bluuebunny/crossref_metadata_2025 huggingface dataset:
“Binge” Versus Steady Drinking: Effects on the Liver in the Ovariectomized Rat
Authors: Gavaler Judith S. , Smith William I. , Van Thiel David H. , Rosenblum Elaine R. , Deal Stephen R. , Allan Marjorie J.
Published: April 2006

Substantial interest exists as to whether or not differential effects in liver injury based on the pattern of alcohol intake exist; and further, if they do, are they simply a function of the total dose over time. A rat model in which ethanol (ETOH) at doses of 12%, 24%, or 36% of total calories was isocalorically administered for 4 months either daily or intermittently (4 days of ETOH, 3 days of control diet, repeatedly) was used to assess this question. There were significant differences in the two feeding pattern groups between 38% ETOH rats for the liver weight corrected for body weight, the fat infiltration score, the total amount of ETOH consumed/mg body weight, the proportion of animals with a fat infiltration score >2, and albumin levels. There was a significant difference between 12% ETOH rats for the liver weight corrected for body weight. Of particular relevance is the comparison to be made between Daily 12% ETOH and Binge 24% ETOH animals, because these two groups consumed an identical total amount of ETOH/mg body weight (Daily: 445 ± 5 vs. Binge: 468 ± 15) and thus these animals are comparable in terms of ETOH dose over time but different in terms of the pattern of ETOH exposure. There were no differences in the liver/body ratio (Daily: 235 ± 6 vs. Binge: 232 ± 4), fat infiltration score (Daily: 2.5 ± 4 vs. Binge: 2.4 ± 0.3), the proportion of animals with a fat infiltration score >2 (Daily: 5/10 vs. Binge: 4/8), or albumin levels (Daily: 3.0 ± 0.1 vs. Binge: 3.1 ± 0.1). These data, in addition to the findings of greater injury in both the 12% and 36% ETOH daily‐fed animals, suggest that it is the cumulative amount, not the pattern of ETOH intake, that determines the liver injury.
Ethanol Increases Apoptotic Cell Death of Thymocytes in Vitro
Authors: Ewald Sandra J. , Shao Hui
Published: April 2006

Exposure of animals to ethanol causes thymic atrophy in adults and fetuses. Whether direct effects of ethanol contribute to thymic atrophy or whether indirect effects are entirely responsible is at present unknown. In the normal animal, large numbers of thymocytes undergo a physiological form of cell death referred to as “apoptosis.” To determine if ethanol affects the process of apoptosis, studies were undertaken in which mouse thymocytes were cultured overnight in the presence or absence of ethanol. Apoptotic cell death was analyzed by flow cytometric quantitation of apoptotic nuclei, by fluorometric measurement of DNA fragments, and by gel electrophoretic analysis of DNA fragments. Ethanol in concentrations of 0.2% to 0.8% produced significantly higher levels of apoptosis than were seen in control cultures. The DNA fragmentation was characterized as apoptotic on the basis of inhibition by aurintricarboxylic acid (an inhibitor of nucleases) and by the presence of characteristic oligonucleosomal‐sized fragments of DNA. The effect of ethanol on apoptosis was additive to that induced by immobilized anti‐CD3 monoclonal antibody. CD4+CD8+ cells underwent apoptosis as indicated by reduction in CD4 and CD8 surface antigen expression. An inhibitor of protein kinases (H‐7) reduced the DNA degradation induced by ethanol and by anti‐CD3. These results suggest that direct effects of ethanol contribute to thymic atrophy in alcohol‐consuming animals.
The Influence of Age on Blood Alcohol Levels and Ethanol‐Associated Immunosuppression in a Murine Model of Ethanol Consumption
Authors: Domiati‐Saad Rana , Jerrells Thomas R.
Published: April 2006

Several study findings indicate that with ethanol ingestion a number of changes occur in the immune system. We studied the effects of ethanol consumption on mice at various ages. We used a murine model in which young (age 6‐8 weeks), middle‐aged (age 12 months), and old (age 24 months) male C57B1/6 mice were pair‐fed either a Leiber‐DeCarli liquid diet containing 7% (v/v) ethanol or an isocaloric control diet. Consumption of ethanol diet for 8 days resulted in high blood alcohol levels in young and old mice; low levels were observed in middle‐aged mice. Middle‐aged mice consumed more ethanol than did either young or old mice and had the lowest percent body weight loss of all three age groups. Proliferation of spleen lymphocytes to T‐cell stimuli (concanavalin A and alloantigens) in both young and old mice fed ethanol was diminished. T‐cell function was unchanged in middle‐aged mice consuming an ethanol diet when compared with that observed in age‐matched mice pairfed control diet. No effect of ethanol on proliferation to lipopolysaccharide was noted in any group. Proliferative response of T cells to soluble anti‐CD3 monoclonal antibody was also decreased in middleaged and old pair‐fed control mice when compared with young control mice. The proliferative response to soluble anti‐CD3 in all three age groups of mice fed ethanol, however, was not significantly affected by ethanol consumption. When platebound anti‐CD3 was used to stimulate purified T cells obtained from young and middleaged pair‐fed control and ethanol‐treated mice, the proliferative response associated with ethanol was diminished in young animals but not in middle‐aged animals. These results show that the immunosuppressive effects of ethanol on T‐cell function are similar in old and young mice; however, middle‐aged animals were affected less. An important finding of this study was the association between blood alcohol levels and the immunosuppression that resulted from ethanol feeding.
Alcohol‐Induced Inhibition of Alveolar Macrophage Oxidant Release in Vivo and in Vitro
Authors: Antony Veena B. , Godbey Steven W. , Hott Jeffery W. , Queener Sherry F.
Published: April 2006

