bluuebunny/crossref_metadata_2025 huggingface dataset:
Adrenocorticotropin Responses Following Administration of Ethanol and Ovine Corticotropin‐Releasing Hormone in the Sons of Alcoholics and Control Subjects
Authors: Waltman Claire , McCaul M. E. , Wand Gary S.
Published: April 2006

Alcoholism is a familial disorder with both genetic and environmental determinants. The sons of alcoholic fathers have been documented to have alterations in several neuroendocrine measures. We investigated the ACTH/cortisol response to ovine corticotropin‐releasing hormone (oCRH) and ethanol in men with and without a family history of alcoholism. Men were defined as family history positive (FHP) (n= 7) if their father was alcoholic; as family history negative (FHN) (n= 16), if their father was nonalcoholic. Ethanol (0.75 g/kg) or placebo was ingested over 15 min, 1 μg/kg oCRH was administered, and plasma ACTH/cortisol levels were determined at –20, 0, 15, 30, 60, and 90 min after oCRH. Following placebo, FHP men had lower peak ACTH response to oCRH than did FHN men (12 ± 2 vs 20 ± 2 pmol/liter, P= 0.04). In FHN men, plasma ACTH response to oCRH was blunted during the ethanol session compared to the placebo session (13 ± 1 vs 20 ± 2 pmol/liter; P= 0.006). In contrast, FHP men had similar ACTH responses to oCRH during ethanol and placebo sessions. Cortisol responses to oCRH were similar in both groups during both sessions. In summary, FHP and FHN nonalcoholic men had different plasma ACTH responses following the administration of oCRH.
Confirming the Factor Structure of the Anticipated Biphasic Alcohol Effects Scale
Authors: Earleywine Mitchell
Published: April 2006

This study of the Anticipated Biphasic Alcohol Effects Scale (A‐BAES) examined the factor structure of expected stimulant and sedative effects on the ascending and descending limbs of the blood alcohol curve. Subjects reported the effects they anticipated they would experience immediately after drinking four drinks (ascending) and 1 1/2 hr later (descending). The proposed 4‐factor model of stimutant and sedative effects on the ascending and descending limbs fit the data significantly better than single‐factor, null, limb‐only, and effect‐only models, suggesting that the A‐BAES has a confirmable structure. In addition, anticipated effects varied with limb of the blood alcohol curve, gender, and drinking habits. Anticipated stimulant effects were higher on the ascending than descending limbs; anticipated sedative effects were higher on the descending than ascending limbs. Women and men differed in their anticipated effects of alcohol, even when differences in drinking habits were controlled. Anticipated sedative effects correlated significantly with alcohol consumption, offering further support for the relation between expectancies and drinking.
Nicotine Dependence Treatment During Inpatient Treatment for Other Addictions: A Prospective Intervention Trial
Authors: Hurt Richard D. , Eberman Kay M. , Croghan Ivana T. , Offord Kenneth P. , Davis Leo J. , Morse Robert M. , Palmen Michael A. , Bruce Barbara K.
Published: April 2006

This study assessed the effect of treating nicotine dependence in smokers undergoing inpatient treatment for other addictions. It was a prospective, nonrandomized, controlled trial with a 1‐year outcome. The subjects were smoking patients (50 controls, 51 in intervention group) in an inpatient addictions treatment unit in a medical center. The enrollment of subjects was sequential: controls were enrolled first, after a 6‐week washout period, intervention subjects were enrolled. Controls received usual care, and the intervention group received nicotine dependence treatment consisting of a consultation, 10 intervention sessions, and a structured relapse prevention program. Smoking cessation rate and abstinence from alcohol or other drug use were the main outcome measures. The confirmed smoking cessation rate at 1 year was 11.8% in the intervention group and 0.0% in the control group (p= 0.027). Nicotine dependence intervention did not seem to interfere with abstinence from alcohol or other drugs (1‐year relapse rate was 31.4% in the intervention group and 34.0% in controls). In this study, nicotine dependence treatment provided as part of addictive disorders treatment enhanced smoking cessation and did not have a substantial adverse effect on abstinence from the nonnicotine drug of dependence.
Limited Postnatal Ethanol Exposure Permanently Alters the Expression of mRNAS Encoding Myelin Basic Protein and Myelin‐Associated Glycoprotein in Cerebellum
Authors: Zoeller R. Thomas , Butnariu Olimpia V. , Fletcher Don L. , Riley Edward P.
Published: April 2006

Experiments were designed to test the hypothesis that ethanol exposure during development can selectively affect the expression of specific isoforms of myelin protein gene expression in the rat cerebellum. We focused on myelin basic protein (MBP) and myelin‐associated glycoprotein (MAG) gene expression. Both of these genes are alternatively spliced to yield 4 (MBP) or 2 (MAG) mRNA isoforms. Prenatal ethanol exposure, delivered to the dams in a liquid diet, did not significantly alter the expression of MBP or MAG gene expression in the cerebellums of 15‐day‐old pups, as measured by quantitative in situ hybridization using specific oligodeoxynucleotide probes. In contrast, postnatal ethanol exposure delivered directly to the pups over a 6‐day period by gastrostomy tube (PN days 4‐10) reduced the expression of specific MBP and MAG isoforms in the cerebellum of animals in adulthood. These data demonstrate that ethanol exposure, especially during the period of rapid myelination, has selective effects on mRNA isoforms encoding specific MBPs and MAG.
Localization of Genes Affecting Alcohol Drinking in Mice
Authors: Phillips Tamara J. , Crabbe John C. , Metten Pamela , Belknap John K.
Published: April 2006

