bluuebunny/crossref_metadata_2025 huggingface dataset:
Alcohol Availability and the Formal Power and Resources of State Alcohol Beverage Control Agencies
Authors: Gruenewald Paul J. , Madden Pat , Janes Kathy
Published: April 2006

The formal powers and resources of state alcohol beverage control agencies place them in a position to regulate access to alcoholic beverages through restrictions on retail distribution and sales. For example, monopoly states restrict access to spirits, and sometimes wine, by allowing retail sales only through state stores. On the other hand, license and monopoly states share in restricting sales through the use of price posting and fixing provisions. The degree to which these powers are realized in restrictions on alcohol outlets (e.g., licenses) and subsequent alcohol consumption (e.g., sales) was investigated in the current study.

In a cross‐sectional analysis of data available from 44 alcohol beverage control (ABC) jurisdictions in the United States, it was shown that states with greater restrictions on retail sales had greater resources for the conduct of ABC activities and lower densities of spirit outlets. These states, however, had greater densities of wine and beer outlets. States with greater marketplace restrictions had more resources for ABC enforcement activities and lower outlet densities across all beverage types. Further, supporting the suggestion that availability and demand may be simultaneously related, greater outlet densities were related to greater alcohol consumption (for beer) and greater levels of consumption were related to greater outlet densities (for wine).
Modification of Resistance to Streptococcus pneumoniae by Dietary Ethanol, Immunization, and Murine Retroviral Infection
Authors: Darban Hamid , Watson Ronald Ross , Darban Jill R. , Shahbazian L. Masoud
Published: April 2006

Hallmarks of the acquired immune deficiency syndrome (AIDS) are immunologic alterations, frequently associated with opportunistic infections. To study such associations, LP‐BM5 murine retrovirus infection was used as a murine model of AIDS. Retrovirally infected and uninfected mice were fed a 5% (v/v) ethanol diet for 55 days and then fed a 7% v/v ethanol diet for the final 7 days to assert the role of ethanol as a cofactor in development of murine AIDS. There was a reduction in polymorphonuclear neutrophils count in ethanolfed groups. Neutrophils increased in retrovirus‐infected groups, except those vaccinated 10 days before challenge with live bacteria. The percentage of splenic lymphocytes in the retrovirus‐infected group was reduced in comparison with controls. Survival of the mice challenged intraperitoneally with Streptococcus pneumoniae was increased by vaccination and suppressed by dietary alcohol. Retrovirus infection caused a much faster death rate after bacterial challenge than nonretrovirus infected controls. Vaccination played an important role in delaying the death rate in all treated groups. Transferring spleen cells from healthy, unimmunized mice also enabled the retrovirally infected mice to survive the bacterial infection longer. Enhancement of resistance to S. pneumoniae by vaccination and transfer of immunocompetent cells to mice immunosuppressed by retroviral infection show the potential to use immunomodulation to affect disease resistance in AIDS.
Surface Exposure of Synaptosomal Gangliosides from Long‐Sleep and Short‐Sleep Mice*
Authors: Ullman M. David , Ventura Robert F. , Draski Laura J. , Deitrich Richard A. , Baker Rodney C.
Published: April 2006

A galactose oxidase/NaB[3H]4 technique was used to examine the relative surface exposure of gangliosides from whole brain synaptosornes of long‐sleep (LS) and short‐sleep (SS) mice. The surface exposure of the monosialoganglioside, GM1, did not differ between the two lines. Surface exposure of the polysialogangliosides GD1a, GDlb, and GT1b, however, was significantly greater in LS synaptosomes than in SS. Hydrolysis of the polysialogangliosides by neuraminidase to the end‐product, GM1, at early time periods occurred more rapidly in LS than in SS synaptosomes. Upon exposure to either 250 mM or 50 mM ethanol, LS synaptosomal ganglioside surface exposure was decreased, but that of SS was increased. Pairwise comparisons of the individual ganglioside classes indicated that the decrease in LS synaptosomal ganglioside surface exposure was attributable to decreases in the polysialogangliosides, compared with controls. The ethanol‐induced increase in SS synaptosomal ganglioside surface exposure, however, was mainly due to an increased surface exposure of only GD1a. These results suggest that intrinsic differences in the surface exposure of gangliosides and/or the magnitude and direction of ethanol‐induced changes in ganglioside surface distribution may reflect biophysical or modulatory mechanisms by which this class of compounds modifies membrane sensitivity to ethanol. These results suggest that further studies should be performed to determine whether gangliosides are factors in genetically determined sensitivity to ethanol.
Effect of Calcitonin on the Alcohol Drinking of Rats
Authors: Laitinen Kalevi , Sinclair David , Nurmi Maria , Hietala Reija , Kröger Heikki , Kiianmaa Kalervo , Salaspuro Mikko
Published: April 2006

