bluuebunny/crossref_metadata_2025 huggingface dataset:
Ethanol Consumption Following Acute Treatment with Methysergide, Fluoxetine, Fenfluramine, and Their Combination
Authors: Lu M.‐R. , Wagner G. C. , Fisher H.
Published: April 2006

Methysergide (MS), a postsynaptic serotonin antagonist, was administered acutely in three experiments in relation to water or 5% ethanol solution intake of 24‐hr, water‐deprived male Sprague‐Dawley rats. In the first experiment, MS significantly increased the consumption of ethanol at doses of 0.25, 2.0, and 4.0 mg/kg. Water intake was significantly increased by MS at the 2.0 mg/kg dose. In the second experiment, which was different from the first one in that MS was administered during the dark cycle, ethanol solution intake was again significantly increased at all three levels. In the third experiment, fenfluramine (FFL) and fluoxetine (FLU) were administered acutely (at 8 mg/kg) after MS (0.25 mg/kg) followed by measuring water or ethanol solution intake. FFL and FLU significantly decreased intake of both water and ethanol solution, a process that was significantly reversed by MS; to a greater degree for FLU (74%) than for FFL (57%). The successful use of MS in increasing ethanol intake in these studies may be due to the low doses used in comparison with earlier unsuccessful attempts. The procedure of treating 24‐hr, water‐deprived rats with acute doses of pre‐ and postsynaptic serotonin agonists and antagonists appears to be a useful model for further elucidation of their interaction in ethanol consummatory behavior.
Influence of Chronic Dietary Ethanol on Cytokine Production by Murine Splenocytes and Thymocytes
Authors: Wang Yuejian , Huang Dennis S. , Giger Paul T. , Watson Ronald R.
Published: April 2006

Prolonged consumption of ethanol (ETOH) results in alterations of host defense via immune modulation, increasing susceptibility to infection. In the present study, effects of chronic dietary ETOH on cytokine production by splenocytes and thymocytes, splenocyte and thymocyte proliferation induced by mitogens, splenic natural killer cell activity, and antibody production (IgA and IgG) were examined. C57BL/6 mice were fed 5% ETOH v/v in the Lieber‐DeCarli liquid diet for 11 weeks. Release of interleukin (IL)‐2, IL‐5, IL‐6, IL‐10, and interferon (IFN)‐γ produced by concanavalin A (Con A) stimulated splenocytes was significantly decreased, whereas secretion of IL‐4 was slightly decreased by chronic dietary ETOH compared with controls. Production of tumor necrosis factor‐α and IL‐6 by lipopolysaccharide‐stimulated splenocytes was significantly and slightly decreased by ETOH compared with controls, respectively. Splenocyte and thymocyte proliferation induced by Con A was significantly inhibited by ETOH, whereas splenocyte proliferation induced by lipopolysaccharide was not affected. Natural killer cell activity was significantly inhibited by ETOH compared with controls. The production of IgA and IgG by splenocytes were also significantly decreased by ETOH compared with controls. The levels of IL‐2, IL‐4, and IL‐6 produced by Con A‐stimulated thymocytes were significantly reduced by dietary ETOH compared with control, whereas production of IFN‐γ by thymocytes was not affected. Our results suggest that chronic dietary ETOH alters the cytokine release, thereby impairing immune response and T‐cell maturation, which increase host susceptibility to infection.
A Neuropsychologic Profile of Adolescent Alcoholics
Authors: Moss Howard B. , Kirisci Levent , Gordon Harold W. , Tarter Ralph E.
Published: April 2006

Male and female adolescents who qualified for a DSM‐III‐R diagnosis of Alcohol Abuse or Dependence and a control sample of nonalcohol‐abusing male and female adolescents were administered a battery of intellectual, achievement, and neuropsychologic tests. Alcohol‐abusing adolescents were found to have significantly lower verbal and full‐scale IQ scores than controls. Furthermore, alcohol‐abusing adolescents were found to have a trend toward lower age‐standardized scores on achievement tests of reading ability and spelling. Surprisingly, alcohol‐abusing adolescents made less perseverative errors and commission errors on a learning and memory task than controls. Control males performed worse on the Wisconsin Card Sort than alcoholic males, whereas alcohol‐abusing females performed worse than control females. In addition, alcoholic subjects scored better than controls on a measure of visual memory sensitivity. The results indicate that adolescent alcohol abusers in general have poorer language skills than adolescents who do not abuse alcohol. However, in contrast to results obtained from studies of adult alcoholics, there is little evidence of significant brain damage as revealed by using neuropsychologic test performance.
Mortality Rates and Predictors of Mortality Among Late‐Middle‐Aged and Older Substance Abuse Patients
Authors: Moos Rudolf H. , Brennan Penny L. , Mertens Jennifer R.
Published: April 2006

This study describes mortality rates and predictors of mortality among late‐middle‐aged and older (55+) substance abuse inpatients (n= 21, 139) in Department of Veterans Affairs (VA) Medical Centers in the 4 years after an index episode of care. A total of 24% of the patients died; this mortality rate was 2.64 times higher than expected. Predictors of earlier mortality included older age and nonmarried status, alcohol psychosis and organic brain disorder diagnoses, and several medical diagnoses, including neoplasms, liver cirrhosis, respiratory, endocrine and metabolic, and blood system disorders. Three proxy indicators of illness severity also predicted mortality: more prior inpatient and outpatient medical care and an index episode in an extended care unit. In contrast, more prior outpatient mental health care and remitted status predicted lower mortality. These diagnostic and treatment indicators can be used to identify patients at heightened risk for premature mortality. Moreover, they show that intensive mental health aftercare and remission of substance abuse may delay mortality, even among older patients who have longstanding substance abuse problems.
Ethanol Administration Alters the Proteolytic Activity of Hepatic Lysosomes
Authors: Donohue Terrence M. , McVicker Daniel L. , Kharbanda Kusum K. , Chaisson Mary L. , Zetterman Rowen K.
Published: April 2006

