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Alcohol and Alcoholism
Volume 40, Number 4, July/August 2005
(Updated July 8, 2005)

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Guilherme Borges, Liliana Mondragón, Maria Elena Medina-mora, Ricardo Orozco, Joaquin Zambrano, and Cheryl Cherpitel.  A case-control study of alcohol and substance use disorders as risk factors for non-fatal injury.  Alcohol and Alcoholism 40(4):257-262, July/August 2005.

Summary:
Using a case-control study design the authors examined the association of alcohol use disorders (AUD) and substance use disorders (SUD) and the risk of non-fatal injuries. AUD and SUD were diagnosed according to criteria of the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) and the International Classification of Diseases, Version 10 (ICD-10). The cases were injured patients (n = 653) 18–65-years-old who attended one emergency department (ED). The controls were subjects (n = 1,131) of the same age group from a representative sample of Mexico City residents. Information on drug and alcohol use was obtained by interview using the World Mental Health version of the Composite International Diagnostic Interview (WMH-CIDI). Among injured patients, the prevalence of substance abuse or dependence within the last 12 months was 12.3% for alcohol and 2.5% for other substances (marijuana, cocaine, tranquilizers, amphetamines, others), compared to 1.8% and 0.3% respectively among controls. Adjusted odds ratios (OR) of injury were 4.95 (95% confidence interval [CI], 2.87–8.52) for alcohol use and 2.58 (95% CI, 0.73–9.17) for other substance use. A significant level of comorbid alcohol and substance use disorders was also found. The authors conclude that efforts should be made to treat or refer ED patients with alcohol and substance use disorders, and that special care should be taken to address comorbid cases.

NIAAA Glossary Terms:  AOD abuse, AOD dependence,
alcohol use disorder classification, accident, injury, trauma, diagnostic criteria, emergency care, case-control study, Mexico, interview, prevalence, marijuana in any form, cocaine, tranquilizers, amphetamines, risk analysis, risk factors, relative risk, comorbidity, multiple drug use, human study


Kerrianne Watt, David M. Purdie, Ann M. Roche, and Roderick J. Mcclure.  The relationship between acute alcohol consumption and consequent injury typeAlcohol and Alcoholism 40(4):263-268, July/August 2005.

Summary:
The relationship between acute alcohol consumption and injury type (nature of injury, body region injured) was quantified in a cross-sectional study, with adjustment for the effect of known confounders (demographic and situational variables, usual drinking patterns, substance use, and risk-taking behavior). The study was conducted between October, 2000 and October, 2001. The participants were patients aged ≥15 years presenting to an emergency department for treatment of an injury sustained in the preceding 24 hours. Three measures of acute alcohol consumption were used: drinking setting, quantity, and beverage type consumed in the 6 hours before injury. Two variables were used to quantify injury type: nature of injury (fracture/dislocation, superficial, internal, and central nervous system injury) and body part injured (head/neck, face, chest, abdomen, external, and extremities). Both were derived from patient medical records. Interviews were conducted with 593 patients. After controlling for relevant confounding variables, logistic regression analyses indicated that there was no significant association between any of the three measures of acute alcohol consumption and injury type. The authors concluded that the effects of acute alcohol consumption are not specific to injury type, and that interventions aimed at reducing the incidence of alcohol-related injury should not be targeted at specific injury types.

NIAAA Glossary Terms:  AOD use pattern, binge AOD use, AOD intake per occasion, acute AODE, accident, injury, trauma, emergency care, alcoholic beverage, drinking venue, bone fracture, skeletal system, central nervous system, head injury, neck, face, thorax, abdomen, arm, leg, medical history, interview, cross-sectional study, confounding variable, human study


Olli Savola, Onni Niemelä, and Matti Hillbom.  Alcohol intake and the pattern of trauma in young adults and working aged people admitted after trauma.  Alcohol and Alcoholism 40(4):269-273, July/August 2005.

Summary:
The relationship of different patterns of alcohol intake to various types of trauma was investigated in a series of consecutive trauma admissions (N = 385; 278 men, 107 women; 16–49 years old). Patients underwent clinical examinations, structured interviews on the amount and pattern of alcohol intake, and measurements of blood alcohol concentration (BAC).  Blood alcohol was detected in 51% of the patients on admission. Binge drinking was the predominant (78%) drinking pattern. Assaults, falls, and biking accidents were the most frequent causes of trauma. Dependent alcohol drinking and binge drinking were significantly more common among patients with head trauma than in those with other types of trauma (77% vs 59%, odds ratio [OR] = 2.38; 95% confidence interval [CI], 1.50
3.77). The OR for sustaining head injury increased sharply with increasing BAC: 1–99 mg/dl, OR = 1.24 (95% CI, 0.55–2.01); 100–149 mg/dl, OR = 1.64 (95% CI, 0.71–3.77), 150–199 mg/dl, OR = 3.20 (95% CI, 1.57–6.53); and >199 mg/dl, OR = 9.23 (95% CI, 4.79–17.79). In conclusion: (1) Binge drinking is a major risk factor for head trauma among trauma patients. (2) Assaults, falls, and biking accidents are the commonest causes for such injuries. (3) The relative risk for head injury markedly increases with increasing BAC. The authors believe that alcohol control measures should feature in policies aiming at preventing trauma-related morbidity and mortality.

NIAAA Glossary Terms:  AOD use pattern, AOD consumption, accident, injury, trauma, emergency care, interview, BAC level, binge AOD use, AOD dependence, risk analysis, risk factors, relative risk, head injury, assault and battery, accidental fall, dose-response relationship, human study


Magorzata Bednarska-Makaruk, Maria Rodo, Cezary Markuszewski, Anna Rozenfeld, Magorzata Swiderska, Boguslaw Habrat, and Hanna Wehr.  Polymorphisms of apolipoprotein E and angiotensin-converting enzyme genes and carotid atherosclerosis in heavy drinkersAlcohol and Alcoholism 40(4):274-282, July/August 2005.

Summary:
The authors investigated the influence of gene polymorphisms of apolipoprotein E (APO E) and angiotensin-converting enzyme (ACE) on carotid artery atherosclerosis in alcohol dependence. Polymorphism of both genes was identified by deoxyribonucleic acid (DNA) analysis in male alcohol-dependent patients (N = 130). Intima-media thickness (IMT) was measured by ultrasonography. Multivariate regression analysis revealed that of all the known risk factors the greatest impact on carotid atherosclerosis in alcoholics was exerted by age, hypertension, low-density lipoprotein (LDL) cholesterol, and fasting plasma glucose levels. Subjects carrying the APO E ε4 allele were more likely to develop atherosclerotic changes in carotid arteries compared with subjects with the ε3/3 genotype (statistically significant in patients under age 50 years). No association was shown between ACE I/D polymorphism and carotid atherosclerosis. Thus APO E polymorphism can increase the risk of carotid atherosclerosis development in alcoholics. The association of the APO E ε4 allele with carotid atherosclerosis was significant in younger patients. Since elevated carotid IMT is considered to be a good marker of increased risk of generalized atherosclerosis, the consequences could involve both cardiac and cerebrovascular events.

NIAAA Glossary Terms:  genetic polymorphism, allele, genotype, AOD dependence, apolipoproteins, angiotensin, athersclerosis, carotid artery, DNA, ultrasonography, multivariate analysis, regression analysis, risk factors, age differences, hypertensive disorder, low density lipoprotein, cholesterol, glucose, plasma, genetic markers, myocardial ischemia, stroke, human study


M. Ceccanti, R. Mancinelli, G. F. Sasso, J. P. Allen, R. Binetti, A. Mellini, F. Attilia, L. Toppo, and M. L. Attilia.  Erythrocyte thiamine (Th) esters: a major factor of the alcohol withdrawal syndrome or a candidate marker for alcoholism itself?  Alcohol and Alcoholism 40(4):283-290, July/August 2005.

Summary:
This study investigated the relationship of alcohol withdrawal syndrome to thiamine and thiamine esters, as well as the diagnostic power of thiamine and its esters. Thiamine and its esters were assessed in a series of alcoholics and in controls using an improved method. No association was found between alcohol withdrawal syndrome severity and thiamine and its esters, although the diagnostic power of thiamine diphosphate and thiamine was very high. Thiamine diphosphate was the most significant among the parameters studied, confirming that erythrocyte thiamine diphosphate is a suitable marker of alcoholism.
Thiamine diphosphate sensitivity across subjects was 84.1%, specificity was 85.4%, positive predictive value was 82.4%, and negative predictive value was 88.0%.

NIAAA Glossary Terms:  AOD withdrawal syndrome, AOD dependence, thiamine, esters, diagnosis, symptom severity, erythrocyte, phosphates, biochemical markers, specificity and sensitivity of measurement, predictive factor, human study


Marina Perfumi, Laura Mattioli, Laura Forti, Maurizio Massi, and Roberto Ciccocioppo.  Effect of Hypericum perforatum CO2 extract on the motivational properties of ethanol in alcohol-preferring rats.  Alcohol and Alcoholism 40(4):291-296, July/August 2005.

Summary:
Extracts of Hypericum perforatum (HPE; St. John's wort) reduce voluntary ethanol intake in different alcohol-preferring rat lines. This study evaluated the effect of the intragastric (IG) administration of a CO2 HPE extract (HP
CO2) on operant ethanol self-administration, as well as on voluntary ethanol intake, after a period of ethanol deprivation in Marchigian Sardinian alcohol-preferring rats. HPCO2 was administered through an indwelling IG catheter 1 hour before the tests. For the self-administration experiments, the rats were trained to self-administer 10% (v/v) ethanol in 30-minute daily sessions under a fixed ratio 1 reinforcement schedule. HPCO2 was also tested on 0.2% w/v saccharin self-administration. For the ethanol deprivation experiments, rats that had a previous experience with voluntary ethanol drinking were deprived of ethanol for 9 days, with water and food freely available; HPCO2 was given by IG injection 1 hour before re-presentation of ethanol. HPCO2 in doses of 31 or 125 mg/kg but not 7 mg/kg, significantly reduced ethanol self-administration, but had no effect on saccharin self-administration. The same doses of the extract abolished the increased ethanol intake following ethanol deprivation. The results provide evidence that HPCO2 markedly reduces the reinforcing properties of ethanol in the self-administration paradigm, as well as the increase of ethanol intake following ethanol deprivation. These findings further support the view that the use of HPE may represent an interesting pharmacological approach in the treatment of alcohol abuse and alcoholism.

NIAAA Glossary Terms:  herbal therapy, antidepressants, animal selectively bred for alcohol preference, laboratory rat, intragastric administration, self-administration of drugs, saccharin, AOD abuse, AOD dependence, drug therapy, animal study


Yong-Kyu Lee, Sung-Woo Park, Young-Kyung Kim, Dai-Jin Kim, Jaeseung Jeong, Hugh Myrick, and Young-Hoon Kim.  Effects of naltrexone on the ethanol-induced changes in the rat central dopaminergic system.  Alcohol and Alcoholism 40(4):297-301, July/August 2005.

Summary:
The opioid antagonist naltrexone may reduce ethanol reward, but the underlying neurochemical mechanisms have not been clarified. The afferent projections to the nucleus accumbens from the ventral tegmental area (VTA) provide a potential substrate by which endogenous opioids may modulate the dopaminergic rewarding effects of ethanol. The authors assessed messenger ribonucleic acid (mRNA) levels of tyrosine hydroxylase (TH), a major regulatory enzyme in  dopamine synthesis and levels of dopamine and its metabolites, after chronic ethanol administration with and without naltrexone. Sprague-Dawley rats were exposed for 4 weeks to 5% ethanol consumption with and without concurrent naltrexone administration. Levels of TH mRNA in the VTA and substantia nigra (SN)
were measured by in situ hybridization, and dopamine and its metabolites in the striatum were measured by high performance liquid chromatography. Chronic ethanol consumption increased TH mRNA levels in the VTA, but produced no significant change in the SN. With naltrexone treatment, ethanol-induced increase in the TH mRNA level was reduced in the VTA. Chronic ethanol consumption did not cause any change in the levels of dopamine and its metabolites in most brain regions. Ethanol consumption with naltrexone treatment significantly increased dopamine level only in the striatum. The results support the presence of interactions of opioid and dopaminergic systems in the VTA in mediating ethanol reward. Thus naltrexone attenuates the ethanol's rewarding properties by interfering with ethanol-induced stimulation of the mesolimbic dopaminergic pathway.

NIAAA Glossary Terms:  naltrexone, opioid receptors, antagonists, endogenous opioids, mRNA, tyrosine, hydroxylases, dopamine, neurotransmitter metabolism, laboratory rat, ethanol, ventral tegmental area, corpus striatum, high pressure liquid chromatography, chronic AODE, dopaminergic neuron, brain reward pathway, mesolimbic system, animal study


I. Pelc, C. Hanak, I. Baert, C. Houtain, P. Lehert, F. Landron, and P. Verbanck.  Effect of community nurse follow-up when treating alcohol dependence with acamprosate.  Alcohol and Alcoholism 40(4):302-307, July/August 2005.

Summary:
This study measured the effect of community nurse follow-up on abstinence and retention rates in alcohol-dependent outpatients treated with acamprosate. Recently detoxified alcohol-dependent patients were prescribed acamprosate for 26 weeks and randomized to either physician-only follow-up, or physician plus regular visits from a community nurse. Drinking behavior in the next 26 weeks was assessed at monthly visits to non-blind clinicians. The cumulative abstinence duration proportion (CADP) was significantly longer (P = 0.03) in the subjects who had received community nurse support (0.57) than in those who had not (0.39). In part, this might be an artefact of the higher retention rate among those followed up by the nurse, in that the method of calculating CADP allocates 100% days of drinking for the month before a failed attendance. Differences favoring community nurse follow-up were seen for time to first drink and clinical global impression. It was concluded that for recently detoxified alcohol-dependent patients treated with acamprosate, follow-up by a community nurse improves patient retention and probably the 6-month drinking outcome.

NIAAA Glossary Terms:  AOD dependence, detoxification, outpatient care, nurse, calcium acetylhomotaurinate, randomized controlled trial, AOD use behavior, AOD abstinence, follow-up study, patient compliance, relapse prevention, human study


Martin Driessen, Wolfgang Lange, Klaus Junghanns, and Tilman Wetterling.  Proposal of a comprehensive clinical typology of alcohol withdrawal — a cluster analysis approach.  Alcohol and Alcoholism 40(4):308-313, July/August 2005.

Summary:
The various courses of alcohol withdrawal were characterized by applying the Alcohol Withdrawal Scale (AWS) was applied to alcohol-dependent patients (N = 217) every 4 hours until withdrawal symptoms had passed (four consecutive scores below 3). Patients were medicated by a standardized treatment scheme according to AWS-scores. Hierarchical cluster analysis and discriminant analysis were applied. Five clusters were identified representing increasing alcohol withdrawal severity. Each cluster is characterized by a combination of the two maximum subscores (vegetative and psychopathological subscore) and three additional psychopathological symptoms (anxiety, disorientation, and hallucination). In 18.4% of the patients, relevant symptoms were not observed (cluster 1), 18.9% developed mild or moderate vegetative symptoms only (cluster 2), and 40.6% additional anxiety (cluster 3). In cluster 4 (11.1%) the most frequent psychopathological symptoms were disorientation and anxiety but no hallucinations, which could be observed only in cluster 5 (11.1%). Discriminant analysis using the maximum subscores at the first day of treatment as independent variables correctly predicted 89.9% of the five clusters. The results support a model of alcohol withdrawal clustering along the two dimensions of vegetative and psychopathological severity. Furthermore, the AWS may be useful for predicting the course of alcohol withdrawal on the first day of treatment.

NIAAA Glossary Terms:  AOD withdrawal syndrome, AOD dependence, symptom severity, cluster analysis, discriminant analysis, anxiety, AODR hallucinosis, predictive factor, variable, characteristic, factor, human study


Carla de Bruijn, Wim van den Brink, Ron de Graaf, and Wilma A. M. Vollebergh.  The craving withdrawal model for alcoholism: Towards the DSM-V. Improving the discriminant validity of alcohol use disorder diagnosis.  Alcohol and Alcoholism 40(4):314-322, July/August 2005.

Summary:
The discriminant validity of the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) and the International Classification of Diseases (ICD-10) classification of alcohol use disorders (AUD) was compared with that of the Craving Withdrawal Model (CWM). The CWM is an alternative classification that requires craving and withdrawal for the diagnosis of alcohol dependence and raises the alcohol abuse threshold to two DSM-IV AUD criteria. Data were derived from The Netherlands Mental Health Survey and Incidence Study, a large representative sample of the general Dutch population. Only non-abstinent subjects (N = 6041) were included in the present study. The DSM-IV, ICD-10, and CWM were compared using the following discriminant variables: alcohol intake, psychiatric comorbidity, functional status, familial alcohol problems, and treatment sought. The year prevalence of CWM alcohol dependence was lower than the prevalence of ICD-10 and DSM-IV dependence (0.3% versuss 1.4% and 1.4%). The year prevalence of abuse was similar for CWM and DSM-IV (4.7% and 4.9%), but lower for ICD-10 harmful use (1.7%). DSM-IV discriminated poorly between normality and abuse and ICD-10 discriminated poorly between harmful use and dependence. In contrast, the CWM distinctions between normality and abuse, and between abuse, and dependence were significant for most of the discriminant variables. The results indicate that CWM improves the discriminant validity of AUD diagnoses. The predictive validity of the CWM for alcohol and other substance use disorders remain to be studied.

NIAAA Glossary Terms:  discriminant validity, diagnostic criteria, alcohol use disorder classification, AOD abuse, AOD dependence, comparative study, AOD intake per occasion, mental health, comorbidity, family AODU history, familial alcoholism, prevalence, survey, human study


Enrique Echeburúa, Ricardo Bravo de Medina, and Javier Aizpiri.  Alcoholism and personality disorders: An exploratory study.  Alcohol and Alcoholism 40(4):323-326, July/August 2005.

Summary:
The International Personality Disorder Examination and the Millon Clinical Multiaxial Inventory-II for personality disorders were used to identify the most frequent personality disorders related to alcohol dependence. Consecutively recruited alcohol-dependent patients (n = 30) attending an outpatient clinic were compared with consecutively recruited psychiatric patients with non-addictive disorders (n = 30) and subjects from the general population
(n = 31) who matched the patient samples on age, gender, and socioeconomic level. At least one personality disorder was found in 40% of the alcohol-dependent patients and 16.6% of the general clinical sample, compared to 6.4% of the normative sample. Dependent personality disorders were most prevalent (13.3%), followed by paranoid and obsessive-compulsive personality disorders (10% each).

NIAAA Glossary Terms:  AOD dependence, personality disorder, obsessive-compulsive disorder, disorder classification, AODR disorder, case-control study, prevalence, AODR paranoia, human study


Charles P. M. Webb, Evelyn J. Bromet, Semyon Gluzman, Nathan L. Tintle, Joseph E. Schwartz, Stanislav Kostyuchenko, and Johan M. Havenaar.  Epidemiology of heavy alcohol use in ukraine: Findings from the world mental health survey.  Alcohol and Alcoholism 40(4):327-335, July/August 2005.

Summary:
Data from the World Mental Health (WMH) Survey were used to study the epidemiology of heavy alcohol use in Ukraine. The WMH Composite International Diagnostic Interview was administered in 2002 to a national probability sample of Ukrainian adults (N = 4,725). An algorithm for classifying past-year heavy alcohol use was developed from self-reports about the quantity and frequency of drinking, and its convergent validity was demonstrated. Prevalences and sociodemographic risk factors were examined separately for men and women. The 12-month rates of heavy alcohol use were 38.7% in men and 8.5% in women (22.0% overall). Among heavy alcohol users, 92% of men and 52% of women consumed at least 80 g of ethanol in a typical drinking day on a monthly basis in the year before the interview. The most significant risk factors in men and women were age (26–54 years for men; 18–25 years for women), living in the Southeast region, being in the labor force whether employed or unemployed, and for men, low education and being the father of a young child. For both sexes, a highly significant linear relationship was found between number of risk factors and heavy alcohol use. The rates for men were similar to those reported in a Russian national survey except for Southeast Ukraine where the rate was over 10% higher. The highest rates were among men who were middle-aged, fathers, and unemployed. Future prospective studies are needed to assess the impact of heavy alcohol use on Ukrainian physical health, mental health, and occupational and social functioning.

NIAAA Glossary Terms:  heavy AOD use, Ukraine, prevalence, risk factors, demographic characteristics, AOD use pattern, AOD use frequency, AOD intake per occasion, gender differences, regional differences, educational level achieved, employed, unemployed, correlation analysis, risk factors, international differences, Russia, age differences, survey, human study


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Alcohol and Alcoholism
Volume 40, Number 3, May/June 2005
(Updated April 15, 2005)

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N. Signorini-Allibe, B. Gonthier, F. Lamarche, H. Eysseric, and L. Barret.  Chronic consumption of ethanol leads to substantial cell damage in cultured rat astrocytes in conditions promoting acetaldehyde accumulation.  Alcohol and Alcoholism 40(3):163-171, May/June 2005.

Summary:
The cerebral cytotoxicity of ethanol was compared with that of its main metabolite acetaldehyde after acute or chronic exposures of rat astrocytes in primary culture. Cytotoxicity was evaluated as reduced cell viability (MTT reduction test) and deoxyribonucleic acid (DNA) damage (characterized by single cell gel electrophoresis. Changes in astrocyte survival and DNA integrity only occurred when the astrocytes were chronically exposed to ethanol (20 mM; 3, 6, or 9 days). In contrast, acute exposure to acetaldehyde strongly affected both viability and DNA integrity in a concentration-dependent manner. The cytotoxic effect of acetaldehyde was also indirectly evaluated after modifications of the normal ethanol metabolism by the use of different inducers or inhibitors. In presence of ethanol, the concomitant induction of catalase (by glucose oxidase) and inhibition of aldehyde dehydrogenase (by methylene blue) led to acetaldehyde accumulation within cells, which was followed by reduced viability and a substantial increase in DNA strand breaks. These results are consistent with a possible major role of acetaldehyde during brain ethanol metabolism. On the other hand, the effects observed after N-acetyl-5-methoxytryptamine (
AMT; melatonin) could also suggest a possible direct ethanol effect and a role for free radical attacks. The results are thus consistent with a possible predominant role of acetaldehyde during brain ethanol metabolism. On the other hand, the effects observed after AMT could also suggest a possible direct ethanol effect and a role for free radical attacks.

NIAAA Glossary Terms:  cytotoxicity, ethanol, acetaldehyde, cerebrum, astrocyte, cell culture study, cultured cell line, electrophoresis, DNA, 
cell function, chronic AODE, acute AODE, ethanol metabolism, enzyme inhibitors, inducible enzymes, catalase, aldehyde dehydrogenases, antioxidants, melatonin, free radicals, oxidative stress, dose-response relationship, laboratory study


Youqing Xu, Maria A. Leo, and Charles S. Lieber.  DLPC attenuates alcohol-induced cytotoxicity in HepG2 cells expressing CYP2E1Alcohol and Alcoholism 40(3):172-175, May/June 2005.

Summary:
This study examined  whether oxidative stress generated by ethanol metabolism via cytochrome P450 2E1 (CYP2E1) could be overcome by using dilinoleoylphosphatidylcholine (DLPC), a harmless antioxidant extracted from soybeans. The question was addressed by determining whether DLPC protects against alcohol-induced cytotoxicity in HepG2 cells expressing CYP2E1. A HepG2 subclone (2E1) expressing CYP2E1 and a control subclone (Neo) were exposed for 2 hours to DLPC (10 µM). Ethanol (100 mM) was then added for 5 days. Ethanol significantly decreased cell viability in the 2E1 cells and increased apoptosis. DLPC attenuated these alterations, with the most significant effects in the 2E1 cells. This was accompanied by a reduction of ethanol-induced oxidative stress, including lower hydrogen peroxide production in the 2E1 cells, but not in the Neo cells. The mitochondrial membrane potential was significantly diminished by ethanol in both cells and was also improved after adding DLPC, but only in the 2E1 cells. Mitochondrial glutathione (GSH) was also partially restored in the 2E1 cells by DLPC, which significantly inhibited CYP2E1 induction by ethanol. Thus DLPC opposes the cytotoxicity induced by alcohol in HepG2 cells expressing CYP2E1, a protective action due, at least in part, to attenuation of alcohol-induced oxidative stress and the alteration in the mitochondrial membrane potential. Based on these beneficial effects of DLPC and its harmlessness, the authors suggest that its therapeutic action be tested in alcoholics.

