bluuebunny/crossref_metadata_2025 huggingface dataset:
Ethnic Differences in Performance of Screening Instruments for Identifying Harmful Drinking and Alcohol Dependence in the Emergency Room
Authors: Cherpitel Cheryl J. , Clark Walter B.
Published: April 2006

This study examines sensitivity and specificity figures associated with screens used to predict harmful drinking and alcohol dependence among current drinkers. The study population comes from a probability sample of emergency room patients in Jackson, MS. Data are presented by gender and injury status (injured versus noninjured) for Blacks and for Whites. The Composite International Diagnostic Interview was used to assess ICD‐10 criteria for harmful drinking and alcohol dependence, which were taken as standards. Predictors include screening instruments (CAGE, AUDIT, brief MAST, TWEAK, and History of Trauma Scale), breathalyzer reading, self‐reported consumption before the injury or noninjury event, quantity and frequency of drinking, and an abbreviated alcohol dependence experiences measure used in general population surveys. Single items from these screening instruments were also tested as predictors. Overall, the TWEAK and the AUDIT performed best in terms of sensitivity and specificity, but variation across subgroups suggests that the search for a good screening instrument for general use must be continued.
Relationship of Protein Calorie Malnutrition to Alcoholic Liver Disease: A Reexamination of Data from Two Veterans Administration Cooperative Studies
Authors: Mendenhall Charles , Roselle Gary A. , Gartside Peter , Moritz Thomas ,   The Veterans Administration Cooperative Study Groups 119 and 275
Published: April 2006

The relationship of protein calorie malnutrition (PCM) to alcoholic liver disease was studied in 666 patients enrolled in two Veterans Administration Cooperative Studies. Some findings of malnutrition could be detected early in 62% of the comparison patients (43 subjects who were alcoholic, but had not yet developed clinical or laboratory evidence of liver injury). In those who had progressed to the stage of liver injury sufficient to manifest clinical jaundice (536 patients), some findings of malnutrition were present in every patient (100%). The degree of malnutrition correlated closely with the development of all the serious complications of the liver disease (ascites, encephalopathy, and hepatorenal syndrome), as well as the overall mortality.

The degree of malnutrition was also important in predicting response to some forms of treatment. When prednisolone, a catabolic adrenal steroid, was used, efficacy was independent of the level of malnutrition. However, a relationship was observed with the severity of the liver injury [quantified by the level of jaundice and coagulopathy, i.e., Maddrey's discriminant function (DF(Maddrey))]. For prednisolone, the response was seen only when the DF was 81‐100 reducing mortality 45%.

When oxandrolone, an androgenic anabolic steroid treatment was given, efficacy was observed only in those with moderate malnutrition (PCM score 60–79% of normal) and maximized with adequate caloric intake reducing mortality 86%. To simplify the method of calculating the PCM score for predicting response to anabolic therapy, a multiple logistic regression model was developed from the parameters used to assess nutritional status: DF(PCM)= 0.098 (peripheral blood lymphocytes) + 0.078 (creatinine height index). Using the DF(PCM), oxandrolone improved survival 42% when the DF(PCM) exceeded 6.5, but was < 11.0. These results suggest that the two DFs should be determined in patients with life‐threatening alcoholic liver injury and the appropriate therapy administered based on the observed results.
Aggressivity in Adolescent Alcohol Abusers: Relationship with Conduct Disorder
Authors: Moss Howard B. , Kirisci Levent
Published: April 2006

Several longitudinal and retrospective studies have documented an association between premorbid aggression and an increased risk for an alcohol‐use disorder in adulthood. However, few data are available examining the relationship between trait aggressivity, alcohol use behavior, and the presence of an early‐onset alcohol use disorder diagnosis among the adolescent population. To address this deficiency, this study had three goals. First, the relationship between aggressivity and adolescent alcohol consuming behavior was examined. Second, the presence and magnitude of trait aggressivity were determined among adolescents who met psychiatric diagnostic criteria for alcohol abuse/ dependence (ALC), while controlling for the presence of a conduct disorder (CD). Third, because CD is overrepresented among adolescent alcohol abuse cases and is a priori defined by the presence of certain aggressive behaviors, the simultaneous contributions of CD and ALC on trait aggressivity were also investigated through structural equation modeling. The results confirm the salience of heightened aggressivity as an essential feature of this early‐onset alcohol‐abusing population and indicate the importance of addressing this behavioral domain in prevention and treatment efforts.
Occupational Stress and the Risk of Alcohol Abuse and Dependence
Authors: Crum Rosa M. , Muntaner Carles , Eaton William W. , Anthony James C.
Published: April 2006

Using prospective data, we examined the relationship between occupational stress and risk for alcohol disorders. Consistent with the Demand/Control model for psychosocial work environments, we hypothesized that individuals working in high‐strain occupations (jobs with high demands and low control) would be at increased risk for alcohol abuse‐dependence relative to those in low‐strain occupations (jobs with low demands and high control). We classified high occupational strain into two categories: (1) jobs with high psychological demands and low control, and (2) those with high physical demands and low control.