Protein accumulation in liver cells contributes to alcohol‐induced hepatomegaly and is the result of an ethanol‐elicited deceleration of protein catabolism (Alcohol Clin Exp Res 1349, 1989). Because lysosomes are active in the degradation of most hepatic proteins, the present studies were conducted to determine whether ethanol administration altered the proteolytic activities of partially purified hepatic lysosomes. Rats were fed liquid diets containing either ethanol (36% of calories) or isocaloric maltodextrin for periods of 2–34 days. Prior to death, all animals were injected with [3H]leucine to label hepatic proteins. Rats subjected to even brief periods of ethanol feeding (2–8 days) exhibited significant hepatomegaly and hepatic protein accumulation compared with pair‐fed control animals. Crude liver homogenates and isolated lysosomal‐mitochondrial and cytosolic subfractions were incubated at 37°C, and the acid‐soluble radioactivity generated during incubation was measured as an index of proteolysis. At neutral pH, in vitro protein breakdown in incubated liver homogenates and subcellular fractions from control and ethanol‐fed rats did not differ significantly. The extent of protein hydrolysis increased when samples were incubated at pH 5.5, which approximates the pH optimum for catalysis by lysosomal acid proteases. Under the latter conditions, partially purified lysosomes from control animals had 2‐fold higher levels of proteolysis than corresponding fractions from ethanol‐fed rats. The difference in proteolytic capacity appeared to be related to a lower latency and a higher degree of fragility of lysosomes from ethanol‐fed rats at the acidic pH. The results suggest that ethanol‐induced alterations in lysosomal membranes may be partially responsible for their altered capacities for protein hydrolysis. Such changes may result from ethanol‐related alterations in lipid metabolism that may affect lysosome biogenesis or the maturation of lysosomes from autophagic vacuoles.
Alterations in Taste Reactivity to Alcohol in Rats Given Continuous Alcohol Access Followed by Abstinence
Authors: Kiefer Stephen W. , Bice Paula J. , Badia‐Elder Nancy
Published: April 2006

Naive, male rats (n= 14) were given continuous access to 10% alcohol and water for a period of 6 weeks. Concurrent taste reactivity tests showed a consistent increase in ingestive responding to a range of alcohol concentrations (100%‐40%) over the course of alcohol access. The rats also showed a consistent decrease in aversive responding over time. These data suggested that the palatability of alcohol increased with alcohol experience. After a 1‐month period of alcohol abstinence, however, ingestive taste reactivity to alcohol returned to the same level as that found when the rats were alcohol naive, whereas aversive responding approached the level seen initially. A separate control group (n= 13) given only water for the same length of time failed to show similar changes in taste reactivity to alcohol solutions.
Effects of Acute and Chronic Ethanol Exposure on Intestinal Microvillus Membrane Lipid Composition and Fluidity
Authors: Bjorkman David J. , Jessop Louise D.
Published: April 2006

Chronic ethanol consumption produces nutrient malabsorption. The mechanisms by which this occurs are poorly understood. One potential mechanism is an alteration in microvillus membrane (MVM) composition and fluidity. The effects of in vivo ethanol exposure on MVM lipid composition and fluidity were determined in rats fed either a standard diet or 15% ethanol in water for 2 months. Acute jejunal exposure to 4% ethanol was also performed in vivo in each feeding group. Acute exposure to ethanol produced an increase in static and dynamic membrane fluidity associated with a decrease in MVM cholesterol regardless of prior ethanol exposure. Chronic ethanol feeding alone did not alter membrane fluidity. Changes in membrane fatty acid composition were minor and variable after both acute and chronic ethanol exposure. Prior chronic ethanol feeding did not prevent the acute effects of ethanol on MVM composition or fluidity. These data support the theory that ethanol acutely disrupts nutrient transport by changing MVM lipid fluidity. The absence of adaptive changes in membrane composition and fluidity may also explain the persistent absorptive defects seen with chronic alcoholism.
Ethanol Inhibits Nonadrenergic, Noncholinergic Neurotransmission in the Anococcygeus Muscle of the Rat
Authors: Knych Edward T.
Published: April 2006

The anococcygeus muscle of the rat is innervated by both excitatory adrenergic and inhibitory nonadrenergic, noncholinergic (NANC) neurons. The transmitter released from NANC neurons appears to be nitric oxide or a related molecule. In vitro, acute administration of ethanol inhibited, in a dose‐dependent manner, NANC‐induced relaxation of anococcygeus muscle obtained from ethanol‐naive animals. Two days of in vivo ethanol administration resulted in an increase in the maximal relaxation induced by stimulation of NANC neurons and in a significant shift to the right of the acute ethanol dose‐response curve for inhibition of NANC relaxation. The sensitivity of the anococcygeus muscle to relaxation induced by the nitric oxide donors, acidified sodium nitrite or sodium nitroprusside, was not altered significantly by acute in vitro or chronic ethanol treatment 2 days in vivo. These data suggest that acutely administered in vitro ethanol inhibits the production of nitric oxide induced by stimulation of NANC neurons. Data further suggest that 2 days of ethanol administration in vivo produce an enhanced responsiveness of the NANC neurons to transmural stimulation and that this enhanced responsiveness accounts for the tolerance to the inhibition induced by the acutely administered ethanol in vitro.
Catalytic Efficiency of Human Alcohol Dehydrogenases for Retinol Oxidation and Retinal Reduction
Authors: Yang Zhong‐Ning , Davis Gerard J. , Hurley Thomas D. , Stone Carol L. , Li Ting‐Kai , Bosron William F.
Published: April 2006