NIAAA Glossary Terms:  ethanol metabolism, cytochrome P450 2E1, antioxidants, cytotoxicity, cell culture study, cultured cell line, alcoholic liver disorder, apoptosis, oxidative stress, peroxide, mitochondria, glutathione, inducible enzymes, protective drug effect, AOD dependence, laboratory study


Kyoko Miyasaka, Hiroko Hosoya, Saeko Takano, Minoru Ohta, Ayako Sekime, Setsuko Kanai, Toshimitsu Matsui, and Akihiro Funakoshi.  Differences in ethanol ingestion between cholecystokinin-A receptor deficient and -B receptor deficient mice.  Alcohol and Alcoholism 40(3):176-180, May/June 2005.

Summary:
Cholecystokinin (CCK) modulates dopamine (DA) release in the nucleus accumbens (NA) through the CCK-A receptor (CCK-AR). The dopaminergic neurotransmission between the ventral tegmental area and the limbic forebrain is a critical neurobiological component of alcohol and drug self-administration. Based on the evidence of interaction between CCK and DA, the authors had found previously that the CCK-AR gene –81A/G polymorphism was associated with alcohol dependence. Since the precise mechanism underlying this association has not been elucidated, the authors examined the role of CCK-AR in ethanol ingestion by comparing CCK-AR gene-deficient (CCK-AR–/–) mice with CCK-BR–/– and wild-type mice. The two-bottle choice protocol was conducted and the righting reflex was examined in these three genotypes. The protein level of dopamine 2 receptor (D2R) in the NA was determined by western blotting. CCK-AR–/– mice consumed more ethanol than CCK-BR–/– and wild-type mice and showed no aversion to high concentrations of ethanol solution. However, the difference was actually in the total fluid consumption; alcohol preference remained unchanged, indicating that the differences were not specific to alcohol. Behavioral sensitivity to ethanol, examined using the righting reflex, did not differ significantly between the groups. D2R expression in the NA was significantly lower in the CCK-BR–/– mice and significantly higher in CCK-AR–/– mice than in wild-type mice. The difference in voluntary ethanol ingestion between CCK-AR–/–
and CCK-BR–/– mice might be attributable in part to the different levels of D2R expression in the NA.

NIAAA Glossary Terms:  ethanol, cholecystokinin, dopamine, nucleus accumbens, dopaminergic receptors, genetic polymorphism, gene knockout technology, genotype, controlled study, animal behavior, righting reflex, laboratory mice, animal study


Isabel J. Pastor, Francisco Javier Laso, Alfonso Romero, and Rogelio González-Sarmiento.  Interleukin-1 gene cluster polymorphisms and alcoholism in Spanish menAlcohol and Alcoholism 40(3):181-186, May/June 2005.

Summary:
Different genes, including those encoding inflammatory cytokines, have been analyzed in an attempt to explain differences in susceptibility to alcoholism and alcoholic liver disease (ALD). Thus it has been reported recently that both the interleukin 1 receptor antagonist (IL1RN) and the IL1ß (IL1B) genes may influence the risk of ALD in Japanese alcoholics. The authors of this study analyzed the distribution of single nucleotide polymorphisms (SNPs) located in the IL1A, IL1B, IL1R1, and IL1RN genes in alcoholic and nonalcoholic Spanish men. Deoxyribonucleic acid samples were obtained from 139 male alcoholics, 78 of whom were diagnosed as alcohol dependent (32 patients with cirrhosis and 46 without ALD) and 61 as alcohol abusers (25 with cirrhosis and 36 without ALD). The controls were 81 age- and sex-matched healthy volunteers. Alleles –511 IL1B*1 and IL1RN*1 were found more frequently in alcoholic patients than in the control group. No association of alcoholism or ALD with polymorphisms in the IL1A and IL1R1 genes was found. It was concluded that the proteins encoded by the IL1RN and IL1B genes may be involved in susceptibility to alcoholism in Spanish men, probably through a different pathway from that involved in the regulation of the inflammatory response.

NIAAA Glossary Terms:  inflammation, cytokines, AOD dependence, alcoholic liver disorder, alcoholic liver cirrhosis, antagonists, interleukin-1, risk factors, genetic polymorphism, genetic correlation analysis, controlled study, allele, gene frequency, human study


Andreas Franke, Inaam A. Nakchbandi, Alexander Schneider, Hermann Harder, and Manfred V. Singer. The effect of ethanol and alcoholic beverages on gastric emptying of solid meals in humans.  Alcohol and Alcoholism 40(3):187-193, May/June 2005.

Summary:
The study examined the effect of pure ethanol, alcoholic beverages, and their non-alcoholic components on gastric emptying of solid meals in humans. Fasting healthy male subjects (N = 16) received 300 ml of the following solutions in random order once a week: 4% and 10% (v/v) ethanol, beer, red wine, 5.5% and 11.4% (w/v) glucose, and water. The test solutions were given either together with a low-calorie (270 kcal, n = 8) or a high-calorie (740 kcal, n = 8) solid meal. Gastric emptying was determined by ultrasonography of the antrum. Gastric half-emptying time (t½) of the high caloric solid meal with water was 131.3 ± 7 minutes. The ingestion of 4% and 10% ethanol (
t½ = 158.8 ± 9.3 and 165.6 ± 6.2 minutes respectively), beer (t½ = 163.1 ± 11 minutes), and red wine (t½ = 186.3 ± 8.4 minutes) resulted in a significantly longer t½ than water. The lag phases after 4% and 10% ethanol, beer, and red wine were not significantly different from that of water (48.1 ± 6.5 minutes). Compared with water, ingestion of 5.5% and 11.4% glucose resulted in a significantly longer t½ (153.8 ± 5 and 168.1 ± 14.4 minutes respectively) by increasing the duration of the lag phase. The high-calorie meals resulted in a doubling of t½ when compared with the low-calorie meals. The effect of the solutions on the gastric emptying times, however, was similar for both test meals. The results led to the following conclusions: (1) ethanol in low concentrations (4% and 10%) prolongs gastric emptying of solid meals; this inhibitory effect is not dose-dependent; (2) alcoholic beverages (beer and red wine) also prolong gastric emptying; the inhibitory effect of red wine, but not of beer, is more pronounced than that of the corresponding ethanol concentration and amount; (3) the inhibitory effect of ethanol and alcoholic beverages is mainly induced by prolongation of the gastric emptying phase (without affecting the lag phase), whereas glucose (5.5% and 11.4%) prolongs the lag phase in a dose-dependent manner; (4) the inhibitory effect of ethanol, beer, and red wine on gastric emptying does not depend on the caloric content of the meal.

NIAAA Glossary Terms:  digestion, stomach emptying, ethanol, beer, red wine, water, glucose, caloric value, dose-response relationship, ultrasonography, human study


Lisa C. Caldwell, Alecia D. Schweinsburg, Bonnie J. Nagel, Valerie C. Barlett, Sandra A. Brown, and Susan F. Tapert.  Gender and adolescent alcohol use disorders on BOLD (blood oxygen level dependent) response to spatial working memoryAlcohol and Alcoholism 40(3):194-200, May/June 2005.

Summary:
The objective was to determine how alcohol use differentially affects brain functioning in male and female adolescents. Adolescents with alcohol use disorders (AUDs; 7 females, 11 males) and control adolescents without AUDs (9 females, 12 males), aged 14–17 years, performed spatial working memory and vigilance tasks during functional magnetic resonance imaging. Gender, AUD, and their interaction were significantly associated with brain activation patterns to the tasks. There were interactions in the superior frontal, superior temporal, cingulate, and fusiform regions, in which females and males with AUDs showed a different brain response from each other and control subjects. Overall, female adolescents with AUDs showed a greater departure from normal activation patterns than male adolescents with AUD. Thus adolescent alcohol involvement may affect male and female brains differently, and adolescent females may be somewhat more vulnerable to adverse alcohol effects. With continued drinking, these adolescents may be at increased risk for behavioral deficits.

NIAAA Glossary Terms:  ethanol, underage AOD use, brain function, adolescent, gender differences, alcohol use disorder classification, controlled study, spatial memory, attention, magnetic resonance imaging, behavioral problem, human study


J.E. Yonker, L.-G. Nilsson, Agneta Herlitz, and R.M. Anthenelli.  Sex differences in spatial visualization and episodic memory as a function of alcohol consumptionAlcohol and Alcoholism 40(3):201-207, May/June 2005.

Summary:
Sex differences in visuospatial ability and in episodic memory have been reliably demonstrated, and studies of alcoholics have consistently documented cognitive deficits in visuospatial ability, problem solving, and memory function. This cross-sectional, population-based study examined whether sex differences in cognitive performance are affected by alcohol consumption. Drinking data were collected from 2,224 randomly sampled adults, aged between 35 and 85 years, who participated in the Betula study on memory, health, and aging. Participants were classified into non-drinking and light, moderate, and heavy drinking subgroups based on sex-adjusted normative values. Cognitive tasks demonstrating clear sex differences, such as episodic memory tasks (favoring women) and spatial visualization tasks (favoring men), were conducted and performance was assessed by sex and by drinking group. After controlling for age and education, overall analyses found expected sex differences in episodic memory and spatial visualization. When these sex differences were examined by drinking group, visuospatial performance favoring men disappeared for the moderate to heavy drinking groups, but higher performance by women on episodic memory tasks was consistent across all alcohol consumption levels. Traditional biomarkers of increased alcohol consumption (gamma-glutamyl transferase and mean corpuscular volume) correlated with the reported drinks/day. The results support the theory that moderate alcohol intake may benefit cognitive function in women, but not necessarily in men.

NIAAA Glossary Terms:  cross-sectional study, gender differences, cognitive ability, AOD consumption, AOD nonuse, light AOD use, moderate AOD use, heavy AOD use, controlled study, random sample, spatial processing impairment, memory, AODR biological markers, gamma glutamyl transferase, mean corpuscular volume, correlation analysis, human study


Andrea Canagasaby and Daniel C. Vinson.  Screening for hazardous or harmful drinking using one or two quantity–frequency questions.  Alcohol and Alcoholism 40(3):208-213, May/June 2005.

Summary:
The accuracy of quantity-frequency (QF) questions in screening for hazardous or harmful drinking was evaluated based on interviews with three groups: patients presenting to emergency departments for care of an acute injury (n = 1,537) or a medical illness (n = 1,151), and community controls interviewed by telephone (n = 1,112). The first question about alcohol was a single alcohol screening question (SASQ), ‘When was the last time you had more than X drinks in one day?’, where X = 4 for women and 5 for men, with any time in the past 3 months considered a positive screen (1 drink = 14 g ethanol). The subsequent alcohol questions were a calendar-based review of recent drinking and the alcohol questions from the Diagnostic Interview Schedule, which included questions about usual frequency and average quantity. Hazardous drinking was defined as drinking >4 drinks in a day or >14 drinks in a week for men (3 and 7 for women). Standard diagnostic criteria were used to define current alcohol use disorders. The areas under the receiver operating characteristic (ROC) curves in identifying hazardous drinking or current alcohol use disorder were compared. The area under the ROC curves in the three samples combined were 0.81 for SASQ (95% confidence interval [CI], 0.79–0.82), 0.80 for a question about average quantity alone (0.79–0.82), and 0.85 for the product of usual frequency times average quantity (0.84–0.86). The QF product and the question about average quantity performed consistently across the three groups. One way to put these findings into practice in clinical settings is to screen first with a single question, such as the SASQ, a single question about typical quantity, or a question about the frequency of heavy drinking such as the third item of the Alcohol Use Disorders Identification Test (AUDIT).

NIAAA Glossary Terms:  alcohol quantity-frequency methods, evaluation study, emergency care, AODR injury, AODR disorder, AOD use screening method, questionnaire, heavy AOD use, alcohol use test, human study


Adam Bisaga, Michael Laposata, Shan Xie, and Suzette M. Evans.  Comparison of serum fatty acid ethyl esters and urinary 5-hydroxytryptophol as biochemical markers of recent ethanol consumption.  Alcohol and Alcoholism 40(3):214-218, May/June 2005.

Summary:
The effects of an acute dose of ethanol on serum fatty acid ethyl esters (FAEE) concentration and urinary 5-hydroxytryptophol (5-HTOL)/5-hydroxyindole-3-acetic acid (5-HIAA) ratio were examined in heavy drinkers (N = 16; 14 males) who were tested in a single, 2-day long session. Six participants received 1.5 g/l of ethanol/l of body water (~0.75 g/kg of body weight, low dose [LD] group) and 10 participants received 2.0 g/l of ethanol (~1.0 g/kg of body weight, high dose [HD] group) in four divided doses every 20 minutes. Blood, urine, and breath samples were collected repeatedly over 36 hours following the ingestion of ethanol and analyzed for the presence of FAEE (blood), 5-HTOL/5-HIAA (urine), and ethanol (breath). Serum gamma-glutamyltransferase (GGT), a marker of chronic ethanol use, was also measured. The breath ethanol level peaked ~1 hour after the last dose, at 95 and 120 mg/dl for the LD and HD groups respectively. The mean urinary 5-HTOL/5-HIAA ratio was significantly elevated 5 and 9 hours after ethanol administration, but returned to baseline at 13 hours. This ratio was twice as high in the HD group compared with the LD group. Serum FAEE levels were significantly elevated at 5 hours after ethanol administration, but not at 13 hours. There were no time-dependent changes in serum GGT levels. It was concluded that measuring FAEE levels and the 5-HTOL/5-HIAA ratio provides a convenient method to detect recent ethanol use, particularly binge drinking. However, the applicability of these measures in detecting ethanol use may be limited in traditional clinical trial settings.

NIAAA Glossary Terms:  fatty acid ethyl esters, hydroxytryptophol, hydroxyindoleacetic acid, breath alcohol analysis, heavy AOD use, ethanol, acute AODE, chronic AODE, blood, urine, gamma glutamyl transferase, AODR biological markers, dose-response relationship, binge AOD use, comparative study, human study


M.J. Emmen, G. M. Schippers, H. Wollersheim, and G. Bleijenberg.  Adding psychologist's intervention to physicians' advice to problem drinkers in the outpatient clinic.  Alcohol and Alcoholism 40(3):219-226, May/June 2005.

Summary:
The effectiveness of a brief psychological intervention for problem drinking was tested among outpatients in a hospital setting. Over a period of 3 years patients who visited an outpatient clinic for general internal medicine were screened by physicians for problem drinking. Of the 4,728 patients screened, 284 (6%) scored positive on problem drinking. The problem drinkers who participated in the intervention study (N = 123) received a computerized baseline assessment and were randomly allocated to a brief psychosocial intervention given by a psychologist (the Dutch version of W.R. Millers' Drinker's Check-Up) (n = 61) or to ‘care as usual’ (n = 62) and were followed-up at 6 months. The outcome measures were alcohol consumption and increased motivation to reduce alcohol consumption. Most patients reduced their alcohol consumption over time, but no differences were found between the intervention and control groups. A slightly, but not significantly, larger proportion of patients who received the intervention increased their motivation to change. No conclusive evidence was found for the effectiveness of adding a brief psychological intervention to the physician's advice for problem drinking among outpatients in a hospital setting.

NIAAA Glossary Terms:  brief intervention, psychosocial treatment method, outpatient care, problematic AOD use, follow-up study, treatment outcome, AOD consumption, motivation, controlled study, human study


G. Rubio, G. Ponce, R. Rodriguez-Jiménez, M.A. Jiménez-Arriero, J. Hoenicka, and T. Palomo.  Clinical predictors of response to naltrexone in alcoholic patients: Who benefits most from treatment with naltrexone?  Alcohol and Alcoholism 40(3):227-233, May/June 2005.

Summary:
The objective was to determine the clinically ascertained variables that are related to satisfactory response to naltrexone treatment of alcohol dependence after detoxification. Intake and outcome variables were measured in a randomized 3-month open-controlled trial
(N = 336 males) comparing the effects of naltrexone plus psychotherapy treatment versus psychotherapy treatment alone on the maintenance of abstinence in the final 28 days. Predictors of a positive response to naltrexone treatment were family history of alcoholism (p = 0.010), early age at onset of drinking problems (p = 0.014), and comorbid use of other drugs of abuse (p < 0.001). Among the subjects not treated with naltrexone, a greater number of predictor variables was associated with lower final 28 days abstinence rates (p = 0.00003), but this was not the case in patients treated with naltrexone (p = 0.844). Patients with these features, suggesting biological vulnerability, overall have poorer outcomes, but they can be improved with naltrexone treatment. The type of alcoholism should be considered before deciding on the pharmacological strategy.

NIAAA Glossary Terms:  naltrexone, psychotherapy, drug therapy, combined modality therapy, treatment outcome, AOD dependence, predictive factor, familial alcoholism, early disease onset, comorbidity, multiple drug use, controlled study, randomized controlled trial, clinical trial, AOD abstinence, human study


Anthony P. Polednak.  Recent trends in incidence rates for selected alcohol-related cancers in the United States.  Alcohol and Alcoholism 40(3):234-238, May/June 2005.

Summary:
Data from cancer registries were used to analyze recent incidence trends for cancer types most strongly associated with alcohol use. Age-standardized annual incidence data for squamous cell carcinomas of the oral cavity and pharynx, esophagus, and larynx diagnosed in the most recent 10-year period (1992–2001) were examined for geographic areas included in the US National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) program of high-quality cancer registries. For all geographic areas combined, incidence levels for these cancers declined over time, with no evidence of a recent plateau or upturn. This also held true for younger adults (20–54 years old at diagnosis). For white males, declines in incidence occurred in each of the 11 geographic areas and were statistically significant in 9. The declines in incidence were consistent with temporal declines in apparent alcohol consumption by state, although the prevalence of binge and heavy drinking in adults increased in some states. Although there was no evidence of a recent plateau in incidence, continued surveillance is needed in view of recent increases in the prevalence of binge and heavy drinking among US adults.

NIAAA Glossary Terms:  incidence, cancer, time series analysis, trend, AODR disorder, AOD consumption, prevalence, binge AOD use, heavy AOD use, squamous cell carcinoma, mouth, oral disorder, pharynx, esophageal disorder, larynx, epidemiology, epidemiological indicators, human study


Kerry S. O'Brien, Joshua M. Blackie, and John A. Hunter.  Hazardous drinking in elite New Zealand sportspeople.  Alcohol and Alcoholism 40(3):239-241, May/June 2005.

Summary:
The link between hazardous drinking and level of participation in sports was examined in university students in New Zealand. Sports science and general university students (N = 427) completed a sporting profile questionnaire that included the Alcohol Use Disorders Identification Test (AUDIT).  Elite athletes (both provincial and international/country level) reported higher rates of hazardous drinking than non-athletes and non-elite athletes. Similar differences were observed in AUDIT subscale scores, with international/country level athletes reporting greater symptoms of alcohol dependence than other groups.

NIAAA Glossary Terms:  sports, heavy AOD use, AODU by athlete, undergraduate student, controlled study, New Zealand, survey, questionnaire, symptom, AOD dependence, human study


Aafje Dotinga, Regina J.J.M. Van Den Eijnden, Willem Bosveld, and Henk F. L. Garretsen.  The effect of data collection mode and ethnicity of interviewer on response rates and self-reported alcohol use among Turks and Moroccans in The Netherlands: An experimental study.  Alcohol and Alcoholism 40(3):242-248, May/June 2005.

Summary:
This study tested the effects of data collection method and interviewer ethnicity on response rates and self-reported alcohol use among second-generation Turks and Moroccans in Rotterdam, The Netherlands. Personal interviews were administered to 269 Turks and 271 Moroccans, and 475 Turks and 482 Moroccans received a mailed questionnaire. Half of the Turks and Moroccans randomly allocated to the interview mode were ethnically matched to the interviewer; the remainder were allocated to a Dutch interviewer. Turks and Moroccans more often responded to a personal interview than to a mailed questionnaire. Ethnicity of the interviewer had no effect on response rates. Turks and Moroccans tended to report higher alcohol use and reported significantly more frequent excessive drinking in the mailed survey than in the personal interview. Both groups reported a higher prevalence of alcohol use during the previous 6 months when interviewed by a Dutch interviewer compared with an ethnically matched interviewer. Thus mail surveys seem most suitable for measuring mean and excessive alcohol use among second-generation Turks and Moroccans.

NIAAA Glossary Terms:  AOD use, AOD consumption, prevalence, self report, data collection, ethnic group, ethnic differences, Morocco, Turkey, Netherlands, interview, questionnaire, comparative study, cultural sensitivity, human study


Jan Van Den Bulck and Kathleen Beullens.  Television and music video exposure and adolescent alcohol use while going out.  Alcohol and Alcoholism 40(3):249-253, May/June 2005.

Summary:
This study examined whether television viewing and exposure to music videos predict alcohol consumption by high school students when they go out. Data were collected in February 2003 (t1) and February 2004 (t2) from a random sample of first- and fourth-year secondary school children (N = 1,648) of Flanders, Belgium. Self-reported general TV viewing and music video exposure at t1 and the quantity of alcohol consumed while going out at t2 were measured. Controls were gender, age group, smoking behavior, and alcohol use (at
t1) and pubertal status (at t2). Overall television viewing per day and music television viewing at t1 significantly predicted the amount of alcoholic beverages adolescents consumed while going out at t2. These results remained significant after controlling for alcohol use at t1, gender, smoking, and pubertal status. TV viewing habits are a significant predictor of alcohol consumption while going out. TV viewing might cause an increase in alcohol consumption or it might be an early symptom of developing alcohol habits.

NIAAA Glossary Terms:  high school student, adolescent, underage drinking, AOD consumption, predictive factor, television, popular culture, Belgium, self report, puberty, controlled study, human study


UPHome Page

Alcohol and Alcoholism
Volume 40, Number 2, March/April 2005
(Updated December 18, 2004)

UPHome Page

Steven Rosenzweig Haugbøl, Bjarke Ebert, and Jakob Ulrichsen.  Upregulation of glutamate receptor subtypes during alcohol withdrawal in rats.  Alcohol & Alcoholism 40(2):89-95, March/April 2005.

Summary:
To investigate glutamate receptor subtypes during alcohol withdrawal, rats were exposed to severe ethanol intoxication for 84 hours (intragastric intubation of ethanol five times a day) then decapitated at 0, 12 and 36 hours after the last dose (n = 7 rats per group). The densities of N-methyl-D-aspartate (NMDA) and 2-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors were studied in membranes from the forebrain by using the (tritium-labeled) specific ligands MK-801 and AMPA respectively. Although no change was observed in the maximal density (Bmax) of MK-801 binding sites at the time of withdrawal, MK-801 binding was increased by 49% 12 hours into the withdrawal reaction compared with the control group and was still increased by 24% (not statistically significant) at 36 hours
. No significant alteration in the Bmax of AMPA binding was detected at the time of withdrawal from chronic ethanol intoxication, but 12 hours into withdrawal AMPA binding was markedly increased by 94%. At 36 hours post alcohol AMPA binding had returned to control levels. No significant alteration in the dissociation constant (KD) of either MK-801 or AMPA binding was observed at any time. It was concluded that NMDA and AMPA receptors are involved in the cerebral hyperactivity of alcohol withdrawal.

