bluuebunny/crossref_metadata_2025 huggingface dataset:
Altered Levels of Prothymosin Immunoreactive Peptide, a Growth‐Related Gene Product, During Liver Regeneration after Chronic Ethanol Feeding
Authors: Silverman Ann L. , Smith Mitchell R. , Sasaki Diane , Mutchnick Milton G. , Diehl Anna Mae
Published: April 2006

Liver regeneration is regulated by the orderly activation of growth‐related genes. Although ethanol impairs induction of liver regeneration by partial hepatectomy, we have not identified ethanol‐associated differences in the hepatic mRNA levels of several proto‐oncogenes, including c‐myc, which peaks 3–6 hr post‐partial hepatectomy. Prothymosin α, a gene encoding a ubiquitous nuclear protein, is activated by c‐myc in resting fibroblasts and has been implicated as a regulator of cell proliferation. Prothymosin a mRNA levels reportedly increase 12–32 hr post‐partial hepatectomy, several hours after c‐myc induction. We sought to determine if chronic ethanol intake alters the expected induction post‐partial hepatectomy of prothymosin α steady‐state mRNA expression and protein levels. Comparing rats chronically fed ethanol with pair‐fed controls, we found no significant differences in steady‐state levels of prothymosin α mRNA; however, we did see a delay in the increase of prothymosin immunoreactive peptide in rats chronically fed alcohol. This suggests that the inhibition in protein levels in ethanol fed rats is not due to lower steady‐state mRNA levels, but may occur post‐transcriptionally. Further data are needed to determine if this finding is important in the inhibition in cell growth following partial hepatectomy in rats chronically fed ethanol.
Ethanol‐Induced Increase in Catalase Activity in Reaggregation Cultures of Rat Brain Cells is Due to Increased Oligodendrocyte Differentiation
Authors: Aspberg Anders , Tottmar Olof
Published: April 2006

Recent studies have shown that ethanol exposure of reaggregation cultures of fetal rat brain cells causes an increased activity and amount of catalase, and also an increased activity of the oligodendrocyte marker enzyme 2′,3′‐cyclic nucleotide 3′‐phosphadiester‐ase (CNP). In the present study, reaggregation cultures were grown in the presence of 40 mM ethanol during 17 days, corresponding to a period in vivo from gestational day 17 to postnatal day 12. The activities of catalase, the peroxisomal marker enzyme acyl‐coenzyme A oxidase and CNP were increased in ethanol‐treated cultures. Immunofluorescence experiments confirmed that catalase mainly resided in oligodendrocytes. By immunoperoxidase staining for CNP followed by image analysis, it was observed that the proportion of CNP‐positive cells, as well as the intensity of staining, was increased in ethanol‐treated cultures. Thus, the previously reported increase in catalase protein and activity in ethanol‐treated cultures might be due to a stimulation, or earlier onset, of oligodendrocyte differentiation.
Acetaldehyde Exposure Causes Growth Inhibition in a Chinese Hamster Ovary Cell Line That Expresses Alcohol Dehydrogenase
Authors: Mapoles John E. , Iwahashi Mieko , Lucas Daniele , Zimmerman Barbara T. , Simon Francis R.
Published: April 2006

Chronic ethanol exposure causes many pathophysiological changes in cellular function due to ethanol itself and/or the effects of its metabolism (i.e., generation of acetaldehyde and redox equivalents). However, the role of each of these effects remains controversial. To address these questions, we have developed a cell line that expresses alcohol dehydrogenase. This cell line permits separate examination of the effects of ethanol and its metabolite acetaldehyde on cell function. An expression vector for the mouse liver alcohol dehydrogenase was constructed and transfected into Chinese hamster ovary cells. Cells expressing alcohol dehydrogenase were identified by screening with allyl alcohol, which is metabolized by alcohol dehydrogenase to the toxic aldehyde acrolein. A number of cell lines were identified that expressed alcohol dehydrogenase. A‐10 cells were selected for further study because of their high sensitivity to allyl alcohol, suggesting a high level of alcohol dehydrogenase expression. These cells expressed a mRNA that hybridizes with the alcohol dehydrogenase cDNA and had an alcohol dehydrogenase activity comparable to murine liver. When cultures of these cells were exposed to ethanol, acetaldehyde was detected in both the medium and cells. The acetaldehyde concentration in the medium remained constant for at least 1 week in culture and was a function of the added ethanol concentration. Chronic exposure of A‐10 cells to ethanol resulted in a dose‐dependent reduction in the number of cells that accumulated over 7 days. Ethanol‐treated cells remained viable, and growth inhibition was reversible. Growth inhibition was blocked by the alcohol dehydrogenase inhibitor 4‐methylpyrazole, suggesting that acetaldehyde and not ethanol was responsible for growth inhibition in these cells.
Alcohol and White Matter Development—A Review
Authors: Lancaster Francine E.
Published: April 2006

This is a review of the literature on the effects of alcohol on white matter development. For many years, human and animal studies have reported the vulnerability of developing white matter to the effects of alcohol. However, until recently, studies on alcohol and white matter were limited by existing technology. New technology documenting the presence of neurotransmitter receptors and ion channels on glial cells now provides a new focus for research on alcohol and white matter development. New research using new technology should enlarge our knowledge of the role of glial cells in brain damage associated with alcohol exposure during development.
A Correlational Study of Carbohydrate‐Deficient Transferrin Values and Alcohol Consumption among Hispanic College Students
Authors: Grange Linda La , Anton Raymond F. , Crow Hal , Garcia Susan
Published: April 2006