Mammalian alcohol dehydrogenase (ADH) is thought to be involved in the reversible oxidation of vitamin A or retinol to retinal for retinoic acid synthesis. Retinoic acid is a potent transcriptional regulator and a morphogen. It was proposed that the competition of consumed ethanol with retinol oxidation by ADH might explain developmental disorders seen with fetal alcohol syndrome. We report herein the dative efficiency (V/Km) of eight human ADH isoenzymes for oxidation of all‐trans‐retinol and reduction of three retinal isomers (all‐frans, Scis, and 134s‐retinal). Class IV σσ and class II ππ isoenzymes are the most efficient forms, with VIKm values ∼100 and 30 times greater, respectively, than class I β1β1 or γ1,γ1. σσ exhibits the highest V/K, (1–2 μm−1min‐−1), followed by ππ, with V/Km of 0.5–0.6 pm−1min−1 for all‐trans‐retinol, all‐trans‐retinal, and 9‐cis‐retinal. ππ also has the lowest Km (11–14 μm) for all‐trans‐retinol and three retinal isomers. αα shows an intermediate efficiency, with V/Km of 0.09–0.2 am−1min−1 and a relatively low Km of 16–24 μm for all four substrates. αα has the highest efficiency of all tested isoenzymes for 13‐cis‐retinal. Class 111 xx is inactive with all the tested retinoids. The contribution of class IV σσ, class II ππ, and even class I αα to retinol oxidation and retinal reduction in vivo will depend on expression of these isoenzymes in specific tissues, relative activities toward free retinol/retinal versus that bound to the cellular retinol binding protein (CRBP or CRBP II) and the concentration of free versus bound retinoids.
Effects of Ethanol, Chlordiazepoxide, and MK‐801 on Performance in the Elevated‐Plus Maze and on Locomotor Activity
Authors: Criswell Hugh E. , Knapp Darin J. , Overstreet David H. , Breese George R.
Published: April 2006

The effects of ethanol, chlordiazepoxide, and MK‐801 on performance in the elevated‐plus maze and on activity measured in a circular activity monitor were compared in Sprague‐Dawley rats to determine whether these effects of ethanol could be explained by its action on either GABAA or NMDA receptors. Both ethanol and chlordiarepoxide produced an increase in the time spent in the open arms of the elevated‐plus maze and in the ratio of open arm to total arm entries, indicative of an anxiolytic action of these drugs. MK‐801 did not alter either the time spent in the open arms or the ratio of open to total arm entries. Chlordiazepoxide and MK‐801 produced an increase in total arm entries that suggested that these compounds were increasing locomotor activity. Ethanol also increased total arm entries, but the effect was not statistically reliable. Following habituation to an activity monitor, neither ethanol nor chlordiazepoxide increased activity in this task, whereas MK‐801 produced a robust increase in locomotion. Additionally, neither ethanol nor chlordiazepoxide blocked the MK‐801‐induced locomotor stimulation. The latter finding suggests that the effects of ethanol on GABAA receptors was not Mocking an increased activity level produced by its antagonism of NMDA. Additionally, these results indicate that the anxiolytic and locomotor action of ethanol in rats parallel the effects of a benzodiazepine and not those of an NMDA antagonist. Finally, these results suggest that the consequence of ethanol's antagonism of NMDA receptor function is more restricted than that produced by MK‐801.
Suppression of Tumor Necrosis Factor Production by Alcohol in Lipopolysaccharide‐Stimulated Culture
Authors: Nair Madhavan P. N. , Schwartz Stanley A. , Kronfol Ziad A. , Hill Elizabeth M. , Sweet Ann M. , Greden John F.
Published: April 2006

Many studies have shown that alcohol consumption is associated with alteration in immune responses and increased incidence of infection in the host. Tumor necrosis factor (TNF) is a potent soluble mediator of immunoregulation and inflammation, and plays a very important role in host's defenses against infection and tumor. We propose that one of the mechanisms of alcohol‐mediated immunosuppression may be due to a defect in the synthesis and release of the TNF. To determine this, we studied the direct effect of alcohol on lipopolysaccharide (LPS)‐induced TNF production by whole blood and total mononuclear cell from normal subjects. Aliquots of blood samples (1 ml) or ficollhypaque separated total mononuclear cells (1 × 106/ml) were cultured with different concentrations of either ethanol or acetaldehyde in the presence or absence of LPS for 4 hr at 37°C. Plasma samples and culture supernatants were assayed for TNF levels in a bioassay using a TNF‐sensitive WEHl 164 sub‐clone 13 cell line. LPS at 10 μg/ml produced a maximal level of TNF compared with lower (1 μg/ml) or higher concentration (50 μg/ml) of LPS. Kinetics studies showed that an incubation time of 4 hr with LPS produced a maximum level of TNF production by blood. Alcohol, as low as 0.1% concentration, produced significant suppression of LPS‐inducted TNF production by whole blood, whereas alcohol at 0.2 and 0.3% concentrations were required to produce a significant suppression of TNF production by separated mononuclear cells. Anti‐TNF‐α antibodies significantly neutralized the LPS‐induced TNF that suggests that blood monocytes may be the primary source of TNF production. Further, significant correlation between TNF production and monocyte numbers was observed. Acetaldehyde one of the primary metabolites of alcohol, did not suppress the LPS‐induced TNF production by whole blood. These studies suggest that alcohol‐induced inhibition of TNF may be one of the mechanisms for immunosuppression in alcoholic patients.
Low Frequency of the ADH2*2 Allele among Atayal Natives of Taiwan with Alcohol Use Disorders
Authors: Thomasson Holly R. , Crabb David W. , Edenberg Howard J. , Li Ting‐Kai , Hwu Hai‐Gwo , Chen Chiao‐Chicy , Yeh Eng‐Kung , Yin Shih‐Jiun
Published: April 2006