A total of 18,571 study subjects were selected in 1980–1984 by taking probability samples of adult household residents at five sites of the Epidemiologic Catchment Area Program. At baseline, participants completed standardized interviews that measured sociode‐mographic variables and assessed whether they had met diagnostic criteria for currently or formerly active alcohol abuse‐dependence syndromes. The interviews were readministered 1 year later to identify cases among the participants. Subjects were sorted into risk sets by age and residence census tract1 and persons with a previous history of alcohol abuse or dependence, as well as those who were over 64 years or had no history of full‐time employment, were excluded. Among the 507 participants included in the risk sets, there were 126 incident cases of alcohol abuse‐dependence and 381 age and residence‐matched noncases. Relative to low‐strain employment, men were found to be 27.5 times more likely to develop alcohol abuse‐dependence if they had been employed in a high‐strain job classified as having high psychological demands and low control (p= 0.008), and 3.4 times at higher risk for an alcohol disorder if they were employed in high‐strain jobs with high physical demands and low control (p= 0.03). No appreciable risk was found for women in any of the high‐strain job categories. The results highlight occupational stress as a potential risk factor for alcohol abuse and dependence, and add to the growing body of literature on relationships between psychosocial work environment and disease states. If confirmed in other studies, these findings identify potential sources of preventive strategies for alcohol disorders.
Autistic Behaviors in Offspring of Mothers Abusing Alcohol and Other Drugs: A Series of Case Reports
Authors: Harris Susan R. , MacKay Linda L. J. , Osborn Jill A.
Published: April 2006

Although autistic‐like behaviors were described even in the earliest reports of fetal alcohol syndrome, it was only recently that fetal alcohol syndrome and autism were reported as a dual diagnosis in six school‐aged children. The purpose of the present series of case reports is to describe marked autistic characteristics in three much younger children (25–36 months) with histories of prenatal exposure to alcohol and other drugs. The behavioral characteristics of these children are described and compared with current diagnostic criteria for autistic disorder. In addition, longitudinal scores on the Bayley Scales of Infant Development are provided to underscore the marked developmental delays shown by each of the children. Limitations of these case reports are discussed with suggestions for future prospective research.
In Utero Ethanol Exposure Elicits Oxidative Stress in the Rat Fetus
Authors: Henderson G. I. , Devi B. G. , Perez A. , Schenker S.
Published: April 2006

Prior studies in our laboratory have shown that exposure of cultured fetal rat hepatocytes to ethanol (E) blocks epidermal growth factor‐dependent replication and that this is paralleled by cell membrane damage, mitochondrial dysfunction, membrane lipid peroxidation (LP), and enhanced generation of reactive oxygen species. These measures of E‐mediated oxidative stress (OS) were mitigated by treatment with antioxidants, and cell replication could be normalized by maintaining cell glutathione (GSH) pools. We have now extended these studies to an in vivo model. Rats were administered E (4 g/kg, po) at 12‐hr intervals on days 17 and 18 of gestation and killed on day 19,1 hr following a final dose of E (a total of 5 doses). Fetal and maternal brain and liver were assayed for signs of OS. The 2‐day in utero E exposure increased membrane LP in fetal brain as evidenced by increased malondialdehyde (MDA) levels from 1.76 ± 0.12 se (nMol/mg protein) to 2.00 ± 0.08 (p < 0.05) and conjugated dienes from 0.230 ± 0.006 se (OD233/mg lipid) to 0.282 ± 0.006 (p < 0.05). In fetal liver, MDA levels increased from 2.39 ± 0.08 se (nMol/mg protein) to 2.87 ± 0.08 (p < 0.05), whereas dienes differed significantly only between ad libitum controls and the E and pair‐fed control groups (p < 0.05). E decreased GSH levels in fetal brain by 19%, from 19.88 ± 0.72 to 16.13 ± 1.06 (nMol/mg protein) (p < 0.05). A10% decrease in GSH was seen in fetal liver (p < 0.05). GSH in maternal brain was decreased by 44% from 47.29 ± 3.38 to 26.60 ± 2.29 (p < 0.05). Other E‐related increases in these OS measures were not observed in maternal organs. E did not decrease α‐tocopherol levels in fetal and maternal brain or in fetal liver (p < 0.05), whereas maternal liver α‐tocopherol content was reduced by 31% (p < 0.05) by E treatment. It is concluded that maternal E consumption can induce an OS in fetal tissues that may contribute to the fetotoxic effects of E.
Changes in the Fatty Acid Profile of Plasma and Adipose Tissue in Rats after Long‐Term Ethanol Feeding
Authors: Gómez‐Tubío A. , Pita M. L. , Tavares E. , Murillo M. L. , Delgado M. J. , Carreras O.
Published: April 2006

The effect of chronic ethanol feeding on the fatty acid composition of plasma and abdominal adipose tissue in rats was studied. Animals were maintained on a 30% ethanol solution in drinking water for 3 and 5 months. Control rats were given water. Caloric intake was similar in control and ethanol‐fed rats at the end of the experimental period. However, a decrease in body weight was observed in rats that had consumed ethanol. Palmitoleic (16:1n7) and oleic (18:1n9) acids increased markedly, and linoleic acid (18:2n6) decreased in the plasma and in the adipose tissue of ethanol‐fed rats with respect to control rats. After 3 months of ethanol ingestion, long‐chain polyunsaturated fatty acids were reduced both in plasma and adipose tissue. When ethanol was administered for 5 months, only plasma long‐chain polyunsaturated fatty acids of the n‐3 series were decreased. This suggest that changes induced by ethanol ingestion in essential fatty acid metabolism is less pronounced when ethanol feeding is maintained for a long period of time.
Exposure of Neonatal Rats to Alcohol by Vapor Inhalation Demonstrates Specificity of Microcephaly and Purkinje Cell Loss But Not Astrogliosis
Authors: Ryabinin Andrey E. , Cole Maury , Bloom Floyd E. , Wilson Michael C.
Published: April 2006

