bluuebunny/crossref_metadata_2025 huggingface dataset:
Evidence for Reduced Dopamine D2 Receptor Sensitivity in Postwithdrawal Alcoholics
Authors: Farren Conor K. , Clare Anthony W. , Ziedonis Douglas , Hammeedi Faiq A. , Dinan Timothy G.
Published: April 2006

Dopamine D2 receptor sensitivity was assessed in the postwithdrawal period in alcoholics. Growth hormone (GH) responses to dopamine D2 agonist bromocriptine were measured in eight DSM‐III‐R alcohol‐dependent subjects who were 2 weeks or more postalcohol withdrawal. Their responses were compared with eight nonalcoholic controls. After an overnight fast, each subject received 1.25 mg of bromocriptine orally, and serial samples of GH were taken over a 3‐hr period. There was a significantly blunted delta GH response (mean ± SE) in the alcoholic group, 2.3 mU/liter (±1.4) relative to controls, 7.7 mU/liter (±1.2) (t= 2.96, df= 14, p= 0.01). There was a significantly blunted peak GH response (mean ± SE) in the alcoholic group, 5.36 mU/liter (±2.1) relative to controls, 9.04 mU/liter (±5.0). This difference also reached statistical significance (t= 2.32, df= 14, p= 0.035). A repeated‐measures ANOVA yielded a significant within‐subjects effect of time [F(4,54) = 4.08, p= 0.0057], a significant with‐in‐subjects effect of group [F(1,14) = 5.6, p= 0.0329], and an almost significant group x time interaction [F(4,54) = 2.45, p= 0.056]. This result implies a relative dopamine D2 receptor subsensitivity in alcoholics in the postwithdrawal period.
Carbohydrate‐Deficient Transferrin in Alcohol and Nonalcohol Abusers with Liver Disease
Authors: Meregalli Maurizio , Giacomini Valter , Lino Silvana , Marchetti Luciano , DeFeo Tullia , Cappellini M. Domenica , Fiorelli Gemino
Published: April 2006

Carbohydrate‐deficient transferrin (CDT) has been demonstrated to be a marker of prolonged heavy alcohol consumption. We compared this marker with γ‐glutamyltranspeptidase (GGT) and mean corpuscular volume (MCV) in alcohol and nonalcohol abusers with liver disease. Our results confirm that the sensitivity of CDT in alcoholics is high, although lower than that of GGT and MCV; however, the specificity of CDT was higher than that of the other two markers. This finding supports the notion that CDT is only partially influenced by the presence of liver damage, whereas increases of GGT and MCV are greatly affected by several factors, including liver damage and drugs. Moreover, we observed that the sensitivity and the specificity of CDT were greater than those of GGT and MCV in younger drinkers.
Neonatal Diagnosis of Fetal Alcohol Syndrome: Not Necessarily a Hopeless Prognosis
Authors: Ernhart Claire B. , Greene Tom , Sokol Robert J. , Martier Susan , Boyd Thomas A. , Ager Joel
Published: April 2006

A neonatal examination for fetal alcohol syndrome (FAS) should promote the guidance of parents, the planning of remediation for affected children, and the collection of prevalence data. A blinded examination of FAS characteristics conducted as part of a large prospective study of disadvantaged alcohol‐exposed infants identified eight neonates who met the published criteria for FAS. These children were followed through the preschool years with a blinded assessment protocol. Seven of these children were found to have no impairment in cognitive and language development, when compared with their peers, and to be of average size. The one child who was mentally and growth retarded at follow‐up who had been diagnosed as FAS might not have been diagnosed FAS using clinical criteria (as opposed to blinded research criteria), because his mother provided in‐pregnancy reports of only low alcohol intake; she later acknowledged drinking an average of over 21 drinks/week during the pregnancy. The findings are positive in that they provide hope for children who present FAS at birth, although concern with adverse outcomes is certainly not dispelled. In particular, the possibility of later‐emerging impairment in more complex tasks is not ruled out.
Specific Impairments in Self‐Regulation in Children Exposed to Alcohol Prenatally
Authors: Kodituwakku P. W. , Handmaker N. S. , Cutler S. K. , Weathersby E. K. , Handmaker S. D.
Published: April 2006

The present study utilizes a conceptual framework derived from theories of cognition to explain the pattern of behavioral and learning problems observed in subjects with fetal alcohol syndrome (FAS) and fetal alcohol effects (FAE). Based on a modern interpretation of Luria's theory of self‐regulation, this study used a neuropsychological test battery to compare 10 subjects (mean age = 13 years) having FAS/FAE with 10 control subjects (mean age = 12 years and 9 months). Subjects with FAS/FAE were relatively high functioning and did not significantly differ from controls with respect to receptive vocabulary. However, those with FAS/FAE exhibited greater difficulty than controls on tasks that involved the manipulation of information and goal management in working memory (e.g., Planning, Controlled Oral Word Association, etc). Both groups performed equally well on some tasks that demanded rule learning (Delayed Response) and response inhibition (Go‐No‐Go). The above impairments were interpreted to be reflective of selective rather than generalized disruptions of neural networks that subserve working memory.
Effects of Ethanol on Cellular Immunity to Facultative Intracellular Bacteria
Authors: Jerrells Thomas R. , Sibley Don
Published: April 2006