NIAAA Glossary Terms: 
glutamate receptors, NMDA receptors, forebrain, cerebrum, receptor ligand binding, tritium, ethanol, AOD intoxication, AOD dependence, AOD withdrawal syndrome, controlled study, laboratory rat, animal study


Gennadiy Novitskiy, Rajani Ravi, James J. Potter, Lynda Rennie-Tankersley, Lan Wang, and Esteban Mezey.  Effects of acetaldehyde and TNF-α[alpha] on the inhibitory kappa B-α[alpha] protein and nuclear factor kappa B activation in hepatic stellate cells.  Alcohol & Alcoholism 40(2):96-101, March/April 2005.

Summary:
Transcription of type I collagen promoters and type I collagen production are enhanced by acetaldehyde and inhibited by tumor necrosis factor-alpha (
TNFα). Nuclear factor kappa B (NF-κB), an inhibitor of type I collagen promoters, is increased by both acetaldehyde and TNFα. This study assessed the effects of acetaldehyde in comparison to the effects of TNFα on inhibitory kappa B-α (IκB-α) protein and NF-κB activation in hepatic stellate cells. Activated rat hepatic stellate cells in culture were exposed to acetaldehyde or TNFα for brief periods, after which the cells were harvested for the determination of IκB-α protein, IκB-α kinase activity and nuclear NF-κB. Acetaldehyde increased IκB-α kinase activity and decreased IκB-α after 10 minutes of exposure, with recovery towards control levels at 20 minutes. In contrast, TNFα resulted in higher IκB-α kinase activity at 20 minutes than at 10 minutes, and similar low IκB-α at both times. Both acetaldehyde and TNFα enhanced nuclear NF-κB (p65), but acetaldehyde alone also increased NF-κB (p50). Thus TNFα and acetaldehyde independently activate NF-κB by rapid enhancement of IκB-α kinase activity and degradation of IkB-α protein. Increased TNFα is the principal mechanism for the elevation of NF-κB in severe alcoholic hepatitis. The elevation of NF-κB due to TNFα enhances liver injury, but inhibits fibrogenesis. In contrast, the effect of acetaldehyde in activating NF-κB is associated with increases in both liver injury and fibrogenesis, indicating that the effects of acetaldehyde on fibrogenesis are mediated by cytokines and by trans-acting factors other than NF-κB.

NIAAA Glossary Terms:  acetaldehyde, tumor necrosis factor-alpha, cytokines, collagen, hepatic stellate cell, protein kinases, gene expression, alcoholic hepatitis, alcoholic liver disorder, fibrosis, cell culture study


Lars Retterstol, Knut Erik Berge, Øivind Braaten, Lars Eikvar, Terje R. Pedersen, and Leiv Sandvik.  A daily glass of red wine: Does it affect markers of inflammation?  Alcohol & Alcoholism 40(2):102-105, March/April 2005.

Summary:
Although epidemiological studies have shown that moderate alcohol consumption is associated with a decreased risk of developing cardiovascular disease, the causal mechanisms are only partly understood. This study tested the hypothesis that the protective effect of red wine is partly mediated through a reduction in inflammation, an important process in the progression of atherosclerosis, in a randomized controlled crossover trial to study the effect of red wine on the levels of the inflammatory markers serum C-reactive protein (CRP) and plasma fibrinogen in healthy subjects (N = 87, mean age 50 years) who were nonsmokers. The subjects were randomized to drink one glass of red wine (150 ml, 15 g alcohol) every day or to undergo a period of total abstention from alcohol. The time on each regimen was 3 weeks. Red wine did not reduce CRP levels and only marginally reduced fibrinogen levels compared with a similar period without alcohol.

NIAAA Glossary Terms:  red wine, moderate AOD use, AOD abstinence, atherosclerosis, inflammation, biological markers, fibrinogen, plasma, protective drug effect, protective factors, clinical trial, controlled study, human study


Elzbieta Wrobel, Dominika Skrok-Wolska, Marcin Ziolkowski, Agnieszka Korkosz, Boguslaw Habrat, Bohdan Woronowicz, Andrzej Kukwa, Wojciech Kostowski, Przemyslaw Bienkowski, and Anna Scinska.  Taste responses to monosodium glutamate after alcohol exposure.  Alcohol & Alcoholism 40(2):106-111, March/April 2005.

Summary:
The effects of acute and chronic exposure to ethanol on taste responses to monosodium glutamate (MSG) a prototypic umami substance (umami is the Japanese term for a postulated fifth taste in addition to sweet, sour, bitter, and salty), were evaluated in male alcoholics (n = 36) and control subjects (n = 25). The participants rated intensity and pleasantness of MSG taste (0.03–10.0%). The effects of acute exposure of the oral mucosa to ethanol rinse (0.5–4.0%) on MSG taste (0.3–3.0%) were examined in a separate experiment with 10 social drinkers. The alcoholic and control groups did not differ in their ratings of intensity and pleasantness of MSG taste. Electrogustometric thresholds were significantly (p < 0.01) higher (i.e. worse) in the alcoholics, and the difference remained significant after controlling for differences between groups in cigarette smoking and coffee drinking. In social drinkers, oral rinsing with ethanol did not alter either intensity or pleasantness of MSG taste. These findings suggest that neither acute nor chronic alcohol exposure alters taste responses to MSG, and that alcohol dependence may be associated with deficient threshold taste reactivity as assessed by electrogustometry.

NIAAA Glossary Terms:  taste perception, sodium glutamate, self report, ethanol, AOD dependence, social AOD use, acute AODE, chronic AODE, specific data collection instrument, subjective variables, controlled study, human study


Marcus Richards, Rebecca Hardy, and Michael E. J. Wadsworth.  Alcohol consumption and midlife cognitive change in the British 1946 birth cohort study.  Alcohol & Alcoholism 40(2):112-117, March/April 2005.

Summary:
This study examined the association between self-reported alcohol consumption and change in memory, speed, and concentration in midlife participants of the 1946 British birth cohort
(903 men and 861 women) enrolled in the Medical Research Council's National Survey of Health and Development. After controlling for educational attainment, occupational social class, and general cognitive ability, an association was found between alcohol consumption and slower memory decline from ages 43 to 53 years in men. In women, alcohol consumption was associated with a more rapid decline in visual search speed over the same age interval. These effects were not explained by a further control for health status (body water weight, smoking, exercise, cardiorespiratory disease, and affective state). While the findings suggest that alcohol consumption is associated with slower memory decline, the negative association between alcohol and psychomotor function in women is a potential cause for concern.

NIAAA Glossary Terms:   middle-aged adult, alcoholic beverage, AOD consumption, cognitive ability, memory, attention, cohort study, longitudinal study, protective factor, gender differences, human study


Annika Jakobsson, Gunnel Hensing, and Fredrik Spak.  Developing a willingness to change: Treatment-seeking processes for people with alcohol problems.  Alcohol & Alcoholism 40(2):118-123, March/April 2005.

Summary:
Treatment-seeking processes, particularly promoting and hindering factors, were studied in men and women with alcohol problems. Open interviews were held with 12 individuals (5 women, 7 men) within a month of their first voluntary treatment for alcohol problems. The interview protocols were analyzed consecutively in accordance with grounded theory methodology. The basic psychosocial process that led to treatment-seeking was found to be developing willingness to change. Sub-processes that supported willingness to change were actuating inner forces, dealing with conflicting feelings and thoughts, and hoping to turn the situation around. These processes were continuously assisted by demanding and caring support from partners, friends, or professionals. In conclusion, the processes that preceded treatment-seeking were highly complex, and both internal and external factors promoted and hindered treatment entry. The most striking hindering factors were the social significance of alcohol and grief related to thoughts of abstaining. Such feelings need to be considered when motivating people to seek treatment for alcohol problems.

NIAAA Glossary Terms:  problematic AOD use, AOD dependence, AOD abstinence, social benefit of AOD, alcoholic beverage, help-seeking behavior, treatment readiness, treatment factors, social support,  patient psychological history, interview, self report, readiness to change, motivation, human study


Matthias J. Müller, Armin Scheurich, Hermann Wetzel, Armin Szegedi, and Martin Hautzinger.  Sequentially adjusted randomization to force balance in controlled trials with unknown prevalence of covariates: Application to alcoholism research.  Alcohol & Alcoholism 40(2):124-131, March/April 2005.

Summary:
Adequate interpretation of treatment outcome studies with small to medium sample sizes (N < 200) requires balancing groups with regard to important factors that sometimes have low prevalence. This study tested a simple procedure for randomizing patients to different treatments in clinical alcoholism research, taking into account relevant background variables. An easily applicable modification of Efron's biased coin method for the randomization of treatments within strata of unknown but low prevalence was compared with the original approach and alternative methods by computer simulation (10,000 runs). The authors provide an application example for a clinical trial in alcoholism research. The sequentially adjusted randomization procedure yielded results similar to Efron's approach without the need to monitor the assignment history throughout the trial. The new method was slightly superior to Efron's approach in randomizing subjects in strata with n ≤ 20, whereas strata with n > 20 favored randomization with Efron's approach. Taking into account all results from simulation, the new approach reached a proportion of acceptable balanced randomization greater than 95% in all stratum sizes. The new method provides three major advantages in clinical trials: (1) it can be easily implemented in any trial without technical equipment; (2) it works with high accuracy in trials with a priori unknown but low numbers of subjects (4 ≤ n ≤ 20) in prognostic relevant strata; and (3) a deterministic assignment tendency is completely avoided, as a random process takes place throughout the assignment procedure.

NIAAA Glossary Terms:  randomized controlled trial, clinical trial, treatment research, AOD dependence, reliability (research methods), research and evaluation method, computer technology, intermethod comparison, validation study


Norman Giesbrecht, Anca Ialomiteanu, and Lise Anglin.  Drinking patterns and perspectives on alcohol policy: Results from two Ontario surveys.  Alcohol & Alcoholism 40(2):132-139, March/April 2005.

Summary:
Studies often have not examined whether attitudes on alcohol policies vary according to a respondent's drinking pattern. This study examined the association between six drinking variables in survey respondents and their views on six alcohol policy topics. Data were available from two telephone interview surveys in Ontario in 2000 (n = 1,294) and 2002 (n = 1,206) of representative samples of adults, aged 18 and older, selected by random digit dialing. The six drinking variables were drinking status, drinking frequency, usual number of drinks, typical weekly volume, frequency of 5 or more drinks per occasion, and Alcohol Use Disorders Identification Test (AUDIT) scores. The six alcohol policy items examined were alcohol taxes, warning labels, density of retail alcohol outlets, privatization of government liquor stores, alcohol advertising, and consultation with health experts on alcohol policy decisions. Logistic regression analyses included five demographic variables: gender, age, marital status, education, and income. There was strong support among males for increased access to alcohol and fewer controls over alcohol policies. This relationship, although not as strong, also emerged for frequent consumers, high volume drinkers, and those with a higher AUDIT score. The authors concluded that government policies that tend to make alcohol more available cater, whether intentionally or not, to young, heavy-drinking males who possibly experience problems related to their drinking behavior.

NIAAA Glossary Terms:  public policy on AOD, AOD use pattern, AOD consumption, AOD intake per occasion, AOD use frequency, heavy AOD use, binge AOD use,  alcohol use test, location and density of AOD outlets, AOD availability, alcoholic beverage sales outlet, sales and excise tax, warning label, AOD product advertising, health care worker, supply reduction policy, survey, interview, random sample, regression analysis, attitude toward AOD, gender differences, age differences, educational level achieved, income, Canada, human study


Diva Eensoo, Marika Paaver, Maarike Harro, and Jaanus Harro.  Predicting drunk driving: Contribution of alcohol use and related problems, traffic behaviour, personality and platelet monoamine oxidase (MAO) activity.  Alcohol & Alcoholism 40(2):140-146, March/April 2005.

Summary:
This study evaluated the predictive value for drunk driving of socioeconomic data, alcohol consumption measures, smoking, platelet monoamine oxidase (MAO) activity, traffic behavior habits, and impulsivity measures. Data were collected from male drunk driving offenders (n = 203) and control subjects (n = 211) using self-report questionnaires, and blood samples were obtained from the two groups.  A combination of variables was identified that predicted correctly about 80% of the subjects in the drunk driving and control groups. Among the health-behavior measures, significant independent discriminators in the final model were alcohol-related problems, frequency of using alcohol, the amount of alcohol consumed, and smoking. Predictive traffic behavior measures were seat belt use and paying for parking. Among the impulsivity measures, dysfunctional impulsivity was the best predictor. Platelet MAO activity and age also had an independent predictive value. The results support the view that drunk driving arises from a combination of various behavioral, biological, and personality-related risk factors.

NIAAA Glossary Terms:  drinking and driving, AOD intoxication, DWI arrest, predictive factor, risk factors, socioeconomic factors, AOD consumption,
AOD use pattern,
monoamine oxidase, driver performance, impulsive behavior, controlled study, questionnaire, self report, blood proteins, platelets, health related behavior, AODR markers, AODR biological markers, AOD use frequency, AOD intake per occasion, AOD consumption, smoking, discriminant analysis, seat belt, age differences, human study


Olivier Ameisen.  Complete and prolonged suppression of symptoms and consequences of alcohol-dependence using high-dose baclofen: A self-case report of a physician  (Case study).  Alcohol & Alcoholism 40(2):147-150, March/April 2005.

Summary:
Using himself as a subject, the author, a physician with alcohol dependence and comorbid anxiety, tested whether the dose-dependent motivation-suppressing effect of baclofen in animals could be transposed to humans and suppress alcohol craving and sustain abstinence. Noting that neurologists safely prescribe up to 300 mg/day of oral baclofen to control spasticity (10 times the dosage currently used for alcohol dependence), the author self-prescribed high-dose baclofen, starting at 30 mg/day, with 20-mg increments every third day and an (optional) additional 20–40 mg/day for cravings, and found that his cravings became easier to combat. After reaching the craving-suppression dose of 270 mg/day (3.6 mg/kg) after 5 weeks, he became free of alcohol dependence symptoms
and has remained  free of those symptoms effortlessly for the ninth consecutive month. His anxiety is well controlled. Somnolence disappeared with a dosage reduction to 120 mg/day, which he has now used for the eighth consecutive month. The author concludes that high-dose baclofen induced complete and prolonged suppression of symptoms and consequences of his alcohol dependence, and relieved his anxiety. He recommends that this model, integrating cure and well-being, be tested in randomized trials under medical surveillance. It offers a new concept: medication-induced, dose-dependent, complete, and prolonged suppression of substance-dependence symptoms with alleviation of comorbid anxiety.

NIAAA Glossary Terms:  baclofen, drug therapy, AOD dependence, ethanol, comorbidity, anxiety, AOD craving, symptom, relapse prevention, case study, self medication, physician, dose-response relationship, human study


Murray Cochrane, Ashley Cochrane, Pramod Jauhar and Elizabeth Ashton.  Acetylcholinesterase inhibitors for the treatment of Wernicke-Korsakoff syndrome–three further cases show response to donepezil (Case study).  Alcohol & Alcoholism 40(2):151-154, March/April 2005.

Summary:
The acetylcholinesterase inhibitor donepezil was used to treat three patients with Wernicke-Korsakoff syndrome for periods of 6 to 8 months. Cognitive testing [Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog), Mini-Mental State Examination (MMSE), Clock drawing test and six-item 2 min recall], and carer questionnaires [Informant Questionnaire (IQ Code) and Neuropsychiatric Inventory (NPI)] were performed at baseline, mid- and endpoint of the treatment period, and post-discontinuation. Partial improvement in cognitive measurements occurred progressively through the treatment period, some of which was sustained after donepezil was discontinued. Carer questionnaires also indicated improvement. Confounding factors require caution when attributing improvements to the medication, but these cases suggest that this option merits further investigation.

NIAAA Glossary Terms:  treatment method, cholinesterase, enzyme inhibitors, drug therapy,  Wernicke-Korsakoff psychosis, cognitive ability, psychiatric status rating scales, questionnaire, health care worker, treatment outcome, clinical study, human study


UPHome Page

Alcohol and Alcoholism
Volume 40, Number 1, January/February 2005
(Updated December 18, 2004)

UPHome Page

Giancarlo Colombo.  Preface to the Special Issue Articles on Alcohol and Cannabis.  Alcohol & Alcoholism 40(1):1, January/February 2005.

(No abstract available)


Fernando Rodríguez de Fonseca, Ignacio del Arco, Francisco Javier Bermudez-Silva, Ainhoa Bilbao, Andrea Cippitelli, and Miguel Navarro.  The Endocannabinoid System: Physiology and Pharmacology.  Alcohol & Alcoholism 40(1):2-14, January/February 2005.

Summary:
The authors review the physiology and pharmacology of the endogenous cannabinoid system, a ubiquitous lipid signaling system that appeared early in evolution and has important regulatory functions throughout the body in all vertebrates. The main endocannabinoids (endogenous cannabis-like substances) are small molecules derived from arachidonic acid, anandamide (arachidonoylethanolamide), and 2-arachidonoylglycerol. They bind to a family of G-protein-coupled receptors, of which the cannabinoid CB1 receptor is densely distributed in areas of the brain related to motor control, cognition, emotional responses, motivated behavior, and homeostasis. Outside the brain, the endocannabinoid system is one of the crucial modulators of the autonomic nervous system, the immune system, and microcirculation. Endocannabinoids are released upon demand from lipid precursors in a receptor-dependent manner and serve as retrograde signaling messengers in GABAergic and glutamatergic synapses, as well as modulators of postsynaptic transmission, interacting with other neurotransmitters including dopamine. Endocannabinoids are transported into cells by a specific uptake system and are degraded by fatty acid amide hydrolase and monoacylglycerol lipase. Recent pharmacological advances have led to the synthesis of cannabinoid receptor agonists and antagonists, anandamide uptake blockers, and potent selective inhibitors of endocannabinoid degradation. These new tools have enabled study of the physiological roles played by the endocannabinoids and have opened up new strategies in the treatment of pain, obesity, neurological diseases including multiple sclerosis, emotional disturbances such as anxiety, and other psychiatric disorders including drug addiction. Recent advances have specifically linked the endogenous cannabinoid system to alcoholism, and cannabinoid receptor antagonism now emerges as a promising therapeutic alternative for alcohol dependence and relapse.

NIAAA Glossary Terms: 
cannabinoids, neurotransmitters,  neurotransmitter receptors, GABAergic neuron, dopamine, glutamate, hydrolases, lipases, synapse, sense of pain, obesity, anxiety, addiction, AOD dependence, antagonists, AODD relapse, AODU treatment method, autonomic nervous system, cognition, cell signaling, arachidonic acid, G-protein-coupled receptors, motivation, homeostasis, literature review


Balapal S. Basavarajappa and Basalingappa L. Hungund.  Role of the Endocannabinoid System in the Development of Tolerance to Alcohol.  Alcohol & Alcoholism 40(1):15-24, January/February 2005.

Summary:
This review evaluates the evidence that the endocannabinoid system is involved in the development of tolerance to alcohol. The identification of a G-protein-coupled receptor, namely the cannabinoid receptor (CB1 receptor), which was activated by
Δ9-tetrahydrocannabinol (THC), the major psychoactive component of marijuana, led to the discovery of endogenous cannabinoid agonists. Until now, four fatty acid derivatives identified to be arachidonylethanolamide (AEA), 2-arachidonylglycerol (2-AG), 2-arachidonylglycerol ether (noladin ether) and virodhamine have been isolated from both nervous and peripheral tissues. Both AEA and 2-AG have been shown to mimic the pharmacological and behavioral effects of THC. The role of the endocannabinoid system in the development of tolerance to alcohol was not known until recently. Recent studies from the authors' laboratory have implicated for the first time a role for the endocannabinoid system in development of alcohol tolerance. Chronic alcohol treatment has been shown to down-regulate CB1 receptors and its signal transduction. The observed down-regulation of CB1 receptor function results from the persistent stimulation of the receptors by AEA and 2-AG, the synthesis of which has been shown to be increased by chronic alcohol treatment. The enhanced formation of endocannabinoids may subsequently influence the release of neurotransmitters. It was found that DBA/2 mice, known to avoid alcohol intake, have significantly reduced CB1 receptor function in the brain, consistent with other studies in which the CB1 receptor antagonist SR 141716A has been shown to block voluntary alcohol intake in rodents. Similarly, activation of the CB1 receptor system promoted alcohol craving, suggesting a role for the CB1 receptor gene in excessive alcohol drinking and development of alcoholism. Ongoing investigations may lead to improved understanding of the mechanisms underlying the development of alcohol tolerance and to development of therapeutic strategies to treat alcoholism.

NIAAA Glossary Terms:  cannabinoids, G-protein-coupled receptors, ethanol, AOD dependence, AOD tolerance, chronic AODE, tetrahydrocannabinol, marijuana in any form, neurotransmitter receptors, psychoactive substances, signal transduction, drug therapy, literature review


Jorge Manzanares, Sergio Ortiz, José M. Oliva, Sandra Pérez-Rial, and Tomás Palomo.  Interactions Between Cannabinoid and Opioid Receptor Systems in the Mediation of Ethanol Effects. 
Alcohol & Alcoholism 40(1):25-34, January/February 2005.

Summary:
Recent advances in the study of the neurochemical circuits involved in the development and treatment of alcohol dependence have identified peptides and receptors as potential key targets in the treatment of problems related to alcohol consumption. The endogenous opioid system is modified by alcohol intake in areas of the brain related to reward systems, and differential basal levels of opioid gene expression are found in rodents with a high preference for ethanol. This suggests a greater vulnerability to alcohol consumption in relation to differences in genetic background. Further evidence of the involvement of opioid peptides in alcohol dependence is the ability of the opioid antagonist naltrexone to reduce alcohol intake in animal models of dependence and in alcohol-dependent patients. Abundant evidence indicates that the activation of cannabinoid receptors stimulates the release of opioid peptides, therefore the cannabinoid receptor antagonists may presumably alter opioid peptide release, thus facilitating the reduction of ethanol consumption. However, little is known about the effects of ethanol on the endogenous cannabinoid system, the vulnerability of cannabinoid receptors to alcohol intake or their neurochemical implications in reducing consumption of alcohol. This article reviews the role of opioid and cannabinoid receptor systems, their vulnerability to alcohol intake and the development of dependence, and the targeting of these systems in the treatment of alcoholism.

NIAAA Glossary Terms:  neurochemistry, neuropeptides, neuropeptide receptors, brain reward pathway, endogenous opioids, gene expression, ethanol, animal selectively bred for AOD preference, naltrexone, antagonists, literature review


Iain S. Mcgregor, Kristy D. B. Dam, Paul E. Mallet, and Jason E. Gallate.  Δ9-THC Reinstates Beer- and Sucrose-seeking Behaviour in Abstinent Rats: Comparison with Midazolam, Food Deprivation and Predator Odour. 
Alcohol & Alcoholism 40(1):35-45, January/February 2005.

Summary:
Recent studies suggest that cannabinoid receptor agonists may promote relapse to drug-seeking behavior after a period of abstinence. In this study, the ability of Δ9-tetrahydrocannabinol (THC) to reinstate previously reinforced responding for alcoholic and non-alcoholic beverages was assessed in rats using a novel lick-based paradigm. Rats were initially given free access to beer (containing 4.5% ethanol v/v), near-beer (a beverage that looks and tastes like beer but contains <0.5% ethanol v/v), or isocaloric sucrose in their home cages for 3 weeks. They were then trained to lick at a tube to self-administer the pre-exposed beverage in operant chambers under a VR10 schedule in 30-minute sessions daily. After about 3 weeks of such access, the rats underwent an extinction procedure, so that licking at the tube produced no reward. Once responding had ceased, the rats were subjected to various reinstatement tests. In Experiment 1, the cannabinoid receptor agonist 
THC (1 mg/kg) significantly reinstated responding, previously reinforced with beer or near-beer. The effect was unlikely to be caused by increased appetite because 24-hour food deprivation had no such effect. Exposure to cat odor in the test chamber failed to reinstate responding for beer or near-beer and caused a complete inhibition of responding. In Experiment 2, THC (0.3 and 1 but not 3 mg/kg) again reinstated beer-seeking behavior while the 1 mg/kg dose also reinstated responding in sucrose trained animals. Midazolam (0.15 mg/kg but not 0.5 or 1.5 mg/kg) produced a modest reinstatement of beer-seeking but had no effect on sucrose-seeking behavior. The finding that THC can reinstate alcohol-seeking provides the impetus for further research into the involvement of the cannabinoid system in alcohol craving. However, the reinstatement of near-beer and sucrose-seeking behavior caused by THC suggests a relatively non-specific effect. This may perhaps be related to the stressor-like effects of cannabinoids, and their ability to activate key neural circuitry in the amygdala and bed nucleus of the stria terminalis.

