bluuebunny/crossref_metadata_2025 huggingface dataset:
Alcohol‐Induced Inhibition of LH Secretion in Intact and Gonadectomized Male and Female Rats: Possible Mechanisms
Authors: Rivier Catherine , Rivest Serge , Vale Wylie
Published: April 2006

Alcohol (EtOH) is reported to decrease gonadotropin secretion, but the mechanisms mediating these changes are not fully understood. The present study examined the ability of acutely or chronically administered EtOH to alter plasma luteinizing hormone (LH) and follicle stimulating hormone (FSH) levels in both male and female rats, and correlated these changes with blood EtOH levels (BALs); investigated possible changes in the pituitary responsiveness of animals exposed to EtOH; and probed the role of the paraventricular nucleus (PVN) of the hypothalamus in mediating alcohol‐induced decreases in plasma LH levels.

The injection of 0.5 g EtOH/kg was accompanied by significantly higher BALs in females compared with males. This dose of alcohol did not alter rectal temperature, and only significantly (p≤ 0.01) decreased plasma LH levels in female rats. These findings were not altered by removal of gonadal steroids. Administration of 2.0 g EtOH/kg was followed by BALs that were comparable in both groups of rats at the 1‐ and 2‐hr time‐points, but were significantly (p≤ 0.01) higher in females 3 hr after treatment. Rectal T measurably decreased in all rats injected with 2 g EtOH/kg, though intact females showed the greatest change. This alcohol treatment also significantly (p≤ 0.01) inhibited immunoreactive LH release in both sexes, but there were no measurable changes in FSH values at any time. Using alcohol regimens which significantly lowered LH values in both sexes, we then showed that neither acute nor prolonged (7 days) treatment of male or female rats with alcohol measurably altered the LH response to 10, 30, or 100 ng gonadotropin‐releasing hormone (GnRH). Finally, we observed that in male rats, destruction of the PVN did not prevent the inhibitory effect of acute alcohol administration on LH secretion.

These results indicate that alcohol‐induced decreases in plasma LH levels are not primarily mediated by changes in pituitary responsiveness to GnRH, and that the PVN is not necessary for the inhibitory effect of alcohol on LH secretion. It is therefore probable that alcohol acts outside the PVN to alter brain neurotransmitters that impact on GnRH‐secreting neurons.
Outcome in Subjects with Alcohol‐Provoked Seizures
Authors: Pieninkeroinen Ilkka P. , Telakivi Tiina M. , Hillborn Matti E.
Published: April 2006

The outcome in 165 subjects with either an unknown (n= 93) or an alcohol‐related (n= 72) seizure etiology, admitted to the emergency room of a general hospital in 1977–1978, was assessed after 10 years on the basis of subsequent hospital records and death‐certificate‐based mortality data. Alcohol and/or drug poisoning was the most frequent cause of death in the group with alcohol‐related seizures. Sixty‐four percent of the deaths in this group were directly related to alcohol abuse. The crude mortality was 45.8 (expected 8.6)/100 persons/10 years in the group with alcohol‐related seizures and 15.1 (expected 6.0)/100 persons/10 years in the other group, the odds ratio between the groups being 4.8. Twenty percent of those with an unknown seizure etiology were found to show alcohol related seizures, while the seizure etiology remained unknown in 59%, and a specific etiology other than alcohol abuse was revealed in 21% during the follow‐up period.

We conclude that alcohol abuse is an important, though often undetected, seizure etiology carrying a poor prognosis. The difference in mortality between the groups was due more to alcoholism than to seizures. There was no difference in mortality between those with a first alcohol‐related seizure and those with previous alcohol‐related seizures.
The Short‐Term Psychological Health of Alcoholic and Non‐Alcoholic Liver Transplant Recipients
Authors: Beresford Thomas P. , Schwartz Joseph , Wilson Deborah , Merion Robert , Lucey Michael R.
Published: April 2006

