bluuebunny/crossref_metadata_2025 huggingface dataset:
Aldehyde Dehydrogenase Activities in the Brains of Rats and Mice Genetically Selected for Different Sensitivity to Alcohol
Authors: Zimatkin Sergey M. , Deitrich Richard A.
Published: April 2006

Aldehyde dehydrogenase activity in brain has been studied for many years. However, the question of its role in the actions of ethanol in the brain has not been resolved. We have utilized mice and rats selectively bred for sensitivity or resistance to the initial hypnotic effects of ethanol to gain some insight into the possible involvement of brain aldehyde dehydrogenase in the actions of ethanol. We compared the levels of aldehyde dehydrogenase activity in the brains of these selected lines of rodents by histochemical methods. It was found that, although aldehyde dehydrogenase activity was detected in many areas of the brain, only in the cerebellar Purkinje cells was there a difference between sensitive and resistant lines of mice or rats. The resistant lines (Short Sleep mice and Low Alcohol Sensitive rats) had statistically higher levels of aldehyde dehydrogenase than did the sensitive lines (Long Sleep mice and High Alcohol Sensitive rats). Although this does not prove that aldehyde dehydrogenase or aldehydes are involved in the central actions of ethanol, it provides another piece of evidence in this direction.
Gene Expression of A‐ and B‐Type Natriuretic Peptides in Response to Acute Ethanol Ingestion
Authors: Wigle D. A. , Watson J. D. , Pang S. C. , Sarda I. R. , Roy R. N. , Flynn T. G.
Published: April 2006

Given that ethanol ingestion is associated with a disruption of water and electrolyte balance in addition to being a significant risk factor for cardiovascular disease, we have investigated the gene expression of ANP and BNP in response to acute doses of ethanol. Wistar rats were administered either a 5 g/kg dose of ethanol or an equivalent volume of water, and atrial and ventricular tissue samples were removed at 30,60, and 120 min for analyses. Although no differences in ANP mRNA were observed between ethanol and water‐treated rats during the time course, BNP mRNA levels in ethanoltreated rats were 43% of those present in water‐treated animals in atrial tissue at 120 min. In ventricular tissue, BNP mRNA levels were reduced similarly to 38% of control. These results suggest a possible differential regulation of A‐ and B‐type natriuretic peptides under the influence of ethanol ingestion.
In Vitro Comparison of the Effects of Ethanol and Acetaldehyde on Dorsal Root Ganglion Neurons
Authors: Bradley Douglas M. , Paiva Michael , Tonjes Laura A. , Heaton Marieta B.
Published: April 2006

Results of previous experiments designed to investigate the role of acetaldehyde, the primary metabolite of ethanol, have been contradictory. Experiments have provided evidence that supports and refutes the idea that acetaldehyde is responsible for the teratogenic effects observed in fetal alcohol syndrome. In the present study, cell culture techniques were used to examine the effects of acetaldehyde, both independently and in conjunction with ethanol. The purpose was to determine whether acetaldehyde had any effect on survival and process outgrowth of dorsal root ganglion (DRG) neurons cultured in vitro. This study revealed that acetaldehyde was as toxic to DRG survival as is ethanol, but had a lesser effect on neurite outgrowth than ethanol. Also, acetaldehyde and ethanol do not act synergistically to damage neurons in culture. The results indicate that, although acetaldehyde is probably not solely responsible for ethanol neurotoxicity, it does exhibit a secondary toxicity that could be the subject of future studies.
Perinatal Maternal Ethanol Effects on Pregnant Mice and on Offspring Viability and Growth: Influences of Exposure Time and Weaning Diet
Authors: Middaugh Lawrence D. , Boggan William O.
Published: April 2006

C57BL/6 mice were maintained on liquid diets containing 27.5% ethanol‐derived calories beginning on gestational day 12. For one group, the liquid diet was replaced with laboratory chow on the morning of gestational day 18, ±24 hr before delivery. For a second group, the diet was continued for 7 days postnatally. Two additional groups were pair‐fed isocaloric sucrose diets, and a final group was maintained on normal laboratory chow. The mice consumed sufficient amounts of diet to provide near 30 g ethanol/kg/day during pregnancy and slightly greater amounts during the first postpartum week. The ethanol diet produced no maternal deaths and did not alter weight gain during gestational days 12–17 of pregnancy. The results confirmed previous reports that dietary ethanol exposure under conditions that have rather minor effects on the pregnant mouse can substantially affect the fetus. As previously reported, when exposure was terminated 24 hr before delivery, neonatal mortality was elevated by ‐30%, but birth weight was not altered. When the diet was extended into the lactation period, mortality was delayed but not reduced, possibly by reducing the severity of ethanol withdrawal. Birthweight was reduced by 10% when exposure continued until birth, suggesting that low birthweights for fetal ethanol‐exposed (FEE) mice can be eliminated by terminating exposure –24 hr before delivery. As in previous reports, FEE mice with normal birthweights had an attenuated preadolescent growth spurt, suggesting that low birthweights and attenuated postnatal growth are likely mediated by different mechanisms. The reduction in periadolescent growth of FEE mice resulted in weight deficits that persisted into adulthood and could not be accounted for by a reduction in calories consumed.
Effect of Pre or Postnatal Exposure to Ethanol on the Total Number of Neurons in the Principal Sensory Nucleus of the Trigeminal Nerve: Cell Proliferation and Neuronal Death
Authors: Miller Michael W.
Published: April 2006

