bluuebunny/crossref_metadata_2025 huggingface dataset:
Alterations in Cortical Visual Evoked Response following Ethanol Feeding in Adult Rats
Authors: Kjellström C. , Rydenhag B. , Sjöström A. , Conradi N. G.
Published: April 2006

A study was performed on the visual‐evoked response (VER) in adult rats that were given an ethanol containing liquid diet for 2 months and examined directly after the exposure period or subjected to a gradual decrease in ethanol over 3 days and total abstinence for 1 week. Control rats showed a first negative peak (N1) directly following the first positive peak (P1). In ethanol‐exposed rats examined without withdrawal, the VER showed an increase in onset latency and a marked distorsion of the N1 region. The existing N1 potential was very sensitive to high‐frequency stimulation. The alterations were partly normalized 1 week after withdrawal. There was no increase in latency to onset of the response or to P1. There remained an increase of latency and a reduced relative amplitude upon high‐frequency stimulation of the N1 peak in ethanol‐exposed rats compared with controls. The mechanisms underlying the changes in the cortical potentials are not clear, but they may be related to the cholinergic, glutamatergic/NMDA and/or noradrenergic cortical systems. The lack of persistent changes in onset and P1 latency may be related to the circumstance that the retinogeniculate impulses are transmitted over glutamatergic kainate receptors, which are relatively resistant to ethanol.
Operant Ethanol‐Reinforced Behavior in P, NP, HAD, and LAD Rats Bred for High Versus Low Ethanol Preference
Authors: Ritz Mary C. , Garcia Joan M. , Protz David , George Frank R.
Published: April 2006

These studies examined the reinforcing effects of ethanol in rats selectively bred for high versus low ethanol drinking in a two‐bottle choice preference task, namely the Preferring (P), Non‐Preferring (NP), High Alcohol Drinking (HAD), and Low Alcohol Drinking (LAD) rats. The results substantiate findings suggesting that genetic factors are significant in determining whether ethanol will come to serve as a reinforcer. P rats exhibited high levels of responding for ethanol compared with the water vehicle, NP and HAD rats exhibited more moderate levels of responding for ethanol, and the behavior of LAD rats suggested that ethanol served only inconsistently as a reinforcer for these rats. Overall, the results suggest the existence of distinct, biologically influenced components of ethanol drinking behavior. Preference appears to measure an inherent facilitative factor allowing animals to initiate ethanol drinking. The operant chamber paradigm appears to measure factors related to whether and to what extent ethanol will serve as a positive reinforcer following conditioned exposure to the drug. Although preferring animals generally find ethanol reinforcing there seems to be little quantitative relationship between degree of preference and whether ethanol will serve as a reinforcer. Lack of preference does not seem to be predictive of lack of reinforcement. Thus, it appears that preference for ethanol and reinforcement from ethanol are somewhat overlapping, but distinct factors that contribute to ethanol drinking. These results suggest the existence of multiple components of behavior mediated by multiple mechanisms that contribute to ethanol drinking.
Sepsis Protects the Heart of Alcoholic Rats from Ischemia‐Reperfusion Injury
Authors: McDonough Kathleen H. , Causey Karen M.
Published: April 2006

We have previously shown that administration of Escherichia coli to a rat induces cardiac dysfunction, but also prevents the myocardium from being further damaged by total ischemia. We have also previously shown that induction of sepsis in a rat that has consumed alcohol as 36% of its caloric intake for 8–10 weeks, results in a potentiation of the cardiac depression resulting from sepsis. In this study, we determined if administration of Gram‐negative bacteria to a chronically alcoholic rat would still protect the heart from ischemia‐reperfusion injury. We tested the protective effect of sepsis using an in vitro, isovolumically contracting heart preparation. Global ischemia was maintained for 35 min, followed by 25‐min reperfusion. In the present experiments, sepsis produced a 40% decrease in cardiac performance, but was also protective of hearts made ischemic the next day. Hearts from septic and alcoholic septic rats recovered 100% of preischemic ventricular function after 35‐min ischemia, whereas hearts from the control and alcohol groups recovered only 80% of preischemic left ventricular performance. Whereas preischemic function was significantly decreased in the septic groups compared with the two nonseptic groups, postishemic function was no longer significantly different in the four groups. Thus, sepsis resulted in development of protection of the hearts from ischemia‐reperfusion injury, even in hearts that were severely compromised by the combination of chronic alcoholism and Gram‐negative sepsis.
Effect of Acute Ethanol Exposure on Cultured Fetal Rat Hepatocytes: Relation to Mitochondrial Function
Authors: Devi B. G. , Henderson G. I. , Frosto T. A. , Schenker S.
Published: April 2006