Alcohol abuse has been associated with an increase in infectious diseases caused by pathogenic and opportunistic microorganisms. Study results obtained from this laboratory and other laboratories have shown that consumption of large amounts of ethanol is associated with numerous changes in the immune system. The purpose of this article is to report findings obtained from this laboratory, as well as review those obtained from other laboratories, from experiments designed to evaluate the effects of ethanol on various components of antimicrobial host‐defense mechanisms. The effects of ethanol on various aspects of immunity obtained with the use of in vivo and in vitro model systems are reviewed as they pertain to antimicrobial defenses. All current data would support the suggestion that ethanol affects both the development of an antigen‐specific immune response and the effector mechanisms of the cellular immune response. Findings obtained from animal models show that ethanol prevents the formation of granulomas in infected tissues, perhaps by inhibiting the response of macrophages to T‐cell cytokines. Data obtained from this laboratory also support the suggestion that the inability of the immune system to control the intracellular growth of microorganisms results in an exaggerated inflammatory response that is responsible for at least a part of the tissue damage.
Prevalence of Cholelithiasis According to Alcoholic Liver Disease: A Possible Role of Apolipoproteins AI and AII
Authors: Poynard Thierry , Lonjon Isabelle , Mathurin Philippe , Abella Annie , Musset Dominique , Bedossa Pierre , Aubert Alain , Naveau Sylvie , Chaput Jean‐Claude
Published: April 2006

Moderate alcohol intakes decreases the risk of gallstones; in contrast, the prevalence of gallstones is increased in patients with alcoholic cirrhosis. The aims of this prospective study were to assess the prevalence of cholethiasis among drinkers according to the histological severity of liver disease, and to estimate the importance of serum apolipoproteins AI and apolipoprotein All as risk factors for gallstones. Among the 320 drinkers included, 53 patients had cholelithiasis. The prevalence increased (p < 0,0001) from 5% in patients with normal liver (1 of 22) and 6% in patients with steatosis only (3 of 47) to 13% in patients with fibrosis (7 of 54), reaching 27% among patients with biopsy‐proven cirrhosis (28 of 103). Among patients with clinically obvious cirrhosis on whom biopsy was not performed mainly because of the severity of liver disease, the prevalence of cholelithiasis reached a maximum of 46% (6 of 13).

Among drinkers with nonsevere liver disease, patients with cholelithiasis were older (59 ± 9 years, mean ± SD vs. 45 ± 11, p= 0.003) with lower apolipoprotein AI (118 ± 37 vs. 163 ± 45mg/dl;p= 0.002) and apolipoprotein All (30 ± 12 vs. 53 ± 20 mg/dl; p= 0.0002) in comparison with patients without cholelithiasis. These differences persisted after considering by multiple logistic regression analysis, sex, and ideal body weight. Alcohol consumption during the last 5 years was lower in patients with cholelithiasis (83 g/day) in comparison with patients without cholelithiasis (142 g/day; p= 0.04).

Among drinkers with severe liver disease, patients with cholelithiasis were slightly older (56 ± 13 vs. 52 ± 12 years; p= 0.07) and were more often female (46% vs. 29%; p= 0.06). Unconjugated serum bilirubin was also slightly higher (30 ± 43 vs. 19 ± 40 μmol/liter; p= 0.08).

In conclusion, alcohol intake could protect drinkers against cholesterol gallstones as long as apolipoprotein Al and apolipoprotein All secretions are increased. In contrast, heavy ethanol‐induced fibrosis in the liver results in decreased apolipoprotein Al and apolipoprotein All secretions and thus, may promote the occurrence of cholesterol gallstones. These relationships could explain the paradox of decrease gallstones prevalence among moderate drinkers and the high prevalence among alcoholic cirrhotics.
Alcoholism among Four Aboriginal Groups in Taiwan: High Prevalences and Their Implications
Authors: Cheng Andrew T. A. , Chen Wei J.
Published: April 2006

An epidemiological study of alcohol use disorders was conducted on population samples from four aboriginal groups in Taiwan (a total of 993 subjects). The survey involved ethnographic observation and a semistructured psychiatric interview. The interview covered a detailed symptom profile that allowed diagnoses to be made according to different diagnostic criteria. The lifetime prevalences of alcoholism according to the ICD‐10 (research criteria) and the DSM‐III‐R criteria were found to be 42.2–54.7% and 44.2–55.5%, respectively, much higher than the rates found in an earlier study (0.11–0.16%) conducted 40 years ago. Men in all groups were found to have higher prevalences, a lower mean age at onset, and a longer mean duration (except in one group) of alcoholism than women. Differences in the distribution of sociodemographic correlates (age, sex, marital status, education, and ethnicity) of ICD‐10 harmful use of alcohol and alcohol dependence were examined by case‐control analysis with logistic regression. The lifetime prevalences of alcohol use disorders were higher than in recent epidemiological surveys conducted elsewhere. Possible biological and sociocultural explanations for the high prevalence of alcoholism among the study populations are discussed.
The Obsessive Compulsive Drinking Scale: A Self‐Rated Instrument for the Quantification of Thoughts about Alcohol and Drinking Behavior
Authors: Anton Raymond F. , Moak Darlene H. , Latham Patricia
Published: April 2006

It has been suggested that a crucial dimension of alcohol “craving” includes the concept of both obsessive thoughts about alcohol use and compulsive behaviors toward drinking. An interview‐based rating scale, the Yale‐Brown Obsessive Compulsive Scale‐heavy drinkers (YBOCS‐hd), has been found useful in quantifying this concept in alcohol‐dependent individuals. A self‐rating scale, the Obsessive Compulsive Drinking Scale (OCDS) has been developed by us as a modification of the YBOCS‐hd. The YBOCS‐hd showed excellent interrater reliability in our hands. The correlation between the YBOCS‐hd and the OCDS total scores obtained on 60 alcohol‐dependent individuals was 0.83. The test‐retest correlation for the OCDS total score was 0.96, and the obsessive and compulsive sub‐scales test‐retest correlations were 0.94 and 0.86, respectively. The internal consistency of the items in the OCDS was high (0.86) and did not improve significantly with removal of individual items. The shared variance between the OCDS scores and alcohol consumption during the period of evaluation was only = 20%, indicating that the dimension measured by the scale was somewhat independent of actual drinking. As such, it might act as an independent measure of the “state of illness” for alcohol‐dependent individuals.