The genomic map locations of specific genes controlling behaviors can be identified by studying a panel of recombinant inbred (RI) mouse strains. The progenitor C57BL/6J (B6) and DBA/2J (D2) strains, and 19 of the BXD RI strains derived from an F2 cross of these progenitors, were tested for 3% and 10% ethanol (EtOH) intake. The test sequence began with two‐bottle free choice between tap water and unsweetened ethanol, and ended with free choice between water and saccharin‐sweetened ethanol. Saccharin preference was also measured. Correlational analyses indicated that 59% of the genetic variance in 10% ethanol and sweetened 10% ethanol consumption was held in common, 24% of the genetic variance in saccharin and sweetened 10% ethanol consumption was held in common, and only 7% of the genetic variance in saccharin and unsweetened 10% ethanol consumption was held in common. These percentages for 3% ethanol solutions were 21%, 36%, and 14%. In addition, the severity of handling‐induced convulsions during ethanol withdrawal was found to be significantly associated with the amount of ethanol consumed from the sweetened ethanol drinking tubes, suggesting that genetic differences in avidity for ethanol could lead to the development of physical dependence. Quantitative trait loci (QTL) analyses revealed that several genetic markers were associated with ethanol consumption levels, including markers for the D2 dopamine receptor. QTL analyses of saccharin and sweetened ethanol consumption identified the sac locus, thought to determine the ability to detect saccharin. In general, our results suggest that saccharin and ethanol consumption are determined by the actions of multiple genes (QTL), some in common, and suggest specific map locations of several such QTL on the mouse genome.
Biometrical Genetic Analysis of Ethanol's Psychomotor Stimulant Effect
Authors: Dudek Bruce C. , Tritto Theresa
Published: April 2006

Hereditary influences on psychomotor stimulant effects of ethanol (ETOH) were studied in a classical Mendelian cross of DBA/2Abg (D2) and C57BL/6Abg (B6) inbred mouse strains. A dose‐response study with nine doses (0–3.5 g/kg ip) indicated that B6 mice lack the activational limb of the biphasic curve ( 1.5 g/kg), as assessed in a 15‐min test. D2 mice ran greater distances and ran faster, at doses up to 2.5 g/kg. B6 mice showed no increments in speed or distance at these doses that activated D2 mice. Several other indices reinforced the conclusion of ETOH‐induced behavioral activation in D2 mice and lack there of in B6 mice (traditional photobeam interruptions—horizontal counts; center distance; vertical movements; inactive time; as well as derived indices of running speed and average length of each movement). The F1, F2, and backcross generations produced dose‐response curves that showed additive inheritance of the activational response to doses below 1.5 g/kg. A second study (n= 1446) examined response to 1.5 g/kg with a within‐subjects design in the full Mendelian cross. This study verified the completely additive mode of inheritance for the total distance measure suggested in the dose‐response study, and showed that sex linkage and sex differences were not present. Narrow sense heritability of the ETOH activation response (indexed by total distance) was calculated at 0.35 and ∼3 loci were estimated to be responsible for the B6/D2 difference. The other phenotypes (described above) also showed strongly additive genetic control. These studies indicate that the psychomotor stimulant effect of ETOH in mice is under genetic influence and that the control mechanism is a simple, small‐sized polygenic system, with an uncomplicated mode of inheritance that should make it amenable to further characterization at a functional level.
Ethanol Consumption and Early Murine Retrovirus Infection Influence Liver, Heart, and Muscle Levels of Iron, Zinc, and Copper in C57BL/6 Mice
Authors: Shahbazian L. Masoud , Wood Steven , Watson Ronald R.
Published: April 2006

The relative and combined roles of ethanol and murine acquired immunodeficiency syndrome (MAIDS) on the mineral status (Fe, Zn, and Cu) of liver (storage site), heart, muscle (nutrient mobile sites) were investigated. C57BL/6 mice were randomly assigned to four groups: (a) uninfected mice fed isocaloric, adequate nutrient diet (NRC), (b) uninfected mice fed the NRC diet with 25% of energy derived from ethanol, (c) LP‐BM5 retrovirus‐infected mice fed the isocaloric NRC diet, and (d) retrovirus‐infected mice fed the NRC diet with 25% of its energy derived from ethanol. The levels of Cu and Zn levels in the liver did not significantly change as a result of ethanol consumption. However hepatic Zn concentration was increased significantly in retrovirus‐infected mice. This may be correlated to the increase in their liver weight. Ethanol administration significantly increased Fe concentration in the liver, yet significantly decreased concentration of Cu in the heart. Retrovirus infection alone, which had not proceeded to murine AIDS, resulted in a significant increase in heart Cu and Zn concentration as compared with uninfected mice. Retrovirus infection in C57BL/6 mice significantly increased Fe and Zn level/g of muscle. Early retrovirus infection alters tissue micronutrient levels, and may thus contribute to immunological changes.
Chronic Ethanol Consumption before Retrovirus Infection is a Cofactor in the Development of Immune Dysfunction during Murine AIDS
Authors: Wang Yuejian , Watson Ronald R.
Published: April 2006