Previous work has shown that calcitonin inhibits eating by rats and that it affects several neurotransmitter systems suspected to play a role in alcohol consumption. The present study was an initial test of whether calcitonin does affect voluntary alcohol consumption by male Wistar rats with prolonged alcohol experience. Calcitonin (20p IU/kg) or saline was injected subcutaneously on 10 consecutive days when the rats (n= 20) had continual access to 10% (v/v) ethanol solution, and to food and water. Using a cross‐over design, the effects of 40 IU/kg calcitonin vs. saline were then examined in a second 10‐day treatment period. Similar patterns of effects were obtained with both calcitonin doses, but the patterns differed with alcohol, food, and water intake. Alcohol drinking showed biphasic changes with both doses, producing highly significant Treatment × Day interactions (p < 1E‐10 and p= 6E‐7): it was significantly reduced on the first day of calcitonin treatment and significantly increased on the last few days. Food intake was reduced on all calcitonin days although most markedly on the first. Water drinking was not altered on the first calcitonin day, but was greatly increased on the second, then gradually returned toward the baseline. In a second experiment, the animals were switched to 1 hr of alcohol access per day, and calcitonin (20 IU/kg) was administered periodically to one group 4 hr before the alcohol access. Alcohol drinking was significantly reduced in all cases when the calcitonin injection was preceded by at least 1 day without calcitonin. It is concluded that the effect of calcitonin on alcohol consumption depends upon the duration of calcitonin treatment: it had a suppressive effect when given only periodically but an enhancing effect when given on consecutive days.
The Effect of Alcohol Withdrawal on Serum Concentrations of Lp(a), Apolipoproteins A‐1 and B, and Lipids
Authors: Huang Charng‐Ming , Elin Ronald J. , Ruddel Mark , Schmitz John , Linnoila Markku
Published: April 2006

Moderate alcohol consumption is associated with a decreased risk of coronary artery disease. The mechanism of the putative protective effect of alcohol intake, however, remains elusive. Recent studies suggest that a ratio of apolipoprotein A‐I/apolipoprotein B and Lp(a) are better indicators of the risk of atherosclerosis than total cholesterol and high density lipoprotein cholesterol. To assess the effect of alcohol on these analytes, we determined the concentration of Lp(a), apolipoprotein A‐I, apolipoprotein B, total cholesterol, and high‐density lipoprotein cholesterol, and calculated low‐density lipoprotein cholesterol in serum of 12 patients meeting DSM‐III‐R criteria for alcohol dependence at the time of admission for treatment of alcohol withdrawal (before). The analyses were repeated after 4 weeks of supervised abstinence on a locked research unit (after). With abstinence, there was a significant increase in the concentration of Lp(a), the atherogenic index and the ratio of low‐density to high‐density lipoprotein cholesterol but a significant decrease in total cholesterol, high‐density lipoprotein cholesterol, apolipoprotein A‐I, and the apolipoprotein A‐I/B ratio. Apolipoprotein B and low‐density lipoprotein cholesterol showed no significant changes before and after alcohol abstinence. Thus, decreased Lp(a) and increased high‐density lipoprotein cholesterol and apolipoprotein A‐I may be factors mediating the putative protective effect of alcohol in coronary artery disease.
Chronic Ethanol and Cocaine‐Induced Hepatotoxicity: Effects of Vitamin E Supplementation
Authors: Pirozhkov Sergei V. , Eskelson Cleamond D. , Watson Ronald R.
Published: April 2006

The mechanisms of chronic cocaine toxicity and its potentiation by ethanol were investigated. Cocaine was administered to male C57BL/6 mice (20 mg/kg by peritoneal injection twice a day) alone or in combination with ethanol‐containing diets (26% of total calories) supplied with a normal (20 IU/liter) or high content (170 IU/liter) of vitamin E. Liver levels of vitamin E, reduced glutathione, ascorbic acid, and hydroxyproline were measured. Accumulation of thiobarbituric acid‐reactive substances, after in vitro stimulation of lipid peroxidation by Fe3+/ADP/ascorbate system, was measured as an index of susceptibility of hepatic membranes to oxidative stress. Plasma alanine aminotransferase, lethality, liver weight, and liver/ body weight ratio were determined to assess the extent of liver toxicity. Consumption of ethanol exacerbated liver toxicity induced by cocaine treatments and reduced survival, but ethanol or cocaine treatments alone caused no or only modest mortality. Ethanol potentiated cocaine‐induced accumulation of collagen in the liver and depletion of ascorbic acid. Hepatotoxicity induced by the combined ethanol plus cocaine treatment was not accompanied by a decrease in intracellular vitamin E or glutathione content. There were no changes in the basic levels and in the rate of accumulation of thiobarbituric acid‐reactive substances in liver homogenates under the lipid peroxidation‐stimulating system in vitro. The toxic effects of ethanol and cocaine were not reduced by the ingestion of vitamin E during short‐term exposure of 21 days of treatment.
Enzymatic Production of Acetaldehyde from Ethanol in Rat Brain Tissue
Authors: Gill K. , Menez J. F. , Lucas D. , Deitrich R. A.
Published: April 2006

The capacity for the brain to produce acetaldehyde (AcHO) from ethanol was determined in rat brain homogenates. Rat brains were perfused with saline‐heparin solution and homogenized in a phosphate buffer. Varying amounts of tissue were incubated with ethanol (0–100 mM) for periods of up to 60 min. The reaction was stopped by the addition of desferrioxamine and ice‐cold perchloric acid. Supernatants were treated with dinitrophenylhydrazine reagent, extracted with isooctane in the presence of an internal standard, and the derivatives were separated by HPLC.

