bluuebunny/crossref_metadata_2025 huggingface dataset:
Neuroreceptor Changes in the Putamen of Alcohol Abusers
Authors: Freund Gerhard , Ballinger William E.
Published: April 2006

The purpose of this study was to determine if alcohol abuse affects muscarink cholinergic and benzodiazepine receptors in histologi‐cally normal brains obtained at autopsy in a general hospital population. Patients were excluded from this study if they had clinical brain (including Wernicke's) disease, died in coma, had liver disease, significant brain atrophy, or dementia severe enough to require institutionalization. We found that muscarinic cholinergic synaptic receptor density determined with [3H]quinuclidinyl benzilate was decreased by 40% in homogenates of the putamen of 27 alcohol abusers compared with 37 matched nonalcoholic controls. In contrast, receptor densities and affinities of benzodiazepine receptors determined with [3H]flunitrazepam were not significantly different in the two groups. Age and death‐autopsy time interval had no significant effects on either wet tissue protein concentrations, yields of protein after centrifugation, or receptor binding. The contributions of age and time interval were each less than 3% of the total variance of protein concentrations and receptor binding. When patients who had received cholinergic, anticholinergic, or benzodiazepine medications before death were excluded or included we observed no significant effects on the final results. Pneumonia, known to be associated with acute hypoxia, and chronic obstructive pulmonary disease, known to be associated with chronic hypoxia, were approximately equally distributed between the two groups and had no significant effects on the results reported here.

It is significant that the loss of muscarinic and the sparing of benzodiazepine receptors in the putamen occurs in histologically normal brains in the absence of significant atrophy and gross dementia. It implies that these changes are early in the development of alcoholic encephalopathy. We have previously reponed a decrease of muscarinic and benzodiazepine receptor binding in the frontal cortex and a decrease of muscarinic but not benzodiazepine receptors in the temporal cortex of alcohol abusers. Taken together, these findings suggest that alcohol neurotoxicity does not simply result in a random loss of neurons and/or their associated synapses with their receptors. Instead, different types of receptors are specifically affected or spared, depending upon their location in different brain regions. This suggests the involvement of region‐ and receptor‐specific mechanisms in alcohol toxicity, which then probably results in specific patterns of altered behavior.
Cognitive Status of Sons of Alcoholic Men
Authors: Tarter Ralph E. , Jacob Theodore , Bremer Deborah A.
Published: April 2006

Sons of community dwelling alcoholic, depressed, and normal men were administered a comprehensive battery of neuropsychological tests. A generalized cognitive deficit was not found in the sons of alcoholics. The sons of alcoholics demonstrated greater ataxia than offspring in the two control groups and also performed more poorly on tests measuring visual scanning and attention, planning ability, and impulse control. These findings raise the possibility that an anterior cerebral dysfunction underlies the cognitive deficit observed in children of alcoholics.
Ethanol‐induced Impairments in Receptor‐mediated Endocytosis of Asialoorosomucoid in Isolated Rat Hepatocytes: Time Course of Impairments and Recovery after Ethanol Withdrawal
Authors: Casey Carol A. , Kragskow Sandra L. , Sorrell Michael F. , Tuma Dean J.
Published: April 2006

Chronic ethanol administration markedly impairs the process of receptor‐mediated endocytosis (RME) of a representative asialoglycoprotein, asialoorosomucoid (ASOR), by the liver. In this study, we further characterized these impairments by identifying the time of onset for ethanol‐induced changes in RME as well as establishing the time course for recovery to normal endocytotic values after ethanol withdrawal. Ethanol administration for 3 days did not alter any aspect of endocytosis examined in this study. After feeding ethanol to rats for 7 days, however, significant decreases in amounts of ligand bound, internalized, and degraded were apparent. These impairments persisted throughout the 5‐week feeding study although the effects were somewhat attenuated with more prolonged ethanol feeding. In addition, an accumulation of intracellular receptors was observed in ethanol‐fed animals relative to controls after 7 days of ethanol feeding. In all cases, recovery of endocytotic values to control levels was partially completed after 2 to 3 days of refeeding control diet and was fully completed after 7 days of refeeding. These results indicate that ethanol feeding for as little as 7 days profoundly impairs the process of RME by the liver. These impairments can be reversed after refeeding control diet for 7 days.
α‐θ Brainwave Training and β‐Endorphin Levels in Alcoholics
Authors: Peniston Eugene G. , Kulkosky Paul J.
Published: April 2006

An α‐θ brainwave biofeedfack training program was applied as a novel treatment technique for chronic alcoholics. Following a temperature biofeedback pretraining phase, experimental subjects completed 15 30‐min sessions of α‐θ biofeedback training. Compared to a nonalcoholic control group and a traditionally treated alcoholic control group, alcoholics receiving brainwave training (BWT) showed significant increases in percentages of EEG record in α and θ rhythms, and increased α rhythm amplitudes. Alcoholics receiving BWT showed a gradual increase in α and θ brain rhythms across the 15 experimental sessions. These experimentally treated alcoholics showed sharp reductions in self‐assessed depression (Beck's Depression Inventory) compared to the control groups. Alcoholics receiving standard medical treatment (abstinence, group psychotherapy, antidepressants) showed a significant elevation in serum β‐endorphin levels at the conclusion of the experiment. This neuropeptide is an index of stress and a stimulant of caloric (e.g., ethanol) intake. Application of brainwave treatment, a relaxation therapy, appears to counteract the increase in circulating β‐endorphin levels seen in the control group of alcoholics. 13‐month follow‐up data indicate sustained prevention of relapse in alcoholics that completed α‐θ brainwave training.
Sensitivity of Liver Mitochondrial Functions to Various Levels of Ethanol Intake in the Rat
Authors: Quintanilla María Elena , Tampier Lutske
Published: April 2006

