bluuebunny/crossref_metadata_2025 huggingface dataset:
The Effect of Acute in Vivo Ethanol Exposure on Follicle Stimulating Hormone Transcription and Translation
Authors: Emanuele M. A. , Tentler J. J. , Halloran M. M. , Emanuele N. V. , Wallock L. , Kelley M. R.
Published: April 2006

The impact of ethanol (EtOH) on male rodent reproduction has been well characterized for luteinizing hormone (LH) with suppression of LH release from the pituitary being reported. We have previously reported that acute ethanol (EtOH) exposure in vivo results in rapid and marked suppression of β‐LH gene expression and protein release from the pituitary. This suppression of β‐LH gene expression was unaccompanied by a change in the common α‐subunit mRNA. To further explore the impact of ethanol on male rodent reproduction, we have expanded our studies to follicle stimulating hormone (FSH) and hypothalamic luteinizing hormone releasing hormone (LHRH) as well as of pituitary protein kinase C (PKC).

Previously castrated male rats were acutely exposed to EtOH and a dramatic reduction in both serum FSH and LH levels was noted at 1.5 and 3 hr after treatment. These levels returned to saline injected control values at 6 and 24 hr. Despite the fall in serum FSH, there was no change in intrapituitary FSH content at any time point; this lack of pituitary FSH depletion in the face of a fall in serum levels is suggestive of impaired FSH release. In contrast to the fall in β‐LH steady‐state mRNA levels seen previously and confirmed in the present studies, there was no change in β‐FSH steady‐state mRNA at any time point suggesting that EtOH has dichotomous effects on the expression of these two gonadotropins.

Pituitary PKC levels were also assessed and found to be unaffected by EtOH at any time point. This enzyme is important in transmembrane signaling for the gonadotropins, and while ETOH is known to affect PKC in other cells, it appears that the effect of EtOH on the gonadotrops is not mediated at this level. Finally, hypothalamic luteinizing hormone releasing hormone (LHRH) content was assessed by radioimmunoassay, and no change was found at any time point in this hypothalamic peptide.

We conclude that the effect of EtOH on pituitary gonadotropin gene expression is not uniform, with β‐LH suppression occurring selectively while β‐FSH is unaltered. The release of both gonadotropins appears to be impaired by EtOH, while pituitary PKC and hypothalamic LHRH content are unchanged.
Ethanol Enhances the Release of Dopamine and Serotonin in the Nucleus Accumbens of HAD and LAD Lines of Rats
Authors: Yoshimoto K. , McBride W. J. , Lumeng L. , Li T.‐K.
Published: April 2006

The effects of intraperitoneal administration of ethanol, 0.5, 1.0, and 2.0 g/kg body weight, on the extracellular concentrations of dopamine (DA), serotonin (5‐HT), and their major metabolites were studied in the nucleus accumbens (ACC) of alcohol‐naive, selectively bred high‐alcohol‐drinking (HAD) and low‐alcohol‐drinking (LAD) lines of rats using the technique of microdialysis. In both lines, the extracellular levels of DA were increased following the injection of 1.0 and 2.0 g of ethanol/kg body weight while only the 2.0‐g/kg dose elevated the concentration of 5‐HT. None of the ethanol doses altered the extracellular levels of the major metabolites of DA and 5‐HT. Dose‐response curves for DA and 5‐HT release indicated no marked difference in the sensitivity to ethanol between the lines. Local perfusion with 60 mM K+ through the microdialysis probe markedly enhanced the release of DA and 5‐HT in the ACC of both lines; there was a small difference between the lines in the amounts of DA, but not 5‐HT, released by K+‐stimulation. Overall, the results indicate that (1) the ACC DA system is more sensitive than the ACC 5‐HT system to intraperitoneal ethanol administration in both lines and (2) there is no evidence for a relationship between alcohol preference and sensitivity of the ACC DA and 5‐HT systems to acute intraperitoneal ethanol administration.
Modulation of F‐met‐leu‐phe Induced Chemotactic Activity and Superoxide Production by Neutrophils during Chronic Ethanol Intoxication
Authors: Bautista Abraham P. , D'Souza Nympha B. , Lang Charles H. , Spitzer John J.
Published: April 2006

Chronic alcohol consumption has been associated with increased migration of neutrophils into liver that could contribute to the development of alcoholic liver disease. Mild endotoxemia may be at least partially responsible for this condition since endotoxemia was shown to be present in virtually all chronic alcoholics. This study examines the release of superoxide anion and chemotactic activity by Kupffer cells and sequestered hepatic as well as blood neutrophils during chronic alcohol intoxication (16 weeks) alone, and following an intravenous injection of Escherichia coli lipopolysaccharide (LPS) (1 mg/kg) 3 hr before cell isolation. Chronic ethanol consumption increased the total neutrophil yield per liver, but did not change the f‐met‐leu‐phe induced chemotactic activity by both hepatic and blood neutrophils. However, the combined insults of ethanol and LPS increased the chemotactic activity and superoxide anion generation by these cells. Plasma from ethanol‐fed rats was highly chemotactic to syngeneic normal rat neutrophils. This activity was increased 1.75‐fold in the plasma obtained from chronic ethanol plus endotoxin‐injected rats. The chemotactic activity of Kupffer cells was not significantly modulated during ethanol intoxication plus endotoxin treatment. The f‐met‐leu‐phe‐induced superoxide anion release by Kupffer cells was enhanced after LPS treatment. Chronic ethanol consumption did not induce any effect on this parameter. These observations suggest that functional alterations in neutrophils during chronic ethanol intoxication may contribute to hepatic injury.
A Placebo‐Controlled Trial of Buspirone in Anxious Inpatient Alcoholics
Authors: Malcolm Robert , Anton Raymond F. , Randall Carrie L. , Johnston Amanda , Brady Kathleen , Thevos Angelica
Published: April 2006

