bluuebunny/crossref_metadata_2025 huggingface dataset:
Alcohol and Congestive Heart Failure
Authors: Waldenström Anders
Published: May 2006

Ethanol has a definite acute negative inotropic effect (decreased contractility). Also, chronic overuse may lead to decreased contractile function of the heart. The symptoms of congestive heart failure in these patients do not differ from any other cause of congestive heart failure. But, on the other hand, the prognosis quo ad vitam for alcoholics seems to be worse when compared with patients with dilated cardiomyopathy. Whether this is due to a more severe form of disease or difficulties to abstain from alcohol and follow medical prescriptions is, however, not clear. It seems that abstention is effective only up to a certain stage of disease. Ethanol interferes with a number of myocardial metabolic steps and cellular mechanisms. A single key factor for the development of cardiac insufficiency can, however, not be pointed out, although it is well known that ethanol interferes with lipid metabolism and fatty acid composition of sarcolemma, as well as the properties of the membrane function of the sarcoplasmic reticulum. Malnutrition and lack of certain vitamins has also been suggested to be important in the development of congestive heart failure in alcoholics.
The Influence of Alcohol Drinking and Alcohol Use Disorders on Psychiatric Disorders and Suicidal Behavior
Authors: Berglund Mats , Ojehagen Agneta
Published: May 2006

The present review reports on the influence of alcohol drinking and alcohol use disorders on psychiatric disorders and suicidal behaviour. The base of the study was previous reviews of the National Institute on Alcohol Abuse and Alcoholism publication Alcohol and Health in 1993 and by Helgason in 1996. Using a defined search strategy in Medline, another 42 articles from 1994 to 1996 were included in the comorbidity part and 19 in the suicidal part. Epidemio‐logical and clinical studies confirm high comorbidity of substance use disorders and other mental disorders. Alcohol abuse worsens the course of psychiatric disorders. Light to moderate alcohol consumption has no documented positive effect on the course. Levels of risk consumption of alcohol in psychiatric disorders have not been well defined. One‐fifth to one‐third of increased deaths rate among alcoholics is explained by suicide. In countries with high alcohol consumption, the suicide rate is also high and is increasing with total increased alcohol consumption. Comorbidity is common among suicide victims, and substance use disorders is most frequently combined with depressive disorders. Interpersonal loss within 6 weeks before suicide is more often present among alcoholics than nonalcoholic suicide victims.
Alcohol Consumption and Stroke: Benefits and Risks
Authors: Hillborn Matti
Published: May 2006

The complex relationship between alcohol consumption and stroke includes both benefits and risks. Regular light‐to‐moderate consumption of alcohol seems to decrease the risk for ischemic stroke by reducing atherothrombotic events, but the undertying mechanism is still unclear. Recent and current (but not previous) heavy drinking increases the risk for both hemorrhagic and ischemic strokes. Young and middle‐aged men are stricken more often than women or elderly persons, probably because they are more often current heavy drinkers. Alcoholic cardiomyopathy is a cause of cardioembolic brain infarction. Cardiac arrhythmias caused by regular heavy drinking or binge drinking can precipitate thrombus formation and propagate already existing thrombi from the heart. The maintenance of high blood pressure by heavy drinking may promote cerebral arterial degeneration, but the effect of drinking habits on aneurysm formation is not known. Acute increases in systolic blood pressure and/or alterations in cerebral arterial tone could serve as mechanisms triggering hemorrhagic strokes during alcoholic intoxication. We lack studies to show that prevention of heavy drinking can efficiently influence the occurrence of strokes.
Contribution of Carbohydrate Deficient Transferrin to Gamma Glutamyl Transpeptidase in Evaluating Progress of Patients in Treatment For Alcoholism
Authors: Allen John P. , Sillamaukee Pekka , Anton Raymond
Published: May 2006

Eight previous investigations have suggested that conjoint consideration of findings on tests for gamma glutamyl transpeptidase (GGT) and carbohydrate deficient transferrin (CDT) substantially enhances sensitivity of screening for alcohol problems while minimally diminishing specificity. Using results from a large clinical trial, the current study evaluated the two tests singly and in combination as measures of three clinically important treatment outcome criteria: any drinking, at least one day of heavy drinking, and at least three consecutive days of heavy drinking during the past month. When scored by quartile, CDT is slightly better at screening for alcohol problems in males than GGT. However, CDT seems less accurate in females than GGT. Use of the two tests in consort moderately improves the individual test accuracy in predicting drinking status for both genders.
Substance Use, Injury, and Risk‐Taking Dispositions in the General Population
Authors: Cherpitel Cheryl J.
Published: May 2006

Alcohol consumption has been found to be associated with injury c occurrence and with risk‐taking dispositions, and these dispositions, themselves, have been found to be associated with injury. Few studies have analyzed both alcohol consumption and risk‐taking dispositions, or illicit drug use, on risk of injury across all types of injuries. Data on risk perception, risk‐taking/impulsivity, sensation seeking, alcohol and drug use, demographic characteristics, and injury in the last year are reported from the 1995 National Alcohol Survey of 4925 respondents living in households in the 48 contiguous states. Moderate drinking, alcohol treatment, drug use, simultaneous use of alcohol and drugs, and risk‐taking dispositions were all positively associated with reporting an injury. In multiple logistic regression, only risk‐taking dispositions maintained significance when other variables were controlled. In separate regressions by ethnicity, risk‐taking dispositions were significant predictors of injury for whites, whereas none of the variables were significant for blacks or Hispanics. Data suggest that risk‐taking dispositions may be more important predictors of injury than either drinking or drug use variables, but this may vary by ethnicity. Risk‐taking disposition may influence the effectiveness of strategies to reduce alcohol‐related injuries; future research is important, therefore, for informing intervention and prevention efforts.
Alcohol Dependence and Abuse Diagnoses: Concurrent Validity in a Nationally Representative Sample
Authors: Hasin Deborah , Paykin Andrea
Published: May 2006