Early exposure to ethanol reduces the number of neurons in many CNS structures in vivo. The present study determined whether such reductions are caused by the death of neurons. Three groups of ethanol‐treated rats were prepared: those exposed to ethanol from gestational day (G) 11 to G19 (during the period of neuronal generation and migration), from postnatal day (P) 4 to P12 (during the period of synaptogenesis), or from P31 to P39 [after the mature structure and function of neurons in the principal sensory nucleus (PSN) of the trigeminal nerve was established]. During these times, pregnant dams or pups were fed a liquid ethanol‐containing diet that produced peak blood ethanol concentrations of 137–157 mg/dl. The number of PSN neurons in mature rats exposed to ethanol pre‐ or postnatally was determined using stereological procedures. The number of PSN neurons was also calculated for rats pair‐fed an isocaloric liquid control diet or fed chow and water ad libitum. The volume of the PSN was not affected by pre‐ or postnatal ethanol exposure. The number of PSN neurons, however, was significantly affected by ethanol exposure in a time‐dependent manner. Prenatal exposure lead to a 27.1 % decrease in neuronal number. Early postnatal exposure led to a smaller decrease (‐15.1%), and late postnatal exposure had no affect on the number of PSN neurons. These data show not only that ethanol directly depresses the proliferation of neuronal precursors, but also that ethanol causes the death of neurons during the period of synaptogenesis.
A Simple Auditory Oddball Task in Young Adult Males at High Risk for Alcoholism
Authors: Ramachandran Gayatri , Porjesz Bernice , Begleiter Henri , Litke Ann
Published: April 2006

The reduction in the amplitude of the auditory P300 in young adult males at high risk for alcoholism has not been as consistently replicated as has been the reduction in the visual P300 amplitude in the same group. The easier nature of the auditory task was thought to be responsible for the inconsistency. We examined the auditory P300 amplitude in a group that has not yet been studied, young adult sons of alcoholics (mean age = 24.9 years, n= 48), and compared them with age and sex‐matched controls (mean age = 27.8 years, n= 23). We found the auditory P300 amplitude to be reduced in the high‐risk group and this reduction to be the greatest over the posterior centro‐parietal and occipital areas when individual leads were examined. We further analyzed the data using current source density, a mathematical transformation that circumvents some of the errors inherent in measuring scalp‐evoked potentials, and found reduced current source density in the high‐risk group in the posterior central and parietal areas. Thus, we found that a simple auditory oddball task was effective in eliciting P300 differences in groups at high and low risk for alcoholism. The clinical significance of the P300 is discussed, as well as the relevance of task difficulty in eliciting auditory P300 differences in young males at high risk for alcoholism.
Elevated Rates of Early Discontinuation from Pharmacotherapy Trials in Alcoholics and Drug Abusers
Authors: Kranzler Henry R. , Escobar Rodrigo , Lee Duk‐Ki , Meza Eduardo
Published: April 2006

The failure of subjects to complete clinical trials is a common problem with important implications for the interpretation of study results. Although a substantial literature exists on the high prevalence of premature termination from psychiatric and substance abuse treatment settings, there has been little attention paid to early discontinuation in clinical trials. There is evidence that the presence of substance abuse predicts higher rates of early discontinuation. This, combined with a recent increase in efforts to develop medications for treatment of substance use disorders, led us to conduct a literature review to determine whether pharmacotherapeutic trials for patients with these disorders have higher rates of premature discontinuation than comparable studies of patients with other psychiatric disorders. Of 267 articles that were initially identified, 83 met predetermined criteria for inclusion in the analysis. As hypothesized, after controlling for a number of potential contributing variables, treatment trials with substance abuse patients showed a significantly poorer retention rate than those of patients with other psychiatric diagnoses. The difference in retention rate was also evident when studies specific to alcohol dependence, the largest subgroup of substance use disorders, were evaluated separately. Although the retrospective nature of the study design limits the conclusions that can be drawn, the results suggest that, in pharmacotherapy trials with alcoholics or other substance abuse patients, particular attention should be paid to enhancing treatment retention.
Evidence of Alcohol‐Related Efficiency Deficits in an Episodic Learning Task
Authors: Nixon Sara J. , Bowlby David
Published: April 2006

Using a component processes model, the current study examined the cognitive processes of alcoholic and community control subjects engaged in the acquisition of new context‐bound (e.g., episodic) information. Of particular interest was whether alcoholics were inferior to controls in the efficiency with which information was acquired and whether there was a gender × group interaction in cognitive efficiency. Alcoholic (n= 16 females; n= 22 males) and community control (n= 21 females; n= 21 males) subjects participated in a serial learning task that consisted of three 12‐item word lists. Standard administration protocols for serial learning tasks were used. On efficiency measures, there were significant differences between groups [F(1,75) = 8.51, p= 0.005] and sexes [F(1,75) = 4.05, p= 0.048]. There was also a group × sex interaction [F(1,75) = 7.73, p= 0.007]. Duncan multiple‐range comparisons revealed alcoholic females to be significantly inferior to control females, but equivalent to male controls and alcoholics. These data are consistent with other studies revealing the sensitivity of cognitive efficiency to alcohol‐related effects and extend previous findings to tasks involving episodic learning tasks.
Cytochrome P4502E1 Genotypes, Alcoholism, and Alcoholic Cirrhosis in Han Chinese and Atayal Natives of Taiwan
Authors: Carr Lucinda G. , Yi Im S. , Li Ting‐Kai , Yin Shih‐Jiun
Published: April 2006

