okamura, Yuji Nakamura, and Hiromasa Ishii; (5) S‐adenosylmethionine affects tumor necrosis factor‐α gene expression in macrophages, by Rajendar K. Chawla, S. Barve, S. Joshi‐Barve, W. Watson, W. Nelson, and C. McClain; (6) Iron, retinoic acid and hepatic macrophage TNFα gene expression in ALD, by Hidekazu Tsukamoto, Min Lin, Mitsuru Ohata, and Kenta Motomura; and (7) Role of Kupffer cells and gut‐derived endotoxin in alcoholic liver injury, by N. Enomoto, K. Ikejima, T. Kitamura, H. Oide, Y. Takei, M. Hirose, B. U. Bradford, C. A. Rivera, H. Kono, S. Peter, S. Yamashina, A. Konno, M. Ishikawa, H. Shimizu, N. Sato, and R. Thurman.
Neuroreceptors and Ion Channels as Targets of Alcohol
Authors: Narahashi Toshio , Kuriyama Kinya , Illes P. , Wirkner K. , Fischer W. , Mühlberg K. , Scheibler P. , Allgaier C. , Minami K. , Lovinger D. , Lallemand F. , Ward R. J. , DeWitte P. , Itatsu T. , Takei Y. , Oide H. , Hirose M. , Wang X. E. , Watanabe S. , Tateyama M. , Ochi R. , Sato N.
Published: April 2006

This article represents the proceedings of a symposium at the 2000 ISBRA Meeting in Yokohama, Japan. The chairs were Toshio Narahashi and Kinya Kuriyama. The presentations were (1) Modulation of neuroreceptors and ion channels by alcohol, by T. Narahashi; (2) Inhibition by ethanol of NMDA and AMPA receptor‐channels, by P. Illes, K. Wirkner, W. Fischer, K. Mühlberg, P. Scheibler, and C. Allgaier; (3) Effects of ethanol on metabotropic glutamate receptors, by K. Minami; (4) Acute alcohol actions on the 5‐HT3 ligand‐gated ion channel, by D. Lovinger; (5) Inhibition of NMDA receptors by MK801 attenuates ethanol‐induced taurine release from the hippocampus, by F. Lallemand, R.J. Ward, and P. DeWitte; and (6) Effect of ethanol on voltage‐operated Ca2+ channels in hepatic stellate cells, by T. Itatsu, Y. Takei, H. Oide, M. Hirose, X. E. Wang, S. Watanabe, M. Tateyama, R. Ochi, and N. Sato.
Recent Research on Alcohol Tolerance and Dependence
Authors: Suwaki Hiroshi , Kalant Harold , Higuchi Susumu , Crabbe John C. , Ohkuma Seitaro , Katsura Masashi , Yoshimura Masami , Stewart Robert C. , Li Ting‐Kai , Weiss Friedbert
Published: April 2006

This article represents the proceedings of a symposium at the 2000 ISBRA Meeting in Yokohama, Japan. The chairs were Hiroshi Suwaki and Harold Kalant. The presentations were (1) Influence of ADH genotypes on acute alcohol withdrawal syndrome in Japanese, by Susumu Higuchi; (2) Use of genetic analyses to refine phenotypes related to alcohol tolerance and dependence, by John C. Crabbe; (3) Neurochemical basis for alcohol dependence, by Seitaro Ohkuma and Masashi Katsura; (4) Adenylyl cyclase and development of tolerance to addictive drugs, by Masami Yoshimura; (5) Tolerance in rat lines selectively bred for alcohol preference, by Robert C. Stewart and Ting‐Kai Li; and (6) Ethanol reinforcement, dependence, and vulnerability to relapse: Interactions between neuroadaptive and conditioning factors, by Friedbert Weiss.
Alcohol and the Pancreas
Authors: Haber Paul , Nakamura Masahiko , Tsuchimoto Kanji , Ishii Hiromasa , Keogh Gregory W. , Apte Minoti V. , Moran Corey S. , Stewart Nancy L. , Crawford Darrell H. G. , Pirola Romano C. , McCaughan Geoffrey W. , Ramm Grant A. , Wilson Jeremy S. , Nishino H. , Kohno M. , Aizawa R. , Tajima N. , Maruyama K. , Takahashi H. , Matsushita S. , Okuyama K. , Yokoyama A. , Nakamura Y. , Shirakura K. , Ishii H. , Conigrave Katherine M. , Hu B. Frank , Camargo Carlos A. , Stampfer Meir J. , Willett Walter C. , Rimm Eric B.
Published: April 2006