The artificial rearing model (AR) of fetal alcohol syndrome (FAS) has been shown to induce several major pathologies in the early postnatal rat brain development: microcephaly, selective neuronal cell loss, and activation of astroglia in the neocortex. The purpose of this study was to determine whether these pathologies were specific to the action of alcohol or, in contrast, could result from confounds attributed to this model of FAS. For this purpose, the pathological effects of AR were compared with those of a vapor inhalation (VI) model of FAS. Our studies showed that the microcephaly that developed after exposure to periodic blood alcohol levels (BALs) of 300–350 mg% during postnatal days 4–9 could be achieved by both AR and VI models of FAS, and thus is independent of the method of alcohol administration. In contrast, the gliosis measured by glial fibrillary acidic protein (GFAP) mRNA levels in cortex, as well as by immuno‐histochemical staining for GFAP, was found only in the AR‐FAS model, but not in the VI model. However, the lack of gliosis in VI was apparently not due to a less intrusive intervention of alcohol, because VI exposure resulted in a reduction in Purkinje cell number comparable with that found after AR or intragastric intubation of alcohol. Based on these observations, we conclude that the activation of gliosis observed after AR is not a specific effect of alcohol, but rather is caused by an interaction of alcohol with as yet unidentified factors present in AR.
Mitochondrial Aldehyde Dehydrogenase Polymorphism in Asian and American Indian Populations: Detection of New ALDH2 Alleles
Authors: Novoradovsky A. , Tsai Su‐Jen L. , Goldfarb L , Peterson R. , Long J. C. , Goldman D.
Published: April 2006

Genetic deficiency of the mitochondrial aldehyde dehydrogenase (ALDH2) is frequent in Asian peoples where it is an important factor negatively regulating drinking behavior. To obtain additional information on gene geography of known ALDH2 alleles, and look for new variants, ALDH2 genes were evaluated in a Chinese population from Taiwan, a Yakut population of Siberia, and in five North American Indian populations. A novel approach based on a single‐strand conformation polymorphism assay, and polymerase chain reaction‐directed mutagenesis was developed for genotyping. In the Taiwan Chinese population, the ALDH22 allele frequency was 0.319 ± 0.025, and this allele was not detected in the Yakut population nor in the five North American Indian populations. However, a new allele, ALDH23, was detected in Pima Indians at a frequency of 0.044 ±0.022, and this allele was also observed in 1 of 49 Pueblo samples. ALDH23 is a silent transition 1464 G → A, and it possibly has a wide distribution among North American Indians. A new subtype of the ALDH22 allele, designated as ALDH22Taiwan, was found in 1 of 174 Chinese from Taiwan. ALDH22Taiwan is characterized by two G → A transitions at bases 1486 and 1510, resulting in Glu → Lys substitutions at both the 479 and 487 positions. Thus, this second nonconservative ALDH2 substitution occurs within the sequence of the already inactive ALDH22 allele.
Alcohol Sensitivity and Smoking History in Men and Women
Authors: Madden P.A.F. , Heath A. C. , Starmer G. A. , Whitfield J. B. , Martin N. G.
Published: April 2006

Many studies have found genetic effects to contribute to alcoholism risk in both men and women. Based on preliminary evidence for shared genetic risk between smoking and drinking problems, a re‐analysis of alcohol challenge data on 412 Australian twins was performed to explore the possibility that smoking may diminish or moderate the intoxicating effects of alcohol. We found history of smoking to be strongly associated with self‐reported intoxication after alcohol challenge in women (women: r = ‐0.44 ± 0.08; men: r = ‐0.21 ±0.08), comparable with self‐reported average weekly consumption of alcohol, which was more strongly associated in men (women: r = ‐0.37 ±0.07; men: r = ‐0.54 ±0.06). Structural equation model‐fitting indicated a strong association between heavy drinking and smoking, but the association between smoking and postalcohol intoxication remained even when the effects of heavy drinking were controlled for. These results prompt the question of whether smoking cigarettes directly influences the transition from moderate to excessive use of alcohol by diminishing feelings of alcohol intoxication.
Alcohol Hangover and Managerial Effectiveness
Authors: Streufert Siegfried , Pogash Rosanne , Braig Daniela , Gingrich Dennis , Kantner Anne , Landis Richard , Lonardi Lisa , Roache John , Severs Walter
Published: April 2006

Twenty‐one male managers who normally drink moderate amounts of alcohol participated in a placebo‐controlled, double‐blind, crossover experiment. Subjects consumed either placebo or alcoholic drinks to attain a breath alcohol level of 0.10 during the evening before participation in Strategic Management Simulations. By the time of arrival at the simulation laboratory on the following morning, breath alcohol levels were measured at 0.00. Questionnaire responses indicated considerable hangover discomfort. Responses to semantic differential evaluative scales suggested that research participants evaluated their own managerial performance in the simulation setting as impaired. However, multiple (validated) measures of decision‐making performance obtained in the simulation task did not show any deterioration of functioning. Previous research had shown considerable performance decrements in the same task setting, while blood/breath alcohol levels ranged from 0.05 through 0.10%. Apparently, complex decision‐making competence by persons who normally consume moderate amounts of alcohol may not be impaired by hangover caused by intoxication during the previous evening that remains at or below a blood alcohol level of 0.10.
Effect of Alcohol Use on Allograft Rejection Rates after Liver Transplantation for Alcoholic Liver Disease
Authors: Van Thiel David H. , Bonet Harry , Gavaler Judith , Wright Harlan I.
Published: April 2006