Genetic factors may play a role in the development of alcoholic liver disease (ALD). Cytochrome P4502E1 (CYP2E1) catalyzes the oxidation of ethanol, producing acetaldehyde and free radicals capable of reacting with and peroxidizing cell membranes. Polymorphisms have been identified in the 5′‐flanking region of the CYP2B1 gene that may alter the transcriptional activity. In our laboratory, no difference in d and c2 allele frequencies was observed between alcoholic patients with or without liver disease in Caucasian men, but there is reported data to the contrary for other populations. To determine if there is a differential susceptibility to ALD between ethnic groups that differ in the frequency of the c2 allele, we studied 30 Han Chinese with severe alcoholic liver disease. Allele frequencies of alcoholics with cirrhosis were compared with 46 alcoholic and 100 nonalcoholic Han individuals without liver disease. To identify the type A (homozygous ford), type B (heterozygous for d and c2) and type C (homozygous for c2) genotypes, DNA encompassing the polymorphisms was amplified by polymerase chain reaction, slot‐blotted, and probed with allele‐specific oligonucleotides. No significant differences in c2 allele frequencies were found: 0.23 for alcoholics with severe liver disease, 0.20 for alcoholics without liver disease, and 0.26 for the normal population. There also was no difference in c2 allele frequencies between alcoholic and nonalcoholic Atayal natives from Taiwan. Therefore, our results suggest that the allelic variations at the CYP2B1 gene locus also do not significantly affect the development of alcoholism or ALD in Han Chinese and Atayal natives of Taiwan.
Indicators of Genetic and Environmental Influence in Alcohol‐Dependent Individuals
Authors: Johnson Eric O. , van den Bree M. B. M. , Pickens Roy W.
Published: April 2006

Although much is known about genetic and environmental influences in alcohol dependence at the population level, little is known about the relative contribution of such influences on individuals. As an initial step toward individual assessment, concordance for the Diagnostic Interview Schedule, version III alcohol symptoms was determined in a sample (n= 113) of male monozygotic (MZ) and dizygotic (DZ) twins. Items were assigned to a genetic or environmental scale on the basis of significant MZ/DZ differences in proband‐wise concordance rates. Weights were assigned to items based on factor analyses. For the genetic scale, significant differences were found between MZ and DZ intraclass correlations. No significant differences were found between MZ and OZ correlations on the environmental scale. When scores on the environmental scale were controlled, genetic scale scores were correlated with earlier age of onset of alcohol problems and a shorter interval between first intoxication and onset of alcohol problems. When scores on the genetic scale were controlled, environmental scale scores were correlated with later age of onset of alcohol problems and a longer interval between first intoxication and onset of alcohol problems. These results suggest it is possible to assess relative influence of genetic and environmental factors in individual cases of alcohol dependence.
Plasma and Urine Salsolinol in Humans: Effect of Acute Ethanol Intake on the Enantiomeric Composition of Salsolinol
Authors: Haber H. , Winkler A. , Putscher I. , Henklein P. , Baeger I. , Georgi M. , Melzig M. F.
Published: April 2006

The tetrahydroisoquinoline (TIQ) salsolinol (SAL), a condensation product of dopamine and pyruvate or acetaldehyde, is one of the neuropharmacologically active alkaloids in mammals. Previous HPLC studies have shown that the R‐enantiomer of SAL is largely predominant, or is the only enantiomer in the urine of healthy subjects, whereas the S‐enantiomer was found predominant in the urine of alcoholics. An enzymatic pathway for SAL formation that is influenced by chronic alcohol intake was proposed. However, our analyses showed that the SAL detectable in human urine and plasma is racemic, at least in healthy subjects. No change of the enantiomeric distribution was observed after an acute alcohol ingestion (1 g alcohol/kg body weight). Using a new method for the resolution of the SAL enantiomers and gas chromatography/mass spectrometry analysis, the SAL enantiomers were quantified in the urine and plasma of 24 subjects before and after the intake of alcohol. Special dietary conditions were observed to avoid interferences by the SAL of the foodstuff. Although the distribution of SAL enantiomers was not changed after alcohol intake, the total urinary SAL output and the plasma concentration of SAL were significantly influenced in different ways. Only five subjects showed a significant increase both in plasma SAL concentration and in the total urinary SAL output, whereas 19 subjects showed decreased or unchanged SAL levels after alcohol administration. Data also show that only the subjects with low baseline levels (mean of 0.148 ng SAL/ml plasma) tend to increase SAL levels after ethanol ingestion, which may imply some genetic basis for the response.
Patterns of Ethanol Consumption in a Continuous Access Situation: The Effect of Adding a Sweetener to the Ethanol Solution
Authors: Samson H. , Files F. , Brice G.
Published: April 2006