Alcohol consumption is known to predispose the host to more frequent and severe bacterial infections, suggesting that alcohol compromises the normal immune function of the lung. The pulmonary alveolar macrophage is the resident host defense cell in the lung and forms the first line of defense against invading microorganisms. One of the mechanisms whereby alveolar macrophages kill bacteria is by releasing toxic oxygen radical species, such as superoxide anion and hydrogen peroxide. We hypothesized that chronic alcohol consumption caused alveolar macrophage dysfunction leading to inhibition of oxidant production when stimulated. Our data demonstrate that alveolar macrophages harvested from alcohol‐treated rats release significantly lower quantity (p < 0.05) of both superoxide anion and hydrogen peroxide when stimulated with several different types of stimuli including heat‐killed Staphylococcus aureus, soluble immune complexes or phorbol myristate acetate. Pair‐fed control rats who received isocaloric quantities of maltose dextrin in their diet to compensate for the alcohol were able to produce oxidants in equal quantities when stimulated, to rats who were fed a normal diet. Similar results were noted in vitro experiments when alveolar macrophages harvested from normal rats were incubated in vitro in alcohol‐containing media and then stimulated with the aforementioned stimuli. Alveolar macrophages, which had been incubated in alcohol for 4 hr, showed significant decreases in their ability to produce superoxide anion. This defect was noticeable for a period up to 8 hr following removal of alveolar macrophages from the alcohol‐containing media. The inability of alveolar macrophages to release oxidants may cause a significant break in their bacteriocidal capacity leading to the establishment of overt pulmonary parenchymal infection.
Decreased Synapse‐to‐Neuron Ratio in Rat Locus Ceruleus Following Chronic Ethanol Feeding
Authors: Kjellström Christer , Almström Susanne , Conradi Nils
Published: April 2006

Effects of chronic ethanol exposure on the synapse‐to‐neuron ratio of rat locus ceruleus were investigated. Male Sprague‐Dawley rats were given an ethanol‐containing liquid diet for 4 months starting at an age of 5 weeks. Littermates, given isocaloric amounts of an ethanol‐free diet, served as control. The animals were perfusion fixed using a mixture of glutaraldehyde and paraformaldehyde. Synapse‐to‐neuron ratio was estimated by the double disector method and calculated from (Ns/A) x (Nsec‐1) / (Nn/A) where Ns/A is the number of synapses per unit area estimated in a disector with a height of one section and Nsec‐1 is height of the disector, i.e., the number of sections, used for estimating the number of neurons per area (Ns/A). The mean estimated synapse‐to‐neuron ratio was 2046 ± 544 (SD) in ethanol‐fed rats and 4291 ± 1171 (SD) in control rats. The difference is statistically significant (p < 0.05). The finding may be of relevance for understanding the development of abuse, tolerance, drug dependence, and abstinence reactions.
The Kindling Model of Alcohol Dependence: Similar Persistent Reduction in Seizure Threshold to Pentylenetetrazol in Animals Receiving Chronic Ethanol or Chronic Pentylenetetrazol
Authors: Kokka Norio , Sapp Douglas W. , Taylor Anna M. , Olsen Richard W.
Published: April 2006

Rats on a chronic intermittent ethanol (CIE) regimen showed a persistent reduction in seizure threshold to the convulsant drug pentylenetetrazol (PTZ). CIE rats were given ethanol by intubation on an alternate day schedule and tested at selected intervals for seizure threshold with PTZ. A significant reduction in seizure threshold, a sign of withdrawal, was observed 20 hr after the first dose. The severity of withdrawal intensified on repetition of the ethanol administration and depression‐hyperexcitability cycle, with the seizure threshold reaching a maximum decrease after 12 doses and remaining reduced up to 60 doses. The reduction in seizure threshold persisted for at least 40 days of no alcohol following the 60th dose. The long‐lasting decrease in seizure threshold following CIE treatment resembled the “kindling” phenomenon produced by chronic administration of PTZ (25 mg/kg, 3 times/week). The CIE rats developed, in addition, a tolerance to the anticonvulsant action of ethanol, which occurred well after the decrease in PTZ seizure threshold, and a tolerance to the hypothermic effect of ethanol, which developed rapidly. PTZ kindled rats that had never been exposed to ethanol also exhibited tolerance to the hypothermic effect of ethanol. We propose that kindling contributes to the mechanism of the development of dependence on central nervous system depressants like benzodiazepines, barbiturates, and alcohol, drugs that act on the γ‐aminobutyric acid‐A receptor chloride ion channel complex. Repeated episodes of depression and withdrawal hyperexcitability are postulated to produce kindling during the repeated withdrawal episodes. In chronic ethanol abuse, the withdrawal stress/hyperexcitability would be repeated many times and lead to the development of dependence as measured by the persistent increase in withdrawal severity, manifested as heightened sensitivity to seizures (kindling). The long‐lasting decreases in seizure threshold following both chronic pentylenetetrazol and chronic intermittent ethanol suggest the possibility that some common mechanisms, such as the involvement of γ‐aminobutyric acid‐A receptors, may underlie the two kindling phenomena.
Effect of Ethanol on Kupffer Cell Function
Authors: Basista Michael H. , Gavaler Judith , Stieffenhofer Anne , Love Kristin , Rosenblum Elaine , Dindzans Vincents J.
Published: April 2006