In response to limited resources and overwhelming clinical need, we previously developed an approach to alcoholic patient selection for liver transplant based on factors reported to predict short‐ and long‐term sobriety in prospective studies of alcoholics. The present study reports follow‐up data comparing alcohol dependent (n= 22, DSM‐3‐R criteria) and non‐dependent (n= 39) subjects followed from 6 months to 3 years post‐transplant. Nine percent of the alcoholics had returned to symptomatic drinking with 14% reporting some exposure to ethyl alcohol. Nearly half (46%) of the non‐alcoholic group reported occasional social alcohol use. The alcoholic patients were less likely to be in their first marriage and more likely to be asked about alcohol use at follow‐up clinic visits. In most other respects the two groups resembled each other more often than they differed. The alcoholic group reported continued high rates of prognostic factors associated with long‐term abstinence although the content of these shifted noticeably between pre‐ and postoperative assessment. Members of both groups reported high frequencies of medication side effects, of missed doses of medications, and of depressive symptoms. Most felt the transplant had improved their lives but had brought on significant financial burden. There were no differences in subjective appraisals of either psychological or physical health between the two groups. These follow‐up data suggest that carefully selected alcohol dependent patients will do as well as non‐dependent patients after liver transplant.
Brain Lesions in Alcoholics
Authors: Charness Michael E.
Published: April 2006

Brain lesions in alcoholics are multifactorial in origin. Ethanol neurotoxicity, Wernicke's encephalopathy, hepatocerebral degeneration, head trauma, central pontine myelinolysis, Marchiafava‐Bignami syndrome, pellagra, and premorbid pathological conditions, such as fetal alcohol syndrome, may all contribute to cognitive dysfunction in alcoholics. With the exception of ethanol neurotoxicity, all of these conditions are associated with specific neuropathological lesions. Wernicke's encephalopathy, the neurological syndrome of thiamine deficiency, is frequently overlooked during life and may cause global dementia as well as the more familiar Korsakoff's amnestic syndrome. Distinguishing ethanol neurotoxicity from nutritional deficiency can be facilitated by magnetic resonance imaging, which can visualize some of the specific macroscopic lesions of Wernicke's encephalopathy, central pontine myelinolysis, cerebellar degeneration, and Marchiafava‐Bignami syndrome. Computerized morphometric studies of alcoholic brains have revealed ventricular enlargement, selective loss of subcortical white matter, and alterations in neuronal size, number, architecture, and synaptic complexity. These lesions tend to be more severe when there is coexisting nutritional deficiency or liver disease, suggesting that ethanol neurotoxicity may not be the sole cause. A search for similar lesions in nonalcoholic Wernicke's encephalopathy and nonalcoholic liver disease will help determine the specificity of these lesions.
Determinants of Ethanol and Acetaldehyde Metabolism in Chronic Alcoholics
Authors: Panés Julián , Caballería Joan , Guitart Raimón , Parés Albert , Soler Xavier , Rodamilans Miguel , Navasa Miguel , Parés Xavier , Bosch Jaurne , Rodés Joan
Published: April 2006

We have studied the factors determining the rate of ethanol and acetaldehyde metabolism in a group of 25 alcoholics with varying degrees of liver lesion (from normal liver to cirrhosis) and in six nonalcoholic cirrhotics. In alcoholics the ethanol metabolic rate was related to hepatic function, estimated either by the aminopyrine breath test (r= 0.70,p< 0.001) or the indocyanine green clearance (r= 0.76,p< 0.01), and was independent of the activity of hepatic alcohol dehydrogenase and hepatic blood flow. In nonalcoholic cirrhotics blood acetaldehyde was always below the detection limit (0.5 μM), but elevated levels were found in 14 out of the 25 alcoholics. Alcoholics with elevated blood acetaldehyde showed a significantly higher ethanol metabolic rate than alcoholics with undetectable acetaldehyde (120 ± 17 mg/kg/hr vs 104 ± 11 mg/kg/hr,p< 0.02), but no differences were observed in the activities of alcohol and aldehyde dehydrogenases. Peak blood acetaldehyde levels were directly related to the ethanol metabolic rate (r= 0.48,p< 0.02), but not to activities of hepatic alcohol or aldehyde dehydrogenases. These results indicate that in chronic alcoholics the main determinant of the ethanol metabolic rate is hepatic function, while the rise of blood acetaldehyde is mainly dependent on the ethanol metabolic rate. Alcohol and aldehyde dehydrogenase activities do not seem to be rate‐limiting factors in the oxidation of ethanol or acetaldehyde.
Repeated Episodes of Ethanol Withdrawal Potentiate the Severity of Subsequent Withdrawal Seizures: An Animal Model of Alcohol Withdrawal “Kindling”
Authors: Becker Howard C. , Hale Robert L.
Published: April 2006