The present study is a double‐blind control trial of buspirone versus placebo in highly anxious alcoholics who recently completed inpatient detoxification for alcoholism. Subjects met DSM‐III‐R criteria for generalized anxiety syndrome and/or other nonpanic forms of anxiety disorders and alcohol dependence. Male veterans aged 21 to 65 were randomized to 45 to 60 mg/day of buspirone (n = 33) or placebo (n = 34). Anxiety scores, as measured by the Hamilton Anxiety Scale and other anxiety measures, declined significantly for both groups, but there were no differential group differences throughout the 6‐month treatment period. Survival analysis measuring time to study drop out, time to first drink, time to 5 consecutive drinking days, and time to first intoxication indicated no significant differences between groups. The number of standard drinks per drinking day for nonabstainers also did not differ between groups. In the present study anxious alcoholics taking buspirone did not receive any benefit over placebo on a number of anxiety and alcohol use measures.
Techniques to Enhance Compliance with Disulfiram
Authors: Allen John P. , Litten Raye Z.
Published: April 2006

Pharmacodynamic benefits of disulfiram in the treatment of alcoholism have yet to be clearly demonstrated. Nevertheless, research does suggest that disulfiram may well have positive effects on drinking if medicational compliance procedures are employed. This paper reviews research on four strategies for enhancing disulfiram compliance: implants, incentives, contracts, end patient information. Generalizations about the strategies are drawn and needs for future research are briefly addressed.
Do Women Develop Alcoholic Brain Damage More Readily Than Men?
Authors: Mann K. , Batra A. , Günthner A. , Schroth G.
Published: April 2006

Chronic alcoholism is related to brain damage (i.e., volume changes) in both men and women. There is an open question whether the brains of women are more vulnerable than those of men to alcohol toxicity. The present follow‐up study focuses on a direct comparison of sex‐related differences in alcoholic brain shrinkage and its reversibility. In a prospective design, a random sample of 65 alcoholics of both sexes (51 males and 14 females) was studied. Computerized tomography brain scans before and after a 6‐week inpatient treatment program with controlled abstinence revealed a significant re‐expansion of the brain as assessed by linear measurements. By controlling for moderating variables such as age, mean daily alcohol consumption, liver dysfunction, etc. the degree of brain shrinkage was found to be similar in men and women despite significantly shorter ethanol expositions in the women. These findings corroborate the hypotheses of other investigators about basic biological differences between the two sexes as to the effects of alcohol. The hypothesis of an enhanced vulnerability of women to acute and chronic complications of alcoholism is supported.
Serum Type I Collagen Propeptide and Severity of Alcoholic Liver Disease
Authors: Niemelä Onni , Blake Joan E. , Orrego Hector
Published: April 2006

We assessed the relationship of serum type I collagen propeptide concentrations with various severity indices of alcoholic liver disease, including clinical and morphological severity, the amount of alcohol consumption, and the serum levels of other components of connective tissue. The serum concentration of the carboxyterminal propeptide of type I procollagen (PICP) was measured with new radioimmunoassay that is devoid of crossreaction caused by type III procollagen‐derived fragments. A significant correlation was found between serum PICP and the Combined Clinical and Laboratory Index (CCLI) (ra. = 0.58, p < 0.001) and the Combined Morphological Index (CMI) (ra= 0.57, p < 0.01). However, PICP was elevated less frequently than serum type III collagen propeptide (PIIINP), type IV collagen or laminin, and the correlations with the latter three parameter with both the CCLI (PIIINP: ra= 0.80, type IV collagen: ra= 0.80 and laminin: ra= 0.81) or CMI (PIIINP: ra= 0.75, type IV collagen: ra= 0.72; and laminin ra= 0.61) were all stronger than that of PICP. Furthermore, although during follow‐up period of 6 months, the mild or moderately drinking patients had significant decrease in PIIINP and the heavily drinking patients had no improvement. PICP was, however, found to improve in both the mild and heavy drinkers. These results point to differences in handling of type I and type III collagen propeptides in alcoholic liver disease. The latter appears to be more sensitive indicator of disease severity, presence of alcoholic hepatitis, and the amount of alcohol intake.
Effect of Ethanol Administration and Withdrawal on Serotonin Receptor Subtypes and Receptor‐Mediated Phosphoinositide Hydrolysis in Rat Brain
Authors: Pandey Subhash C. , Piano Mariann R. , Schwertz Dorie W. , Davis John M. , Pandey Ghanshyam N.
Published: April 2006

The effect of short‐term (15 days) and long‐term (60 days) ethanol treatment and withdrawal on agonist‐stimulated phosphoinositide (PI) hydrolysis, serotonin receptor subtypes (5HT1A and 5HT2), and α1‐adrenergic receptors were studied in rat cerebral cortex. Short‐term ethanol treatment had no significant effect on serotonin (5HT), norepinephrine (NE), and calcium ionophore (A23187)‐stimulated [3H]‐inositol‐l‐phosphate ([3H]‐IP1) formation and 5‐HT2 receptors as measured by 125I‐lysergic acid diethylamide (125I‐LSD) binding, in rat cerebral cortex. However, 15 days of ethanol treatment, followed by 24 hr of withdrawal resulted in a decrease in Bmax of 125I‐LSD binding without significant change in KD1 as well as a decrease in 5HT‐stimulated [3H].IP1 formation in rat cerebral cortex. 5HT1A and α1‐adrenergic receptors were determined by using [3H]‐8‐hydroxy‐2‐(di‐N‐propylamino)tetralin and [3H]‐prazosin as radioligand, respectively. We also observed that long‐term ethanol treatment had no significant effect on Bmax and KD of 5HT21, 5HT1A, and α1‐ adrenergic receptors, as well as NE and A23187‐stimulated [3H]‐IP1 formation, but significantly decreased the 5HT‐stimulated [3H]‐IPl formation in rat cerebral cortex. It is possible that a decrease in 5HT‐induced PI turnover after long‐term ethanol exposure may be due to a decrease in coupling of 5HT2 receptors to G protein or PLC enzyme, whereas the decrease in 5HT‐induced PI turnover after withdrawal may be due to a decrease in functional 5HT2 receptor number.
Proopiomelanocortin Messenger RNA is Decreased in the Mediobasal Hypothalamus of Rats Made Dependent on Ethanol
Authors: Scanlon Martin N. , Lazar‐Wesley Eliane , Grant Kathleen A. , Kunos George
Published: April 2006