One hundred and forty‐eight U.S. college students from a small southwestern university were asked to provide or complete the following: the Michigan Alcoholism Screening Test (MAST), a structured alcohol‐use interview, and a 10‐ml blood sample to be assayed for carbohydrate‐deficient transferrin (CDT) levels and γ‐glutamyl‐transpeptidase (GGTP) activity. Using the data obtained in the interview, only 2 females and 5 males were identified as heavy drinkers. Conclusions regarding the efficacy of the biochemical markers are therefore limited. It was found that CDT levels were significantly and positively correlated with various measures of alcohol consumption among males. There was no similar association between CDT, or GGTP, and alcohol consumption within the female sample.
Injury and the Role of Alcohol: County‐Wide Emergency Room Data
Authors: Cherpitel Cheryl J.
Published: April 2006

The purpose of this study is to describe variables associated with injury in an emergency room (ER) sample that is representative of an entire U.S. county. A probability sample (n= 3717) of ER patients from the county hospital, 3 of the 0 community hospitals, and the three health maintenance organization hospitals in a single Northern California county were breathalyzed and interviewed at the time of the ER visit. Injured were most likely to consume only 1 or 2 drinks within el hr of injury occurrence. Twenty‐three percent reported feeling drunk at the time of the event, and of these, 45% felt the event would not have happened if they had not been drinking. Breathalyzer reading, feeling drunk at the time of the event, and quantity‐frequency (Q‐F) of usual drinking were found to be predictive of admission to the ER with an injury, whereas breathalyzer reading, Q‐F, and being injured in someone's home were predictive of reporting drinking prior to injury. Although feeling drunk at the time of the event and usual drinking patterns are predictive of injury occurrence, drinking prior to the event may not entail large quantities of alcohol consumed, but relatively small amounts consumed in close proximity to the injury event. These alcohol consumption variables may vary, however, depending on the type, cause, and severity of injury.
Substance Disorder Among 100 American Indian Versus 200 Other Patients
Authors: Westermeyer Joe , Neider John
Published: April 2006

The purpose of this study was to examine the demographic and clinical Characteristics among American Indian (Al) patients and other patients with Psychoactive Substance Use Disorders (PSUD). The study was conducted at a university‐based, alcohol‐dfug program in the Upper Midwest. One hundred Al patients presenting sequentially with PSUD were contrasted with 200 other patients (selected at random from 620 patients) presenting at the same clinical facility during the same period with PSUD. Data included demographic characteristics, current DSM‐Ill‐R PSUD diagnoses, previous treatment for PSUD, and family history of PSUD. Findings indicated several special aspects of PSUD among Al patients, which have implications for program planning and treatment evaluation.
Anticipated Biphasic Effects of Alcohol Vary with Risk for Alcoholism: A Preliminary Report
Authors: Earleywine Mitchell
Published: April 2006

Twenty‐five sons of alcoholic fathers and 114 sons of nonalcoholic fathers reported the stimulant and sedative effects they expected alcohol would produce on both the ascending and descending limbs of the blood alcohol curve. High‐risk subjects anticipated more stimulation on the ascending limb, and more sedation on the descending limb than low‐risk subjects. These results are comparable to some studies of subjective responses to alcohol in high‐ and low‐risk men, and to previous work on risk and anticipated effects. These expectancies may contribute to risk‐related differences in responses to alcohol, as well as the development of problem drinking.
A Comparison of the Alcohol Dependence Scale and Clinical Diagnosis of Alcohol Dependence in Male Medical Outpatients
Authors: Willenbring Mark L. , Bielinski John B.
Published: April 2006

The Alcohol Dependence Scale (ADS) is a brief self‐report instrument designed to assess the alcohol dependence syndrome. Although previous studies have reported its validity, it has only been studied in populations who were presenting for assessment or treatment of alcohol problems, and recent studies have shown lower mean scores than would be expected. To assess its utility in a primary medical setting, we retrospectively examined our experience in two groups of medical outpatients: an early intervention group and a group of medically ill alcoholics. We administered the ADS to 61 male veterans being referred to a special clinic for alcohol‐related medical problems. Subjects were also assessed for alcohol dependence by experienced clinicians using a DSM‐III‐R checklist. ADS scores overall were much lower than would be expected, especially in the medically ill alcoholics. When subjects were dichotomized into dependent or nondependent, there was poor agreement between the two methods. The correlation between the scores was significant, however, end lowering the cut‐point on the ADS from 13/14 to 213 improved agreement. Medically ill alcoholics who are not presenting for assessment or treatment of alcohol problems may either lack insight into their drinking habits or may be reluctant to disclose them. Although conclusions from this study are tentative until more formal studies are done, it may be most prudent to use other instruments, such as the Michigan Alcoholism Screening Test, in medical outpatients. If the ADS is used, lowering the cut‐score to 213 may reduce false negatives. Further research on the use of the ADS in different settings and with different populations is clearly needed.
Measurement of Alcohol Use and Misuse in a Cohort of Students Followed from Grade 6 Through Grade 12
Authors: Shope Jean T. , Copeland Laurel A. , Dielman T.E.
Published: April 2006