The effect of the addition of sucrose to an ethanol solution upon daily intake patterns was examined in a continuous‐access operant situation with Wistar rats. Rats were first initiated to self‐administer orally a 10% ethanol (v/v) solution using the sucrose‐substitution procedure in 30‐min limited‐access conditions. When then studied in a continuous‐access operant situation (23 hr ethanol access), substantial increases in ethanol consumption were found when varying concentrations of sucrose were added to the ethanol solutions presented. This increased consumption was found to be a complex function of both an increase in the number of drinking occurrences each day and in the size of each drinking occurrence. When 2% sucrose was compared with 2% sucrose/10% ethanol, the consumption of the sweetened ethanol was greater than consumption of the sweetener alone, suggesting that the ethanol added to the ability of the solution to maintain behavior beyond that of the sucrose alone. This study supports the use of sweetened ethanol solutions for the study of ethanol drinking patterns, and as a model system for examining factors involved in the regulation of ethanol consumption.
Failure to Find Postshock Increases in Ethanol Preference
Authors: Fidler Tara L. , LoLordo Vincent M.
Published: April 2006

Volpicelli et al. (Alcohol Clin Exp Res 14:913–916, 1990) found that rats given a choice between drinking 5% ethanol and water showed enhanced ethanol preference after daily sessions of shock, relative to No‐Treatment controls. In our first experiment, rats were given a choice between 5% ethanol and isocaloric sucrose after daily sessions of shock. On shock days, rats received either 2 or 60 shocks over 1 hr. The 60‐Shock group increased its ethanol preference from the baseline phase to the postshock phase, whereas the 2‐Shock group decreased its ethanol preference from the baseline phase to the shock phase. However, the ethanol preferences of the two groups were not significantly different from each other during any phase. In four subsequent experiments, Shock, No‐Shock, and No‐Treatment groups were given a choice between 5% ethanol and water. The experiments varied on: whether the treatments and measurements of consumption occurred in the light versus dark phase of the cycle, and whether there was one measurement per day or four. Baseline ethanol preference varied widely between experiments. In none of the experiments did shock differentially enhance ethanol preference. The findings of Volpicelli et al. were not replicated.
Development and Characterization of a Binge Drinking Model in Mice for Evaluation of the Immunological Effects of Ethanol
Authors: Carson Edmond J. , Pruett Stephen B.
Published: April 2006

This study describes the development and characterization of a binge drinking model in which a single dose of ethanol (EtOH) is administered by gavage to B6C3F1 mice. Blood EtOH levels were monitored over time after administration of EtOH at doses of 3.0–7.0 g/kg. Peak levels were in the range of 0.2–0.5%, and clearance was complete within 2–12 hr. Substantial increases in blood corticosterone levels were noted. Behavioral changes in EtOH‐treated mice aged 8 weeks ranged from no effect (3–4 g/kg) to severe ataxia (6–7 g/kg). In mice aged 16 weeks, a dosage of 7 g/kg caused loss of the righting reflex in some animals and severe ataxia in most of the others. Clinical chemistry results did not indicate biologically important changes in general physiological/homeostatic systems in EtOH‐treated mice, but there were indications of minor liver damage at the 7 g/kg dosage. Thus, administration of EtOH to B6C3F1 mice by gavage produces behavioral changes, changes in blood EtOH levels, and probably glucocorticoid levels representative of at least some human binge drinkers. The model was used to evaluate the effects of binge drinking on antibody responses, and the results indicate the model will be useful for such studies.
Effects of Chronic Alcohol Consumption and Aging on Dopamine D2 Receptors in Fischer 344 Rats
Authors: Tajuddin Nuzhath F. , Druse Mary J.
Published: April 2006

Aging and chronic alcohol consumption are each accompanied by significant changes in dopamine and dopamine receptors. This study extended previous work by investigating the combined effects of chronic alcoholism and aging on total dopamine D2 receptors in brain areas associated with the nigrostriatal and mesocorticolimbic systems. In addition, the effects of chronic alcohol consumption and aging on the high‐affinity state of D2 receptors and their conversion to the low‐affinity form is included. Quantitative autoradiography was used to assess [3H]spiperone‐labeled D2 receptors in tissue sections from 5‐ to 14‐ and 24‐month Fischer 344 rats that were pair‐fed a control or 6.6% (v/v) ethanol‐containing liquid diet for 6 weeks. In addition, D2 receptors were determined in rats given the control liquid diet ad libitum. The results of these experiments demonstrated age‐related changes in the nigrostriatal system. There was an age‐related loss of total dopamine D2 receptors in the rostral and caudal striatum (∼25% decrease in Bmax). This decline in D2 receptors may be associated with changes in motor function. Despite the age‐related decline in D2 receptors, there were no significant differences in the proportion of striatal receptors in the high‐affinity form or in their conversion to the low‐affinity state. Both aging and chronic alcohol consumption produced significant changes in the concentration of D2 receptors in brain areas associated with the mesocorticolimbic system. That is, the specific binding of [3H]spiperone was decreased in the frontal cortex of aged rats. In addition, chronic alcoholism was associated with a significant increase (∼20%) in the Bmax for D2 receptors in the nucleus accumbens. Nonetheless, neither age nor chronic alcohol consumption altered the proportion of high‐affinity D2 receptors in the nucleus accumbens or their conversion to the lower affinity state. The observed changes in D2 receptors in the frontal cortex and nucleus accumbens are of interest because of the involvement of the mesocorticolimbic dopamine areas in the rewarding properties of alcohol and other drugs of abuse. Although aging and chronic alcoholism both produced significant changes in dopamine D2 receptor concentrations, alcohol did not accentuate the age‐related loss of D2 receptors. We cannot eliminate the possibility that a more prolonged exposure or higher ethanol dose may potentiate age‐related changes in the dopaminergic system.
Alcohol Modulates Alveolar Macrophage Tumor Necrosis Factor‐α, Superoxide Anion, and Nitric Oxide Secretion in the Rat
Authors: D'Souza Nympha B. , Nelson Steve , Summer Warren R. , Deaciuc Ion V.
Published: April 2006