It is thought that certain actions of ethanol involve an interaction with endogenous opioids, including proopiomelanocortin‐derived pep‐tides such as β‐endorphin. To examine this possibility, we used a sensitive and specific assay for proopiomelanocortin mRNA to obtain an estimate of the activity of the endorphinergic system in the mediobasal hypothalamus and the pituitary of rats exposed for 10 days in an inhalation chamber to either ethanol or water. This protocol causes dependence in the ethanol‐exposed group, as demonstrated by the presence of withdrawal seizures after cessation of treatment. While ethanol treatment did not affect proopiomelanocortin mRNA levels in the pituitary, the level in hypothalamus was significantly lower in the ethanol‐treated animals than in controls. These results suggest that some effects of ethanol may involve the hypothalamic endorphinergic system.
Membrane Biogenesis in the Presence of Ethanol
Authors: Slomiany Amalia , Grabska Maria , Grzelinska Ewa , Yamaki Ken‐ichiro , Kasinathan Chinnaswamy , Slomiany Beatrix A. , Slomiany Bronislaw L.
Published: April 2006

To investigate the effect of ethanol on the intracellular transport in gastric epithelial cells, the in vitro system, generating transport vesicles which transfer mucus glycoprotein apopeptide (apomucin) from rough endoplasmic reticulum (RER) to Golgi, was assembled. The vesicles, generated from gastric mucous cell RER microsomes and labeled with [3H]palmitic acid, were isolated from the maternal RER and characterized. The electron microscopy revealed that these RER products consisted of 80 to 100 nm smooth membrane vesicles, while the immunochemical analyses showed that they contain apomucin but were devoid of the characteristic integral proteins of the RER membrane. Incubation of apomucin transporting vesicles with Golgi in the presence of UDP‐[3H]galactose resulted in the formation of glycosylated mucin and fusion of the vesicles with Golgi.

Formation of ER transport vesicles was dependent on the supply of lipid precursors, and the activity of phosphoglyceride and sphingolipid synthesizing enzymes. In the presence of 60 and 120 MM ethanol, the vesicles were formed, but their lipid composition was modified. The results suggest that ethanol‐induced membrane alterations are initiated at the early stages of the membrane biogenesis and are first reflected in the lipid composition of the intracellular transport vesicles.
Life Transitions, Work, and Alcohol: An Overview and Preliminary Data
Authors: Roman Paul M. , Blum Terry C.
Published: April 2006

The interrelations between age, life transitions, drinking, and work roles are considered. Increased focus of age‐related research on employed adults is suggested. The relevance of concepts of age stratification and life transitions is discussed. Data from an ongoing study of the clients of employee assistance programs are presented to demonstrate relationships between age, job characteristics, and drinking problems.
Gender‐Role Attitudes, Job Competition and Alcohol Consumption among Women and Men
Authors: Parker Douglas A. , Harford Thomas C.
Published: April 2006

Attempting to account for greater alcohol consumption among women, social scientists have argued that traditional gender roles and gender‐role attitudes concerning the division of labor in the family have provided women with a moral or cultural protection against heavier drinking but that the “breakdown” of this protection has allowed for greater alcohol use. This paper assesses the breakdown argument using data from two representative samples: a sample of 12,069 young adults in the United States and a sample of 1,367 employed men and women in metropolitan Detroit. Our analysis indicates that among young women the nontraditional role of employment and nontraditional gender‐role attitudes concerning responsibilities for household labor and child care are associated with greater alcohol consumption. However, among the employed, our analysis indicates that it is not nontraditional women and traditional men but rather traditional women and nontraditional men who have greater alcohol use–it is the women and men who believe that they have substantial obligations at home and who have intense competition at the workplace that consume a greater quantity of alcohol.
DSM‐III‐R and the Proposed DSM‐IV Alcohol Use Disorders, United States 1988: A Nosological Comparison
Authors: Grant Bridget F. , Harford Thomas C. , Hasin Deborah S. , Chou Patricia , Pickering Roger
Published: April 2006

The purpose of the present study was to compare DSM‐III‐R and the proposed DSM‐IV diagnostic criteria for alcohol abuse and dependence in a representative sample of the United States general population. Alcohol abuse and dependence diagnostic categories were contrasted in terms of prevalence and overlap. The prevalence of DSM‐III‐R diagnoses of alcohol abuse and dependence combined (8.63%) was greater than the corresponding DSM‐IV diagnoses (6.00%). Disaggregation of abuse and dependence diagnoses showed that the major discrepancy between the classification systems resided between the abuse categories. Reasons for the discrepancies are discussed in terms of differences in the content of the DSM‐III‐R and DSM‐IV abuse categories, in the relationship that each abuse category shares with its respective dependence category, and the impact of the DSM‐III‐R duration criterion.
Characteristics of a New Urine, Serum, and Saliva Alcohol Reagent Strip
Authors: Tu Guang‐chou , Kapur Bhushan , Israel Yedy
Published: April 2006

We have tested an ethanol reagent strip developed at the Addiction Research Foundation of Ontario. Alcohol dehydrogenase and nicotinamide adenine dinucleotide, in the presence of pyrazole, react with ethanol to yield acetaldehyde plus reduced nicotinamide adenine dinucleotide. The latter reduces iodonitrotetrazolium chloride in the presence of diaphorase, generating an intense red color. The rate of color development is proportional to the concentration of ethanol. Color is compared at a specific time against a calibrated color scale ranging from green (negative) to red, representing alcohol concentrations of 0, 25,50, 100, 200, and 400 mg/dI(0‐0.4%; 0–87 mmol/liter).