Mitochondrial function appears to be an early target for ethanol toxicity, however it is not clear to what extent the effects of ethanol, which occur at levels of intake lower than those already reported in the literature, can induce an alteration of it. To produce different levels of ethanol intake, the spontaneous consumption of ethanol by genetically low (UChA) and genetically high (UChB) rats, as well as the forced intake obtained by offering 10% v/v ethanol solution as the only source of drinking fluid, were employed.

The O2 uptake by liver mitochondria of rats submitted to these conditions in the presence of glutamate + malate, succinate or ascorbate + TMPD, was measured polarographically with a Clark electrode at 25°C. Results indicate that alterations of the hepatic mitochondrial function can be detected at levels of ethanol intake much lower than those previously reported. Whereas, a level of a daily ethanol intake of 2–3 g/kg body weight in UChA rats under free choice was insufficient to produce detectable changes in the mitochondrial function, the latter was decreased in the high ethanol consumers (UChB), which drank 4–5 g/kg per day under free choice conditions, and in both strains forced to drink 10% ethanol as only source of fluid, which produced intakes of about 7 g/kg per day. Therefore, mitochondrial dysfunction may contribute to effects observed even at low levels of ethanol intake.
Effect of Ethanol and Stress on Plasma Catecholamines and Their Relation to Changes in Emotional State and Performance
Authors: Vogel Wolfgang H. , Netter Petra
Published: April 2006

The “tension reduction hypothesis” of ethanol was investigated with respect to stress‐ and ethanol‐induced changes of plasma catecholamines and their relations to changes in emotional state and performance. Twenty‐two healthy male volunteers were tested under the influence of 0.8 g/kg ethanol and compared to 22 matched controls receiving a placebo drink. Stress was induced by mental arithmetic applied prior to and 45 min after fluid consumption. Plasma epinephrine (E) and norepinephrine (NE) obtained from an indwelling cannula inserted 50 min prior to stress application were determined prior to and after each stress session. Percentage changes were compared within and between groups and correlated with respective changes of emotional states and performance in mental arithmetic. While ethanol decreased performance and stress‐related emotional arousal, it did not affect stress‐induced changes in plasma catecholamines. Rather, the fluid (ethanol as well as placebo) increased NE levels. Emotional tension reduction was associated with low resting or average levels of E in the placebo group but this relationship was disrupted by ethanol. High NE resting levels and drink induced increases predicted emotional tension reduction with placebo but an increase in stress induced depression with alcohol. “Biochemical tension reduction” (represented by both reduced E and NE stress response) may be predicted from generally lower levels of activation and elation by alcohol but not with the placebo condition. Although performance was positively related to low NE resting levels and stress responses, no influence of alcohol on this relationship was observed. It is concluded that alcohol‐induced emotional tension reduction is not mediated by a reduction of catecholamine release since increases and high levels of NE in particular seem to reflect positive changes of mood.
Acute Alcohol Infusion Suppresses Endotoxin‐induced Serum Tumor Necrosis Factor
Authors: D'Souza Nympha B. , Bagby Gregory J. , Nelson Steve , Lang Charles H. , Spitzer John J.
Published: April 2006

Tumor necrosis factor (TNF) is suggested to play an important role in host defense as well as in eliciting some of the metabolic alterations in endotoxemia. Bacteria and their products are involved in triggering the production and release of TNF. Alcohol consumption is known to suppress the immune system and increase susceptibility to infections. The present study was undertaken to investigate the effect of acute ethanol administration on the ability of endotoxin to increase circulating TNF levels and to determine the relationship between blood ethanol levels and endotoxin‐induced serum TNF. A 50% decrease in serum TNF levels was seen 1–1.5 h after endotoxin challenge in conscious rats with blood alcohol levels between 75–175 mg/dl. A dose‐related depression of serum TNF was observed with increasing blood alcohol levels. This was accompanied by a markedly diminished hyperlactacidemia seen following endotoxin administration. These data suggest that impaired TNF release may have a role in the altered immune response of alcoholics to infection.
Psychophysiological Effects of Alcohol‐related Stimuli: I. The Role of Stimulus Intensity
Authors: McCaul Mary E , Turkkan Jaylan S , Stitzer Maxine L
Published: April 2006