Alcoholic liver disease is a major cause of liver disease and has become an ever‐increasing indication for liver transplantation (LTx). Follow‐up studies have reported a higher rate of alcohol recidivism in patients transplanted for alcoholic hepatitis, compared with those transplanted for endstage alcohol‐associated cirrhosis. It is assumed widely that recurrent alcohol use is associated with reduced compliance with immune suppression and, as a result, an increased risk of graft rejection and loss. To assess this question, 209 alcoholic patients transplanted for either alcoholic hepatitis with cirrhosis or cirrhosis alone between January 1, 1986 and December 31, 1991 were followed, with a mean follow‐up of 4.4 ± 0.6 years. There were 175 episodes of acute cellular rejection (ACR) that occurred in 137 patients, for an overall rejection rate of 83.7% or at a rate of 1.25 episodes/patient with rejection. The rate of ACR was three times as great in those who remained alcohol‐abstinent (2.24 episodes/patient), compared with those who admitted to continued alcohol use (0.75 episodes/patient) (p < 0.01). A total of 33 episodes of chronic rejection occurred in 26 patients, for an overall rate of 12.4%. As was the case for ACR, the chronic rejection rate was greater among those who were continuously alcohol‐abstinent, compared with those who intermittently used alcohol after successful LTx.

There were no differences in the mean FK 506 or cyclosporin A levels in the groups with and without a rejection episode at the time the rejection episode was documented by liver biopsy. Contrary to generally accepted opinion, these data suggest that continued use of alcohol by liver transplant recipients is associated with a reduction, not an increase, in the rate of rejection.
Longitudinal Changes in Magnetic Resonance Imaging Brain Volumes in Abstinent and Relapsed Alcoholics
Authors: Pfefferbaum A. , Sullivan E. V. , Mathalon D. H. , Shear P. K. , Rosenbloom M. J. , Lim K. O.
Published: April 2006

Chronic alcoholism is associated with smaller volumes of cortical gray matter and white matter and a complementary increase in brain cerebrospinal fluid (CSF) volumes, relative to age norms. This longitudinal study quantified the extent of brain volume changes associated with abstinence and drinking at three time points in chronic alcoholics. We obtained magnetic resonance imaging (MRI) on 58 alcoholic men after an average of 12 days (MRI‐1) and 32 days (MRI‐2) of sobriety. In addition, 58 healthy control subjects were scanned at a comparable interval. At MRI‐3, 11 controls and 39 alcoholics were rescanned, 2–12 months after MRI‐2; 19 alcoholics had abstained, and 20 had resumed drinking. Axial MRI slices were segmented into cortical gray matter, white matter, and CSF and summed over seven slices; lateral and third ventricular volumes were also estimated. MRI volume changes were corrected using an estimate of interscan measurement error caused by head positioning differences, and then divided by the interval to yield rates of change (slopes). From MRI‐1 to MRI‐2, the alcoholic group showed declines in CSF volumes of the lateral ventricles and posterior cortical sulci, and a trend toward an increase in anterior cortical gray matter volume relative to the control group. From MRI‐2 to MRI‐3, third ventricular volumes decreased in the abstainers relative to the relapsers and controls; cortical white matter volume decreased in the relapsers. In the relapsers, lifetime consumption of alcohol (as of MRI‐1) predicted later vulnerability to white matter volume decline and third ventricular enlargement with resumption of drinking. These data suggest that improvement in cortical gray matter, sulcal, and lateral ventricular volumes occur early in the course of abstinence, and that improvement in third ventricular volume appears later with continued abstinence. Resumption of drinking after a short period of abstinence arrests third ventricular volume improvement and produces white matter volume loss.
Abnormalities of the Corpus Callosum in Children Prenatally Exposed to Alcohol
Authors: Riley Edward P. , Mattson Sarah N. , Sowell Elizabeth R. , Jernigan Terry L. , Sobel David F. , Jones Kenneth Lyons
Published: April 2006

For 20 years, it has been known that fetal alcohol syndrome (FAS) is associated with abnormal brain development. Early autopsy studies point to the corpus callosum as one area affected by heavy alcohol exposure. Little is known, however, about the integrity of the brain in alcohol‐exposed children who survive the perinatal period. This study was designed to assess the corpus callosum in living children exposed to high doses of alcohol prenatally. Thirteen children with histories of significant prenatal alcohol exposure and 12 normal control children were evaluated using magnetic resonance imaging. Using the midsagittal section, images were measured for the area of the corpus callosum using a computer‐assisted measurement technique. In addition to the overall area, five equiangular regions were determined for each corpus callosum. Of the 13 alcohol‐exposed children assessed, two had agenesis of the corpus callosum. The remaining alcohol‐exposed children had significantly smaller overall callosal areas, as well as smaller regional areas of four of the five callosal regions, when compared with the normal control children. Importantly, when corrected for brain size, three of the five callosal regions were still smaller in the alcohol‐exposed children, although overall area of the corpus callosum was no longer significantly different. These results suggest that prenatal exposure to high levels of alcohol is associated with abnormalities of the corpus callosum. They verify callosal agenesis in children with FAS, which previously had only been noted in autopsy reports. The current findings further document selective reductions in the area of certain regions of the corpus callosum after in utero alcohol exposure, extending our current understanding of alcohol's teratogenic effects on brain development. There is also some indication that the selective reduction in the area of the corpus callosum is similar to that reported in attention deficit disorder.
Effect of Chronic Alcoholism on Human Muscle Glycogen and Glucose Metabolism
Authors: Vernet Maria , Cadefau Joan Aureli , Balagué Antoni , Grau Josep M. , Urbano‐Márquez Alvaro , Cussó Roser
Published: April 2006