The addition of 4‐methyl pyrazole (an alcohol dehydrogenase inhibitor) or metyrapone (a cytochrome P450 inhibitor) had no effect on the amount of recovered AcHO. On the other hand, treatment with the catalase inhibitors sodium azide, cyanamide, or 3‐amino‐1,2,4‐triazole blocked the production of AcHO while the addition of exogenous peroxide or a peroxide‐generating system enhanced the production of AcHO. Overall, these results suggest that AcHO may be produced in the brain during alcohol intoxication, through the action of the enzyme catalase.
Differences in Hepatic Microsomal Cytochrome P‐450 Isoenzyme Induction by Pyrazole, Chronic Ethanol, 3‐Methylcholanthrene, and Phenobarbital in High Alcohol Sensitivity (HAS) and Low Alcohol Sensitivity (LAS) Rats
Authors: Lucas Danièle , Ménez Jean‐François , Berthou François , Cauvin Jean‐Michel , Deitrich Richard A
Published: April 2006

High and low alcohol sensitivity (HAS and LAS) rats have been selected for their differences in ethanol‐induced sleep time. Liver monooxygenase activities were studied in HAS and LAS rats before and after treatments with known inducers such as chronic ethanol, pyrazole, 3‐methylcholanthrene (3‐MC) and phenobarbital (PB) to determine whether the selection procedure also selected for differences in the cytochrome P‐450 (P‐450) inducibility. This previously has been shown with long sleep (LS) and short sleep (SS) mice, which were selected using a similar criterion. 3‐MC and PB, in conjunction with chronic ethanol treatment, were used in order to evaluate the interactions of ethanol with these inducers. Prior to treatment, total P‐450 content was slightly lower in LAS than in HAS rats. However, both lines displayed the same microsomal monooxygenase activities related to different P‐450 isozymes. This was demonstrated by ethoxyresorufin deethylation (EROD) for cytochrome P‐450 1Al (CYP1A1), acetanilide hydroxylation (ACET) for CYP1A2, pentoxyresorufin dealkylation (PROD) for CYPPB, 1‐butanol oxidation (BUTAN) and N‐nitrosodimethylamine demethylation (NDMA) for CYP2E1. After the different treatments, HAS rats did not differ from LAS rats in their CYP2E1 inducibility. However, pyrazole, PB and 3‐MC treatment led to differences in CYP1A and CYP2B monooxygenase activities between the two lines. The enhancement of PROD by pyrazole treatment was less prominent in LAS (1.7‐fold of the control value) than in HAS rats (3.8‐fold). After 3‐MC treatment, EROD activity was increased 120‐fold in LAS rats but only 48‐fold in HAS thus showing a greater sensitivity of LAS rats to 3‐MC (similar to the LS and SS mice). On the other hand, ACET was more enhanced in HAS (4.8‐fold) than in LAS (2.7‐fold) rats. Interaction of chronic ethanol with PB resulted in a 65% increase of ACET only in HAS rats. Interaction of chronic ethanol with 3‐MC resulted in a 25% decrease of EROD or ACET induction in both lines, when compared with induction of 3‐MC alone. A general interaction between rat line, ethanol diet, and 3‐MC showed that PROD activity was increased 3‐fold in LAS rats by 3‐MC but not by ethanol + 3‐MC. These data suggest that HAS and LAS rats differ in their regulatory mechanism of induction of both CYP1A and 28 and that chronic ethanol administration interferes with the induction of CYP1A1, 1A2 and 2B enzyme activities.
A Gastric Alcohol Dehydrogenase in the Baboon: Purification and Properties of a ‘High‐Km,’ Enzyme, Consistent with a Role in ‘First Pass’ Alcohol Metabolism
Authors: Algar Elizabeth M. , VandeBerg John L. , Holmes Roger S.
Published: April 2006

The major isozyme of alcohol dehydrogenase in baboon stomach, ADH3, has been purified to homogeneity and characterized with a range of alcohol and aldehyde substrates. Using Kcat/Km, values as an indication of substrate efficacy, medium‐chain length aliphatic alcohols and aldehydes were identified as the preferred substrates. ADH3 showed ‘high‐Km’ properties with respect to ethanol, and is expected to significantly contribute to ‘first‐pass’ metabolism of alcohol. The enzyme exhibited more than two orders of magnitude higher turnover of substrate than the baboon liver ‘low‐Km’ ADH, and may play a role in the rapid metabolism of a wide range of ingested alcohols in the diet.
Chronic Ethanol Consumption Induces Accumulation of Proteins in the Liver Golgi Apparatus and Decreases Galactosyltransferase Activity
Authors: Guasch Rosa , Renau‐Piqueras Jaime , Guerri Consuelo
Published: April 2006

The effect of chronic ethanol consumption on labeled glycoprotein secretion and galactosyltransferase activity has been analyzed in cis‐ and trans‐Golgi apparatus fractions isolated from rat liver. Rats were injected intraperitoneally with 3H‐leucine, after different chase periods (30, 60, 180 min), and the radioactivity of the different subcellular fractions as well as of the isolated Golgi apparatus was measured. Chronic alcohol treatment induces an increase in liver weight as well as an enhancement of total liver protein. Ethanol treatment produces a significant accumulation of labeled proteins in isolated Golgi apparatus fractions after a 60‐ and 180‐min chase. An accumulation of labeled proteins in the cytosolic fraction was observed only after 180 min. The alcohol treatment also induces a significant decrease in the activity of galactosyltransferase in both liver homogenate and Golgi apparatus fractions. These results suggest that an impairment of Golgi apparatus functions, including glycosylation and glycoprotein trafficking, could be one of the mechanisms involved in the accumulation of hepatic protein and thus in the pathogenesis of alcohol‐induced injury in the liver of chronic ethanol‐consuming animals.
The Role of Instructional Set on Alcoholic Performance
Authors: Jo Nixon Sara , Errico Austin L. , Parsons Oscar A. , Leber William R. , Kelley Cynthia J.
Published: April 2006

