bluuebunny/crossref_metadata_2025_split huggingface dataset:
Gender Differences in Pharmacokinetics of Alcohol
Authors: Baraona Enrique , Abittan Chaim S. , Dohmen Kazufumi , Moretti Michelle , Pozzato Gabriele , Chayes Zev W. , Schaefer Clara , Lieber Charles S. 
Published: April 2006

Background: The enhanced vulnerability of women to develop alcohol‐related diseases may be due to their higher blood alcohol levels after drinking, but the mechanism for this effect is debated.Methods: Sixty‐five healthy volunteers of both genders drank 0.3 g of ethanol/kg of body weight (as 5%, 10%, or 40% solutions) postprandially. Blood alcohol concentrations were monitored by breath analysis and compared with those after intravenous infusion of the same dose. First‐pass metabolism was quantified (using Michaelis‐Menten kinetics) as the route‐dependent difference in the amount of ethanol reaching the systemic blood. Gastric emptying was assessed by nuclear scanning after intake of 300 μCurie of technetium‐labeled diethylene triamine pentacetic acid in 10% ethanol. The activities of alcohol dehydrogenase isozymes were assessed in 58 gastric biopsies, using preferred substrates for γ‐ADH (acetaldehyde) and for ς‐ADH (m‐nitrobenzaldehyde) and a specific reaction of χ‐ADH (glutathione‐dependent formaldehyde dehydrogenase).Results: Women had less first‐pass metabolism than men when given 10% or 40%, but not 5%, alcohol. This was associated with lower gastric χ‐ADH activity; its low affinity for ethanol could explain the greater gender difference in first‐pass metabolism with high rather than with low concentrations of imbibed alcohol. Alcohol gastric emptying was 42% slower and hepatic oxidation was 10% higher in women. A 7.3% smaller volume of alcohol distribution contributed to the higher ethanol levels in women, but it did not account for the route‐dependent effects.Conclusions: The gender difference in alcohol levels is due mainly to a smaller gastric metabolism in females (because of a significantly lesser activity of χ‐ADH), rather than to differences in gastric emptying or in hepatic oxidation of ethanol. The concentration‐dependency of these effects may explain earlier discrepancies. The combined pharmacokinetic differences may increase the vulnerability of women to the effects of ethanol.
Quantitative Autoradiography of Mu‐Opioid Receptors in the CNS of High–Alcohol‐Drinking (HAD) and Low–Alcohol‐Drinking (LAD) Rats
Authors: Learn Jennifer E. , Chernet Eyassu , McBride William J. , Lumeng Lawrence , Li Ting‐Kai 
Published: April 2006

Background: The binding of [3H]DAMGO to mu‐opioid sites was measured in the CNS of selectively bred high–alcohol‐drinking (HAD) and low–alcohol‐drinking (LAD) rats to test the hypothesis that high alcohol preference is associated with higher densities of mu‐opioid receptors.Methods: Adult, alcohol‐naïve male HAD and LAD rats from replicate line 1 were decapitated and their brains frozen in isopentane. Brain sections were incubated with 5 nM [3H]DAMGO, and nonspecific binding was determined in the presence of unlabeled DAMGO. Films were exposed for 60 days, then analyzed using quantitative autoradiography.Results: The densities of [3H]DAMGO binding sites were measured within subregions of neocortex, limbic system, basal ganglia, diencephalon, and brainstem. LAD rats had significantly higher [3H]DAMGO binding (10–30%) than HAD rats within the anterior dorsal hippocampus (CA2), posterior hippocampus (dorsal CA1, and ventral CA1, CA3, and dentate gyrus), thalamus (medial dorsal, lateral, medial dorsal, central, ventral lateral, ventral medial, and ventral medial geniculate nuclei), habenula, and amygdala. No significant interline differences were found in the prefrontal, cingulate, frontal, parietal, temporal, occipital or entorhinal cortices, olfactory tubercle, nucleus accumbens, lateral septum, ventral tegmental area, hypothalamus, caudate‐putamen, substantia nigra, claustrum, central gray, or superior colliculus.Conclusions: The present findings with the HAD and LAD lines do not support the hypothesis that high alcohol preference is associated with higher densities of CNS mu‐opioid receptors. Instead, the present results, in combination with previously published findings, suggest that the mu‐opioid system may play a complex role in regulating high–alcohol‐drinking behavior.
Sociodemographic and Individual Predictors of Alcohol Policy Attitudes: Results From a US Probability Sample
Authors: Latimer William W. , Harwood Eileen M. , Newcomb Michael D. , Wagenaar Alexander C. 
Published: April 2006