To determine the effect of alcohol on carbohydrate metabolism, 48 human muscle biopsies from chronic alcoholics were studied. The level of glycogen and the activities of the enzymes catalyzing glycogen and glucose metabolism were analyzed. Chronic alcohol intake produced an increase in glycogen concentration and a decrease in pyruvate kinase activity before the first signs of myopathy appeared. When myopathy was present, glycogen decreased. These changes may contribute to the decline in skeletal muscle performance in these patients.
Ethanol Inhibition of AMPA and Kainate Receptor‐Mediated Depolarizations of Hippocampal Area CA1
Authors: Martin David , Tayyeb M. I. , Swartzwelder H. Scott
Published: April 2006

Longitudinal hippocampal slices were prepared from adult female rats. The excitatory amino acids, α‐amino‐3‐hydroxy‐5‐methyl‐4‐isoxazole propionate (AMPA) and kainic acid, were applied to area CA1, and the resulting depolarizations were measured using the grease‐gap electrophysiological technique. Agonist dose‐response curves were generated in the presence and absence of various concentrations of ethanol. Ethanol (25–200 mM) significantly attenuated the depolarizations that were produced by each agonist. In addition, we found that ethanol potently antagonized kainate‐induced depolarizations across the agonist concentration‐response curve, whereas it significantly suppressed only AMPA responses that were induced with moderate‐to‐high agonist concentrations.

These results indicate that ethanol has potent antagonist actions against non‐N‐methyl‐d‐aspartate (NMDA) excitatory amino acid‐induced neuronal depolarizations in hippocampal area CA1. Moreover, the relative potency of ethanol depends on the specific excitatory agonist tested and the concentration of that agonist. This suggests that, in addition to the known effects of ethanol on NMDA receptor‐mediated activity, it may also potently attenuate ongoing “fast” glutamatergic synaptic activity in the hippocampus.
Effect of Ethanol Consumption on Adult Rat Liver Mitochondrial Populations Analyzed by Flow Cytometry
Authors: Mateos Antonio , Orfao Alberto , Almeida Angeles , Martin Maria Isabel , Lopez‐Mediavilla Casilda , Medina Jose Maria , Fermoso Julio
Published: April 2006

In the present study, the effects of administering ethanol to adult male rats on the distribution of the low fluorescence population (LFP) and high fluorescence population (HFP), and the rhodamine‐123 fluorescence intensity of these groups of mitochondria are analyzed by flow cytometry. Our results show that ethanol administration to adult male rats induces a redistribution of the HFP and LFP mitochondrial populations leading to an increase of the less functional HFP mitochondria. In addition, ethanol induced an increase in the mean intensity of green fluorescence of the HFP that is probably related to an increased number of rhodamine‐123 binding sites per mitochondria resulting from mitochondria enlargement.
GABAA Receptor Function and Binding in Stably Transfected Cells: Chronic Ethanol Treatment
Authors: Klein Ronald L. , Mascia Maria Paola , Whiting Paul J. , Harris R. Adron
Published: April 2006

Effects of chronic ethanol exposure on GABAA receptors may contribute to tolerance and dependence to alcohol. Ethanol treatment of mice and rats can produce alterations of GABAA receptor binding, function, and subunit mRNA and protein levels. We treated a cell line (PA3 cells) that stably expresses GABAA receptors chronically with ethanol. Expression of bovine α1β1 and γ2L GABAA receptor sub‐units genes in these cells is controlled by a dexamethasone‐sensitive promoter, and this provides an excellent system to study the regulation by chronic ethanol treatment of receptors with a defined subunit composition. The actions of the GABA agonist muscimol on receptor function (35Cl‐ uptake) were not affected by 100 mM ethanol treatment for 4 days, but the actions of flunitrazepam (1 μM) were decreased in cells treated with ethanol. The functional coupling between benzodiazepine and GABA sites on the receptors was affected by chronic ethanol treatment in a manner consistent with results from mice. Ethanol treatments (50or 100 mM) for 4 days did not affect the affinity (Kd) or receptor density (Bmax) of [3H]flunitrazepam binding, or the levels of α1 subunit mRNA, or α1, or β1 subunit proteins. These results demonstrate that the regulation of the stably expressed GABAA receptors by chronic ethanol, in the absence of neuronal receptor gene promoters, is posttranscriptional and likely posttranslational.
Harman and Norharman in Alcoholism: Correlations with Psychopathology and Long‐Term Changes
Authors: Rommelspacher H. , Dufeu P. , Schmidt L. G.
Published: April 2006

In the search for mechanisms specific for alcoholism, it has become evident that β‐carbolines (BCs; e.g., harman and norharman) are compounds that may act on brain reward systems, thereby mediating an increase in voluntary ethanol (ETOH) drinking in animals. This study was undertaken to analyze relationships between these compounds and clinical variables (e.g., family history, personality data, and affect) in alcoholics and to trace the time course of blood concentrations in subjects abstaining from alcohol for at least 6 months. Nonalcoholics were investigated during sober and ETOH‐loading conditions (1 g ETOH/kg body weight). Levels of harman were elevated in the chronically intoxicated alcoholics and correlated with the scores on the self‐rating depression (SDS) and the self‐rating anxiety (SAS) scales. The group of alcoholics with at least one alcoholic parent had higher levels than the group without such a history. Levels remained elevated for 6 months. Norharman levels were only slightly elevated on the day of admission. They were correlated to high harm avoidance and SDS scores. A family history of alcoholism and the severity of alcoholism as assessed by the number of ICD‐10 criteria fulfilled were correlated with norharman levels. Long‐term observation revealed elevated levels of norharman after 3 months of abstinence, but not after 6 months. The association of harman levels with anxiety and depression demonstrated in the present study suggests that alcoholics with high harman levels use alcoholic beverages as self‐medication in an attempt to overcome possible anxiogenic/depressiogenic actions of harman. Norharman levels are less strongly associated with these mood states, but significantly correlated to harm avoidance tendencies. It has been suggested that the activity of the indolergic neurons is relatively high in individuals with a high harm avoidance score. Biosynthesis of norharman might be stimulated under these conditions (tryptamine serves as precursor).
Abnormal Development of the Cerebellar Vermis in Children Prenatally Exposed to Alcohol: Size Reduction in Lobules I–V
Authors: Sowell Elizabeth R. , Jernigan Terry L. , Mattson Sarah N. , Riley Edward P. , Sobel David F. , Jones Kenneth Lyons
Published: April 2006