The Alcohol Dependence Syndrome concept has had a widespread influence on the major nosological classification systems, most recently with its operationalization as DSM‐IV alcohol dependence. Although many studies have provided evidence of the validity of the Alcohol Dependence Syndrome in clinical samples, little validation work has been conducted in general population samples on DSM‐IV alcohol dependence or the distinction of DSM‐IV alcohol dependence from DSM‐IV alcohol abuse. We therefore examined the cross‐sectional validity of DSM‐IV alcohol dependence and abuse in 27,616 household residents who participated in a 1992 national survey on alcohol use disorders. Validity was investigated by testing the association of a set of five “criterion” variables, external to the alcohol diagnostic criteria, with dependence and abuse diagnoses. Results indicated that dependence diagnoses were significantly associated with all criterion variables when compared with those with no diagnosis and also when compared with alcohol abuse. This supported the separation of dependence from abuse. Abuse diagnoses were associated with some, but not all, criterion variables when compared with subjects with no diagnosis. This report replicates many aspects of a similar investigation in a community sample of household residents. Implications for the next steps in research are discussed.
Chronic Ethanol Upregulates NMDA and AMPA, but Not Kainate Receptor Subunit Proteins in Rat Primary Cortical Cultures
Authors: Chandler L. Judson , Norwood Dean , Sutton Greg
Published: May 2006

The present study examined the effects of chronic ethanol exposure on the expression of N‐methyl‐D‐aspartate (NMDA), α‐amino‐3 hydroxy‐5‐methyl‐4‐isoxalone (AMPA) and kainate receptor subunit proteins in rat cortical neuronal cultures grown in media containing 2 mM (high) or 0.1 mM (low) glutamine. lmmunoblot analysis of NMDA (NR1, NR2A, NR2B, and NR2D), AMPA (GluR1 and GluR2/3), and kainate (GluR6/7) subunit polypeptides in 3‐, 5‐, 8‐, 10‐, and 12 day‐old‐cultures showed that NMDA receptor subunits NR1, NR2A, and NR2B and AMPA receptor subunits GluR2/3 progressively increased as a function of time, whereas levels of NMDA subunit NR2D were high at day 3 and progressively declined to barely detectable levels by day 12. Levels of AMPA subunit GluR1 and the kainate subunit GluR6/7 remained stable throughout the time course. Replacing the culture media with low glutamine media at culture day 5 did not alter the levels of subunit proteins measured at culture days 9 and 13. However, exposure of low glutamine cultures to 100 mM ethanol for 4 days (starting at culture day 9) significantly increased the levels of NMDA receptor subunits (NR1, NR2A, and NR2B) and AMPA receptor subunits (GluR1 and GluR2/3), but had no effect upon kainate receptor subunits (GluR6/7) or the synapse‐associated proteins synapsin I and PSD‐95. In contrast, chronic ethanol did not alter the levels of any of these subunit proteins in cells grown in high glutamine. These data demonstrate that under certain experimental conditions, prolonged exposure to ethanol upregulates NMDA and AMPA receptor subunit proteins, but has no effect upon kainate receptor subunit proteins. Because we have previously shown that acute ethanol can inhibit NMDA and AMPA, but not kainate, receptor function in these cultures, the increase in subunit expression likely reflects an adaptive response to the inhibitory effects of ethanol and suggests that both NMDA and AMPA receptors may play an important role in adaptation of the CNS to chronic ethanol.
A Comparative Evaluation of Substance Abuse Treatment: II. Linking Proximal Outcomes of 12‐Step and Cognitive‐Behavioral Treatment to Substance Use Outcomes
Authors: Finney John W. , Moos Rudolf H. , Humphreys Keith
Published: May 2006

This study examines the linkages in the treatment process chains that are thought to underlie two prevalent approaches to substance abuse treatment, traditional 12‐Step treatment and cognitive‐behavioral treatment. The focus is on the “proximal outcomes” specified by the two treatment approaches and their relation to “ultimate” substance use outcomes assessed at a 1‐year follow‐up. A total of 2687 men who received treatment in 15 Department of Veterans Affairs substance abuse treatment programs were assessed at treatment entry, at or near discharge, and at a 1‐year follow‐up. Based on the results of factor analyses, composite proximal outcomes variables were constructed to assess 12‐Step cognitions, 12‐Step behaviors, cognitive‐behavioral beliefs, substance‐specific coping, and general coping. Correlation analyses indicated that some of the proximal outcome composites assessed at treatment discharge were linked to 1 ‐year outcomes, but the relationships were weak (r= .09 to .15). At follow‐up, the cross‐sectional relationships between the proximal outcome composites and two substance use outcomes were stronger, but still modest in magnitude (r= .16 to .39). The weak predictive findings suggest some mechanism is needed to sustain treatment‐induced change on proximal outcomes so that positive ultimate outcomes can be achieved more frequently. In this regard, participation in continuing care was associated with enhanced maintenance of treatment gains on proximal outcomes. However, the modest cross‐sectional relationships between proximal and substance use outcomes at follow‐up suggest that the theories on which 12‐Step and cognitive‐behavioral substance abuse treatments are based are not sufficiently comprehensive.
A Comparative Evaluation of Substance Abuse Treatment III. Examining Mechanisms Underlying Patient‐Treatment Matching Hypotheses for 12‐Step and Cognitive‐Behavioral Treatments for substance Abuse
Authors: Ouimette Paige Crosby , Finney John W. , Gima Kristian , Moos Rudolf H.
Published: May 2006