Kupffer cells are resident macrophages in the liver and are important in both local and systemic immune responses. We evaluated the ability of Kupffer cells in vitro to respond to immune stimulation after both acute exposure to ethanol and after long‐term ethanol consumption of ethanol. Triplets of female Wistar rats were fed a liquid diet containing 0, 12, or 36% ethanol isocalorically for 112 days. When killed, the Kupffer cells were isolated by collagenase perfusion and adhered to plastic 24‐well plates. They were then stimulated with 10 μg/ml lipopolysaccharide for 4.5 hr. Synthesis of procoagulant activity (PCA) and tumor necrosis factor (TNF), expressions of macrophage response to immune stimuli, were measured by a one‐step clotting assay and L929 cytotoxicity assay, respectively. Within each of the 10 triplets, PCA and TNF levels were normalized and expressed as a percentage of the zero ethanol isocaloric control rat. The high ethanol group had significantly lower baseline and stimulated PCA and TNF levels than the low ethanol group. For evaluation of the effect of acute exposure to ethanol, Kupffer cells were stimulated with lipopolysaccharide and varying concentrations (0–400 mg/dl) of ethanol. Cells were incubated for 4.5 hr and assayed for PCA and TNF activity. There was dose‐dependent inhibition of PCA and TNF, with increasing concentrations of ethanol. These results indicate that whereas exposure to high levels of ethanol depresses Kupffer cell function, lower levels may be immunostimulatory.
Effects of Manipulating Food Availability on Ethanol Self‐Administration by P Rats in a Continuous Access Situation
Authors: Files Forrest J. , Andrews Christine M. , Lewis Roderic S. , Samson Herman H.
Published: April 2006

Male rats from the alcohol‐preferring (P) line were housed in operant chambers in which food, water, and ethanol (10% v/v) were available continuously 23 hr per day. Over a period of weeks, the fixed ratio (FR) requirement for food reinforcement was gradually increased from FR 1 to FR 64. The response requirements for water and ethanol remained constant throughout the experiment. As the FR requirement for food reinforcement increased, the total number of food‐reinforced responses increased significantly, whereas the total number of food pellets delivered per day and total calories per day decreased significantly. Conversely, ethanol intake (g/kg) and the percentage of total calories from ethanol increased significantly as the response requirement for food reinforcement increased. The increase in ethanol intake was accounted for largely by an increase in the number of ethanol drinking bouts per day rather than an increase in the number of dippers presented per bout. The results support the hypothesis that the manipulation of environmental variables, such as FR requirement for food reinforcement, can influence the ethanol self‐administration of P rats; an effect observed previously with nonselected Long‐Evans rats.
Maternal Ethanol Ingestion Effects on Fetal Rat Brain Vitamin A as a Model for Fetal Alcohol Syndrome
Authors: Grummer Mary A. , Langhough Rebecca E. , Zachman Richard D.
Published: April 2006

Fetal embryo, head, and brain tissue from different gestational age were analyzed for retinol content, nuclear retinoic acid receptor and cytosolic retinoic acid binding protein levels after maternal ethanol ingestion and compared with fetal levels in control diet pregnancies. Retinol levels in fetal embryo and brain of ethanol‐ingesting pregnancies were 2‐ to 3‐fold higher than fetal embryo and brain of ethanol‐ingesting pregnancies were 2‐to 3‐fold higher than fetal embryo and retinol of control pregnancies. Nuclear retinoic acid receptor was lower in 10‐day embryo of ethanol pregnancies and apparently unaffected in fetal head and brain by maternal ethanol consumption at other days of gestation. In fetal head there was a significant overall ethanol effect on cytosolic retinoic acid binding protein, with increased levelsin fetal tissue from ethanol‐consuming pregnancies. These observations of altered embryo, fetal head, and fetal brain retinol and receptor protein levels support the hypothesis of a possible role of vitamin A in fetal alcohol syndrome.
Changes in Microsomal Phospholipases and Arachidonic Acid in Experimental Alcoholic Liver Injury: Relationship to Cytochrome P‐450 2E1 Induction and Conjugated Diene Formation
Authors: Nanji Amin A. , Zhao Shuping , Lamb Robert G. , Sadrzadeh S. M. Hossein , Dannenberg Andrew J. , Waxman David J.
Published: April 2006

We evaluated the role of changes in microsomal phospholipases (A and C) and arachidonic acid in the intragastric rat feeding model. The experimental animals (male Wistar rats), divided into 4–5 rats/group, were fed the following diets: corn oil and ethanol and corn oil plus dextrose. One set of groups was killed after 2 weeks of feeding, and the second set was killed after 1 month. For each animal, microsomal analysis of cytochrome P‐450 2E1 (CYP 2E1) and fatty acids was done. Fourteen animals had analyses of phospholipase C (PLC) and phospholipase A (PLA), and 10 animals had measurements of conjugated dienes. A significant correlation was obtained between the level of CYP 2E1 and the decrease in arachidonic acid (AA) from baseline levels (r= 0.69, p < 0.01). The decrease in AA also correlated with the increase in conjugated dienes (r= 0.70, p < 0.05). PLA and PLC activities were both significantly increased in the corn oil and ethanol groups. The activity of PLC correlated with the decline in AA (r= 0.69, p < 0.01). The correlations noted between the decrease in microsomal AA and CYP 2E1 induction and conjugated diene formation suggest that these processes may be interlinked especially in regard to generation of lipid peroxides that may play a role in alcoholic liver injury.
The Effects of the Timing of Ethanol Exposure during the Brain Growth Spurt on the Number of Cerebellar Purkinje and Granule Cell Nuclear Profiles
Authors: Hamre Kristin M. , West James R.
Published: April 2006