This article represents the proceedings of a workshop at the 2000 ISBRA Meeting in Yokohama, Japan. The presentations were (1) Phenotypic alteration of myofibroblast during ethanol‐induced pancreatic injury: its relation to bFGF, by Masahiko Nakamura, Kanji Tsuchimoto, and Hiromasa Ishii; (2) Activation of pancreatic stellate cells in pancreatic fibrosis, by Paul S. Haber, Gregory W. Keogh, Minoti V. Apte, Corey S. Moran, Nancy L. Stewart, Darrell H.G. Crawford, Romano C. Pirola, Geoffrey W. McCaughan, Grant A. Ramm, and Jeremy S. Wilson; (3) Pancreatic blood flow and pancreatic enzyme secretion on acute ethanol infusion in anesthetized RAT, by H. Nishino, M. Kohno, R. Aizawa, and N. Tajima; (4) Genotype difference of alcohol‐metabolizing enzymes in relation to chronic alcoholic pancreatitis between the alcoholic in the National Institute on Alcoholism and patients in other general hospitals in Japan, by K. Maruyama, H. Takahashi, S. Matsushita, K. Okuyama, A. Yokoyama, Y. Nakamura, K. Shirakura, and H. Ishii; and (5) Alcohol consumption and incidence of type 2 diabetes, by Katherine M. Conigrave, B. Frank Hu, Carlos A. Camargo Jr, Meir J. Stampfer, Walter C. Willett, and Eric B. Rimm.
Ethanol and Protein Metabolism
Authors: Cunningham Carol C. , Preedy Victor R. , Paice Alistair G. , Hesketh John E. , Peters Timothy J. , Patel Vinood B. , Volpi Elena , Mawatari Kazunori , Masaki H. , Mori M. , Torii Kunio
Published: April 2006

This article represents the proceedings of a workshop at the 2000 ISBRA Meeting in Yokohama, Japan. The chairs were Carol C. Cunningham and Victor R. Preedy. The presentations were (1) Ribosomal content, ribosomal localization and the levels of ribosomal protein mRNA and rRNA in rat skeletal muscle exposed to ethanol, by Alistair G. Paice, John E. Hesketh, Timothy J. Peters, and Victor R. Preedy; (2) Altered hepatic mitochondrial ribosome structure after chronic ethanol administration, by Vinood B. Patel and Carol C. Cunningham; (3) Clinical aspects of hepatic protein metabolism and alcohol, by Elena Volpi; and (4) Effects of oral intake of alanine plus glutamine on ethanol metabolism and ethanol‐related depression in motor activity, by Kazunori Mawatari, H. Masaki, M. Mori, and Kunio Torii.
Association of Polymorphism in the Alcohol Dehydrogenase 2 Gene With Alcohol‐Induced Testicular Atrophy
Authors: Yamauchi Masayoshi , Takeda Kunihiko , Sakamoto Kazuhiko , Searashi Yasuyuki , Uetake Shinichiro , Kenichi Hashimoto , Toda Gotaro
Published: April 2006

Background: Alcohol abuse can induce testicular atrophy, but it only occurs in some alcoholics. Alcohol dehydrogenase (ADH) is located principally on the Leydig cells.

Methods: To investigate whether genetic polymorphism of alcohol dehydrogenase (ADH) 2 and aldehyde dehydrogenase (ALDH) 2 was related to alcoholic testicular atrophy, we determined restriction fragment‐length polymorphisms of the ADH2 and ALDH2 genes in 43 Japanese male alcoholics and 50 healthy subjects. An orchidometer was used to determine the testicular size.

Results: Less than 16 ml in testicular size was defined as testicular atrophy. Testicular atrophy was found in 24 (55.8%) cases out of 43 alcoholics. Digestion with MaeIII and Mbo II after polymerase chain reaction amplification showed that the ADH21 allele frequency was significantly higher in patients with testicular atrophy than in those without testicular atrophy (χ2= 4.665, p= 0.031), whereas no significant association was observed between testicular atrophy and the ALDH2 gene.

Conclusions: The ADH21 allele may be associated with alcoholic testicular atrophy.
Effects of Ethanol on L‐Arginine Transport in Rat Ito Cells in Relation to Nitric Oxide Production
Authors: Saibara Toshiji , Ono Masafumi , Iwasaki Shinji , Maeda Takashi , Onishi Saburo , Hayashi Yoshihiro , Enzan Hideaki
Published: April 2006

Background: Nitric oxide (NO) is a potent mediator of hepatic sinusoidal hemodynamics that is synthesized in the hepatic stellate cells (Ito cells, fat‐storing cells) and affects these cells. NO production may depend on the induction of inducible nitric oxide synthase and on transport of extracellular L‐arginine. The precise mechanism that controls NO production in stellate cells was characterized recently.