Abnormalities of the cerebellar vermis have been well documented in animal models of fetal alcohol syndrome. At this point, it is not known if the same brain region is affected in humans prenatally exposed to alcohol. In this study, the area of the cerebellar vermis was measured from brain magnetic resonance images of 9 children and young adults with prenatal alcohol exposure and 24 control subjects in the same age range. Six of the exposed children met standard criteria for fetal alcohol syndrome. The remaining three subjects had significant histories of prenatal exposure to alcohol, but did not have enough of the classic facial features for the diagnosis. For each subject with a suitable midsagittal section, three vermal areas were circumscribed: anterior vermis (vermal lobules I–V), posterior vermis (vermal lobules VI and VII), and the remaining vermal area (including lobules VIII–X). Statistical analyses revealed that the anterior region of the vermis was significantly smaller in subjects with prenatal alcohol exposure, whereas the posterior region and the remaining vermal area did not differ between groups. Previous findings from an animal model of neonatal alcohol exposure have documented Purkinje cell loss in vermal lobules I–V and IX–X, with notable sparing in lobules VI–VII. Thus, the results of both studies indicate similar patterns of abnormal brain development in the anterior vermal region, with apparent sparing in the posterior vermal region. Our findings, for the first time, suggest that regionally specific Purkinje cell death may also occur in humans prenatally exposed to alcohol.
Carbohydrate‐Deficient Transferrin Evaluation in Dry Blood Spots
Authors: Bean Pamela , Sutphin Mary Susan , Necessary Patricia , Agopian Melkon S. , Liegmann Karsten , Ludvigsen Carl , Peter James B.
Published: April 2006

The aim of this study was to assess the performance of the isoelectric focusing/immunoblotting/laser densitometry (IEF/IB/LD) procedure to evaluate carbohydrate‐deficient transferrin (CDT) derived from dry blood spots. Serum specimens obtained from insurance applicants were analyzed for CDT by IEF/IB/LD. Dry blood spots derived from 50 serum specimens were analyzed by IEF/IB/LD. A comparative analysis of these serum specimens and the paired dry blood spots by IEF/IB/LD shows a highly significant correlation of the CDT values (r= 0.94, p < 0.0001). Stability studies indicate that, under proper storage conditions (2–3 days at room temperature, 2 weeks at 4°C, or frozen at or below –20°C indefinitely), dry blood spots can be used as a source of CDT for analysis by IEF/IB/LD, thus simplifying sampling, storage, and transportation of specimens to the testing site.
Human Immunodeficiency Virus‐Type 1 Infection in an Inner‐City Alcohol Treatment Program
Authors: Schleifer Steven J. , Keller Steven E. , LaFarge Stephanie , Dhaibar Yeshuschandra , Shiflett Samuel C. , Eckholdt Haftan M.
Published: April 2006

The human immunodeficiency virus (HIV) infection rate was examined in a selected cohort of healthy clients of an inner‐city alcohol treatment center from 1990 through 1993. These subjects were also participating in a research protocol (n= 258) designed to assess immunity and HIV risk behaviors in inner city alcohol‐dependent persons. Healthy alcohol‐abusing heterosexual clients (165) had HIV testing conducted in an inner‐city ambulatory alcohol treatment center between September 1990 and December 1993. Respondents were 93.9% African‐American and 3.6% Hispanic; 72.1 % were male. Anonymous HIV‐1 antibody testing was conducted retrospectively for an additional 80 subjects who participated in the research protocol during the same interval, but for whom HIV‐1 antibody testing was not conducted clinically at the time. HIV infection rate among the clinic‐tested subjects (n= 165) was 4.4% for individuals who were exclusively alcohol‐dependent, 1.4% for non‐injecting drug use (IDU) mixed substance abusera, and 46.8% for clients with a history of IDU. Rates did not differ among cohorts tested in different years. Among non‐injecting drug users tested in the clinic, all infected respondents (n= 3) were women (p= 0.03). Among those tested anonymously (n= 80), however, infection rate for exclusively alcohol‐dependent persons was 16.7%, non‐IDU mixed abusers 11.1%, and injecting drug users 48.3%, with seropositive males as well as females in each group. HIV infection rates for the pooled samples (n= 245) were 8.7% for exclusively alcohol‐dependent persons, 5.1% for mixed abusers, and 54.5% for injecting drug users. Among non‐injecting drug users, exclusively alcohol‐dependent women had a significantly higher (p < 0.01) infection rate (20.0%) than the remaining females and males. Infection rates among exclusively alcohol‐dependent males, male and female polysubstance non‐IDU abusers, and injecting drug users were comparable with that seen in an earlier screening in the same clinic in 1989, with apparently little diffusion of infection from the IDU population to other substance abusers. An exception seemed to be exclusively alcohol‐dependent females, who show substantially elevated rates. Age, housing, and other social differences may help segregate substance‐abusing populations in the relatively small Newark metropolitan area, although not protecting exclusively alcohol‐dependent females.
Alcohol Reactions in Subjects of European Descent: Effects on Alcohol Use and on Physical and Psychomotor Responses to Alcohol
Authors: Whitfield J. B. , Martin N. G.
Published: April 2006