This study was conducted to determine whether alcoholic and control subjects respond differently to manipulations that either enhance personal involvement (PI) or reduce negative affect (R, relaxation) on tests of neuropsychological function. In Phase 1, 48 male alcoholics and 36 male control subjects completed neuropsychological tasks under standard instructional sets. In Phase 2, subjects completed equivalent forms of these tests under one of three randomly assigned conditions; the PI condition in which subjects were encouraged to identify specific ways of improving their performance, the R condition in which subjects participated in a short relaxation exercise designed to reduce anxiety, or a No Treatment (NT) condition in which no attempt to manipulate the subjects' involvement or affect was made. Alcoholics were inferior to controls in both Phase 1 and Phase 2 [Fs (1,82) > 5.03, ps < 0.03]. The experimental manipulation differentially affected measures of negative affect and effort in the predicted direction. There were no group × condition interactions. Alcoholic and control subjects responded comparably to the experimental manipulations. This investigation, in combination with others using related manipulations, reinforces the hypothesis that alcohol‐related cognitive dysfunction reflects an underlying deficit in brain states.
Relationship of Insulin Resistance to Protein‐Energy Malnutrition in Patients with Alcoholic Liver Cirrhosis: Effect of Short‐Term Nutritional Support
Authors: Wahl Denis G. , Dollet Jean‐Marc , Kreher Manuel , Champigneulle Bruno , Bigard Marc‐André , Gaucher Pierre
Published: April 2006

Protein‐energy malnutrition (PEM) and insulin resistance (IR) are common features of alcoholic liver cirrhosis (ALC). In order to determine a relationship between them, nutritional status and glucose homeostasis were studied in 26 patients with ALC. Nutritional status was assessed through dietary, anthropometric, and biological parameters. An IR index (M/I) was obtained from the euglycemic insulin clamp technique. M/I was significantly correlated with accurate markers of PEM (albumin, transthyretin, and retinol‐binding protein) but not with other markers of liver dysfunction. Nine patients were studied before and after nutritional support: M/I was significantly improved as were serum markers of PEM. Other markers of liver dysfunction were also significantly improved. These findings suggest that PEM could be responsible, in part, for IR in patients with ALC who are frequently malnourished. Moreover, nutritional support improved insulin sensitivity in these patients.
Brain Morphologic Characteristics of Cirrhotic Alcoholics and Cirrhotic Nonalcoholics: An MRI Study
Authors: Barthauer Linda , Tarter Ralph , Hirsch William , Van Thiel David
Published: April 2006

Cirrhotic alcoholics, cirrhotic nonalcoholics, and normal controls were compared on planimetric and subjective ratings of the MRI of the brain. The results indicated that the cirrhotic alcoholics exhibited more gross pathology than the nonalcoholic cirrhotics on ratings of frontal, parietal, and cerebellar atrophy; however, these groups were more similar to each other than they were different on planimetric measurements. The results are discussed in terms of the etiology and localization of the neuropathologic sequelae found commonly among alcoholics.
Fetal Alcohol Syndrome: A Case Report of Neuropsychological, MRI, and EEG Assessment of Two Children
Authors: Mattson Sarah N. , Riley Edward P. , Jernigan Terry L. , Ehlers Cindy L. , Delis Dean C. , Jones Kenneth L. , Stern Catherine , Johnson Kathleen A. , Hesselink John R. , Bellugi Ursula
Published: April 2006

Neuropsychological, neuroanatomical, and electrophysiological data are presented on two subjects with fetal alcohol syndrome (FAS). Both boys had intelligence quotients in the mentally deficient range and were found to have several other severe, specific deficits. Magnetic resonance imaging showed abnormalities of the corpus callosum, and reductions in the size of the basal ganglia and thalamic structures. No focal abnormalities were noted in the electroencephalogram records, although the electroencephalograms of both boys were moderately abnormal for their age group. A multidisciplinary approach to the study of FAS, hopefully will lead to a more unified concept of the disorder and perhaps indicate specific areas of vulnerability.
The Relationship of Outlet Densities to Alcohol Consumption: A Time Series Cross‐Sectional Analysis
Authors: Gruenewald Paul J. , Ponicki William R. , Holder Harold D.
Published: April 2006

The implementation of regulations on access to alcoholic beverages, whether through beverage taxes or restrictions on the availability of this commodity through alcohol outlets, has often been proposed as a legitimate and politically feasible approach to the prevention of alcohol‐related problems. Empirical studies of the effects of these approaches to regulation on alcohol consumption and problems, however, have not been unanimous in their support of these preventive measures. While support exists for the suggestion that increases in alcohol beverage prices reduce consumption and have preventive effects upon the occurrence of problems, relatively little evidence exists for the supposition that the regulation of alcohol availability will have similar preventive effects. The lack of evidence in support of the latter thesis rests primarily upon the difficulty of obtaining sufficient data to examine comprehensive models of access to alcohol.

The current paper analyzes aggregate time series cross‐sectional data from states of the U.S. to evaluate the relationships between alcohol beverage prices, availability, and alcohol sales within one analytic model. The model relates beverage prices and alcohol availability directly to alcohol sales in the context of an assumed simultaneous relationship between sales and availability. The results show that, independent of the effects of beverage prices, and controlling for the endogeneity of sales and availability, physical availability of alcohol was directly related to sales of spirits and wine.
Effects of Ethanol Concentration and Fixed‐Ratio Requirement on Ethanol Self‐Administration by P Rats in a Continuous Access Situation
Authors: Files Forrest J. , Andrews Christine M. , Lewis Roderic S. , Samson Herman H.
Published: April 2006

Rats, from the alcohol preferring (P) line, were placed in operant chambers in which food pellets, water, and 10% ethanol (v/v) were available continuously for 23 hr/day. During Experiment 1, the effects of changing ethanol concentration and response requirement for ethanol were examined. Ten percent and 20% ethanol (v/v) were available on two fixed ratio (FR) schedules, FR 1 and FR 4, for 2 weeks each. During Experiment 2, the effects of increasing the response requirement for ethanol were investigated. Starting with FR 4, the FR requirement for ethanol doubled during 2‐week intervals until FR 32 was in effect. For the final phase of these studies, water was placed in the dipper for 1 week followed by a return to 10% ethanol in the dipper.