The present study extends previous research on conditioning factors in the physiological and subjective responses to naturalistic alcohol‐related stimuli. Specifically, the effects of differential alcohol ingestion histories and of stimulus intensity were examined on the occurrence of conditioned responses in the laboratory. Twelve alcoholic subjects and twelve moderate drinkers participated in a single experimental session consisting of randomized presentations of three types of stimulus trials. Each trial included gustatory and visual presentation of alcohol, pepper juice (as a control for stimulus intensity) or water. Both alcohol and pepper juice stimuli significantly increased heart rate and skin conductance responses as compared with water stimuli. In contrast, subjects Significantly increased self‐report ratings of high and feel different following alcohol stimuli only. Physiological and subjective responses were similar in alcoholics and social drinkers with the exception of significantly higher self‐reported craving in alcoholic subjects. These findings suggest that stimulus intensity contributes to the magnitude of physiological but not subjective responses to alcohol‐related stimuli.
Length Changes in Dendritic Networks of Cerebellar Purkinje Cells of Old Rats after Chronic Ethanol Treatment
Authors: Pentney R. J. , Quackenbush L. J. , O'Neill M.
Published: April 2006

Dendritic networks of cerebellar Purkinje neurons from aging ethanol‐treated Fisher 344 rats were analyzed for metric changes in terminal and internal segments of the networks. Mean lengths of three categories of dendritic segments were determined. No significant metric changes in segment lengths were detectable immediately at the termination of 24 weeks of ethanol treatment, but significant changes were apparent after 8 weeks of recovery from ethanol treatment. Return to a diet of standard laboratory chow was associated with a period of dendritic extension in networks from pair‐fed control rats but not in those from the ethanol‐treated rats. The mulling significant differences in mean segment length were restricted to the paired terminal segments at the peripheral tips of the bifurcating networks. Unpaired terminal segments and internal segments of the networks showed no significant changes in length during the recovery period.
Effect of Three Alcohol Doses on Breathing during Sleep in 30–49 Year Old Nonobese Snorers and Nonsnorers
Authors: Scrima Lawrence , Hartman Paul G. , Hiller F. Charles
Published: April 2006

To test the effect of alcohol ingestion and snoring on deep‐disordered breathing (SDB), the sleep and respiration of 31 nonobese healthy males ages 30‐49 (15 snorers, 16 nonsnorers) were studied overnight after alcohol ingestion. Subjects received placebo, 0.32, 0.65, and 0.81 g alcohol/kg body weight prior to their evening bedtime, with each dose given on one of four nonconsecutive nights in a repeated‐measures counterbalanced design. On each night, respiration was assessed by recording respiratory effort from inter‐costal surface electromyography (EMG), ventilation from oral and MMI thermistors, and arterial oxygen saturation (SaO2) from an ear oximeter (BIOX III). Snorers had significantly: (a) more total SDB, (b) more obstructive deep apnea (OSA), and (c) lower minimum SaO2 than nonsnorers after the placebo and each alcohol dose. Snorers had more hypoxic events than nonsnorers after each alcohol dose but not after placebo. Increasing alcohol dose caused a statistically significant (p= 0.0004) decrease in minimum SaO2 in snorers only, but this decrease was small and probably not clinically important. Alcohol did not cause significant increases in SDB and hypoxic events, and did not have different effects on SDB and hypoxic events for snorers versus nonsnorers. Because this experiment included only nonobese 30–49‐year‐old males, these results do not imply that alcohol has no significant effects on obese subjects or those older than 50.
Sensitivity to Ethanol Hypnosis and Modulation of Chloride Channels Does Not Cosegregate with Pentobarbital Sensitivity in HS Mice
Authors: Allan Andrea M. , Harris R. Adron
Published: April 2006

Several findings suggest that barbiturates and alcohol produce their sedative effects through a common neural and possibly a common genetic mechanism. We tested this hypothesis by examining the correlation between ethanol and pentobarbital sedative effects in individual animals from a genetically heterogeneous population. The duration of pentobarbital‐induced hypnosis (sleep‐time) was unrelated to the sleep‐time produced by ethanol in heterogeneous stock (HS) mice. Therefore, the present study also examined the effect of ethanol, pentobarbital, and flunitrazepam on muscimol‐stimulated chloride flux into brain membranes prepared from HS mice selected for differences in pentobarbital‐ and ethanol‐induced sleep‐time. Brain membranes from mice selected for differences in ethanol sleeptime were differentially responsive to ethanol‐ and flunitrazepam‐, but not to pentobarbital‐induced augmentation of muscimol‐stimulated chloride flux. No differences in augmentation of chloride flux by ethanol, pentobarbital, or flunitrazepam were found in membranes prepared from mice differentially sensitive to pentobarbital hypnosis. The ability of muscimol to stimulate chloride uptake was not related to ethanol or pentobarbital sensitivity. These findings suggest that sensitivity to ethanol is not likely to be genetically linked to pentobarbital sensitivity.
Alcohol Exposure in Utero Results in Diminished T‐cell Function and Alterations in Brain Corticotropin‐Releasing Factor and ACTH Content
Authors: Redei Eva , Clark William R. , McGivem Robert F.
Published: April 2006