Ethanol exposure during development is particularly deleterious to cerebellar Purkinje cells and granule cells, but the mechanism(s) underlying this sensitivity and the variables which affect it remain unknown. One important variable that has not been fully investigated, is the timing of the ethanol exposure. Ethanol exposure during the brain growth spurt causes a differential loss of Purkinje cells across the 10 lobules of the vermal cerebellum. However, whether or not changing the timing of the ethanol exposure during the brain growth spurt alters the extent and location of the loss of Purkinje cells within the cerebellar vermis has not been investigated. Moreover, the loss of cerebellar granule cells has been shown to parallel the loss of Purkinje cells, leading to the conclusion that the loss of granule Cells occurred as a function of the loss of their targets, the Purkinje cells. The purpose of this study was to address both issues. Male rat pups were exposed to ethanol, via an artificial‐rearing method, during one of the following 2‐day time periods: postnatal days (PD) 4–5, 5–6, 6–7, 7–8, 8–9, 9–10, or 12–13. Gastrostomy control (GC) and suckle control (SC) groups also were included. All pups were sacrificed on PD21. The number of Purkinje cell nuclear profiles from three vermal sections were counted in all groups, while the number of granule cell nuclear profiles in the ten lobules was estimated from pups in selected groups. No loss of Purkinje cells was observed in pups exposed to ethanol on PD7‐8 or at any of the later exposure times. Additionally, among the three exposure groups in which significant Purkinje cell loss was observed (PD4‐5, PD5‐6 and PD6‐7), seven lobules exhibited significant differences particularly between the PD4‐5 and PD6‐7 groups. The group with the greatest loss of Purkinje cells (PD4‐5) also was the group with the greatest loss of granule cells. A significant loss of granule cells did not occur without a corresponding loss of Purkinje cells. The loss of both the Purkinje and granule cells was affected by the timing of the ethanol exposure, and that the extent and the location of Purkinje cell loss were extremely sensitive to the effects of the timing of the ethanol exposure.
Personality Characteristics of Sisters and Spouses of Male Alcoholics
Authors: Hill Shirley Y.
Published: April 2006

Sisters of alcoholics from high‐density multigenerational families were assessed to determine personality characteristics. Spousal similarity was evaluated in proband/spouse pairs and in spouse pairs from the parental generation, allowing for comparisons of selection versus contagion as explanations for this similarity.

Sisters were found to differ from control women with respect to Alienation and Social Closeness from the Multidimensional Personality Questionnaire, and Scale 6 (Paranoia) from the Minnesota Multiphasic Personality Inventory. Only spouses from the parental generation were similar on Alienation, suggesting that exposure over time (contagion) leads to greater similarity in parents from High‐Risk families. Modest correlations in spouse pairs from both generations suggest that assortative mating for Social Closeness occurs among the parents of these individuals from High‐Risk families, and further suggest that a diminished level of Social Closeness for sisters of alcoholics may be mediated in part by additive genetic variance. It is concluded that assortative mating for particular traits may contribute to increased risk for alcoholism. Also, failure to mate assortatively for other traits (e.g., Traditionalism, Harm Avoidance) may also contribute to increased rates in High‐Risk families.
Acute and Chronic Alcohol Tolerance in Humans: Effects of Dose and Consecutive Days of Exposure
Authors: Bennett Robert H. , Cherek Don R. , Spiga Ralph
Published: April 2006

Male social drinkers received doses of either 0.75 or 1.0 g/kg body weight of alcohol over 5 consecutive days. The beverage was divided into three equal drinks, and subjects performed an eye‐hand coordination motor task after each drink. The breath alcohol concentration (BAC) was assessed at each performance measurement period. Performance was also assessed when the BAC level on the descending limb of the BAC curve was similar to each of the three BAC measurements on the ascending curve. Each group developed chronic tolerance (comparing the daily postalcohol performance with the daily prealcohol performance) by the 4th day of exposure. The development of a degree of acute tolerance (assessed by comparing the performance on the ascending and descending limbs of the BAC curve) was not observed consistently in the 1.0 g/kg dose group, but was seen in more than half of the subjects in the 0.75 g/kg dose group by the 4th and 5th day of exposure.
Toward an Alcohol Treatment Entry Model: A Comparison of Problem Drinkers in the General Population and in Treatment
Authors: Weisner Constance
Published: April 2006

Building on a model used in the health services literature, this article examines differences among problem drinkers in treatment and in the general population to understand treatment utilization further. Discriminant function analysis showed significant differences between treated and untreated groups for men and women. For women, lifetime general treatment history, ethnicity, and employment were major contributors to the model; for men, the most important variables were social consequences, treatment history, and employment. For women, only the domain of individual predisposing variables provided a unique contribution to the model (p < 0.01). For men, the individual predisposing (p < 0.001), need (p < 0.001), and enabling (p < 0.01) domains did so. Findings indicate important differences in the factors that influence treatment entry for women and men.
Subtypes of Early Age Onset Alcoholism
Authors: Mezzich Ada , Tarter Ralph , Kirisci Levent , Clark Duncan , Buckstein Oscar , Martin Cynthia
Published: April 2006