This study examined several hypotheses for matching patients to 12‐Step and cognitive‐behavioral (CB) treatments in a multisite evaluation of VA inpatient substance abuse programs. A total of 804 male patients in five 12‐Step programs, and 1069 male patients in five CB programs completed an intake, discharge, and 1‐year follow‐up questionnaire. The findings did not support the notion that certain patient characteristics would differentially predict better outcomes after 12‐Step and CB treatment. This conclusion held when the purest 12‐Step and CB programs were used, and when patients who received the full dose of treatment (i.e., treatment completers) were examined separately. Process analyses of the hypothesized mechanisms underlying the patient‐treatment matching effects did not yield the expected links among patient characteristics, proximal outcomes, and 1‐year outcomes. Our conclusion is that there is no advantage to matching men with substance abuse problems to 12‐Step or CB treatments based on the patient attributes measured here.
Lack of an Allelic Association Between Polymorphisms of the Dopamine D2 Receptor Gene and Alcohol Dependence in the German Population
Authors: Sander Thomas , Ladehoff Murat , Samochowiec Jerzy , Finckh Ulrich , Rommelspacher Hans , Schmidt Lutz G.
Published: May 2006

Our study examined recent claims of an association of theTaqI A1 allele and the functional – 141C Ins allele of the dopamine D2 receptor (DRD2) gene with alcohol dependence. Genotypes of theTaqI A and −141C insertion/deletion polymorphisms were assessed in 196 German nonalcoholic controls and 310 German alcohol‐dependent subjects, including two more homogeneous subgroups selected by either a history of parental alcoholism (n= 108) or by a history of severe physiological alcohol withdrawal symptoms (n= 99). We found no association between any of the biallelic variants or the A1/Ins haplotype and alcohol dependence (p> 0.05). Our present association results failed to replicate evidence that either theTaqI A1 allele or the functional Ins allele or the A1/Ins haplotype of theDRD2gene confers vulnerability to alcohol dependence in the German population.
Comparison of Ethanol Metabolism in Male and Female Cynomolgus Macaques (Macaca fascicularis)
Authors: Green K. L. , Szeliga K. T. , Bowen C. A. , Kautz M. A. , Azarov A. V. , Grant K. A.
Published: May 2006

The physiological consequences of drinking ethanol differ among men and women; however, the biological basis of this gender difference is unknown. Our study characterized sex‐related blood ethanol concentration (BEC) 60 min postethanol administration and ethanol elimination rates in male and female monkeys and across the phases of the menstrual cycle. Subjects were male (n= 4) and female (n= 4) cynomolgus monkeys (Macaca fascicularis) with a history of ethanol exposure and maintained at a lean body weight by food restriction. On three separate occasions, each monkey was administered 1.0 g/kg ethanol intragastrically and blood samples (20 μl) were collected every 60 min over a 5‐hr period. For females, three phases of the menstrual cycle were determined by the presence of menses and plasma progesterone levels. There was no effect of menstrual cycle on mean 60 min BECs or mean rates of elimination. Mean BECs 60 min after 1.0 g/kg ethanol were: males = 86 mg/dl (± 2; n= 4) and females = 82 mg/dl (± 5; n= 4). There was no effect of sex on the highest BEC measured, which occurred at the 60 min time point in all subjects. Female monkeys did have faster average rates of ethanol elimination [34 ± 2 (mg/dl)/hr] compared with males [23 ± 1 (mg/dl)/hr). The sex differences in metabolism of ethanol found with the macaque monkey model correlates well with human subject studies and suggests this is an appropriate model to further explore gender differences in response to ethanol.
Ethanol Induces Cell Death and Cell Cycle Delay in Cultures of Pheochromocytoma PC12 Cells
Authors: Luo Jia , West James R. , Cook Robert T. , Pantazis Nicholas J.
Published: May 2006

Animal models have clearly established that ethanol exposure can deplete neurons in the developing nervous system. However, the mechanism by which ethanol reduces cell number is unclear. In our study, cultures of pheochromocytoma cells, a neuronal‐like cell line, were maintained in media, which supported cell proliferation. Although cell numbers continued to increase in the presence of ethanol, this increase was partially inhibited by ethanol exposure. This inhibitory effect was concentration and duration dependent. Cell proliferation was still partially inhibited after removal of ethanol, but this inhibition was temporary and disappeared after a 24‐hr recovery period in ethanol‐free conditions. Further study indicated that ethanol partially inhibited the increase in cell numbers by two mechanisms: (1) studies with vital stains indicated that ethanol induced cell death; (2) experiments using synchronized pheochromocytoma cell cultures showed that ethanol can induce cell cycle delay, thereby lengthening the doubling time of the cells. Analysis by flow cytometry indicated that with ethanol exposure, the cells accumulated in the G1 phase of the cell cycle. Our results suggest that in the developing nervous system, ethanol may limit the numbers of proliferating, neuronal precursor cells by two simultaneous mechanisms, cell death and cell cycle delay.
Effects of Alcohol Use and Gender on the Dynamics of EKG Time‐Series Data
Authors: DePetrillo Paolo B. , White Kenneth V. , Liu Ming , Hommer Daniel , Goldman David
Published: May 2006