Studies from our laboratory have shown that short‐term ethanol exposure inhibits epidermal growth factor‐dependent replication of cultured fetal rat hepatocytes, along with a drop in ATP level, and that these effects could be caused, at least in part, by ethanol‐induced oxidative stress. In these prior studies, mitochondrial morphology was abnormal and membrane lipid peroxidation products were increased, along with reduced transmembrane potential and enhanced permeability to sucrose. To define the effects of ethanol on mitochondrial function further, the present study examines the impact of ethanol exposure on mitochondrial electron transport chain components. A 24‐hr exposure of cultured fetal rat hepatocytes to ethanol (2.5 mg/ml) reduced mitochondrial complex I activity by 16% (p < 0.05), complex IV by 28% (p < 0.05), and succinate dehydrogenase by 23% (p < 0.05). This reduction was paralleled by lower ADP translocase activity (24%, p < 0.05) and diminished mitochondrial glutathione (GSH) (20%, p < 0.05). Pretreatment with 0.1mm S‐adenosyl methionine, before ethanol exposure, normalized mitochondrial GSH along with activities of complex I, complex IV, and succinate dehydrogenase. A 3‐hr exposure of isolated mitochondria (which do not metabolize ethanol) to ethanol (2.5 mg/ml), inhibited the activities of complex I (19%, p < 0.05), complex IV (24%, p < 0.05), and of ATP synthesis (20%, p < 0.05). It is concluded that: (1) short‐term ethanol exposure modestly decreases ATP synthesis by inhibiting activities of fetal hepatic mitochondrial electron transport chain components; (2) ethanol, in the absence of acetaldehyde (as in the isolated mitochondria), can directly impair mitochondrial respiratory chain components; and (3) protection from some of the adverse effects of ethanol by pretreatment with S‐adenosyl methionine suggests that these effects are secondary to depletion of mitochondrial GSH.
Macrophages Are a Major Source of Acetaldehyde in Circulating Acetaldehyde‐Albumin Complexes Formed after Exposure of Mice to Ethanol
Authors: Wickramasinghe S. N. , Mawas F. , Hasan R. , Brown I. N. , Goldin R. D.
Published: April 2006

C57BL mice were depleted of macrophages by an intravenous injection of liposome‐encapsulated dichloromethylene diphosphonate (DCMDP), and control mice were uninjected or injected with empty liposomes. One day after injection, a proportion of the DCMDP‐treated and control mice was continuously exposed to ethanol vapor for 4 days. Albumin fractions were separated from the sera of both ethanol‐unexposed and ethanol‐exposed animals and tested for cytotoxicity against a monolayer of A9 cells using two indicators of cytotoxicity: detachment of adherent cells and a decrease in the ability of cells to reduce tetrazolium. The results show that, in mice exposed to ethanol, macrophages are a major source of the acetaldehyde in circulating cytotoxic acetaldehyde‐albumin complexes and presumably also of free acetaldehyde.
Ethanol Sensitivity of Brain NMDA Receptors in Mice Selectively Bred for Differences in Response to the Low‐Dose Locomotor Stimulant Effects of Ethanol
Authors: Daniell Laura C. , Phillips Tamara J.
Published: April 2006

Brain NMDA receptor responses and their sensitivity to ethanol in vitro were determined in replicate lines of FAST and SLOW mice, selectively bred for differences in sensitivity to the locomotor stimulant effects of a low dose of ethanol. L‐Glutamate‐stimulated increases in the intracellular free calcium concentration (Ca1) were determined in microsacs, a cell‐free brain membrane preparation, isolated from hippocampus or cerebral cortex. Previous work showed that l‐glutamate‐stimulated increases in Ca1 in microsacs are mediated by activation of NMDA receptors. The concentration response for l‐glutamate‐stimulated increases in Ca, did not differ between the lines in either hippocampal or cerebrocortical microsacs. Ethanol produced a concentration‐dependent decrease in l‐ glutamate‐stimulated increase in Ca1 in hippocampal and cerebrocortical microsacs from SLOW mice, but this effect of ethanol was reduced or absent in microsacs isolated from FAST mice. Resting Ca1 and the ability of a high ethanol concentration to increase resting Ca1 did not differ between the lines. These results suggest that differences in the sensitivity of brain NMDA receptors to the effects of ethanol determine, at least in part, differences in the locomotor stimulant effects of low doses of ethanol in FAST and SLOW mice. These differences are not due to ethanol effects on resting Ca1.
Differences in Ethanol Sensitivity of Brain NMDA Receptors of Long‐Sleep and Short‐Sleep Mice
Authors: Daniell Laura C. , Phillips Tamara J.
Published: April 2006

Long‐Sleep (LS) and Short‐Sleep (SS) mice, selectively bred mice that differ in the duration of anesthesia produced by an acute dose of ethanol, were used to determine the possible association of differing ethanol sensitivity of brain NMDA receptors with differing sensitivity to the anesthetic effects of ethanol in vivo. NMDA receptor‐mediated responses were determined by measurement of l‐glutamate‐stimulated increases in free intracellular calcium concentration (Cal) using the fluorescent indicator for Ca1, Indo 1, in microsacs (a cell‐free brain membrane vesicle preparation) isolated from hippocampi or cerebral cortices of the two mouse lines. In the absence of added drugs, NMDA responses did not differ between the two lines in hippocampal or cerebrocortical microsacs. However, a high concentration of ethanol (200 mm) inhibited NMDA responses in hippocampal microsacs from LS mice. In contrast, a moderate concentration of ethanol (50 mm) stimulated NMDA responses in hippocampal microsacs isolated from SS mice. In cerebrocortical microsacs, ethanol inhibited NMDA responses in the two lines to an equivalent degree. MK‐801, a noncompetitive blocker of NMDA receptors, blocked NMDA responses at lower concentrations in hippocampal microsacs from LS mice than in SS mice, but produced a similar degree of inhibition of NMDA responses in cerebrocortical microsacs from the two lines. A high concentration of ethanol (200 mm) increased resting Ca1 in hippocampal microsacs from LS mice but not in hippocampal microsacs from SS mice, and increased resting Cal in cerebrocortical microsacs isolated from both lines of mice equally. The small change in resting Ca, produced by MK‐801 in cerebrocortical microsacs did not differ between the two lines. These results show that hippocampal NMDA receptors of LS and SS mice differ in their sensitivity to ethanol, possibly because of differences in allosteric modulation at the MK‐801 site or some other site that interacts with the MK‐801 site of the NMDA receptor.
Dose‐Response Relationships in Hepatic Injury Produced by Alcohol and Carbon Tetrachloride
Authors: Plummer John L. , de la M. Hall Pauline , IIsley Anthony H. , Cmielewski Patricia L. , Ahern Michael J. , Williams Richard A.
Published: April 2006