Forty‐three adolescents qualifying for a DSM‐Ill‐R diagnosis of alcohol abuse/dependence were classified according to the internalizing‐externalizing behavior dimension. Two clusters were identified. The majority of subjects clustered into a group characterized by behavioral dyscontrol and hypophoria (history of suicide attempts) (cluster 2), whereas the other group was primarily featured by negative affect (cluster 1). Cluster 2 subjects demonstrated more severe alcohol and drug use‐related problems, behavioral disturbances, and general psychopathology; lower prevalence of depressive disorders; and less severe anxiety disorders. These results, implicating two variants of adolescent alcohol abuse/dependence, suggest the need to tailor differential treatments to adolescents with alcohol abuse/dependence based on personality characteristics and clinical presentation.
Atypical Liver Alcohol Dehydrogenase in the Spanish Population: Its Relation with the Development of Alcoholic Liver Disease
Authors: Vidal Francesc , Perez Jaume , Panisello Joima , Toda Roca , Gutierrez Cristina , Richart Cristobal
Published: April 2006

The presence of atypical liver alcohol dehydrogenase (ADH) was determined in samples of liver tissue from 222 alcoholic and nonalcoholic subjects to determine its prevalence in the Spanish population, and to evaluate the possible relationship between the presence of this isoenzyme and the development of alcoholism and alcoholic liver disease. Alcoholic patients were classified into the following groups: control subjects, with normal liver pathology (group 1), patients with noncirrhotic liver disease (group 2), and patients with cirrhosis of the liver (group 3). Nonalcoholic subjects were also divided, following the same criteria, into groups 4, 5, and 6, respectively.

The prevalence of atypical ADH in the population analyzed was 16.2%. Atypical ADH was present in 14.9% of alcoholics and in 17.4% of nonalcoholics (P=ns). There were no significant differences when the prevalence of atypical ADH of alcoholic and nonalcoholic patients with similar degrees of liver pathology was compared (group 1 vs. 4, group 2 vs. 5, and group 3 vs. 6). The prevalence of atypical ADH was also similar in cirrhotic patients with respect to those of noncirrhotic liver disease and control patients, either in alcoholic or nonalcoholic groups.

Our findings indicate that the prevalence of atypical ADH in the Spanish population is similar to that reported for other Caucasian groups. Moreover, the presence of atypical ADH does not play a role in the development of alcoholism nor in the development of alcoholic liver disease in the population analyzed.
Decline in Alcohol Use Among 7‐12th Grade Students in New York State, 1983‐1990
Authors: Barnes Grace M. , Welte John W. , Dintcheff Barbara A.
Published: April 2006

The prevalence and patterns of alcohol use and alcohol‐related problems were determined in two large representative samples of 7‐12th grade students in New York State in 1983 and 1990. Comparable sampling procedures and measures were used in both surveys. Logistic regression analyses showed that overall drinking, heavy drinking, and alcohol‐related problems decreased significantly for the population as a whole; furthermore, all subgroups according to age, gender, and racial/ethnic status showed significant declines in alcohol use and related problems over this time period. The social context of this change is discussed.
Effects of Ethanol on Cultured Fetal Astroglia
Authors: Lokhorst Denise K. , Druse Mary J.
Published: April 2006

This study investigated the effects of a 4‐day ethanol exposure on cultured rhombencephalic astroglia. The contents of astroglial protein and DNA, and astroglial uptake of serotonin (5‐HT) were determined. Fetal rhombencephalic astroglia were examined because of this laboratory's evidence that in utero ethanol exposure markedly impairs the development of serotonergic neurons, which are located in this fetal brain area, and because of the recently demonstrated importance of local support glia in neuronal development.

The results of these experiments demonstrated that protein was significantly reduced in astroglia cultured in ethanol at either 150 or 300 mg/dl. In addition, these astroglia exhibited decreased [3H]5‐HT uptake per well. However, no significant ethanol‐associated differences were detected when [3H]5‐HT uptake was expressed per mg protein rather than per well. In contrast to the effects of a 4‐day ethanol exposure, the acute ethanol exposure did not significantly alter astroglial uptake of [3H]5‐HT/well. In addition, the 4‐day exposure to 50 to 300 mg/dl of ethanol did not significantly alter astroglial DNA content.

In summary, it appears that a 4‐day exposure of cultured fetal rhombencephalic astroglia to 150 to 300 mg/dl of ethanol reduces astroglial protein content and astroglial 5‐HT uptake. A reduction in total astroglial proteins, potentially including those that act as essential growth factors, could contribute to some of the ethanolassociated alterations in central nervous system development.
Increased Natural Killer Cell Activity in a Model of Immunoglobulin A Nephropathy Secondary to Chronic Alcohol Consumption
Authors: Razani‐Boroujerdi Seddigheh , Tokuda Sei , Smith Suzanne Meleg
Published: April 2006

We investigated natural killer (NK) cell activity in an animal model of ethanol‐induced immunoglobulin A (IgA) nephropathy. Two groups, of 10 rats each, received a continuous intragastric infusion of liquid diet through a permanent cannula for 6 weeks. The alcoholic group was infused additionally with intragastric ethanol, representing from 32% to 40% of the caloric requirement. The group of control rats received an isocaloric diet supplemented with glucose instead of alcohol. IgA nephropathy was observed in all the alcoholic rats but in none of the controls. NK cell activity was investigated in the two groups by measuring the cytotoxicity of spleen cells using the chromium release method. NK cell activity was found to be significantly increased in the alcoholic rats. In view of the known modulation of IgA synthesis by NK cells, we suggest that increased NK cell activity may be a contributing factor to the high levels of circulating IgA seen in IgA nephropathy secondary to chronic alcohol consumption.
Age‐Related Differences in Sensitivity to Alcohol in the Rat
Authors: York James L. , Chan Arthur W. K.
Published: April 2006