NIAAA Glossary Terms:  beer, dealcoholized beverage, sucrose, laboratory rat, reinforcement, AOD-seeking behavior, operant conditioning, tetrahydrocannabinol, midazolam, AOD craving, amygdala, brain, animal study


Gian Luigi Gessa, Salvatore Serra, Giovanni Vacca, Mauro A. M. Carai, and Giancarlo Colombo.  Suppressing Effect of the Cannabinoid Cb1 Receptor Antagonist, Sr147778, on Alcohol Intake and Motivational Properties of Alcohol in Alcohol-preferring Sp Rats.  Alcohol & Alcoholism 40(1):46-53, January/February 2005.

Summary:
The effect of the newly synthesized cannabinoid CB1 receptor antagonist SR147778 on alcohol intake and the motivational properties of alcohol was investigated in selectively bred Sardinian alcohol-preferring (sP) rats. In Experiment 1, repeated intraperitoneal (i.p.) administration of SR147778 (0.3–3 mg/kg twice daily) specifically suppressed the acquisition of alcohol drinking behavior in alcohol-naive rats exposed to the two-bottle "alcohol or water" choice regimen for 24 hours/day. In Experiment 2, an acute i.p. administration of SR147778 (2.5–10 mg/kg) specifically reduced alcohol intake in alcohol-experienced rats that were given alcohol and water under the two-bottle choice regimen in daily sessions of 4 hours. In Experiment 3, an acute i.p. administration of SR147778 (0.3–3 mg/kg) suppressed the "alcohol deprivation effect" (the extra-intake of alcohol occurring after a period of alcohol abstinence). In Experiment 4, an acute i.p. administration of SR147778 (0.3–3 mg/kg) specifically suppressed the extinction responding for alcohol, i.e. the maximal number of lever responses reached in the absence of alcohol in rats trained to lever-press for alcohol (measure of the motivational properties of alcohol). In Experiment 5, the combination of 3 mg/kg of SR147778 (i.p.) and 0.5 g/kg of alcohol (i.p.), a dose comparable with those usually consumed by sP rats in each drinking binge, failed to induce any conditioned taste aversion. These results extend to SR147778 the anti-alcohol profile of the prototype cannabinoid CB1 receptor antagonist, rimonabant (SR141716), and strengthen the hypothesis that the cannabinoid CB1 receptor is part of the neural substrate mediating alcohol intake and the motivational properties of alcohol.

NIAAA Glossary Terms:  cannabinoids, tetrahydrocannabinol, neurotransmitter receptors, antagonists, ethanol, AOD consumption, AOD intake per occasion, animal selectively bred for AOD preference, laboratory rat, AOD abstinence, motivation, animal model


F. Lallemand and P. De Witte.  Ethanol Induces Higher BEC in Cb1 Cannabinoid Receptor Knockout Mice While Decreasing Ethanol Preference.  Alcohol & Alcoholism 40(1):54-62, January/February 2005.

Summary:
Previous studies using the CB1 cannabinoid receptor antagonist SR 141716 have shown that CB1 cannabinoid receptors are involved in the behavioral effects induced by chronic ethanol administration in Wistar rats. These studies have now been extended to investigate the effect of acute and chronic alcoholization on blood ethanol concentration (BEC) and ethanol preference in CB1 knockout (-/-) mice. BEC was monitored for 8 hours in both  CB1-/- male mice and CB1 male wild-type (+/+) mice, which had received an acute intraperitoneal (i.p.) injection of ethanol in 1, 3, or 5 g/kg doses. Ethanol preference was assayed in both groups of male mice in non-forced ethanol administration and forced chronic pulmonary alcohol administration for 14 and 39 days, respectively. After an acute i.p. ethanol injection of 5 g/kg,
CB1-/- mice showed a significantly higher BEC during the ethanol elimination stage than the CB1+/+ mice. However, those in the 1 and 3 g/kg groups showed no significant difference. A 2–3 fold increase in BEC was observed in CB1-/- mice on days 10 and 11 after commencement of forced chronic pulmonary alcoholization in comparison with CB1+/+ mice, although comparable BEC values were assayed in both groups on day 12. In addition, these  mice showed a significantly lower preference for ethanol than CB1+/+ mice. The studies on CB1-/- and CB1+/+ mice clearly confirm the involvement of CB1 receptor on ethanol induced behavioral effects and also reveal that CB1 receptors may be implicated in ethanol absorption/distribution, particularly after administration of high ethanol doses.

NIAAA Glossary Terms:  ethanol, AOD consumption, BAC, gene knockout technology, intraperitoneal administration, cannabinoids, neurotransmitter receptors, antagonists, animal study, comparative study, laboratory mice


Travis J. Worst and Kent E. Vrana.  Alcohol and Gene Expression in the Central Nervous System.  Alcohol & Alcoholism 40(1):63-75, January/February 2005.

Summary:
This literature review describes recent research focusing on the analysis of gene and protein expression relevant to understanding ethanol consumption, dependence, and effects, in order to identify common themes. A selective literature search was used to collate the relevant data. Over 160 genes have been individually assessed before or after ethanol administration, as well as in genetically selected lines. Techniques for studying gene expression include Northern blots, differential display, real time reverse transcriptase polymerase chain reaction (RT-PCR), and in situ hybridization. More recently, high throughput functional genomic technology, such as DNA microarrays, has been used to examine gene expression. Recent gene expression analyses have dramatically increased the number of candidate genes (nine array papers have highlighted 600 novel gene transcripts that may contribute to alcohol abuse and alcoholism). Although functional genomic experiments (transcriptome analysis) have failed to identify a single alcoholism gene, they have illuminated important pathways and gene products that may contribute to the risk of alcohol abuse and alcoholism.

NIAAA Glossary Terms:  gene expression, central nervous system, ethanol, AOD consumption, AOD abuse, AOD dependence, acute AODE, chronic AODE, genetic technology, Northern blotting, reverse transcriptase polymerase chain reaction, gene transcription, genome, DNA, risk factors, literature review


Dai-Jin Kim, Su-Jung Yoon, Bomoon Choi, Tae-Suk Kim, Young Sup Woo, Won Kim, Hugh Myrick, Bradley S. Peterson, Young Bin Choi, Yong-Ku Kim, and Jaeseung Jeong.  Increased Fasting Plasma Ghrelin Levels During Alcohol Abstinence.  Alcohol & Alcoholism 40(1):76-79, January/February 2005.

Summary:
The peptide hormone ghrelin antagonizes the action of leptin and is thereby thought to regulate feeding behavior. The actions of ghrelin and leptin appear to be mediated by the neuropeptide Y (NPY) and Agouti-related protein (AGRP) system. Recent studies have suggested that leptin and NPY play significant roles in the pathophysiology of alcoholism. The present study sought to determine whether ghrelin is associated with the state and duration of abstinence in alcoholics. Fasting plasma ghrelin levels were compared between alcoholics (n = 47) during a period of abstinence and control subjects (n = 50). Fasting plasma ghrelin levels were higher in abstinent alcoholics than in controls, there was a positive correlation between ghrelin levels and the duration of abstinence, and daily alcohol intake prior to abstinence was inversely related to ghrelin levels. These findings suggest that ghrelin plays a role in the pathogenesis of alcohol dependence, particularly during the abstinence period, in individuals with chronic alcoholism.

NIAAA Glossary Terms:  peptides, hormones, leptin, antagonists, neuropeptide Y, pathogenesis, AOD dependence, AOD abstinence, AOD intake per occasion, controlled study, correlation analysis, human study


K. Junghanns, U. Tietz, L. Dibbelt, M. Kuether, R. Jurth, D. Ehrenthal, S. Blank, and J. Backhaus.  Attenuated Salivary Cortisol Secretion under Cue Exposure Is Associated with Early Relapse.  Alcohol & Alcoholism 40(1):80-85, January/February 2005.

Summary:
The aim was to determine if the risk of relapse in alcohol dependence is predicted by the subjective experience of cue exposure (CE) and/or cortisol reactivity to alcohol cues. Salivary cortisol and self-ratings of "tension" and "desire to drink" were measured in detoxified alcohol-dependent inpatients (N = 32) during CE sessions conducted in the first and third week of motivation enhancement therapy. Subjects completed the Toronto Alexithymia Scale (TAS-20) and the Abbreviated Alcohol Expectancy Questionnaire (B-AEQ) towards the end of the inpatient treatment to measure emotional self-awareness and the expected positive effects of alcohol. Six weeks after the end of the inpatient treatment, 15 patients were abstinent. Relapse was verified or was presumed for 17 patients. Those who had relapsed had shown an attenuated response to CE in the third week as an inpatient but did not differ from abstainers in subjective reaction to cues. Subjective ratings of CE were not related to salivary cortisol or relapse but showed several associations with factors one and two of the TAS-20. The expectancy of enhanced social contacts by using alcohol (factor 1 of the B-AEQ) correlated negatively with the decline in salivary cortisol during the CE session in the third week of treatment. Subjective ratings of CE correlated with Alexithymia scores. In conclusion, alcoholics who use alcohol to enhance their social contacts typically lack hypothalamo-hypophyscal-pituitary-adrenocortical (HPA) reactivity in the early period of abstention. They are at an increased risk of early relapse and perhaps use alcohol to increase cortisol secretion again.

NIAAA Glossary Terms:  AOD dependence, AOD abstention, cue reactivity, cortisol, saliva analysis, hypothalamic-pituitary-adrenal axis, expectancy, correlation analysis, sociability, social behavior, alexithymia, human study


Jun-Ichi Iga, Takahide Taniguchi, and Tetsuro Ohmori.  Acute Abdominal Distension Secondary to Urinary Retention in a Patient after Alcohol Withdrawal.  Alcohol & Alcoholism 40(1):86-87, January/February 2005.

Summary:
The authors report a case of symptomatic abdominal distension due to urinary retention after alcohol withdrawal. The timing of the onset suggests that it was induced by alcohol withdrawal. Several cases of alcohol-induced bladder dysfunction have been reported previously, but the mechanism of its development is varied and unclear.

NIAAA Glossary Terms:  case study, bladder function, urinary system disorder, urination, abdomen, AOD withdrawal syndrome, AOD dependence, human study


UPHome Page


Alcohol and Alcoholism
Volume 39, Number 6, November/December 2004
(Updated November 11, 2004)

UPHome Page

Sally Casswell.  Alcohol Brands in Young Peoples' Everyday Lives: New Developments in Marketing (Commentary).  Alcohol and Alcoholism 39(6):471-476, November/December 2004.

Summary:
The author discusses the response of young people to new developments in alcohol marketing, what this marketing does for the alcohol industry, and the need for new policy responses.  The new developments are likely to be important for young people because of their use of new technology and the role of brands in their lives.

NIAAA Glossary Terms: adolescent, young adult, marketing strategy, alcoholic beverage industry, public policy on AOD, targeted advertising, commentary


Jim Slattery.  Pragmatic Trials and the ARES Study (Commentary).  Alcohol and Alcoholism 39(6):477, November/December 2004.

(No abstract available)


A. M. Brind, A. Hurlstone, D. Edrisinghe, I. Gilmore, N. Fisher, M. Pirmohamed, and A. A. Fryer. The Role of Polymorphisms of Glutathione S-transferases Gstm1, M3, P1, T1 and A1 in Susceptibility to Alcoholic Liver Disease.  Alcohol and Alcoholism 39(6):478-483, November/December 2004.

Summary:
It has been proposed that oxidative stress is an important factor in the pathogenesis of alcohol-related liver damage. Because there is evidence for genetic susceptibility to alcohol-related liver disease, the authors of this study compared the frequency of polymorphisms of glutathione S-transferases (GSTs), a group of enzymes that protect against oxidant stress. GSTM1, GSTM3, GSTP1, GSTT1, and GSTA1 were analyzed by polymerase chain reaction (PCR) on leucocyte DNA in patients with alcohol-related chronic liver disease, heavy drinkers, and normal controls. Genotype frequences of GSTM1, GSTM3, or GSTP1 did not differ significantly among patients, drinking, and non-drinking controls from the three centers partcipating in the study. There was a significant increase in the GSTT1 null alcoholic liver disease (ALD) patients in Liverpool (UK) compared with corresponding non-drinking controls (26.3 and 14.6% respectively; p = 0.044, odds ratio (OR) = 2.1; 95% confidence interval [CI], 1.1–4.7), but this was not observed in the Birmingham and North Staffordshire cohorts. For GSTA1, the –69 CC genotype was associated with increased risk of ALD in the Liverpool group, but with a reduced risk in the North Staffordshire group. This case-control study was unable to demonstrate a reproducible significant association of GST polymorphisms with susceptibility to ALD, but further study of GSTA1 and GSTT1 may be warranted.

NIAAA Glossary Terms:  alcoholic liver disorder, heavy AOD use, AOD nonuse, chronic AODE, genetic theory of AODU, genetic polymorphism, gene frequency, genotype, genetic correlation analysis, polymerase chain reaction, DNA, leukocytes, transferases, glutathione, isoenzymes, risk analysis, case-control study, human study


Pascal Perney, Pierre Portalès, Jacques Clot, François Blanc, and Pierre Corbeau.  Diminished CD4+ T Cell Surface CCR5 Expression in Alcoholic Patients.  Alcohol and Alcoholism 39(6):484-485, November/December 2004.

Summary:
The C-C chemokine receptors, particularly the CCR5, appeared to play an important role in T cell-mediated inflammatory reactions. This study was assessed the impact of chronic alcohol consumption on CCR5 expression in vivo. Alcoholic men (n = 14) hospitalized for detoxification were compared with age-matched controls (n = 49). The CD4+ T cell surface CCR5 densities were drastically lower in alcoholics, averaging 5,319 molecules/cell (95% confidence interval [CI], 4477–6162], compared to the controls, 10,944 molecules/cell (95% CI, 9,929-11,959; p < 10-4). It was concluded that chronic alcohol consumption is associated with significantly decreased CCR5 expression, which could favor Th1/Th2 imbalance.

NIAAA Glossary Terms:  cytokines, chronic AODE, AOD dependence, receptors, T lymphocyte, in vivo study, case-control study, detoxification, hospital, human study


Frédéric Lallemand, Philippe Soubrié, and Philippe De Witte.  Effects of CB1 Cannabinoid Receptor Blockade on Ethanol Preference after Chronic Alcohol Administration Combined with Repeated Re-exposures and Withdrawals.  Alcohol and Alcoholism 39(6):486-492, November/December 2004.

Summary:
SR141716A is a cannabinoid CB1 brain receptor antagonist that differentially affects the ethanol preference of chronically alcoholized rats when administered during cycles of ethanol exposure and withdrawal. This study investigated ethanol preference in chronically alcoholized rats that underwent regular withdrawal periods during which SR141716A was administered. SR141716A at two different doses was administered intraperitoneally to Wistar rats at the end of a 4-week period of chronic alcoholization, as they began a 10-day cycle of alcohol withdrawal. The withdrawal period was followed by another 10-day period of chronic ethanol exposure. A second set of experiments included an additional cycle of ethanol withdrawal and re-exposure. Preference for ethanol versus water started at the end of the first or second chronic ethanol re-exposure for a period of at least 30 days. In rats pretreated with the higher dose of SR141716A (10 mg/kg/day), ethanol preference during free choice was significantly increased after two ethanol re-exposures. In contrast, pretreatment with the lower SR141716A dose (3 mg/kg/day) induced no significant change in ethanol intake during the free choice followed by either one or two ethanol re-exposures. Thus SR141716A at a 10 mg/kg/day dose significantly increased ethanol preference which was dependent on both the number of ethanol withdrawals and chronic ethanol re-exposures, while 3 mg/kg/day had no significant effect on ethanol preference.

NIAAA Glossary Terms:  cannabinoids, antagonists, receptors, brain, ethanol, AOD preference, chronic AODE, AOD withdrawal syndrome, AOD intake per occasion, animal study, laboratory rat


Stefan Bleich, Kristina Bayerlein, Udo Reulbach, Thomas Hillemacher, Dominikus Bönsch, Birgit Mugele, Johannes Kornhuber, and Wolfgang Sperling.  Homocysteine Levels in Patients Classified According to Lesch's Typology.  Alcohol and Alcoholism 39(6):493-498, November/December 2004.

Summary:
Because it has been suggested that elevated total plasma homocysteine levels might preduct alcohol withdrawal seizures, total plasma homocysteine levels were investigated in actively drinking alcoholic patients who were classified according to Lesch's typology. Total plasma homocysteine levels were determined in 144 non-abstinent chronic alcoholics (115 men, 29 women; aged 22-67 years). The patients were classified according to Lesch's typology (LT) and were divided into two groups: LT 1 (n = 27) and LT 2 to 4 (n = 117). Patients with or without a history of alcohol withdrawal seizures were differentiated within these groups. All patients with a history of alcohol withdrawal seizures had significantly elevated plasma homocysteine concentrations at admission compared with those without seizures (Mann-Whitney U, p < 0.001). Furthermore, patients classified as LT 1 who suffered from an alcohol withdrawal seizure (n = 12) had significantly higher plasma homocysteine levels (Z = –2.31, p = 0.02) compared to the corresponding types 2 to 4 (n = 24). A logistic regression analysis revealed that withdrawal seizures were best predicted by a high homocysteine level at admission; this was even more pronounced in LT 1 (Wald's chi-squared  = 10.7; odds ratio [OR] = 1.24; 95% confidence interval [CI], 1.03-1.51; p < 0.001) when compared with LT 2 to 4 (chi-squared = 10.6; OR = 1.06; 95%CI, 1.03-1.14; p = 0.004). The authors believe this is the first study to evaluate homocysteine levels in patients who were classified according to Lesch's typology. They conclude that homocysteine levels on admission may be a useful screening method to identify actively drinking patients at risk of alcohol withdrawal seizures, especially in Lesch type 1 alcoholics.

NIAAA Glossary Terms:  [homocysteine], [Lesch's typology], AOD dependence, AOD withdrawal syndrome, AODR seizure, predictive factor, risk factors, alcohol use disorder classification, plasma, regression analysis, statistical estimation, medical screening and diagnostic method, clinical study, human study


Bykov, M. Palmén, L. Piirainen, and K. O. Lindros.  Oral Chronic Ethanol Administration to Rodents by Agar Gel Diet.  Alcohol and Alcoholism 39(6):499-502, November/December 2004.

Summary:
This article describes a new method for chronic ethanol administration to rodents as an alternative to current procedures, which are labor intensive and require specially designed equipment. A commercial liquid diet preparation was made into a gel by addition of 0.5% agar. The gel, containing 5.3% ethanol, was offered in Falcon tubes equipped with a feeding opening. Ingestion of the gel by C57/Bl mice resulted in high blood ethanol levels (average 43 mM), and marked liver steatosis and significantly increased serum alanine aminotransferase levels developed after 6 weeks. Administration of ethanol in a nutritionally adequate gel provides a simple method for studies on chronic ethanol effects in rodents.

NIAAA Glossary Terms:  ethanol, AOD consumption, chronic AODE, diet, nutritional value or requirement, alcoholic liver disorder, fatty liver, alanine aminotransferase, animal study, laboratory mice, laboratory study


Nathaniel C. O. Khaole, Vijay A. Ramchandani, Denis L. Viljoen, and Ting-kai Li.  A Pilot Study of Alcohol Exposure and Pharmacokinetics in Women with or Without Children with Fetal Alcohol Syndrome.  Alcohol and Alcoholism 39(6):503-508, November/December 2004.

Summary:
Alcohol exposure and alcohol pharmacokinetics were compared in women (n = 10) who had given birth to children with fetal alcohol syndrome (FAS) and women who had not given birth to FAS children (n = 20). The FAS mothers and the controls were studied to determine how they metabolize alcohol in a single limited-access quasi-experimental session of voluntary alcohol consumption in which they had free choice to consume any amount of their favorite beverage for about 2.5 hours, but their drinking was terminated if their breath alcohol concentration (BrAC) exceeded 150 mg%. BrAC was measured during ethanol consumption and for several hours afterward, for estimation of alcohol exposure and pharmacokinetics. FAS mothers consumed significantly more alcohol and achieved significantly higher peak BrAC levels than controls. The rate of decline of alcohol from the circulation varied twofold across subjects but did not differ significantly between the two groups. This study found no difference in alcohol pharmacokinetics in free-choice drinking by non-pregnant women who either have given or have never given birth to FAS children. However, mothers of FAS children tended to consume more alcohol per session. The authors recommend further studies in larger samples to confirm these findings and to examine drinking patterns and other factors that may increase the risk of FAS in children of women who drink alcohol during pregnancy.

NIAAA Glossary Terms:  fetal alcohol syndrome, mother, alcoholic beverage, AOD consumption, AOD intake per occasion, ethanol metabolism, pharmacokinetics, breath alcohol analysis, controlled study, human study


Adele Mckinney and Kieran Coyle.  Next Day Effects of a Normal Night's Drinking on Memory and Psychomotor Performance.  Alcohol and Alcoholism 39(6):509-513, November/December 2004.

Summary:
The effects of a "normal" evening of alcohol drinking on cognitive performance was investigated in social drinkers (N = 48; 33 women, 15 men; 18-43 years of age). Participants were required to consume their usual quantity of any type of alcoholic beverage in their chosen company (hangover situation), but the timing of drinking was restricted to the period between 22:00 and 02:00 hours on the night before testing. Testing included memory and psychomotor performance tests. Testing was also performed after an evening of abstinence (no-hangover situation), following a counterbalanced design using repeated measures, with time of testing (09:00, 11:00, and 13:00 hours) and order of testing (hangover/no hangover; no hangover/hangover) as "between-participant" factors in the analysis. Test sessions were conducted a week apart. The morning after alcohol (mean consumption: 14.7 units for men; 10.4 units for women), free recall was impaired at 09:00 hours and delayed recognition and psychomotor performance were impaired throughout the morning, despite blood alcohol levels of zero or very nearly zero. It was concluded that memory and psychomotor performance are impaired on the morning after heavy social drinking.

NIAAA Glossary Terms:  cognitive and memory disorder, psychomotor impairment, social AOD use, alcoholic beverage, hangover (any AOD substance), AOD abstinence, BAC, gender differences, human study


Claudia I. Rupp, W. Wolfgang Fleischhacker, Armand Hausmann, Dolores Mair, Hartmann Hinterhuber, and Martin Kurz.  Olfactory Functioning in Patients with Alcohol Dependence: Impairments in Odor Judgements.  Alcohol and Alcoholism 39(6):514-519, November/December 2004.

Summary:
Olfactory judgements were assessed in nonamnesic and nondemented patients with alcohol dependence. Alcohol-dependent patients (n = 30) and healthy control subjects (n = 30), well matched for gender, age and smoking status, and screened for olfactory sensitivity, were asked to rate intensity, familiarity, edibility and pleasantness of 16 odors using visual rating scales. Compared with controls, alcohol-dependent patients showed lower scores in odor familiarity and impaired edibility judgments. These impairments were bilateral; independent of age, gender, general mental abilities, and length of abstinence; and not attributable to smoking or impaired olfactory sensitivity. No differences were evident between groups in odor intensity and pleasantness judgments. The results extend prior findings of alcohol-related olfactory deficits, indicating impairments in olfactory processes of odor familiarity and edibility in alcohol-dependent patients. Although the basis of these deficits is still unknown, the finding of a distinct pattern of olfactory function, with spacing of perception of pleasantness and familiarity, suggests that there is no generalized olfactory impairment but that neural olfactory networks may be affected differently.