Dose‐response relationships were examined for the production of hepatic fibrosis and cirrhosis by combined exposure of male Porton rats to alcohol and carbon tetrachloride. Alcohol was administered orally in Lieber‐DeCarli liquid diet at levels of 75, 150, or 300 kcal/ liter, giving mean daily intakes of 2.29, 4.61, and 8.16 g/kg/day, respectively. Carbon tetrachloride was administered by inhalation at concentrations of 10, 20, or 40 ppm, 6 hr/night, 5 nights/week. Liver biopsies were taken at intervals up to a maximum treatment period of 20 weeks. All four rats that received the high dose of both agents, and 1 of 4 that received the medium alcohol and high carbon tetrachloride treatments, were cirrhotic by 10 weeks. Two of the 4 rats that received the low alcohol and high carbon tetrachloride dose were cirrhotic at 20 weeks. Cirrhosis was not observed in rats that received the low or medium carbon tetrachloride dose, but some degree of hepatic fibrosis was observed in all treatment groups. Severity of fibrosis was significantly associated with both dose of alcohol and dose of carbon tetrachloride received. It is concluded that, in the alcohol‐carbon tetrachloride rat model for chronic liver injury, both alcohol and carbon tetrachloride contribute to the response in a dose‐related manner. Hepatic injury was observed even when relatively low doses of these agents are administered together.
Use of Transgenics, Null Mutants, and Antisense Approaches to Study Ethanol's Actions
Authors: Wehner Jeanne M. , Bowers Barbara J.
Published: April 2006

Behavioral and biochemical responses mediating ethanol's actions have been difficult to study in humans and animals because of their complex polygenic nature. Recent progress in the creation of new animal models using recombinant DNA technology has provided a set of genetic tools by which the role of specific candidate genes in ethanol's actions can be examined. These techniques include the creation of transgenic and null mutant mice, as well as manipulation of protein synthesis with antisense treatments. These techniques are reviewed, and their potential applications to alcohol research are discussed.
A Strategy for the Identification of Candidate Genes for Alcohol‐Related Phenotypes and Other Human Disorders Using Rapid Polymerase Chain Reaction Mapping of Gene‐Based Sequence‐Tagged Sites
Authors: Berry Rebecca , Walter Nicole A. R. , Stevens T. J. , Rubano Todd , Wilcox Andrea S. , Hopkins Janet A. , Sikela James M.
Published: April 2006

We describe a method for the rapid identification and mapping of human genes, including those possibly contributing to disease and alcohol‐related phenotypes. New human genes are identified from cDNA libraries through single‐pass sequencing into the 3′ untranslated (3′UT) regions of human brain cDNAs. Primers derived from the 3′UT region sequences [representing gene‐based, sequence‐tagged sites (STSs)] are used for polymerase chain reaction (PCR) analyses of the CEPH megabase insert yeast artificial chromosome (YAC) DNA pools. With this approach, ∼18,000 megabase YACs can be screened and a single YAC identified using only 52 PCR reactions. The YAC localization in conjunction with other mapping techniques, such as PCR mapping to human chromosomes using somatic cell hybrids, allows identification of chromosomal band locations. In this manner, each gene can be associated with its own STS, which in turn specifies both a corresponding genomic clone and specific location in the genome. These locations can be compared with the purported locations of disease genes. The locations of the STSs can also be compared with those of Quantitative Trait Loci implicated for quantitative traits (e.g., alcohol‐related phenotypes) on the basis of synteny between the mouse and human genes. Using this strategy, we found candidates for 78 human disease/syndrome genes among the first 220 genes mapped.
Rabbit Liver Class III Alcohol Dehydrogenase: A Cathodic Isoform with Formaldehyde Dehydrogenase Activity
Authors: Keung Wing‐Ming , Kunze Lisa , Holmquist Barton
Published: April 2006

Electrophoresis of rabbit liver homogenate on starch gel followed by activity staining revealed multiple forms of alcohol dehydrogenase (ADH) which, based on their electrophoretic mobilities, had been tentatively labeled as class “I,” class “II,” and dass “III” ADHs. The class II enzyme has now been purified to homogeneity by ion exchange and affinity chromatography and, except for an isoelectric point of 7.7, close: resembles human class III ADH. It is a homodimer of molecular weight near 80,000 with a similar amino acid composition and comparable kinetic parameter for the oxidation of primary alcohols. Like the rat, human, and Escherichia coli class III ADHs, the rabbit enzyme is a glutathione‐dependent formaldehyde dehydrogenase, and catalyzes the oxidation of S‐hydroxymethylglutathione and the hemithiolacetal of 8‐thiooctenolc acid. Ethanol up to 3 M does not saturate the enzyme, whereas longer chain primary alcohols exhibit Michaelis‐Menten kinetics. Key Words: XX‐ADH, FDH.
Acute Ethanol Impairs Spatial Memory But Not Stimulus/Response Memory in the Rat
Authors: Matthews Douglas B. , Simson Peter E. , Best Phillip J.
Published: April 2006