Genetic variation at two polymorphic alcohol dehydrogenase loci, ADH2 and ADH3, and at the polymorphic mitochondrial aldehyde dehydrogenase locus, ALDH2, may influence the risk of developing alcoholism by modulating the rate of elimination of ethanol and the rate of formation and elimination of acetaldehyde. Populations differ in allele frequencies at these loci. We determined the genotypes at all three of these loci in Atayal natives of Taiwan. The frequencies of ADH2′2, ADH3′1, and ALDH2′1 alleles (0.91, 0.99, and 0.95, respectively) were significantly higher among the Atayal than among a predominantly Han Chinese population from Taiwan. Among the Atayal, the group with alcohol use disorders (alcohol dependence and alcohol abuse) had a significantly lower frequency of the ADH2′2 allele (0.82) than those without alcohol use disorders (0.91). The ADH2*2 allele encodes the β2 subunit; isozymes containing β2 sub‐units oxidize alcohol faster in vitro than the β1β1 isozyme encoded by ADH2*1. Thus, the simplest explanation for these data is that individuals with a β2 isozymes have a higher rate of ethanol oxidation, which is a deterrent to alcohol abuse and dependence in some individuals. The Atayal with alcohol use disorders also had a lower frequency of ALDH2*2 than the controls; this allele is known to be responsible for the alcohol‐flush reaction among Asians, and thereby deters drinking.
Effects of Physostigmine on Male Offspring Sired by Alcohol‐Treated Fathers
Authors: Abel Ernest L.
Published: April 2006

Male rats were intubated with either 3, 2, or 0 g/kg alcohol, twice daily, for 7 months and were then bred to untreated females. At 18 and 58–62 days of age, male offspring were tested for passive avoidance learning. At 82–88 days of age, another group of male offspring were tested for open field activity after receiving 0, 0.1, or 0.4 mg/kg physostigmine, a cholinesterase inhibitor. Offspring sired by alcohol‐treated fathers required more trials to reach criterion in the passive avoidance task at 18 days of age, but did not differ significantly at 58–62 days of age. These offspring were more active in the open field compared with controls after receiving vehicle, but did not differ from controls after receiving physostigmine. These results suggest animals sired by alcohol‐treated fathers are more active than controls, and this effect is cholingergically mediated. These results are of interest because of their possible relevance to the hyperactivity noted in children born to alcoholic fathers.
Alcohol and Aggression: Effects of Personal Threat on Human Aggression and Affective Arousal
Authors: Zeichner Amos , Alien Joseph D. , Giancola Peter R. , Lating Jeffrey M.
Published: April 2006

Theorists have attempted to account for the relationship between alcohol intoxication and a wide range of aggressive behaviors by ascribing alcohol‐related aggression to the disinhibiting effects of alcohol and to its disruptive effects on cognitive processes. Allocation of attention and situational threat have been thought to mediate alcohol‐related aggression. In the present study, 72 male social drinkers received either alcohol, a placebo, or a nonalcoholic beverage and were exposed to either threatening or nonthreatening personal information. Measuring levels and duration of aggressive responses on a Taylor‐Buss aggression machine, intoxicated subjects were found to be generally more aggressive under threatening than under nonthreatening information conditions. Intoxicated subjects also reported relatively large increases in anger, depression, and tension following the aggression task, which appeared to be affected by the type of information received. These findings concur with and refine previous models suggesting that alcohol focuses the drinker's attention to salient cues in threatening circumstances, thus increasing the likelihood of aggressive behavior.
Family History of Alcoholism in Women with Generalized Anxiety Disorder Who Have Premenstrual Syndrome: Patient Reports of Premenstrual Alcohol Consumption and Symptoms of Anxiety
Authors: McLeod Daniel R. , Foster Giraud V. , Hoehn‐Saric Rudolf , Svikis Dace S. , Hipsley Pamela A.
Published: April 2006

This study sought to determine whether family history of alcoholism is related to patient reports of premenstrual alcohol consumption and whether family history of alcoholism is related to severity of anxiety‐related symptoms, in women who suffer simultaneously from both premenstrual syndrome and generalized anxiety disorder. Fifty‐four women with generalized anxiety disorder and prospectively demonstrated premenstrual syndrome were questioned about family history of alcoholism and alcohol consumption patterns across the menstrual cycle. Seventy‐six percent of the sample reported having an alcoholic first‐ or second‐degree relative. Furthermore, 74% of those women having a paternal‐side family history of alcoholism, but only 22% of those without such a family history, reported increased alcohol consumption premenstrually. Forty‐one of these women were assessed by means of psychiatric rating scales during both the premenstrual and follicular phases of the menstrual cycle. During the premenstrual, but not the follicular, phase of the menstrual cycle, women with a paternal‐side family history of alcoholism experienced more severe anxiety‐related somatic, but not psychic, symptoms of anxiety, than those without such a family history. These findings suggest that family history of alcoholism may be related to premenstrual alcohol consumption patterns and to the severity of premenstrually experienced somatic symptoms of anxiety in women with premenstrual syndrome, and that these women may be self‐medicating with alcohol.
Alcohol Norms, Expectancies, and Reasons for Drinking and Alcohol Use in a U.S. Versus a Japanese College Sample
Authors: Nagoshi Craig T. , Nakata Takayuki , Sasano Kanji , Wood Mark D.
Published: April 2006