NIAAA Glossary Terms:  smell, olfactory perception, olfactory system disorder, AOD dependence, controlled study, human study


Paul Kiritzé-Topor, Dominique Huas, Claude Rosenzweig, Sylvie Comte, François Paille, and Philippe Lehert.  A Pragmatic Trial of Acamprosate in the Treatment of Alcohol Dependence in Primary CareAlcohol and Alcoholism 39(6):520-527, November/December 2004.

Summary:
The effectiveness of pharmacotherapy with acamprosate (calcium acetylhomotaurinate) was assessed in alcohol-dependent patients treated in a naturalistic primary care setting in France. The ARES (Acamprosate et Répercussions Économiques et Sociales; Acamprosate and Economic and Social Repercussions) study was performed by 149 general practitioners treating patients fulfilling standard diagnostic criteria (DSM-IV) for alcohol dependence. Exclusion criteria included contraindications to acamprosate, co-medication with naltrexone, and multiple substance abuse. Eligible patients were randomized either to standard care alone or standard care with acamprosate, using an open-label design and followed up quarterly for a period of 1 year. The primary outcome variable was the change from baseline on the Alcohol-Related Problems Questionnaire (ARPQ). Secondary efficacy variables were abstinence, Clinical Global Impression, quality of life measured with the SF-36, and incidence of adverse events. A total of 422 patients were included, 348 (82%) of whom completed the protocol as planned. At the end of the study, patients in the acamprosate group had significantly better outcomes in terms of total ARPQ score, change from baseline (-2.61 vs -3.44), and number of subjects with no alcohol-related problem. On average, patients treated with acamprosate had one less alcohol-related problem than the controls. The number needed to treat in order to save one additional patient from alcohol-related problems compared to standard care was 7.14. Statistically significant differences in favor of the acamprosate group were observed for all secondary efficacy outcome measures including quality of life.

NIAAA Glossary Terms:  AOD dependence, AOD abstinence, drug therapy, calcium acetylhomotaurinate, primary care, general practitioner, randomized controlled trial, follow-up study, treatment follow-up, treatment outcome, AODR disorder, diagnostic criteria, quality of life, adverse drug effect, clinical study, human study


Alan De Sousa and Avinash De Sousa.  A One-year Pragmatic Trial of Naltrexone vs Disulfiram in the Treatment of Alcohol Dependence.  Alcohol and Alcoholism 39(6):528-531, November/December 2004.

Summary:
The efficacy of naltrexone and disulfiram in preventing an alcoholic relapse in routine clinical practice were compared. Alcohol-dependent men (N = 100) were randomly allocated to a year of treatment with either naltrexone or disulfiram. Patients, their accompanying family member, and the treating psychiatrist were aware of the nature of treatment given. Alcohol consumption, craving, and adverse events were recorded by the treating psychiatrist weekly for the first three months, then every two weeks for the rest of the year. Serum gamma-glutamyl transferase (GGT) was measured at the start and the end of the study. At the end of the year, 97 patients were still in contact. Relapse, the consumption of >5 drinks (40 g of ethanol) in a 24-hour period, occurred at a mean of 119 days with disulfiram and at 63 days with naltrexone (p = 0.020). Mean serum GGT, which had not differed between the two groups initially, was 117 U/l with naltrexone and 85 U/l with disulfiram (p = 0.038) at the end of the study. Abstinence throughout the study was maintained by 86 percent of the patients with disulfiram compared to 44% with naltrexone (p = 0.0009), but patients allocated to naltrexone had significantly less craving. It was concluded that disulfiram is superior to naltrexone in preventing a relapse among alcohol-dependent men with family support. The authors recommend comparison between these treatments in other settings and in different types of alcoholics.

NIAAA Glossary Terms:  AOD dependence, AOD craving, AOD abstinence, AODD relapse, relapse prevention, alcohol relapse prevention agents, disulfiram, naltrexone, drug therapy, gamma glutamyl transferase, family support, clinical trial, comparative study, human study


Mauri Aalto and Kaija Seppä.  Usefulness, Length and Content of Alcohol-related Discussions in Primary Health Care: The Exit Poll Survey.  Alcohol and Alcoholism 39(6):532-535, November/December 2004.

Summary:
Patients' opinions of the usefulness of alcohol-related discussions with general practitioners (GPs), the time used for the discussion, and the discussion's main content were evaluated based on an exit poll survey of 2,000 consecutive patients immediately after GP consultations. The response rate was 60.2% (N = 1,203). Of the patients 11.6% (n = 139) reported that they were asked or advised about alcohol during the consultation. The time used for discussion about alcohol for most patients was less than 4 minutes, longer for heavy drinkers than for non-heavy drinkers. The main topics of the discussion dealt with quantities consumed and harm caused by alcohol. The majority of the patients (81%) reported that discussions concerning alcohol were useful; heavy drinkers and non-heavy drinkers did not differ in this assessment. In summary, discussions about alcohol in primary health care were rare and short, but patients' opinions about their usefulness were mainly positive.

NIAAA Glossary Terms:  general practitioner, primary health care, alcoholic beverage, AOD use pattern, brief intervention, survey, harm reduction, human study


T. Alwyn, B. John, R. J. Hodgson, and C. J. Phillips.  The Addition of a Psychological Intervention to a Home Detoxification Programme.  Alcohol and Alcoholism 39(6):536-541, November/December 2004.

Summary:
The aim was to determine whether a relatively brief psychological intervention adds to the effectiveness of home detoxification. Participants (N = 91) were randomly assigned to either the psychological intervention or treatment as usual. Community psychiatric nurses were trained to administer the brief psychological intervention involving motivational interviewing, coping skills training, and social support. A manual was developed in order to standardize the training and implementation. At the 3-month and 12-month follow-ups, the psychological intervention resulted in significant positive changes in alcohol consumption, abstinent days, social satisfaction, self-esteem, and alcohol-related problems. A cost analysis revealed that the cost of the psychological intervention was one-ninth that of inpatient treatment. It was concluded that adding a psychological intervention to a home detoxification program was successful and cost-effective.

NIAAA Glossary Terms:  AOD dependence, AOD consumption, AOD abstinence, AOD effects and AODR problems, home health care, detoxification, psychological counseling, coping skills, social support, nurse, follow-up study, patient satisfaction, self-esteem, cost-effectiveness of AOD health services, evaluation study, human study


Falk Kiefer and Klaus Wiedemann.  Combined Therapy: What Does Acamprosate and Naltrexone Combination Tell Us?  Alcohol and Alcoholism 39(6):542-547, November/December 2004.

Summary:
Both acamprosate (calcium acetylhomotaurinate) and naltrexone have been shown to be efficacious for relapse prevention in the treatment of alcoholism, but there is limited evidence as to whether combined treatment with these drugs is efficacious and safe. The authors of this article reviewed the three pre-clinical and four clinical studies that have been published to date on either the combined tolerability or efficacy of these agents. The available data show no occurrence of severe adverse events during combined treatment. The most significant side-effects reported are diarrhea and nausea. Pre-clinical studies of the efficacy of combined treatment are not yet conclusive, but clinical data show the superiority of combined treatment compared with both placebo and acamprosate monotherapy. The synergistic effect of combined treatment remained after 12 weeks of drug-free follow-up. The combination of acamprosate with naltrexone in a clinical sample seems to be efficacious and safe. Numerous alcohol dependent patients could benefit from the combination, particularly those who respond insufficiently on monotherapeutic treatment with either acamprosate or naltrexone.

NIAAA Glossary Terms:  drug therapy, relapse prevention, AOD dependence, AODD relapse, naltrexone, calcium acetylhomotaurinate, combination drug therapy, beneficial vs adverse drug effect, synergistic drug interaction, literature review, animal study, human study, clinical trial


Odd Nilssen.  Long-term Effect of Brief Intervention in At-risk Alcohol Drinkers: A 9-year Follow-up Study.  Alcohol and Alcoholism 39(6):548-551, November/December 2004.

Summary:
The long-term effect of brief intervention with people who consume alcohol at levels considered risky were assessed in a 9-year follow-up study. The participants were 338 men and women attending a general population screening study in 1986 who were identified as at-risk drinkers. They were randomly assigned to one of three groups, two of which received slightly different brief interventions and the third group serving as controls. After 1 year alcohol intake was 50% lower in the intervention groups and 20% higher in the control group. The controls were then advised to reduce their drinking. This article reports outcomes in 247 subjects (73.1%) from the 1986 study who were re-assessed 9 years after these interventions. Serum gamma-glutamyl transferase (GGT) was examined and compared with values in 1986. A "pseudo-control" group was established to compare "treated" and "untreated" subjects. After 9 years, the mean GGT levels in the original study groups were significantly reduced. The reductions achieved in the three original groups did not significantly differ from each other, but they were significantly greater than in the "pseudo-control" group. Brief intervention therefore appears to have a longlasting impact. At 9 years follow-up, the at-risk drinkers displayed GGT values close to that of the background population.

NIAAA Glossary Terms:  follow-up study, AOD user, problematic AOD use, amount of AOD use, high-risk group, brief intervention, gamma glutamyl transferase, controlled study, comparative study, evaluation, health risk assessment , human study


Cheryl J. Cherpitel, Yu Ye, and Jason Bond.  Alcohol and Injury: Multi-level Analysis from the Emergency Room Collaborative Alcohol Analysis Project (ERCAAP)Alcohol and Alcoholism 39(6):552-558, November/December 2004.

Summary:
The relationship between individual-level characteristics and site-level contextual variables on the association of acute alcohol use and injury was analyzed. Blood alcohol concentrations (BAC) and survey data were collected at the time of emergency department (ED) visits, between 1985 and 2003 on probability samples of injured and non-injured patients (n = 18,438) from 31 EDs in seven countries (Argentina, Canada, Italy, Mexico, Poland, Spain, USA). Data analysis with hierarchical linear modeling with control for gender and age revealed that  BAC and self-reported alcohol consumption were predictive of an injury (compared to a non-injury), with odds ratios of 1.51 and 1.58 respectively. The likelihood of injury given a positive BAC and self-report was less for heavier drinkers (those reporting five or more drinks on an occasion) than for lighter drinkers, and was greater in societies with greater detrimental drinking patterns than those with lower detrimental patterns. The results suggest a moderate but robust association of a positive BAC and self-report with admission to the ED for an injury, which is modified by the patient's usual heavier drinking and by societal drinking patterns.

NIAAA Glossary Terms:  emergency care, injury, AOD consumption, heavy AOD use, light AOD use pattern, BAC, self-report, predictive factor, risk factors, risk analysis, relative risk, statistical modeling, international differences, cultural patterns of drinking, human study


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Alcohol and Alcoholism
Volume 39, Number 5, September/October 2004
(Updated August 24, 2004)

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D. Colin Drummond.  An alcohol strategy for England: The good, the bad and the uglyAlcohol & Alcoholism 39(5):377-379, 2004.

(No abstract available.)


Salim Mottagui-Tabar, Shane McCarthy, Jana Reinemund, Björn Andersson, Claes Wahlestedt, and Markus Heilig.  Analysis of 5-hydroxytryptamine 2C receptor gene promoter variants as alcohol-dependence risk factorsAlcohol & Alcoholism 39(5):380-385, September/October 2004.

Summary:
The objective was to determine whether polymorphic variants of the 5-hydroxytryptamine 2C (HTR2C) receptor gene promoter are associated with alcohol dependence. Allele frequencies of five HTR2C promoter polymorphisms were compared in a Nordic population of alcohol dependent individuals (males: n = 309; females: n = 127) and ethnically matched controls (males: n = 83; females: n = 190) in whom any diagnosis of substance disorder was excluded. Alcohol dependent subjects were subtyped into Type I (late onset) and Type II (early onset) alcoholics. None of the individual polymorphisms were significantly associated with alcohol dependence. A common promoter haplotype (GAGG) exhibited different distribution frequencies between males and females (Type I), but this association became non-significant when Bonferroni's multiple-testing correction was applied. Although no association was found between alcohol dependence and five common promoter polymorphisms, and the constituted haplotypes, the analysis tends to indicate gender and sub-type differences. The authors suggest a follow-up study using larger samples to improve the power to detect the genetic influences of HTR2C in alcohol dependence.

NIAAA Glossary Terms:  genetic polymorphism, risk factors, AOD dependence, receptors, allele, gene frequency, Scandinavia, early AODU onset, late AODU onset, Cloninger's typology, haplotype, gender differences, genetic correlation analysis, human study


Johannes Frank, Karin Witte, Wieland Schrödl, and Christine Schütt.  Chronic alcoholism causes deleterious conditioning of innate immunity.  Alcohol & Alcoholism 39(5):386-392, September/October 2004.

Summary:
The immune consequences of chronic alcoholism were examined in relation to the known association between alcoholism and greater incidence and severity of infections. In 36 alcoholics without liver disease the following measures of immune competence were measured at the commencement of withdrawal from alcohol: the immunophenotypes of cells, acute phase proteins, the endotoxin-neutralizing capacity (ENC) of the serum, titers of anti-lipopolysaccharide (LPS) antibodies, and ex vivo cytokine inducibility in T cells and monocytes. The cytokines examined were tumor necrosis factor-alpha (TNF-α), interleukin (IL)1β, IL1RA, IL4, IL6, IL8, IL10, and IL12. The results were compared to those from healthy volunteers. Measures were repeated after 8-13 days of abstinence. LPS-binding protein (LBP) and soluble CD14 (sCD14) were significantly increased in patients' sera at the outset of withdrawal, whereas reduced titers of anti-LPS immunoglobulin G (p
= 0.012) and a reduced ENC (p = 0.001) were measured. Only ENC rapidly returned to normal values after withdrawal therapy. Cytokine induction with phorbol ester showed no significant alterations in patients' T cells. Patients' monocytes, however, responded to LPS stimulation with significantly enhanced production of IL1β, but significantly reduced production of TNF-α and IL12. While IL1 and TNF-α responses normalized after withdrawal, impaired IL12 response persisted throughout the observation period of 2 weeks. It was concluded that alcoholism causes a prolonged LPS-mediated hypoinflammatory conditioning of the innate (but not the adaptive) immune system that is not reversed immediately after withdrawal and predisposes to infections and sepsis by blunting initial response to pathogens.

NIAAA Glossary Terms:  AOD dependence, AOD abstinence, immune system, immune response, infection, alcoholic liver disorder, antibodies, tumor necrosis factor-alpha, T lymphocyte,  interleukin, lipopolysaccharide, pathogenesis, human study


María Dolores Mayas, María Jesús Ramírez-Expósito, María Jesús García, Pilar Carrera, and José Manuel Martínez-Martos.  Ethanol modulates neuropeptide-degrading aminopeptidases at synapse level in calcium-dependent conditions.  Alcohol & Alcoholism 39(5):393-405, September/October 2004.

Summary:
The effects of ethanol on alanyl-, arginyl-, cystyl-, leucyl- and tyrosyl-aminopeptidase activities were studied under basal and K+-stimulated conditions at the synapse level, using mouse frontal cortex synaptosomes and their incubation supernatant in a Ca2+-containing or Ca2+-free medium . Under basal conditions, synaptosome aminopeptidase activities showed an inhibitory or biphasic response depending on the concentration of ethanol and the aminopeptidase assayed. Supernatant activities showed a more complex response. Under K+-stimulated conditions, ethanol inhibited all synaptosome aminopeptidases assayed in presence of Ca2+. However, different responses were obtained in the absence of Ca2+ depending on the concentration of ethanol used. In the supernatant, the highest concentration of ethanol inhibited the K+-stimulated increase on aminopeptidase activities, although the lowest concentration enhanced the release in presence of Ca2+. In absence of Ca2+, ethanol blocked the K+-stimulated decrease or increased the activity depending on the concentration of ethanol. The changes on aminopeptidase activities induced by ethanol may reflect the functional status of their corresponding endogenous substrates. Ethanol may influence opioid peptides, oxytocin, vasopressin, and the brain renin-angiotensin system through their degrading enzymes.

NIAAA Glossary Terms:  ethanol, synaptosome, peptides, enzymes, amino acids, alanine, arginine, cystine, leucine, tyrosine, potassium, calcium, opioids, oxytocin, vasopressin, renin, angiotensin, enzymes, animal study, laboratory mice


Hiroshi Kinoshita, Michael S. Harbuz, Minori Nishiguchi, Harumi Ouchi, Takako Minami, Takao Utsumi, Hiroyuki Motomura, and Shigeru Hishida.  High alcohol preferring (HAP) and low alcohol preferring (LAP) rats show altered proopiomelanocortin (POMC) messenger RNA expression in the arcuate nucleusAlcohol & Alcoholism 39(5):406-409, September/October 2004.

Summary:
Proopiomelanocortin (POMC) and neuropeptide Y gene expression in the arcuate nucleus of the hypothalamus were compared in high alcohol preference (HAP) rats and low alcohol preference (LAP) rats under basal conditions using in situ hybridization histochemistry. Expression of POMC mRNA was was significantly higher in HAP rats than in LAP rats, but the two rat lines did not differ in neuropeptide Y mRNA expression. The results suggest that an endogenous opioid system may contribute to alcohol preference in these rat lines.


Justin Grobe, Neil Rowland, and Michael Katovich.  Role of angiotensin II and the subfornical organ in the pharmacological actions of ethanolAlcohol & Alcoholism 39(5): 410-417, September/October 2004.

Summary:
This study investigated whether angiotensin II mediates the hypothermic effects of ethanol and whether the effects of angiotensin are mediated centrally. It was also hypothesized that the subfornical organ (SFO) is a site responsible for the alterations in body temperature and aerial righting reflex mediated by ethanol and for the modulation of ethanol consumption in rats. Experiments were conducted to evaluate the role of both peripheral and central administration of losartan, a selective angiotensin type 1 receptor antagonist, on ethanol-induced hypothermia. Subsequent studies were undertaken in SFO-lesioned rats to evaluate the effects of SFO-lesion on alcohol intake, the thermal response to alcohol and angiotensin, and the aerial righting reflex. Selective antagonism of the angiotensin II type 1 receptor, administered either peripherally or centrally, attenuated not only the fall in colonic temperature but also attenuated the transient rise in tail skin temperature that was associated with ethanol administration. The thermal responses to both angiotensin and ethanol were similarly attenuated in SFO-lesioned rats. Likewise the aerial righting reflex, which has previously been shown to be impaired by losartan treatment, was also significantly attenuated in SFO-lesioned animals. Alcohol intake, as determined by a 48-hour, two-bottle preference test also revealed that SFO-lesioned animals consumed significantly less alcohol (ethanolic beer) than did controls. It was concluded that ethanol-induced temperature responses are mediated by the renin-angiotensin system and that this interaction is mediated centrally. The results also demonstrate that the SFO is a site that mediates several neurobiological effects of ethanol, possibly via the renin-angiotensin system.


Ken D. Sumida, Tauseef Qureshi, Michael J. Catanzaro, Steven M. Arimoto, and Janeen M. Hill.  Chronic alcohol consumption yields sex differences in whole-body glucose production in ratsAlcohol & Alcoholism 39(5):418-426, September/October 2004.

Summary:
The effects of chronic alcohol consumption (8 weeks) on glucose kinetics, in the absence and presence of an acute ethanol dose (4 g/kg), were examined in fasted (48 hours) male and female Wistar rats. Primed continuous infusions of tritium- and carbon 14-labeled glucose were used to assess rates of glucose appearance (Ra), glucose disappearance (R d), and apparent glucose carbon recycling. After injecting the male and female controls with water (4 g/kg), there were no significant alterations in glucose kinetics. Compared to controls, chronic alcohol-fed female animals (injected with water) demonstratedsignificantly lower glucose Ra, blood glucose concentration, and apparent glucose carbon recycling for most of the experimental period. In separate groups injected with ethanol, the glucose Ra fell by 31% for male rats fed the control diet (MC), 43% for male rats fed the ethanol diet (ME), 29% for female rats fed the control diet (FC), and 42% for female rats fed the ethanol diet (FE). Compared to controls (MC and FC), the blood glucose concentration was significantly lower before and after the ethanol injection for FE. In addition, FE animals had significantly lower rates of glucose Ra and glucose carbon recycling compared to controls before and after the ethanol injection. ME animals demonstrated similar declines in glucose Ra (compared to FE), but only after the ethanol injection. Conversely, ME were able to match the decrease in glucose Ra with comparable declines in glucose Rd resulting in blood glucose concentrations that did not differ from controls. Thus chronic alcohol consumption results in sex differences in whole-body glucose production and glucose regulation.


A. Vakili, K. Tayebi, M. R. Jafari, M. R. Zarrindast, and B. Djahanguiri.  Effect of ethanol on morphine state-dependent learning in the mouse: involvement of gabaergic, opioidergic and cholinergic systems.  Alcohol & Alcoholism 39(5):427-432, September/October 2004.

Summary:
This study examined the effect in mice of acute administration of ethanol when it replaced morphine in a step-down passive avoidance task on the test day and the effects of antagonists of GABAergic,opioidergic, and cholinergic systems on ethanol's actions. Morphine (5 mg/kg, s.c.) was administered as pre-training and 24 hours later as pre-test drug, and the latencies were measured. Ethanol (0.125, 0.25, 1, and 2 g/kg, i.p.) was administered instead of pre-test morphine. Antagonists of GABAergic (bicuculline 0.5, 1, and 2 mg/kg, i.p.), opioidergic (naloxone 0.06, 0.25, and 1 mg/kg, i.p.), and cholinergic (atropine 0.625 and 1.25 mg/kg, i.p. and mecamylamine 0.5, 1, and 2 mg/kg, i.p.) systems were co-administered with ethanol (0.25 g/kg, i.p.) on the test day. Locomotor activity was measured as well. Pre-training morphine impaired memory on the test day; memory was restored when the same dose of morphine was used as pre-test drug. All four doses of ethanol replaced pre-test morphine and enhanced memory. This effect was prevented by all of the antagonists studied. No significant changes were seen in the locomotor activity of the animals treated with ethanol or antagonists compared to the proper controls. It was concluded that GABAergic, endogenous opioidergic, and cholinergic systems are involved in the memory recall improvement by ethanol when it replaced morphine on the test day.


Marc A. Schuckit and Tom L. Smith.  Changes over time in the self-reported level of response to alcoholAlcohol & Alcoholism 39(5):433-438, September/October 2004.

Summary:
This study investigated whether the number of alcohol drinks needed for an effect decreases between the teens and age 40. Data were available from the 20-year follow-up of 202 men who had originally been chosen at age 20 as nonalcoholic subjects from families at high and low risk for alcoholism. The number of drinks required for effects was determined through the Self-Report of the Effects of Alcohol questionnaire (SRE) and included subjects' recollection of their intensity of reaction early in their drinking careers as well as recent response to alcohol at the 15- and 20-year follow-ups. Overall, there was a slight decrease in the drinks required for effects across the three time points which became significant when recent drinking and depressant medication use were evaluated as covariates. When nonalcoholic or light-drinking subjects were evaluated separately, the decrease in the number of drinks needed for effects was more prominent. Among heavier drinkers, there was an increase in the number of drinks required for effects over time. The findings were generally similar for men with and without alcoholic relatives. The results suggest that development of a more intense reaction to alcohol, or fewer drinks needed for an effect, with increasing age may only be relevant to lighter drinkers. Among heavier drinkers, the finding that more drinks are required for effects may be relatively stable over time.


A. Van Den Bruel, B. Aertgeerts, K. Hoppenbrouwers, M. Roelants, and F. Buntinx.  CUGE: A screening instrument for alcohol abuse and dependence in studentsAlcohol & Alcoholism 39(5):439-444, September/October 2004.

Summary:
The CUGE questionnaire consists of four questions: Have you ever felt you ought to Cut down on drinking?; “Have you often driven Under the influence?; Have you ever felt bad or Guilty about your drinking?; “Have you ever had a drink first thing in the morning to steady your nerves or get rid of a hangover (Eye opener)? The CUGE has been described as a promising screening device for problem drinking in students. This cross-sectional study assessed the diagnostic value of this new questionnaire in a new and independent population of freshmen. The study participants were freshmen of the Catholic University of Leuven (Belgium). All students received a questionnaire containing the CUGE and the Composite International Diagnostic Interview Instrument (CIDI) as a reference test. The CUGE was found to have very high sensitivity (91%) and a reasonable specificity (76.3%) in this validation group. It was concluded that the CUGE is an excellent screening instrument in this student population. In addition, the CUGE is a short questionnaire requiring only yes or no answers, which makes it easy to apply as a part of broad routine questionnaires.