Female F344 rats of three different ages (4, 13, and 25 months) were tested for sensitivity to the ataxic, hypothermic, and hypnotic effects of injected ethanol. Challenges with ethanol sufficient to produce similar blood alcohol concentrations (BACs) in all age groups at the time of testing were observed to produce greater ataxia in old rats (25 months > 13 months > 4 months). Old rats also were observed to recover the righting reflex at lower BACs than those present in young or middle age rats. BAC at a target rectal temperature of 36°C was observed to be lower in old than in young or middle‐age rats when measured as body temperature was falling after doses of 3.0 g/kg to old and 3.5 g/kg to young and middle rats. However, no differences among groups in BAC at target temperature (36°C) were observed as body temperature was recovering from peak hypothermia back up to 36°C. With the exception of the last observation cited, these findings appear to confirm and extend earlier reports of increased target tissue sensitivity to ethanol with advancing age in rodents.
Effects of In Utero Administration of Alcohol on Glutathione Levels in Brain and Liver
Authors: Reyes Edward , Ott Stephnine , Robinson Barbara
Published: April 2006

Previous studies in our laboratory have shown that the ontogenic development of γ‐glutamyltranspeptidase (γ‐GTP) activity is delayed by the in utero administration of alcohol. γ‐GTP is responsible for the degradation and recycling of glutathione (GSH) via the γ‐glutamyl cycle. In this study, we examined the effects of the in utero administration of alcohol on GSH levels in gestational age 21‐day‐old (g21) rats. Pregnant rats were placed on a liquid diet containing either 35% ethanol‐derived calories (35% EDC) or a pair‐fed (PF) diet or a lab chow (LC) diet starting on day 1 of gestation and maintained on their respective diets until gestational day 21. On gestational day 21, the pups were delivered by Cesarean section and brains and livers removed and prepared for analysis of GSH, γ‐GTP, or γ‐glutamylcysteine synthetase (γ‐GCSyn). GSH levels in brain and liver were found to be significantly lower in the offspring of the 35% EDC‐treated mothers than from the PF and LC controls. γ‐GTP activity was higher in brain and liver of the 35% EDC group than the PF group. γ‐GCSyn, the enzyme involved in the rate‐limiting step of GSH synthesis, was not affected in liver, but was found to be decreased in brain of the 35% EDC and PF groups when compared with the LC group. GSH is involved in many cellular reactions that appear to protect the cell from damage. The depletion of GSH by alcohol during development may make the developing fetus more susceptible to the toxic effects of alcohol or the free radicals generated by its metabolism.
Fetal Alcohol Exposure Attenuates Lipopolysaccharide‐Induced Fever in Rats
Authors: Yirmiya Raz , Pilati Michelle L. , Chiappelli Francesco , Taylor Anna N.
Published: April 2006

Exposure to alcohol in utero can lead to long‐lasting impairments of immune functions and to decreased resistance to infectious agents. We studied the effects of fetal alcohol exposure (FAE) in rats on the core body temperature response to an exogenous challenge of the immune system with lipopolysaccharide (LPS). We report that FAE rats show markedly decreased LPS‐induced fever [i.e., they require a higher dose than control rats to show any LPS‐induced hyperthermia (50 μg/kg vs. 10 μg/kg)], and even with the higher LPS dose they manifest a weaker hyperthermia, which declines faster than in control animals. These results suggest that FAE produces an impairment in the release of endogenous pyrogens and/or in the neural substrate for body temperature regulation. This impairment may account for at least some of the decreased resistance to infections observed in FAE animals and humans.
Concurrent Validation of Substance Abusers Self‐Reports Against Collateral Information: Percentage Agreement VS. k Vs. Yule's Y
Authors: Hoffmann Norman G. , Ninonuevo Fred G.
Published: April 2006

The ability for chemical users to give an accurate self‐report of (ubrbnce use vs. abstinence has been questioned. This study hatlgated its concurrent validity, against collateral ratings. The results indicated that validity of reports of chemical use must be evaluated in the context of the validity of other types of information. Chemical use items were corroborated about as often as such nonchemical use items as reports of emergency room visits, arrests, md hospitalizations, thus arguing against the presence of a specific denlal syndrome or overarching tendency toward self‐misrepresenletion. Relative concurrent validities seemed more a function of such factors as item salience and specificity. No consistent trend in patient over‐or underreporting of chemical use was found. The choice of concurrent validation statistic is important and can influence interpretation of results. Current standards such as percentage agreement and K were seen as flawed; comparisons of results based on these two measures, as well as Yule's Y led to the conclusion that Yule's Y is the statistic of choice.
Antisocial Behavior, Family History, and Alcohol Dependence Symptoms
Authors: Harford Thomas C. , Parker Douglas A.
Published: April 2006

Drawing on data from the National Longitudinal Survey of young adults, this study examines the effects of antisocial behavior on alcohol dependence among young men and women in the United States. An analysis of the data from the study indicates that there are effects of antisocial behavior and that these effects cannot be attributed to a lower social class family of origin or to a positive family history of alcoholism. The analysis also indicates that the strongest effects are found among young adults with both antisocial behavior and a positive family history.
Sexuality of Alcoholic Postmenopausal Women:Effects of Duration of Alcohol Abstinence
Authors: Gavaler Judith S. , Rizzo Alberto , Rossaro Lorenzo , Van Thiel David H. , Brezza Ennio , Deal Stephen R.
Published: April 2006