The long‐term teratogenic effects of prenatal ethanol exposure during the last week of gestation on immune responsiveness and levels of pituitary ACTH and hypothalamic corticotropin‐releasing factor (CRF) were examined in Sprague‐Dawley rats. Immune responsiveness was measured by T‐lymphocyte proliferation in response to mitogenic stimulation with Con A (3 μg/ml) in spleen and thymus cells of 21‐old‐day male refs who were exposed to alcohol in utero. The proliferative response was 8‐fold lower in spleen and twofold lower in thymus cells from alcohol‐exposed animals compared to responses measured in control rats. Thymus weight was significantly smaller at birth in alcohol exposed males, but significantly larger at 21 days of age compared to Controls. Alterations in the content of ACTH and CRF, hormones, known to be direct or indirect modulators of immune responsiveness, were also observed in alcohol exposed males. Hypothalamic Content of CRF and pituitary content of ACTH were significantly lower in alcohol exposed males on postnatal Day 1, but hypothalamic ACTH content was significantly higher compared to controls. These results indicate that alcohol exposure during the last week of gestation can produce alterations of the hypothalamic‐pituitary‐adrenal function in addition to teratogenic effects on the immune system which have been previously observed only with a much longer alcohol exposure regimen
Laboratory Markers as Compared to Drinking Measures before and after Inpatient Treatment for Alcoholism
Authors: Keso Lauri , Salaspuro Mikko
Published: April 2006

A study group, consisting of 60 male and 13 female alcohol‐dependent patients, participated in an inpatient treatment for alcoholism. They were interviewed about their alcohol use before the treatment period and bimonthly for 8 months after it.

It was found that the correlations between laboratory markers and average daily alcohol intake are very low (range, ‐0.01‐0.23) in alcoholics with high alcoholic intake level (before the treatment period).

It was also found that the correlations between the laboratory tests and the drinking measures after the initial assessment undergo large changes. The correlation between GOT and average daily alcohol intake before the treatment period was 0.07 (p= NS) and 2 months after the treatment period 0.55 (p < 0.001). The tong period of abstinence, the change to a lower level of akohd consumption, and improved accuracy of reporting akohd intake were probably causative in this change.

GGT proved to have the highest correlations with the drinking measures during the follow‐up and MCV before the treatment period. The frequency measure, number of drinking days, gave consistently higher correlations with the laboratory markers than the measure of drinking amount, average daily alcohol intake.

Laboratory markers, GGT and MCV, are well suited for outcome evaluation of drinking behavior of alcoholics after inpatient treatment for alcoholism or other comparative periods of abstinence.
Acute Hypocalcemic Effect of Ethanol in Dogs
Authors: Money Samuel R. , Petroianu Andy , Kimura Keichu , Jaffe Bernard M.
Published: April 2006

Ethanol has been shown to reduce serum calcium in multiple animal studies. However, in human studies done using lower doses of alcohol, only inconclusive results have been obtained. This study was undertaken to evaluate the effects of varying doses of oral ethanol on total serum calcium. Fin adult mongrel dogs (17‐25 kg) were divided into three groups which differed in the dosage of ethanol given. Group I animals received 0.5 g/kg of either Group II, 1.0 g/kg ethanol; and Group III, 2.0 g/kg of ethanol. Venous Mood was sampled for estimation of concentrations of total serum calcium and ethanol. In the animals in Group I, serum calcium levels were unchanged by the ethanol. In both Groups II ad III, significant reductions in serum calcium were demonstrated, which occurred within 5 min of intoxication. The mean decrease in serum calcium in Group III animals was significantly greater than that in either Group I and II. We conclude that the rapid hypocalcemic effect requires a threshold amount of ethanol before it becomes chemically evident. This critical value in dogs approximated 1 g/kg which results in a mean peak serum alcohol Concentration of 117 ± 6 mg/dl.
Acceleration of Ethanol Metabolism by Past Thiamine Deficiency
Authors: Martin Peter R. , Impeduglia Giovanni , Giri P. Rathna , Karanian John
Published: April 2006

Six months after severe thiamine deficiency, when their body and liver weights had normalized, male Sprague‐Dawley rats were exposed to constant ethanol vapor concentrations for 6 days in an inhalation chamber and Mood ethanol concentrations (BECs) were determined. Previously induced thiamine deficiency was associated with about a 50% reduction of BECs and a significant increase in liver alcohol dehydrogenase (ADH) activity suggesting a persistent acceleration of ethanol metabolism. No significant changes were found in liver aldehyde dehydrogenase activity, plasma levels of thyroxine, testosterone, or estradid, or brain or liver histology. Plasma growth hormone concentrations were about 60K lower in the experimental group than in controls, but this effect of previous thiamine deprivation did not correlate with changes in ADH activity. Therefore, it remains to be elucidated how thiamine deficiency‐induced central nervous system alterations may contribute to the development of metabolic tolerance to ethanol.
Noninvasive Estimation of Blood Alcohol Concentrations by Eye Vapor Analysis Using an Electrochemical Fuel Cell Detector
Authors: Giles H. G. , Sandrin S. , Saldivia V.
Published: April 2006

A widely used breath analysis instrument was adapted for the non‐invasive determination of Mood alcohol in small animals. The instrument's response to ethanol in vapor above the lacrimal fluid was analyzed subsequent to taking vapor samples from a small eye cup for 15 sec. After ethand administration (1.5 g/kg, orally) to rats, eye vapor measurements and venous Mood samples were obtained over 5 hr. Eye vapor measurements were transposed into Mood alcohol Con‐ns and compared with concentrations obtained by gas chromatographic analysis of blood. The correlation of concentrations obtained by the two methods yielded correlation coefficients of 0.93 and 0.95 depending on the calculation used. Eye vapor response and blood alcohol concentration were also found to be highly correlated (r= 0.98) after alcohol administration to mice and sampling for 2.5 hr after ethanol administration. Kinetic profiles obtained by eye vapor analysis and gas chromatography are virtually identical. The method described allows widespread use of a new, noninvasive approach to alcohol analysis in laboratory animals.
Mechanisms of Alcohol‐induced Suppression of B‐Cell Response
Authors: Aldo‐Benson Marlene
Published: April 2006

Several investigators have shown that alcohol can suppress the production of antibodies by animals and humans. The studies reported here were designed to determine whether alcohol has a direct effect on the B‐lymphocyte and to determine which stage of the B‐cell response is inhibited by alcohol.