Self‐reports of reactions to small amounts of alcohol, obtained between 1990 and 1992, were compared with reports of alcohol use, obtained in 1990–1992 and also in 1979–1981, in twin subjects of European descent. Data on subjective, physiological, psychomotor, and metabolic responses to a test dose of alcohol, taken in 1979–1981, were also available. Alcohol reactions were more common in women than in men, and were associated with less alcohol use, both at the time that information about reactions was obtained and as recorded on average 12 years previously, in both sexes. Physiological and psychomotor responses to alcohol were similar across the reaction groups, except that deterioration in standing steadiness was greater in those who subsequently reported adverse reactions to alcohol. Contrary to expectation, skin temperature changes after alcohol were less in the subjects who reported always reacting to alcohol than in the other groups. Subjective reports of intoxication were greatest in subjects who subsequently reported alcohol reactions. The pattern of twin pair concordance for reactions suggests low heritability, so alcohol reactions in subjects of European descent are not caused by a single gene of high penetrance of the type found in the Asian alcohol flush reaction.
Voice of the Victims
Authors: Erickson Carlton K.
Published: April 2006

Over the past 10 years, I have been privileged to conduct educational forums for audiences containing many recovering alcoholics or otherwise chemically dependent persons. In these forums about the addictive diseases, their treatment, and research possibilities, significant interaction with the audience members occurs. During these interactions, certain anecdotal phenomena seem to predominate. The repetitive nature of these reports suggests the need for systematic investigation. As with editorial comments in major medical journals, observed phenomena and unanswered questions from the victims can be valuable in the generation of testable hypotheses. Perhaps the ideas presented herein will be useful in the development of future research on alcohol abuse and alcohol dependence.
In Utero Exposure to Ethanol Alters mRNA for Insulin‐Like Growth Factors and Insulin‐Like Growth Factor‐Binding Proteins in Placenta and Lung of Fetal Rats
Authors: Fatayerji Nabil , Engelmann Gary L. , Myers Thomas , Handa Robert J.
Published: April 2006

Insulin‐like growth factors I and II (IGF‐I and IGF‐II) play a role in regulating fetal growth and development. Their actions in target tissues are modulated in part by binding to IGF binding proteins 1 and 2 (IGFBP‐1 and IGFBP‐2). In this study, we examined the effect of fetal exposure to alcohol on IGF‐I and IGF‐II and IGFBP‐1 and IGFBP‐2 mRNA in placenta and fetal lung tissue. Timed‐pregnant Sprague‐Dawley dams were fed a diet consisting of 35% ethanol‐derived calories [alcohol‐fed (AF)], an isocaloric diet with sucrose substituted for alcohol (pair‐fed; PF), or ad libitum rat chow (CF). Alcohol feeding began on gestational age (G) 14. At G20, dams were killed, and we examined placenta and fetal lung for the steady‐state levels of mRNA for IGF‐1 and IGF‐II and for IGFBP‐1 and IGFBP‐2. In all dams, body weight increased throughout gestation, and there were no differences between the three groups. At G20, the mean weight for the fetuses from the AF group was lower (p < 0.001) than the fetuses from the CF and PF groups. Steady‐state mRNA levels were detected in fetal lung and in placentas by Northern‐blot hybridization analysis and semiquantitated by slot‐blot hybridization analysis. Multiple transcripts for IGF‐I and IGF‐II, 1.8 kb species for IGFBP‐1 and 1.6 kb species for IGFBP‐2 were detected from total RNA isolated from the fetal lung and placenta. Slot‐blot hybridization analysis of fetal lung RNA showed that IGF‐I mRNA was significantly increased (p < 0.001) in AF males and females by 4.0 ± 0.28‐fold and by 3.25 ± 0.2‐fold, respectively. IGF‐II transcript levels were not affected. IGFBP‐1 and IGFBP‐2 were increased in AF males, whereas only IGFBP‐2 was increased in AF females. In the placenta, there was a significant increase in IGFBP‐1 and IGFBP‐2 transcripts [(p < 0.001) 1.75 ± 0.5‐fold and 3 ± 0.53‐fold increase, respectively]. No differences between the groups in serum levels of IGFBP‐1 or ‐2 were detected when measured by Western‐blot analysis. The increased gene expression for IGFBPs within fetal lung and placenta may decrease bioavailability of locally synthesized IGFs that may contribute to the fetal growth retardation observed in this model system.
Fetal Ethanol Exposure: Hypothalamic‐Pituitary‐Adrenal and β‐Endorphin Responses to Repeated Stress
Authors: Weinberg Joanne , Taylor Anna N. , Gianoulakis Christina
Published: April 2006