The present studies investigate how acutely administered ethanol (ETOH) affects the use of spatial memory. Previous electrophysiological results have shown that acutely administered ETOH alters the firing of hippocampal neurons and that prenatal or chronic exposure to ETOH produces deficits on spatial learning tasks, tasks dependent on the hippocampus. In contrast, it has also been demonstrated that acutely administered ETOH does not impair spatial localization. In the current studies, rats were trained to perform a spatial or stimulus/response task under saline. After training, rats were injected with ETOH, and the use of spatial or stimulus/response memory was tested. Acutely administered ETOH impaired the use of spatial memory, but not the use of stimulushesponse memory. Because the use of spatial memory requires an intact hippocampus, the present studies suggest that acutely administered ETOH selectively impairs behaviors dependent on the hippocampus.
Validated Fluorimetric HPLC Analysis of Acetaldehyde in Hemoglobin Fractions Separated by Cation Exchange Chromatography: Three New Peaks Associated with Acetaldehyde
Authors: Chen Hui‐Min , Scott B. Keyes , Braun Karen P. , Peterson Charles M.
Published: April 2006

Stable hemoglobin‐acetaldehyde adducts present in hemoglobin fractions separated by polyaspartic acid cation exchange chromatography were quantified by fluorimetric HPLC. The fluorescent species eluted from the HPLC was confirmed by mass spectrometry to be consistent with the expected product from reaction of acetaldehyde, 1,3‐cyclohexanedione (CHD), and ammonium ion. Hemolysate (2.2 mM hemoglobin) was incubated in equivalent volumes of either phosphate‐buffered saline or 5 mM acetaldehyde at 37°C for 30 min and washed three times with H2O to remove free acetaldehyde and labile adducts before the injection of 14.7 mg hemoglobin onto the cation exchange column. Fluorimetric HPLC analysis of hemolysate samples either with or without in vitro reaction with acetaldehyde revealed that most acetaldehyde resides in the hemoglobin Ao fraction. The reaction with acetaldehyde in vitro resulted in a significant increase in fast‐eluting minor hemoglobin species on cation exchange chromatography concomitant with increased acetaldehyde in the HbA1a+b HbA1c and HbA1‐Acn fractions. We report three new cation exchange Chromatographic peaks after reaction with acetaldehyde: HbA1‐ACH‐3, HbA1c‐1, and HbA1c‐1. Each new peak was found to associate with a significant quantity of CHD‐reactive acetaldehyde. These experiments provide additional evidence that stable adducts form between acetaldehyde and hemoglobin and that these adducts occur in multiple hemoglobin species separated by cation exchange chromatography. Further characterization and structural assignment of these species are warranted in view of their potential utility as markers for ethanol intake.
Group Similarities in Beliefs Concerning the Causes of Alcohol Problems and the Effectiveness of Means of Overcoming Problem Alcohol Use
Authors: Peralta Christine D. , Danko George P. , Johnson Ronald C.
Published: April 2006

Four hundred and eight respondents, who did or did not know persons close to themselves with alcohol problems, from four different racial/ethnic groups (with one group, Filipinos, categorized in terms of whether they were born in the Philippines or in the US.) rated the importance of 19 different causes of problem alcohol use and 22 different means of overcoming problem alcohol use. Rank‐order correlations across sexes, persons differing in exposure to problem drinkers, and ethnic groups were nearly all in the 0.90's regarding causation. Correlations of Caucasians' ratings with those of other groups were high, but only in the 0.60's and 0.70′9, chiefly because Caucasians were more prone to regard problem alcohol use as hereditary and as a disease, and less likely to believe problem use to result from social factors. All across‐group correlations concerning beliefs about the effectiveness of means of overcoming problems were in the 0.90's. Some of the means of treatment regarded most highly by all groups have not been demonstrated to be effective.
Comparison of Direct Interview and Family History Diagnoses of Alcohol Dependence
Authors: Rice John P. , Reich Theodore , Bucholz Kathleen K. , Neuman Rosalind J. , Fishman Roberta , Rochberg Nanette , Hesselbrock Victor M. , Nurnberger John I. , Schuckit Marc A. , Begleiter Henri
Published: April 2006

Using data from The Collaborative Study on the Genetics of Alcoholism, we compare direct interview diagnoses of alcohol dependence to those obtained by history from family members. Using a requirement of three or more positive implications by history, the specificity, sensitivity, and positive predictive values are 98%, 39%, and 45%, respectively.

A logistic analysis found the gender of the relative and alcoholism in the informant to be significant, but not the gender of the informant. The partial odds ratio of a diagnosis at interview associated with a positive family history diagnosis was 13.6. The relationship between the informant and relative was significant, with negative reports from an offspring or mate more influential than a negative report from a parent or second‐degree relative.