Objective: Public views on alcohol policies have facilitated legislative change. Given limited resources, however, policy makers and prevention advocates cannot make haphazard attempts to mobilize public resources. This investigation reports sociodemographic and individual traits predicting attitudes on alcohol policies designed to reduce underage alcohol consumption. Previous studies have examined single‐item measures of alcohol policy. We examined predictors of multi‐item scales measuring five core dimensions of alcohol policy.Methods: A survey of public attitudes on alcohol policies was administered to a US national probability sample of 7021 adults.Results: Women, infrequent drinkers, and adults with greater knowledge about or concern for youth exhibited the greatest support across five alcohol policy scales. Older adults favored policies that restrict alcohol use in public places, whereas younger adults favored an increase in alcohol taxes to address underage alcohol use.Conclusions: Individual factors such as alcohol use frequency and concern for youth explained larger proportions of variance in alcohol policy attitudes than did sociodemographic factors. Consistent with previous research, political orientation, parental status, employment status, and marital status did not predict attitudes on alcohol policy.
Pro‐ and Anti‐Inflammatory Gene Expression in the Murine Small Intestine and Liver After Chronic Exposure to Alcohol
Authors: Fleming Sherry , Toratani Satoshi , Shea‐Donohue Terez , Kashiwabara Yoshiko , Vogel Stefanie N. , Metcalf Eleanor S. 
Published: April 2006

Background: Endotoxin has been proposed to play a primary role in ALD, by initiating an inflammatory cascade within the liver. Although the source of these cytokines has been presumed to be circulating monocytes or tissue macrophages, ethanol‐induced, nonhepatic sources of soluble mediators recently have been identified. One potential, but not clearly defined, extrahepatic source of cytokines in ALD is the intestine. In the current study, we hypothesized that alcohol would alter cytokine expression within the small intestine of mice exposed to ethanol and that LPS would alter levels of cytokine expression even more dramatically.Methods: Mice were fed a modified Lieber‐DeCarli liquid ethanol or control diet for up to 14 days prior to injecting either saline or LPS. Plasma alanine aminotransferase (ALT) and cytokine levels, histology, and RT‐PCR of pro‐ and anti‐inflammatory cytokine gene expression were determined from distal ileum and liver samples. Translocation of intestinal bacterial flora also was assessed.Results: Ethanol exposure upregulated basal gene expression of IL‐1β, TNF‐α, IL‐6, and iNOS in the distal ileum, but similar effects of ethanol on the liver were not observed. In contrast, LPS challenge of ethanol‐exposed mice increased intestinal gene expression of some cytokines, but decreased expression of others. These effects were not associated with bacterial translocation. Also, ethanol alone induced a modest increase in both ICAM‐1 and TLR4 mRNA expression in the intestine, but expression of both molecules was inhibited in mice that received both ethanol and LPS. Finally, whereas basal levels of hepatic IL‐11 mRNA were not elevated by exposure to ethanol, intestinal IL‐11 mRNA levels were increased more than100‐fold.Conclusions: These studies are the first to show that ethanol affects cytokine gene expression in the ileum and identifies the ileum as a potential target for ethanol effects. In addition, our results suggest that IL‐11 expression may be enhanced in the intestine to help repair or protect this organ from alcohol‐induced damage. Collectively, these studies suggest that both pro‐ and anti‐inflammatory soluble mediators in the intestine maintain and exacerbate the local hepatic response to ethanol.
Responsivity and Development of Tolerance to the Motor Impairing Effects of Moderate Doses of Ethanol in Alcohol‐Preferring (P) and ‐Nonpreferring (NP) Rat Lines
Authors: Bell Richard L. , Stewart Robert B. , Woods James E. , Lumeng Lawrence , Li Ting‐Kai , Murphy James M. , McBride William J. 
Published: April 2006