Chronic ethanol (EtOH) consumption has been presumed to be a cofactor in the development of acquired immune deficiency syndrome (AIDS). AIDS is identified as a major public health priority in the United States, with heavy economic and social impact. In the present study, we tested this hypothesis that EtOH users are more predisposed to immunosuppression because of retrovirus infection in murine AIDS. Adult female C57BL/6 mice were fed 4.5% (v/v) in liquid diet and control diets for 10 weeks. Then all mice were infected with LP‐BM5 retrovirus, causing murine AIDS, and were fed control liquid diets without EtOH. Interleukin (IL)‐2 production produced by concanavalin A (Con A)‐stimulated splenocytes was suppressed during murine AIDS. It was further inhibited in EtOH‐fed mice compared with controls at 6 weeks postinfection, whereas decreased level of interferon‐γ during murine AIDS was not further affected in EtOH‐fed mice. The levels of IL‐5, IL‐6, and IL‐10 secreted by Con A‐induced splenocytes, elevated during murine AIDS, were significantly further enhanced in EtOH‐fed mice compared with controls at 6 weeks postinfection, whereas retrovirus‐induced elevated release of IL‐6 and tumor necrosis factor‐α, produced by lipopolysaccharide (LPS)‐stimulated splenocytes, were further increased in EtOH‐fed mice compared with controls at 6 and 9 weeks postinfection, respectively. Con A‐ and LPS‐induced splenocyte proliferation, inhibited by retrovirus infection, was significantly further suppressed in EtOH‐fed mice compared with controls. These results suggest that dietary EtOH consumption before retrovirus infection aggravated progression of immune dysfunction, because it modified production of immunological regulatory cytokines and immune functions.
Changes in GABAergic and Non‐GABAergic Synapses During Chronic Ethanol Exposure and Withdrawal in the Dentate Fascia of LS and SS Mice
Authors: Fifková Eva , Eason Helen , Bueltmann Kenneth , Lanman Jason
Published: April 2006

Ethanol‐sensitive LSIBG and ethanol‐insensitive SSIBG mice were exposed to ethanol (23.5% ethanol‐derived calories) for 4 months. Half of the animals was sacrificed at this time and the other half was withdrawn from the ethanol diet for 1 month. GABA immunoelectron microscopy was used to study the impact of the treatments on synaptic contacts in the dentate molecular layer. In the LS mice a significant loss of non‐GABAergic axospinous synapses (26.7%; p < 0.05) was observed during ethanol exposure which was followed by a loss of GABAergic synapses on dendritic shafts (54.7%; p < 0.01) during withdrawal. In the SS mice there was a significant decrease in the non‐GABAergic axospinous synapses (23.5%; p < 0.05) and a significant increase in axodendritic synapses (63.3%; p < 0.05) during ethanol exposure. The observed changes in the GABAergic and non‐GABAergic innervation of the dentate fascia induced by ethanol were observed in the projection zone of the perforant path. They could adversely affect the hippocampal physiology with a consequent impairment of mnemonic functions.
Effect of Alcohol on Platelet‐Activating Factor Acetylhydrolase Activity in Pregnant and Nonpregnant Mice
Authors: Saleh Abdelaziz A. , Church Michael W. , Johnston John M.
Published: April 2006

Platelet‐activating factor (PAF) induces platelet aggregation and hypotension. It has been implicated in embryonic implantation, fetal lung maturation, and parturition. Alcohol abuse is associated with platelet dysfunction, chronic hypertension, and alcohol‐related birth defects. We hypothesized that alcohol may cause, in part, these effects by increasing the activity of PAF‐acetylhydrolase (PAF‐AH), thereby decreasing PAF concentration. Pregnant mice were given 3.5 g/kg of alcohol orally twice daily from gestation days 7–17. PAF‐AH was measured on gestation days 5, 14, and 19 in pregnant females. Nonpregnant females were treated and sampled at parallel time intervals. Pair‐fed and untreated control groups were also used. The maternal plasma PAF‐AH decreased with gestational age in the untreated controls. Alcohol significantly increased PAF‐AH levels in both the pregnant and nonpregnant animals. PAF deficiency might contribute to the tocolytic action of alcohol, as well as some alcohol‐related pregnancy complications.
Liver Microsomal Fatty Acid Composition in Ethanol‐Fed Rats: Effect of Different Dietary Fats and Relationship to Liver Injury
Authors: Nanji Amin A. , Sadrzadeh S. M. Hossein , Dannenberg Andrew J.
Published: April 2006

The rat intragastric feeding model for alcoholic liver disease was used to study the effect of different diets on the fatty acid composition of liver microsomes. Rats were fed corn oil and ethanol (CE), saturated fat and ethanol (SF+E) or corn oil and dextrose (CD) for either 2 or 4 weeks. Rats were also fed saturated and dextrose (SF+D) for 4 weeks. In comparison with the CD diet, lower levels of arachidonic acid were detected in rats fed the CE, SF+E, and SF+D diets. However, the diet‐induced changes in levels of arachidonic acid varied as a function of length of feeding. In rats fed the CE diet, we detected a significant decrease in the level of arachidonic acid compared with CD animals. Conversely, in rats fed the SF+E diet, the level of arachidonic acid increased compared with the SF+D group. In addition, a significant correlation was noted between levels of oleic acid and arachidonic acid in both corn oil (r=–0.85, p < 0.01) and saturated fat (r=–0.76, p < 0.05) groups. However, the changes in levels of arachidonic acid and oleic acid were in opposite directions in the two groups. Levels of docosahexaenoic acid decreased between the 2 and 4 weeks in animals maintained on the CE diet. Levels of stearic acid increased between 2 and 4 weeks in rats fed the SF+E diet. The lowest level of linoleic acid was detected in the SF+D and SF+E groups, but levels of linoleic acid remained constant in all groups throughout the study. Histological evaluation indicated that ethanol‐induced liver injury was limited to rats fed the diet containing corn oil for 4 weeks. Thus, diet‐dependent differences in liver microsomal fatty acid composition may help to explain why ethanol‐induced liver injury occurs in rats fed corn oil, but not saturated fat.
Role of Magnesium and Calcium in Alcohol‐Induced Hypertension and Strokes as Probed by In Vivo Television Microscopy, Digital Image Microscopy, Optical Spectroscopy, 31P‐NMR, Spectroscopy and a Unique Magnesium Ion‐Selective Electrode
Authors: Altura Burton M. , Altura Bella T.
Published: April 2006