Prior experience with ethanol (EtOH) withdrawal may sensitize an individual to subsequent withdrawal episodes. It has been hypothesized that the progressive intensification of the EtOH withdrawal syndrome following repeated episodes of EtOH intoxication and withdrawal may represent the manifestations of a “kindling” mechanism. The purpose of this study was to develop an animal model of EtOH withdrawal that is sensitive to the effects of prior withdrawal experience. Adult male C3H mice were chronically exposed to EtOH vapor in inhalation chambers prior to withdrawal testing. A multiple withdrawal (MW) group received 3 cycles of 16 hr EtOH vapor separated by 8‐hr periods of abstinence; a single withdrawal (SW) group received a single bout of EtOH exposure (16 hr); a third group (SW‐CONT) experienced a single withdrawal episode after receiving the equivalent amount of EtOH intoxication as the MW group (16 × 3 = 48 hr), but in a continuous (uninterrupted) fashion; and a fourth group (C) served as controls, not receiving any EtOH exposure throughout the study. Severity of the withdrawal response was assessed by scoring handling‐induced convulsions hourly for the first 10 hr and then at 24 hr postwithdrawal. The results indicated that the severity of EtOH withdrawal seizures was significantly greater in animals that had a prior history of withdrawal episodes (MW group) in comparison to a separate group of animals that were tested following a single withdrawal from the same 16‐hr intoxication period (SW group). Moreover, the intensity of withdrawal seizures in MW animals was significantly greater than in animals exposed to an equivalent total amount of intoxication (48 hr), but only withdrawn a single time (SW‐CONT group). Differences in the severity of EtOH withdrawal seizures due to differences in prior withdrawal experience do not appear to be related to compromised health of the animals or to differences in the level of intoxication (blood EtOH levels) immediately preceding withdrawal assessment. As such, these results support the “kindling” hypothesis of EtOH withdrawal and provide a model with which to study potential mechanisms underlying the phenomenon.
Treatment of Pregnant Alcohol‐Consuming Rats with Buspirone: Effects on Serotonin and 5‐Hydroxyindoleacetic Acid Content in Offspring
Authors: Tajuddin Nuzhath F. , Druse Mary J.
Published: April 2006

This laboratory previously demonstrated that in utero ethanol exposure markedly impairs the development of the serotonergic system in rat brain. Developmental abnormalities could be detected as early as G15 in the brainstem and G19 in the cortex. Because of the importance of fetal serotonin (5‐HT) and 5‐HT1A receptors for the normal development of 5‐HT containing neurons, we initiated studies to determine whether administration of a 5‐HT1A agonist, buspirone, to pregnant rats could overcome the adverse effects of in utero ethanol exposure on the developing serotonergic system in offspring.

Female, Sprague‐Dawley rats were given daily subcutaneous injections of buspirone (4.5 mg/kg) from gestational day 13 (G13) to G20. 5‐HT and 5‐hydroxyindoleacetic acid (5‐HIAA) content were determined in the cortex and cortical regions. These experiments demonstrated that the ethanol‐associated abnormalities in the development of the serotonergic system can be partially overcome by in utero exposure to buspirone. Specifically, whereas untreated ethanol rats had a deficiency of 5‐HT and/or 5‐HIAA in whole cortex on PN5, and in the motor cortex on PN19 and 35, no significant differences were detected in these regions of the age‐matched offspring of buspirone‐treated, ethanol‐fed rats. In contrast, the 5‐HT and 5‐HIAA deficiency in the somatosensory cortex of 19‐dayold offspring of ethanol‐fed rats was not corrected by in utero buspirone treatment.