We investigated the effect of alcohol (ethanol) on the ability of the alveolar macrophage to produce tumor necrosis factor‐α (TNF‐α), superoxide anion (O2−), and nitric oxide (NO)—three critical components of pulmonary host defense. Male rats were treated with alcohol either acutely (priming dose 175 mg/100 g of body weight, followed by a 7‐hr continuous intravenous infusion of 30 mg/100 g of body weight/hr) or chronically (12–14 weeks of feeding ethanol in a liquid diet). Three hours before sacrifice, the rats received an intravenous injection of saline or lipopolysaccharide (LPS; Escherichia coli, 026:B6, 100 μg/100 g of body weight). Alveolar macrophages (AMs) were then isolated by bronchoalveolar lavage and assessed for their in vitro capacity to produce TNF‐α, O2−, and NO spontaneously and in response to different stimuli. Acute alcohol administration suppressed in vitro LPS‐stimulated AM TNF‐α secretion by 52%. AMs from both pair‐ and alcohol‐fed rats secreted TNF‐α spontaneously in culture. However, the AMs from chronic alcohol‐fed group secreted 42–53% less TNF‐α spontaneously and in response to LPS, interferon‐γ (IFN‐γ) or IFN‐γ+ LPS compared with the AMs from pair‐fed group. Systemic LPS treatment inhibited in vitro‐LPS‐stimulated AM TNF‐α secretion (50%) only in the control rats. Acute alcohol administration enhanced significantly in vitro phorbol 12‐myr‐istate 13‐acetate (PMA)‐ and opsonized zymosan (OPZ)‐induced AM O2− secretion (4‐ and 1.8‐fold, respectively). Systemic LPS treatment primed the AMs from control rats to secrete 83% more O2− in response to PMA but not OPZ; however, in the acute alcohol‐treated group, it suppressed both PMA (54%)‐ and OPZ (66%)‐induced AM O2− release (loss of priming effect of LPS). Chronic alcohol feeding suppressed PMA‐induced AM O2− secretion (40%) without affecting the OPZ‐induced release. Although systemic LPS treatment had no significant effect on PMA or OPZ‐induced AM O2− secretion in the pair‐fed group, it enhanced the PMA‐stimulated AM O2− release (88%) in the alcohol‐fed group. AMs recovered from control or acute alcohol‐treated rats did not secrete NO spontaneously in vitro. However, AMs from both pair and chronic alcohol‐fed rats secreted NO spontaneously with AMs from chronic alcohol‐fed group secreting 34% less. Both acute and chronic alcohol treatment inhibited AM NO secretion in response to IFN‐γ, LPS, and IFN‐γ+ LPS significantly. Systemic LPS had no effect on AM NO production in response to different in vitro stimuli in any of the treatment groups. These data suggest that: (1) both acute and chronic alcohol administration to rats inhibit AM TNF‐α and NO secretion; (2) acute and chronic alcohol treatment have differential effects on AM O2− secretion; and (3) alcohol‐induced alteration in AM TNF‐α, O2−, and NO secretion may in part explain the increased susceptibility of alcohol‐consuming individuals to pulmonary infections.
Effects of Prenatal Alcohol Exposure and Aging on Auditory Function in the Rat: Preliminary Results
Authors: Church Michael W. , Abel Ernest L. , Kaltenbach James A. , Overbeck George W.
Published: April 2006

This study investigated select aspects of peripheral and central auditory dysfunction, as well as the pathological effects of aging, in an animal model of fetal alcohol syndrome (FAS). Pregnant rats consumed liquid alcohol diets containing 0, 17.5, or 35% ethanol‐derived calories, from gestation day 7 to parturition. A fourth group was untreated. Offspring of these mothers were tested for auditory and neurological function, using the auditory brainstem response at 6, 12, and 18 months of age. Some animals in the alcohol‐exposed groups showed a peripheral auditory disorder in the form of congenital sensorineural hearing loss. This was correlated with punctate lesions and malformed stereocilia on the auditory sensory receptor cells of the inner ear. Alcohol‐exposed animals also showed a central auditory processing disorder characterized by prolonged transmission of neural potentials along the brainstem portion of the auditory pathway. Animals in the highest dose group also showed an augmentation in the age‐related deterioration of auditory acuity. Thus, increased peripheral and central auditory dysfunctions and pathological deterioration of auditory function in old age may be sequelae of FAS. Such morbidities have important implications for the long‐term clinical assessment and management of FAS patients.
Polydrug Use in an Inpatient Treatment Sample of Problem Drinkers
Authors: Martin Christopher S. , Clifford Patrick R. , Maisto Stephen A. , Earleywine Mitchell , Kirisci Levent , Longabaugh Richard
Published: April 2006