We were able to interpolate the color observed between the calibrated blocks. When tested on urine, serum/plasma, and saliva, ethanol concentration determined by the reagent strip correlates well with ethanol concentration as determined by gas chromatography or by automated enzymatic analysis (r= 0.92–0.98, p < 0.001; slope 0.83–1.16). The reagent strip was shown to be used appropriately by nonexperienced individuals following a 1‐min explanation (reagent strip values, r= 0.92; p < 0.001, slope = 0.97, versus gas chromatography). The reagent strip does not react with methanol (wood alcohol), isopropanol (rubbing alcohol), and ethylene glycol (antifreeze) often found in accidental poisonings. In 379 clinical samples obtained without exclusion criteria from 12 hospital emergency rooms and a liver clinic, the sensitivity of the reagent strip in detecting ethanol was 98%. Specificity was 99%. The reagent strip was found to have virtually unlimited stability under refrigeration (4°C) and to be stable for 3 to 4 months at room temperature (22‐23°C). The reagent strip should be valuable in a number of clinical settings in which rapid assessment of alcohol intoxication or of alcohol consumption, using either of the biological fluids (urine/serum/saliva), is wanted and in which a specific and sensitive method to determine alcohol requiring no instrumentation is needed.
Alcohol Expectancies and Behavioral and Emotional Responses to Placebo Versus Alcohol Administration
Authors: Nagoshi Craig T. , Noll Richard T. , Wood Mark D.
Published: April 2006

Forty normal drinking males were recruited for a study of “responses to alcohol.” Following the completion of an alcohol use questionnaire that included measures of expectancies of alcohol effects, subjects were randomly assigned to either receive the actual 0.6 g/kg dose of ethanol to bring their peak blood alcohol concentration (BAC) to near 0.075 g/dl or to receive a placebo dose. Neither the subject nor the tester was aware of the condition to which the subject had been assigned. Prior to dosing and at repeated ½‐hr intervals following dosing, subjects were tested on a battery of motor coordination, perceptual speed, reaction time, and mood measures. Significant alcohol effects were found for several measures, but the only significant interaction of individual differences in expectancies of alcohol effects with alcohol dosing occurred for self‐perceived intoxication. Subjects who expected more disinhibition after alcohol dosing and who were administered alcohol reported more intoxication than those expecting less disinhibition, while no expectancy effect was found for subjects administered the placebo.
Obsessive and Compulsive Characteristics of Alcohol Abuse and Dependence: Quantification by a Newly Developed Questionnaire
Authors: Modell Jack G. , Glaser Frederick B. , Mountz James M. , Schmaltz Stephen , Cyr Louis
Published: April 2006

The purpose of the this study was to develop an instrument for measuring the obsessive and compulsive characteristics of drinking‐related thought and behavior in subjects who abuse or are dependent on alcohol, and to quantify the extent to which drinking‐related thought and behavior in these subjects resemble the obsessions and compulsions seen in obsessive‐compulsive disorder (OCD). To achieve these goals, the Yale‐Brown Obsessive Compulsive Scale (Y‐BOCS) was modified to reflect obsessionality and compulsivity specifically related to heavy drinking rather than to obsessions and compulsions generally. The modified Y‐BOCS (Y‐BOCS‐hd) was administered to 62 subjects satisfying DSM‐III‐R criteria for alcohol abuse or alcohol dependence and 62 matched normal controls. The data showed that the Y‐BOCS‐hd is a sensitive and specific instrument for measuring the obsessive and compulsive characteristics of drinking‐related thought and behavior in alcohol‐abusing and alcohol‐dependent populations, and that there are specific and quantifiable similarities between these characteristics and the obsessions and compulsions of OCD. The data also indicated that the Y‐BOCS‐hd may be a useful screening instrument for the presence of alcohol abuse and dependence.
Obsessive and Compulsive Characteristics of Craving for Alcohol in Alcohol Abuse and Dependence
Authors: Modell Jack G. , Glaser Frederick B. , Cyr Louis , Mountz James M.
Published: April 2006

The purpose of this study was to quantify the extent to which subjective ratings of craving for alcohol in the alcohol‐abusing or dependent person (herein, alcoholic) correlate with measurable and specific characteristics of obsessions and compulsions. The Yale‐Brown Obsessive Compulsive Scale modified to reflect obsessionality and compulsivity specifically related to heavy drinking (Y‐BOCS‐hd) was used for this purpose.