In following a cohort of students from grade 6 through grade 12 for the purpose of evaluating an Alcohol Misuse Prevention Study curriculum, a substudy of the measurement of alcohol use and misuse was conducted. The 6‐year follow‐up of young people over time afforded a good opportunity to assess the adequacy of the initially chosen measures to 1) provide data with statistically desirable properties, and 2) be sensitive to and representative of the wide range of alcohol use and misuse patterns among adolescents as they mature. Revised measures of alcohol use and misuse were developed from the data responding to the same questionnaire items that had been used throughout the study. The revised measures demonstrated good psychometric properties and may be useful in other studies.
Gender Differences in the Brain: Implications for the Study of Human Alcoholism
Authors: Lancaster Francine E.
Published: April 2006

Gender differences in alcohol intake and response to alcohol may be influenced by basic variations in the organization and modulation of male and female brains. Although a number of genetic, social, environmental, and metabolic factors have been proposed to explain the gender differences observed in risk for alcoholism, alcohol intake, and medical consequences of excessive alcohol intake, very little attention has been given to the role of gender differences in the brain regarding alcohol use. Recent evidence documents the influence of neurosteroids on neurotransmitter activity in the brain and the impact of alcohol on neurosteroid levels. Neurosteroids are found in different levels in males and females during development and throughout life, depending on factors such as age, stage of development, estrous and menstrual cycles, and stress. This study discusses the hypothesis that many of the gender differences observed concerning alcohol use and misuse are determined by gender differences in the brain, which in turn differentially influence the behavioral and neurochemical responses of males and females to alcohol.
Carbohydrate‐Deficient Transferrin and γ‐Glutamyltransferase as Markers of Heavy Alcohol Consumption: Gender Differences
Authors: Anton Raymond F. , Moak Darlene H.
Published: April 2006

Carbohydrate‐deficient transferrin (CDT) has been described as a more specific and sensitive marker of recent heavy alcohol consumption as compared with the current tests now available, such as γ‐glutamyltransferase (GGT). Most of the data generated from European populations have not compared the utility of CDT and GGT in the detection of heavy alcohol consumption as a function of gender. We examined the ability of both CDT and GGT to discriminate between 42 men and 18 women with heavy alcohol consumption (>60 g/day) admitted to an alcohol detoxification center and a group of controls matched for age, race, and gender. CDT was higher, but GGT lower, in control females compared with males. Both CDT and GGT were higher in patients of both genders. At specificities >90%, the sensitivity of CDT for detecting male alcohol abusers was 79% and for female alcohol abusers 44%. For GGT, the sensitivities were 65% and 44%, respectively. When both tests were used simuttaneously, the sensitivity for the detection of alcohol abusers increased to 95% for males and 72% for females. Receiver Operator Characteristic analysis tended to confirm the superiority of CDT over GGT in the detection of heavy alcohol consumption in males, but not in females. A positive relationship was found between serum iron levels and CDT in control females but in no other group.

The concordant findings of this American study with those in similar French and Finnish clinical populations, utilizing similar assay techniques, suggest that the measurement of CDT is clinically more useful than GGT in detecting recent heavy alcohol consumption in males. Because serum CDT and GGT levels appear to be independently associated with heavy alcohol consumption, their combined measurement should increase the sensitivity of detection of this condition.
Hormonal Derangements in Patients with Severe Alcohol Intoxication
Authors: Hirschl Michael M. , Derfler Kurt , Bieglmayer Christian , Roggla Hannelore , Zeiner Andrea , Seidler Dan , Laggner Anton N.
Published: April 2006

Controversial results of fluid and electrolyte derangements in patients with moderate alcohol intoxication have been described. However, no information is available about severe alcohol intoxication. We investigated differences of hormonal disorders between alcohol‐habituated and alcohol‐naive subjects with severe ethanol intoxication. The hormonal derangements and recommendations on therapy of these patients are discussed.

Thirty‐three patients [10 alcohol‐naive (group A) and 23 alcohol‐habituated (group 8) subjects] with severe alcohol intoxication (blood ethanol > 200 mg/dl) were selected for the study. Electrolytes and osmolarity of serum and urine, blood ethanol, vasopressin, renin, and aldosterone were determined on admission 2, 4, and 6 hr later. Fluid balance was calculated for each hour. All patients received isotonic saline solution according to urine production.

Group A: On admission, serum osmolarity was increased (308 mOsmol/kg). Concomitantly, vasopressin level was elevated on admission (9.12 pglml). Increased serum osmolarity was correlated with elevated vasopressin levels (r= 0.8211; p < 0.005). Serum electrolytes, renin, and aldosterone values were within normal ranges.

Group B: On admission, vasopressin level was significantly decreased (0.9 pg/ml), despite an elevated serum osmolarity (309 mOsmol/kg). Serum osmolarity remained high despite a sufficient fluid substitution. In addition, vasopressin level remained suppressed over the observation period. Aldosterone level was significantly increased on admission (319 ng/ml). Accordingly, serum sodium was increased from 142 to 148 mM/liter, and serum potassium was decreased from 3.9 to 3.4 mM/liter.