The results from Experiment 1 indicated that when the FR requirement was decreased from FR 4 to FR 1, ethanol‐reinforced responding decreased but total daily intake increased. Lowering the FR requirement did not affect the number of ethanol bouts per day but bout size increased. Ethanol concentration had no effect on bout size but the number of bouts per day decreased when the concentration was increased to 20%. Since bout size was unchanged by increasing the ethanol concentration, intake per bout increased at 20% ethanol. The results from Experiment 2 indicated that increasing the response requirement for ethanol decreases ethanol intake. When water was placed in the dipper, responding decreased to the lowest levels observed in the experiment. When ethanol was returned to the dipper, responding returned to baseline levels. Overall, the results indicate that while P rats may consume more ethanol than other lines of rats, their behavior can be modified by environmental variables in a manner somewhat similar to heterogeneous nonselected Long‐Evans rats.
Ethanol Ingestion Increases Susceptibility of Mice to Listeria monocytogenes
Authors: Saad Assad Joe , Domiati‐Saad Rana , Jerrells Thomas R.
Published: April 2006

Excessive consumption of alcohol is associated with an increase in the frequency and severity of infectious diseases. Ethanol adversely affects specific and nonspecific aspects of the immune response. We used a murine model to determine whether ethanol ingestion impairs host mechanisms of resistance to Listeria monocytogenes. Naive mice and mice immune to L. monocytogenes were pair‐fed either a Leiber‐DeCarli liquid diet containing 7% (v/v) ethanol or an isocaloric control diet for 7 days. Then, nonimmune mice were given a sublethal dose of L. monocytogenes and studied 2 and 5 days after infection, and immune mice were challenged with a lethal dose of L. monocytogenes and studied 5 days after infection. Multifocal liver abscesses developed in nonimmune ethanol‐treated and control mice 2 days after infection. Bacterial colony counts in the spleens were similar between the two groups; however, counts in the livers were slightly higher in ethanol‐treated mice as compared with those in control mice. Five days after infection the nonimmune ethanoltreated mice had large necrotizing liver granulomas and organ bacterial colony counts 100 to 1000 times higher than those in control mice. Immune ethanol‐treated mice had large areas of liver necrosis and inflammation containing numerous Gram‐positive bacilli, whereas immune control mice had small, well‐formed granulomas and much less necrosis. Organ bacterial colony counts were about 100 times higher in immune ethanol‐treated mice as compared with those in immune control mice. Liver enzyme levels and mortality were significantly higher in ethanol‐treated immune and nonimmune mice as compared with those in immune and nonimmune control mice. Data support the suggestion that ethanol consumption impairs the development and expression of T cell‐mediated immunity of mice to L. monocytogenes, resulting in increased susceptibility to infection with this organism.
Effects of Ethanol on Cultured Fetal Serotonergic Neurons
Authors: Lokhorst Denise K. , Druse Mary J.
Published: April 2006

In utero ethanol exposure impairs the development of several neurotransmitter systems, including the serotonergic system. However, at present the mechanism by which in utero ethanol exposure damages the developing brain is unknown. This research examined the possibility that ethanol directly impairs the development of serotonergic neurons. This hypothesis was assessed by examining the content of serotonin (5‐HT), 5‐HT uptake, and 5‐HT immunopositive neurons in cultures of fetal rhombencephalic neurons that were exposed to ethanol for 4 days in vitro. In addition, the effects of in vitro ethanol exposure on protein and DNA content of cultured rhombencephalic neurons were determined.

These studies demonstrated that a 4‐day exposure of cultured rhombencephatic neurons to 50 to 300 mg ethanol/dl did not affect 5‐HT content, 5‐HT uptake, or the proportion of 5‐HT immunopositive neurons. In addition, this ethanol exposure had no significant effect on protein or DNA content. Additional studies, using a 4‐day exposure to 450 mg ethanol/dl also did not detect significant differences in 5‐HT uptake or in protein or DNA content.

The marked differences in the findings of the present in vitro and previous in vivo studies may be due to the fact that the ethanol exposure in vivo was longer than that in vitro, and included the period of early development of serotonergic neurons and their progenitors. Alternatively, the differences may be due to ethanol‐associated alterations in maternal or fetal factors (e.g., hormones, amino acids, and growth factors) that are necessary for the normal development of the serotonergic system in vivo. Normal concentrations of such factors in the serum‐containing media may have protected the cultured neurons from the damaging effects of ethanol.
Influence of Thyrotropin‐Releasing Hormone and Catecholaminergic Interactions on CNS Ethanol Sensitivity
Authors: French Thomas A. , Masserano Joseph M. , Weiner Norman
Published: April 2006