Gregory E. Skipper, Wolfgang Weinmann, Annette Thierauf, Patrick Schaefer, Gerhard Wiesbeck, John P Allen, Michael Miller, and Friedrich Martin Wurst.  Ethyl glucuronide: A biomarker to identify alcohol use by health professionals recovering from substance use disordersAlcohol & Alcoholism 39(5):445-449, September/October 2004.

Summary:
Ethyl glucuronide (EtG), a direct metabolite of alcohol, offers an extended window for assessing drinking status (up to 5 days) in abstinence-based monitoring programs. Urine samples were obtained from 100 participants in a physician monitoring program and additional samples were subsequently obtained "for cause," "to verify positive urine alcohol, when drinking was denied," and "in high-risk individuals." All participants had signed contracts agreeing to remain abstinent from mood-altering drugs, including alcohol, and had agreed to random urine testing. EtG was determined using LC/MS-MS. The main outcome measure was urine specimens positive for EtG versus specimens positive based on standard testing for alcohol and other drugs. None of the initial 100 random urine samples was positive for alcohol using standard testing, but 7 were positive for EtG (0.5-196 mg/l), suggesting recent alcohol use. Subsequent EtG testing was performed clinically during the course of monitoring. Of the 18 tests performed to date, 8 of 8 performed "for cause" were positive for EtG but negative for all other drugs including urine alcohol; all were confirmed positive by self-reported drinking by the patient when confronted with the positive test result. Of 6 tests performed to "confirm a positive urine alcohol," 2 were positive for EtG and confirmed positive by self-reported drinking. For the other 4 samples, especially 2 from a diabetic, possible in vitro fermentation is discussed. The results suggest that the rate of unrecognized alcohol use among physicians in monitoring programs is higher than previously reported. These programs can be strengthened by Incorporating EtG testing into alcohol abstinence monitoring.


Nicholas S. Aberle, II, Larry Burd, Bonnie H. Zhao, and Jun Ren.  Acetaldehyde-induced cardiac contractile dysfunction may be alleviated by vitamin B1 but not by vitamins B6 or B12Alcohol & Alcoholism 39(5):450-454, September/October 2004.

Summary:
Chronic alcohol exposure leads to a deficiency of group B vitamins and increased risk of alcoholic cardiomyopathy. This study examined the effect of group B vitamin supplementation on cardiac contractile dysfunction induced in rat ventricular myocytes by the alcohol metabolite acetaldehyde. Mechanical contractile properties were evaluated by an IonOptix SoftEdge® system. Protein damage and apoptosis were determined by protein carbonyl and caspase-3 assays respectively. Short-term (4-6 hours) culture of myocytes with acetaldehyde (10 µM) depressed peak shortening amplitude, maximal velocity of shortening/relengthening, and shortened duration of shortening but not duration of relengthening. Acetaldehyde exposure also enhanced protein carbonyl formation and apoptosis in ventricular myocytes. The acetaldehyde-induced mechanical defects, protein damage, and apoptosis were prevented by vitamin B1 (10 µM), an essential vitamin required for DNA synthesis and repair. Vitamin B6 (10 µM) attenuated acetaldehyde-induced impairment of shortening duration. Vitamin B12 (1 mM) attenuated acetaldehyde-induced reduction in maximal velocity of shortening/relengthening. Unlike vitamin B1, none of the other acetaldehyde-elicited alterations in myocyte mechanical function were affected by vitamin B6 or vitamin B12. Vitamin B6 and vitamin B12 partially, but significantly, attenuated the acetaldehyde-induced carbonyl formation without affecting acetaldehyde-induced apoptosis. The findings provide evidence that vitamin B1 supplementation may protect against acetaldehyde-induced cytotoxicity by preventing protein damage and apoptotic cell death in ventricular myocytes.


Kathryn Graham, Andrée Demers, Jürgen Rehm, and Gerhard Gmel.  Problems with the graduated frequency approach to measuring alcohol consumption: Results from a pilot study in Toronto, Canada.  Alcohol & Alcoholism 39(5):455-462, September/October 2004.

Summary:
A telephone survey was used to evaluate advantages and disadvantages of the graduated frequency approach to assessing alcohol consumption. The approach asks about the frequency of alcohol consumption at mutually exclusive quantity levels (i.e. 12 or more drinks, at least 8 drinks but less than 12, etc.). The subjects were 464 adults aged 18 and older in Toronto, Canada, who were contacted by random digit dialing and given computer-assisted interviews. Respondents reported higher frequency and volume of drinking on the graduated frequency measure compared to overall and beverage-specific quantity-frequency type measures. However, at least 16% of graduated frequency responses included double-counting on frequency estimates. When these cases were excluded or corrected, differences between the graduated frequency and quantity-frequency measures mostly disappeared. Graduated frequency was superior to quantity-frequency measures for identifying heavy episodic drinkers, but had little advantage over the weekly recall method except for identifying very infrequent (i.e., less often than twice a month) heavy drinkers. Because the graduated frequency has a high rate of response errors in terms of measuring frequency of alcohol consumption, it was concluded that other combinations of measures, including alternate measures of heavy episodic drinking, should be considered.


Rosa Alati, Stuart Kinner, Jake M. Najman, Greg Fowler, Kerrianne Watt, and David Green.  Gender differences in the relationships between alcohol, tobacco and mental health in patients attending an emergency departmentAlcohol & Alcoholism 39(5):463-469, September/October 2004.

Summary:
The nature of the association between usual alcohol consumption, tobacco use, and symptoms of anxiety and depression were examined in a cross-sectional survey of 812 patients aged 16-84 presenting for treatment over a 14-day period to an emergency department in Queensland, Australia. Measures included sociodemographic data; the Alcohol Use Disorders Identification Test (AUDIT) to measure moderate, hazardous, and harmful alcohol consumption; and the Hospital Anxiety and Depression Scale (HADS) to measure state anxiety and depression. Gender differences were evident. For men, there was a U-shaped relationship between alcohol consumption and anxiety/depression, and a linear association between smoking and anxiety. For women, alcohol consumption and anxiety/depression showed a more linear relationship, but there was no significant relationship between tobacco use and anxiety/depression. Thus there may be important gender differences in the relationships between alcohol consumption, tobacco use, and mental health status. This study supports previous evidence that the mental health status of non-drinkers is worse than that of moderate drinkers, but only among males.


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Alcohol and Alcoholism
Volume 39, Number 4, July/August 2004
(Updated on July 16, 2004)

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John M. Littleton, Philippe De Witte, Raye Litten, Gian Luigi Gessa, Rainer Spanagel, Henry Kranzler, Philippe Lehert, Bankole Johnson, John Saunders, Mats Berglund, Adron Harris, Raymond Anton, and Karl Mann.  Development in Treating Alcohol Dependence: An International Perspective: Summary of a Symposium Held at the ESBRA Congress, Prague, 13 September 2003Alcohol & Alcoholism 39(4):271-275, July/August 2004.

Summary:
This article summarizes a symposium on development of pharmacological agents for the treatment  of alcohol dependence that was held at the Congress of the European Society for Biomedical Research on Alcoholism in Prague, Czech Republic, in September 2003. Few medications exist for the treatment of alcohol dependence. Better collaboration between academia and the pharmaceutical industry is needed to develop, license, and market effective medications for treating alcohol dependence. Methodologies that span the divide between preclinical and large-scale clinical studies are needed to provide enough information on safety, toleration, drug-interaction profile, and efficacy to guide development decisions. Because of the heterogeneity of alcohol dependence, development of an effective medication is likely to be enhanced by clearer choices about the characteristics of the population. Careful consideration of potential mechanism of action of the putative therapeutic medication should allow the appropriate choice of drinking endpoint. It may be necessary for the pharmaceutical industry in collaboration with academia to develop new approaches for determining appropriate treatment endpoints with regulatory bodies. The investment risk to industry should be appraised not only in terms of the rather poor results of previous marketing efforts but with a view to the opportunity to penetrate a potentially enormous and largely untapped market.


Luca Valenti, Tullia De Feo, Anna Ludovica Fracanzani, Erika Fatta, Mario Salvagnini, Sarino Arico, Giorgio Rossi, Gemino Fiorelli, and Silvia Fargion.  Cytotoxic T-lymphocyte Antigen-4 A49g Polymorphism Is Associated with Susceptibility to and Severity of Alcoholic Liver Disease in Italian PatientsAlcohol & Alcoholism 39(4):276-280, July/August 2004.

Summary:
This study examined whether the functional A49G polymorphism of cytotoxic T-lymphocyte antigen-4 (CTLA-4) plays a role in susceptibility to alcoholic liver disease (ALD) and influences disease severity in Italian alcohol abusers. CTLA-4 is a T-cell surface molecule that modulates T-lymphocyte activation and influences the risk of developing alcohol-induced autoantibodies. The subjects were 183 patients with chronic ALD (61 cirrhosis), 115 patients with end-stage hepatitis C virus (HCV) cirrhosis, 102 patients with non-alcoholic fatty liver disease (NAFLD), 93 healthy subjects, and 43 heavy drinkers without liver disease. CTLA-4 gene polymorphism was analyzed by restriction analysis. The CTLA-4 polymorphism was found more frequently in patients with ALD than in patients with HCV chronic hepatitis and NAFLD, healthy subjects (p < 0.0001), and heavy drinkers without liver disease (p = 0.02). In patients with ALD, homozygosity for the CTLA-4 polymorphic allele (G/G genotype) was more frequent in subjects with cirrhosis (p = 0.047), and was independently associated with the risk of cirrhosis (odds ratio = 3.5; p = 0.03). The CTLA-4 polymorphic G allele, probably by interfering with the immune response, may confer susceptibility to ALD and, in homozygous state, to alcoholic cirrhosis.


Jan Calissendorff, Kerstin Brismar and Sven Röjdmark.  Is Decreased Leptin Secretion after Alcohol Ingestion Catecholamine-mediated?  Alcohol & Alcoholism 39(4):281-286, July/August 2004.

Summary:
Catecholamines (CA) inhibit leptin secretion, and alcohol appears to have a similar effect. This study tested the hypothesis that CA act as mediators of alcohol's inhibitory effect on leptin secretion. Seven healthy subjects participated in two experiments, performed in random order, 1 week apart. In experiment A, three identical doses of ethanol (0.45 g/kg) were ingested at regular intervals between 09:00 and 12:00 hours. The alcohol doses were given against a background of oral placebo administered at 08:00 and 12:00 hours. In experiment B, identical doses of alcohol were ingested against a background of oral propranolol (40 mg at 08:00 and 20 mg at 12:00 hours). Pulse rates, and serum levels of ethanol, insulin, insulin-like growth factor (IGF)-1, and leptin, were determined at regular intervals throughout the experiments. Urinary CA excretion was also determined. Propranolol (experiment B) decreased the pulse rate significantly, compared with placebo (experiment A), but did not change the urinary excretion of adrenaline and noradrenaline. Alcohol ingestion raised the serum ethanol levels similarly in the two experiments but did not affect the insulin or IGF-1 levels. Serum leptin levels declined similarly in the two experiments; the percentage decline from baseline was 28.6 ± 5.4% in experiment A and 29.0 ± 2.9% in experiment B. It was concluded that the declining serum leptin concentration after acute ingestion of alcohol does not appear to be CA-mediated nor to be caused by changed secretion of insulin or IGF-1. A direct inhibitory effect of alcohol on the adipocytes is possible, but increased disposal of leptin via hepatic metabolism or renal excretion could also contribute.


Young-hoon Kim, Joo-cheol Shim, Deanna L. Kelly, Jeong-goo Lee, Young-soo Seo, and Robert R. Conley.  Cortisol Response to Buspirone in Extended Abstinent AlcoholicsAlcohol & Alcoholism 39(4):287-289, July/August 2004.

Summary:
Cortisol response to buspirone was evaluated in alcoholic inpatients with extended abstinence (at least 3 months) to determine 5-HT1A receptor sensitivity in alcoholism. Cortisol levels were significantly lower in the alcoholics than in the normal controls from 60 minutes through to 150 minutes after administration of 30 mg buspirone. The results show that cortisol response to buspirone was significantly decreased in alcoholic patients compared to normal controls, reflecting decreased 5-HT1A receptor sensitivity.


Rafael Castilla, Raúl González, Dalia Fouad, Enrique Fraga, and Jordi Muntané.  Dual Effect of Ethanol on Cell Death in Primary Culture of Human and Rat HepatocytesAlcohol & Alcoholism 39(4):290-296, July/August 2004.

Summary:
The effect of a broad range of ethanol concentrations on apoptosis and necrosis was evaluated in primary cultures of human and rat hepatocytes. Hepatocytes were isolated from human hepatectomies and male Wistar rats. After cell culture stabilization, ethanol (0–10 mmol/l) was added and parameters were measured 24 hours later. Apoptosis was studied by DNA fragmentation, iodide propidium–DNA staining, caspase-3 activity, and annexin V binding in hepatocytes. Necrosis was evaluated by lactate dehydrogenase (LDH) release. Malondialdehyde (MDA) and reduced glutathione/oxidized glutathione ratio (GSH/GSSG) were used as parameters of oxidative stress. Ethanol dose-dependently enhanced all parameters associated with apoptosis in human and rat hepatocytes. Low and high ethanol concentrations induced opposite actions against cell necrosis: low ethanol concentrations (1–2 mmol/l) reduced LDH release from human and rat hepatocytes, whereas the highest ethanol concentration (10 mmol/l) induced a sharp increase in cell necrosis. The effect of ethanol on cell necrosis was related to lipid peroxidation in hepatocytes. It was concluded that ethanol differentially regulates apoptosis or necrosis in cultured hepatocytes. Although ethanol dose-dependently induced apoptosis, low ethanol concentrations were able to reduce basal lipid peroxidation and necrosis in hepatocytes. The highest ethanol concentration induced apoptosis and necrosis in hepatocytes.


Sergio Ortiz, José M. Oliva, Sandra Pérez-rial, Tomás Palomo, and Jorge Manzanares.  Differences in Basal Cannabinoid Cb1 Receptor Function in Selective Brain Areas and Vulnerability to Voluntary Alcohol Consumption in Fawn Hooded and Wistar Rats.  Alcohol & Alcoholism 39(4):297-302, July/August 2004.

Summary:
The functional activity of cannabinoid CB1 receptor was compared in alcohol-preferring Fawn Hooded and alcohol nonpreferring Wistar rats under naïve conditions. Cannabinoid CB1 (WIN-55,212)-stimulated [35S]-GTPs binding autoradiography, and cannabinoid CB1 receptor gene expression were measured in rats of both strains that received only water. Compared to Wistar rats, Fawn Hooded rats showed significantly lower cannabinoid CB1 receptor stimulated [35S]-GTPs binding in cingulate cortex (Cg), caudate-putamen (CPu), nucleus accumbens (Acc), ventromedial hypothalamic nucleus (VMN), amygdaloid area (AMG), fields (CA1, CA3) of the hippocampus and dentate gyrus (DG). No differences were found either in substantia nigra pars reticulata (SNr) or CA2 field of the hippocampus. In addition, cannabinoid CB1 receptor gene expression was lower in Cg, CPu, VMN and CA3 field of the hippocampus in Fawn Hooded than in Wistar rats. The investigators speculate that lower cannabinoid function appears to be related to greater vulnerability to alcohol consumption. Cannabinoid CB1 receptor may represent a key target in the treatment of alcohol dependence.


Victor De Freitas, Patrícia Da Silva Porto, Marco Assunção, António Cadete-Leite, José Paulo Andrade, and Manuel Maria Paula-Barbosa.  Flavonoids from Grape Seeds Prevent Increased Alcohol-induced Neuronal Lipofuscin FormationAlcohol & Alcoholism 39(4):303-311, July/August 2004.

Summary:
The authors previously found that prolonged oxidative stress caused by chronic ethanol consumption leads to increased formation of lipofuscin in hippocampal and cerebellar neurons.
Their present study examined whether flavanols would impede ethanol-induced lipofuscin accumulation in hippocampal and cerebellar neurons. Flavanols are abundant in the human diet and they exert a powerful in-vitro antioxidant action.  Adult rats were fed for 6 months either with 20% ethanol solution or with the same solution to which a mixture of grape seed catechins and oligomeric procyanidins (200 mg/l) was added. Controls ingested either tap water or water supplemented with the antioxidant compound. The total amount of lipofuscin in the hippocampal CA1 and CA3 pyramids and in the cerebellar Purkinje cells was estimated with unbiased stereological methods. The mean volume of the neurons was estimated with the nucleator and the volumetric density of lipofuscin was calculated by point counting. Flavanols prevented the accumulation of neuronal lipofuscin in the ethanol-fed animals (i.e. under conditions of increased oxidative stress) but not in the water-drinking controls. The neuronal volume did not differ among the groups studied. The findings show that consumption of flavanols can reduce the effects of oxidative activity caused by alcohol consumption, indicating that these compounds might display neuronal beneficial effects under oxidative stress.


Hannu Alho, Pekka Sillanaukee, Anne Kalela, Olli Jaakkola, Seppo Laine, and Seppo T. Nikkari.  Alcohol Misuse Increases Serum Antibodies to Oxidized LDL and C-Reactive Protein.  Alcohol & Alcoholism 39(4):312-315, July/August 2004.

Summary:
The relationship of alcohol consumption with serum antibodies to oxidized low-density lipoprotein (oxLDL) and the inflammation marker C-reactive protein (CRP) was examined in a study comparing 280 men with evidence of alcohol misuse by having self-reported alcohol consumption values over 280 g absolute ethanol/week and 250 age-matched moderate drinkers. Serum samples were analyzed for antibodies to oxLDL, CRP, total cholesterol, high-density lipoprotein (HDL)-cholesterol, triglycerides, carbohydrate-deficient transferrin (CDT), and gamma-glutamyl transferase (GGT). The characteristics of the top and bottom half of the alcohol misusers, in regard to weekly alcohol consumption, were compared with the controls. Serum antibody titers to oxLDL were higher in the top half and the levels of CRP, HDL-cholesterol, triglycerides, GGT, and CDT were elevated in both the top half and the bottom half of the alcohol misusers, compared to controls. Based on the results, the authors propose that alcohol misuse may result in increased inflammation leading to oxidation of LDL.


Kalousová Marta, Zima Tomá, Popov Petr, Paek Pavel, Braun Martin, Soukupová Jiina, Pelinková Kvta, and Kientsch-Engel Rosemarie.  Advanced Glycation End-products in Patients with Chronic Alcohol Misuse.  Alcohol & Alcoholism 39(4):316-320, July/August 2004.

Summary:
The aim was to determine serum levels of advanced glycation end-products (AGE) in patients with chronic alcohol misuse and to examine their relationship to markers of nutrition and inflammation. Study participants were 23 heavy drinkers treated for chronic alcohol misuse and 22 healthy controls. Studied parameters included AGE (fluorescence, CML – carboxymethyllysine and pentosidine), lipids, glucose, albumin, leptin, prealbumin, C-reactive protein (CRP), and pregnancy-associated plasma protein A (PAPP-A). AGE fluorescence was significantly higher in chronic alcoholics than in healthy subjects, while CML was only slightly but not significantly elevated, and pentosidine levels did not differ. In alcoholics, AGE correlate significantly negatively with leptin (r = –0.46,
p < 0.05) and pentosidine with prealbumin (r = –0.43, p < 0.05), otherwise there was no relationship between AGE and other biochemical parameters (glucose, cholesterol, albumin, CRP, PAPP-A). The findings suggest a more complex relationship among advanced glycation, oxidative stress and metabolism of ethanol and their link to nutrition and nutrition-associated parameters. AGE as a result of oxidative stress might be similarly linked to increased cardiovascular risk of heavy alcohol drinkers, as are malnutrition and inflammation, but further studies are needed to confirm this hypothesis.


A. Narberhaus, D. Segarra, M. Giménez, X. Caldú, C. Junqué, N. Bargalló, and F. Botet. Differential Cerebral and Neuropsychological Consequences in Dizygotic Twins with Prenatal Alcohol Exposure.  Alcohol & Alcoholism 39(4):321-324, July/August 2004.

Summary:
A 13-year-old preterm dizygotic twin pair with prenatal alcohol exposure was studied with neuropsychological tests and volumetric magnetic resonance imaging. Neuropsychological and brain structural findings differed between the twins. The twin with the more affected phenotype had large-scale cognitive deficits and significant atrophy in several brain structures. In both subjects white matter volume was reduced relative to the whole cerebral volume. The neuropsychological and neuroimaging data reflect long-term consequences of prenatal alcohol exposure.


Peter M. Miller, Steven M. Ornstein, Paul J. Nietert, and Raymond F. Anton.  Self-report and Biomarker Alcohol Screening by Primary Care Physicians: The Need to Translate Research into Guidelines and Practice.  Alcohol & Alcoholism 39(4):325-328, July/August 2004.

Summary:
Knowledge and use of alcohol self-report and biomarker screening were assessed in a survey of 48 primary care physicians. Knowledge of the biomarkers mean corpuscular hemoglobin (MCV) and gamma-glutamyltransferase (GGT) was as good as knowledge of non-biomarker screening tools (CAGE questionnaire, Alcohol Use Disorders Identification Test [AUDIT]) although use was significantly less. Knowledge and use of the biomarker carbohydrate-deficient transferrin (CDT) was extremely low. It was concluded that there has been little translation of alcohol biomarker research into guidelines for primary care medicine. Most physicians report they would use these tests more frequently with additional knowledge about availability and use.


Jim Harasymiw, Julie Seaberg, and Pamela Bean.  Detection of Alcohol Misuse Using a Routine Test Panel: The Early Detection of Alcohol Consumption (EDAC) Test.  Alcohol & Alcoholism 39(4):329-335, July/August 2004.

Summary:
The derivation and validation of the Early Detection of Alcohol Consumption (EDAC) test are described. EDAC uses linear discriminant function (LDF) analysis for the identification of alcohol misuse. This form of LDF aims to predict a categorical dependent variable (alcohol misuse) on the basis of several independent, predictor variables (routine laboratory tests). EDAC was developed to classify individuals as heavy or light drinkers using a database of 1,599 subjects recruited from 25 sites in the USA. The predictor variables for the LDF were 36 routine chemistry and hematology analytes. The EDAC model produced 80.7% sensitivity and 84.4% specificity, with an overall correct classification rate of 82.5%. Using a stepwise method, 20 of the 36 routine tests used in the LDF were selected as the optimal predictor variables. The top three variables with the highest contribution in the stepwise EDAC model were: bilirubin ratio (direct to total), aspartate aminotransferase, and albumin. The study shows that LDF analysis in conjunction with new, user-friendly computer packages is a practical and cost-effective laboratory tool for detecting excessive drinking using blood constituents ordered routinely in a variety of clinical settings. Diagnostic performance can be adjusted to achieve higher specificity rates.


H. Nyblom, U. Berggren, J. Balldin, and R. Olsson.  High AST/ALT Ratio May Indicate Advanced Alcoholic Liver Disease Rather than Heavy Drinking.  Alcohol & Alcoholism 39(4):336-339, July/August 2004.