Response to hyperosmolality due to severe alcohol intoxication is different in alcohol‐naive and alcohol‐habituated subjects. In contrast to alcohol‐naive subjects, vasopressin secretion of alcohol‐habituated subjects was suppressed rather than elevated despite hyperosmolality. Additionally, in these patients, hyperaldosteronism was observed leading to hypernatremia and hypokalemia. Therefore, infusions containing sodium should be avoided in alcohol‐habituated patients.
Co‐Morbidity of Lifetime Psychiatric Disorder Among Male Alcoholic Patients
Authors: Penick Elizabeth C. , Powell Barbara J. , Nickel Elizabeth J. , Bingham Stephen F. , Riesenmy Kelly R. , Read Marsha R. , Campbell Jan
Published: April 2006

The lifetime co‐morbidity of major psychiatric disorders among male alcoholics was examined with the structured Psychiatric Diagnostic Interview (PDI), which was administered to 928 patients undergoing alcoholism treatment at six Veterans Administration Medical Centers. Thirty‐eight percent were positive for alcoholism only; 62% fulfilled inclusive lifetime diagnostic criteria for at least one other additional psychiatric syndrome. Thirty percent satisfied criteria for one additional syndrome; 16% for two additional syndromes; 12% for three; and 4% for four or more disorders in addition to alcoholism. Depression and antisocial personality were the most frequently identified co‐occurring syndromes (36% and 24%, respectively) followed by drug abuse and mania (17% each). The additional psychiatric syndromes in this sample were clearly not randomly distributed; instead, certain disorders tended to cluster together such as: drug abuse and antisocial personality; mania and depression; depression and anxiety disorder; and schizophrenia and affective disorder. Implications for classification and treatment are discussed.
Helicobacter Infection and Gastric Ethanol Metabolism
Authors: Salmela Katja S. , Salaspuro Mikko , Gentry R. Thomas , Methuen Taina , Höök‐Nikanne Johanna , Kosunen Timo U. , Roine Risto P.
Published: April 2006

The organism frequently colonizing the stomach of patients suffering from chronic active gastritis and peptic ulcer disease–Helicobacter pylori–possesses marked alcohol dehydrogenase (ADH) activity. Consequently, Helicobacter infection may contribute to the capacity of the stomach to metabolize ethanol and lead to increased acetaldehyde production. To study this hypothesis, we first determined ADH activity in a variety of H. pylori strains originally isolated from human gastric mucosal biopsies. ADH activity was also measured in endoscopic gastric mucosal specimens obtained from H. pylori‐positive and ‐negative patients. Furthermore, we used a mouse model of Helicobacter infection to determine whether infected animals exhibit more gastric ethanol metabolism than noninfected controls.

Most of the 32 H. pylori strains studied possessed clear ADH activity and produced acetaldehyde. In humans, gastric ADH activity of corpus mucosa did not differ between H. pylori‐positive and ‐negative subjects, whereas in antral biopsies ADH activity was significantly lower in infected patients. In mice, gastric ADH activity was similar or even lower in infected animals than in controls, depending on the duration of infection, despite the fact that the infectious agent used–Helicobacter felis–showed ADH activity in vitro. In accordance with this, Helicobacter infection tended to decrease rather than increase gastric ethanol metabolism in mice. In humans, it remains to be established whether the observed decrease in antral ADH activity associated with H. pylori infection can lead to reduced gastric first‐pass metabolism of ethanol.
Neurochemical Correlates of Sympathetic Activation during Severe Alcohol Withdrawal
Authors: Hawley Rollin J. , Nemeroff Charles B. , Bissette Garth , Guidotti Alessandro , Rawlings Robert , Linnoila Markku
Published: April 2006

Cerebrospinal fluid (CSF) was obtained from 17 patients during acute alcohol withdrawal. Eight of these 17 patients had a second lumbar puncture a mean of 11.9 ± 8.1 (sd) days later, when the clinical signs of alcohol withdrawal had subsided. CSF 3‐methoxy‐4‐hydroxyphen‐ylglycol concentrations declined significantly (p < 0.05) during the course of alcohol withdrawal from 52.0 ± 22.1 (sd) to 39.6 ± 12.6 pM/ml. In early withdrawal, there was a significant positive correlation between CSF norepinephrine (NE) and corticotropin releasing hormone (CRH) concentrations (r= 0.95, p <0.001). Both NE and CRH concentrations correlated positively with diastolic blood pressure (r= 0.88, p < 0.001 and r= 0.62, p < 0.05, respectively). In all samples, CSF 5‐hydroxyindole acetic acid concentrations correlated positively with CSF‐homovanillic acid concentrations (r= 0.83, p < 0.001). These findings indicate significant perturbations of the noradrenergic neuronal system and a change in CRH‐NE interactions during acute alcohol withdrawal.
Elderly First Time Admitted Alcoholics: A Descriptive Study on Gender Differences in a Clinical Population
Authors: Österling Agneta , Berglund Mats
Published: April 2006

All patients ≥60 years of age who were first‐time admitted to the Department of Alcohol Diseases in Malmö during 1988–1992 were investigated, a total of 218 men and 64 women. Several clinical variables were assessed addressing gender differences. The sex ratio (female:male) in this elderly population was compared with the corresponding ratio of one decade previously (1978‐1982). The main findings were that similarities were more common than dissimilarities, except age of onset problem drinking that occurred significantly later in the female patients (p < 0.05). Sex ratios indicated a significant convergence of female patients to that of males during 1988–1992, compared with one decade earlier (1:3.4 and 1:7.8, respectively; p < 0.01). The former ratio resembled the one found in the younger age groups. Conceivable explanations of the convergence are discussed herein.
Longitudinal Observations of Monoamine Oxidase B in Alcoholics: Differentiation of Marker Characteristics
Authors: Rommelspacher Hans , May Torsten , Dufeu Peter , Schmidt Lutz G.
Published: April 2006

The marker characteristics of monoamine oxidase B (MAO B) in human platelets were investigated in a clinical study of 59 alcoholics (diagnosed according to the criteria of ICD‐10) observed over a period of 6 months. Demographic and family history were obtained by a structured interview, including the substance abuse section of CIDI (Composite International Diagnostic Interview). The patient's personality was assessed by Cloninger's Tridimensional Personality Questionnaire (TPQ). Blood samples were first drawn during chronic intoxication (day of admission to the hospital for detoxication), after short‐term abstinence (8 days later), medium‐term (3 months later), and long‐term abstinence (6 months later).