Hurst analysis of EKG data obtained from a population of alcoholic (n= 13) and nonalcoholic (n= 48) subjects was undertaken. Potential subjects (n= 120) were screened using the Schedule for Affective Disorders and Schizophrenia and Structured Clinical Interview for DSM‐III instruments. Data from subjects with a diagnosis of current alcohol dependence were analyzed. Subjects with diagnoses such as major depression, bipolar disorder or schizophrenia (Axis I diagnoses), or personality disorders (Axis II diagnoses) were excluded from analysis. Subjects undergoing testing were free of alcohol and illicit drugs. Alcoholic subjects had no clinical evidence of alcohol withdrawal symptoms at the time of testing. EKG data were obtained with eyes open or with eyes closed. Approximately 3.5 min of data were obtained for each condition. Alcoholic subjects had less complex heart rate dynamics as evidenced by higher values ofH= 0.18 ± 0.05 (mean ± SEM), compared with healthy comparison subjects with H= 0.09 ± 0.02, p <0.014 for the eyes closed condition, and H= 0.17 ± 0.05 (mean ± SEM) compared with healthy comparison subjects with H= 0.07 ± 0.02, p < 0.011 for the eyes open condition. A gender effect was seen, with female subjects showing evidence of more complex heart rate dynamics than male subjects.
Acute Effect of Alcohol on Estradiol, Estrone, Progesterone, Prolactin, Cortisol, and Luteinizing Hormone in Premenopausal Women
Authors: Sarkola Taisto , Mäkisalo Heikki , Fukunaga Tatsushige , Eriksson C. J. Peter
Published: May 2006

Background: Heavy alcohol consumption is associated with menstrual irregularities, including anovulation, luteal‐phase dysfunction, recurrent amenorrhea, and early menopause. In addition, moderate to heavy alcohol intake has been found to increase the risk of spontaneous abortions and breast cancer. These adverse effects could at least in part originate from alcohol‐mediated changes in hormone levels.

Method: The acute effect of alcohol on the hormone balance in women using oral contraceptives (OC+) and also in nonusers (OC‐), was evaluated in 30 OC– and 31 OC+ subjects, representing the whole period of the menstrual cycle. It was also evaluated in 40 OC‐ and 47 OC+ subjects during the midcycle phase and in 10 OC+ subjects with unknown cycle phase.

Result: We found that among subjects who used oral contraceptives, estradiol levels increased and progesterone levels decreased after intake of alcohol (0.5 g/kg). No dose effect (0.34‐1.02 g/kg) on progesterone was observed in a substudy on 10 OC+ subjects. With regard to estrone levels, no effect was observed, although a significant increase was found in the estradiol‐to‐estrone ratio. Among subjects not using oral contraceptives, progesterone levels decreased after intake of alcohol (0.5 g/kg). No effect was found in estradiol, estrone, or the estradiol‐to‐estrone ratio during midcycle in this study group. A transient elevating effect of alcohol (0.5 g/kg) on prolactin levels was observed in both study groups. We found that alcohol (0.5 g/kg) had no significant effect on luteinizing hormone (LH) levels among subjects not using oral contraceptives, and observed a decline among subjects using oral contraceptives at midcycle.

Conclusions: We suggest that the estradiol and progesterone effects are related to decreased steroid catabolism, resulting from the alcohol‐mediated increase in the hepatic NADH‐to‐NAD ratio. The transient effect on prolactin levels may reflect acute changes in opioid and dopamine levels in the hypothalamus. The present findings regarding female sex steroids may be of relevance in the association between moderate to heavy alcohol consumption and the development of breast cancer.
Examination of Judgments of Drunkenness, Binge Drinking, and Drunk‐Driving Tendencies in Teens With and Without a Family History of Alcohol Abuse
Authors: Turrisi Rob , Wiersma Kimberly
Published: May 2006

Background:The present study examined judgment processes of individuals with and without a family history of alcohol abuse. Despite the alarming statistics involving alcohol‐related consequences in this population, very little is known about what judgment processes they use or how beneficial these processes are at preventing intoxication and alcohol‐related consequences.

Methods: Participants were 270 individuals, 16‐18 years old, screened on the basis of the history of family alcohol abuse. Individuals were asked to (1) make judgments of drunkenness in relation to the legal limits in response to factorially manipulated external cues on number of drinks, time taken to consume, and type of beverage, using the methodology of Jaccard and Turrisi (1987), and (2) answer several questions regarding their alcohol‐related behaviors.

Results: Our results indicated that individuals with a positive family history of alcohol abuse were more likely to make judgmental errors and underestimate their drunkenness relative to individuals without a positive family history of alcohol abuse. Moreover, the errors in judgments were more pronounced in situations involving moderate to heavy alcohol consumption. Finally, family history was found to moderate the relationship between underestimation errors and drinking, and drinking and driving tendencies. For individuals with a positive family history of alcohol abuse, the more they tended to underestimate their drunkenness, the more likely they were to binge drink and drive after drinking.

Conclusions: The findings suggest that judgmental errors tend to be an important process variable in the relationship between family history and alcohol‐related behavioral tendencies. The findings are discussed with respect to potential behavioral antecedents (e.g., student binge drinking) and development of prevention programs geared toward training students to make more accurate judgments, using external cues.
Association Between Drinking‐Related Antisocial Behavior and a Polymorphism in the Serotonin Transporter Gene in a Japanese Population
Authors: Ishiguro H. , Saito T. , Akazawa S. , Mitushio H. , Tada K. , Enomoto M. , Mifune H. , Toru M. , Shibuya H. , Arinami T.
Published: May 2006

Background: Involvement of the serotoninergic system (S/S) in alcoholism has been suggested in both mice and humans. Previous studies have suggested the S/S genotype of the serotonin transporter gene promoter polymorphism to be associated with severe alcohol dependence marked by severe withdrawal symptoms. It has also been associated with alcoholics who exhibit a dissocial personality disorder.