These results suggest that the abnormal development of cortical projections of serotonergic neurons may be due in part to the low fetal 5‐HT content in ethanol‐exposed rats and may potentially be overcome by in utero treatment with a 5‐HT1A agonist. However, additional studies are needed to elucidate the importance of dose and timing of buspirone administration, and the effects of in utero buspirone exposure on other components of serotonergic and nonserotonergic neurons.
Anticipated Stimulant and Sedative Effects of Alcohol Vary with Dosage and Limb of the Blood Alcohol Curve
Authors: Earleywine Mitchell , Martin Christopher S.
Published: April 2006

Anticipations of alcohol's effects reportedly covary with the amount consumed. Alcohol's stimulant and sedative properties also may contribute to alcohol consumption. Anticipations of stimulant and sedative effects have not been investigated extensively. The present study examined the stimulant and sedative effects subjects anticipated experiencing if they were on the ascending or descending limb of the blood alcohol curve after consuming two or four standard drinks. One hundred sixty‐six undergraduates reported anticipating greater stimulant effects than sedative effects on the ascending limb of the blood alcohol curve, and greater sedative effects than stimulant effects on the descending limb. Subjects also reported anticipating larger effects with larger doses. Men tended to anticipate smaller effects than women. These results support the notion that specific anticipated effects vary with dosage and the limb of blood alcohol curve, suggesting that the study of anticipated effects of alcohol should employ these variables.
Development and Validation of the Biphasic Alcohol Effects Scale
Authors: Martin Christopher S. , Earleywine Mitchell , Musty Richard E. , Perrine M. W. , Swift Robert M.
Published: April 2006

Alcohol produces stimulant and sedative effects, and both types of effect are thought to influence drinking practices. This article describes the development and preliminary validation of the Biphasic Alcohol Effects Scale (BAES), a self‐report, unipolar adjective rating scale designed to measure both stimulant and sedative effects of alcohol. An initial pool of 12 stimulant and 12 sedative items was derived from previous alcohol effect measures, and from descriptors of intoxication generated by subjects during interviews conducted on both the ascending and descending limbs of the blood alcohol curve. This item pool was administered to a sample of sober college students twice, with a 2‐week inter‐test interval. Items that were difficult to comprehend, or that had high ratings or low test‐retest reliability, were eliminated, resulting in a seven‐item stimulant subscale and a seven‐item sedative subscale. These subscales showed high internal consistency in a sober state, which was not improved by additional item deletion. The data from this study also provided a basis for revising the instructions for the BAES. The new 14‐item instrument was then given to 30 male and 12 female nonalcoholics on the ascending and descending limbs of the blood alcohol curve, after the administration of either 0.75 ml/kg alcohol (males) or 0.65 ml/kg alcohol (females). Internal consistency was high for both BAES subscales on both limbs of the blood alcohol curve (Cronbach's alpha = 0.85 to 0.94), and was not improved by additional item deletion. Factor analyses conducted on both limbs of the blood alcohol curve supported the proposed factor structure of the BAES. A predicted interaction of subscale and limb was observed, with stimulant ratings higher than sedative ratings during rising blood alcohol concentrations (BACs), and sedative ratings higher than stimulant ratings during falling BACs. These data provide some initial validation of the BAES as a self‐report measure of the stimulant and sedative effects of alcohol.
Does Psychomotor Sensitivity to Alcohol Predict Subsequent Alcohol Use?
Authors: Rodriguez Lawrence A. , Wilson James R. , Nagoshi Craig T.
Published: April 2006