When used during a prospective 12‐week treatment research study, initial results indicate that the OCDS seems to validly measure a dimension of alcohol dependence, because it decreased from baseline during alcohol reduction and increased in relationship to relapse drinking. The ease of administration (5 min), reliability, and concurrent validity of the OCDS makes it particularly suitable as a screening and outcome measurement tool for various types of clinical treatment and research protocols.
Carbohydrate‐Deficient Transferrin Levels in a Female Population
Authors: La Grange Linda , Anton Raymond F. , Garcia Susan , Herrbold Charlotte
Published: April 2006

Female college students (n= 49) from a small southwestern United States university participated in the 9‐month study. Data collected included the assessment of drinking habits and other related substance use habits and serum levels of carbohydrate‐deficient transferrin (COT). Each subject provided an interview and blood sample on three occasions at 90‐day intervals. Appended to the interview were a series of questions regarding stage of menstrual cycle and the diagnoses of certain diseases. The CDT values obtained were consistent with those obtained in other studies. Moderate‐drinking subjects had significantly higher CDT values than did the abstainers and light drinkers. Females using oral contraceptives had significantly higher CDT values than those who were not taking oral contraceptives. Finally, although CDT values varied over time, they did not appear to vary as a function of menstrual cycle stage.
Alcohol‐Related Aggression in Males and Females: Effects of Blood Alcohol Concentration, Subjective Intoxication, Personality, and Provocation
Authors: Giancola Peter R. , Zeichner Amos
Published: April 2006

This study tested the combined predictive ability of blood alcohol concentration (BAC), subjective intoxication, and aggressive personality traits on physical aggression in males and females in Highland Low‐provocation conditions. Sixty intoxicated White social drinkers (30 males and 30 females) competed against a fictitious opponent on a modified version of the Taylor aggression paradigm in which subjects both received and delivered electric shocks to their opponents in provoking and nonprovoking conditions. Provocation conditions (High and Low) were defined by the intensity of the shocks the subjects received. Aggression was operationalized as the intensity of the shocks selected by the subjects. Results indicated that, for males in the High‐provocation condition, aggressive personality traits, subjective intoxication, and BAC were effective predictors of physical aggression. However, in the Low‐provocation condition, only aggressive personality traits and BAC predicted aggression. None of the variables were effective predictors of aggression for intoxicated females.
Effect of Alcohol and Electrical Stimulation on Leakage of Creatine Kinase from Isolated Fast and Slow Muscles of Rat
Authors: Amaladevi Bellamakonda , Pagala Sobhan , Pagala Murali , Namba Tatsuji , Grab David
Published: April 2006

Binge drinking of alcohol may lead to acute alcoholic myopathy with rhabdomyolysis, which is characterized by skeletal muscle damage, elevated serum creatine kinase (CK), and myoglobinuria. This study was undertaken to test whether alcohol acts directly on the skeletal muscles to enhance the leakage of CK, and to assess the influence of fiber‐type composition and repetitive contractions of the muscle on the effect of alcohol. After 4 hr of incubation in normal physiological solution at 37°C, mean leakage of CK was 0.7 units/mg from isolated rat extensor digitorum longus (EDL), which has more fast‐twitch glycolytic muscle fibers, and 1.2 units/mg from the soleus, which has more slow‐twitch oxidative muscle fibers. Ethanol at 0.1, 0.2, and 0.5% concentrations caused significantly greater increase in leakage of CK from soleus than from EDL. In normal physiological solution, electrical stimulation at 1 Hz for 4 hr increased the leakage of CK by about the same degree in both EDL and soleus. In the presence of 0.1 and 0.2% ethanol, electrical stimulation markedly potentiated the alcohol‐induced leakage of CK from both soleus and EDL. These results indicate that alcohol increases the leakage of CK by acting directly on skeletal muscle fibers, especially of the slow‐twitch oxidative type, and that repeated muscle contractions potentiate the alcohol effect. These studies suggest that exercise may increase the chances of rhabdomyolysis in the alcoholics.
Sensitivity of Nucleus Accumbens Neurons In Vivo to Intoxicating Doses of Ethanol
Authors: Criado José R. , Lee Rong‐Sheng , Berg Greta I. , Henriksen Steven J.
Published: April 2006

The nucleus accumbens septi (NAcc) is considered an important component of the final common pathway involved in the reinforcing properties of ethanol. We studied the effects of intraperitoneal administration of ethanol on spontaneous, glutamate‐activated, and fimbria‐activated NAcc neurons in acute anesthetized and freely moving unanesthetized rats. Ethanol significantly reduced the firing rate of spontaneous and glutamate‐activated NAcc neurons in both electrophysiological preparations. Stimulation of the ipsilateral fimbria evoked single‐unit activity in NAcc neurons with two characteristic latencies (early, 7.21 ± 0.74 msec; late, 18.24 ± 0.66 msec). Intoxicating doses of ethanol inhibited the recruitment of late, but not of early, fimbria‐activated NAcc neurons. These data demonstrate electrophysiological evidence for the existence of neurons in the core region of the NAcc that are sensitive and insensitive to acute systemic ethanol administration.
In Utero Exposure to Ethanol Affects Postnatal Development of T‐ and B‐Lymphocytes, But Not Natural Killer Cells
Authors: Wolcott R. Michael , Jennings Stephen R. , Chervenak Robert
Published: April 2006