B‐lymphocyte lines specific for the antigen dinitrophenyl were used to study the effect of alcohol on the B‐lymphocyte. As little as 100 mg% of alcohol inhibited the response of these pure B‐cell lines to stimulation by either antigen (dinitrophenyl‐Ficoll) or anti‐μ antibody. Since no other cell types were present in the system the suppressive effect was on the B‐cell itself. However, alcohol did not inhibit membrane depolarization induced by antigen crosslinking of immunoglobulin receptors, and it did not inhibit activation of the phosphotidyl inositol pathway by receptor crosslinking.

When alcohol was added to antigen stimulated B‐lymphocyte lines for varying periods during the immune response it was found that antibody production was inhibited if 150 mg% alcohol was present from 30 to 48 hr after the antigen was added to lymphocytes. Thirty six to 48 hr is the time required for a stimulated mature B‐lymphocyte to enter the proliferative phase of the immune response. These data raise the possibility that low doses of alcohol can inhibit antigen induced B‐cell proliferation.
Influence of Ethanol Consumption on Natural Killer Cell Activity in Mice
Authors: Meadows Gary G. , Blank Sally E. , Duncan Deborah D.
Published: April 2006

Alcohol is a known suppressant to the immune system, and alcoholics frequently have impaired humoral and cell‐mediated immunity. Several studies indicate that alcohol modulates natural killer (NK) cell activity. NK cells provide important defense against certain infectious diseases, spontaneously arising tumors and, in particular, to blood‐borne metastasizing tumor cells. Evaluation of the effects of alcohol on NK cells is complicated by many factors including: the level and duration of alcohol abuse, polydrug use, the subject's age, and nutritional and health status. This study examined the effects of 1 and 2 weeks of alcohol consumption on baseline and interleukin 2 (IL‐2) stimulated murine NK cell activity. Well nourished female C57BL/6 mice were given continuous access to 20% w/v ethanol as the sole fluid source and consumed about 40% of their total caloric intake as ethanol. Splenic baseline and IL‐2 stimulated NK cell activity were significantly lower in ethanol‐consuming groups compared to control groups after the 1‐ and 2‐week test periods. The average daily intake of ethanol, blood alcohol concentration, and the percentage of ethanol‐derived calories were not associated with the decreased NK cell activity of the experimental animals; nor did any other measured parameter appear to serve as an indicator of ethanol modulation of splenic NK cell activity. Whether this immunosuppression results from the “direct” modulation of ethanol or from indirect factors is presently unknown.
Ethanol: An Enhancer of Transplantation Antigen Expression
Authors: Singer Dinah S. , Parent Leslie J. , Kolber Michael A.
Published: April 2006

Major histocompatibility antigens (MHC) play a pivotal role in the immune response. Abnormal expression of MHC antigens has been correlated with aberrant regulation of the immune response. Studies on the effect of ethanol on class I MHC antigens demonstrate that ethanol significantly enhances their cell surface expression in a variety of cell lines in vitro. These changes in cell surface levels reflect increased intracellular protein synthesis and increased steady state mRNA levels. The effective ethanol concentrations (0.1‐1.0%) are physiologically attainable. Measurement of class I MHC antigens on peripheral blood lymphocytes in a population of acutely ethanol‐intoxicated patients showed a highly significant increase relative to controls. The possibility that the elevated levels of MHC antigens induced by ethanol may play a role in the evolution of ethanol‐related disease is discussed.
Mechanisms of Suppression of Cellular Immunity Induced by Ethanol
Authors: Jerrells Thomas R. , Peritt David , Marietta Cheryl , Eckardt Michael J.
Published: April 2006

Previous study findings from this laboratory and other laboratories have established that ethanol administration to experimental animals or ingestion by human beings results in many changes in the immune system. The major effort in this laboratory is the study of the mechanisms by which ethanol down‐regulates the responses of thymus‐derived lymphocytes. By using a rat model of ethanol intoxication we have described a defect in lymphocyte proliferation to concanavalin A. In the current report data, preliminary and definitive, are presented that show our approach to determining the mechanisms of ethanol‐associated impairments in the immune system, especially the defect in lymphocyte proliferation. We have found that purified thymus‐derived lymphocytes from the spleens of ethanol‐treated rats have an inherent defect in their response to mitogenic stimulation. This defect is not caused by the direct effects of ethanol on the cells and probably is not caused by an inability of the cells from ethanol‐treated animals to produce the lymphocyte growth factor interleukin 2. Data are also presented that indicate that corticosteroids, produced most abundantly in this model by withdrawal from ethanol, play a role in the down‐regulation of the response of spleen cells to mitogenic stimulation.
Analogical Reasoning Abilities of Recovering Alcoholics
Authors: Gardner Michael K. , Clark Elaine , Bowman Mary Ann C. , Miller Patrick J.
Published: April 2006