Methods: Kinetic analysis of L‐arginine transport and reverse transcription‐polymerase chain reaction for cationic amino acid transporter (CAT) were carried out by using stellate cells prepared from the male Wistar rat. The effect of ethanol on L‐arginine transport and NO production of stellate cells was assessed in the presence of tumor necrosis factor (TNF)‐α and interferon (IFN)‐γ.

Results: The L‐arginine transport system functioning in the hepatic stellate cells was system y+, possibly mediated by CAT‐1 and CAT‐2B (Km∼50 μM). IFN‐γ in combination with TNF‐α induced NO production with an enhancement in CAT‐2B mRNA expression and L‐arginine transport, whereas L‐arginine transport and NO production were suppressed by coincubated ethanol.

Conclusions: In hepatic stellate cells, ethanol has suppressive effects on NO production and extracellular L‐arginine transport in the presence of TNF‐α and IFN‐γ. The estimated Km of L‐arginine transporter in hepatic stellate cells is very similar to the physiological L‐arginine concentration in portal vein. Our findings may support the merit of further studies on the modulation of NO production via access to portal blood L‐arginine concentration to control disturbed hepatic sinusoidal blood flow in patients with alcoholic liver disease.
A Variant of Des‐γ‐Carboxy Prothrombin Was Increased in Alcoholic Liver Disease Without Hepatocellular Carcinoma
Authors: Ohhira Motoyuki , Saito Hiroyuki , Suzuki Yasuaki , Naraki Toru , Sakurai Shinobu , Ohtake Takaaki , Suzuki Masako , Ohhira Masumi , Fujimoto Yoshinori , Kohgo Yutaka
Published: April 2006

Serum variants of des‐γ‐carboxy prothrombin (DCP) recognized by two different monoclonal antibodies, 19B7 and MU‐3, were measured in patients with alcoholic liver disease (ALD), and the values were compared with those of viral liver disease (VLD) and hepatocellular carcinoma (HCC). In the assay that used 19B7 antibody, DCP levels in ALD and HCC were significantly higher than that of VLD, although there was no significant difference in the values between ALD and HCC. In the assay that used MU‐3 antibody, DCP level of HCC was significantly higher than those of ALD and VLD, although there was no significant difference in values between ALD and VLD. The ratio of 19B7/MU‐3 assay values was significantly higher for ALD than the ratios for VLD and HCC. It is suggested that ALD has a different DCP variant pattern compared with VLD and HCC, which suggests that ALD has a different mechanism of DCP production.
Polymorphism of the Neuropeptide Y Gene: An Association Study With Alcohol Withdrawal
Authors: Okubo Takehito , Harada Shoji
Published: April 2006

Background: Neuropeptide Y (NPY) exists in both the central and peripheral nervous system and is thought to modulate many functions such as feeding behavior, anxiety‐associated behavior, circadian rhythm, seizure modulation, and hormone secretion. Recent studies have revealed that NPY influences alcohol consumption in mice and that alcohol‐preferring rats showed lower concentrations of NPY‐like immunoreactivity compared with alcohol‐nonpreferring rats in several brain regions.

Methods: In the present study, we analyzed the whole coding region and 5′‐untranslating region of the NPY gene for 163 Japanese male alcoholics with different withdrawal symptoms (93 with delirium tremens, 71 with seizures, 49 with hallucinations) and 98 Japanese male controls. ALDH2 genotypes of all subjects tested were ALDH2*1 homozygote.

Results: Three polymorphic nucleotide substitutions, namely −121C/A (promoter), 1258G/A (exon 2), and 5671C/T (exon 3), were detected in both groups. Substituting C to A in the −121 locus produced a putative binding site of GATA‐1 and GATA‐2. Also, −90G/A (promoter) as a rare variant and 5642–5651 single nucleotide repeats T10/T11 (intron 2) were found. Polymorphism (C/T) at the 1128 locus has been reported to be associated with a higher serum cholesterol level in obese white subjects, but such a polymorphism was not found in our samples. The genotypical distributions for these polymorphic loci (−121C/A, 1258G/A, 5642‐5651 T10/T11, and 5671C/T) were not significantly different between the alcoholics and controls. However, frequency of the T allele and frequency of the genotype that possessed T alleles (CT, TT) at the 5671 locus were significantly higher in patients with seizure than in those without seizure (p < 0.05, p < 0.02).