It is not known why alcohol ingestion poses a risk for development of hypertension, stroke and sudden death. Of all drugs, which result in body depletion of magnesium (Mg), alcohol is now known to be the most notorious cause of Mg‐wasting. Recent data obtained through the use of biophysical (and noninvasive) technology suggest that alcohol may induce hypertension, stroke, and sudden death via its effects on intracellular free Mg2+ ([Mg2+]), which in turn alter cellular and subcellular bioenergetics and promote calcium ion (Ca2+) overload. Evidence is reviewed that demonstrates that the dietary intake of Mg modulates the hypertensive actions of alcohol. Experiments with intact rats indicates that chronic ethanol ingestion results in both structural and hemodynamic alterations in the microcirculation, which, in themselves, could account for increased vascular resistance. Chronic ethanol increases the reactivity of intact microvessels to vasoconstrictors and results in decreased reactivity to vasodilators. Chronic ethanol ingestion clearly results in vascular smooth muscle cells that exhibit a progressive increase in exchangeable and cellular Ca2+ concomitant with a progressive reduction in Mg content. Use of 31P‐NMR spectroscopy coupled with opticalbackscatter reflectance spectroscopy revealed that acute ethanol administration to rats results in dose‐dependent deficits in phosphocreatine (PCr), the [PCr]/[ATP] ratio, intracellular pH (pHi), oxyhemoglobin, and the mitochondrial level of oxidized cytochrome oxidase aa3 concomitant with a rise in brain‐blood volume and inorganic phosphate. Temporal studies performed in vivo, on the intact brain, indicate that [Mg2+], is depleted before any of the bioenergetic changes. Pretreatment of animals with Mg2+ prevents ethanol from inducing stroke and prevents all of the adverse bioenergetic changes from taking place.

Use of quantitative digital imaging microscopy, and mag‐fura‐2, on single‐cultured canine cerebral vascular smooth muscle, human endothelial, and rat astrocyte cells reveals that alcohol induces rapid concentration‐dependent depletion of [Mg2+], These cellular deficits in [Mg2+], seem to precipitate cellular and subcellular disturbances in cytoplasmic and mitochondrial bioenergetic pathways leading to Ca2+ overload and ischemia. A role for ethanol‐induced alterations in [Mg2+], should also be considered in the well‐known behavioral actions of alcohol.
Screening for Pregnancy Risk‐Drinking
Authors: Russell Marcia , Martier Susan S. , Sokol Robert J. , Mudar Pamela , Bottoms Sidney , Jacobson Sandra , Jacobson Joseph
Published: April 2006

The efficacy of alcohol screening questionnaires, the TWEAK, TACE, NET, MAST, and CAGE, in detecting periconceptional riskdrinking, 1 oz absolute alcohol/day, was investigated in 4743 African‐American women attending an inner‐city prenatal clinic who had reported ever drinking. Sensitivity, specificity, positive predictive value, efficiency, follow‐up rates, and receiver operating characteristics of the questionnaires were examined to compare the overall effectiveness of the questionnaires and their performance at cutpoints defining positive scores ranging from 1 to 3. Relatively little difference between TWEAK, T‐ACE, and MAST was seen in the receiver operating characteristic accuracy indices; NET and CAGE lagged behind. Sensitivity/specificity scores for the two questionnaires most sensitive at cut‐point 1 were TWEAK (87/72) and T‐ACE (83/75). At cut‐point 2, sensitivity was optimized with respect to specificity; TWEAK (79/83) was significantly more sensitive than T‐ACE (70/85; p = 0.002). At cut‐point 3, the two most sensitive tests were MAST (61/92) and TWEAK (59/94). In general, measures of merit were not greatly affected by the time between conception and the administration of the screens. Screening was most sensitive for women interviewed during the first 15 weeks of pregnancy; riskdrinkers tended to delay entry into prenatal care, increasing positive predictive values associated with screening later in pregnancy.

This study confirms the utility, when screening for risk‐drinking during pregnancy, of brief questionnaires that assess alcohol intake indirectly by asking women about their tolerance to alcohol's effects, psychological consequences of drinking, and significant others' concern about their drinking. It validates T‐ACE and provides preliminary data indicating that TWEAK may outperform T‐ACE.
Low‐Level Hyperbaric Antagonism of Ethanol's Anticonvulsant Property in C57BL/6J Mice
Authors: Davies Daryl L. , Mørland Jørg , Jones Brenda L. , Alkana Ronald L.
Published: April 2006

This study investigated the ability of hyperbaric exposure to antagonize ethanol's anticonvulsant effect on isoniazid (INH)‐induced seizures. Drug‐naive, male C57BL/6 mice were injected intraperitoneally with saline, 1.5, 2.0, or 2.5 g/kg ethanol followed immediately by an intramuscular injection of 300 mg/kg of INH. The mice were then exposed to either 1 atmosphere absolute (1 ATA) air, 1 ATA helium‐oxygen gas mixture (heliox), or 12 ATA heliox at temperatures that offset the hypothermic effects of helium. Ethanol increased the latency to onset of myoclonus in a dose‐dependent manner. Exposure to 12 ATA heliox antagonized ethanol's anticonvulsant effect at 2.0 and 2.5 g/kg, but not at 1.5 g/kg. Ethanol also increased the latency to onset of clonus in a dose‐dependent manner beginning at 2.0 g/kg. Exposure to 12 ATA heliox antagonized this anticonvulsant effect. When exposed to 12 ATA heliox, the blood ethanol concentrations at time to onset of myoclonus were significantly higher in mice treated with 2.5 g/kg of ethanol as compared with blood ethanol concentrations of mice exposed to 1 ATA air. These findings extend the acute behavioral effects of ethanol known to be antagonized by hyperbaric exposure and support the hypothesis that low‐level hyperbaric exposure blocks or reverses the initial action(s) of ethanol leading to its acute behavioral effects.
Influence of Ethanol Intake on Mammary Gland Morphology and Cell Proliferation in Normal and Carcinogen‐Treated Rats
Authors: Singletary Keith W. , McNary Minnie Q.
Published: April 2006

Alcohol consumption has been reported to increase breast cancer risk in a majority of epidemiological studies and to enhance, at specific dietary concentrations, both the initiation and promotion stages of chemically induced rat mammary tumorigenesis. However, there is limited information regarding possible mechanisms for this effect.