Highly significant correlations were found in the alcoholic population (n= 62) between subjectively rated craving for alcoholic beverages and several of the Y‐BOCS‐hd questions regarding alcohol‐related thoughts and drinking behavior. Additionally, mean craving scores were considerably greater in the alcoholic population than the matched control population (n= 62). The data suggest that craving shares specific features in common with the obsessions of obsessive‐compulsive disorder and that the existence of craving is dependent on the presence of obsessive thoughts about drinking. Positive correlations between craving and measures of compulsive drinking behavior also were found; compulsive drinking behavior, however, may reflect the consequences of craving rather than a fundamental characteristic of craving itself. The data show that despite difficulties in defining the term craving, it is clearly a phenomenon that is experienced or endorsed by most alcoholic subjects and is not by most persons who do not abuse alcohol.
Urinary 5‐Hydroxytryptophol: A Possible Marker of Recent Alcohol Consumption
Authors: Voltaire Annette , Beck Olof , Borg Stefan
Published: April 2006

Urinary 5‐hydroxytryptophol (5‐HTOL) is currently being evaluated as a marker of recent alcohol consumption. To compensate for urinary dilution, the molar ratio between 5‐HTOL and 5‐hydroxyin‐ dole‐3‐acetic acid (5‐HIAA) is used. The 5‐HTOL/S‐HIAA ratio showed a satisfactory degree of individual stability when it was followed in a group of teetotallers for 1 month. The mean value of 5‐HTOL/5‐HIAA in a group of 69 persons abstaining from alcohol was 7.6 (pmoles 5‐HTOL/nmoles 5‐HIAA). Ninety‐seven percent had values ranging from 4 to 17, with no value exceeding 20. A group of healthy volunteers were tested 12 hr after alcohol consumption and showed a dose‐dependent and statistically significant elevation in the 5‐HTOL/5‐HIAA ratio. Four regular alcohol consumers who were followed during a period of 3 months of drinking had elevated values of the 5‐HTOL/5‐HIAA ratio in 60% of their urine samples. The present study indicates that urinary 5‐HTOL/5‐HIAA is a sensitive and reliable marker of recent alcohol consumption. We propose that a 5‐HTOL/5‐HIAA ratio >20 (pmoles/nmoles) can be used to indicate recent alcohol consumption. This limit gives a low frequency of false positives; the statistical probability of having a value >20 during abstinence from alcohol was calculated to be <0.001.
Alcohol Dehydrogenases in the Brain of Mice
Authors: Rout Ujjwal K.
Published: April 2006

Alcohol dehydrogenase (ADH) phenotypes were investigated in the brain of 15 different inbred mice by isoelectric focusing followed by staining of enzyme activities. The Class III ADH activity was detected in all the strains studied, whereas the Class II ADH activity was found only in few strains (including the alcohol‐preferring strain—C57BL/6J) having the “a” allele (ADH‐C22) for this isozyme in stomach. The inbred strains having the “b” allele (ADH‐C21) for the Class II ADH in stomach (including the alcohol avoiding strains—BALB/c, CBA/H, C3H/He, DBA/2J, and SJL/J) demonstrated null variant for this phenotype in their brain. The Class I ADH activity was very low or absent in the brain extracts of all the strains studied. The ADH activities were confined to the cytosolic fractions of brain and were higher in the extracts of cerebral hemispheres than in cerebellum. The genetic linkage studies showed that the locus for the brain Class II ADH is closely linked to the “Adh gene complex” on chromosome 3 of mice.
Ethanol Exposure Results in a Transient Decrease in Human Platelet cAMP Levels: Evidence for a Protein Kinase C Mediated Process
Authors: DePetrillo P. B. , Swift R. M.
Published: April 2006

At concentrations between 2 and 32 mM, ethanol is shown to depress human platelet cAMP levels. The effect is biphasic, maximal at 30 sec, with platelet concentrations of cAMP returning to baseline values at higher ethanol concentrations and at longer incubation times. The cAMP lowering effect of ethanol can be blocked by a phosphodiesterase (PPDE) inhibitor, 3‐isobutyl‐1‐methyl‐xanthine (IBMX), at a concentration of 2 mM, suggesting that an increase in PPDE activity may be responsible for this effect. Exposure of platelets to 1‐(5‐isoquinolinylsulfonyi)‐2‐methylpiperazine (H7), a protein kinase C (PKC) inhibitor, blocks the ethanol‐induced decrease in platelet cAMP, suggesting ethanol may be acting through activation of PKC.
Ethanol‐Induced Suppression of Cell‐Mediated Immunity in the Mouse
Authors: Jayasinghe Ruani , Gianutsos Gerald , Hubbard Andrea K.
Published: April 2006

Among its many effects on multiple organ systems, ethanol abuse also elicits potent immunomodulatory effects as well. Increased susceptibility to disease as well as increased severity in infection is well documented in alcoholics and may be related to an altered immune response. A mouse model has been developed in which C57BI/6 mice are fed a nutritionally adequate liquid diet in which ethanol provides 27% of total calories (3.75% ethanol) in order to examine the effects of short‐term, low dose ethanol administration on cell mediated immunity. All mice were evaluated for percentage of plasma ethanol, impaired motor skills and impaired delayed type hypersensitivity to sheep erythrocytes. Animals fed the ethanol diet for 5, 10, or 15 days evidenced plasma ethanol concentrations between 0.13% and 0.23% as well as significantly impaired motor skills. Mice maintained on the ethanol diet 8 days prior to erythrocyte sensitization and on the 6 days between sensitization and challenge demonstrated a significant reduction of 58% in footpad swelling. Moreover, mice fed ethanol for only the 6 days between erythrocyte sensitization and challenge also demonstrated a significant decrease of 35% in this delayed type immune response. However, animals administered ethanol prior to sensitization and then switched to control diet between sensitization and challenge evidenced a normal cell‐mediated immune response to the sheep erythrocytes. Thus, it appears that the critical time of low dose ethanol‐induced immunosuppression is between immunogen sensitization and challenge.
The Discriminative Stimulus Properties of Acute Ethanol Withdrawal (Hangover) in Rats
Authors: Gauvin David V. , Youngblood Bradley D. , Holloway Frank A.
Published: April 2006