Summary:
The ratio of serum aspartate aminotransferase to serum alanine aminotransferase (AST/ALT ratio) as a diagnostic marker in medical populations was assessed. Laboratory tests were viewed retrospectively in three groups: patients with alcohol dependence consecutively admitted to an alcohol and drug treatment unit for treatment of withdrawal (W) symptoms(n = 313) ;  patients with alcohol abuse or dependence consecutively admitted to surgical or medical wards with various primary somatic (S) diagnoses, e.g. respiratory, gastrointestinal, and metabolic, (n = 78) ; and patients with alcohol abuse or dependence consecutively admitted to surgical or medical wards for treatment of alcohol-related liver cirrhosis (C) and its complications(n = 48) . Groups were compared on the pattern of patients' AST/ALT ratios using, for Groups S and C, laboratory data from patients' first admission for their condition. There was a significant rise in the AST/ALT ratio from the W to the S patients, and from the S to the C patients. The ratio in the W group was 1.0 in 64% of the patients, and only exceptionally 2. In the C group, 69% had a ratio of 2, and 8% a ratio of 1.0. The mean ratio was midway in the S group. There was a progressive decline in aspartate (AST/ALT) ratios in the C group after admission. Thus most patients with high alcohol consumption but without severe liver disease do not have an AST/ALT ratio above 1. High AST/ALT ratio suggests advanced alcoholic liver disease rather than heavy drinking.


Olli Savola, Onni Niemelä, and Matti Hillbom.  Blood Alcohol Is the Best Indicator of Hazardous Alcohol Drinking in Young Adults and Working-age Patients with Trauma.  Alcohol & Alcoholism 39(4):340-345, July/August 2004.

Summary:
A study was carried out to determine the most effective marker of hazardous alcohol drinking in trauma patients. The subjects were 349 trauma patients aged 16–49 years admitted into a general hospital trauma center. Information on the amount and pattern of alcohol drinking was obtained by interview. Blood or breath alcohol concentration (BAC), serum gamma-glutamyl transferase (GGT), aspartate aminotransferase (AST), carbohydrate-deficient transferrin (CDT), and the mean corpuscular volume (MCV) of erythrocytes were measured as markers of alcohol consumption. In this series, 8% of all trauma patients were found to be dependent drinkers, 61% were frequent binge drinkers, 17% infrequent binge drinkers, 8% light-to-moderate drinkers, and 6% nondrinkers. On admission, the BAC test was positive in 68% of the hazardous drinkers (i.e. dependent drinkers or frequent binge drinkers). Using a cut-off level of >0 mg/dl, the sensitivity of the BAC test for identifying hazardous drinking was 68% (95% confidence interval [CI], 61–73%), its specificity was 94% (95% CI, 87–97%), and its positive predictive value was 96% (95% CI, 92–98%). GGT, MCV, CDT and AST were less accurate indicators of hazardous drinking. BAC was the least expensive marker. Two-thirds of the trauma patients were hazardous drinkers, and BAC on admission was an accurate indicator of this. The authors recommend that BAC be used systematically in trauma centers if patients are to be selected for alcohol intervention.


J. B. Davies, F. McConnochie, A. Ross, D. Heim, and B. Wallace.  Evidence for Social Learning in the Self-presentation of Alcohol Problems.  Alcohol & Alcoholism 39(4):346-350, July/August 2004.

Summary:
This study examined the extent to which problem alcohol users' self-reports of drinking pattern and symptomatology derive primarily from a functional, learned social-cognitive schema (referred to as a "script" in this paper), rather than from acts of recall or memory. Using a between-groups design with one repeated (within-subjects) measure, problem drinkers and non-problem drinkers were asked to complete a questionnaire about drinking behavior and symptoms. Each group filled in the questionnaire twice, under both of two conditions. In the first condition, they used the questionnaire to describe their own drinking and in the second condition they described the drinking of the other group. Using analyses of variance for the different sub-scales of the questionnaire, no overall differences were found between the two groups on four of the five subscales. However, clear and significant differences were found between the two conditions. That is, both groups were able to produce clearly differentiated scripts for both problem drinking and non-problem drinking. These findings, together with related findings from other sources, suggest that "scripts" for problem drinking and for non-problem drinking can be elicited from both problem-drinking and non-problem-drinking groups. The data support conclusions from an earlier study, suggesting that subjects may use learned "scripts" rather than recall when responding to certain types of questionnaires.


Peter Anderson, Eileen Kaner, Sonia Wutzke, Michelle Funk, Nick Heather, Michel Wensing, Richard Grol, Antoni Gual, and Leo Pas on Behalf of the WHO Brief Intervention Study Group.  Attitudes and Managing Alcohol Problems in General Practice: An Interaction Analysis Based on Findings from a WHO Collaborative StudyAlcohol & Alcoholism 39(4):351-356, July/August 2004.

Summary:
This study examined whether the attitudes of general practitioners (GPs) towards working with drinkers moderated the impact of training and support on screening and brief intervention activity in routine practice. The participants were 340 GPs from four countries who were part of a World Health Organization randomized controlled trial to evaluate the effectiveness of training and support in increasing screening and brief alcohol intervention. GPs' self-reported attitudes towards working with drinkers were measured with the
Shortened Alcohol and Alcohol Problems Perception Questionnaire. Training and support increased screening and brief intervention rates only for GPs who already felt secure and committed in working with drinkers. Training and support did not improve attitudes towards working with drinkers and worsened the attitudes of those who were already insecure and uncommitted. To enhance the involvement of GPs in the management of alcohol problems, interventions that increase both actual experience and address practitioners' attitudes is required. Such support could take the form of on-site support agents and facilitators.


Miriam Bottlender and Michael Soyka.  Impact of Craving on Alcohol Relapse During, and 12 Months Following, Outpatient Treatment.  Alcohol & Alcoholism 39(4):357-361, July/August 2004.

Summary:
The relationship between craving in abstinent alcohol-dependent patients and relapse during and after completion of an intensive outpatient treatment program was investigated in a prospective study. Participants were interviewed at entry to an outpatient treatment program, at the end of the program, and at follow-up 12 months later. The
Obsessive Compulsive Craving Scale (OCDS) total score by Anton et al. (1995) and the three-factor model by Kranzler et al. (1999) were used to measure craving. OCDS was administered at the beginning of treatment when all patients were abstinent, and at the end of treatment in those who were abstinent and had completed the program. The treatment program was completed by 74 of 103 alcohol-dependent patients, and 97% of the completers were personally re-interviewed at the 12-month follow-up. Thirty-two patients (31%) who relapsed during the treatment phase had significantly higher craving as measured by the total OCDS score and significantly higher scores on the "obsessions" and "drinking control and consequences" subscales compared to abstinent patients. Of the 74 patients who completed the program 16% had a major relapse in the next 12 months. Major relapse was predicted by the total OCDS score and the subscale "obsessions." Thus OCDS total score predicts relapse in outpatient treatment. Treatment and aftercare of patients with high craving should be intensified. In this study design, the subscales of Kranzler et al.'s three-factor model (1999) provided little information gain compared to the OCDS total score.


Tomi Lintonen, Salme Ahlström, and Leena Metso.  The Reliability of Self-reported Drinking in Adolescence.  Alcohol & Alcoholism 39(4):362-368, July/August 2004.

Summary:
The reliability of adolescents' self-reported drinking and perceived drunkenness was evaluated using data from two waves of a cross-sectional school-based questionnaire survey with representative cluster samples (the
European School Survey Project on Alcohol and Other Drugs, ESPAD) in Finland. Fifteen-year-old respondents numbered 2,161 in 1995 and 3,109 in  1999, and their response rates were 94% and 90% respectively. The measurements analyzed were open-ended and a set of closed-category questions about the latest drinking occasion. The set of three closed questions used in 1995 yielded mean amounts of 0.066 (girls) and 0.087 (boys) liters of pure alcohol whereas the figures obtained from the open question were 0.085 (girls) and 0.118 (boys) liters. With the closed set extended in 1999 into five questions, the two figures among girls were 0.077 (closed) and 0.077 (open) liters; the corresponding figures among boys were 0.113 (closed) and 0.117 (open) liters. Individual level correlations between the two measures among girls were 0.69 in 1995 and 0.69 in 1999; and 0.69 (1995) and 0.65 (1999) among boys. The numbers of students reporting specific beverage type use were higher when using closed questions compared with an open question. Drunkenness self-reports related logically to amounts of alcohol drunk. The adolescent drinking amount self-reports seem reasonably reliable and valid both on a population and individual level. A set of closed questions may capture the amount drunk even better than an open question.


L. Zhu, D. M. Gorman, and S. Horel.  Alcohol Outlet Density and Violence: A Geospatial Analysis Alcohol & Alcoholism 39(4):369-375, July/August 2004.

Summary:
The relationship between alcohol outlet density and violent crime was examined in an ecologic study with control for neighborhood sociostructural characteristics and the effects of spatially autocorrelated error. The study sample comprised 188 census tracts from the City of Austin, Texas and 263 tracts from the City of San Antonio, Texas. Data on neighborhood social structure, alcohol density, and violent crime were collected from archival sources, and analyzed using bivariate, multivariate, and geospatial methods. Using ordinary least squares analysis, neighborhood sociostructural covariates explained close to 59% of the variability in violent crime rates in Austin and close to 39% in San Antonio. Adding alcohol outlet density in the target and adjacent census tracts improved the explanatory power of both models. Alcohol outlet density in the target census tract remained a significant predictor of violent crime rates in both cities when the effects of autocorrelated error were controlled for. In Austin, the effects of alcohol outlet density in the adjacent census tracts also remained significant. The final model explains 71% of the variance in violent crime in Austin and 56% in San Antonio. The findings show a clear association between alcohol outlet density and violence, and suggest that the issues of alcohol availability and access are fundamental to preventing alcohol-related problems within communities.


UPHome Page


Alcohol and Alcoholism

Volume 39, Number 3, May/June 2004

UPHome Page

G. Pöschl and H. K. Seitz.  ALCOHOL AND CANCERAlcohol & Alcoholism 39(3):155-165, May/June 2004.

Summary:
Literature on chronic alcohol consumption as a risk factor for cancer is reviewed. The article covers epidemiological studies and studies of potential mechanisms by which alcohol stimulates carcinogenesis.

Epidemiology
Chronic alcohol use is a significant risk factor for cancers of the upper alimentary tract including the oropharynx, larynx, esophagus, and liver. The cancer risk associated with alcohol is much lower in the large intestine and the breast, but the high prevalence of cancers in those sites makes even a small increase in risk important, particularly in persons who are at higher risk for other reasons. Epidemiological evidence for a significant association between alcohol and cancer in other organs is inconclusive and controversial.

Mechanisms
Evidence from animal studies suggests that ethanol is a cocarcinogen or a tumor promoter rather than a carcinogen.

Acetaldehyde
Acetaldehyde, a product of ethanol metabolism, appears to be most responsible for alcohol-associated carcinogenesis; it is carcinogenic and mutagenic, binds to DNA and proteins, destroys folate, and causes hyperproliferation. Acetaldehyde is produced by tissue alcohol hydrogenases, cytochrome P 4502E1, and through oxidative metabolism by bacteria in the upper and lower gastrointestinal tract. Polymorphisms of genes coding for acetaldehyde metabolizing enzymes modulate its production and degradation. Acetaldehyde is also increased by smoking and poor oral hygiene. In addition to increasing acetaldehyde production by altering oral bacterial flora, cigarette smoke itself contains acetaldehyde, as do certain alcoholic beverages.

Other mechanisms
Other mechanisms by which alcohol stimulates carcinogenesis include (1) induction of cytochrome P-4502E1, which is associated with enhanced production of free radicals and enhanced activation of procarcinogens in alcoholic beverages; (2) altered metabolism and distribution of carcinogens; (3) changes in cell cycle behavior such as cell cycle duration leading to hyperproliferation; (4) nutritional deficiencies, such as methyl-, vitamin E-, folate-, pyridoxal phosphate-, zinc- and selenium deficiencies; (5) immune system alterations that  increase susceptibility to virus infections such as hepatitis B virus and hepatitis C virus; (6) local mechanisms that lead to tissue injury such as cirrhosis of the liver, a major prerequisite for hepatocellular carcinoma; and (7) increase in estradiol, which may be at least partly responsible for breast cancer risk.


Michael A. Dawes and Bankole A. Johnson. PHARMACOTHERAPEUTIC TRIALS IN ADOLESCENT ALCOHOL USE DISORDERS: OPPORTUNITIES AND CHALLENGES.  Alcohol & Alcoholism 39(3):166-177, May/June 2004.

Summary:
The authors discuss the design and implementation of studies of the use of medications as adjuncts to psychosocial treatments for adolescent alcohol use disorders (AUDs), an approach that holds the promise of improved efficacy over psychosocial treatments alone. Such studies should consider the developmental risks of the chosen medication, short-term effects on the clinical disorder, factors affecting compliance and retention, and age-specific pharmacokinetics and should include systematic safety monitoring. Potential benefits of the medication to decrease alcohol use should be weighed against potential long-term effects on brain development. Selection of clinically meaningful subtypes of adolescents with AUDs for medication trials should be based on multifactorial models of complex neurodevelopmental disorders. Multifactorial models will be necessary to select samples in which specific gene-gene and gene-environment interactions predict response to medication. Subtypes in samples of adolescents with AUDs are likely to have differential response to medication as a function of age of onset, family history of disorder, and comorbid psychopathology. Findings from preclinical and treatment studies in adults and from pilot treatment studies in adolescents suggest that particular serotonergic agents, opioid antagonists, and agents that modulate excitatory amino acids and GABAergic transmission might be effective. Future medication trials for adolescents with AUDs should use specific combinations of medications, based on specific hypotheses involving key neurotransmitter systems that putatively modulate treatment response. Combined medications may have additive effects on particular neurotransmitter systems or synergistic effects across two or more neurotransmitter systems, resulting in greater decrease in alcohol consumption than with single medications.


M. Negoro and I. Wakabayashi.  NEW SIMPLE METHOD FOR PURIFICATION OF CLASS I ALCOHOL DEHYDROGENASEAlcohol & Alcoholism 39(3):178-182, May/June 2004.

Summary:
A new and simple method for purification of rat class I alcohol dehydrogenase (ADH, EC 1.1.1.1) was developed. The initial purification step after ammonium sulfate precipitation of the cytosolic fraction of rat liver was affinity chromatography with immobilized p-hydroxyacetophenone as a ligand. The eluant was then separated by using ion-exchange chromatography. Homogenous class I ADH, as judged by the results of SDS–PAGE and confirmed by the amino-acid sequence of peptides degraded from a 39 kDa protein, was obtained with a high yield (57%). The purified ADH showed kinetic constants of 1.3 mmol/l for Km and 62.4 per min for Kcat with ethanol as a substrate. A similar method using p-hydroxyacetophenone affinity chromatography was also used for the successful purification of ADH from yeast.


Pierre Mormede, Anthony Colas, and Byron C. Jones.  HIGH ETHANOL PREFERRING RATS FAIL TO SHOW DEPENDENCE FOLLOWING SHORT- OR LONG-TERM ETHANOL EXPOSURE.  Alcohol & Alcoholism 39(3):183-189, May/June 2004.

Summary:
This study examined whether high ethanol preferring (HE) rats, which consume large amounts of alcohol daily, could become alcohol-dependent by repeated exposures of varying lengths and withdrawals of alcohol, both in short- and long-term ethanol exposure. Male and female HEP rats were subjected to short (14 days) or long (20 weeks) exposure to 10% ethanol in a two choice (vs. water) test. During the short- and long-term ethanol exposures, the animals were repeatedly deprived of ethanol for 5 days followed by reinstatement of the two-choice test. Pharmacological agents (morphine and naltrexone), adulteration of ethanol by quinine, and addition of saccharine to water were also applied to test the lability of a possible alcohol deprivation effect. Compared to predeprivation, deprivation, in every case, produced a high initial intake of ethanol that lasted 0.5 hour, with no significant increase in intake thereafter. Even after several months of continuous high ethanol consumption, the rats were sensitive to adulteration of the alcohol solution by quinine (reducing their alcohol intake) and still preferred a saccharine solution when presented as a free choice with the alcohol solution. Pretreatment with morphine increased ethanol consumption in the first 0.5 hour following deprivation, whereas naltrexone reduced it. It was concluded that a major component of alcohol drinking by HEP rats is probably taste reinforcement. Although these rats consume large quantities of ethanol both in the short- and long-term, they do not show a robust alcohol deprivation effect.


C.V. Dayas, R. Martin-Fardon, A. Thorsell and F. Weiss.  CHRONIC FOOTSHOCK, BUT NOT A PHYSIOLOGICAL STRESSOR, SUPPRESSES THE ALCOHOL DEPRIVATION EFFECT IN DEPENDENT RATS.  Alcohol & Alcoholism 39(3):190-196, May/June 2004.

Summary:
This study examined the effects of different types of stress on the alcohol deprivation effect, the temporary increase in alcohol consumption seen after periods of abstinence. Alcohol dependent rats previously trained to self-administer alcohol received either no stress (controls), chronic daily intermittent footshock (10 min/day for 7 days) or daily injections of lipopolysaccharide, a physiological stressor (for 7 days). Alcohol-reinforced responding was then measured for 20 days. Only control rats and those treated with lipopolysaccharide exhibited an alcohol deprivation effect and increased consumption. The results suggest that chronic footshock may not be appropriate for studying the impact of stress on alcohol consumption.


Arthur Tomie, Jillian M. Uveges, Kelly M. Burger, Patricia Patterson-Buckendahl, and Larissa A. Pohorecky.  EFFECTS OF ETHANOL SIPPER AND SOCIAL OPPORTUNITY ON ETHANOL DRINKING IN RATS.  Alcohol & Alcoholism 39(3):197-202, May/June 2004.

Summary:
The effects of pairing ethanol sipper conditioned stimulus with social opportunity unconditioned stimulus on conditioned stimulus-directed ethanol drinking were evaluated in Long-Evans male rats. The rats (n = 32) were deprived of neither food nor water, and the concentration of unsweetened ethanol (3% to 16%) in the sipper conditioned stimulus was increased across sessions. Group Paired/Ethanol (n = 12) received the ethanol sipper conditioned stimulus for 10 s immediately before 15 s of social opportunity unconditioned stimulus. Control groups received water rather than ethanol in the sipper conditioned stimulus (Paired/Water), or ethanol sipper conditioned stimulus and unconditioned stimulus presentations randomly (Random/Ethanol), or ethanol sipper conditioned stimulus but no social opportunity unconditioned stimulus (Sipper Only). Mean ethanol intake in the Paired/Ethanol and Random/Ethanol groups exceeded 1.0 g/kg when the sipper conditioned stimulus contained 12%, 14% and 16% ethanol, and higher fluid intakes were observed in the Paired/Ethanol and Random/Ethanol groups than in the Paired/Water and Sipper Only groups. Thus social opportunity increased ethanol drinking, and more so than water drinking; however, autoshaping did not induce additional ethanol drinking beyond that observed in random controls.


Inmaculada Azorín, Manuel Portolés, Pilar Marín, Francisco Lázaro-Diéguez, Luis Megías, Gustavo Egea and Jaime Renau-Piqueras.  PRENATAL ETHANOL EXPOSURE ALTERS THE CYTOSKELETON AND INDUCES GLYCOPROTEIN MICROHETEROGENEITY IN RAT NEWBORN HEPATOCYTES.  Alcohol & Alcoholism 39(3):203-212, May/June 2004.

Summary:
This study examined in hepatocytes whether prenatal alcohol exposure affects the main cytoskeleton elements and also analyzed whether ethanol induces glycoprotein microheterogeneity by altering the sugar composition of glycoproteins. Livers from 0-day newborn control and prenatally exposed rats were used. Lectin blotting was used to determine the carbohydrate moiety of glycoproteins and
immunoblotting, immunofluorescence, and immunogold were used to analyze t
he content and intracellular distribution of cytoskeleton proteins. Prenatal alcohol exposure delayed the post-Golgi transport of albumin but not of transferrin. Prenatal alcohol exposure also increased the levels of cytokeratin and tubulin but decreased the amount of tubulin capable of assembling into functional microtubules. Prenatal exposure to alcohol perturbed cytokeratin and tubulin distribution and induced microheterogeneity in several glycoproteins. Thus alcohol-induced retention of proteins in fetal hepatocytes could be the result of an alteration of glycoprotein biosynthesis and cytoskeleton-mediated transport.


Sven Barnow, Gabriele Schultz, Michael Lucht, Ines Ulrich, Ulrich-W. Preuss, and Harald-J. Freyberger.  DO ALCOHOL EXPECTANCIES AND PEER DELINQUENCY/SUBSTANCE USE MEDIATE THE RELATIONSHIP BETWEEN IMPULSIVITY AND DRINKING BEHAVIOUR IN ADOLESCENCE?  Alcohol & Alcoholism 39(3):213-219, May/June 2004.

Summary:
This study investigated whether aggressive and delinquent behavior problems predict subsequent adolescent drinking behavior and the extent to which this association is mediated by alcohol expectancies and peer delinquency/substance use. Adolescents approximately 15 years old (N = 147) were interviewed about their drinking behavior and completed several self-rating questionnaires about their peers. As proposed by the Acquired Preparedness Model (APM), behavioral problems were found to be related to quantity and frequency of alcohol consumption. This relationship was mediated by alcohol expectancies. Positive correlations were found between drinking behavior and peer delinquency/substance use, aggression/delinquency, and alcohol expectancies. The association between behavioral problems and drinking decreased dramatically if peer delinquency/substance use was accounted for. Hierarchical regression analysis showed that both alcohol expectancies and peer delinquency/substance use predicted alcohol consumption of adolescents at the 1-year follow-up beyond the effects of age, sex, family history of alcoholism and aggression/delinquency of respondents. It was concluded that alcohol expectancies and peer delinquency/substance use are both crucial to the amount and frequency of adolescent alcohol use and should be considered in designing prevention and intervention strategies in this age group.


Derek Heim, Simon C. Hunter, Alastair J. Ross, Neelam Bakshi, John B. Davies, Kirsty J. Flatley, and Nasar Meer.  ALCOHOL CONSUMPTION, PERCEPTIONS OF COMMUNITY RESPONSES AND ATTITUDES TO SERVICE PROVISION: RESULTS FROM A SURVEY OF INDIAN, CHINESE AND PAKISTANI YOUNG PEOPLE IN GREATER GLASGOW, SCOTLAND, UK.  Alcohol & Alcoholism 39(3):220-226, May/June 2004.

Summary:
Data on the prevalence of alcohol consumption were gathered and perceptions of community responses to alcohol and service provision were assessed in Pakistani, Indian, and Chinese young people (N = 174) aged 16-25 years in Greater Glasgow, Scotland, UK. Purposive sampling techniques were used in the survey and data were collected using an interviewer-administered questionnaire. Alcohol consumption in these populations is currently lower than in the general population. Alcohol consumption was found to be negatively associated with self-reported importance of religion and positively associated with having friends of the same ethnicity who drink. There was a lack of consensus among participants on whether service provision should be part of the mainstream or specialist for black and minority ethnic individuals. It was concluded that alcohol consumption may be increasing among these Pakistani, Indian, and Chinese young people and that service provision could benefit by including specialist services for black and minority ethnic groups, in addition to culturally sensitive mainstream services.


X. Sgouros, M. Baines, R. N. Bloor, R. McAuley, L. O. Ogundipe, and S. Willmott.  EVALUATION OF A CLINICAL SCREENING INSTRUMENT TO IDENTIFY STATES OF THIAMINE DEFICIENCY IN INPATIENTS WITH SEVERE ALCOHOL DEPENDENCE SYNDROME.  Alcohol & Alcoholism 39(3):227-232, May/June 2004.

Summary:
A Thiamine Deficiency Questionnaire was developed and its reliability in identifying thiamine deficiency was assessed in patients with severe alcohol dependence.  Severely alcohol dependent patients (N = 58) received sociodemographic, medical, psychiatric, and alcohol use assessment, including administration of the Thiamine Deficiency Questionnaire.  Red blood cell thiamine pyrophosphate concentration was used as the standard for testing the questionnaire's validity. Univariate 2 x 2 diagnostic test tables and multivariate analysis were performed. A set of eight questionnaire items had a predictive power of 73.7%. Two of the items -- "missed meals due to lack of funds" and the clinical co-occurrence of medical conditions potentially related to poor nutrition -- were highly specific. The Michigan Alcohol Screening Test and serum gamma-glutamyltransferase were moderately predictive. It was concluded that early recognition of thamine deficiency could be improved by screening that combines sociodemographic, clinical and biological factors, and/or standardized questionnaires.