A group of 22 matched healthy nonalcoholics served as controls studied under sober conditions and during acute intoxication (4 hr after ingestion of 1 g ethanol/kg body weight). All platelet samples were investigated with 6 kynuramine concentrations as substrate (fluorometric assay) in the absence and presence of 200 itim ethanol (ETOH) in vitro.

MAO B activity was significantly reduced in alcoholics during chronic intoxication (Vmax: 2.70 ± 0.15 nmol/min/mg protein) compared with sober (Vmax: 3.25 ± 0.23 nmol/min/mg protein) and acutely intoxicated controls that turned to normal during abstinence. However, MAO B activity obtained during medium‐ and long‐term abstinence was significantly lowered in patients with high novelty‐seeking and impulsiveness scores in the TPQ, a history of suicide attempts, or an alcoholic mother. The affinity of MAO B (Km values) was unchanged in alcoholics at any time investigated. Addition of ETOH in vitro reduced the affinity. This effect was less pronounced when the blood had been obtained during chronic intoxication and after short‐term abstinence, suggesting tolerance toward ETOH.

It is demonstrated that reduced MAO B values may serve as state and trait markers of alcoholism and that they can be disentangled in a longitudinally designed study.
Fitting a Two‐Parameter Logistic Item Response Model to Clarify the Psychometric Properties of the Drug Use Screening Inventory for Adolescent Alcohol and Drug Abusers
Authors: Kirisci Levent , Tarter Ralph E. , Hsu Tse‐Chi
Published: April 2006

The suitability of fitting a two‐parameter logistic item response model to the Drug Use Screening Inventory (DUSI) was assessed. In a sample of 846 adolescents, each of the 10 domains was found to be unidimensional. Invariance of the item parameters across different groups was also observed. The reliability coefficient, based on item response theory, was found to be superior. The results of these analyses indicate that the DUSI has sound psychometric properties.
Gender Differences in Patterns of Alcohol Consumption in Spain
Authors: Alvarez F. Javier , del Río M. Carmen
Published: April 2006

Gender differences in alcohol consumption components, hazardous alcohol consumption, and drinking patterns among Spaniards were analyzed. The study was conducted in the fall of 1992 on 2,500 individuals, aged 14–70 years, who lived in the region of Castile and Leon (Spain). Males drank more frequently (with a high intake of alcohol), were more likely to be hazardous drinkers, and started drinking earlier than females. Both sexes drank beer in a similar way, but not wine and spirits. Males and females gave similar reasons for drinking and showed similar patterns of “family” drinking, although sex differences in other patterns of alcohol consumption were found. The relevance of results was discussed.
Chronic Alcohol Ingestion: Nerve Growth Factor Gene Expression and Neurotrophic Activity in Rat Hippocampus
Authors: Baek Jae‐Kyeong , Heaton Marieta B. , Walker Don W.
Published: April 2006

Chronic ethanol treatment induces memory deficits accompanied by anatomical and biochemical changes in basal forebrain and hippocampus. Cholinergic neurons in the septohippocampal pathway are especially vulnerable to alcohol neurotoxicity. Several studies showed that an adequate supply of neurotrophins, such as Nerve Growth Factor and Brain‐Derived Neurotrophic Factor, is required for the normal function and survival of cholinergic neurons in basal forebrain and medial septal nuclei. We tested the hypothesis that chronic alcohol ingestion may alter the gene expression level of Nerve Growth Factor in hippocampus, the major source of neurotrophins to the cholinergic neurons in the septohippocampal pathway. We measured Nerve Growth Factor protein and Nerve Growth Factor mRNA contents using sensitive two‐site ELISA and Northern analysis. We also tested the endogenous neurotrophic activity, including and excluding Nerve Growth Factor, contained in 5%, 2%, 1%, 0.5% and 0.1% (w/v) hippocampal tissue extracts on sympathetic ganglia neurons. Twenty‐eight weeks of chronic ethanol treatment did not reduce Nerve Growth Factor protein, Nerve Growth Factor mRNA, or total neurotrophic activity contained in the rat hippocampus when measured on sympathetic ganglia neurons.
Influence of Thiamine on the Behavioral Sensitivity to Ethanol
Authors: Gauvin D. V. , Briscoe R. J. , Goulden K. L. , Wojnicki F. H. E. , Russin R. , Martin P. R. , Holloway F. A.
Published: April 2006