Over the past 30 years in the United States, there have been marked secular increases in polydrug use. Alcohol and other substance use disorders are highly comorbid. Yet, little research has characterized patterns of polydrug use in persons with alcohol dependence. In particular, little is known about this population's use of alcohol and other drugs in combination or on the same day, which is termed simultaneous polydrug use (SPU). This research assessed patterns of SPU in 212 problem drinkers who participated in an alcohol treatment outcome study. Subjects were given a Time‐Line Follow‐Back interview that assessed the use of alcohol and nine other drug classes for each day of the 120 days before treatment entry. A majority of subjects (61%) reported SPU during this assessment interval. Subjects who reported SPU were disproportionately younger, male, and unmarried, compared with those who did not report SPU. The most common alcohol/drug combinations were alcohol with cocaine (60% of subjects who reported SPU), alcohol with marijuana (51 % of SPU subjects), and alcohol with sedatives (31 % of SPU subjects). The most common three‐drug combination was alcohol, cocaine, and marijuana (23% of SPU subjects). Alcohol use and drug use were associated at the event level, significantly more than association predicted by the base rates of the individual behaviors. Time‐Line Follow‐Back data correlated highly with a questionnaire measure of SPU. Results indicate that polydrug use is an important focus for assessment and intervention in alcohol treatment programs.
High Alcohol‐Related Premature Mortality in France: Concordant Estimates from a Prospective Cohort Study and National Mortality Statistics
Authors: Zureik Mahmoud , Ducimetière Pierre
Published: April 2006

This study examines the magnitude of alcohol‐related premature death in the French population, which still has the highest average alcohol intake in the world and a relatively low coronary heart disease mortality rate. Two data sources were used: the national mortality data in 1990 and a prospective mortality experience in a cohort of 2,687 middle‐aged working men examined in 1980–1985 and followed‐up during an average of 9.3 years. In the general population study, alcohol‐related premature mortality (35–64 years) was calculated using alcohol‐attributable fractions (AAFs) derived from studies of alcohol involvement in deaths from various causes. In the cohort, it was estimated from AAFs and attributable risk using both alcohol exposure prevalence and relative risks of death according to alcohol intake categories. In 1990, estimates of 19.1% and 13.0% of all premature deaths in French men and women were attributed to alcohol. Digestive diseases followed by malignant neoplasms in men and by unintentional injuries in women were major contributors to the total number of alcohol‐related premature deaths. In the cohort study, 90 deaths occurred during the follow‐up period. The estimation of alcohol‐related premature mortality using AAFs was 24.4%. The relative risk of total mortality (adjusted for age, smoking habits, and body mass index) for men who consumed >60 ml/day of alcohol, compared with those who consumed 0–25 ml/day was 1.9 (95% confidence interval: 1.1–3.5). The consumption of 26–60 ml/day was not associated with reduced risk of mortality, and the adjusted relative risk for this group was 1.3 (95% confidence interval: 0.7–2.5). The estimated attributable risk of premature mortality caused by consumption of >25 ml/day of alcohol was 29.9%. This study reports the persisting high alcohol‐related premature mortality in the French general population, as well as in middle‐aged working men. The results suggest that efforts should be paid to reduce further the consumption of alcohol in France.
Sensitivity and Specificity of Carbohydrate‐Deficient Transferrin as a Marker of Alcohol Abuse Are Significantly Influenced by Alterations in Serum Transferrin: Comparison of Two Methods
Authors: Sorvajärvi Katja , Blake Joan E. , Israel Yedy , Niemelä Onni
Published: April 2006

Despite a number of investigations suggesting the value of carbohydrate‐deficient transferrin (CDT) as a marker of alcohol abuse, a variety of issues on the applicability of CDT measurements in clinical settings have remained unexplored. Earlier studies in this field have focused on the relationship of CDT and the amount of alcohol consumption or presence of liver disease, whereas the influence of alterations in serum transferrin concentrations on CDT has received less attention. In this study, we compared two different methods for measuring CDT (CDTect and %CDT) and total transferrin concentrations in a sample of 83 alcohol abusers (20 patients with alcoholic liver disease and 63 heavy drinkers who were devoid of liver disease, despite excessive alcohol consumption) and 89 controls, who were social drinkers or abstainers. The control population included 53 hospitalized patients with expected abnormalities in serum transferrin concentrations caused by conditions such as negative iron balance, pregnancy, or nonalcoholic liver disease. Both methods gave significantly higher values in alcohol abusers than in controls (p < 0.01), but the overall sensitivity for detecting alcohol abuse was clearly higher for CDTect (59%) than for %CDT (34%). The correlation between the results obtained by the two methods (r= 0.629) significantly improved, when the CDTect values were replaced by the ratio of CDTect/total transferrin (r= 0.770) (p < 0.05). There was a positive correlation between the CDTect and serum transferrin (r= 0.201, p < 0.01), which was significant both in the alcoholics (r= 0.240, p < 0.05), and especially in the controls (r= 0.727, p < 0.001). A significant inverse correlation emerged between %CDT and total transferrin (r= ‐0.302, p < 0.01). The sensitivities of CDTect and %CDT for correctly classifying alcohol abusers in the subgroup of alcoholic liver disease patients were 90% and 70% and in the subgroup of heavy drinkers without liver disease (49% and 22%), respectively. Specificities for CDTect and %CDT in this sample were 81% and 100%, respectively. However, in the subgroup of hospitalized control patients with abnormal serum transferrin, the specificity of CDTect was only 48%. According to present data, CDTect seems to be more sensitive than %CDT for detecting alcohol abuse. However, any alteration in serum total transferrin concentration markedly decreases the assay specificity. This should be considered when interpreting the assay results in patients with elevated serum transferrin, such as iron deficiency, pregnancy, or liver diseases.
Prenatal Exposure to Alcohol and Marijuana: Effects on Motor Development of Preschool Children
Authors: Chandler Lynette S. , Richardson Gale A. , Gallagher Jere D. , Day Nancy L.
Published: April 2006