Background: Research comparing the alcohol‐preferring (P) and ‐nonpreferring (NP) rat lines has detected an apparent association between ethanol preference and lower responsivity to ethanol, as well as the capacity to develop and maintain tolerance to ethanol's effects. However, past studies of tolerance to ethanol's effects generally involved relatively high doses. The present study examined recovery from functional impairment induced by moderate doses of ethanol after a single dose (responsivity) and after multiple doses (development of tolerance) in the P and NP rat lines.Method: Adult female P and NP rats were trained, for 5 consecutive days, to stay on an oscillating bar for 120 sec. Rats were then assigned to one of three groups to receive 1.0, 1.25, or 1.5 g/kg ethanol for 5 consecutive test days. Rats were tested each day at 15‐min intervals, following intraperitoneal injection, until recovery to the 120 sec criterion.Results: On the first test day, NP rats took longer to recover to criterion than the P rats following the 1.0 and 1.25 g/kg doses, whereas at the 1.5 g/kg dose no line difference was evident. Trunk blood alcohol concentrations (BACs), associated with time to recovery, indicated higher values for the P than NP rat on day 1 following injection of the two lower doses. Compared to day 1, NP rats demonstrated significantly shorter times to recovery beginning on day 2 following injections of the 1.0 and 1.25 g/kg doses. However, NP rats did not show significantly different recovery times on days 2–5 compared to day 1 following injection of the 1.5 g/kg dose. The shorter recovery times at the 1.0 and 1.25 g/kg doses were associated with BACs at recovery on day 3 being equal to or greater than values obtained on day 1. In contrast, compared to day 1, P rats did not show shorter recovery times until days 3 and 5 following the 1.0 and 1.25 g/kg doses, respectively. However, P rats did demonstrate shorter recovery times on day 2 and higher BACs on day 3 compared to day 1 following the 1.5 g/kg dose.Conclusion: With regard to motor impairment, lower responsivity to moderate doses of ethanol may be a factor associated with high alcohol‐seeking behavior. The present results confirm past research supporting an association between ethanol preference and low ethanol responsivity but at doses that are more reflective of those self‐administered by P rats.
Chronic Alcohol Consumption and Cerebral Indices of Oxidative Stress: Is There a Link?
Authors: Götz M. E. , Janetzky B. , Pohli S. , Gottschalk A. , Gsell W. , Tatschner T. , Ransmayr G. , Leblhuber F. , Gerlach M. , Reichmann H. , Riederer P. , Böning J. 
Published: April 2006

Background: It is still difficult to define the biochemical mechanisms that cause alterations in neuronal function and plasticity and neuronal cell loss in the brains of alcohol‐dependent patients.Methods: To evaluate the extent of cerebral alcohol‐induced oxidative stress ex vivo, we investigated the levels of glutathione (GSH), its oxidation product glutathione disulfide (GSSG, produced by GSH‐peroxidases), and the activities of catalase and superoxide dismutases (SOD). In addition, selected brain regions from up to 22 subjects (versus controls) were studied post mortem to compare the amount of oxidized DNA‐base 8‐hydroxy‐2′‐deoxyguanosine (8‐OHdG) with levels of deoxyguanosine (dG) in mitochondrial and nuclear DNA.Results: The most prominent findings showed significantly decreased GSH/(GSH+2GSSG) molar redox (oxidation‐reduction) ratios in the corpus mamillare and cerebellum, which appeared due to an increase in GSSG caused by chronic alcohol intake. Catalase activity was increased in only the frontal cortex, whereas decreased catalase activity was found in the corpus callosum. In contrast, neither copper‐zinc‐superoxide dismutase (CuZnSOD) and manganese‐superoxide dismutase (MnSOD) activities nor 8‐OHdG/dG molar ratios were altered, although a tendency toward higher OHdG/dG ratios in temporal and parietal cortex from alcohol‐dependent patients could be detected when mitochondrial DNA was analyzed selectively.Conclusions: We propose that decreased brain GSH/(GSH+2GSSG) molar redox (oxidation‐reduction) ratios in alcohol‐dependent patients may reflect neural impairment due to increased peroxide production after chronic alcohol consumption. However, future experiments, investigating the activities of enzymes and cofactors involved in GSH synthesis and metabolism in the human brain, will have to validate the specificity of these results for oxidative stress.
Genetic Correlations Between Initial Sensitivity to Ethanol and Brain cAMP Signaling in Inbred and Selectively Bred Mice
Authors: Kirstein Shelli L. , Tabakoff Boris 
Published: April 2006

