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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 w