Conclusion: Our data suggested that a C to T substitution at the 5671 locus of the NPY gene may be associated with seizure during alcohol withdrawal.
Structural Requirements of Alkanol Interaction Sites on Human α2β4 Neuronal Nicotinic Acetylcholine Receptors Expressed in Xenopus Oocytes: Effects of Linear and Branched‐Chain Alkanols
Authors: Godden Elizabeth L. , Dunwiddie Thomas V.
Published: April 2006

Background: Nicotine and alcohol are both drugs of abuse that are frequently used concurrently, but little is known about the interactions between these agents at the molecular level. The neuronal subgroup of nicotinic acetylcholine receptors (nAChRs) are members of a neurotransmitter‐gated ion channel superfamily and have been used extensively to characterize the interactions of ethanol with these channels. Previous work has shown that both the direction and the magnitude of the modulatory effects of n‐alcohols and several fluorinated analogs on nAChRs can be predicted based upon the molecular volume of the alkanol. However, size (molecular volume) is only one of several determinants of binding‐site interactions; shape and flexibility of the interacting ligand and/or the site itself (i.e., structural constraints) and alkanol hydrophobicity are also likely to be involved.

Methods: Two‐electrode voltage‐clamp electrophysiology was used to investigate the effects of alkanols on the α2β4 human neuronal nicotinic acetylcholine receptor ectopically expressed in Xenopus oocytes.

Results: ACh‐induced currents mediated by α2β4 nAChRs were potentiated by 1‐ and 2‐propanol, whereas 1‐pentanol and several branched‐chain pentanol isomers only inhibited channel activity. 1‐Butanol had a biphasic concentration‐response curve, producing a nearly 2‐fold increase in current at lower concentrations and >50% inhibition at higher concentrations. Other four‐carbon alcohols such as 2‐butanol and 2‐methyl‐1‐propanol also facilitated responses at lower concentrations and inhibited at higher concentrations, whereas 2‐butene‐1‐ol and 2‐methyl‐2‐propanol only inhibited responses. The effects of these alkanols on ACh responses were the result of changes in both the potency as well as the efficacy of ACh at these receptors.

Conclusions: Although molecular volume and hydrophobicity both correlate well with the potencies of linear alkanols in modulating the activity of α2β4 nAChRs, these relationships break down almost completely when comparing the structural isomers of these agents. The structure of the interacting alkanol significantly affects the potency and efficacy of alkanols at the nAChR, and this occurs independently of differences in molecular volume and hydrophobicity.
Influence of Alcohol Consumption on Serum Immunoglobulin E Levels in Atopic and Nonatopic Adults
Authors: Vidal C. , Armisén M. , Domínguez‐Santalla M. J. , Gude F. , Lojo S. , González‐Quintela A.
Published: April 2006

Background: Total and specific serum immunoglobulin E (IgE) are routinely used as diagnostic tools in allergy clinics. Several studies have demonstrated an increase of total serum IgE concentrations in alcoholics, but the possible influence of lower quantities of ethanol intake on serum IgE values has not been fully evaluated. This study was aimed at analyzing the influence of alcohol intake on both total and specific serum IgE concentrations in patients studied in an allergy clinic.

Methods: A total of 460 patients were included in the study. According to skin‐prick tests to common aeroallergens, 325 were classified as atopics and 135 as nonatopics. Most atopic patients (253; 78%) were allergic to mites. Alcohol consumption was recorded as the number of standard (10‐g) drinking units regularly consumed per week. Two hundred subjects (43%) were abstainers, and 260 (57%) were regular consumers of a median of 30 g of alcohol per week. Total serum IgE was measured in all patients by latex‐enhanced nephelometry. Serum‐specific IgE was assayed by fluoroenzymeimmunoassay.

Results: Total serum IgE increased along with ethanol consumption. On multivariate analysis, regular alcohol consumption greater than 70 g per week was associated with increased total serum IgE levels, even when adjusting for age, sex, atopy, and smoking. Among house‐dust mite–allergic patients, specific serum IgE values against the house dust mite Dermatophagoides pteronyssinus were higher in regular alcohol consumers than in abstainers. This difference was not observed among patients allergic to grass pollen (Lolium perenne).

Conclusions: Alcohol consumption, even in moderate quantities, is associated with increased total and specific IgE concentrations in subjects studied in an allergy clinic. Alcohol intake should be taken into account in epidemiological studies of total serum IgE levels.