Background: Several lines of evidence have suggested a role for cAMP (adenosine 3′,5′‐cyclic monophosphate) signaling in the acute and chronic effects of ethanol. This study investigated whether there is a genetic correlation between cAMP synthesis in the brain and the acute effects of ethanol [alcohol sensitivity or acute functional tolerance (AFT)].Methods: By using nine inbred strains of mice, we measured initial sensitivity and AFT to ethanol with a test of balance on a dowel. Initial sensitivity was defined by the blood ethanol concentration (BEC0) at the loss of balance on a dowel after an ethanol injection [1.75 g/kg intraperitoneally (ip)]. When mice were able to regain balance on the dowel, BEC1 was determined, and a second ethanol injection was given (2 g/kg ip). Upon final regaining of balance, BEC2 was determined. AFT was defined by the difference between BEC1 and BEC2 (AFT =ΔBEC = BEC2− BEC1). Cyclic AMP synthesis was measured in whole‐cell preparations in the cerebellum and other brain areas of mice of the nine inbred strains.Results: Significant differences in BEC0 and AFT were seen among the mice of the nine inbred strains. Cerebellar basal and forskolin‐ and isoproterenol‐stimulated cAMP production differed significantly between the strains, and BEC0 was found to correlate significantly with forskolin‐ and isoproterenol‐stimulated cAMP accumulation in the cerebellum (r= 0.70 and 0.94, respectively). When we measured cAMP production in mesencephalic and telencephalic tissue in three strains of mice that differed significantly in isoproterenol‐stimulated cAMP accumulation in the cerebellum, significant differences between strains were found only in telencephalic tissue. The relative relationship between the rank order of the three strains for cAMP accumulation in the telencephalon and initial sensitivity to ethanol was identical to that seen with the cerebellum. However, AFT did not correlate with cAMP accumulation in the cerebellum or any other brain area tested.Conclusions: These results suggest that cAMP‐generating systems of the cerebellum and possibly the brain areas contained in telencephalic tissues (e.g., basal ganglia) may have an important relationship to an animal's initial sensitivity to the incoordinating effects of ethanol.
Combining Ondansetron and Naltrexone Treats Biological Alcoholics: Corroboration of Self‐Reported Drinking by Serum Carbohydrate Deficient Transferrin, A Biomarker
Authors: Ait‐Daoud Nassima , Johnson Bankole A. , Javors Martin , Roache John D. , Zanca Nursen A. 
Published: April 2006

Background: Recently, we showed by using self‐report that combining ondansetron (4 μg/kg twice a day) and naltrexone (25 mg twice a day) was effective at reducing drinking and increasing abstinence among early‐onset alcoholics (EOAs), who are characterized by a range of antisocial behaviors and high biological and familial disease predisposition. Here, we investigated whether the self‐reported differences in drinking would be corroborated by measurements of serum carbohydrate‐deficient transferrin (CDT) level, a sensitive, reliable, and well‐validated marker of transient alcohol consumption.Method: An 8‐week double‐blind clinical trial was performed in which 20 EOAs were randomized to receive ondansetron (4 μg/kg twice a day) and naltrexone (25 mg twice a day) or placebo as an adjunct to weekly standardized cognitive behavioral therapy. Serum CDT was assessed at weeks 0 (baseline), 4, and 8.Results: Log serum CDT was significantly lower in the ondansetron and naltrexone group (group mean, 1.44 ± 0.076) compared with the placebo group (group mean, 1.82 ± 0.113), as evidenced by a main effect of group [F (1,15) = 7.2, p= 0.017; effect size = 0.32], visit [F (1,16) = 11.2, p= 0.004; effect size = 0.41], and an interaction between group and visit [F (1,16) = 27.54, p < 0.001; effect size = 0.63].Conclusions: The combination of ondansetron plus naltrexone was superior to placebo at reducing serum CDT. This corroborated our self‐reported drinking data and demonstrated that the medication combination is an effective treatment for EOAs.
The Identification of Alcohol Intoxication by Police
Authors: Brick John , Carpenter John A. 
Published: April 2006