The effect of intrauterine exposure to ethanol on lymphocyte development in the neonatal period was studied in C57BI/6J mice. Mice were bred, and then the female mice were assigned to 1 of 3 diet groups, 25% ethanol‐derived calories (EDC), pair‐fed control, or ad libitum laboratory chow. At birth, all offspring were cross‐fostered to surrogate mothers who had been fed laboratory chow. At weekly intervals, the neonatal mice were weighed, and 4 mice from each group were used to assess the development of splenic lymphocytes. The total number of splenocytes was similar in all three groups at each sampling. The number of T‐cells, B‐cells, and natural killer (NK) cells was measured by flow cytometry. T‐cells and NK cells did not vary significantly among the three diet groups. However, the total number of B‐cells was decreased for the first 3 weeks of life in the ethanol‐exposed animals. The function of the T‐cells and B‐cells was determined by assessing the response to lipopolysaccharide, pokeweed mitogen, phytohemagglutinin, and concanavalin A. The response to all four mitogens was significantly reduced in the ethanol‐exposed animals and did not recover to control levels until 4–5 weeks of life. Ethanol exposure had no significant effect on the kinetics of acquisition of NK lytic function, as assessed by determining the killing of chromium‐51 labeled YAC‐1 tumor target cells. These data show that prenatal exposure to ethanol causes a transient immunodeficiency in some, but not all compartments of the immune system.
Ethanol Increases GABAA Responses in Cells Stably Transfected with Receptor Subunits
Authors: Harris R. Adron , Proctor William R. , McQuilkin Susan J. , Klein Ronald L. , Mascia Maria Paola , Whatley Valerie , Whiting Paul J. , Dunwiddie Thomas V.
Published: April 2006

Ethanol enhancement of GABAA receptor function has been found in some, but not all, studies. These results suggest the existence of ethanol‐sensitive and ‐resistant receptors that may differ in subunit composition, although methodological differences (e.g., 38Cl‐ flux versus membrane currents) could also contribute to the different results. To examine these possibilities, we used mouse L(tk‐) cells stably transfected with α1+β or α+β1+γ2L GABAA receptor subunit DNAs and compared 38Cl flux with whole‐cell, patch‐clamp measurements of GABAA receptor function. Both techniques detected a similar modulation of the GABA receptor by ethanol, flunitrazepam, and pentobarbital. The potentiating action of ethanol required the ‐γ‐subunit and was maximal at a concentration of 10 mm. Similar ethanol potentiation was obtained with brief (20 msec) or long (2 sec) applications of GABA. Analysis of data obtained from individual cells expressing α1β1‐γ2L subunits showed considerable variability in sensitivity to ethanol, particularly with concentrations of 30 and 100 mm. Ethanol potentiated GABA action if the cells were grown on coverslips coated with polylysine, but had no effect on GABAA receptors of cells grown on uncoated coverslips. Thus, ethanol action was influenced by the growth matrix. Taken together, these data indicate that a y‐subunit is necessary, but not sufficient, for ethanol sensitivity in this cell system. We suggest that posttranslational processing, particularly receptor phosphorylation, may also be important and that stably transfected cells will be useful in elucidating these events.
Cell Cycle Kinetics in Fetal Rat Cerebral Cortex: Effects of Prenatal Treatment with Ethanol Assessed by a Cumulative Labeling Technique with Flow Cytometry
Authors: Miller Michael W. , Kuhn Peter E.
Published: April 2006

The effects of ethanol on the cell cycle kinetics of cortical precursor cells during the period of cortical neuronogenesis [between gestational day (G) 12 and G21] was systematically examined. Samples of dissociated cortical cells were harvested from the cerebral cortices of 13‐, 15‐, 17‐, 19‐, and 21‐day‐old fetuses. The fetuses were obtained from pregnant rats: (a) fed a liquid diet containing 6.7% (v/v) ethanol (Et) ad libitum, (b) pair‐fed an Isocaloric liquid control diet (Ct), or (c) fed chow and water (Ch) ad libitum. Before harvesting the cells, the fetuses were administered a series of 1–5 injections of bromodeoxyuridine (BrdU). The proportion of cells that incorporated the BrdU was assessed. Using these raw data, the S‐phase length (TB, total cell cycle length (Tc), and the growth fraction (GF; the fraction of the total population that was actively cycling) were determined with a cumulative labeling procedure. The T3 was –8–9 hr, regardless of either the date of the injection or the dietary treatment of the dam. On the other hand, the Tc for the Ct‐ and Ch‐treated rats increased over the gestational period. That is, the Tc was shortest on G13 and longest on G21. The Tc for Et‐treated rats, however, did not change between G13 and G21. For the Ch‐ and Ct‐treated groups, the GF decreased > 15‐fold between G13 and G21. The decline (5‐fold) for the Et‐treated group over the same period, however, was not as great as it was for the Ct‐treated fetuses. Thus, by G17 (and thereafter), the GF for Et‐treated fetuses was significantly greater than it was for the Ct‐treated group. Ethanol treatment has opposite effects on the two cortical germinal zones; it stimulates the proliferation of subventricular cells, whereas it inhibits the proliferation of ventricular cells). Thus, the ethanol‐induced changes in the Tc and the GF reflect the combined effects of ethanol on the two cortical proliferative zones.
Effects of Neonatal Ethanol Exposure on Saccharin Consumption
Authors: Barron Susan , Razani L. Jill , Gallegos Roger A. , Riley Edward P.
Published: April 2006