The role of catecholamine neuronal systems in mediating the analeptic and thermogenic effects of thyrotropin‐releasing hormone (TRH) was examined in long‐sleep (LS) and short‐sleep (SS) mice. TRH [0.1 to 40 μg, intracerebroventricularly (icv)] was associated with a reduction in the sleep times of LS mice, but no dose of TRH had any effect on sleep times of SS mice. However, TRH (20 μg, icv) produced a 1.0° to 1.5°C attenuation of the ethanol‐induced hypothermia in both LS and SS mice. TRH did not change the rate of ethanol elimination in either line of mice, suggesting that the reduction in LS sleep times and attenuation of LS and SS hypothermia were due to decreased CNS ethanol sensitivity rather than an increase in the rate of ethanol metabolism. TRH (20 μg, icv) given alone produced an activation of central and peripheral catecholamine systems in LS, but not SS mice, as reflected by an increase in the invivo tyrosine hydroxylase (TH) activity in the brain and adrenal gland. TRH, given with ethanol, prevented or attenuated ethanol‐induced decreases in the brain and adrenal gland in vivo TH activity in LS mice but not SS mice. Thus, there was an association between the ability of TRH to produce an activation of catecholamine neuronal systems (increased rate of catecholamine biosynthesis) and the analeptic action of TRH to reduce the CNS depressant effects of ethanol (decreased sleep times). TRH was able to attenuate the hypothermic effect of ethanol in both LS and SS mice, despite a lack of effect on TH activity, suggesting that catecholamine neurons may not have a major role in the thermogenic action of TRH in LS and SS mice.
Detection of a CA Repeat Polymorphism in the Rat Class I Alcohol Dehydrogenase Gene
Authors: Carr L. G. , Koivisto T. , Eriksson C. J. P. , Crabb D. W.
Published: April 2006

Differences in the amount of alcohol dehydrogenase (ADH) expressed in liver could play a role in altering ethanol metabolic rates and thus influence alcohol consumption. There is an alternating purine‐pyrimidine repeat length polymorphism in the first intron of mouse Adh‐1. Mouse strains that lack 101 basepairs of this 288 basepairs alternating sequence express only half as much ADH mRNA and have lower ADH‐A2 activity, suggesting that this alternating sequence might modify transcription of the gene. The rat class I ADH gene also has a CA repeat in the first intron. A polymerase chain reaction (PCR) method was used to amplify the CA repeat region in different rat lines to determine whether this CA repeat is polymorphic in the rat and if so, if different length repeats correlate with the drinking behavior of rats selectively bred for high [preferring (P); high alcohol drinking (HAD); Alko, Alcohol (AA) lines] and low [non‐preferring (NP); low alcohol drinking (LAD); Alko, Non‐Alcohol (ANA) rat lines] alcohol drinking. A CA repeat polymorphism was detected in rat class I ADH of these different rat lines, but there was no difference in the length of the repeat between the high and low drinking rats in each line. Liver ADH activity was also not significantly different between two rat lines that have different CA repeat lengths. Thus, there is CA repeat length polymorphism in the first intron of rat class I ADH, which may be useful in genomic mapping, but it is not associated with differences in ADH activity or drinking behavior in these rat lines.
Aversive Reactions and Alcohol Use in Europeans
Authors: Whitfield J. B. , Martin N. G.
Published: April 2006

Two hundred subjects of European descent completed a questionnaire about alcohol use and reactions to alcohol. Eleven subjects (5.5%) reported that they always experienced unpleasant reactions after small amounts of alcohol, and these subjects reported significantly lower levels for quantity and frequency of habitual alcohol use, and fewer drinks in the preceding 7 days, than the other subjects. Reactions to alcohol, either genetic or acquired, can therefore be significant in determining alcohol use in non‐Asian groups.
Ethanol Alters the Metabolic Response of Isolated, Perfused Rat Liver to a Phagocytic Stimulus
Authors: D'Souza Nympha B. , Bagby Gregory J. , Lang Charles H. , Deaciuc Ion V. , Spitzer John J.
Published: April 2006

Intercellular communication in the liver is a potentially important mechanism for the regulation of hepatic metabolism. Since alcohol (ethanol, ETOH) can interact with both parenchymal and nonparenchymal cells, the present study was performed to assess the possible effects of ETOH on the nonparenchymal cell‐to‐hepatocyte signal traffic by studying the glycogenolytic and glycolytic response of the perfused rat liver to colloidal carbon, a phagocytic stimulus for Kupffer and sinusoidal endothelial cells. Livers from fed rats were perfused with hemoglobin‐free Krebs Ringer bicarbonate buffer containing ETOH (20 mm) or acetaldehyde (1 mm). Twenty minutes after initiating the infusion of ETOH or acetaldehyde, colloidal carbon was infused and the rate of carbon uptake, glucose, lactate and pyruvate output, and oxygen consumption were determined. In control livers, carbon stimulated the output of glucose (60%), lactate (25%), and pyruvate (53%), without affecting the lactate/pyruvate ratio. ETOH, but not acetaldehyde, enhanced the carbon effect on glucose output (38%), but suppressed the increased lactate and pyruvate output (48% and 91% respectively) resulting in a dramatic 10‐fold increase in the lactate/pyruvate ratio. By using inhibitors of cyclooxygenase or alcohol dehydrogenase (indomethacin and 4‐methylpyrazole, respectively) in the presence of carbon and/or ETOH, we determined that: (1) following carbon stimulation prostaglandins are the likely mediators secreted by nonparenchymal cells that increase carbohydrate output; and (2) the ETOH‐induced enhancement of carbonstimulated glycogenolysis is also mediated by prostaglandins and is not dependent on the oxidative metabolism of ETOH.
The Role of Antisocial, Affective, and Childhood Behavioral Characteristics in Alcoholics' Neuropsychological Performance
Authors: Glenn Susan Wagner , Errico Austin L. , Parsons Oscar A. , King Andrea C. , Nixon Sara Jo
Published: April 2006