This study investigated analogical reasoning abilities of alcoholics who had been abstinent from alcohol for at least 1 year. Their performance was compared to that of nonalcoholic controls matched as a group for education, age, and gender. Solution times and error rates were modeled using a regression model. Results showed a nonsignificant trend for alcoholics to be faster, but more error prone, than controls. The same componential model applied to both groups, and fit them equally well. Although differences have been found in analogical reasoning ability between controls and alcoholics immediately following detoxification, we find no evidence of differences after extended periods of sobriety.
Elevated Concentrations of Acetone and Unidentified Compounds in the Breath of Alcohol Abusers
Authors: Phillips Michael , Greenberg Joel , Martinez Victoriano
Published: April 2006

A highly sensitive gas chromatographic assay was used to measure volatile organic compounds in the breath. Samples of breath from three groups of subjects were studied: normal volunteers (n= 15), acutely intoxicated alcohol abusers (n= 11), and abstinent alcohol abusers (n= 13). Acetone levels were significantly higher in the acutely intoxicated subjects than in the normals (p < 0.05) or the abstinent alcohol abusers (p < 0.05). Chromatographic peaks arising from 13 unidentified compounds in the breath were observed; two of these unidentified compounds were observed only in the intoxicated and abstinent alcohol abusers. Statistically significance was achieved in only one unidentified peak; elevated levels of this compound were seen in both acutely intoxicated alcohol abusers (p < 0.01) and in the abstinent alcohol abusers (p < 0.01) when they were compared to normal subjects.
Decreased in Vivo Rate of Ethanol Metabolism in the Suckling Rat
Authors: Zorzano Antonio , Herrera Emilio
Published: April 2006

Blood concentrations of ethanol and acetaldehyde were determined in suckling rats after a single oral ethanol gavage. These results were compared with the hepatic activities of alcohol and aldehyde dehydrogenase. After intragastric administration of 3 g/kg body weight of ethanol, ethanol concentrations were much higher in suckling rats than in adult animals, especially at 90, 120, and 180 min after its administration. In addition, acetaldehyde concentrations were undetectable in suckling rats as opposed to adult rats, in whom micromolar concentrations were detected. Thus, 5‐ to 30‐day‐old rats seem to have a limited capacity for in vivo ethanol metabolism. The analysis of hepatic alcohol dehydrogenase activity revealed that it was very low at birth and it increased progressively with time attaining adult levels after 20 days of life. The alcohol dehydrogenase activity present in the liver of suckling rats presented similar Km values and sensitivity to pyrazole as adult rat liver. Thus, the pattern of in vivo ethanol elimination during the suckling period is not explained by hepatic alcohol dehydrogenase activity. Whether that diminished ethanol metabolism is due to slower intestinal ethanol absorption, different ethanol distribution in the body, or diminished hepatic capacity for NADH reoxidation remains to be studied.

At birth, hepatic aldehyde dehydrogenase activity was low and it increased reaching adult levels during the suckling period. Adult levels for the component of low Km were attained earlier than for the component of high Km. The low affinity hepatic aldehyde dehydrogenase component in the newborn was different from that in the adult as assessed by kinetic studies and by its sensitivity to disulfiram. Nevertheless, the fact that acetaldehyde was not detected after ethanol ingestion in suckling rats, suggests that there is enough hepatic aldehyde dehydrogenase activity to metabolize all the acetaldehyde generated in liver by alcohol dehydrogenase.
Pathological Changes in Peripheral Nerves in Experimental Fetal Alcohol Syndrome
Authors: Baruah J. K. , Kinder D.
Published: April 2006

The peripheral nerve pathology is described in experimental fetal alcohol syndrome. The marked retraction and shrinkage of axons with vacuolar spaces in the periaxonal area are the striking features. The direct toxicity of ethanol or its metabolites on the nerve fibers is considered to be the cause for pathological changes. Additional biochemical factors, pyridoxal phosphate dependent enryme‐depletion in the genesis of nerve damage, is proposed.
Assessment of the Transferrin Index in Screening Heavy Drinkers from a General Practice
Authors: Poupon Renée E. , Schellenberg François , Nalpas Bertrand , Weill Jacques
Published: April 2006

The aim of this study was to assess the performance of the transferring (Tf) index in screening heavy drinkers and to compare its performance to that of gamma glutamyl transpeptidase (GGT). Tf index, GGT, and transaminase activities were determined in a group of 173 subjects (49% males) recruited in a family doctor's practice (age: 54 ± 1.5 yr; daily alcohol intake: 32 ± 3.5 g; mean ± SEM). Tf subfractions were quantified by isoelectric focusing and immunofixation on polyacrylamide gel. The Tf pl 5.7 to 5.4 ratio, or Tf index, was used as a marker of excessive drinking, with a cut‐off point at 7%. Alcohol consumption was assessed through a face‐to‐face interview. Excessive drinkers were defined as those with a daily alcohol intake greater than 80 g over at least 2 years; 20 were classified as excessive drinkers (alcohol consumption: 92–232 g/day). All but four had normal transaminase activities indicating the low prevalence of hepatic impairments in this sample. The Tf index was found to have a sensitivity of 4570, specificity 89%, positive predictive value 3570, negative predictive value 92%. The corresponding results for GGT were 5270, 80%, 2770, and 92%. respectively. Concordance between the Tf index and GGT was assessed by the kappa coefficient (κ) which was 0.22 indicating poor agreement between the two markers in selecting excessive drinkers (perfect association: κ= 1, no association: κ= 0).
Hepatic Synthesis of Apoproteins of Very Low Density and High Density Lipoproteins in Perfused Rat Liver: Influence of Chronic Heavy and Moderate Doses of Ethanol
Authors: Lakshman M. R. , Chirtel Stuart J. , Chambers Laura C. , Campbell Barbara S.
Published: April 2006