We derived a recursive equation to combine a variable number of family history reports, wherein the probabilities associated with a single report are computed from the logistic analysis. This permits the use of family history information both as a proxy for an uninterviewed relative, as well as a second source of information to be used in the analysis of genetic family data.
Alcohol and Other Drug Use Among Hispanics in New York State
Authors: Welte John W. , Barnes Grace M.
Published: April 2006

Surveys have generally shown that Hispanics in the United States have lower than the national average rates of drinking, along with average rates of heavy drinking and drug use. Acculturation has been shown to be related to drinking and drug use. This study reports results from a large general population telephone survey conducted in New York State. Hispanic New York State residents were lower than the national average in drinking and heavy drinking when demographic variables were held constant. Gender differences in substance use were greater for Hispanics than for non‐Hispanics, with males higher than females. Among Hispanic groups, Puerto Ricans were high and Dominicans were low in drug use. Among Hispanics, more frequent use of English was associated with higher drinking and drug use rates. Traditional Hispanic attitudes and closeness to country or origin were not related to substance use.
Spatial Learning Deficits in Preschool Children of Alcoholics
Authors: Schandler Steven L. , Thomas Connie S. , Cohen Michael J.
Published: April 2006

When compared with nonalcoholics, chronic alcoholics and their children show significant deficits in the processing of visuospatial information. The literature supports two possible explanations of a visuospatial processing deficit in the child of an alcoholic (COA) when compared with the child of a nonalcoholic (NCOA). Ether the COA may suffer cognitive disruptions produced by personal and social development within an alcoholic family, or the COA may inherit or very early develop alterations in central nervous system substrates of neurocognitive operations. The present study was designed to continue our examinations of visuospatial information processing differences and the source of these differences in COAs. An evaluation of very young subjects not only assisted in providing a more complete view of visuospatial processing across the COA's life span, but also helped explain why the deficit occurs. Thirty matched male and female preschool children, aged 35.8–51.6 months, served as participants. Fifteen children were COAs from families in which the biological father and two other relatives had an alcoholism history. The other group of 15 children were NCOAs. Each child performed a visuospatial learning task similar to the task used in previous studies of older COAs. The visuospatial learning performance of the preschool COAs was inferior to that displayed by preschool NCOAs. The patterns of correct, error, and nonresponses emitted by the preschool COAs and the interrelationships of these data closely resembled the data from our previous studies of older children, adolescent, and adult COAs. The consistency of the deficit and its underlying processes in COAs sampled across the life span from different family environments support a model of visuospatial deficit that is more neurocognitive inheritance than personal/developmental.
Prenatal Ethanol Consumption Alters the Expression of Cellular Retinol Binding Protein and Retinoic Acid Receptor mRNA in Fetal Rat Embryo and Brain
Authors: Grummer Mary A. , Zachman Richard D.
Published: April 2006

The mechanism by which prenatal ethanol ingestion causes fetal alcohol syndrome (FAS) is unknown. We hypothesize that ethanol disrupts the normal function of retinoids in embryogenesis and differentiation, resulting in FAS. The present work was designed to determine if prenatal ethanol ingestion affects the expression of cellular retinol binding protein (CRBP) and nuclear retinoic acid receptors (RARs). Paired timed pregnant rats were fed a liquid diet, one group treated with 36% of carbohydrate calories replaced with ethanol. Maternal serum retinol concentrations during pregnancy peaked on the 6th day of pregnancy, but no difference was noted between the ethanol and control group. At the 12th and 20th day of gestation, embryos or fetal brain were removed, and RNA was isolated for Northern hybridization. The abundance of CRBP mRNA was significantly elevated by ethanol consumption in both the 12‐day embryo (relative density of control: 1.00 ± 0.10; vs. ethanol: 1.87 ± 0.30, p < 0.05) and 20‐day fetal brain (relative density of control: 1.00 ± 0.09; vs. ethanol: 1.46 ± 0.09, p < 0.01). In the embryo, ethanol ingestion resulted in a decrease in the level of RAR‐β mRNA (control: 1.00 ± 0.05; vs. ethanol: 0.71 ± 0.07, p < 0.01), but had no effect on RAR‐α or RAR‐γ mRNA. In contrast to the embryo, the expression of both the 3.7‐ and 2.7‐kb RAR‐α transcripts was significantly greater in day 20 fetal brain of ethanol‐treated rats (3.7‐kb RAR‐α control: 1.00 ± 0.11; vs. ethanol: 1.65 ± 0.06;p < 0.001;2.7‐kb RAR‐α control: 1.00 ± 0.14; vs. ethanol: 1.74 ± 0.27, p < 0.05), whereas RAR‐β and RAR‐γ expression were not altered. These observations suggest that altered vitamin A function is a potential factor in the embryopathy of prenatal ethanol exposure.
Effects of Ethanol on Glucose Transporter Expression in Cultured Hippocampal Neurons
Authors: Hu Iris C. , Singh Sant P. , Snyder Ann K.
Published: April 2006

Glucose transport was studied in primary hippocampal neuron cultures exposed to ethanol. Immunofluorescent staining with antibodies against neuron‐specific enolase and glial fibrillary acidic protein identified ∼95% of the cultured cells as neurons. Western blot analysis was conducted with polyclonal antisera to glucose transporter isoforms GLUT1 and GLUT3. As previously seen in astrocytes, GLUT1 protein was regulated by the culture medium glucose content. Exposure to 50 and 100 mM of ethanol for 5 hr induced dose‐dependent reductions in GLUT1 and GLUT3 protein. In contrast, GLUT1 mRNA abundance was increased relative to controls under the same conditions. Glucose uptake, measured with the nonmetabolized analog, 2‐deoxy‐d‐glucose, was reduced by 50 and 100 mM of ethanol in four experiments. These results indicate a direct effect of ethanol on neuronal glucose transporter expression, which may play a role in the neurotoxic effects of alcohol.
Hormonal and Chemical Influences on the Expression of Class 2 Aldehyde Dehydrogenases in Rat H4IIEC3 and Human HuH7 Hepatoma Cells
Authors: Crabb David W. , Stewart Mark J. , Xiao Qing
Published: April 2006