Two hundred eighty‐two students at Arizona State University in the U.S. and 339 students at Okayama University in Japan completed a questionnaire on their alcohol use, expectancies of the effects of alcohol on their own and others' moods and behaviors, the desirability of these effects, norms of signifiant others for levels of alcohol use and the subject's desire to comply with these norms, and reasons for drinking and not drinking alcohol. Although frequencies of current drinkers versus abstainers did not differ between the two samples, the U.S. students began regular alcohol use at a significantly earlier age, currently drank more alcohol, had higher alcohol expectancies for emotional responses, and endorsed more celebratory reasons for drinking than their Japanese counterparts. U.S. students, however, had lower expectancies for flushing and lower perceived norms for drinking. Hierarchical multiple regressions performed using data from the current drinkers indicated that expectancies of disinhibition and especially aggressiveness after alcohol use, alcohol norms, celebratory (but not pathological) reasons for drinking, and reasons for not drinking were more predictive of reported levels of alcohol use among the US. students as compared with the Japanese students.
Abstinent Alcoholics Exhibit an Exaggerated Stress Response to 2‐Deoxy‐D‐Glucose Challenge
Authors: George David T. , Lindquist Teresa , Alim Tanya , Flood Marilyn , Eckardt Michael J. , Linnoila Markku
Published: April 2006

Chronic excessive alcohol consumption can significantly disturb the hypothalamic control of glucose metabolism; however, the mechanism and clinical significance of this disturbance are poorly understood. We used 2‐deoxy‐o‐glucose (2‐DG), which produces intracellular glucoprivation, to compare neurochemical, physiological, and behavioral responses to glucoprivic stress between alcoholics abstinent for 3 weeks and healthy volunteers. Twenty‐six male alcoholics and 15 male healthy volunteers received intravenous infusions of placebo, 12.5 mg/kg, and 25.0 mg/kg of body weight of 2‐DG over 30 min on three separate days, following a random‐ordered, double‐blind procedure. Minimal effects were obsewed following administration of the 12.5 mg/kg of body weight dose of 2‐DG. Following 25.0 mg/kg, alcoholics showed both exaggerated ACTH and cortisol responses and greater increases in caloric intake when compared with controls. Although anxiety, desire to consume alcohol, plasma progesterone, and sympathetic and adrenal medullary activity all increased following 2‐DG, these responses did not differ between alcoholics and controls. The present findings suggest certain specificity for the exaggerated hypothalamic and adrenocortical responses to mild glucoprivic stress in 3‐week‐abstinent alcoholics.
Correlations of Alcohol Consumption with Related Covariates and Heritability Estimates in Older Adult Males Over a 14‐ to 18‐Year Period: The NHLBI Twin Study
Authors: Reed Terry , Slemenda Charles W. , Viken Richard J. , Christian Joe C. , Carmelli Dorit , Fabsitz Richard R.
Published: April 2006

Consistent maximum‐likelihood heritability estimates of consumption of alcoholic beverages were observed at three separate times during a 14‐ to 18‐year period in adult twin males initially aged 42‐–56 years in 1969–1973. Log transformation of the average number of drinks/ week of the returnees to all three examinations was examined relative to potential covariates representing both antecedents of drinking alcohol and consequences of alcohol consumption. Significant relationships were noted for 38 of the covariates at one or more of the separate examinations, including positive correlations with smoking, coffee consumption, high‐density lipoprotein cholesterol, mean corpuscular volume, systolic blood pressure, uric acid and behavioral measures, and negative correlations with blood urea nitrogen, red blood cell count, tea consumption, and tricep skinfolds. Analysis of the average alcohol consumption adjusted for nine independent covariater selected from multiple stepwise regression resulted in a modest decline in maximum‐likelihood heritability estimates compared with unadjusted data, but little difference from heritability estimates obtained when abstainers from alcohol (no alcoholic beverages consumed at all three examinations) were excluded. The most striking effect of omitting abstainers from alcohol was the decline in the intraclass correlations in dizygotic twins. Bivariate analyses of alcohol and individual covariates revealed the phenotypic correlation between alcohol consumption and a measure of hostility was primarily environmental, that for high‐density lipoprotein, smoking and coffee drinking with alcohol was primarily genetic, and the phenotypic correlation between alcohol consumption and mean corpuscular volume had both significant genetic and environmental correlations. Comparison with other twin studies in males suggested relatively consistent estimates of genetic variance, despite wide variation in subject characteristics, study design and methods, and measure of alcohol consumption.
A 6‐Year Follow‐Up of Alcoholics After Long‐Term Outpatient Treatment
Authors: Ojehagen Agneta , Berglund Mats , Moberg Ann‐Louise
Published: April 2006