The effects of 6 weeks of heavy and moderate ethanol feeding to rats upon lipids and lipoprotein metabolism were determined. As compared to the control group, the heavy ethanol feeding resulted in the following changes: liver weight/kilogram body weight increased by 48% (p < 0.001) with a concomitant 52% increase (p < 0.001) in liver protein/kilogram body weight and a 2.75‐fold (p < 0.001) increase in liver total lipids/kilogram body weight. in contrast, liver DNA/kilogram body weight or per liver was not affected significantly. Plasma cholesterol and triglycerides were higher by 53% (p < 0.01) and 77% (p < 0.01), respectively. Liver cholesterol and triglycerides were 4.4‐fold and 3.6‐fold higher (p < 0.001), respectively. Plasma total A, was 1.72‐fold higher (p < 0.001), whereas there was no significant difference in plasma apo E levels between the two groups. However, plasma high density lipoproteins (HDI) apo E was 48% lower (p < 0.02) while the very low density lipoproteins (VLDL) E was 2.15‐fold higher (p < 0.02).

Hepatic total protein synthetic rate in the ethanol group was not significantly different from the control group. In contrast, labeled leucine incorporation into the total secretory proteins was inhibited by 36% (p < 0.01) in ethanol‐fed group. Specifically, inhibitions of the synthetic rates of various secretory proteins in the ethanol group compared to the control group were as follows: by 55% (p < 0.005) for total VLDL apoproteins, by 44% (p < 0.05) for apo A1 protein, by 55% (p < 0.001) for total apo E proteins, by 62% (p < 0.001) for VLDL apo E, by 52% (p < 0.001) for HDL apo E and by 50% (p < 0.001) for transferrin. In contrast, moderate ethanol feeding for six weeks did not alter any of the above parameters. Thus, impaired synthesis/secretion of VLDL and HDL could be the major cause for fatty liver after alcohol abuse.
Prenatal Exposure to Ethanol Alters the Ontogeny of the β‐Endorphin Response to Stress
Authors: Angelogianni P. , Gianoulakis C.
Published: April 2006

To determine whether prenatal exposure to ethanol alters the response of the β‐endorphin (β‐EP) system to stress, the effect of two types of stressful stimuli, ether and cold, was examined in the offspring of rats which during pregnancy were: (a) fed with an ethanol‐containing diet; (b) pair‐fed with an isocaloric sucrose diet; and (c) fed ad libitum with standard lab chow (basic control group). The effect of stress on the content of β‐EP in the serum, pituitary gland and hypothalamus, as well as on the serum corticosterone and hypothalamic corticotropin‐releasing factor (CRF) content was examined. Pups prenatally exposed to ethanol had significantly higher serum β‐EP levels on Day 1 and higher serum corticosterone levels on Days 1‐3 when compared to their pair‐fed or basic controls. On all days tested pituitary β‐EP content was lower in the offspring of the ethanol‐treated rats than in the control groups. There was no difference in the total hypothalamic β‐EP content between the three treatment groups; however, during the first 10 days of life a higher concentration (ng/mg protein) of β‐EP was observed in the hypo‐thalami of the ethanol and the pair‐fed group when compared to the basic control pups. Hypothalamic CRF levels, though significantly lower in the pups exposed to ethanol in utero than in the control groups on Day 3, increased significantly in the ethanol group between Days 14 and 22, while no significant change was observed during this period in either of the control groups. From Days 1 to 10 significant elevations in serum corticosterone, levels were observed following both types of stress in the pair‐fed and the basic control group, while no significant response, to either type of stressful stimuli, was observed prior to Day 14 in the pups exposed to ethanol prenatally. On Day 14 cold stress induced small increases in the serum β‐EP and corticosterone levels of the offspring treated prenatally with ethanol which, however, were less pronounced than the elevations observed in both of the control groups. Furthermore, exposure to ether stress on Day 14 elicited no response by the β‐EP system of the ethanol‐exposed offspring. In contrast, the 22‐day‐old offspring of the ethanol‐treated rats exhibited greater elevations in serum β‐EP and corticosterone levels, following stress, than the offspring of the pair‐fed and basic control groups. The elevations of serum β‐EP levels following stress were associated with small decreases in the pituitary β‐EP and hypothalamic CRF contents. Thus, the response of the β‐EP system to stress was modified by prenatal exposure to ethanol, being suppressed at early postnatal life and enhanced at later stages of development. The transition from reduced to enhanced responsiveness seemed to occur during the third week of life.
Effects of Alcohol on the Acoustic‐Phonetic Properties of Speech: Perceptual and Acoustic Analyses
Authors: Pisoni David B. , Martin Christopher S.
Published: April 2006