We studied the effect a variety of hormones and chemical stimuli on the activity of low Km aldehyde dehydrogenase (ALDH) in rat H4IIEC3 hepatoma cells and ALDH activity in human HuH7 hepatoma cells. The low Km enzyme in H4IIEC3 cells reflects ALDH2 activity, and the ALDH activity in HuH7 likely represents ALDH5. Of the steroid hormone family, thyroid hormone, progesterone, and dihydrotestosterone increased low Km ALDH activity ∼50%, whereas dexamethasone and estradiol had little effect. Insulin decreased the activity of low Km ALDH. None of these hormones affected the activity of ALDH in HuH7 cells. Among second messengers, 8‐bromo‐cAMP and A23187 increased low Km ALDH activity; HuH7 ALDH activity again was unchanged. Exposure of the cells to 22 mM ethanol reduced low Km activity by ∼20%, whereas hydrogen peroxide, tumor necrosis factor‐α, and interleukin‐β had little effect. Ultraviolet light increased the HuH7 ALDH activity. Retinaldehyde or retinoic acid reduced the HuH7 ALDH activity, but had no effect on low Km ALDH activity. These data suggest that low Km ALDH2 can be regulated by hormones and may not be constitutive as previously thought, and that the HuH7 ALDH is regulated differently.
Mutations Affecting Sensitivity to Ethanol in the Nematode, Caenorhabditis elegans
Authors: Morgan Phil G. , Sedensky Margaret M.
Published: April 2006

Mutations in nine genes have been identified in the nematode, Caenorhabditis elegans, which control sensitivity to ethanol. The interaction of these genes has been examined and used to determine a genetic pathway controlling sensitivity to ethanol. The nature of this pathway indicates that ethanol exerts its anesthetic actions at more than one site of action. These results also indicate that ethanol is similar in its effects to the volatile anesthetics, enflurane and isoflurane.
Influence of an n‐6 Polyunsaturated Fatty Acid‐Enriched Diet on the Development of Tolerance during Chronic Ethanol Administration in Rats
Authors: Meehan E. , Beaugé F. , Choquart D. , Leonard B. E.
Published: April 2006

This study investigates the effects of n‐6 polyunsaturated fatty acids (PUFAs), in the form of dietary Evening Primrose Oil (EPO) and safflower oil, on the development of tolerance to ethanol. The degree of fluorescence polarization of the fluoroprobes DPH, PROP‐DPH, and TMA‐DPH in isolated cortical synaptosomal membranes was measured. In addition, the development of tolerance, as shown by changes in synaptosomal membrane fluidity after an acute in vitro ethanol challenge, was also determined after 20 weeks of ethanol administration, either alone or together with a PUFA‐enriched diet. Although the administration of EPO‐enriched diet did not significantly render the inner core of the cortical synaptosomal membrane tolerant to the acute ethanol challenge, concomitant administration of ethanol and EPO was found to increase further the rigidity and tolerance to the acute ethanol challenge in the inner core. Chronic administration of safflower oil, which lacks γ‐linolenic acid (18:3, n‐6) but like EPO contains linoleic acid, either alone or together with chronic ethanol had no effect on synaptosomal membrane fluidity after an acute ethanol challenge. The results suggest that γ‐linolenic acid or its metabolites may have an important role to play in the development of tolerance to chronic ethanol.
Dose‐Dependent Effects of Acute In Vivo Ethanol Exposure on Extracellular Glutamate Concentration in the Cerebral Cortex of the Near‐Term Fetal Sheep
Authors: Reynolds James D. , Penning Donald H. , Dexter Franklin , Atkins Barry , Hrdy Jim , Poduska Dan , Chestnut David H. , Brien James F.
Published: April 2006

The cerebral cortex is a target site of ethanol teratogenesis. l‐Glutamate is a major excitatory neurotransmitter that plays an important neurotrophic role in brain development. It has been proposed that optimal function of the glutamate neuronal system is required for normal brain development; overactivation could lead to excitotoxic‐induced neuronal injury, whereas underactivation could delay/restrict brain development. The objective of this study was to test the hypothesis that acute in vivo ethanol exposure alters basal glutamate release in the fetal cerebral cortex. The experimental approach involved measuring fetal cortical extracellular glutamate concentration using the technique of in vivo microdialysis. Near‐term fetal sheep were chronically instrumented with a microdialysis probe placed in the parasagittal cortex. At 124 ± 3 days of gestation, the effects of maternal intravenous infusion of 2 g or 4 g ethanol/kg maternal body weight or an equivalent volume of saline, given as four equally divided doses over 5 hr, on fetal cerebral cortical extracellular glutamate concentration were determined. None of the three treatment regimens produced fetal or maternal demise during the time course of the study. There was an ethanol dose‐dependent increase, p= 0.005, in extracellular glutamate concentration in the fetal cerebral cortex. This increase was paroxysmal in nature and was not directly related to the fetal blood ethanol concentration. In view of the proposed role for glutamate in neuronal development, this apparent ethanol‐induced increase in glutamate release may be important in the pathogenesis of ethanol teratogenesis involving the cerebral cortex.
Stage‐Dependent Effects of Ethanol on Cranial Neural Crest Cell Development: Partial Basis for the Phenotypic Variations Observed in Fetal Alcohol Syndrome
Authors: Cartwright Martina M. , Smith Susan M.
Published: April 2006