Methods: We examined the polymorphism in 166 Japanese alcoholics who experienced withdrawal seizure or delirium and 290 Japanese controls.

Results: The S/S genotype was not increased in the patients. Exploratory analyses showed significantly less frequent S allele and S/S genotype frequencies in the alcoholics with a history of drinking‐related arrests than in the controls (p= 0.009 and p= 0.03, respectively), perhaps reflecting previously reported harm avoidance personality traits associated with S/S. Alcoholics with the L allele had a significantly earlier onset of alcohol dependence than those with the S/S genotype (p= 0.01).

Conclusions: The present study failed to provide supportive evidence for an association of the S/S genotype with severe alcoholism marked by physical withdrawal symptoms or with antisocial behaviors among the Japanese. Although our data support involvement of the central serotoninergic system in some types of alcoholism, the potential association findings of this study emerged as only exploratory and, therefore, should be understood as tentative until replicated in other studies.
Putative Hemochromatosis Gene Mutations and Alcoholic Liver Disease With Iron Overload in Japan
Authors: Sohda Tetsuro , Takeyama Yasuaki , Irie Makoto , Kamimura Seiichiro , Shijo Hiroshi
Published: May 2006

It is well known that alcoholic liver disease is associated with iron overload. To study the role of hemochromatosis gene mutations on the pathogenesis of alcoholic liver disease (ALD), we have analyzed C282Y and H63D mutations on the chromosomes obtained from 95 Japanese alcoholics. Patients were divided in two groups [i.e., 64 alcoholic patients with liver damage (group I) and 31 alcoholics without liver damage (group II)]. In group I, biochemical examinations showed that serum levels of iron and ferritin were significantly high, and unsaturated iron binding capacity levels were low, compared with those of group II. An analysis by means of allele‐specific polymerase chain reaction demonstrated that C282Y mutation was not observed in both groups I and II. H63D mutation was observed in only two heterozygotes of group I and in one heterozygote of group II. Results could not indicate the relationship between ALD and these mutations. We speculate that other causes of iron overload may exist in ALD with iron overload.
Superoxide Anion Release Into the Hepatic Sinusoid After an Acute Ethanol Challenge and Its Attenuation by Kupffer Cell Depletion
Authors: Yokoyama Hirokazu , Fukuda Masahiko , Okamura Yukishige , Mizukami Takeshi , Ohgo Hideki , Kamegaya Yoshitaka , Kato Shinzo , Ishii Hiromasa
Published: May 2006

Superoxide anion release into the hepatic sinusoids and subsequent damage to the endothelial cells of the hepatic sinusoids after ethanol challenge was examined. A 250 mg/kg body weight/hr dose of ethanol was given to rats for 3 hr, and superoxide anion release into the hepatic sinusoids was examined in a liver perfusion model using the cytochrome c method. Ethanol treatment resulted in superoxide anion release into the hepatic sinusoids (0.20 ± 0.01 vs. 0.12 ± 0.02 o.d., p< 0.05) and an increase in the purine nucleoside phosphorylase/alanine aminotransferase ratio in the liver perfusate, a marker of damage to the endothelial cells of the hepatic sinusoids (0.003 ± 0.002 vs. 0.008 ± 0.002; p < 0.05). Tumor necrosis factor‐alpha was not detectable in either group, and there were no significant differences in the population of hepatic macrophages, leukocytes, or Kupffer cells between the two groups. To clarify the role of Kupffer cells in the mechanism, 10 mg/kg of body weight of gadolinium chloride was given to rats twice, 24 hr apart, resulting in depletion of ED2‐positive cells from the hepatic lobules. The superoxide anion release after the ethanol challenge was significantly attenuated in the Kupffer cell‐depleted rats, compared with the controls (0.14 ±0.02;p <0.05, compared with ethanol alone). The change was associated with a significant decrease in the purine nucleoside phosphorylase/alanine aminotransferase ratio in the liver perfusate (0.004 ± 0.002; p < 0.05, compared with ethanol alone). Ethanol causes superoxide anion release into the hepatic sinusoid and subsequent damage to the sinusoidal endothelial cells. These changes were reduced by Kupffer cell depletion. This supports the view that Kupffer cell depletion has a protective effect on ethanol‐induced liver injury.
Fetal Associative Learning Mediated Through Maternal Alcohol Intoxication
Authors: Abate Paula , Pepino Marta Yanina , Dominguez Héctor Daniel , Spear Norman E. , Molina Juan Carlos
Published: May 2006

Background:

The aim of the present study was to analyze whether alcohol as an unconditioned stimulus is capable of supporting associative learning in near‐term fetuses.

Methods:

In experiment 1, we determined pharmacokinetic profiles of alcohol and of an aromatic substance (cineole) in amniotic fluid and maternal blood during late gestation. The results obtained through gas chromatographic analysis allowed a second experiment in which we explicitly paired peak levels of cineole with peak levels of alcohol in amniotic fluid and blood, by intragastrically administering cineole and ethanol to the dams during gestational days 17 through 20 (paired condition). Control groups were dams given cineole 4 hr before commencement of an acute state of alcohol intoxication (long‐delay group) or were only exposed to water administrations (water control group). The progeny were evaluated during postnatal day 16 in terms of behavioral responsiveness to intraorally infused solutions (cineole or alcohol presented in milk vehicle, or milk alone).