Gerda M. Saletu-Zyhlarz, Oliver Arnold, Peter Anderer, Stefan Oberndorfer, Henriette Walter, Otto M. Lesch, Jobst Böning, and Bernd Saletu.  DIFFERENCES IN BRAIN FUNCTION BETWEEN RELAPSING AND ABSTAINING ALCOHOL-DEPENDENT PATIENTS, EVALUATED BY EEG MAPPING.  Alcohol & Alcoholism 39(3):233-240, May/June 2004.

Summary:
The brain function of drug-free, detoxified alcoholics was compared with that of normal controls, using computerized quantitative electroencephalograph (EEG) analysis and subsequent EEG mapping. Differences were also determined between patients relapsing or abstaining during 6 months of relapse prevention therapy, pharmacologically supported by either flupentixol decanoate 10 mg or placebo i.m. every 2 weeks. Drug-free, detoxified patients (N = 22) diagnosed as alcohol-dependent were subdivided into abstainers (n = 11) and relapsers (n = 11), and compared with age- and sex-matched normal healthy controls. A 3-minute vigilance-controlled EEG (V-EEG) was obtained and analyzed off-line by multi-lead EEG power spectral analysis and subsequent mapping methods. Compared with controls, the drug-free, detoxified, alcohol-dependent patients showed aberrant brain function characterized by a decrease in delta and slow alpha and an increase in beta activity as well as an acceleration of the total centroid. These findings were more pronounced in relapsing than in abstaining patients. After 6 months of treatment, abstaining patients showed an increase in slow activity, a decrease in fast alpha, an acceleration of the delta/theta centroid and a deceleration of the alpha centroid, reflecting a normalization of brain function. Thus EEG maps of alcohol-dependent patients differ significantly from those of normal controls and patients suffering from other mental disorders and therefore may be used for diagnostic purposes. The quantitative EEG may also be of prognostic value as relapsing patients show significantly more pronounced hyperarousal of the central nervous system than abstainers.


Annemiek Schadé, Loes A. Marquenie, Anton J. L. M. Van Balkom, Maarten W. J. Koeter, Edwin De Beurs, Wim Van Den Brink and Richard Van Dyck.  ALCOHOL-DEPENDENT PATIENTS WITH COMORBID PHOBIC DISORDERS: A COMPARISON BETWEEN COMORBID PATIENTS, PURE ALCOHOL-DEPENDENT AND PURE PHOBIC PATIENTS.  Alcohol & Alcoholism 39(3):241-246, May/June 2004.

Summary:
What are the clinical characteristics of treatment-seeking alcohol-dependent patients with a comorbid phobic disorder? Are alcohol dependence and other clinical characteristics of comorbid patients different from those of "pure" alcohol-dependent patients? Are the anxiety symptoms and other clinical characteristics of comorbid patients different from those of "pure" phobic patients?  To answer these questions, three groups of treatment-seeking patients were compared on demographic and clinical characteristics: (1) alcohol dependent patients with a comorbid phobic disorder (n = 110), (2) alcohol-dependent patients (n = 148), and (3) patients with social phobia or agoraphobia (n = 106). Assessment took place at least 6 weeks after detoxification to ensure valid diagnosis of the comorbid disorders. Comorbid patients scored high on depressive symptoms and general psychopathology: 25% of patients had a current and 52% a lifetime depressive disorder. The majority had no partner and were unemployed; had a high incidence of other substance use (benzodiazepine, cocaine, cannabis); and a substantial proportion had been emotionally, physically, and sexually abused. They did not have a more severe, or different type of alcohol dependence than "pure alcohol-dependent patients or a different anxiety disorder than "pure" phobic patients. It is recommended that these findings be taken into account when diagnosing and treating alcohol-dependent patients with a comorbid phobic disorder.


Brigitte Maggia, Sandrine Martin, Corinne Crouzet, Pascal Richard, Pierre Wagner, Jean-Louis Balmès and Bertrand Nalpas.  VARIATION IN AUDIT (ALCOHOL USED DISORDER IDENTIFICATION TEST) SCORES WITHIN THE FIRST WEEKS OF IMPRISONMENT.  Alcohol & Alcoholism 39(3):247-250, May/June 2004.

Summary:
Alcohol problems are suspected to be highly prevalent among prisoners, but often only more flagrant problems are detected. This restricts possibilities for intervention in alcohol misuse and reduces opportunities for preventive efforts. This study examined the retest reliability of the Alcohol Use Disorder Identification Test (AUDIT) in screening prisoners. The AUDIT was administered for the first time on the day of entry to prison and again about 15 days later. The results were analyzed according to two AUDIT thresholds: a score of 8 or higher and 12 or higher. The study was completed by 47 of 75 consecutive entering male prisoners. At the first AUDIT administration, 19.1% of the 47 prisoners met criteria for a probable alcohol problem; the percentage rose to 59.6% (p = 0.0001) at the second AUDIT administration. The proportion of subjects with a score 12 or higher (probably alcohol dependent) was 10.6% the first time versus 42.6% the second time (p = 0.0001). In the 19 prisoners who scored positive at the second administration only, changes in answers to the 10 items were coherent with a total score growing from 3.0 to 18.1 (p = 0.0001). No prisoner had a lower score on the second AUDIT administration. Confirmation of the AUDIT results could not be obtained since alcohol problems are not routinely assessed at entry, although those obtained at the second administration fit well with previously reported prevalences. It was concluded that  administration of the AUDIT, for estimating prevalence or entering appropriate prisoners into more detailed assessment or interventions, should be deferred until some weeks after imprisonment.


Anders Hammarberg, Peter Wennberg, Olof Beck and Johan Franck.  A COMPARISON OF TWO INTENSITIES OF PSYCHOSOCIAL INTERVENTION FOR ALCOHOL DEPENDENT PATIENTS TREATED WITH ACAMPROSATE.  Alcohol & Alcoholism 39(3):251-255, May/June 2004.

Summary:
Two levels of psychosocial intervention in combination with acamprosate medication for the treatment of alcohol dependence were compared. Seventy patients were prescribed acamprosate and randomized to minimal or extended psychosocial intervention. Minimal psychosocial intervention patients met a psychiatrist for 20–30 minute sessions on four occasions during a 6 month period. Extended psychosocial intervention patients were offered 10–15 sessions with a psychiatric nurse in addition to the visits to the psychiatrist and were trained to use behavioral and cognitive coping skills to deal with high-risk situations in line with a manual developed for relapse prevention. Patients were assessed four times during the 24-week study by self-report and laboratory tests. On average, patients reported a decline in days with heavy drinking and in cumulative number of drinking days. No significant differences between patients in minimal and extended psychosocial intervention were found with respect to heavy drinking, cumulative number of drinking days, number of days to first drink, or biological markers of alcohol consumption. Treatment success was significantly predicted by higher age and lower level of education. Adding more intensive individual treatments appears to add no extra improvement beyond that obtained by prescribing acamprosate and offering an infrequent consultation with a physician.


Cheryl J. Cherpitel, Jacek Moskalewicz and Grazyna Swiatkiewicz.  DRINKING PATTERNS AND PROBLEMS IN EMERGENCY SERVICES IN POLAND.  Alcohol & Alcoholism 39(3):256-261, May/June 2004.

Summary:
Drinking patterns and problems were examined in an emergency service in Poland. A probability sample of 734 emergency service patients in a large public hospital in Warsaw were interviewed and given breath alcohol analysis. Breath analysis was positive in 2.5% of the sample. All the positives were male and injured. Injured males were significantly more likely than non-injured males to report heavy problem drinking, but no differences were found for females. Among injured males who reported drinking prior to the event, nearly 50% reported feeling drunk, and over 75% said drinking caused their injury. The findings point to substantial alcohol-involvement of injured males in this population and suggest that emergency services may be a productive venue for identifying patients who would benefit from a brief intervention.


Kaija Seppä, Tuija Lahtinen, Susanna Antila and Mauri Aalto.  ALCOHOL DRINKING AMONG EMERGENCY PATIENTS — ALCOMETER USE AND DOCUMENTATIONAlcohol & Alcoholism 39(3):262-265, May/June 2004.

Summary:
Emergency service physicians' use of the alcometer breath analysis test and their documentation of alcohol-related findings in their patients were measured over one weekend, during which 100 adults attended a university hospital emergency clinic. Data were collected on patients' alcohol consumption, physicians' use of an alcometer, and alcohol-related documentation. Heavy drinkers were defined by the patient's response to a written questionnaire: Five-Shot total score 3 points, and/or 7 drinks per one occasion.  Of the 96 patients who completed the questionnaire, 26 (27%) were heavy drinkers. The alcometer was used in 7% of patients including 5 of the 26 heavy drinkers (10%), and information on alcohol use was entered in the medical records of only 12 of the 26 heavy drinkers (46%). There was no documentation on alcohol in the records of 6 of the 20 patients whose visit was considered by the physician to be primarily alcohol-related. When documentation was present, drinking quantities were not usually recorded.


Robert Patton, Catriona Hilton, Michael J. Crawford and Robin Touquet.  THE PADDINGTON ALCOHOL TEST: A SHORT REPORT.  Alcohol & Alcoholism 39(3):266-268, May/June 2004.

Summary:
The Paddington Alcohol Test, designed to screen for alcohol related problems in accident and emergency department patients, is presented in a slightly modified form. Its concordance with with the Alcohol Use Disorders Identification Test (AUDIT) if fairly good, but it can be administered in about one fifth of the time needed for the AUDIT. Its scoring of units is rapid and specific to the UK. The Paddington Alcohol Test is recommended for use in UK accident and emergency departments.



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Alcohol and Alcoholism

Volume 39, Number 2, March/April 2004

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Hèlen Koch, Gert-Jan Meerkerk, Joost O. M. Zaat, Maria F. Ham, Rob J. P. M. Scholten, and Willem J. J. Assendelft.  Accuracy of carbohydrate-deficient transferrin in the detection of excessive alcohol consumption: A systematic review.  Alcohol & Alcoholism 39(2):75-85, March/April 2004.

Summary:
Based on their systematic review of the literature, the authors conclude that the validity of carbohydrate-deficient transferrin (CDT) as a diagnostic tool remains questionable. Some studies report higher levels of sensitivity than others; if these studies can be confirmed by others CDT is a useful diagnostic tool in unselected populations. However, more methodologically sound, comparable studies are needed before firm conclusions can be drawn.


Ray Hodgson. Family interventions for alcohol problems.  Alcohol & Alcoholism 39(2):86-87, March/April 2004.

Summary:
Part of the growing body of evidence demonstrating that family interventions should be towards the top of the list of effective alcohol prevention and treatment approaches was presented at a recent conference held by the UK Alcohol Education and Research Council.


Sergio Ortiz José M. Oliva, Sandra Pérez-Rial, Tomás Palomo, and Jorge Manzanares. Chronic ethanol consumption regulates CB1 receptor gene expression in selected regions of rat brain. Alcohol & Alcoholism 39(2):88-92, March/April 2004.

Summary:
Results indicated that chronic ethanol consumption reduced cannabinoid CB1 receptor gene expression in selected regions of the rat brain, supporting an interaction between ethanol consumption and the endogenous cannabinoid receptor. The findings further suggested that cannabinoid CB1 receptor may be a new pharmacological target for treating ethanol dependence.


Rafal A. Derlacz, Adam K. Jagielski, Anna Kiersztan, Katarzyna Winiarska, Jakub Drozak, Piotr Poplawski, Michal Wegrzynowicz, Katarzyna Chodnicka, and Jadwiga Bryla.  Amino-acid-dependent, differential effects of ethanol on glucose production in rabbit kidney-cortex tubule.  Alcohol & Alcoholism 39(2):93-100, March/April 2004.

Summary:
In the presence of alanine, ethanol-induced decrease in glucose production and elevation of reactive oxygen species might cause a limited generation of reduced nicotinamide adenine nucleotide phosphate (NADPH), resulting in a decrease in the ratio of intracellular reduced glutathione (GSH) to oxidized glutathione (GSSG) (GSH:GSSG ratio). On the contrary, aspartate might protect against reactive oxygen species generation, so intensive gluconeogenesis supports NADPH generation resulting in the maintenance of a high intracellular GSH:GSSG ratio.


Maria L. V. Dizon, Lou Ann Brown, and  Stephen M. Black. Brain nitric oxide synthase levels increase in response to antenatal ethanol exposure.  Alcohol & Alcoholism 39(2):101-105, March/April 2004.

Summary:
Ethanol may exert its toxic effects antenatally through a mechanism of altered nitric oxide availability from the enzyme nitric oxide synthase.


Eleni Oekonomaki, Georgios Notas, Ioannis A. Mouzas, Vasilios Valatas, Panagiotis Skordilis, Constantinos Xidakis, and Elias A Kouroumalis.  Binge drinking and nitric oxide metabolites in chronic liver disease.  Alcohol & Alcoholism 39(2):106-109, March/April 2004.

Summary:
In healthy controls and patients with chronic viral hepatitis, binge drinking causes a significant increase of serum nitrites and nitrites (NOx) that is evident after 12 hours and returns to pre-drinking levels after 24 hours. In patients with cirrhosis, serum NOx levels are constantly elevated and do not increase with drinking.


M. Parmahamsa, K. Rameswara Reddy, and N. Varadacharyulu.  Changes in composition and properties of erythrocyte membrane in chronic alcoholics. Alcohol & Alcoholism, 39(2):110-112, March/April 2004.

Summary:
The authors investigated alterations in cholesterol and phospholipid contents as well as fluidity and lipid peroxidation in erythrocyte membranes from alcoholics. Studies of fluorescent hydrocarbon pyrene mobility in the bilayer of erythrocytes from alcoholics indicated increased microviscosity and a consequent decrease in membrane fluidity. An enhancement in the lipid peroxidation of erythrocytes from alcoholics indicated structural membrane damage resulting from oxidative stress.


Klaus Junghanns, Jutta Backhaus, Clemens Veltrup, Jürgen Dageförde, Hartmut Brückmann, and Tilman Wetterling.  Mildly disturbed hepatic and pancreatic function during early abstention from alcohol is associated with brain atrophy and with disturbed psychometric performance.  Alcohol & Alcoholism 39(2):113-118, March/April 2004.

Summary:
The authors investigated the relation of liver status and pancreatic function to central nervous system disorders during early abstention from alcohol. After detoxification even mildly disturbed liver and pancreatic parameters, but not fatty liver itself, were associated with signs of brain atrophy and impaired psychometric performance.


A. Scheurich, M. J. Müller, A. Szegedi, I. Anghelescu, C. Klawe, B. Lörch, B. Kappis, H.-G. Bialonski, S. Haas, and M. Hautzinger.
Neuropsychological status of alcohol-dependent patients: Increased performance through goal-setting instructions. 
Alcohol & Alcoholism 39(2):119-125, March/April 2004.

Summary:
The effects of goal-setting instructions on neuropsychological performance were assessed in alcohol-dependent patients and control subjects. Despite neuropsychological deficits in reasoning and psychomotor functioning, alcohol-dependent patients early in recovery were responsive to goal setting and were able to increase their neuropsychological performance. It is concluded that goal-setting strategies might be useful in cognitive rehabilitation and therapy of alcohol-dependent patients.


Hasan Mirsal, Ayhan KalyoncuÖzkan Pekta, Devran Tan, and Mansur Beyazyürek. Childhood trauma in alcoholics. Alcohol & Alcoholism, 39(2):126-129, March/April 2004.

Summary:
The relationship between childhood trauma and alcoholism was evaluated in a controlled study. Significant differences were found between alcoholics and control subjects on traumatic life experiences in childhood. The results suggested a positive correlation beween childhood trauma and anxiety and affective symptoms in alcoholics.


W. Miles Cox, Harold Rosenberg, C. Hazel A. Hodgins, John I. Macartney, and Ken A. Maurer.  United Kingdom and United States healthcare providers' recommendations of abstinence versus controlled drinking. Alcohol & Alcoholism 39(2):130-134, March/April 2004.

Summary:
Health care providers in the United Kingdom and the United States read case histories and gave a recommendation in each case for controlled drinking versus abstinence. Overall, abstinence was recommended more strongly for higher-severity problem drinkers, those with higher social support, and female clients. Controlled drinking was more often recommended in the UK than in the US. However, the degree to which drinkers' problem severity, social support and sex each affected respondents' ratings depended on the level of one or more of the other variables and the country of the respondents.


Helena Hansson, Ulla Zetterlind, Kirsten Åberg-Örbeck, and Mats Berglund. Two-year outcome of coping skills training, group support and information for spouses of alcoholics: A randomized controlled trial.  Alcohol & Alcoholism 39(2):135-140, March/April 2004.

Summary:
Three different intervention programs for spouses of alcoholics (Coping Skills Training, Group Support, and Information) were evaluated. Improvements of coping behaviour, psychiatric symptoms and hardship noted at the 12-month follow-up examination were still evident in all groups at the 24-month follow-up examination. The three groups scored similarly at 24 months on the Coping Behaviour Scale, Symptom Checklist 90 (SCL-90), Hardship Scale, and AUDIT. Spouses with SCL-90 scores above the general population means showed significantly less improvement in the Information group than in the two therapy groups combined.


U. Schneider, T. Kroemer-Olbrisch, F. Wedegärtner, K. F. Cimander, and T. Wetterling.  Wishes and expectations of alcoholic patients concerning their therapy.  Alcohol & Alcoholism 39(2):141-145, March/April 2004.

Summary:
Alcoholic patients were given a questionnaire to assess their wishes and expectations concerning their therapy. Some treatment components were equally important to men and women (a life without alcohol, individual sessions during therapy), but women attached more importance than men to "strengthening of self-esteem" and "an environment of tranquillity and security."


Jim McCambridge, Simon Platts, David Whooley, and John Strang.  Encouraging GP alcohol intervention: Pilot study of change-oriented reflective listening (CORL).  Alcohol & Alcoholism 39(2):146-149, March/April 2004.

Summary:
This pilot study tested the feasibility and potential value of a brief motivational enhancement intervention targeting general practitioners (GPs) in relation to alcohol and compared data obtained with similar attempts to influence GP intervention with drug users. GPs not involved in the treatment of drug dependence received by telephone a "change-orientated reflective listening" (CORL) intervention. There was no change over time in the sample as a whole, and evidence of benefit among individual practitioners was very modest. Comparisons with cannabis and drug misuse intervention targets suggest that it may be more difficult to alter GPs' views on intervening with drinkers.


Andreas Fellgiebel, Thomas Siessmeier, Georg Winterer, Hartmut Lüddens, Klaus Mann, Lutz G Schmidt, and Peter Bartenstein. Increased cerebellar PET glucose metabolism corresponds to ataxia in Wernicke-Korsakoff syndrome.  Alcohol & Alcoholism, 39(2):150-153, March/April 2004.

Summary:
The possiblility of a relationship between cerebellar glucose metabolism and recovery from ataxia in the first months of acute Wernicke-Korsakoff (W-K) syndrome was investigated in a follow-up study. Clinical status and cerebral glucose metabolism were assessed in two patients with alcoholic W-K syndrome who were followed up over a 4- and 9-month period. Initially both patients showed severe ataxia and elevated cerebellar glucose metabolism that decreased corresponding to the restitution of stance and gait. It was concluded that increased cerebellar glucose metabolism at the onset of W-K syndrome may reflect the reorganization process of disturbed motor skills and may indicate cerebellar plasticity.




Alcohol and Alcoholism
Volume 39, Number 1, January/February 2004

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Ritson B.  Alcohol Licensing Laws: Proposals for Changes in  Scottish Law.  Alcohol and Alcoholism 39(1):2-7, January/February 2004.

"It is unknown whether emphasis on local review, server training and some restrictions on bar venues offering discount pricing, will be sufficient to alter current trends in alcohol-related problems."

Aradottir S, Moller K, Alling C. Phosphatidylethanol Formation and Degradation in Human and Rat Blood.  Alcohol and Alcoholism 39(1):8-13, January/February 2004.

"The rat is not suitable as a model for assaying [phosphatidylethanol] in blood as a consequence of ethanol intake. Human blood seems to be particular in its ability to synthesize [phosphatidylethanol] and to maintain a stable level of [phosphatidylethanol] due to the lack of degrading activity."

Okulicz-Kozaryn I, Mikolajczak P, Kaminska E et al. Effect of Naltrexone Administration on Short-term Memory in Chronically Ethanol-treated Outbred Rats.  Alcohol and Alcoholism 39(1):14-19, January/February 2004.

"Naltrexone–ethanol interaction does not seem to produce any negative effect on the short-term memory in outbred rats."

Verlaan M, Te Morsche RHM, Roelofs HMJ et al. Genetic Polypmorphisms in Alcohol-metabolizing Enzymes and Chronic Pancreatitis.  Alcohol and Alcoholism 39(1):20-24, January/February 2004.

"These data suggest that the presence of the CYP2E1 intron 6 DD genotype might confer a higher risk of alcoholic [chronic pancreatitis]."

Miyasaka K, Yoshida Y, Matsushita S et al. Association of Cholecystokinin-A Receptor Gene Polymorphism with Alcohol Dependence in a Japanese Population.  Alcohol and Alcoholism 39(1):25-28, January/February 2004.

"The CCK-AR gene -81A/G polymorphism, especially in the -81G allele, may be associated with intractable alcoholism."

Linke S, Brown A, Wallace P. Down Your Drink: A Web-based Intervention for People with Excessive Alcohol Consumption.  Alcohol and Alcoholism 39(1):29-32, January/February 2004.

"Web site interventions for excessive drinkers are feasible and merit evaluation of their effectiveness."

Wurst F. M, Alexson S, Wolfersdorf M et al. Concentration of Fatty Acid Ethyl Esters in Hair of Alcoholics: Comparison to other Biological State Markers and Self Reported-Ethanol Intake.  Alcohol and Alcoholism 39(1):33-38, January/February 2004.

"The data suggest that CFAEE is a potentially valuable marker of chronic intake of high quantities of ethanol."

Chung W. Type of Alcoholic Beverage and High-risk Drinking: How Risky Is Beer Drinking in Korea?  Alcohol and Alcoholism 39(1):39-42, January/February 2004.

"In Korea, unlike in many western countries, beer is not the highest risk beverage. The relatively high price of beer in Korea is likely to be one influence."

Hao W, Su Z, Liu B et al. Drinking and Drinking Patterns and Health Status in the General Population of Five Areas of China.  Alcohol and Alcoholism 39(1):43-52, January/February 2004.

"The rate of alcohol use was higher in men than in women, and the annual alcohol consumption per capita was higher than that in the 1990s in the selected areas."

Zhu W, Volkow N. D, Ma Y. Relationships between Ethanol-induced Changes in Brain Regional Metabolism and Its  Motor, Behavioural and Cognitive Effects.  Alcohol and Alcoholism 39(1):53-58, January/February 2004.

"These findings suggest that the contrasting effects of alcohol in basal ganglia versus the insula are involved in the perception of ‘feeling drunk’ and that its contrasting effects in cerebellum versus those in frontal and parietal cortices are involved in its motor incoordinating effects."

Anttila P, Jarvi K, Latvala J, Niemela O. Method- dependent Characteristics of Carbohydrate-deficient Transferrin Measurements in the Follow-up of Alcoholics.  Alcohol and Alcoholism 39(1):59-63, January/February 2004.

"The data indicate distinct differences and method-dependent rates of normalization in [carbohydrate-deficient transferrin] assays, possibly reflecting different degrees of transferrin desialylation in the alcoholics. The present findings should be considered in studies on alcohol markers for monitoring abstinence."

Malyutina S, Bobak M, Kurilovitch S, Nikitin Y, Marmot M.  Trends in Alcohol Intake by Education and Marital Status in an Urban Population in Russia between the Mid 1980s and the Mid 1990s.  Alcohol and Alcoholism 39(1):64-69, January/February 2004.

"All indices of alcohol consumption in men increased between the mid 1980s and the mid 1990s."


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