Changes in sensitivity to ethanol's rate‐decreasing effects on operant performance were examined in control rats and cohorts that received diet‐induced or diet + pyrithiamine‐induced thiamine deficiency. Seven groups of male Sprague‐Dawley rats (12 rats/group) were trained in a 5‐cycle lever‐press operant task under a fixed‐ratio 30 schedule of food reinforcement. Once trained to maintain consistent operant performance across all 5 cycles, each rat was tested with various doses of ethanol injected at the beginning of each timeout cycle. Each group of rats demonstrated equivalent saline baseline operant performance and ED50for ethanol's rate‐suppressing effects. Training sessions were suspended and rats received either a short‐ (9 days) or long‐term (5‐week) exposure to regular rat chow diet or thiamine‐deficient diet, and received either saline or pyrithia‐mine injections in a 2 × 2 design. Three additional control groups were maintained on a regular rat chow diet and received supplemental injections of either thiamine + pyrithiamine injections, thiamine + saline injections, or saline + pyrithiamine injections. The controlled diet phase continued until the development of overt signs of thiamine deficiency, at which time thiamine supplements were administered for 4 days. In phase 3, all rats were retrained in the operant task and a second ethanol dose‐effect function was generated. A history of thiamine deficiency and recovery failed to shift the behavioral dose‐effect functions significantly for ethanol and their associated blood alcohol curves. Most interestingly, significant behavioral sensitization to ethanol's rate suppressant effects was demonstrated in the two control groups of rats receiving regular rat chow diet in combination with supplemental injections of thiamine and either saline or pyrithiamine. The control group receiving regular rat chow diet and twice daily injections of saline and pyrithiamine failed to demonstrate overt signs of thiamine deficiency or significant shifts in the behavioral dose‐effect functions. We suggest a possible interaction between a surfeit of extracellular thiamine levels, and a subsequent decrease in magnesium levels may be involved in the development of increases in ethanol sensitivity.
Alcohol Acceptance, Preference, and Sensitivity in Mice.
Authors: Rodriguez Lawrence A. , Plomin Robert , Blizard David A. , Jones Byron C. , McClearn Gerald E.
Published: April 2006

Although the recombinant inbred strain method was designed for molecular genetic analysis of linkage, it also provides powerful quantitative genetic analyses of heritability and genetic correlations. Measures of alcohol acceptance, alcohol preference, and hypnotic dose sensitivity (HDS) were assessed in 21 strains of mice from the BXD Rl series. Sex differences were found to be significant at a phenotypic level. However, heritability estimates for acceptance, preference, and HDS are similar in males and females. Heritability estimates for the three measures are ∼0.20 for acceptance and preference, and 0.10 for HDS. Analyses of genetic correlations reveal that acceptance and preference share some degree of genetic influence, although they mostly operate under different genetically mediated mechanisms. HDS did not show a significant genetic relationship to either acceptance or preference. Strong correlations were obtained when acceptance, preference, and HDS strain means were correlated across male and female recombinant inbreds, suggesting substantial genetic similarity across sexes.
Daidzin, an Antioxidant Isoflavonoid, Decreases Blood Alcohol Levels and Shortens Sleep Time Induced by Ethanol Intoxication
Authors: Xie Chang‐I , Lin Renee C. , Antony Veena , Lumeng Lawrence , Li Ting‐Kai , Mai Kai , Liu Chenjiang , Wang Qing‐duan , Zhao Zhi‐hong , Wang Gui‐fang
Published: April 2006

The extract from an edible vine, Pueraha lebata has been reported to be efficacious in lessening alcohol intoxication. In this study, we have tested the efficacy of one of the major components, daidzin, from this plant extract. When ethanol (40% solution, 3 g/kg body weight) was given to fasted rats intragastrically, blood alcohol concentration (BAC) peaked at 30 min after alcohol ingestion and reached 1.77 ± 0.14 mg/ml (mean values ±sd, n = 6). If daidzin (30 mg/kg) was mixed with the ethanol solution and given to animals intragastrically, BAC was found to peak at 90 min after alcohol ingestion and reached only 1.20 ± 0.30 mg/ml (n = 6) (p < 0.05 vs. controls). The ability of daidzin to delay and decrease peak BAC level after ethanol ingestion was also observed in fed animals, in both fasted and fed rats given alcohol without daidzin, BAC quickly declined after reaching its peak at 30 min. By contrast, BAC levels receded more slowly if daidzin was also fed to the animals. Daidzin showed a chronic effect. Rats fed daidzin for 7 days before ethanol challenge, but not on the day of challenge, also produced lower and later peak BAC levels. Interestingly, daidzin, whether fed to rats only once or chronically for 7 days, did not significantly alter activities of either alcohol dehydrogenase or mitochondrial aldehyde dehydrogenase in the liver. Further experiments demonstrated that daidzin shortened sleep time for rats receiving ethanol intragastrically (7 g/ kg) but not intraperitoneally (2 g/kg). To test whether daidzin delayed stomach‐emptying, [Clpolyethylene glycol was mixed with ethanol and fed to rats. It was found that, 30 min after intragastric feeding, more ethanol and [14C]polyethylene glycol remained in the stomach if rats were also given daidzin. Because daidzin is an isoflavonoid glucoside that possesses strong antioxidant activity, two other antioxidants (i.e., vitamin E and thioctic acid) were tested. Similar to daidzin, these two antioxidants also delayed and suppressed peak BAC, as well as shortened sleep time induced by alcohol ingestion. We conclude that: (1) daidzin is effective in countering alcohol intoxication; (2) suppression of BAC by daidzin is due mainly to delay of stomach‐emptying, but not to accelerated clearance of ethanol in circulation by liver enzymes; and (3) the effect of daidzin may in part be due to its antioxidant activity.
Spontaneous and Ethanol‐Stimulated In Vitro Release of β‐Endorphin by the Hypothalamus of AA and ANA Rats
Authors: de Waele Jean‐Pascal , Kiianmaa Kalervo , Gianoulakis Christina
Published: April 2006