Fetal alcohol syndrome (FAS) is characterized by growth retardation, mental deficiencies, and numerous craniofacial and neuronal anomalies; the type and severity of these defects may be related to the time and dose of maternal ethanol exposure. Ethanol administered during presomitic stages results in the typical FAS craniofacial phenotype and is accompanied by a loss of cranial neural crest cells (CNCCs) through ethanol‐induced cell death. However, the stage‐specific effects of ethanol on the CNCC population is unknown. We examined the effects of ethanol on CNCC populations by treating in ovo chick embryos with a single ethanol dose (0.43 mmol/egg) at various stages of CNCC development, and corresponding to the first 3–4 weeks of human gestation. Ethanol treatment induced cell death and reduced CNCC populations in patterns consistent with observed dysmorphologies of CNCC‐derived cranial structures. The precise population affected was dependent on the timing of ethanol exposure. Treatment at gastrulation or neurulation induced cell death and losses of CNCC populations, particularly those in rostral positions, and resulted in more severe craniofacial defects. In contrast, treatment at early somitic stages (4–16 somites) induced cell death, primarily within caudal CNCC populations, but resulted in less severe craniofacial defects, suggesting an increased capacity for recovery. These results suggest that there are distinct developmental windows during which the CNCCs may be particularly susceptible to ethanol‐induced cell death. We conclude that ethanol exposure seems to affect specific events adversely during neural crest development. The timing of embryonic ethanol exposure relative to CNCC development could account, in part, for the heterogenous craniofacial defects observed in FAS.
GABAergic Transmission in the Nucleus Accumbens Is Involved in the Termination of Ethanol Self‐Administration in Rats
Authors: Hodge Clyde W. , Chappelle Ann M. , Samson Herman H.
Published: April 2006

Long‐Evans rats (n= 12) were trained to lever‐press on a fixed‐ratio 4 schedule of reinforcement with ethanol (10% v/v) presented as the reinforcer. After implantation of bilateral stainless‐steel guide cannulae aimed at the nucleus accumbens, site‐specific microinjections of muscimol (1–30 ng) and bicuculline (1–10 ng) were tested for effects on ethanol‐reinforced responding. Baseline response patterns were characterized by initial high rates that terminated abruptly after ∼20 min. Muscimol administration in the nucleus accumbens decreased the total number of ethanol‐reinforced responses and obtained reinforcers. Bicuculline also decreased ethanol‐reinforced responses and reinforcers at the highest dose tested. When a dose of bicuculline (1 ng) that was ineffective by itself was coadministered with an effective dose of muscimol (10 ng), the muscimol‐induced decreases in responding were blocked. Analysis of response patterns showed that muscimol decreased ethanol self‐administration by terminating responding, normally lasting 20 min, after ∼10 min with no changes in local response rate. Bicuculline decreased total responding by producing parallel, but nonsignificant, changes in time course and response rate. These data suggest that GABAergic transmission in the nucleus accumbens is involved in the termination, but not the onset or maintenance of ethanol self‐administration. The specificity of this effect gives emphasis to the importance of measuring behavioral parameters, as well as products of behavior (such as intake volume) in the study of ethanol self‐administration.
Contrasting Self‐Report Screens for Alcohol Problems: A Review
Authors: Maisto Stephen A. , Connors Gerard J. , Allen John P.
Published: April 2006

Current trends in conceptions of alcohol problems and provision of health care put increased emphasis on identifying individuals whose alcohol use and problems cover a range of severity. The purpose of this study is to begin to provide information on the relative utility of self‐report measures designed to identify (screen for) individuals with alcohol problems. To achieve this goal, the empirical literature on contrasts of self‐report screening measures was reviewed, and 13 relevant studies across diverse settings and subject populations were identified. The review showed that the CAGE, the Michigan Alcoholism Screening Test (MAST), and the short MAST (sMAST) have been the most widely studied self‐report instruments to screen for alcohol problems. Direct comparisons show the MAST to be more sensitive than the CAGE, but with elderly patients the CAGE may perform better than the MAST. Furthermore, available data suggest that the CAGE and the sMAST perform comparably. Finally, the CAGE, MAST, and sMAST all perform best when predicting criteria most similar to those the instruments were designed to reflect. The study concludes with a discussion of priorities for research on screening instruments.
Influence of Social Desirability Response Set on Self‐Report for Assessing the Outcome of Treated Alcoholics
Authors: Yoshino Aihide , Kato Motoichiro
Published: April 2006

We studied the influence of the social desirability response set on self‐reporting by alcoholics on the outcome of treatment. Seventy‐one treated alcoholics gave answers based on the social desirability scale (SDS) and 19 alcohol‐related items designed to evaluate abstinence, and were diagnostically interviewed. The serum γ‐glutamyl‐transpeptidase (GGT) level was used as an external standard to evaluate the validity of self‐reporting. As SDS scores increased, both the rate of abstinence reported by the subjects and the coefficient between the self‐report and diagnostic interview increased. However, the GGT level was significantly low in subjects who reported abstinence than those who reported drinking, regardless of SDS score. Thus, the social desirability response set may not be associated with a conscious response bias in alcohol‐related self‐reports, but may be associated with a good outcome of alcoholism.
γ‐Glutamyltranspeptidase and Carbohydrate Deficient Transferrin: Alternative Measures of Excessive Alcohol Consumption
Authors: Litten Raye Z. , Allen John P. , Fertig Joanne B.
Published: April 2006