The present studies were conducted to examine a possible mechanism for the promoting effect of ethanol on chemically induced mammary tumorigenesis. The influence of chronic ethanol intake by female rats on the progress of differentiation and on the rate of target structure cell proliferation of the mammary gland was evaluated. Results of these studies indicate that ethanol intake at 20% and 30% of calories by female rats between the ages of 55 and 94 days (a period associated with the promotion stage of experimental mammary tumorigenesis) results in a delay in the differentiation of the mammary gland. This delay in gland maturation observed for rats consuming ethanol was evidenced by an increase in the quantity of less mature terminal‐end bud (TEB) structures and a decrease in the quantity of more mature alveoler bud structures. The DNA labeling index of the target structure TEB increased significantly for rats consuming ethanol. These changes in mammary gland maturation and in TEB DNA labeling index were observed for both normal and carcinogen‐treated rats consuming ethanol. Also, serum progester‐one, but not estradiol, was significantly decreased for animals consuming ethanol at 30% of calories compared with isocaloric controls. The correlation of these changes in the mammary gland with the reported enhancement by ethanol of the promotion stage of experimental rat mammary tumorigenesis is discussed.
Markedly Enhanced Cytochrome P450 2E1 Induction and Lipid Peroxidation Is Associated with Severe Liver Injury in Fish Oil—Ethanol‐Fed Rats
Authors: Nanji Arnin A. , Zhao Shuping , Sadrzadeh S. M. Hossein , Dannenberg Andrew J. , Tahan Steven R. , Waxman David J.
Published: April 2006

We evaluated the role of changes in cytochrome P‐450 2E1 (CYP 2E1) and lipid peroxidation in relation to development of severe liver injury in fish oil–ethanol‐fed rats. The experimental animals (male Wistar rats) were divided into 5 rats/group and were fed the following diets for 1 month: corn oil and ethanol (CO+E) or corn oil and dextrose (CO+D), and fish oil and ethanol (FO+E) or fish oil and dextrose (FO+D). For each animal, microsomal analysis of CYP 2E1 protein, aniline hydroxylase activity, fatty acid composition, and conjugated dienes was conducted. Also, evaluation of severity of pathology was done for each rat. The mean ± SD of the pathology score was significantly higher (p < 0.01) in the FO+E (6.0 ± 1.3) group than in the CO+E group (3.0 ± 0.5). No pathological changes were evident in the dextrose‐fed controls. The CYP 2E1 protein levels (mean ± SD) were significantly higher (p < 0.01) in the FO+E group (13.1 ± 2.0) compared with the CO+E (4.7 ± 1.2) and FO+D (1.8 ± 0.5) groups. Higher levels of eicosapentaenoic and docosa‐hexaenoic acids and lower levels of arachidonic acid were detected in liver microsomes from rats fed fish oil compared with corn oil. A significant correlation was obtained between CYP 2E1 protein and conjugated diene levels (r= 0.78, p < 0.01). Our results showing markedly increased CYP 2E1 induction and lipid peroxidation in the FO+E group provides one possible explanation for the greater severity of liver injury in this group.
Effect of Postnatal Ethanol Exposure on Expression of Differentiation Antigens of Murine Splenic Lymphocytes
Authors: Giberson Pamela K. , Blakley Barry R.
Published: April 2006

Ethanol is a recognized immunosuppressive agent in the chronic alcoholic. However, the effects of ethanol exposure on the developing immune system have not been extensively investigated. This study evaluated the effects of early postnatal ethanol exposure, via breast milk, on splenic lymphocyte differentiation antigen expression in offspring reared by ethanol‐fed mice. Maternal mice were fed a liquid diet containing 20% ethanol‐derived calories during pregnancy (E‐P), pregnancy and lactation (E‐PL), or lactation (E‐L). Ad libitumfed (C) and pair‐fed (PF) control groups, fed a control liquid diet, were included. Expression of differentiation antigens on splenic lymphocytes from 21‐day‐old offspring reared by females in 1 of the 3 ethanol exposure conditions was evaluated by flow cytometry. Offspring reared by E‐P females had similar numbers of splenic lymphocytes as offspring reared by C and pair‐fed during pregnancy (PF‐P) females. In contrast, offspring reared by E‐PL and E‐L females had fewer splenic lymphocytes than both PF‐PL and PF‐L (respectively), and C offspring. The number of Thy 1.2+, CD4+, CD8+, and IgG+ (B‐cell) splenic lymphocytes was reduced in E‐PL and E‐L offspring compared with PF and C offspring. E‐P offspring had fewer CD4+ and IgG+ splenic lymphocytes than C, but not PF‐P, offspring. The percentage of Thy 1.2+ splenic lymphocytes was significantly reduced among E‐PL and E‐L offspring compared with PF‐PL and PF‐L (respectively), and C offspring. These results suggest that ethanol exposure of female mice during pregnancy, pregnancy and lactation, or lactation alone, alters the phenotypic development of splenic lymphocytes of offspring reared by these females. The greatest effect on differentiation antigen expression occurred when females consumed ethanol during the period of lactation. We speculate that direct exposure of the nursing offspring to ethanol via the breast milk was responsible for the reductions in specific splenic lymphocyte populations. These data demonstrate that mice reared by females fed ethanol during the early postnatal period have a marked depletion of each of the major subpopulations of splenic lymphocytes, and that Thy 1.2+ lymphocytes are differentially sensitive to ethanol.
Effects of Ethanol on Structural Parameters of Rat Brain Membranes: Relationship to Genetic Differences in Ethanol Sensitivity
Authors: Avdulov Nicolai A. , Wood W. Gibson , Harris R. Adron
Published: April 2006