Gross motor development of preschool children prenatally exposed to alcohol and marijuana was assessed as part of a longitudinal study. Most mothers in the study were light to moderate users and discontinued or decreased use of alcohol and marijuana after the first trimester of pregnancy. The women were of lower socioeconomic status, half of the sample was African‐American, and most were single. Gross motor development was evaluated with balance and ball‐handling items at 3 years. Balance items included walking on a line, walking on a balance beam, standing on one foot, standing on tiptoes, and stair climbing and descent. Ball‐handling items included catching, throwing, and kicking a ball. Refusal to perform items was also recorded. Prenatal alcohol and marijuana exposure did not negatively affect gross motor development. The composite score on the Stanford‐Binet Intelligence Scale, age at assessment, gender, and examiner were significant predictors of gross motor performance and of refusal to participate in the balance items. The ponderal index, number of siblings, current income, examiner, current maternal use of tranquilizers, and first trimester exposure to amphetamines were also significant predictors of balance skills. Gender and number of hospitalizations predicted refusal to participate in balance items, whereas hearing and vision problems predicted refusal on ball‐handling items. The components of timing, speed, and fine motor control have not been addressed in this study, and therefore it is premature to conclude that there is no impact of prenatal substance use on motor development.
Changes in Human Plasma Nerve Growth Factor Level after Chronic Alcohol Consumption and Withdrawal
Authors: Aloe L. , Tuveri M. A. , Guerra G. , Pinna L. , Tirassa P. , Micera A. , Alleva E.
Published: April 2006

Numerous studies reported in recent years have shown that withdrawal from chronic consumption of drugs induces high levels of anxiety, both in humans and in animal models. In the present study, we demonstrated that withdrawal from chronic consumption of either ethanol or heroin causes a significant increase in plasma nerve growth factor, suggesting that the resulting anxiety condition triggers the release of this molecule. Although the functional significance of this phenomenon needs to be better defined, it is hypothesized that the increased levels of circulating nerve growth factor might be involved in homeostatic adaptive and/or reparative mechanisms.
A Prospective, High‐Risk Study of the Relationship between Tobacco Dependence and Alcohol Use Disorders
Authors: Sher Kenneth J. , Gotham Heather J. , Erickson Darin J. , Wood Phillip K.
Published: April 2006

This study examined the extent to which tobacco dependence (TD) and alcohol use disorders (AUDs) reciprocally influenced each other in a mixed‐gender sample of 452 individuals (n= 232 biological family history of paternal alcoholism, n= 220 no first‐ or second‐degree family history of alcoholism) who were assessed once early in their freshman year of college, ∼3 years later when many were college seniors, and ∼3 years later when many had entered or were entering the work force. AUDs were more prevalent in men than women, in individuals with a family history of alcoholism, and decreased overall with time. TD was more prevalent in those with a family history of alcoholism, showed increasing rates of use over time, and was less prevalent but more stable than AUDs. Transitional probabilities indicated that although a previous AUD or TD diagnosis increased the likelihood of being diagnosed with the other disorder at a later time, comorbid AUDs and TD did not significantly affect the likelihood of recovery from either disorder. Finally, path analysis revealed significant reciprocal relationships between AUDs and TD diagnoses (each predicting the other over time), and significant prediction of AUDs and TD by family history of alcoholism at the first and third times of assessment. Findings supported two general models of AUD/TD comorbidity: a shared vulnerability model and a reciprocal influence model.
Inhibitory Mechanism of Intestinal Ethanol Absorption Induced by High Acetaldehyde Concentrations: Effect of Intestinal Blood Flow and Substance Specificity
Authors: Kinoshita Hiroshi , Ijiri Iwao , Ameno Setsuko , Fuke Chiaki , Fujisawa Yoshihide , Ameno Kiyoshi
Published: April 2006

This study describes the effects of high blood acetaldehyde concentrations on the intestinal absorption of ethanol and 2‐butanone using an in situ single‐pass perfusion technique on the rat intestine and the colored microsphere method to measure intestinal blood flow. We found that high blood acetaldehyde concentrations inhibit intestinal ethanol absorption in an inverse proportion to peak acetaldehyde concentrations, decrease intestinal blood flow, and inhibit intestinal absorption of 2‐butanone. The decrease of the intestinal blood flow, induced by high blood acetaldehyde concentrations, is a major mechanism inhibiting intestinal ethanol absorption, but other mechanisms are also thought to inhibit absorption. Therefore, inhibition by high acetaldehyde concentrations is not the only factor affecting ethanol absorption.
Effects of Chronic Ethanol Administration on the Endocytosis of Cytokines by Rat Hepatocytes
Authors: Tuma Dean J. , Todero Sandra L. , Barak‐Bernhagen Mary , Sorrell Michael F.
Published: April 2006