Both γ‐glutamyltranspeptidase and carbohydrate‐deficient transferrin have been extensively researched as biological markers of heavy alcohol consumption. The current study briefly describes each test, identifies subject variables that influence their relative sensitivities and specificities, and examines issues surrounding use of the two markers in combination. In addition, this study suggests five design features that should characterize projects evaluating the validity of biochemical markers.
Evaluation of the Alcopatch, a Transdermal Dosimeter for Monitoring Alcohol Consumption
Authors: Phillips Michael , Greenberg Joel , Andrzejewski Jerzy
Published: April 2006

Background: The Alcopatch is an improved transdermal dosimeter for the measurement of alcohol consumption, by detection of ethanol in fluid excreted from the skin. The device is worn as a band around the ankle and provides a visual signal in the event of tampering. Methods: Fourteen volunteers wore duplicate Alcopatches for a period of 7 or 8 days, while keeping a written record of their beverage alcohol consumption. Ethanol concentration in the Alcopatch was measured by gas chromatography and correlated with self‐reported consumption. Results: All alcohol consumption in excess of 0.25 g/kg/day resulted in measurable levels of ethanol in the Alcopatch. A positive correlation was observed between the reported consumption of ethanol (in g/kg/day) and the concentration of ethanol in the Alcopatch (square root, in mg/dl) (y= 0.91x + 0.28, r= 0.61) in 12 of 14 subjects. Conclusions: The Alcopatch detected the consumption of beverage alcohol with high sensitivity and specificity over a period of 7 to 8 days and may be useful for the study of target populations.
Alcohol, Tumor Necrosis Factor, and Tuberculosis
Authors: Nelson Steve , Mason Carol , Bagby Greg , Summer Warren
Published: April 2006

Alcohol exerts potent suppressive effects on the immune system that significanty increase host susceptibility to a variety of infections, particularly pneumonia. Historically, tuberculosis has been strongly associated with alcohol abuse. Although the relationship between alcohol abuse and tuberculosis is widely appreciated, the basic mechanisms by which alcohol immunosuppresses the host remain to be clarified. A major obstacle in furthering our understanding of this association has been the difficulty in distinguishing between the effects of alcohol per se and the other frequent sequelae of alcoholism such as nutritional deficiencies, liver disease, cigarette smoking, hygienic factors, and lifestyle. This article focuses on the role of tumor necrosis factor‐alpha (TNF) in host defense and how alcohol modulates the activity of this important cytokine. While TNF's role in mediating the lethal consequences of infection has been the subject of much conjecture, this review focuses on the emerging evidence that TNF is an essential factor in the normal immune response to numerous infections, including tuberculosis.
Correlates of Alcohol‐Related Problems in African‐American and White Gynecologic Patients
Authors: Lozina Cherelle , Russell Marcia , Mudar Pamela
Published: April 2006

The purpose of this study was to assess racial differences in the risk of alcohol‐related problems associated with alcohol consumption, regular psychoactive drug use, a family history of alcohol‐related problems, sociodemographic factors (age and education), and social roles (work, marital, and parental) among nonabstaining African‐American and White gynecologic outpatients. In addition, work, marital, and parental roles were investigated to determine whether they mediated or explained racial differences observed in relationships between these factors and alcohol‐related problems. Respondents were 630 African‐American women and 769 White women aged 13–77 who were systematically sampled from three obstetric/gynecologic clinics and two private practices in Erie County, New York. Hierarchical multiple regression analysis was used to test the significance of main effects of these factors on alcohol‐related problems, to test the interactive effects of race with each factor, and to test the interactive effects of social roles with alcohol consumption, the only factor for which a racial difference was observed in its relationship with alcohol‐related problems.

Overall, results indicated that correlates of alcohol‐related problems were similar for African‐American and White women. Higher risk of alcohol‐related problems was associated with lower levels of education and lack of work and parental roles. In addition, married women who drank heavily were at higher risk of alcohol‐related problems than unmarried women who drank heavily. The fact that White women were more likely than African‐American women to be married contributed to the observation that the relationship between alcohol consumption and alcohol‐related problems was stronger among White women than among African‐American women.
High‐Risk Drinking across the Transition from High School to College
Authors: Baer John S. , Kivlahan Daniel R. , Marlatt G. Alan
Published: April 2006

Alcohol use and related problems were studied from the senior year in high school to the first autumn in college for 366 heavy drinking students. Four risk factors‐subject sex, family history of drinking problems, prior conduct problems, and type of college residence‐were evaluated as predictors of: (1) differential changes in drinking rates, (2) differential changes in alcohol‐related problems, and (3) alcohol dependence symptoms during the first college term. Results suggest that both dispositional and environmental factors are associated with changes in drinking rates and the existence of dependence symptoms. Increases in the frequency of drinking were specifically and strongly associated with residence in a fraternity (men) or sorority (women). Three risk factors were associated with increased quantity of drinking: male gender, residence in a fraternity or sorority, and a history of conduct problems. Prior conduct problems were also consistently associated with dependence symptoms during the first term in college. A family history of alcohol problems was not consistently related to changes in use rates or problems, although some analyses suggest interactive effects. Early interventions on college campuses should target individuals using additive risk profiles.