Previous studies demonstrated that both the spontaneous and ethanol‐stimulated release of β‐endorphin (β‐EP) like‐peptides (β‐EPLPs) by the hypothalami of the ethanol‐preferring C57BL/6 mice is more pronounced than by the hypothalami of the ethanol‐avoiding DBA/2 mice. The objective of the present studies was to investigate the effects of various concentrations of ethanol on the in vitro release of β‐EP peptides by the hypothalami of the ethanol‐preferring Alko‐Alcohol (AA) and ethanol‐avoiding Alko Non‐Alcohol (ANA) lines of rats. Results indicated that although the spontaneous release of hypothalamic β‐EPLPs was higher by the ANA than by the AA rats, the percentage increase following exposure to various concentrations of ethanol was similar in both lines of rats. Furthermore, the release of hypothalamic β‐EPLPs following exposure to 30 mM ethanol was significantly higher than the release following exposure to 10 mM ethanol in the AA, but not the ANA, rats. Analysis of the released β‐EPLPs with Sephadex G‐75 and reversed phase HPLC indicated that the nonacetylated β‐EP1‐31 was the major component in the hypothalamic perifusates of the AA rats, whereas the shorter and acetylated forms of β‐EP were the predominant components in the hypothalamic perifusates of the ANA rats. Because the shorter and acetylated forms of β‐EP are devoid of opioid activity, their pronounced release by the hypothalami of the ANA rats may be important in maintaining their low ethanol consumption, even after long‐term access to ethanol solutions.
Effect of Chronic Alcohol Consumption on the Human Locus Coeruleus
Authors: Baker K. G. , Halliday G. M. , Harper C. G.
Published: April 2006

Despite reduced levels of noradrenaline and increased cortical β‐adrenergic receptor binding, there is controversy regarding the effect of chronic alcohol consumption on the noradrenergic neurons of the locus coeruleus (LC). The aim of this study is to investigate the effects of chronic alcohol consumption on the LC; in particular, to determine whether or not there is any alteration in the size or number of neurons, or other significant changes in this nucleus. Eight chronic alcoholics without additional medical complications and eight age‐matched controls were selected for this study. Immunohistochemis‐try with antibodies against tyrosine hydroxylase (TH) was used to visualize TH‐positive neurons in spaced serial 50‐μm sections throughout the length of the LC. These neurons were counted and no correction factors applied. There was no significant loss of TH‐positive neurons in the LC of alcoholics compared with controls who had up to 20% variation in the number of neurons between individuals. This confirms published results from one alcoholic without complications, but contradicts recent findings of a significant neuronal loss in five alcoholics, all with liver pathology. Our analysis suggests that central noradrenergic neurons in alcoholics without significant medical complications are not susceptible to alcohol neurotoxicity.
Effects of Chronic Alcohol on Immunoreactive β‐Endorphin Secretion from Hypothalamic Neurons in Primary Cultures: Evidence for Alcohol Tolerance, Withdrawal, and Sensitization Responses
Authors: Boyadjieva N. I. , Sarkar D. K.
Published: April 2006

Endogenous opioid peptides are known to be involved in the alcohol tolerance and dependence following alcohol abuse. However, the cellular mechanisms involved in the ethanol tolerance and dependence are not well established. We have previously shown that low concentrations of ethanol stimulate immunoreactive β‐endorphin (IR‐β‐EP) release from the cultured hypothalamic neurons and that chronic ethanol exposure desensitizes these neurons to ethanol challenges. In this study, we determined the IR‐β‐EP response to increasing doses of ethanol during the desensitizing phase of moderate ethanol doses to test whether the cultured IR‐β‐EP‐secreting neurons develop tolerance to ethanol following constant exposure. We also determined IR‐β‐EP responses following withdrawal from chronic ethanol challenge and compared the IR‐β‐EP secretory response to various doses of ethanol in ethanol‐naive and ethanol‐preexposed cultures. The IR‐β‐EP responses to increasing doses of ethanol (50‐150 mM) were markedly reduced in the cultures preexposed to a 50 mM dose of ethanol when compared with those that were naive to ethanol. The ethanol‐exposed cultures showed hypersecretion of IR‐β‐EP after removal from 48 hr of constant ethanol, as compared with ethanol‐naive cultures. When ethanol‐preexposed cultures were challenged with various doses of ethanol 4 days after ethanol withdrawal, the cultures showed higher IR‐β‐EP secretory responses than did the ethanol‐naive cultures. These data suggest that IR‐β‐EP secretory neurons in primary cultures develop tolerance to chronic ethanol, show withdrawal response after removal of chronic ethanol exposure, and develop sensitization following repeated ethanol challenges.
Alcohol/“Low‐Dose” Carbon Tetrachloride‐Induced Cirrhosis in Rats Using Different Methods of Alcohol Feeding
Authors: Plummer John L , de la M. Hall Pauline , Cmielewski Patricia L. , Ilsley Anthony H. , Ahern Michael J.
Published: April 2006

Cirrhosis may be reliably produced in rats by exposing them to low levels of carbon tetrachloride vapor while feeding alcohol in the Lieber‐DeCarli liquid diet. This study aimed to determine whether alternative cheaper and more convenient ways of feeding alcohol would also allow the production of cirrhosis. Animals were fed alcohol in the Lieber‐DeCarli diet, in a gel diet, or by addition of alcohol + sucrose to their drinking water, and were exposed to carbon tetrachloride vapor 6 hr/night, 5 nights/week. After 12 weeks of treatment, all animals (4 of 4) receiving alcohol in the Lieber‐DeCarli diet, but only two in each of the gel and drinking water groups, were cirrhotic. The variable results with the gel diet may be due to loss of alcohol by evaporation from the gel. Alcohol intake in the group receiving alcohol in drinking water was greater than in those receiving Lieber‐DeCarli diet. We suggest that the increased carbohydrate intake due to addition of sucrose to the water exerted a protective effect on the liver.
Prenatal Ethanol Exposure: Susceptibility to Convulsions and Ethanol's Anticonvulsant Effect in Amygdala‐Kindled Rats
Authors: Kim C. Kwon , Dalal Suntanu , Pinel John P. J. , Weinberg Joanne
Published: April 2006