The effects of chronic ethanol administration on the endocytosis of three representative cytokines were investigated in isolated rat hepatocytes. When hepatocytes were isolated from rats that were fed an ethanol liquid diet for 12 to 13 weeks, these cells exhibited a decreased ability to internalize and degrade transforming growth factor‐α, tumor necrosis factor‐α and interleukin‐6, compared with hepatocytes from the pair‐fed controls. This impaired endocytosis of all three cytokines was accompanied by significant decreases in the amount of hepatocyte surface‐bound cytokine. Changes in cytokine binding to surface receptors and reduced rates of receptor‐cytokine complex internalization into the cells seem to be major contributors to defective endocytosis in hepatocytes from the ethanol‐fed rats. Impaired hepatocyte endocytosis could lead to altered steady‐state levels of cytokines in the liver and modified physiological responses to cytokines. These changes could affect homeostasis among the various cell types in the liver and could contribute to liver dysfunction and injury.
Naltrexone Persistently Reduces Rats' Intake of a Palatable Alcoholic Beverage
Authors: Gardell Luis R. , Hubbell Christopher L. , Reid Larry D.
Published: April 2006

Rats were given 30 days of opportunity to take a sweetened alcoholic beverage and water for 2 hr/day. At first, they took little alcohol, but subsequently took, on average, 2.3 g/kg of alcohol/daily session. They also took sufficient water, during the 2‐hr period, to maintain their health and to steadily gain weight. At the end of the 30 days, they were divided into four groups so that their intakes of alcohol were similar. All groups continued on the daily regimen, but each group received different injections. One group received placebos, whereas the other two groups received either 5.0 or 10.0 mg/kg, respectively, of naltrexone daily, 30 min before the drinking session. The fourth group received 5.0 mg/kg of naltrexone 12.5 hr before the session and another 5.0 mg/kg 30 min before the session. This regimen of dosing and daily opportunities to drink continued for 30 days. With the end of injections, subjects continued on the regimen for another 5 days. Naltrexone, dose‐relatedly, reduced rats' intake of alcoholic beverage. Furthermore, with respect to reducing intake of alcohol, no tolerance or refractoriness were observed across the 30 days of dosing. Within a couple of days after dosing, levels of intake returned to predosing levels.
Application of Decision Theory to DUI Assessment
Authors: Leshowitz Barry , Meyers Jonathan M.
Published: April 2006

The application of decision theory to screening of driving under the influence (DUI) offenders is illustrated in an evaluation study that investigated the validity of a structured interview and a survey instrument. These findings are examined graphically using the relative operating characteristic (ROC). This graph relates the proportion of true‐positive cases to the proportion of false‐positive cases for various placements of the decision cut‐off score. The ROC'S two principal parameters, test sensitivity and examiner bias, are used to provide a complete quantitative description of the performance of two screening instruments. A major goal of this study is to show how a new measure of examiner bias, the “cost ratio,” improves the evaluation of DUI screening programs.
Behavioral and Cognitive Measurements Predict Scores on the MAST: A 3‐Year Prospective Study
Authors: Deckel A. Wallace , Hesselbrock Victor
Published: April 2006

This experiment examined the ability of neuropsychological and behavioral tests of anterior brain functioning to predict changes in alcohol‐related behaviors 3 years after the initial evaluation. One hundred four young adult subjects, sixty‐six of whom had a positive family history of alcoholism, filled out the Michigan Alcoholism Screening Test (MAST), self‐rated the frequency with which they consumed alcohol, and completed a retrospective test of childhood hyperactivity/impulsivity/conduct problems (Wender Behavioral Checklist). Eighty‐three of the subjects also completed a neuropsychological battery consisting of cognitive tests of executive functioning (i.e., Trails, Categories Test, Similarities) and motor tests (i.e., TPT, hand dynamometer, finger tapping). Subjects returned to complete the alcohol‐related measures during a second testing session 3 years later. Changes in MAST scores, and in alcohol consumption, between the first and second test session were computed, and median splits classified subjects into “high” versus “low” change groups. After factor analysis of the cognitive and behavioral data, hierarchical logistic regression equations assessed the ability of the cognitive and behavioral variables, as well as the presence of a positive family history of alcoholism, to predict future changes in the alcohol outcome measures. Scores from the WENDER behavioral checklist predicted future changes in the MAST scores (p = 0.0026), with more impaired scores associated with higher MAST scores. Tests of executive functioning, in subjects with a positive family history of alcoholism, predicted alcohol consumption (p = 0.033). None of the other predictor variables showed any relationship to the alcohol‐related outcome measures.
Carbohydrate‐Deficient Transferrin and Gamma‐Glutamyl Transferase Levels during Disulfiram Therapy
Authors: Helander Anders , Carlsson Sten
Published: April 2006

Serum samples for quantification of carbohydrate‐deficient transferrin (CDT) and γ‐glutamyl transferase (GGT) were collected from alcohol‐dependent men and women upon admission to the hospital for detoxification, and repeatedly over a 3‐ to 5‐week period of supervised disulfiram administration as outpatients. On admission, 10 of 12 patients showed CDT concentrations above the conventional cutoff limits, whereas 6 had elevated GGT values. Normalization usually occurred within 1 to 3 weeks of disulfiram treatment, after which CDT and GGT leveled out at a relatively stable individual baseline level. However, in those patients with the highest values on admission, the decline continued during the entire observation period. The time for normalization of GGT was typically longer than for CDT. In four male patients who had taken disulfiram regularly (400–800 mg every second or third day) for at least 3 months before entering the study, the CDT and GGT concentrations were stable over time and all fell within normal limits. The present results indicate that disulfiram treatment does not influence the serum level of CDT. It is also suggested that consecutive CDT and GGT measurements during outpatient treatment with disulfiram after detoxification can be used to identify the individual baseline (Le., abstinence) values for CDT and GGT, and, furthermore, for monitoring treatment outcome.