Prenatal ethanol exposure has been associated with alterations in a variety of sexually dimorphic behaviors in rats. This study examined the effects of neonatal ethanol exposure on saccharin consumption, a sexually dimorphic behavior in rats. Subjects were Sprague‐Dawley rats that were artificially reared (AR) from postnatal day (PN) 4‐PN12 through gastrostomy tubes with ethanol exposure limited to PN4‐PN10. The AR groups included two ethanol doses (6 g/kg/day and 4 g/kg/day) and an isocaloric maltose‐dextrin control. A sham surgery control group was also included. The AR subjects were returned to their dams on PN13. At 21 days of age, subjects were housed with one same‐sex sibling and free access to rat chow and water until testing. Subjects were tested for saccharin preference and consumption at 110 days of age. Typically, male rats consume less saccharin than females, and this was evident in the 4 g/kg ethanol group and both control groups. However, this was not apparent among the 6 g/kg ethanol‐exposed males. Furthermore, saccharin preference seemed to be reduced in the females exposed to 6 g/kg ethanol. These data suggest that the “sensitive period” for ethanol's effects on sex differences in saccharin consumption extends into postnatal life.
Taste Reactivity in High Alcohol Drinking and Low Alcohol Drinking Rats
Authors: Kiefer Stephen W. , Badia‐Elder Nancy , Bice Paula J.
Published: April 2006

High alcohol drinking (HAD) and low alcohol drinking (LAD) rats were tested, in three exposures, for taste reactivity to five concentrations of alcohol (5%, 10%, 20%, 30%, and 40%, v/v), water, and one concentration each of sucrose and quinine. Of the three reactivity exposures, one was done before a 3‐week period of continuous access to water and 10% alcohol, the second test was done immediately after the consumption period, and the final reactivity test was done after 1 month of alcohol abstinence. The results showed that the groups did not differ in reactivity on the initial test. After the consumption tests (when the HAD rats consumed significantly more alcohol than the LAD rats), differences in reactivity were found: HAD rats produced significantly more ingestive responses (which promote consumption) and significantly fewer aversive responses (which facilitate fluid rejection) than LAD rats. These differences were maintained even after 1 month of alcohol abstinence. The present data replicate an earlier experiment with alcohol‐preferring (P) rats and alcohol‐non‐preferring (NP) rats, and indicate that the selective breeding process does not produce differences in the innate perception of the taste of alcohol. However, after experience with drinking alcohol, rats selectively bred for high alcohol consumption exhibit a palatability shift reflected by high ingestive responding and little or no aversive responding. Such a shift would clearly contribute to the maintenance of high levels of alcohol consumption.
Chronic Alcohol Intoxication Enhances the Expression of CD18 Adhesion Molecules on Rat Neutrophils and Release of a Chemotactic Factor by Kupffer Cells
Authors: Bautista Abraham P.
Published: April 2006

Chronic alcohol intoxication has been associated with increased migration of inflammatory leukocytes to the liver that may contribute to the development of alcoholic hepatitis in susceptible individuals. Thus, this work was performed to examine the mechanism by which neutrophils [polymorphonuclear neutrophils (PMNs)] are sequestered in the liver during prolonged consumption of alcohol. Male Sprague‐Dawley rats were fed with Sustacal supplemented by 36% alcohol, or isocaloric diet for 16 weeks. Circulating blood PMNs were collected and examined for CD18 (β2‐integrin) adhesion molecule expression. Monoclonal antibody 1F12, an anti‐CD18 antibody and potent neutropenic agent, was used to detect CD18 on PMNs. More than 97% of neutrophils obtained from pair and ethanol‐fed rats were positive for the antibody. Fluorescence intensity of fluorescein iso‐thiocyanate‐1F12 binding to PMNs from ethanol‐fed rat was significantly enhanced 2‐fold compared with the pair‐fed controls. The release of chemoattractant and free radical‐generating activity in culture supernatants of Kupffer cells was also examined. Twenty‐four hr culture supernatants of Kupffer cells from chronic alcoholic rats enhanced the migration and superoxide anion generation by normal PMNs, compared with those of the pair‐fed rats. Antirat interleukin‐8 antiserum inhibited chemotactic activity and superoxide generating capacity of culture supernatants. These results suggest that upregulation of adhesion molecules on PMNs and chemotactic factor release from Kupffer cells may contribute, at least in part, to enhanced migration of inflammatory leukocytes to the liver during chronic alcohol intoxication.
Acetaldehyde‐Serum Protein Adducts Inhibit Interleukin‐2 Secretion in Concanavalin A‐Stimulated Murine Splenocytes: A Potential Common Pathway for Ethanol‐Induced Immunomodulation
Authors: Braun Karen P. , Pearce Richard B. , Peterson Charles M.
Published: April 2006