Fluorescent probes located in different membrane regions were used to evaluate effects of ethanol (50 and 100 mM) on structural parameters (protein distribution, fluidity of total and annular lipid, and thickness of the bilayer) of synaptic plasma membranes (SPMs) from brain cortex of High‐Alcohol Sensitivity (HAS) and Low‐Alcohol Sensitivity (LAS) rats. An experimental procedure based on radiationless energy transfer from tryptophan of membrane proteins to pyrene, 1,3‐bis‐(1‐pyrene)propane(pyr‐C3‐pyr), or 1,6‐diphenyl‐1,3,5‐hexatriene (DPH), as well as pyr‐C3‐pyr monomer‐eximer formation and DPH polarization, and energy transfer from pyrene monomers to 1‐anilinonaphthalene‐8‐sulfonic acid (ANSA) was utilized. The efficiency of energy transfer from tryptophan to pyrene was sensitive to protein clustering induced in SPMs by concanavalin A. Efficiency of energy transfer from pyrene monomers to ANSA was different for vesicles of dimyristoyl phosphatidyl choline, dipalmitoyl phosphatidyl choline, and distearoyl phosphatidyl choline, consistent with differences in the thickness of these lipid bilayers. Without ethanol, there were no significant differences between the structural parameters of SPMs from HAS and from LAS rats. Addition of ethanol (50 mM) changed protein distribution (increased clustering) only in membranes from HAS rats and had no effect on the structure of membranes from LAS rats. A larger concentration of ethanol (100 mM) changed the fluidity of annular and total lipid in both lines of rats, but changed protein distribution and decreased thickness of the membranes from HAS rats with no effect on these parameters in SPMs from LAS animals. Ethanol (50 and 100 mM) decreased the binding affinity of ANSA for membranes from HAS, but not LAS rats. Genetic differences in ethanol sensitivity of HAS and LAS rats may be related to effects of ethanol on protein mobility, protein‐protein interactions, or membrane thickness, but do not appear to be due to effects of ethanol on the fluidity of membrane lipids.
An Examination of the Alcohol Consumption and Peptic Ulcer Association—Results of a National Survey
Authors: Chou S. Patricia
Published: April 2006

Excessive alcohol consumption causes damages to the stomach or duodenum by impairing the integrity of the mucosal barrier. The aim of this study was to estimate the association between alcohol consumption and peptic ulcer, utilizing a large representative sample of the U.S. population, while controlling for cigarette smoking and major sociodemographic variables. Results indicated that alcohol consumption only minimally increased the odds of peptic ulcer. Thus, this study offers little support for the association between ethanol intake and peptic ulcer.
Volumetric Magnetic Resonance Imaging Quantification of Longitudinal Brain Changes in Abstinent Alcoholics
Authors: Shear Paula K. , Jernigan Terry L. , Butters Nelson
Published: April 2006

Magnetic resonance imaging (MRI) of the brain was performed on a group of 24 recently detoxified, male alcoholics approximately 1 month after their date of last drink. The imaging was repeated 3 months later, at which point 9 subjects had resumed drinking and 15 had maintained abstinence. Contrasts between these two drinking groups revealed that, despite comparable baseline values, the Abstainers exhibited volumetric white matter increases and cerebrospinal fluid reductions over the follow‐up interval, whereas the Drinkers did not show significant change on either of these MRI indices. These results provide the first evidence suggestive of significant volumetric white matter increase with abstinence.
Indexing Withdrawal in Mice: Matching Genotypes for Exposure in Studies Using Ethanol Vapor Inhalation
Authors: Terdal Erik S. , Crabbe John C.
Published: April 2006

Withdrawal Seizure‐Prone (WSP) and ‐Resistant (WSR) mice have been bidirectionally selected for severity of handling‐induced convulsions (HIC) following withdrawal from 72 hr of chronic ethanol vapor inhalation. During selection, daily injections of the alcohol dehydrogenase inhibitor, pyrazole, were used to enhance and stabilize blood ethanol concentrations (BEC). After 26 generations of selection, WSR mice show lower withdrawal BEC than WSP mice exposed to the same ethanol vapor concentrations. Because it is desirable to compare mice maintained at the same BEC to assess correlated responses to selection, this has necessitated exposing WSR mice to higher ethanol vapor concentrations than WSP mice to achieve matched chronic BEC. The experiments reported herein demonstrate two methods for producing matched withdrawal BEC: (1) by exposing mice to the same ethanol vapor concentration and varying the pyrazole dose; and (2) by administering only ethanol at different vapor concentrations and selecting some mice with approximately the same BEC. When exposed to the same ethanol vapor concentration, WSR mice given 1.0 mmol/kg pyrazole had withdrawal BEC equivalent to WSP mice given 0.75 mmol/kg pyrazole. However, WSP mice had much more severe withdrawal HIC than WSR mice. WSP and WSR mice metabolized ethanol at the same rate following withdrawal. The basis for the differential effectiveness of pyrazole is unknown. We also exposed mice to higher ethanol vapor concentrations in the absence of pyrazole. By exposing WSR mice to higher concentrations than WSP, roughly equivalent BEC on withdrawal was achieved. Because BEC are more variable in the absence of pyrazole, it was necessary to select animals of each genotype to achieve relatively matched BEC. Again, WSP mice had much more severe HIC on withdrawal than WSR.
Reduced Serotonergic Immunoreactive Fibers in the Forebrain of Alcohol‐Preferring Rats
Authors: Zhou Feng C. , Bledsoe Sharon , Lumeng Larry , Li Ting‐Kai
Published: April 2006