Results:

Mouthing responsiveness to cineole was strongly affected by the nature of prenatal treatments. Pups in the paired prenatal condition mouthed significantly less than did long‐delay and water controls. Physical and behavioral measures allowed us to reject the possibility that these effects were due to teratogenic effects of alcohol during late gestation.

Conclusions:

These results indicate that before birth, rat fetuses are capable of acquiring associative memories supported by the unconditioned properties of alcohol. This associative memory can be expressed during infancy through a significant reduction in mouth movements in the presence of the specific orosensory cue explicitly paired with alcohol interoceptive effects in utero.
The Value of CAGE, CUGE, and AUDIT in Screening for Alcohol Abuse and Dependence Among College Freshmen
Authors: Aertgeerts B. , Buntinx F. , Bande‐Knops J. , Vanderrneulen C. , Roelants M. , Ansoms S. , Fevery J.
Published: May 2006

Background:

This study attempted to (1) determine the prevalence of alcohol problems in college freshmen, (2) assess the performance of both the CAGE and the Alcohol Use Disorders Identification Test (AUDIT) questionnaires in this population, and (3) assess the possibility of improving the CAGE and/or AUDIT.

Methods:

A sample of 3564 consecutive college freshmen, with a mean age of 18 years, at the Catholic University of Leuven, (Belgium) completed, during a cross‐sectional study, a questionnaire assessing drinking behavior and identifying students at risk as defined by DSM‐IV criteria. The questionnaire also included the CAGE questionnaire and the AUDIT. Calculations of sensitivity, specificity, negative predictive value, positive predictive value, likelihood ratios, and receiver operating characteristic curves for different scores of the CAGE and the AUDIT were performed, using DSM‐IV criteria as the reference standard.

Results:

The area under the receiver operating characteristic curve of the CAGE and the AUDIT was 0.76 and 0.85, respectively. The cutoff score of 1 for the CAGE was associated with a sensitivity of 42%, a specificity of 87%, a positive predictive value of 36%, and a negative predictive value of 90%. A score of 6 or more for the AUDIT gave a sensitivity of 80%, a specificity of 78%, a positive predictive value of 37%, and a negative predictive value of 77%. These results were related with a prevalence of 14.1% of alcohol problems. Replacing one question of the CAGE by “often driving under the influence'’resulted in the CUGE (acronym for “cut down, under influence, guilty feelings, and eye opener”), with an area under the curve of 0.96, a positive likelihood ratio of 8.7, and a negative likelihood ratio of 0.04.

Conclusions:

Prevalence of alcohol problems in college students is confirmed to be high. When screening for alcohol problems in a college freshmen population, one question seems extremely important. The newly constructed CUGE questionnaire may improve screening efforts in students, compared with existing questionnaires.
Ability of Baclofen in Reducing Alcohol Intake and Withdrawal Severity: I—Preclinical Evidence
Authors: Colombo Giancarlo , Agabio Roberta , Carai Mauro A.M. , Lobina Carla , Pani Marialaura , Reali Roberta , Addolorato Giovanni , Gessa Gian Luigi
Published: May 2006

Background:

The similarities between the pharmacological effects of the γ‐aminobutyric acid receptor agonist, baclofen, and the alcohol‐substituting agent, γ‐hydroxybutyric acid, led us to investigate whether baclofen was capable of reducing (a) ethanol withdrawal syndrome in ethanol‐dependent rats and (b) voluntary ethanol intake in ethanol‐preferring rats.

Methods:

In experiment 1, Wistar rats were rendered physically dependent on ethanol by the repeated administration of intoxicating doses of ethanol for 6 consecutive days. Baclofen was acutely administered intraperitoneally at doses of 10, 20, and 40 mg/kg. In experiment 2, baclofen (0, 2.5, 5, and 10 mg/kg, intraperitoneally) was administered once a day for 14 consecutive days to ethanol‐preferring sP rats that had continuous access to ethanol (10%, v/v) and water under the two‐bottle free choice regimen.

Results:

In experiment 1, baclofen dose‐dependently decreased the intensity of ethanol withdrawal signs; furthermore, 20 mg/kg of baclofen protected from audiogenic seizures in ethanol‐withdrawn rats. In experiment 2, baclofen selectively and dose‐dependently reduced voluntary ethanol intake; a compensatory increase in water intake left total fluid intake virtually unchanged.

Conclusions:

These results are in close agreement with those of a preliminary clinical study and suggest that baclofen may constitute a novel therapeutic agent for alcoholism.
Ability of Baclofen in Reducing Alcohol Craving and Intake: II—Preliminary Clinical Evidence
Authors: Addolorato Giovanni , Caputo Fabio , Capristo Esmeralda , Colombo Glancarlo , Gessa Gian Luigi , Gasbarrini Giovanni
Published: May 2006

Background:

Accumulating evidence shows the efficacy of the γ‐aminobutyric acid (GABAB) receptor agonist baclofen in reducing alcohol intake in rats, but no studies have been performed in alcoholics. In the present preliminary study we investigated the effect of short‐term baclofen administration on craving for alcohol, ethanol intake, and abstinence from alcohol in alcoholic individuals.