Chronic alcoholics demonstrate cognitive deficits when compared with nonalcoholics. These deficits are typically attributed to the direct effects of ethanol and its metabolites on the central nervous system (CNS). There are other factors, however, that differentiate alcoholics from controls, such as personality or behavioral characteristics. These factors may affect neuropsychological performance and thus alter the interpretation of alcoholic cognitive deficits as resulting solely from alcohol's toxic effects. To investigate this question, male and female alcoholics and peer nonalcoholic controls were compared on personality, behavioral, and cognitive measures. Alcoholics had greater numbers of antisocial behaviors, childhood behavioral disorder symptoms (CBD), and affective symptomatology, and had poorer neuropsychological performance than controls. The three personality and behavioral factors were positively intercorrelated with each other, and were negatively related to cognitive performance. The CBD factor proved to be the most consistent predictor of neuropsychological performance for both alcoholics and controls, and males and females. While the behavioral factors differentiated alcoholics from controls and predicted performance, significant differences between the groups in cognitive performance still remained when these factors were taken into account.
Teratogenic Effects of Alcohol on Infant Development
Authors: Jacobson Joseph L. , Jacobson Sandra W. , Sokol Robert J. , Martier Susan S. , Ager Joel W. , Kaplan‐Estrin Melissa G.
Published: April 2006

Results of previous studies of effects of drinking during pregnancy on standardized tests of infant development have varied, depending on level of exposure. This study of 382 Black, inner city infants confirmed effects of moderate‐to‐heavy prenatal alcohol exposure on Bayley Scale performance originally observed in a White, middle class cohort. Effects of second and third trimester drinking were as strong or stronger than those of drinking at the time of conception. New methods for reducing the Bayley Scale data suggested specific deficits relating to emergence of the ability to imitate modeled behavior and the development of standing and walking. The incidence of very poor performance (bottom 10th percentile) on the Bayley Mental Development Index more than doubled in children whose mothers averaged at least 0.5 oz absolute alcohol per day during pregnancy, indicating that this exposure has a clinically meaningful impact at markedly lower levels than those associated with full fetal alcohol syndrome. Clinically meaningful effects on the Psychomotor Development Index, by contrast, were seen only in the infants of heavy drinking mothers with overt symptomatology of alcohol abuse. Adverse effects on Bayley Scale performance were more prevalent in the infants of women more than 30 years of age.
Detection of Alcoholism in Schizophrenia Using the MAST
Authors: McHugo Gregory J. , Paskus Thomas S. , Drake Robert E.
Published: April 2006

The classification accuracy of the Michigan Alcoholism Screening Test (MAST) for detecting alcoholism in a community sample of 75 schizophrenic outpatients was assessed, as a replication and extension of Searies et al. (1990). The criterion diagnosis of alcohol use disorder was based on the convergence of ratings from multiple sources. The MAST classified 85% of the sample correctly, and item based analyses showed that various subsets were equally effective, indicating a high degree of redundancy among MAST items. Differences between our sample and that of Searies et al. influenced the choice of MAST items for optimal detection and classification, and males were consistently classified more correctly than females. These results suggest that the construction of a brief and accurate detection instrument for alcohol use among schizophrenic patients may be possible, although attention to subpopulation differences will be required.
DRD2 Dopamine Receptor Genotype, Linkage Disequilibrium, and Alcoholism in American Indians and Other Populations
Authors: Goldman David , Brown Gerald L. , Albaugh Bernard , Robin Rob , Goodson Susan , Trunzo Marie , Akhtar Longina , Lucas‐Derse Susan , Long Jeffrey , Linnoila Markku , Dean Michael
Published: April 2006

We defined interpopulation differences in the frequency of the dopamine D2 receptor DRD2/Taq1 A1 allele, which has previously been associated with alcoholism. Frequencies of the A1 allele in unrelated subjects were 0.18 to 0.20 (se = 0.02 to 0.03) in several Caucasian populations previously assessed, 0.38 (±0.05) in American Blacks (n= 44), 0.63 (±0.07) in Jemez Pueblo Indians (n= 23), and 0.80 (± 0.04) in Cheyenne Indians (n= 52). The existence of large interpopulation differences in the frequency of the Taq1 alleles suggests that associations to disease status could readily be generated or masked if disease and control groups were uneven in ethnic composition. To address the possibility that the 4‐fold higher frequency of the A1 allele in Cheyenne Indians was related to an increased vulnerability to alcoholism in that population, 47 Cheyenne Indians were psychiatrically interviewed and blind‐rated. However, there was no significant difference between interviewed controls (0.73 ± 0.06, n= 24), subjects with alcoholism and/or drug abuse (0.74 ± 0.06, n= 23) and noninterviewed population controls (0.87 ± 0.05, n= 20). Legitimate association of the DRD2/Taq1 allele to alcoholism would presumably require it to be in linkage disequilibrium (nonrandom association) with a functional mutation at DRD2 or elsewhere. The level of disequilibrium would vary between populations and could place an upper bound on the strength of an association. To provide a model for the extent and variation of disequilibrium at DRD2, the level of linkage disequilibrium between the Taq1 RFLP and a second DRD2 polymorphism, the SSCP variant in the immediate 3’region of the gene, was determined in three populations. The normalized disequilibrium values were 0.36 In U.S. Caucasians (n= 48), 0.34 in Finns (n= 86), and 0.78 in Cheyenne Indians (n= 34).
What Triggers the Resolution of Alcohol Problems Without Treatment?*
Authors: Sobell Linda C. , Sobell Mark B. , Toneatto Tony , Leo Gloria I.
Published: April 2006