The present experiments assessed the effects of prenatal ethanol exposure on the susceptibility to convulsions and on the anticonvulsant effect of ethanol using the electrical kindling model of epilepsy in rats. Adult male Sprague‐Dawley rats from prenatal ethanol (E), pair‐fed (PF), and ad libitum‐fed control (C) treatment groups were tested following the implantation of a stimulation electrode in the left amygdala complex. The same rate viete tested in tout consecutive experiments.

Both E and PF rats showed a slightly slower rate of kindling than C rats, as measured by convulsion class but not as measured by forelimb clonus duration (experiment 1). However, the groups did not differ significantly in the electrical stimulation threshold for kindled convulsions (experiment 2). Furthermore, prenatal ethanol exposure had no significant effect on the dose‐response curve for ethanol's (0, 0.9, 1.1, 1.3, and 1.5 g/kg, ip) anticonvulsant effect (experiment 3), or on the rate of tolerance development to ethanol's (1.5 g/kg, ip) anticonvulsant effect (experiment 4) on kindled convulsions. Thus, prenatal exposure to ethanol does not appear to have long‐term effects on the susceptibility to convulsions or on the anticonvulsant effect of ethanol in adult male rats in the kindling model as used in the present experiments.
Identifying Alcoholism Vulnerability Alleles
Authors: Goldman David
Published: April 2006

Identification of vulnerability alleles is one starting point for elucidating the web of interactions leading to alcoholism so that treatment and prevention can be improved. Heritability studies indicate that vulnerability alleles exist. Two molecular approaches for identifying them, direct analysis of candidate genes and genetic linkage, are highlighted in this review. Methodological problems that have been partially addressed and limitations for the applicability of the genetic findings are discussed.
1‐Week Withdrawal from 8 Weeks Alcohol Consumption Protects the Heart from Sepsis‐Induced Dysfunction
Authors: McDonough Kathleen H.
Published: April 2006

Gram‐negative sepsis causes a depression of the myocardium such that ventricular function curves generated on isolated perfused hearts removed from septic rats are displaced downward and to the right of control. Alcohol consumption can also cause a depression of the myocardium, especially if the period of alcohol feeding is prolonged. However, even before overt changes in the myocardium can be measured as a result of alcohol consumption, chronic alcoholism can result in a potentiation of sepsis‐induced cardiac depression (Am. J. Physiol. 250:H1857‐H1863, 1991). The purpose of the present study was to determine if 1 week of withdrawal of alcohol from the diet after 8 weeks of alcohol consumption would reverse the potentiation by alcohol of sepsis‐induced cardiac depression. Animals were fed an ethanol‐containing diet in which ethanol contributed 36% of the total calories. Rats were fed this diet or a control liquid diet for 8 weeks, and then some animals were taken off the alcohol diet and placed on the control diet for 1 week. Sepsis was induced in control‐fed, alcohol‐fed or withdrawal animals by the administration of Escherichia coli into the dorsal subcutaneous space. Nonseptic animals received sterile saline in this space. The following day animals were anesthetized, and the hearts were removed and studied as isolated working hearts. Hearts removed from septic and alcohol septic animals showed severe depression of cardiac contractile performance. Hearts from the withdrawal group, however, were less compromised by sepsis and showed only a few signs of cardiac dysfunction. Withdrawal from alcohol for 1 week thus resulted in protection of the heart from sepsis‐induced cardiac depression.
Apoptosis and Bcl‐2 Protein Expression in Experimental Alcoholic Liver Disease in the Rat
Authors: Yacoub Liliane K. , Fogt Franz , Griniuviene Brone , Nanji Amin A.
Published: April 2006

We used the intragastric feeding rat model to investigate the relationship between severity of alcoholic liver injury, apoptosis, bcl‐2 protein expression, and lipid peroxidation. Rats were fed ethanol with different dietary fats (saturated fat, corn oil, and fish oil) for a 1‐month period. Apoptosis was evaluated using an immunohistochemical method, and flow cytometry. Bcl‐2 protein concentrations in liver were evaluated by Western blot analysis and lipid peroxidation by measurement of conjugated diems. Pathological changes (fatty liver, necrosis, and inflammation) were present in com oil‐ethanol and fish oil‐ethanol groups only. The highest number of apoptotic cells were seen in the group of rats exhibiting her Injury. The fish oil‐ethanol‐fed group had the highest concentrations of bcl‐2 protein; this protein was localized in the bile duct epithelial and inflammatory cells. A significant correlation was seem between bcl‐2 protein assessed densitometrically and the number of inflammatory cells/mm2 (r= 0.78, p < 0.02) and conjugated diene levels (r= 0.82, p < 0.01). Increased numbers of apoptotic cells were seen in rats developing ethanol‐induced pathological liver injury. Increased bcl‐2 protein concentrations are associated with the presence of inflammatory cells and lipid peroxidation.