Methods:

Ten male current alcoholic individuals were admitted to the study. Baclofen was orally administered for 4 weeks, at a dose of 15 mg/day refracted in three times per day for the first 3 days, with the dose increased to 30 mg/day for the remaining 27 days. Each subject was checked as an outpatient every week for the 4 weeks; at each visit (T0‐T4) craving level was evaluated by the Alcohol Craving Scale (ACS), and abstinence from alcohol was assessed based on the individual's self‐evaluation, family member interview, and the main biological markers of alcohol abuse. A self‐reported alcohol intake was recorded as the mean number of standard drinks consumed per day.

Results:

Nine subjects completed the study; of these, two subjects continued to drink alcohol although they substantially reduced their daily drinks in the first week of treatment, whereas seven maintained abstinence throughout the experimental period. Craving was significantly reduced from the first week of the drug administration (p < 0.01) and remained so throughout the entire treatment period. Participants also reported that obsessional thinking about alcohol disappeared. Values of γ‐glutamyltranspeptidase, alanine aminotransferase, and mean cellular volume significantly decreased by the end of the study. Tolerability was fair in all participants; headache, vertigo, nausea, constipation, diarrhea, abdominal pain, hypotension, increased sleepiness, and tiredness were present as side effects in the first stage of the treatment. No participants showed craving for the drug.

Conclusions:

With the limitations of the low number of individuals evaluated and the open design, this preliminary clinical study supports the preclinical evidence on the effect of baclofen in reducing alcohol intake. The anticraving properties of the drug suggest a possible role of baclofen in the treatment of individuals with alcohol problems.
Neurophysiological Findings and Drinking Levels in High‐Alcohol‐Drinking (HAD) and Low‐Alcohol‐Drinking (LAD) Rats
Authors: Slawecki C. J. , Betancourt M. , Li T‐K. , Ehlers C. L.
Published: May 2006

Background:

Specific neurophysiological profiles, such as reduced P300 amplitude or altered spectral power in the EEG, have been associated with a risk for alcoholism in several clinical populations. In certain rodent models, high versus low alcohol consumption is associated with similar neurophysiological differences. For example, alcohol‐preferring (P) rats have increased spectral power and decreased P300 amplitudes compared with alcohol‐nonpreferring (NP) rats. In the present study, the neurophysiological profiles of high‐alcohol‐drinking (HAD) and low‐alcohol‐drinking (LAD) rats were assessed (1) to determine if their electrophysiological profiles are similar to P and NP rats and (2) to examine the relationship of these neurophysiological indices to ethanol drinking.

Methods:

Ethanol‐naïve HAD and LAD rats were implanted with cortical and amygdalar recording electrodes. Baseline EEG and event‐related potentials (ERPs) then were assessed. Subsequently, all rats were trained to self‐administer ethanol by using a sucrose‐substitution procedure.

Results:

Baseline EEG and ERP (i.e., pre‐ethanol exposure) were assessed based on line (HAD versus LAD) and actual ethanol consumption (high drinkers versus low drinkers). At baseline, ethanol‐naïve HAD rats displayed significantly greater power in the cortical EEG and decreased amygdala N1 ERP amplitude compared with ethanol‐naïve LAD rats. Similar EEG and ERP profiles have been observed when P and NP rats are compared. No differences in P300 between lines were observed, but high‐drinking rats, independent of line, had significantly decreased P300 amplitude in the amygdala compared with low‐drinking rats.

Conclusions:

These data suggest there are some similarities in EEG and ERP profiles of P and HAD rats compared with NP and LAD rats. Furthermore, the data suggest that decreased P300 amplitude in the amygdala is associated with increased limited access ethanol drinking.
Efficacy of Dexfenfluramine in the Treatment of Alcohol Dependence
Authors: Romach Myroslava K. , Sellers Edward M. , Kaplan Howard L. , Somer Gail R. , Gomez‐Mancilla Baltazar
Published: May 2006

Background:

A substantial body of evidence supports a role for serotonin in modulating alcohol intake, which suggests that this neurotransmitter represents a promising target for pharmacotherapy development for alcohol use disorders. Dexfenfluramine, a serotonin releaser and reuptake inhibitor, decreases alcohol self‐administration by rats. Its greater potency and several mechanisms of action suggest it should be more effective in treating alcohol dependence than drugs that only inhibit serotonin reuptake.

Methods:

We conducted an 11 week, randomized, double‐blind trial that compared oral placebo and dexfenfluramine 7.5, 15, 22.5, and 30 mg bid in 136 alcohol‐dependent patients. A brief behavioral intervention was offered concurrently.

Results:

The majority of subjects were male (72%), and the age of the group was 44 ± 11 years (mean ± SD). Both placebo‐ and drug‐treated groups significantly reduced alcohol consumption compared with baseline (a 55% decrease in mean drinks per day; p < 0.01), but there were no significant differences between drug and placebo groups or dose effects for most outcome measures.

Conclusions:

Our results with dexfenfluramine are further evidcnce that serotonergic medications on their own do not significantly reduce alcohol consumption in alcohol‐dependent individuals. Combination pharmacotherapy with agents that act on different receptors or neurotransmitter systems (e.g., naltrcxone plus dexfenfluramine) may be one way to enhance serotonergic effects on drinking behavior and should be considered in future medication development clinical trials.
Test Characteristics of Carbohydrate‐Deficient Transferrin and γ‐Glutamyltransferase in Alcohol‐Using Perimenopausal Women
Authors: van Pelt Johannes , Leusink Geraline L. , van Nierop Peter W.M. , Keyzer Jules J.
Published: May 2006

Background:

The application of biochemical markers to detect heavy alcohol use in women has shown disappointing results until now. We evaluated carbohydrate‐deficient transferrin (CDT) by the CDTcct® method and γ‐glutamyltransferase (GGT) in a large cohort of alcohol‐using perimenopausal women studied primarily for osteoporosis.