Data from 42 male and 58 female subjects who participated in the Colorado Alcohol Research on Twins and Adoptees (CARTA) project were subjected to model‐fitting analyses. The aim of the present study was to use linear structural equation models to determine whether differences in previously measured psychomotor sensitivity to alcohol predict differences in self‐reported alcohol consumption over a 4‐year period. LISREL model‐fitting results indicate that, for male subjects, only rail walking insensitivity is predictive of alcohol use reported 2 years after their initial CARTA testing. For females, only hand steadiness sensitivity is predictive of alcohol use reported 2 years after their initial CARTA testing. The results for males support a hypothesis that would consider alcohol insensitive individuals at greater risk for alcohol abuse. The female results, however, would argue against such a hypothesis.

With only one measure of sensitivity predicting alcohol use at only one out of four time points, in both men and women, the overall results suggest that our three measures of psychomotor sensitivity to alcohol are, in general, poor predictors of alcohol consumption in this sample.
Increased Metabolism of Acetaminophen in Chronically Alcoholic Patients
Authors: Girre C. , Hispard E. , Palombo S. , N'Guyen C. , Dally S.
Published: April 2006

The aim of this work was to determine whether the metabolism of acetaminophen increases in chronic alcoholics, and consequently whether the production of its hepatotoxic metabolite is enhanced. For this purpose, the pharmacokinetics of acetaminophen were compared in 12 alcoholic men and 12 healthy controls. After a 12‐hr fast, the patients (on the 3rd hospital day) and volunteers were given 1 g of oral acetaminophen at 8.00 AM. Venous blood samples were drawn before drug intake and at regular intervals after to evaluate plasma acetaminophen concentrations. The elimination half‐life of acetaminophen was significantly shorter in the alcoholic patients than in the controls (1.70 ± 0.55 vs. 2.84 ± 0.30 hr, p < 0.001). Similarly, total plasma acetaminophen clearance was significantly higher in the patients than in the controls (29.19 ± 13.37 vs. 24.45 ± 11.10 1/hr, p < 0.05). These results confirm that the metabolism of acetaminophen increases in chronic alcoholism and consequently suggest that its potential liver toxicity might be enhanced.
Alcohol Use and Periodic Limb Movements of Sleep
Authors: Aldrich Michael S. , Shipley James E.
Published: April 2006

Alcohol causes significant sleep disturbance but the causes are not well understood. We investigated the relationship between alcohol use and periodic limb movements in a large population of patients at a sleep disorders center. The likelihood of having a clinically significant number of periodic leg movements (more than 20 per hour of sleep) was increased 3‐fold in women who consumed two or more alcoholic drinks per day compared with those who did not (25% versus 8%). A similar relation was found among men (22% versus 13%). In addition, women who consumed two or more drinks per day were more likely to report symptoms of restless legs and to be diagnosed with restless legs syndrome. These findings suggest that periodic leg movements contribute to sleep disturbance in a significant proportion of alcohol users. Alcohol use may increase the frequency of periodic leg movements in susceptible individuals. On the other hand, subjects with symptoms related to periodic leg movements may be using alcohol to relieve symptoms, or the movements may be secondary to alcohol‐induced sleep disturbance.
CDT by Anion‐Exchange Chromatography Followed by RIA as a Marker of Heavy Drinking Among Men
Authors: Sillanaukee Pekka , Seppä Kaija , Löf Kari , Koivula Timo
Published: April 2006