Variable immunobiological changes occur with alcohol consumption. Previous studies have shown that acetaldehyde forms stable adducts with serum proteins, including albumin. These adducts are elevated in persons and animals consuming ethanol. We examined the effect of serum protein‐acetaldehyde adducts formed with fetal bovine serum (FBS) on concanavalin A‐stimulated murine splenocytes. Interleukin‐2 (IL‐2) secretion and IL‐2 receptor (IL‐2R) expression were determined as a function of the effect of the acetaldehyde‐protein adduct(s). FBS was incubated with acetaldehyde (500,100, 50, 25, 10, and 0 μm) for 1 hr at 37°C. Excess acetaldehyde was removed by ultrafiltration using a 500 molecular weight cut‐off membrane in 3 volumes. Free as well as bound acetaldehyde was quantified using fluorigenic HPLC before and after incubation. Recovered acetaldehyde correlated with the amount added (r2= 0.996). Splenocytes were cultured for 48 hr in complete medium containing 5% acetaldehyde‐treated and 5% untreated FBS with 4 μg/ml concanavalin A. Although cell viability was unchanged, acetaldehyde‐treated FBS mixed with native FBS decreased IL‐2 secretion in a dose‐dependent manner. The percentage of cells expressing IL‐2R was reduced only at the highest acetaldehyde‐FBS dose. Therefore, immunological effects ascribed to ethanol may result in part from the toxic properties of acetaldehyde‐protein adducts on IL‐2 secretion.
Decrease in Cytochrome P4502E1 as Assessed by the Rate of Chlorzoxazone Hydroxylation in Alcoholics during the Withdrawal Phase
Authors: Lucas Danièle , Ménez Catherine , Girre Catherine , Bodénez Pierre , Hispard Eric , Ménez Jean‐François
Published: April 2006

To evaluate cytochrome P4502E1 (CYP2E1) induction in alcoholics, the ratio of the concentrations of 6‐hydroxychlorzoxazone (6‐OH‐CHZ) and chlorzoxazone (CHZ) was measured in blood 2 hr after CHZ ingestion using a HPLC method. This ratio was determined in controls and in alcoholic patients after 1, 2, 3, 4, 5, 8, and 21 days withdrawal. It was found to be 0.34 ± 0.03 in 30 controls and 1.05 ± 0.14 in 41 alcoholic patients within 2 days following ethanol withdrawal. This ratio decreased rapidly during withdrawal as attested by the short half‐life of CYP2E1, which was found to be 2.5 days. Patients tested for CHZ metabolism after 8 or 21 days alcohol abstinence displayed the same ratio as controls [0.35 ± 0.03 (n= 28) and 0.31 ± 0.03 (n= 34), respectively]. No correlation was observed between γ‐glutamyltransferase, carbohydrate‐deficient transferrin values, the amount of alcohol consumed/day, and the 6‐OH‐CHZ/CHZ ratio. There was no influence of smoking on the rate of CHZ hydroxylation, because smokers displayed the same ratio as nonsmokers [0.33 ± 0.025 (n= 62) and 0.33 ± 0.02 (n= 30), respectively]. The CHZ hydroxylation ratio seems to be a good reflection of the hepatic and extrahepatic CYP2E1 activity in humans.
Loss of Reproductive Competence at an Earlier Age in Female Rats Exposed Prenatally to Ethanol
Authors: McGivern Robert F. , McGeary John , Robeck Stephanie , Cohen Sherryl , Handa Robert J.
Published: April 2006

Previous studies have shown that prenatal ethanol exposure can partially masculinize or defeminize neurobehavioral development of female rats. An early age of onset of anovulation is one of the primary characteristics of partial defeminization. Consequently, we examined the occurrence of anovulation in fetal alcohol‐exposed (FAE) female rats at 2,6, and 12 months of age using both vaginal cytology as well as wheel‐running behavior. We assessed the ability of estrogen and progesterone to elicit proprioceptive behaviors and lordosis at 2 and 17 months of age. Female subjects were derived from Sprague‐Dawley dams administered an ethanol liquid diet (35% ethanol‐derived calories), a pair‐fed isocaloric liquid diet, or fed lab chow from days 14 to 22 of gestation. Litter representatives were placed in a computer‐monitored wheel‐running apparatus under a 12‐hr lighting schedule from 49 to 60 days of age. Vaginal smears were taken from littermates during this same period. This same procedure was conducted again from 180 to 196 and from 380 to 396 days of age, except that vaginal cytology was examined in the same animals immediately after wheel‐running behavior was studied. At 2 months of age, a normal cyclical pattern of wheel‐running, characteristic of 4‐ to 5‐day estrus cycles, was observed in all animals. No differences were detected in mean activity levels during the wheel‐running period. This was accompanied by normal cyclic vaginal cytology and normal proprioceptive behaviors and lordosis. At 6 months of age, FAE females exhibited significantly reduced wheel‐running. This was associated with a loss in the cyclical increase in wheel‐running in 8 of 16 FAE females compared with 1 of 15 controls. Vaginal cytology confirmed the significant increase in the number of acyclic FAE females compared with controls at this age in these same animals. At 12–13 months of age, wheel‐running activity was significantly reduced in all treatment groups compared with earlier ages, with no differences observed between groups. This was accompanied by a loss of cyclicity in 50–70% of controls and 100% of FAE animals. At 17 months of age, proprioceptive behavior and the lordosis quotient in FAE females was not different from that observed in controls. However, the quality of the lordotic response was found to be significantly less in FAE females. Overall, these results indicate that the window of reproductive competence in females may be shortened by prenatal alcohol exposure.
Carbohydrate‐Deficient Transferrin–A Valid Marker of Alcoholism in Population Studies? Results from the Copenhagen City Heart Study
Authors: Grønbæk Morten , Henriksen Jens H. , Becker Ulrik
Published: April 2006

Carbohydrate‐deficient transferrin (CDT) was analyzed by a modified radioimmunoassay test in a random population sample of 400 individuals, and results were compared with reported alcohol intake derived from a structured questionnaire. Among the 180 men, the test was found to be acceptable with respect to detecting harmful alcohol intake (<35 beverages/week) and alcohol intake above the recommended level (21 beverages/week), although the positive predictive values were low. Among the 220 women, the test was invalid with low predictive values.