The predictors of the long‐term outcome in alcoholics (n= 50) who had been treated in a 2‐year outpatient treatment program were investigated. Previously, the sample had been followed up personally 2 years after the termination of treatment. This study is a repeated, independent follow‐up of the same sample over a 4‐year period, 3–6 years after termination of treatment. Outcome could be categorized in 38 subjects. Patients with a favorable outcome during at least 2 years of the 4‐year follow‐up period (n= 21), who were categorized as a positive outcome group, were compared with the other patients (n= 17). There was no significant correlation between initial patient characteristics and outcome 3–6 years after treatment. Drinking outcome during the 1st half‐year of treatment had no correlation to positive drinking outcome in years 3–6, whereas there was a positive correlation for later phases of treatment and outcome reaching a significant level during the 2nd and 4th half‐year of treatment. A favorable drinking outcome during years 1–2 after treatment had a positive significant correlation to outcome in years 3–6 after treatment [i.e., 80% of the patients with a favorable outcome during the 1st follow‐up period also had a positive outcome during the 2nd follow‐up period, and 72% of those who had an unfavorable outcome during the 1st follow‐up period had an unfavorable outcome also during the 2nd follow‐up period (x2 test = 10.4, p < 0.001). Psycho‐social adjustment at the 6‐year follow‐up did not differ significantly between subjects in the positive outcome group and subjects in the negative outcome group.
Treatment Outcome of Alcoholics with and without Cocaine Disorders
Authors: Brower Kirk J. , Blow Frederic C. , Hill Elizabeth M. , Mudd Sharon A.
Published: April 2006

The treatment outcome literature suggests that alcoholics with coexisting drug dependence have worse prognoses. We compared three groups of inpatients treated on the same hospital unit for disorders of alcohol only (n= 51), cocaine only (n= 27), or both disorders (dual group, n= 27). At follow‐up, we contacted 105 (81%) of 129 patients at a mean of 13.4 ± 4.1 months after discharge. The three groups significantly and equivalently decreased their consumption of substances at follow‐up, and they also had equivalent improvements in employment and in medical and psychiatric well‐being. A nonsignificant trend existed for greater abstinence in the alcohol group (53%) than in the dual group (35%), and with regression analysis diagnostic group and stable residence predicted abstinence in the past 30 days. Elapsed time before using alcohol was equivalent for the two alcohol groups, and relapse to alcohol preceded relapse to cocaine by 1 month on average. In sum, outcomes were more similar than different for the three groups. Although specific treatments to enhance abstinence for cocaine users are indicated, clinicians should approach cocaine‐using alcoholics with equal optimism for improvement as with other alcoholics.
Electroencephalographic and Autonomic Predictors of Relapse in Alcohol‐Dependent Patients
Authors: Bauer Lance O.
Published: April 2006

Measures of electroencephalographic and autonomic activity were recorded from 17 alcohol‐dependent patients (after 7–10 and 14–17 days of abstinence) and 14 age‐matched non‐drug‐dependent controls (after comparable intervals). The alcohol‐dependent group was divided into subgroups of abstinence‐prone or relapse‐prone patients, based on their 3‐month posttreatment outcome. Data analyses revealed that relapse‐prone patients evidenced more electroencephalographic 8‐activity at the vertex lead, and a larger amplitude carotid pulse than abstinence‐prone patients and controls. The implications of these preliminary findings for relapse prediction and typological development are discussed.
Frontal P300 Decrements in Antisocial Personality Disorder
Authors: Bauer Lance O. , O'Connor Sean , Hesselbrock Victor M.
Published: April 2006

Event‐related potentials (ERPs) were recorded from 83, 21‐ to 25‐year‐old nonalcoholic men varying in alcoholism vulnerability due to the presence/absence of an alcoholic family history or a personal history of antisocial personality disorder. ERPs were elicited by a visual oddball task in which the target was presented more frequently than the nontarget, in order to elicit impulsive or perseverative responding. Analyses of N200 and P300 revealed no group differences in the nontarget response. However, analyses of the target response revealed a significantly smaller P300 in the antisocial personality (ASP)+ group compared with the ASP‐ group. The P300 decrement was limited to frontal electrode sites and is interpreted as indicating the presence of subtle anterior brain dysfunction among ASP+ subjects.
Estimating Alcohol Involvement in Trauma Patients: Search for a Surrogate
Authors: Treno Andrew J. , Cooper Kirby , Roeper Peter
Published: April 2006

This study explores the potential for the development of a surrogate for alcohol‐involved traumatic injury. It presents a bivariate probit analysis that simultaneously models likelihoods of patients being tested for blood alcohol content (BAC) and having positive BACs given testing using 17,356 adult trauma cases selected from the California Regional Trauma Registry. It concludes that patient and injury characteristics predict both testing and BAC, and that a weighting scheme may be profitably used to determine changes in levels of alcohol‐involved trauma in populations over time in the absence of empirical measurement of BAC.
Adult Offspring of Alcoholic Women as Family History Informants
Authors: Smith Elizabeth M. , Przybeck Thomas R. , Bradford Susan E. , Gogineni Aruna , Spitznagel Edward L.
Published: April 2006

Eighteen years after their mothers had been hospitalized for alcoholism, adult offspring were asked if any of their 1st‐degree relatives had ever had a drinking problem. Proband and informant characteristics that affect the validity of reports of maternal drinking problems given by adult offspring of alcoholic women were identified. A history of alcohol‐related medical problems in the mother was associated with reporting maternal alcoholism. Being African‐American, having a history of suicide attempts in the mother, and having a good maternal posttreatment outcome were associated with false‐negative reports. Adding multiple offspring informants increased sensitivity to 86%. Female alcoholic offspring tended to underreport maternal alcoholism.
NMR Investigation of the Futile Cycling of Ethanol in Chronic Alcoholic Rats
Authors: Jucker Beat M. , Barnard Maria L. , Shulman Robert G.
Published: April 2006