Carbohydrate‐deficient transferrin, CDT, had previously been reported to be an excellent marker for alcoholism. The present population‐based study examined the diagnostic value of CDT among consecutive middle‐aged males including 122 social drinkers (mean alcohol consumption 88 ± 79 g per week) and 77 non‐alcoholic heavy drinkers (301 ± 195 g/wk). Ninety‐six men with a well‐documented history of chronic alcoholism (≥1000 g/wk) were used as a reference group. The CDT (containing mainly isotransferrin with pl = 5.8 and 5.9) was separated by anion exchange chromatography and assayed by RIA. The CDT values of social drinkers (mean ± SD = 14 ± 5 U/I) were significantly lower than those of heavy drinkers (19 ± 13 U/I, p < 0.01) and alcoholics (34 ± 18 U/I, p < 0.001). In the whole material CDT correlated positively with alcohol consumption (r= 0.53, p < 0.001). At a specificity of 91.8%, CDT found 28.6% of the heavy drinkers and 79.2% of the alcoholics; the best traditional marker, GGT, with a specificity of 86.9%, found 35.1% and 64.6%, respectively. In conclusion, CDT is a specific marker, which is superior to traditional markers for identifying alcoholics. Unfortunately, it does not seem to provide additional power for identifying the important group, non‐alcoholic heavy drinkers.
Effect of Haloperidol on Measures of Craving and Impaired Control in Alcoholic* Subjects
Authors: Modell Jack G. , Mountz James M. , Glaser Frederick B. , Lee Jeannette Y.
Published: April 2006

We recently proposed that alcoholics suffer from a functional defect within the basal ganglia/limbic striatum or its modulation by dopaminergic projections from the ventral tegmentum, and that inhibition of striatal output caused by the prodopaminergic effects of alcohol ingestion induces or exacerbates craving and impaired control over alcohol consumption in alcoholic individuals. To test this hypothesis, 16 subjects with a diagnosis of alcohol dependence or abuse were studied in a double‐blind, placebo‐controlled experiment in which the effects of the D‐2 antagonist haloperidol on measures of craving and impaired control were assessed before and after administration of a priming dose of alcohol. Subjects were pretreated with 0.015–0.025 mg/kg haloperidol (experimental condition) or 2 ml normal saline (control condition), and subsequently consumed 0.4–0.6 g/kg ethanol as their preferred alcohol‐containing beverage. Significant increases in subjectively rated craving for alcohol and perceived difficulty resisting additional alcohol consumption occurred following the priming dose of alcohol when subjects were pretreated with saline. In contrast, no significant changes in reported ability to resist additional alcohol occurred when subjects were pretreated with haloperidol, and reported levels of craving decreased relative to baseline following haloperidol pretreatment. Subjects also consumed about 25% less optionally available alcohol when pretreated with haloperidol than when pretreated with saline. These findings support the hypothesis that craving and impaired control are induced or exacerbated by the prodopaminergic effects of alcohol consumption.
Serum Carbohydrate‐Deficient Transferrin as a Marker of Alcohol Consumption in Patients with Chronic Liver Diseases
Authors: Bell Helge , Tallaksen Chantal , Sjahelm Tone , Weberg Ragnar , Raknerud Nils , Ørjasaeter Harsald , Try Kenneth , Haug Egil
Published: April 2006

We meesured serum levels of carbohydrate deficient transferrin (CDT) in 420 subjects: 100 healthy blood donors, 82 healthy employses, 70 abstaining patients with different chronic nonalcoholic liver disease, 16 abstaining patients with alcoholic fatty liver, 50 abstaining patients with alcohotic liver cirrhosls, 25 abusing patients with alcoholic fatty liver, 41 abusing patients with alcoholic liver cirrhosis, and 36 patients with alcohol dependence syndrome with a daily ethanol consumption of 173 ± 120 g the last 4 weeks before blood was drawn. In controls the serum level of CDT was significantly higher in females compared with males (17.7 ± 5.1 and 13.7 ± 3.8 units/liter, respectively), and the upper normal limit was defined as 27 and 20 units/liter. Sixty‐two of 102 (60.8%) abusing patients with alcoholic liver disease had increased levels of CDT compared with 1 of 66 abstaining (1.5%) patients with alcoholic liver disease, and 10 of 70 (14.3%) abstaining patients with nonalcoholic liver disease among them 3 with primary biliary cirrhosis and 2 with chronic autoimmune hepatitis. No correlation was found between serum CDT and γ‐glutamyltranspeptidase (GGT), AST, ALT, and mean red cell volume (MCV). The sensitivity and specificity for serum CDT was 61 and 92%, respectively, compared with 85 and 18% for GGT and 70 and 66% for MCV. No advantage was gained by using the CDT/transferrin ratio. Our study confirms that CDT is a specific marker for chronic alcohol abuse, except in few patients with other chronic liver diseases. Serum CDT seems to be a better indicator of abstention than GGT; AST and MCV in patients with alcoholic liver disease. However, in our hands CDT is not so sensitive for alcohol abuse in patients with liver disease as reported earlier in unselected alcoholics
Effect of Bedtime Ethanol on Total Inspiratory Resistance and Respiratory Drive in Normal Nonsnoring Men
Authors: Dawson Arthur , Lehr Patricia , Bigby Barbara G. , Mitler Merrill M.
Published: April 2006