Little is known about the sexuality of alcoholic postmenopausal women, and even less is known about the influence of abstinence on self‐assessed measures of sexual function. We now report findings in 60 postmenopausal women to whom a standardized questionnaire was administered. The responses provided information related to not only perceptions of sexuality, but also sexual behavior and performance. Women were categorized as alcohol abstinent (AA) for >l year (long AA, n = 33) or el year (short AA, n = 27). There were no differences between the groups in age, age at menarche, age at menopause, or age at onset of heavy drinking and alcohol dependence. The mean response rate to 12 sexuality‐related questions was comparable in the long AA and short AA groups (83.8% and 85.6%, respectively), and reflected the prevalence of having a regular sexual partner (76% and 85%, respectively). There were statistical differences between the two groups with respect to sexual desire, arousability, and responsiveness during alcohol abstinence, but not during alcohol dependence. Further, there were significant differences with respect to measures of current sexuality:higher proportions of long AA women reported sex being important, as well as their sexual life and intercourse being satisfying. Taken together, these findings suggest that alcoholic postmenopausal women abstinent from alcohol for longer than 1 year report greater satisfaction with the sexual aspects of their lives than women abstinent for a shorter period of time.
Hypothalamic‐Pituitary‐Thyroid Axis in Chronic Alcoholism. II. Deiodinase Activities and Thyroid Hormone Concentrations in Brain and Peripheral Tissues of Rats Chronically Exposed to Ethanol
Authors: Baumgartner Andreas , Heyne Andrea , Campos‐Barros Angel , Köhler Ralf , Müller Frank , Meinhold Harald , Rommelspacher Hans , Wolffgramm Jochen
Published: April 2006

Thyroxine (T4), triiodothyronine (T3) concentrations, and the activities of the three deiodinase isoenzymes were measured in different brain regions and peripheral tissues of rats. According to an animal model of alcohol addiction, “behaviorally” dependent rats having lost control over their intake of ethanol were compared with alcohol‐naive controls and ethanol‐experienced, but “controlled” consumers. The two kinds of alcohol‐experienced rats were investigated either 24 hr or 3 months after ethanol withdrawal. The results of these four groups were compared with those of an ethanol‐naive control group.

During withdrawal, the activities of type II 5′‐deiodinase (which catalyzes deiodination of T4, and T3 in the CNS) in both the “behaviorally dependent” rats and the “controlled drinkers” were significantly lower than in the alcohol‐naive controls in the frontal cortex, parieto‐occipital cortex, hippocampus, and striatum, but not in the cerebellum or pituitary. Probably as a result, the tissue concentrations of T4 were higher in areas of the CNS in the groups exposed to alcohol. However, the T3 concentrations were normal. No relevant differences were seen between the activities of type III 5‐deiodinase (which catalyzes the further deiodination of T3) observed in these groups. Atter 3 months of abstinence, the type II 5′‐deiodinase activities had almost returned to nomal in both “controlled drinkers” and “behaviorally dependent” animals, whereas type III 5‐deiodinase activity was inhibited, possibly to maintain physiological concentrations of T3 during abstinence. Indeed, the tissue levels of T3 were normal in the areas of the CNS, and the T4 levels were still elevated. However, the liver concentrations of T3 and T4 were significantly lower in the “behaviorally dependent” animals than in the “controlled” drinkers after 3 months of abstinence, whereas no differences were found between the T4 and T3 concentrations in the areas of the CNS investigated in the two groups exposed to ethanol.

These results suggest that chronic administration of ethanol affects intracellular thyroid hormone metabolism in both rat CNS and liver in a highly complex manner. No direct evidence of ethanolinduced enhancement of tissue uptake or concentrations was obtained. However, taking into account the numerous similarities between the clinical picture of hyperthyroidism and the symptomatology of alcoholism, it may be hypothesized that ethanol may directly influence any step in the as yet unknown biochemical cascade of thyroid hormone function.
Hormone Levels and Personality Traits in Abusive and Suicidal Male Alcoholics
Authors: Bergman Bo , Brismar Bo
Published: April 2006

This study presents personality and biochemical correlates to abusive and suicidal behavior in 49 male alcoholics. Our hypothesis was that neuroendocrine and personality characteristics reflect a postulated regulatory mechanism that determines the direction of aggression either outward (abusive) or inward (suicidal). Eleven patients (22%) had physically abused someone on one occasion and 15 (31%) constituted a more violent subgroup with repeated instances of abuse. Thirteen (27%) had attempted suicide at least once. There was a significant positive correlation between the number of abusive and suicidal events (r=0.33). The violent subgroup with repeated episodes of physical abuse had elevated levels of serum testosterone and low levels of cortisol when compared with the rest of the sample. Aggressive, antisocial, and impulsive personality traits were common. Suicidal alcoholics did not differ from the rest regarding hormone levels, but exhibited high impulsivity and muscular tension on the personality test. It is suggested that the high impulsivity without aggressive traits makes them exhibit autoaggressive rather than abusive behavior. Both the abusive and suicidal alcoholics partly had a history typical of the type 2 alcoholic. We propose that these two categories constitute subgroups of the type 2 alcoholic determined by a combination of genetic predisposition to alcoholism, certain personality traits, and, with regard to the violent group, also hormone disturbances. We find it highly justified to identify and treat these subgroups because of their harmful acting‐out behavior.
Effects of MK 801 and Diazepam on the EEG of P and NP Rats
Authors: Robledo P. , Lumeng L. , Li T.‐K. , Ehlers C. L.
Published: April 2006