This report summarizes the results of a series of studies that examined the effects of alcohol on the acoustic‐phonetic properties of speech. Audio recordings were made of male talkers producing lists of sentences under a sober condition and an intoxicated condition. These speech samples were then subjected to perceptual and acoustic analyses. In one perceptual experiment, listeners heard matched pairs of sentences from four talkers and were required to identify the sentence that was produced while the talker was intoxicated. In a second perceptual experiment, Indiana State Troopers and college undergraduates were required to judge whether individual sentences presented in isolation were produced in a sober or an intoxicated condition. The results of the perceptual experiments indicated that groups of listeners can significantly discriminate between speech samples produced under sober and intoxicated conditions. For acoustic analyses, digital signal processing techniques were used to measure acoustic‐phonetic changes that took place in speech production when the talker was intoxicated. The results of the acoustical analyses revealed consistent and well‐defined changes in speech articulation between sober and intoxicated conditions. Because speech production requires fine motor control and timing of the articulators, it may be possible to use acoustic‐phonetic measures as sensitive indices of sensory‐motor impairment due to alcohol consumption.
Prenatal Ethanol Exposure Decreases Hippocampal Mossy Fiber Zinc in 45‐Day‐Old Rats
Authors: Savage Daniel D. , Montano Christine Y. , Paxton Linda L. , Kasarskis Edward J.
Published: April 2006

The long‐term consequences of prenatal ethanol exposure on histochemically detectable hippocampal mossy fiber zinc was examined using a recently developed quantitative histofluorescence procedure. Pregnant Sprague‐Dawley rats were maintained throughout gestation on one of three dietary regimens: (a) a liquid diet containing either 3.35% ethanol, (b) an isocalorically matched liquid diet pair‐fed to the 3.35% ethanol group, or (c) lab chow ad libitum. At 45 days of age, offspring from each of the three diet groups were sacrificed for determination of hippocampal mossy fiber zinc and zinc analysis of selected tissues by atomic absorption spectroscopy.

Hippocampal mossy fiber zinc was reduced by 36% in dorsal and 20% in ventral hippocampal formation stratum lucidum of rats exposed to the 3.35% ethanol diet compared to the offspring of the pair‐fed control and ad libitum control dams. No significant differences in zinc: TS‐Q histofluorescence were observed between the ad libitum and pair‐fed control groups. No significant differences were observed among groups in tissue wet weight or tissue zinc concentration in any of the brain or other body regions analyzed. These results indicate a long lasting prenatal ethanol exposure‐induced reduction in hippocampal mossy fiber zinc in the absence of changes in any indices of total body zinc nutriture. These results suggest that prenatal exposure to relatively low blood ethanol levels (30–40 mg/dl) has subtle, yet long‐lasting effects in the hippocampal formation, a brain region important in the process of memory consolidation.
Verbal and Nonverbal Right Hemisphere Processing by Chronic Alcoholics
Authors: Cermak Laird S. , Verfaellie Mieke , Letourneau Lynn , Blackford Susan , Weiss Susan , Numan Bobbi
Published: April 2006

The theory that chronic alcoholism produces a right hemisphere deficit has generally been tested using visuospatial tasks. The present report tested the theory using three tasks that tap functions, ether than visuospatial abilities, which have been failed by patients with right hemisphere damage. The first task assesses the ability to draw a correct inference by integrating information from two unrelated sentences. The second taps the patient's capacity to appreciate humor. The third requires the patient to interpret the emotion displayed in a face. On all three tasks, the pattern of responses of Chronic alcoholics differed from that of patients with right hemisphere damage. Thus, the right hemisphere deficit theory fails to gain support from this investigation. On the other hand, the chronic alcoholics' performance was impaired relative to contemporary controls on the first two tasks, although not on the last On the first two tasks, alcoholics' impairment approximated, and in one instance exceeded, that seen in normal elderly controls. Thus, a premature aging hypothesis received modest support from this study.
Effects of Alcohol Ingestion on in Vitro Susceptibility of Peripheral Blood Mononuclear Cells to Infection with HIV and of Selected T‐Cell Functions
Authors: Bagasra Omar , Kajdacsy‐Balla Andre , Lischner Harold W.
Published: April 2006

A role for the biological effects of alcohol is postulated in the increased risk of AIDS known to be associated with chronic alcohol abuse and alcohol consumption during sexual activity. In pilot experiments peripheral blood mononuclear cells from healthy volunteers were studied before and after a single ingestion of 0.7 to 3.1 liters of beer or an equivalent dose of ethanol in other beverages. After moderate alcohol consumption there was increased human immunodeficiency virus (HIV) replication in peripheral blood mononuclear cells during 28 days of culture without mitogen stimulation as indicated by overnight syncytium formation with SUP‐T1 indicator cells and by increased levels of HIV p24 antigen in the culture supernates. There was also decreased ability of lymphocytes to produce interleukin 2 and soluble immune response suppressor activity after stimulation with concanavalin A, the former, possibly both, for over 4 days after alcohol ingestion. These preliminary data extend well‐known immunosuppressive effects of chronic alcohol ingestion to acute ingestion and raise the question: Could even casual alcohol consumption enhance HIV infectivity and/or enhance the progression of latent HIV infection?