CDT was compared with other known markers of high alcohol intake, and it was observed that CDT had higher sensitivity and specificity than AST and short Michigan Alcoholism Screening Test (sMAST) in men, whereas the positive and negative predictive values were low in all tests. A combination of CDT and AST proved to be a better marker of both harmful alcohol intake and alcohol intake above the recommended level than the other markers. Neither CDT, AST, CDT/AST, nor sMAST proved to be useful as markers of alcohol intake in women. There were no differences between the values for pre‐ and postmenopausal women

These results from a population survey indicate that CDT is a marker of alcohol intake among men, although not ideal, but CDT cannot be used in the screening of harmful alcohol intake in women
Auditory P300 in Young Alcoholics: Regional Response Characteristics
Authors: Cohen H. L. , Wang W. , Porjesz B. , Begleiter H.
Published: April 2006

An auditory oddball paradigm was used to record the P300 component of the event‐related potential (ERP) in a group of medication‐free, chronic male alcoholics (n= 51, mean = 32.2) and a control group (n= 25, mean = 27.2). Each subject received a binaurally presented series of high (1600‐Hz)‐ and low (600‐Hz)‐frequency tones. The designation of the rare tone (0.125 probability) was alternated across subjects. When the subject detected the rare tone, he made a button press as quickly as possible to record his reaction time. Scalp recordings using the entire 10/20 System, as well as interpolated placements, were made from 31 electrodes. For purposes of statistical analyses, five regional electrode groups were created: F (frontal), C (central), P (parietal), O (occipital), and T (temporal). The results of MANOVA indicated that control P300 amplitudes were significantly greater than those of the alcoholics in all five regions, whereas there were no P300 latency differences between groups in any region. Regional response differences between the groups were also compared with measures of surface energy (SE) (Wang et al., 1994). SE is a recently developed, reference‐free global field measure that uses the entire scalp potential field and treats potentials at different positions differently. SE was significantly reduced in the alcoholics compared with the controls in both the C (p < 0.0003) and P (p < 0.0006) regions, although there were no differences in its distribution. Within the alcoholics, we identified a low‐density (LD; n= 16) and high‐density (HD; n= 22) subgroup based on the number of their alcoholic relatives (LD, no alcoholic relatives; HD mean = 4.4 alcoholic relatives/individual). Statistical analyses revealed that, in the O region, LD individuals had significantly larger P300 amplitudes than did HD individuals. Moreover, although there were no differences between LD and control P300 amplitudes in any region, HD subjects had significantly reduced P300 amplitudes compared with controls in every region. These findings suggest that genetic factors may contribute to the deficits observed. Moreover, these deficits may precede the onset of alcoholism and may function as critical phenotypic markers for its development.
Relationship between Alcohol‐Related Expectancies and Anterior Brain Functioning in Young Men at Risk for Developing Alcoholism
Authors: Deckel A. Wallace , Hesselbrock Victor , Bauer Lance
Published: April 2006

This experiment examined the relationship between anterior brain functioning and alcohol‐related expectancies. Ninety‐one young men at risk for developing alcoholism were assessed on the Alcohol Expectancy Questionnaire (AEQ) and administered neuropsychological and EEG tests. Three of the scales on the AEQ, including the “Enhanced Sexual Functioning” scale, the “Increased Social Assertiveness” scale, and items from the “Global/Positive Change scale,” were used, because each of these scales has been found to discriminate alcohol‐based expectancies adequately by at least two separate sets of investigators. Regression analysis found that anterior neuropsychological tests (including the Wisconsin Card Sorting test, the Porteus Maze test, the Controlled Oral Word Fluency test, and the Luria‐Nebraska motor functioning tests) were predictive of the AEQ scale scores on regression analysis. One of the AEQ scales, “Enhanced Sexual Functioning,” was also predicted by WAIS‐R Verbal scales, whereas the “Global/Positive” AEQ scale was predicted by the WAIS‐R Performance scales. Regression analysis using EEG power as predictors found that left versus right hemisphere “difference” scores obtained from frontal EEG leads were predictive of the three AEQ scales. Conversely, parietal EEG power did not significantly predict any of the expectancy scales. It is concluded that anterior brain functioning is associated with alcohol‐related expectancies. These findings suggest that alcohol‐related expectancy may be, in part, biologically determined by frontal/prefrontal systems, and that dysfunctioning in these systems may serve as a risk factor for the development of alcohol‐related behaviors.
Alcohol Modulation of Human Normal T‐Cell Activation, Maturation, and Migration
Authors: Chiappelli Francesco , Kung Michelle , Lee Patricia , Pham Lanchi , Manfrini Ercolano , Villanueva Pablo
Published: April 2006