Background: The identification of alcohol intoxication by police, bartenders, social hosts, and potential passengers is an important issue in the prevention of alcohol‐related driving accidents. This study examines the ability of police officers to correctly identify and make ratings of the sobriety of target drinkers presented on video.Methods: Raters were asked to determine (1) whether the target drinker had been drinking alcohol, (2) whether it was “okay” to serve the target another drink, and (3) whether the target drinker was “okay” to drive. A rater confidence score for each target evaluated, as well as demographic characteristics about the raters, was obtained.Results: Drinkers were accurately targeted to low (0.08–0.09%), medium (0.11–0.13%), and high (0.15–0.16%) blood alcohol concentrations (BACs) by using a method previously described. At lower BACs, most police officers were unable to identify whether or not targets had been drinking. Raters were “pretty sure” that targets in the 0.15–0.16% range had been drinking and “not sure” whether or not they should be served another drink or drive a car.Conclusions: The ability of raters to reliably identify target drinkers who were too intoxicated to drive safely was not obtained until the BACs were relatively high. These results suggest that prevention measures must focus on improving behavioral observations made of potential drunk drivers. Implications for bartenders and social hosts are discussed.
Serotonin Transporter Promoter Polymorphism Genotype Is Associated With Behavioral Disinhibition and Negative Affect in Children of Alcoholics
Authors: Twitchell Geoffrey R. , Hanna Gregory L. , Cook Edwin H. , Stoltenberg Scott F. , Fitzgerald Hiram E. , Zucker Robert A. 
Published: April 2006

Background : Serotonergic (5‐HT) dysfunction has been implicated in the etiology of both behavioral disinhibition (BD) and negative affect (NA). This work extends our previous finding of relationships between whole blood 5‐HT and both BD and NA in pubescent, but not prepubescent, children of alcoholics and continues examination of a hypothesized role of 5‐HT dysfunction in alcoholism risk. The long and short (L and S) variants of the 5‐HT transporter gene‐linked polymorphic region (5‐HTTLPR) are responsible for differing transcriptional efficiencies in 5‐HT uptake. Although associations have been found between the SS 5‐HTTLPR genotype and severe alcoholism and neuroticism, recent reports describe relationships between the LL genotype and both low level of response to alcohol and alcoholism diagnosis and a predominance of the LL genotype in early‐onset alcoholics.Methods: This report is from an ongoing prospective study of the development of risk for alcoholism and other problematic outcomes in a sample of families classified by father's alcoholism subtype. This study examines relationships between 5‐HTTLPR genotype and both child BD (Child Behavior Checklist Aggressive Behavior) and NA (Child Behavior Checklist Anxious/Depressed) in offspring from 47 families.Results: Results showed significantly higher levels of BD and NA in the 16 children with the LL genotype than the 46 SS or SL children.Conclusions: Behaviors of undercontrol, which occur at increased rates in children of alcoholics, may be genetically influenced through the regulation of the 5‐HT transporter. Due to the small sample size and the preliminary nature of our findings, replication is necessary.
P3 Event‐Related Potential, Dopamine D2 Receptor A1 Allele, and Sensation‐Seeking in Adult Children of Alcoholics
Authors: Ratsma Joëlle E. , van der Stelt Odin , Schoffelmeer Anton N. M. , Westerveld Andries , Boudewijn Gunning W. 
Published: April 2006

Background : Research has indicated a close relationship between the P3 event‐related potential and the dopamine D2 receptor A1 allele in individuals at high risk for alcoholism. Other research has suggested an association between the dopamine D2 receptor A1 allele and sensation‐seeking. In this study, we further examined the relationships between the P3, the A1 allele, and sensation‐seeking in a sample of nonalcoholic adult children of alcoholics.Methods: Participants (n= 57; range, 19–30 years; 41 women), who performed a visual novelty oddball task to elicit the P3, were asked to fill in personality questionnaires, including Zuckerman's Sensation‐Seeking Scale, and were classified according to the presence of the dopamine D2 receptor A1 allele. The effects of sex, age, and socioeconomic status were assessed to determine whether these variables affected the relations between the P3, the A1 allele, and sensation‐seeking.Results: A small P3 amplitude was associated with high sensation‐seeking, particularly with high disinhibition. The presence of the A1 allele was also associated with high disinhibition, but only in men. By contrast, P3 amplitudes and latencies were not associated with the presence of the A1 allele.Conclusions: Although a small P3 amplitude, high sensation‐seeking, and the presence of the A1 allele were all associated with alcoholism risk, these findings indicate that these three characteristics together do not reflect a common risk factor in alcoholism.