We have previously reported that bedtime ethanol (2.0 ml/kg of 100 proof vodka) increases upper airway closing pressure in males who habitually snored but were otherwise healthy. We also observed that some of these snorers developed obstructive apneas. To explore this phenomenon in more detail, we measured the inspiratory resistance (RI) and respiratory drive after bedtime ethanol in 10 nonobese men (ages 23 to 33) with no history of snoring. Subjects went to bed wearing a tightly fitting valved mask over the nose and mouth that allowed measurement of inspiratory and expiratory flow, pressure in the mask, and endtidal CO2. We measured RI by calculating the pressure difference between the mouth and a balloon positioned in the midesophagus. Respiratory drive was quantified by the inspiratory occlusion pressure (P0.1), the ventilatory response to hyperoxic hypercapnia (ΔVE/ΔPETCO2), and the ventilatory response to isocapnic hypoxia (ΔVE/ΔS,O2). Measurements were made during waking and during stage 2 NREM sleep on two nights: (1) when the subjects drank 1.5 ml/kg of 100 proof vodka in orange juice over a 30‐min period 15–45 min before lights out and (2) when the orange juice contained less than 0.1 ml of vodka floating on the top. Eight of the nine men in whom we had technically adequate measurements showed a rise in RI during NREM sleep above the waking level on both control and ethanol nights and the sleeping RI was greater on the ethanol than on the control night. There was a tendency for P0.1 to be higher during sleep and greater on the ethanol night, suggesting that the neural output to the respiratory muscles was not depressed and may have been stimulated by the inspiratory “loading” secondary to the increased RI. The hypercapnic response was significantly depressed during sleep. Whereas the response tended to be less on the ethanol than on the control night, the difference was not significant. The hypoxic response showed little change from waking to sleeping and no significant change with ethanol. We speculate that inspiratory loading due to increased upper airway resistance tends to stimulate respiratory drive and thereby partially offsets the depressant effect of ethanol on the central respiratory chemoreceptors.
Urinary Level of L‐Fucose as a Marker of Alcoholic Liver Disease
Authors: Yamauchi Masayoshi , Kimura Kazuo , Maezawa Yoshihiko , Ohata Mituru , Mizuhara Yuji , Hirakawa Junichi , Nakajima Hisato , Toda Cotaro
Published: April 2006

The urinary levels of L‐fucose were measured in 93 alcoholics: 20 of these were without liver disease, 57 with noncirrhotic alcoholic liver disease, and 16 with alcoholic liver cirrhosis. In addition, patients with cirrhosis due to viral infection, and healthy subjects were evaluated. The mean urinary L‐fucose concentration showed significantly higher values in patients with alcoholic liver disease and alcoholic liver cirrhosis when compared with the healthy subjects or the chronic alcoholics without liver disease (p < 0.001). The urinary L‐fucose level was also significantly higher (p < 0.001) in cases of alcoholic liver cirrhosis than in noncirrhotic alcoholic liver disease (384 ± 97 vs. 240 ± 95 μmol/g of creatinine). No difference was observed between the healthy subjects and chronic alcoholics without liver disease (143 ± 29 vs. 155 ± 60 μmol/g of creatinine). The urinary level of L‐fucose was significantly higher with alcoholic cirrhosis (384 ± 97 μmol/g of creatinine) than with viral cirrhosis (265 ± 42 μmol/g of creatinine) (p < 0.001). The measurement of urinary L‐fucose may be a useful marker of alcoholic liver disease.
A Time Series Analysis of the Impact of the Alcohol Warning Label on Antenatal Drinking
Authors: Hankin Janet R. , Sloan James J. , Firestone Ira J. , Ager Joel W. , Sokol Robert J. , Martier Susan S.
Published: April 2006