We are interested in the characterization of the effects of alcohol on human T‐cell activation, maturation, and migration, because this cell population is crucial in the initiation, regulation, and propagation of cellular immunity. We and others have described the effects of both acute and chronic exposure of human immune cells to ethanol (EtOH) in vitro. Herein, we briefly, review these reports and expand this body of literature with the inclusion of new data recently obtained in our laboratory. We confirm the blunting effects of EtOH on the production of interleukin‐2 and mitogen proliferative response following T‐cell mitogen stimulation, and on the expression of membrane markers of activation. We show that EtOH significantly alters the expression of the CD4 cell‐associated marker of activation, CD26. We report the effect of EtOH on the expression of the homing receptor CD62L by CD4+ cells, and on their ability to adhere by a CD18‐mediated process to a defined cellular substratum. Furthermore, we demonstrate the effects of EtOH and EtOH and 0‐endor‐phin pretreatment on the activation of CD4+ lymphocytes endowed with the homing receptor CD62L.
Fetal Alcohol and Thymocyte Phenotypes in Offspring: Response to Food Deprivation
Authors: Taylor Anna N. , Tio Delia L. , Chiappelli Francesco
Published: April 2006

Restriction of food availability is a reliable stimulus that leads to significant hypothalamo‐pituitary‐adrenal (HPA) activation to which rats do not habituate. Based on our previous data that indicated that the HPA response to some, but not all, stressful stimuli is significantly greater in adult offspring of Sprague‐Dawley dams exposed to 35% alcohol during the last 2 weeks of gestation than that of control rats and on the mounting neuroendocrine‐immune literature that describes the role of pituitary‐adrenal products in modulating cellular immunity, we hypothesized that the outcomes of food restriction would be significantly more marked in fetal alcohol‐exposed (FAE) offspring, compared with control rats. Data we report herein show that–whereas food restriction at 30–35 days of age produced significant changes in body weight, thymus weight‐to‐body weight ratio, adrenal weight‐to‐body weight ratio, plasma corticosterone levels, and in thymocyte number, as well as in the percentage and absolute number of CD4+ and CD8+ thymocytes that express CD45RC–FAE and control rats were equally affected. We conclude that food restriction is another example of a stressful stimulus that fails to distinguish satisfactorily between FAE and control rats of prepubertal age.
Effects of Disease‐Related Cues in Alcoholic Inpatients: Results of a Controlled “Alcohol Stroop” Study
Authors: Stetter Friedhelm , Ackermann Klaus , Bizer Andreas , Straube Eckart R. , Mann Karl
Published: April 2006

We tested the hypothesis that alcoholics develop a disease‐related attentional bias. Therefore, alcohol‐related, but task‐irrelevant, words should cause a specific perceptual‐processing bias. We investigated this by using a special color‐naming task. We subjected 40 male alcohol‐dependent inpatients and 40 healthy male controls (matched according to age and verbal la) to a modified card version of the Stroop colornaming task that consisted of a neutral and an alcohol word condition (“Alcohol Stroop”). Alcoholic inpatients performed significantly poorer than the control group under the critical experimental condition (color‐naming of disease‐related words), as compared with the noncritical condition (color‐naming of neutral words; p = 0.03). Concerning the possible neuropsychological impairment of the patients, no effects could be found on the reaction time of the “Standard Stroop” using only neutral words (i.e., color‐naming of incongruent color words administered without time limitation). The information processing bias on the “Alcohol Stroop” thus qualifies as a cognitive process, which is independent from putative neuropsychological deficits of alcoholic patients and might represent an essential feature of alcoholic psychopathology. The “Alcohol Stroop” contributes to the experimental psychopathology of alcoholism.
Development and Initial Validation of a Measure of Drinking Urges in Abstinent Alcoholics
Authors: Bohn Michael J. , Krahn Dean D. , Staehler Beth A.
Published: April 2006

Although drinking urges and cravings are commonly reported by alcoholics, prospective studies have found inconsistent associations between such urges and drinking relapses. Previous studies have measured drinking urges by use of single‐item ratings of alcohol craving or other measures of unknown reliability and validity. To permit improved evaluation of hypotheses regarding alcohol craving, a 49‐item questionnaire that reflects several urge‐related domains was developed and pretested. Items assessed subjects'desire for a drink, expectations of positive effects following drinking, relief of withdrawal and negative affect following drinking, and intention to drink. Exploratory and confirmatory factor analyses of the responses of 351 abstinent, treatment‐seeking alcoholics indicated that alcohol urges are best described by a single factor. Based on these analyses, an internally consistent, reliable, and psychometrically valid 8‐item scale, the Alcohol Urge Questionnaire (AUQ), was developed. Data indicated that AUQ scores were strongly related to alcohol dependence severity and to cognitive preoccupation with alcohol, and that they declined with prolonged abstinence. The AUQ may be useful in alcoholism treatment research and in laboratory studies of reactivity to alcohol or other manipulations.
Acute Effects of Alcohol on P300 in Asians with Different ALDH2 Genotypes
Authors: Wall Tamara L , Ehlers Cindy L.
Published: April 2006

Asian men were genotyped for alleles of aldehyde dehydrogenase (ALDH2) and tested on two separate occasions following oral administration of placebo and 0.75 ml/kg alcohol. Sixty minutes after beverage ingestion, event‐related potentials were elicited using an auditory oddball paradigm. Repeated measures ANOVA revealed that alcohol produced significant increases in P300 latency and significant decreases in P300 amplitude compared with placebo. Subjects with ALDH2*1/2*2 genotype (n= 14) demonstrated some significantly greater P300 effects after alcohol than subjects with ALDH2*1/2*1 genotype (n= 15), despite equivalent blood alcohol concentrations. These data suggest that neurocognitive functioning may be more impaired following alcohol in subjects with an ALDH2*2 allele. These findings further suggest that a genetically controlled factor (deficiency in ALDH enzyme activity) might contribute to a decreased likelihood of alcohol intake and protection from alcoholism, because of an enhanced sensitivity to alcohol.