This study investigated natural recoveries (self‐change) from alcohol problems, and overcame several methodological problems that affected the few previous studies of this phenomenon. Three groups of individuals who had resolved an alcohol problem without treatment were interviewed about their drinking history, life events that occurred during the year prior to their resolution, and factors that helped maintain their resolution. As a control for prevalence of life events, a control group of nonresolved, nontreated alcohol abusers were interviewed about events in a randomly selected year. Collaterals were interviewed for all subjects. No life event or constellation of events was differentially associated with the resolutions across the three resolved groups or differentiated the resolved and nonresolved groups. Interviews with resolved subjects were qualitatively analyzed—the majority (57%) of recoveries were characterized as Involving a “cognitive evaluation” or appraisal of the pros and cons of drinking. Spousal support was reported by the greatest number of resolved subjects as having helped them maintain their resolution. Findings from this study may provide direction for developing new treatment strategies and for accelerating self‐change among problem drinkers in the community. The study also demonstrates the importance of using a control group, without which very different conclusions might have been drawn.
A Genetic Familial Study of Monoamine Oxidase B Activity and Concentration in Alcoholics
Authors: Devor Eric J. , Cloninger C. Robert , Kwan Sau‐Wah , Abell Creed W.
Published: April 2006

Platelet monoamine oxidase B (MAO B) activity and concentration were studied in a small sample of alcoholic families (n= 8) and in 20 unrelated, nonalcoholic controls. Complex segregation analyses of familial data indicated that both activity and concentration are controlled by a single major gene locus with a multifactorial background effect accounting for 0–50% of the variance. When the alcoholic family members (n= 24) were compared with the controls, all determinations of activity display significant differences, whereas MAO B concentration levels showed no difference. These results indicated that the lowered MAO B activities frequently reported among alcoholics do not reflect a change in the number of MAO B macromolecules expressed in platelets, but could be caused by the presence of an inhibitor or by a polymorphic or variant form of the enzyme.
MAST Scores, Alcohol Consumption, and Gynecological Symptoms in Endometriosis Patients
Authors: Perper Maria M. , Breitkopf Lyle J. , Breitstein Robert , Cody Ronald P. , Manowitz Paul
Published: April 2006

Alcohol consumption (quantity, frequency, and pattern) and alcoholrelated problems were determined in endometriosis patients (n= 137), patients with other gynecological disorders (n= 91), and normal control subjects (n= 98). Participants completed a self‐administered questionnaire, including the Michigan Alcoholism Screening Test (MAST), questions to determine the quantity and frequency of alcohol use, and questions regarding the relationship between gynecological symptoms and alcohol intake. The percentage of endometriosis patients with MAST scores greater than five or seven was significantly greater than that of normal control subjects (p= 0.045 and p= 0.009, respectively), but did not differ from that for patients with other gynecological disorders. Endometriosis patients with high MAST scores (≥5) tended to consume more alcohol on a yearly basis than normal control subjects with high MAST scores (p= 0.07). Among participants who experienced gynecological symptoms and were not abstainers, 31% of endometriosis patients, 9.5% of normal control subjects, and 14.3% of patients with other gynecological disorders reported increasing their alcohol consumption when experiencing gynecological symptoms. Endometriosis patients tended to differ in this regard from normal control subjects (p= 0.058) and were significantly different from patients with other gynecological disorders (p= 0.039). The evidence suggests that the gynecological problems of endometriosis may be a major medical correlative of alcoholism in women.
Drinking Patterns and Correlates of Drinking Among Pregnant Teenagers
Authors: Cornelius Marie D. , Day Nancy L. , Cornelius Jack R. , Geva Diklah , Taylor Paul M. , Richardson Gale A.
Published: April 2006

Many adolescents drink, and the rate of teenage pregnancy is increasing, yet the effect of drinking among pregnant teenagers has received little attention. We present a description of the drinking patterns of 124 pregnant teenagers attending a prenatal clinic in Pittsburgh. Sixty‐nine percent of the women were African‐American, and the average age was 16 years (range 13–18 years). Eighty‐two percent drank the year before pregnancy, while 54%, 19%, and 15% drank during the first, second, and third trimesters, respectively. All substance use decreased between the first and third trimesters, with the exception of tobacco, which rose significantly. Binge drinking (5+ drinks/occasion) occurred in 31% of the sample before pregnancy, rose to 35% in the first trimester, and then fell precipitously. Binge drinkers during pregnancy were more likely to be white and heavier users of tobacco, marijuana, and cocaine. Binge drinkers experienced alcohol and tobacco use and sexual intercourse earlier than nonbinge drinkers. Binge drinking in the first trimester may be considered a risk factor for infants of adolescents.
Similar Effects of Ethanol and tert‐Butanol on Amino Acid Concentrations in Rat Serum and Liver
Authors: Hagman Mats , Eriksson Tomas , Kitson Kathryn E.
Published: April 2006

Both metabolic and nonmetabolic mechanisms have been proposed to the plasma amino acid decreasing effect of an acute ethanol load. We used tert‐butanol, an alcohol that is only minimally metabolized, as a tool to explain the mechanism behind the amino acid decreasing effect of ethanol. Acute administration of tert‐butanol was found to exert a decreasing effect on rat serum amino acid concentrations similar to that of ethanol, indicating that the mechanism of the amino acid decreasing effect of ethanol is primarily due to ethanol itself and not to its oxidation. Ethanol and tert‐butanol also had similar effects on liver amino acid concentrations, including an increase in the glycine concentration and decreases in the concentrations of glutamate, alanine, leucine, and tyrosine.