Twenty male Sprague‐Dawley rats were trained to discriminate pentylenetetrazole (PTZ, 15 mg/kg, intraperitoneally) from saline (SAL) under a drug discrimination procedure. Test sessions were conducted with 10 randomly selected subjects. Tests with various doses of PTZ resulted in a dose‐dependent increase in the percentage of total session responses emitted on the PTZ‐appropriate lever without a significant change in response rates across a wide range of test PTZ doses. Rats did not generalize the PTZ stimulus to ethanol (ETOH) up to ETOH test doses that completely suppressed responding. High acute ETOH doses (2, 3, and 4 g/kg) administered at various time points prior to discrimination test sessions engendered responding on the PTZ‐appropriate level in a quantitative fashion, that was dose‐ and time‐dependent. This acute ETOH delayed effect from these high doses replicates our previously published study using a Drug 1‐Drug 2 discrimination task with Chlordiarepoxide and PTZ. More importantly, we suggest that the present behavioral assay may be a sensitive animal analogue of human “hangover” phenomena.
Serum Type I Collagen and N‐terminal Peptide of Type III Procollagen in Patients with Alcoholic Liver Disease: Relationship to Liver Histology
Authors: Trinchet Jean‐Claude , Hartmann Daniel J. , Pateron Dominique , Munz‐Gotheil Cécile , Callard Patrice , Ville Gérard , Beaugrand Michel
Published: April 2006

This study compared, in patients with alcoholic liver disease, the serum concentration of N‐terminal peptide of type III procollagen and of a novel serum marker, type I collagen, with liver histological data and assessed the role of these markers in the diagnosis and followup of liver changes. Ninety‐six patients (mean age 51 years, 61 men and 35 women) were included. All had alcoholic liver disease diagnosed on usual clinical, biochemical, and histological criteria. Two histological scores, one for alcoholic hepatitis and one for fibrosis, were established. Serum N‐terminal peptide of type III procollagen and type I collagen were assayed by liquid phase radioimmunoassay. Significant correlations between serum type I collagen and score of fibrosis (r= 0.34, p < 0.001) and between serum N‐terminal peptide of type III procollagen and score of alcoholic hepatitis (r= 0.60, p < 0.0001) were noted. There was no significant correlation between serum aminotransferases and the score of alcoholic hepatitis. In 25 patients with alcoholic hepatitis reassessed between 3 and 6 months, serum N‐terminal peptide of type III procollagen significantfy decreased (p= 0.05) as did the score of alcoholic hepatitis, but serum type I collagen and the score of fibrosis were not modified. These serum markers of collagen metabolism could be useful for the assessment and follow‐up in patients with alcoholic liver disease.
In Utero Ethanol Exposure Decreases the Biosynthesis of Phosphatidylserine in Rat Pup Cerebrum
Authors: Hu Zhong‐yi , Sun Grace Y. , Rhodes Philip G.
Published: April 2006

Phosphatidylserine is enriched in the brain and has been implicated to play a role in regulating neuronal membrane functions. In this study, three experimental protocols were used to examine the effects of in utero ethanol exposure on phosphatidylserine biosynthesis in rat pup brain, namely, (1) assay of the serine base‐exchange enzyme activity in brain microsomes, (2) incubation of brain slices with [3H] serine, and (3) incorporation in vivo of [3H]serine into phosphatidylserine as well as serine‐related phospholipids in brain. Results from all three protocols point to a decrease in phosphatidylserine biosynthesis in newborn rat pup cerebrum on exposure to ethanol in utero compared with the pair‐fed controls. When in utero ethanol‐exposed pups were nursed by mothers given a chow diet, the differences gradually returned to control levels by 17 days of age. The decrease in phosphatidylserine biosynthesis may be important in explaining some of the neuronal deficits associated with in utero ethanol exposure.
Alterations in Brain Polyribosomal RNA Translation and Lymphocyte Proliferation in Prenatal Ethanol‐Exposed Rats
Authors: Tewari Sujata , Diano Marcel , Bera Rimal , Nguyen Quoc , Parekh Hemalatha
Published: April 2006

The long‐term effects of prenatal ethanol exposure on the properties of brain polysomes and the proliferative responses of lymphocytes to mitogenic stimulation in adult offspring were assessed. Female Sprague‐Dawley rats either ingested the control or 6.6% ethanol‐containing Lieber‐DeCarli liquid diet during the 3rd trimester of pregnancy. Controls were age‐matched and pair‐fed. At 42 to 72 days of age, ethanol effects were evaluated on the (1) polysomal properties in the cerebral hemispheres, cerebellum, and hippocampal regions of the brain after translation in a messenger RNA (mRNA)‐dependent rabbit reticulocyte lysate system and (2) immunologic functions of lymphocytes cultured from spleen cells by measuring their responses to mitogenic stimulation.

Results showed long‐term adverse effects of in utero ethanol exposure on the polysomal RNA translation in each of the three brain regions tested with free polysomal mRNAs affected more than the bound polysomal mRNAs. Of these, the hippocampal region appeared to sustain the most injurious effects. In addition, a suppression of the mitogen‐induced lymphocyte proliferative responses were present under these conditions. The degree of suppression varied with the specific mitogen used. Data suggest that the ethanol effects on the CNS and lymphocyte proliferation are most possibly irreversible, and in the case of the CNS, a post‐translational modification by ethanol is indicated. The reduced lymphocyte responses are suggestive of a possible interference by ethanol of the synthesis of interleukin‐2 (IL‐2) and/or a reduced binding of IL‐2 with its receptor (IL‐2 receptors).
Effect of Ethanol on the Release of Prostaglandins from Ovine Fetal Brain Stem during Gestation
Authors: Sinervo Ken R. , Smith Graeme N. , Bocking Alan D. , Patrick John , Brien James F.
Published: April 2006