Weight gain efficiency differences previously reported between alcohol‐fed rats and their controls were investigated. Additionally, the futile cycling of ethanol proposed to explain such differences was studied by NMR spectroscopy. Male Sprague‐Dawley rats were fed a nutritionally adequate diet containing 36% of the calories as alcohol, and their paired controls were fed an isocaloric diet for 1 f weeks to establish conditions of chronic alcohol feeding. Normalized metabolic efficiencies varied significantly during the initial 2‐week period (6.86 ± 0.51 vs. 2.83 ± 0.18 g/kcal × 10−2) for control and alcohol‐fed groups, respectively, and to a lesser extent over the entire feeding period (6.41 ± 0.78 vs. 4.60 ± 0.27 g/kcal × 10−2) for control and alcohol‐fed groups, respectively. Alcohol‐induced weight gain inefficiency in metabolism has previously been studied and explained by a variety of different biochemical and physiological mechanisms. One possible pathway of energy wastage may occur due to ethanol futile cycling from ethanol to acetaldehyde through the microsomal ethanol oxidation system pathway, and simultaneously from acetaldehyde to ethanol via the ADH pathway. This futile cycle represents a net loss of 6 ATP/cycle, corresponding to the loss of two reducing equivalents (NADH and NADPH). 1H NMR spectroscopy was used to test for this cycling in blood extracts after administration of 1,1‐2H2ethanol. No futile cycling was detected either during the initial 2 weeks of feeding or after the entire feeding period.
Effect of Ethanol on Human Colon Carcinoma CaCo‐2 and HT‐29 Cell Lines during the Maturation Process
Authors: Malagolini Nadia , Dall'Olio Fabio , Turrini Ileana , Cessi Carlo , Serafini‐Cessi Franca
Published: April 2006

The aim of the study was to ascertain whether the exposure to ethanol of human colon carcinoma CaCo‐2 and HT‐29 cell lines affects the differentiation process. As an index of enterocytic differentiation, the expression of sucrase, alkaline phosphatase, α2,6‐sialyltransferase toward the N‐acetyllactosaminic sequence, and β1,4‐N‐acetylgalactosaminyltransferase (β1,4GalNAc‐transferase) was examined. The latter enzyme is responsible for the biosynthesis of Sd* carbohydrate histo‐blood antigen, which mainly occurs in human colonic cells; its expression in CaCo‐2 cells depends strictly on the enterocytic differentiation. The addition of ethanol in the culture medium resulted in a significant increment of sucrase and α2,6‐sialyltransferase activities in both cell lines, as well as theβ1,4GalNAc‐transferase activity in CaCo‐2 cells and alkaline phosphatase activity in HT‐29 cells. The increment was dose‐dependent in the range between 50 and 200 mm ethanol and evident after 2 days of exposure in both cell systems. These results support the notion that, as occurs for cell lines of different origin, the ethanol in vitro positively affects the differentiation of intestinal cells, namely along the enterocytic lineage. The putative mechanism by which ethanol interferes with the maturation process of colonic cells is discussed.
Expression of Tumor Necrosis Factor‐α and Interleukin‐6 Cell‐Surface Receptors of the Alveolar Macrophage in Alcohol‐Treated Rats
Authors: D'Souza Nympha B. , Nelson Steve , Summer Warren R. , Deaciuc Ion V.
Published: April 2006

The hypothesis was tested that alcohol may modulate alveolar macrophage cytokine receptors, thus interfering in lung immune defense mechanisms. Male rats were treated with alcohol either acutely (7 hr continuous intravenous alcohol infusion at a rate of 30 mg/100 g body weight/hr after a priming dose of 175 mg/100 g body weight) or chronically (feeding an alcohol‐containing liquid diet for 12–14 weeks). Three hr before killing, the rats received an intravenous injection of Gram‐negative bacterial lipopolysaccharide (LPS; Escherichia coll, O26:B6, 100 μg/100 g body weight). After anesthesia with sodium pentobarbital, the trachea was cannulated, and the lungs excised and lavaged to obtain alveolar macrophages. The recovered cells were used to measure the binding of recombinant human [125I]tumor necrosis factor‐α (TNF‐α) and [125I]interleukin‐6 (IL‐6). Kd and Bmax, were determined at 4°C, thus reflecting only the cell‐surface binding sites and their affinity. Two binding sites were detected for both cytokines: high‐affinity (Kd1 in the range of 20–110 pM), low‐capacity (Bmax, in the range of 1–13 fmol/105 cells), and low‐affinity (Kd2 in the range of 0.6–1.3 nM), high‐capacity (Bmax2 in the range of 34–100 fmol/105 cells). Acute alcohol treatment significantly decreased Bmax1 (39%) and Bmax (79%) for TNF‐α, whereas chronic alcohol feeding abrogated the Bmax1 (Bmax1= 0), without affecting Bmax2. In the acute group, LPS had an effect similar to that of alcohol. Alcohol administration did not modify the LPS effects. The following changes were monitored for IL‐6 binding. Acute alcohol treatment markedly reduced (86%) Bmax2. LPS administration to saline‐infused group increased Kd1 (122%) and Bmax1 (197%), and significantly diminished (72%) Bmax2 These effects of LPS were not altered by alcohol administration, with the exception of Kd1 which was decreased (43%) by LPS administration to acutely, alcohol‐intoxicated rats. In the chronic treatment group, alcohol feeding increased Bmax2 (426%), an effect that was not modified by LPS injection.