Our previous study indicated that 5‐hydroxytryptamine (5‐HT) immunoreactive fiber densities were decreased in specific areas of the brain in alcohol‐preferring rats (P) when compared with alcohol‐nonpreferring rats (NP). The results of our current study show that there are quantitative and qualitative differences in 5‐HT innervation in other selected regions of the forebrains of P rats. The 5‐HT fiber density in the brains of young adult P and NP rats was measured by immunocytochemistry and quantitative image analysis. A routine error of two‐dimensional quantitation of nerve fiber was addressed and an adjustment was made. The amount of 5‐HT fibers was significantly lower in CA4 and fasciola cinereum of the dorsal hippocampus, caudate‐putamen, and hypothalamus of the P as compared with NP rats (unpaired Student's t tests).

In examining the fiber types, we found that, in the frontal cortical and hippocampal regions, where normally fine 5‐HT fibers with small varicosities and thick 5‐HT fibers with large varicosities coexist, fewer fine 5‐HT fibers were seen in P rats as compared with NP rats the fine fibers are known to be vulnerable to abusive drugs. These observations indicate that (a) there are quantitative differences in 5‐HT innervation or that the 5‐HT in some 5‐HT fibers is reduced to a level undetectable by immunocytochemistry, and (b) the fine 5‐HT fibers are specifically reduced to a greater degree in the selected brain regions of P rats when compared with that of NP rats. The involvement of the 5‐HT system in the alcohol abuse is discussed.
Role of the GTP‐Binding Protein Go in the Suppressant Effect of Ethanol on Voltage‐Activated Calcium Channels of Murine Sensory Neurons
Authors: Huang Guo‐Jie , McArdle Joseph J.
Published: April 2006

Whole‐cell and single‐channel recording techniques were used to investigate the acute, in vitro effects of ethanol on the function of voltage‐activated Ca2+ channels in cultured neurons derived from dorsal root ganglia (DRG) of embryonic mice. Although 5.4 MM ethanol produced a sustained increase of the amplitude of the whole‐cell Ca2+ current (ICa), 43.2 mM ethanol had a time‐dependent biphasic effect. That is, within 0.5 min of exposure to 43.2 MM ethanol, the maximal amplitude of ICa initially increased before declining to a new steady‐state value. As anticipated, the facilitatory and inhibitory effects of ethanol on ICa were associated with an increase and decrease, respectively, in the probability of single‐channel open events. Pretreatment of DRG with 200 ng/ml of pertussis toxin abolished the inhibitory, but not the facilitatory, effect of 43.2 mM ethanol on ICa Pretreatment with pertussis toxin also prevented the reduction of the probability of single‐channel opening caused by 43.2 mM ethanol. Similarly, dialysis of neurons with polyclonal antibodies against the a‐subunit of Go but not G., abolished the inhibitory effect of 43.2 mM ethanol on ICa These data demonstrate concentration‐ and time‐dependent biphasic effects of ethanol on the activity of Ca2+ channels. The inhibitory effect of ethanol requires activation of the a‐subunit of Go, which then decreases the probability of Ca2+ channel opening.
Effects of Ethanol Consumption on Enriched Natural Killer Cells from C57BL/6 Mice
Authors: Gallucci Randle M. , Mister Linda J. , Meadows Gary G.
Published: April 2006

Ethanol (20% w/v) given to female, C57BL/6 mice in their drinking water was previously shown to suppress natural killer (NK) cell cytolytic activity in a mixed splenocyte population. The present study was designed to examine the hypothesis that ethanol consumption independently results in inhibition of NK cell cytolytic activity. Mice were given 20% w/v ethanol in the drinking water for 2 weeks, and splenic NK cells were enriched up to 88% based on surface expression of NK1.l. Cytolytic activity of these freshly enriched NK cells from ethanol‐consuming mice against YAC‐1 lymphoma cells was inhibited an average of 41% relative to water‐drinking controls. Cytolytic activity of enriched NK cells from ethanol‐consuming mice was stimulated to levels equal to control water‐drinking mice after 16‐ to 18‐hr incubation in 1000 units/ml recombinant interleukin 2. These data indicate that in vitro cytolytic activity of NK cells from ethanol‐consuming mice is inhibited in the absence of other modulatory leukocytes.
Detection of Alcoholism in Three Populations by the Brief‐Mast
Authors: Chan Arthur W. K. , Pristach Edward A. , Welte John W.
Published: April 2006

The brief MAST (B‐MAST) questionnaire was used to detect alcoholism in three populations, namely, alcoholics in treatment, clinical outpatients, and the general population. Nearly all the alcoholics in treatment tested positive in the 8‐MAST (99.2%), for lifetime as well as for current (past year) alcohol‐related problems. Among the clinical outpatients and general population, 35.6% and 20.2% respectively, tested positive for lifetime alcohol problems, but only 19.6% and 7.6%, respectively, tested positive for past‐year alcohol problems.