Prostaglandins (PGs) have been implicated as mediators of the ethanol‐induced suppression of ovine fetal breathing movements (FBM). The objectives of the present study were to determine the ontogeny of the in vitro efflux of PGE2 and β‐keto PGF1α in ovine fetal brain stem during the second half of gestation and to determine the effect of in vitro ethanol exposure on the efflux of these PGs. Ovine fetal brain stem tissue was obtained at mean gestational ages of 80 days (n= 6), 105 days (n= 10), and 135 days (n= 16) by rapid excision following maternal euthanization. Tissue slices (400 μM thickness) were prepared from the lower pons‐medulla region of the brain stem. After a 1‐hr equilibration period in artificial cerebrospinal fluid, efflux of PGE2 and 6‐keto PGF1α in the brain stem was determined using the brain slice‐superfusion method, and the PGE2 and 6‐keto PGF1α concentrations in the superfusate were determined by specific radioimmunoassay. The mean spontaneous efflux of PGE2 and 6‐keto PGF1α expressed as pmol PG/gram wet weight of tissue/5‐min collection period was, respectively, 31.9 ± 4.2 and 26.6 ± 2.4 at 80 days, 38.3 ± 5.2 and 29.6 ± 2.2 at 105 days, and 57.4 ± 3.1 and 27.1 ± 1.1 at 135 days of gestation. In vitro exposure to 20, 40, and 80 mM ethanol did not affect PG efflux in the brain stem at 80 and 105 days of gestation. In vitro ethanol exposure decreased PGE2 and 6‐keto PGF1α efflux at 135 days of gestation to 36.8 ± 5.3% and 41.6 ± 4.3% of spontaneous efflux within 15 min, respectively; this effect of ethanol was not dose‐dependent. The data do not support the hypothesis that ethanol increases PG efflux in the ovine fetal brain stem. In view of these findings and the data implicating PGs in the mechanism of ethanol‐induced suppression of FBM, it is possible that ethanol acts at either central sites rostral to the brain stem (i.e., upstream CSF) or peripheral sites to increase the synthesis of PGs and their efflux into the systemic circulation, with subsequent transfer to the respiratory control region(s) of the brain stem.
Isradipine and Other Calcium Channel Antagonists Attenuate Ethanol Consumption in Ethanol‐Preferring Rats
Authors: Fadda F. , Garau B. , Colombo G. , Gessa G. L.
Published: April 2006

The present work is concerned with studying of the ability of different calcium channel antagonists to modify voluntary ethanol ingestion by rats selectively bred for high ethanol preference. The compounds were given S.C. thrice daily for 5 days at doses that did not produce locomotor impairment. While nifedipine, darodipine, and verapamil (each at the dose of 20 mg/kg thrice daily) produced a modest reduction in ethanol intake, isradipine (at the dose of 1 mg/kg three times a day) reduced ethanol intake by over 70%.

For all compounds, the reduction in ethanol intake was compensated by a proportional increase in water consumption and the inhibitory effect persisted throughout the 5 days of treatment. The data indicate that calcium channel antagonists exhibit quite different potency in reducing ethanol preference, however this action is a general property of this class of compounds.
Effects of Ethanol on Glucose Utilization by Cultured Mammalian Embryos
Authors: Snyder A. K. , Jiang F. , Singh S. P.
Published: April 2006

We have previously observed correlations between placental glucose transfer and growth of fetuses of ethanol (EtOH)‐fed and control rats. In the present study, whole mammalian embryos were used to define the interaction of glucose supply and the effects of EtOH on growth and differentiation. Rat embryos were cultured in 75% normal rat serum from day 9.5 to day 11.5 of gestation. EtOH produced dose‐dependent reductions of embryo protein content (mean ± SEM = 212 ± 5, 171 ± 11, 141 ± 16, and 113 ± 9 μg/embryo in the presence of 0, 25, 50, and 100 mM EtoH, respectively). Somite number was 25.7 ± 0.3, 23.4 ± 0.7, 21.8 ± 0.7, and 21.1 ± 0.4 under the same conditions. Exposure to ethanol during the first 24 hr in culture decreased embryo protein content to the same extent as exposure for the entire 48‐hr culture period. After 46 hr in culture, control and ethanol‐exposed embryos were incubated with 14C‐glucose for 2 hr. Ethanol produced dose‐dependent reductions of CO2 production, anabolic utilization, lactate release, and total glucose utilization. Glucose supplementation (300 mg/dl) significantly increased embryo protein content and each of these glucose utilization parameters. When glucose utilization was expressed relative to embryo protein content, incorporation of the label into embryonic tissues was significantly reduced by ethanol and increased by glucose supplementation. Embryo protein content correlated closely (r= 0.871, p < 0.0001) with anabolic glucose utilization. Thus, ethanol directly affects embryo glucose utilization, both as an energy source and as a synthetic substrate, in addition to its effects on placental glucose transfer.
Activation of Glycolysis with Isoproterenol but not Digoxin Reverses Chronic Alcohol Depression in Hamster Hearts
Authors: Auffermann Wolfgang , Buser Peter , Wu Shao , Parmley William W. , Wikman‐Coffelt Joan
Published: April 2006