These data suggest that: (1) both acute and chronic alcohol administration to rats differentially affects the alveolar macrophage cell‐surface receptors for TNF‐α and IL‐6, and (2) alcohol‐induced alterations in these two cytokine receptors may in part mediate alcohol effects on lung immune defense.
Ethanol Modulates the Hormone Secretory Responses Induced by Epidermal Growth Factor in Choriocarcinoma Cells
Authors: Wimalasena Jay , Beams Faith , Caudle Michael R.
Published: April 2006

Analysis of clinical data has implicated ethanol (EtOH) as an embryotoxic agent and as an agent that disrupts normal placental structure and function. Because epidermal growth factor (EGF) is an important regulator of placental function, we have studied the effects of EtOH on EGF‐induced hormone secretion using JEG‐3 choriocarcinoma cells that serve as a model for trophoblast cells. EtOH at physiological (5‐100 mm) concentrations modulated effects of EGF in a time and dose‐dependent manner. EGF‐induced P4 secretion was increased by 20–100 mM EtOH after a 2‐day pretreatment of cells with EtOH, but not after a 6‐day pretreatment. Preincubation with 50 mM EtOH doubled the P4 responses to 50 and 100 ng/ml EGF. Although a 2‐ or 4‐day preincubation of cells with 10–50 mM EtOH increased the secretion of E2 in response to 20 ng/ml EGF, a 6‐day preincubation inhibited the secretory response to EGF. Pretreatment of cells with 10–50 mm, but not 100 mm EtOH for 2 to 6 days enhanced the human chorionic gonadotropin (hCG) secretory response to EGF. At 50 mm EtOH, the secretion of hCG in response to EGF was increased 2‐fold. EtOH also increased basal hCG secretion in a dose‐dependent manner between 10–50 mm EtOH. These results suggest that EtOH may modulate EGF‐stimulated hormone secretion from cells of placental origin. Such alterations, if they occur in vivo, may impact on the function of the placenta and could potentially explain the pathophysiology of alcohol toxicity during pregnancy.
Seizures during Ethanol Withdrawal Are Blocked by Focal Microinjection of Excitant Amino Acid Antagonists into the Inferior Colliculus and Pontine Reticular Formation
Authors: Riaz Awais , Faingold Carl L.
Published: April 2006

Physical dependence on ethanol can result in seizure susceptibility during ethanol withdrawal. In rats, generalized tonic‐clonic seizures are precipitated by auditory stimulation during the ethanol withdrawal syndrome. Excitant amino acids (EAAs) are implicated as neurotransmitters in the inferior colliculus and the brain stem reticular formation, which play important roles in the neuronal network for genetic models of audiogenic seizures (AGSs). Ethanol blocks the actions of EAAs in various brain regions, including the inferior colliculus. In this study, dependence was produced by intragastric administration of ethanol for 4 days. During ethanol withdrawal, AGSs were blocked by systemic administration of competitive or noncompetitive NMDA antagonists 3‐((±)‐2‐carboxypiperazin‐4‐yl)‐propyl‐1‐phosphonic acid (CPP) or dizocilpine (MK‐801). Focal microinjections of NMDA or non‐NMDA antagonists into the inferior colliculus or the pontine reticular formation also inhibited AGSs. MK‐801 was the most potent anticonvulsant systemically. When injected into the inferior colliculus, CPP had a more potent anticonvulsant effect than either MK‐801 or the non‐NMDA antagonist 6‐cyano‐7‐nitroquinoxa‐line‐2,3‐dione. The inferior colliculus was more sensitive than the pontine reticular formation to the anticonvulsant effects of both competitive NMDA and non‐NMDA antagonists. The results of the present support the idea that continued ethanol administration may lead to development of supersensitivity to the action of EAAs in inferior colliculus and pontine reticular formation neurons. This may be a critical mechanism subserving AGS susceptibility during ethanol withdrawal.
Differential Effects of Ethanol on Baroreceptor Heart Rate Responses of Conscious Spontaneously Hypertensive and Normotensive Rats
Authors: Abdel‐Rahman Abdel A.
Published: April 2006

This study investigated the acute effects of ethanol (0.25, 0.5, or 1 g/kg, iv) on mean arterial pressure, heart rate, and gain of the baroreceptor reflex control of heart rate (BRS) in conscious spontaneously hypertensive rats (SHRs) and age‐matched Wistar rats. BRS was substantially lower in the SHRs as compared with the Wistar rats when measured by phenylephrine (‐0.95 ± 0.16 vs. ‐2.02 ± 0.22 beats/min/mm Hg) or nitroprusside (‐1.90 ± 0.2 vs. ‐3.02 ± 0.32 beats/min/mm Hg). None of the doses of ethanol influenced BRS in the SHR. In contrast, ethanol attenuated BRS in Wistar rats, but this effect was dependent on the dose used and the type of response. The lower doses attenuated the reflex tachycardic response, but had no effect on the reflex bradycardic response. On the other hand, the 1 g/kg dose of ethanol attenuated the reflex bradycardic but not the tachycardic response. Ethanol produced a pressor effect (15‐25 mm Hg; 5‐min duration), which was neither dose‐ nor strain‐dependent. However, only in the SHR mean arterial pressure remained elevated (10‐15 mm Hg above control) for 20 min in response to the 0.5 g/kg dose of ethanol, and its recovery coincided with the occurrence of a slowly developing negative chronotropic response. Ethanol produced a dose‐related negative chronotropic effect in both strains of rats that was of longer duration in the SHR, particularly with the 1 g/kg dose. It is possible that the bradycardic effect of ethanol influenced negatively its pressor effects. Data suggest that, in conscious rats, ethanol: (1) attenuates BRS in normotensive rats but not in the SHR; (2) causes a brief pressor effect that is not related to its dose, the level of arterial pressure, or its influence on the gain of the baroreceptor reflex; and (3) elicits dose‐related bradycardic responses that are of longer duration in the SHR, particularly with the higher dose. This negative chronotropic effect of ethanol may limit its pressor effect in SHRs.