Previous studies provide evidence that fetal ethanol exposure induces hypothalamic‐pituitary‐adrenal (HPA) and pituitary β‐endorphin (β‐EP) hyperresponsiveness to acute stressors. The present study demonstrates significant effects of in utero ethanol exposure on the parallel response patterns of the HPA axis and the pituitary β‐EP system to repeated exposures to a stressor, restraint stress, and indicates sex differences in response. Together, data from the two experiments indicate that, after repeated restraint exposures, fetal ethanol‐exposed (E) males and females both show significantly increased plasma levels of adrenocorticotropin (ACTH), and E males also show significantly increased plasma levels of β‐endorphin‐like immunoreactivity (β‐EPLIR), compared with their respective pair‐fed and control counterparts. Marginal increases in the corticosterone response of E males and the β‐EPLIR response of E females, compared with their controls, were also observed. In addition, delayed or deficient habituation to restraint stress was observed in the β‐EPUR response of E males and the ACTH response of E females. These data demonstrate that fetal E‐exposed males and females both exhibit hormonal hyperresponsiveness and/or deficits in recovery after repeated exposures to restraint stress, but that the patterns of response may differ depending on the number and duration of restraint exposures, the time course measured, and whether the endpoint measured is corticosterone, ACTH, or β‐EPLIR. In addition, the finding that E and pair‐fed animals both differed from their respective controls in certain developmental and hormonal measures suggests that prenatal nutritional factors may play a role in mediating some of the changes that are observed.
Limited Ethanol Exposure Selectively Alters the Proliferation of Precursor Cells in the Cerebral Cortex
Authors: Miller Michael W.
Published: April 2006

The present in vivo study tests the hypothesis that limited (4‐day) exposure to ethanol differentially affects the proliferation of cortical precursors in the two cortical germinal zones [the ventricular zone (VZ) and the subventricular zone (SZ)] and their descendants in the mature brain. The offspring of pregnant rats fed a liquid diet containing 6.7% (v/v) ethanol when prosencephalic stem cells [gestation day (G) 6–69], VZ cells (G12–G15), and SZ cells were proliferating (G18–G21) throughout much of gestation (G6–G21). In addition, the offspring of rats pair‐fed a liquid control diet or fed chow were examined. The pregnant dams were administered with bromodeoxyuridine (BrdU) on either G15 or G21. The ratio of the number of cells that incorporated BrdU to the total number (the labeling index) was determined 1‐hr postinjection (i.e., on G15 or G21) or on postnatal day 60. Ethanol treatment between G6 and G21 reduced the ratio of cells labeled by an injection of BrdU on G15 in the fetus and in the adult, and increased the ratio of cells labeled on G21. Regardless of when the injection was placed, ethanol treatment between G6 and G9 had no effect upon the ratio of BrdU‐labeled cells in the fetus or mature cortex. Exposure from G12 to G15 decreased the number of VZ cells in the fetus and the number of immunolabeled cells in the adult cortex labeled by an injection on G15. This exposure had no effect on the incorporation by SZ cells. In contrast, ethanol exposure from G18 to G21 increased the labeling indices for fetal SZ cells and for cells in the adult, but it had no effect on the ratio of labeled VZ cells. Although ethanol had no apparent effect on the proliferation of stem cells, it did alter the proliferation of cells in the VZ and SZ. These effects are time‐dependent and underlie the ethanol‐induced changes in the number of cells in the adult.
Effect of Chronic Ethanol Consumption on the Activities of Residual Small Bowel Brush‐Border Enzymes after Proximal Jejunum Resection in the Rat
Authors: Zucoloto Sergio , Braulio Valeria B. , Santos Gilda C. , Ramalho Fernando S. , Scandar Maria Paula M. , de Freitas Osvaldo , de Oliveira José Alberto Mello
Published: April 2006

Ethanol consumption has a toxic effect on the epithelium of the small bowel, but enterocyte maturity is very difficult to measure under these circumstances. However, when ethanol intake is combined with enterectomy, enterocyte immaturity is greater, permitting an easier separation of these two effects. In a group of rats (13 male Wistar rats weighing ∼220 g) fed a liquid diet containing 35% ethanol for 4 weeks after resection of the proximal jejunum, the residual small intestine brush border maltase, sucrase, and lactase activities were similar to those of a pair‐fed control group (13 animals). However, alkaline phosphatase activity was decreased in the mucosa and in the enterocyte brush border, probably because of the lower activity of this enzyme in the jejunum‐ileum remnant of the alcoholic group.
Ethanol at Pharmacologically Relevant Concentrations Inhibits Contractility of Isolated Smooth Muscle Cells of Cat Esophagus
Authors: Keshavarzian All , Muska Brian , Sundaresan Ramamoorthy , Urban Glenn , Fields Jeremy
Published: April 2006

Acute ethanol, in both man and cats, decreases contractility of both lower esophageal sphincter (LES) and smooth muscle portion of the lower esophageal (LE) body. Because these inhibitory effects were not abolished, in cats, by cervical vagotomy or intravenous tetrodotoxin, we surmised a direct inhibitory effect of ethanol on muscle cells. Accordingly, to test this possibility, we exposed isolated, esophageal smooth muscle cells (LES and LE) to ethanol (0–150 mM) for 0 to 40 min, and then a contractile agent, carbachol, or its vehicle was added. Thirty seconds later, cells were fixed and cell shortening was measured as an index of contractility. In the absence of ethanol, carbachol dose‐dependently induced shortening of muscle cells from both LE and LES. Ethanol significantly attenuated carbachol‐induced maximal shortening of cells from both LE and LES. Potency for carbachol in LES (but not LE) was also decreased by ethanol. Isolated muscle cells remained viable after incubation with ethanol. Thus inhibition by ethanol: can occur directly on esophageal muscle; occurs at pharmacologically relevant ethanol concentrations; and is not simply caused by cytotoxicity of ethanol.