The purpose of this study was to confirm that an agent, which increases diastolic [Ca2+]i namely digoxin, depresses cardiac performance, mitochondrial activity, and glycolysis in chronic alcohol‐treated and myopathic hearts, and that an agent, which lowers diastolic [Ca2+]i namely isoproterenol, activates cardiac performance, mitochondrial activity, and glycolysis in these animals. Energy levels, glycolysis, mitochondrial activity, hemodynamics, and cAMP were studied in isolated hearts from three groups of animals, i.e., 9‐month control hamsters, hamsters given 50% alcohol until 9 months of age, and 6‐month‐old cardiomyopathic hamsters in heart failure. Isolated hearts were perfused with either a control medium, a medium containing isoproterenol, digoxin, or digoxin + isoproterenol. Measurement of phosphomonoester sugars, and glucose‐6‐phosphate, were used to assess glycolytic activity. Oxygen consumption was used to analyze mitochondrial activity. All hearts perfused with either isoproterenol or isoproterenol + digoxin showed an increase in developed pressure, rate‐pressure‐product, and a decrease in end‐diastolic pressure. Isoproterenol activated mitochondrial activity and glycolysis in hearts from myopathic and chronic alcohol hamsters. Based on 31P‐NMR studies, isoproterenol or isoproterenol + digoxin improved the over‐all energy state of hearts from cardiomyopathic hamsters, but not hearts from control and chronic alcohol hamsters. Digoxin alone augmented the rate‐pressure‐product and oxygen consumption in control hearts but not hearts from myopathic and chronic alcohol hamsters. Digoxin caused an increase in end‐diastolic pressure in myopathic and chronic alcohol hearts but not control hearts. Digoxin depressed glycolysis and worsened the energy state in hearts from cardiomyopathic and chronic alcohol hamsters, but not hearts from control hamsters. In conclusion digoxin, but not isoproterenol nor isoproterenol + digoxin, depressed cardiac performance and glycolysis as well as high energy phosphates in cardiomyopathic and chronic alcohol hearts. Isoproterenol added to digoxin negated the adverse effects of digoxin in cardiomyopathic and chronic alcohol hearts.
Effect of Acute Alcohol Administration on TNF‐α Binding to Neutrophils and Isolated Liver Plasma Membranes
Authors: Deaciuc I. V. , D'Souza Nympha B. , Bagby G. J. , Lang C. H. , Spitzer J. J.
Published: April 2006

The mechanisms underlying the effects of alcohol (ethanol, ETOH) on host defense are poorly understood. ETOH modulation of the cytokine regulatory network is one possible way by which ETOH could alter nonspecific immune function. In this study we examined the ability of acute alcohol intoxication to alter lipopolysaccharide (LPS)‐induced changes in tumor necrosis factor (TNF)‐α binding to neutrophils and isolated liver plasma membranes. Rats were injected intravenously with a primed constant infusion of ETOH for 7 hr to maintain blood ETOH concentration at approximately 35 mm. Four hours after the start of ETOH infusion, the animals received intravenously either sterile saline or LPS (100 μg/100 g body weight) and were sacrificed at the end of ETOH infusion. Blood neutrophils and liver plasma membranes were isolated, and TNF‐α binding characteristics determined using recombinant human [125I]TNF‐α. ETOH treatment alone induced a significant decrease (51%) of neutrophil Bmax for TNF‐α, without affecting the cytokine binding to plasma membranes. LPS, with or without ETOH, significantly decreased (61%) neutrophil Bmax for TNF‐α and increased (115%) its binding to liver plasma membranes. The KD values of binding to either neutrophils or liver plasma membranes were not altered by ETOH or LPS treatment of animals. By decreasing the cytokine binding to neutrophils, ETOH may impair the control exerted by TNF‐α on cell function, thus damaging host defense.
Activation, Attention, and Visuospatial Learning in Adults With and Without a Family History of Alcoholism
Authors: Schandler Steven L. , Cohen Michael J. , Antick Jennifer R.
Published: April 2006

While recent evidence shows visuospatial information processing deficits to be present in chronic alcoholics, it remains unclear whether such deficits are present prior to alcohol abuse in persons at risk for developing alcoholism. If present, it is also unclear whether the information processing mechanisms underlying these deficits are the same in alcoholics and persons at risk for alcoholism. This study investigated visuospatial information processing psycho‐physiological activation in adults with and without a family history of alcoholism. Thirty matched nonalcoholics served as participants. Fifteen persons were from families in which at least one biologic parent and one other relative had a history of alcoholism. Another group of 15 persons had no family history of alcoholism. In addition to displaying atypical patterns of learning‐contingent physiological activation, participants with a family history of alcoholism displayed visuospatial learning that was significantly poorer than persons with no family history of alcoholism. The learning and physiological activation displayed by the participants with a family history of alcoholism were similar to those displayed by previously studied alcoholics using a similar learning task. The data suggest that visuospatial learning deficits may reflect an antecedent to, rather than a consequence of, chronic alcohol abuse.
Using Adapted Short MASTs for Assessing Parental Alcoholism: Reliability and Validity
Authors: Crews Timothy M. , Sher Kenneth J.
Published: April 2006

In previous research adapted versions of the Short Michigan Alcoholism Screening Test (SMAST) have been employed to assess an individual's father's (F‐SMAST) and mother's alcohol abuse (M‐SMAST). However, to date psychometric information on these forms has been limited. In order to more broadly assess the psychometric properties of these forms, several critical issues in five related studies were addressed. The samples for the five studies were drawn from a college population at a large midwestern university. Overall, the reliability and validity of the adapted SMASTs appears to be quite good. The F‐SMAST demonstrated high reliability (from the standpoint of internal consistency, temporal stability, and reliability across siblings) as well as validity (both in respect to convergence with an interview measure and with father's own report on a parallel instrument). Furthermore, shortening both of these instruments to nine‐item versions appears to improve their reliability and validity. For researchers and clinicians interested in assessing parental history of alcoholism, the F‐SMAST and M‐SMAST would appear to be a reliable and valid paper‐and‐pencil measure.