The sensitivity/specificity of the B‐MAST (lifetime) was 64.7%/ 90.0% and 48.30//96.4% in the clinical outpatients and general population, respectively. Even lower sensitivity (28.2%) was obtained when the B‐MAST was used to detect past‐year alcohol problems in the general population sample. The poor sensitivity of the B‐MAST in the general population was probably because most of the B‐MAST questions deal with severe alcohol problems, and they are not sufficiently sensitive to detect those who drank heavily but who had not yet developed these alcohol problems. Anomalous responses to the two questions about “normal drinker” and to the question about “attendance in AA meeting” also contributed (<3%) to inflated positive B‐MAST scores. There were gender differences, and to a lesser extent, racial differences (Whites versus Blacks), in the responses to individual 8‐MAST questions in the three subject populations, with more males than females in each group reporting more alcohol‐related problems. However, there were no gender and racial differences in the average B‐MAST scores among those clinical outpatients and general population subjects who tested positive.
Alcohol‐Related Dementia in the Institutionalized Elderly
Authors: Carlen Peter L. , McAndrews Mary Pat , Weiss Rachel T. , Dongier Maurice , Hill Jeanne‐Marie , Menzano Enrique , Farcnik Karl , Abarbanel Jacob , Eastwood M. Robin
Published: April 2006

This study examined the distribution of alcohol‐related and other dementias in a sample of 130 cognitively impaired residents of long‐term care facilities in a Northern Ontario community. Study procedures entailed standardized psychiatric, neurological, and neuropsychological evaluations. Diagnoses of dementia of the Alzheimer type (DAT) and vascular dementia were based on criteria of the National Institute of Neurological and Communicative Disorders and Stroke and the Alzheimer's Disease and Related Disorders Association. The diagnosis of alcohol‐related dementia (ARD) was based on extensive review of medical history to assess before alcohol abuse and stabilization or improvement in cognitive functioning following institutionalization in conjunction with no other identifiable cause of dementia. ARD comprised 24% of this population compared with DAT (35%), vascular dementia (19%), and other causes (22%). The ARD group was, on average, 10 years younger than the other groups. It had nearly twice the average length of institutionalization and had milder cognitive impairment on both clinical ratings and neuropsychological tests. A diagnosis of ARD was present in the medical records for only 25% of patients in this group. These findings suggest that ARD may be more common than previously suspected in the distribution of dementias in long‐term care facilities.
1994 Draft DSM‐IV Criteria for Alcohol Use Disorders: Comparison to DSM‐III‐R and Implications
Authors: Hasin Deborah , Grant Bridget
Published: April 2006

In 1994, DSM‐IV will be published, with new criteria for alcohol abuse and dependence. Implications of the changes in criteria for alcohol use disorders were investigated by comparing the diagnoses made by the DSM‐IV criteria and DSM‐III‐R criteria. The study was conducted in a sample of 424 patients in an inpatient alcohol rehabilitation unit in the New York metropolitan area. DSM‐III‐R and DSM‐IV criteria showed similar results and high agreement for any alcohol use disorder (abuse and dependence combined). Alcohol dependence was also consistently diagnosed with DSM‐III‐R and DSM‐IV criteria. Agreement between DSM‐III‐R and DSM‐IV abuse diagnoses was very low. Compared with DSM‐III‐R, DSM‐IV classified over three times as many patients as alcohol abusers, although those with alcohol dependence still overwhelmingly dominated the sample. With some fluctuations, the results were stable over Black, Hispanic, and White subgroups of patients. The direction of the findings was consistent with results from a national general population survey in that the prevalence of alcohol abuse increased in both studies. However, the clinical results alone would not have suggested the marked changes in relative prevalence of abuse and dependence that occurred in the general population when DSM‐IV criteria were used in place of DSM‐III‐R. Research on diagnostic criteria limited to patient samples omits important information on the implications of changing aspects of the diagnostic criteria. The need for a coherent theory of alcohol abuse is highlighted.
Effects of Ethanol on Human Natural Killer Cell Activity: In Vitro and Acute, Low‐Dose In Vivo Studies
Authors: Ochshorn‐Adelson Miriam , Bodner Gershon , Toraker Per , Albeck Henrik , Ho Ann , Kreek Mary Jeanne
Published: April 2006

Chronic use of ethanol may cause a variety of immunological abnormalities in humans. In this study, we have determined the effects of an acute, low dose of ethanol (0.5 g/kg), administered either intravenously or orally, to normal, nonalcoholic male volunteers, on natural killer cell (NK) activity. We have also examined the effects of a 4‐hr incubation with ethanol, in concentrations ranging from 0 to 320 mg/dl, on human NK activity in vitro. NK activity was measured by the 51Cr release assay technique in all of these studies, using peripheral blood mononuclear cells prepared from blood obtained from healthy, nonalcoholic volunteers. Eight subjects received ethanol in vivo; cells from nine subjects were used for the in vitro studies. Blood ethanol concentrations were determined at multiple time points before and after ethanol administration for the in vivo studies; for the in vitro studies, ethanol concentrations were measured from each assay sample both before and after the incubation period. Gas chromatography was used for determinations of both blood alcohol and medium ethanol concentrations. Results of the in vivo studies showed that a single dose of ethanol (0.5 g/kg), administered either intravenously (with resultant peak blood levels transiently up to 89 mg/dl) or orally (with resultant peak blood levels transiently up to 40 mg/dl at the time of the NK assay), did not alter NK activity. However, results of the in vitro studies showed a significant dose‐dependent decrease (p < 0.001) in NK activity when ethanol exposure was sustained for 4 hr at concentrations of 80 mg/ dl and above. We conclude that one of the possible causes for a higher incidence of certain viral infections and malignant tumors among chronic alcoholics may be due, in part, to this observed direct effect of ethanol on NK cytotoxicity.