Methods:

CDT and GGT were measured in 431 women aged 46 to 54 years, who were selected from a large cohort (n= 8503) of pre‐, peri‐, and postmenopausal women. Their alcohol intake was known from questionnaires and face‐to‐face interviews. Three groups were constructed for statistical analysis: those drinking on average less than 7 alcoholic drinks per week (n= 103), those drinking 7 to 34 per week (n= 280), and those drinking at least 35 per week (n= 48).

Results:

The mean values of CDT and GGT of the three groups increased with an increasing alcohol intake, but there was a poor correlation between CDT and GGT in the complete study group (r= 0.3). The specificities of CDT and GGT were comparable, 83% and 78%, respectively. The sensitivities for CDT and GGT were 30% and 50%, respectively. A logistic regression model could assign, overall, 77% of the women correctly in relation to their alcohol intake: 43% of the women drinking at least 35 drinks per week and 92% of the women drinking less than 7 drinks per week.

Conclusions:

The test characteristics of both GGT and CDT are not good enough to be used as biochemical markers for detecting heavy alcohol use in women. The use of a logistic regression model offers an advantage, because both numeric values of CDT and GGT are taken into account instead of arbitrary cutoff values.
Alcohol and the Continuation of Early Marital Aggression
Authors: Quigley Brian M. , Leonard Kenneth E.
Published: May 2006

Background: Husband alcohol use has frequently been found to be related to husband‐to‐wife marital violence. Research has demonstrated a prospective link between husband alcohol use before marriage and husband‐to‐wife aggression in the first year of marriage. The present study examined the relationships of husband violence, marital conflict, and couple's alcohol use in the first year of marriage to husband‐to‐wife marital violence in the second and third years of marriage.

Methods: Newlywed couples were recruited at the time of marriage and were interviewed regarding alcohol use and experience with violence before marriage, 1 year after marriage, and 3 years after marriage.

Results: Year l violence was predictive of subsequent marital violence. Husband and wife drinking patterns in the first year of marriage interacted to predict violence in later years. The most violence in subsequent years occurred in couples where the husband was a heavy drinker and the wife was not. Husbands who were violent in year 1 were more likely to be violent in later years. When no violence occurred in the first year, frequent use of verbal aggression in year 1 was predictive of violence in subsequent years.

Conclusions: The predictive value of husband drinking patterns for subsequent violence extends beyond the transition to marriage. The fact that husband and wife alcohol use interacted to predict future aggression suggests that the relationship between husband alcohol use and marital violence is not spurious nor the result of conflict and violence promoting alcohol use. The findings may reflect multiple instances of acute intoxication and/or alcohol‐related stress and conflict within the relationship, both of which may increase the likelihood of aggression.
Ethanol Inhibition: The Humoral and Cellular Immune Response to Hepatitis C Virus NS5 Protein After Genetic Immunization
Authors: Encke J. , Wands J.R.
Published: May 2006

Background: The combination of chronic hepatitis C virus (HCV) and ethanol may increase viral replication, impair cellular immunity, and result in severe and progressive liver disease. Because HCV nonstructural proteins play a major role in viral elimination, we examined the cellular and humoral immune responses after genetic immunization against NS5 in a chronic ethanol mouse model.

Methods: Mice were fed an ethanol or isocaloric pair‐fed control liquid diet and were immunized with HCV NS5‐expression plasmid.

Results: The humoral and cellular arms of the immune system were significantly impaired in ethanol‐fed mice. Abstinence partially reversed the inhibitory effects on antibody levels and the CD4+ proliferative immune response but did not restore the CD8+ cytotoxic T‐cell response to this HCV nonstructural protein. Furthermore, we determined whether murine interleukin‐2 coadministration with the NS5 expression plasmid would reverse the inhibitory effects of chronic ethanol consumption; again, partial restoration was observed for B‐cell and CD4+ T‐cell activity, but not for cytotoxic T cells.

Conclusions: These results suggest that the high rate of chronic HCV infection in alcoholics may be due to ethanol's effects on antiviral immune responses.
Discriminative‐Stimulus Effects of Triazolam in Light and Moderate Drinkers
Authors: Rush Craig R. , Kelly Thomas H. , Fillmore Mark T. , Hays Lon R.
Published: May 2006

Background:The results of previous laboratory experiments with humans suggest that light and moderate drinkers respond differentially to the effects of benzodiazepines. The aim of this study was to further assess the behavioral effects of a benzodiazepine in light and moderate drinkers.

Methods:To accomplish this aim, 12 volunteers (6 light drinkers and 6 moderate drinkers) learned to discriminate 0.375 mg of triazolam, a triazolobenzodiazepine hypnotic. After they learned this discrimination, a test‐of‐novel‐doses phase was conducted in which a range of doses of triazolam (0, 0.06, 0.125, 0.25, and 0.375 mg) was tested in both groups of volunteers. The subject‐rated and performance‐impairing effects of triazolam were assessed concurrently.

Results:There was not a significant difference between the groups in terms of the number of trials needed to learn the discrimination, nor did the proportion of light and moderate drinkers who learned to accurately discriminate 0.375 mg of triazolam differ significantly. The discriminative‐stimulus, subject‐rated, and performance‐impairing effects of triazolam were an orderly function of dose but did not differ across the light and moderate drinkers.

Conclusions:Future studies should examine the discriminative‐stimulus effects of a lower dose of triazolam (e.g., 0.25 mg) in light and moderate drinks or use a fading procedure to determine differences in terms of the lowest discriminable dose.