The selectively bred alcohol‐preferring (P) and alcohol‐nonpreferring (NP) rats have been shown to possess a number of behavioral and electrophysiological differences in response to alcohol. We sought to evaluate whether or not P and NP rats would respond differently to other sedative‐hypnotic drugs related to ethanol. EEG recordings were conducted following systemic administration of the NMDA receptor antagonist MK 801 (0.1 mg/kg, ip) and the GABA/benzodiazepine receptor complex agonist diazepam (1.5 mg/kg, ip). Nine P and nine NP rats were implanted with bipolar stainless steel electrodes in the frontal cortex, the dorsal hippocampus, the ventral thalamus, and the anterior amygdala. In the vehicle condition, P rats showed significantly greater power of the EEG in the slow frequencies as compared with NP rats in the frontal cortex. Furthermore, P rats were found to have lower peak θ frequency (6–8 Hz) than NP rats in the frontal cortex, the dorsal hippocampus, and the ventral thalamus. MK 801 produced a significantly greater increase in the mean power of the EEG in NP rats in the 8–16 Hz than in P rats, whereas diazepam was found to decrease θ peak frequency (6–8 Hz), but more so in NP rats that in P rats. These data suggest that, in addition to differential responsiveness to alcohol, P and NP rats also differ in response to drugs that modify GABA and glutamate neurotransmission.
Ethanol Has Direct Effects on Human Choriocarcinoma Cell Steroid Hormone Secretion
Authors: Wimalasena Jay
Published: April 2006

Clinical observations indicate that ethanol (EtOH) consumption has significant detrimental effects on pregnancy. However, there is a paucity of information on effects of EtOH on human placental function. We have used JEG choriocarcinoma cells that have many of the functional capabilities of syncytiotrophoblasts, as a model to study direct effects of EtOH on placental function. Between 20–100 mM EtOH decreased rate of cell growth by 25%, but no decrease in [35S]methionine incorporation into protein was noted. EtOH decreased in a dose‐dependent manner the secretion of progesterone (P4) in response to cAMP when added with cAMP or when cells were pretreated with EtOH for 2 days. But after 4 or 6 days of pretreatment with EtOH, the P4 response to cAMP was increased by EtOH. Furthermore, EtOH increased the stimulation of P4 secretion by Forskolin. The development of this response was dependent on the period of exposure to EtOH. EtOH also increased estradiol (E2) secretion by unstimulated JEG cells in a dose‐ and time‐dependent manner and increased cAMP stimulated E2 secretion >2‐fold following 4 days of pretreatment with EtOH. These results suggest that EtOH may directly alter hormone secretion by placental cells and such perturbations of endocrine function of the placenta may be responsible for some of the effects of EtOH on pregnancy.
Effect of Chronic Alcohol Consumption on the Morphology of the Oral Mucosa
Authors: Maier H. , Weidauer H. , Zöller J. , Seitz H. K. , Flentje M. , Mall G. , Born I. A.
Published: April 2006

Chronic alcohol consumption is a major risk factor for oral and pharyngeal cancer. Besides other mechanisms a toxic effect of ethanol and/or its metabolite acetaldehyde on the oral mucosa and resulting increased cell regeneration seem to play an important role in tumor promotion. In the present study the effect of chronic ethanol consumption on the morphology of the oral mucosa of 40 male wistar rats that had been fed nutritionally adequate liquid diets containing 36% of total calories either as ethanol or isocaloric carbohydrates for 6 months was investigated. Morphometric analysis showed that in the ethanol rats the size of the basal cell nuclei of the oral mucosa from the floor of the mouth, the edge of the tongue and the base of the tongue were significantly enlarged (p < 0.001). The size of the basal cell layer in these rats was increased, and the stratification of the cells was altered. The percentage of cells in the S‐phase of the cell cycle was significantly higher in the ethanol‐fed rats (p < 0.01). Mean epithelial thickness of the mucosa from the floor of the mouth was significantly reduced in the ethanol rats (p < 0.01). In conclusion, the reported findings indicate, that chronic ethanol consumption causes oral mucosal atrophy associated with hyper‐regeneration, which may result in an enhanced susceptibility of the mucosal epithelium toward chemical carcinogens.
Effect of Maternal Ethanol Consumption on in Vitro Tumor Necrosis Factor, Interleukin‐6 and Interleukin‐2 Production by Rat Milk and Blood Leukocytes
Authors: Na Hyung R. , Seelig Leonard L.
Published: April 2006

It has been shown that the transfer of immunity via lactation plays an important role in providing eariy protection to the neonate. Maternal ethanol consumption also results in a reduced transfer of immunity to their neonates against a Trichinella spiralis infection. Because of the known presence of cytokines in milk and their important role in inflammation, we tested the effects of maternal ethanol consumption on cytokine production by milk and blood cells from T. spiralis‐ infected rats. With T. spiralis antigen, Concanavalin A (Con A) or lipopolysaccharide stimulation, milk cells from both ethanol‐treated and pair‐fed groups were capable of producing tumor necrosis factor (TNF), interleukin (IL)‐6 and IL‐2. There were no differences between groups for TNF or IL‐6 production by milk cells. Milk cells from the ethanol group produced a significantly higher amount of IL‐2 upon Con A stimulation, as compared with that from the pair‐fed group (16 ± 4 units/106 cells vs. 4 ± 1 units/106 cells, p < 0.05). After stimulation with Con A, blood cells from the ethanol group produced significantly lower amounts of TNF (17 ± 15 units/106 cells) than that from the pair‐fed group (102 ± 64 units/106 cells, p < 0.05). The amount of TNF and IL‐6 produced by milk cells was significantly lower, as compared with that produced by blood cells. This study suggests that ethanol consumption has some modulatory effects on cytokine production by milk and blood cells.