In a sample of over 12,000 African‐American gravidas, we tested the hypothesis that the Federal Beverage Labeling Act of 1988 has decreased antenatal drinking. Results of time series analysis indicated a 7‐month lag in the impact of the alcohol warning label. Controlling for population changes, antenatal drinking began to fall as of June 1990. However, this decrease was small in size and did not impact on the heaviest drinkers. Seasonal trends in drinking were also detected, with peaks around the end of the year and the summer.
Ethanol Exposure Increases Total Protein Kinase C Activity in Human Lymphocytes
Authors: DePetrillo Paolo B. , Liou Caspar S.
Published: April 2006

Human circulating lymphocytes were isolated and incubated with ethanol. Cytosolic, membrane‐bound and total detergent extractable protein kinase C (PKC) activities were measured. Exposure to ethanol (100 mm) resulted in an increase in PKC activity, with membrane‐associated PKC activity increasing with respect to cytosolic activity at 5 min of exposure. Higher concentrations of ethanol up to 200 mm were associated with increases in total detergent extractable PKC activity. Ethanol was the most potent of a series of straight chain alcohols studied for their effects on detergent‐extractable PKC activity.
Saccharin Intake Predicts Ethanol Intake in Genetically Heterogeneous Rats as Well as Different Rat Strains
Authors: Overstreet David H. , Kampov‐Polevoy Alexey B. , Rezvani Amir H. , Murrelle Lenn , Halikas James A. , Janowsky David S.
Published: April 2006

Saccharin and ethanol intakes were measured in seven strains of rats known to differ in their preferences for ethanol: The Fawn‐Hooded (FH), alcohol‐preferring (P) and Maudsley Reactive rats have been reported to drink ethanol voluntarily, whereas the alcohol‐nonpreferring, Maudsley Nonreactive and Flinders Line (FSL and FRL) rats do not. Saccharin and ethanol intakes were highly correlated (r =+0.61) over all strains, with the FH rats drinking the most of both solutions. Correlation coefficients between pairs of drinking versus nondrinking rat strains were even higher. In a second experiment, genetically heterogeneous F2 progeny from cross‐breeding the ethanol‐preferring FH rats with the ethanol‐nonpreferring Flinders Resistant Line (FRL) rats were studied. The results indicated a high positive correlation between saccharin and ethanol intakes (+0.65). These findings suggest that the association between saccharin and ethanol intakes previously reported in rat strains with different preferences for ethanol may have a similar genetic basis.
Ventral Tegmental Microinjections of Quinpirole Decrease Ethanol and Sucrose‐Reinforced Responding
Authors: Hodge Clyde W. , Haraguchi Miki , Erickson Heidi , Samson Herman H.
Published: April 2006

The effects of microinjections in the ventral tegmental area (VTA) of the dopamine D2/D3 agonist quinpirole on ethanol‐ and sucrosereinforced responding were tested. Two groups of Long‐Evans rats were trained to lever press on a fixed‐ratio 4 schedule with 10% ethanol (v/v) (n= 8) and 75% sucrose (w/v) (n= 10) presented as the reinforcer. Weekly bilateral injections of quinpirole were tested in the ethanol group (0.0, 0.001, 0.01, 0.1, and 1.0 μg/μl) and sucrose group (0.0, 0.01, 0.1, 1.0, and 10.0 μg/μl). Quinpirole dose dependently decreased ethanol‐ and sucrose‐reinforced responding, but the dose‐effect curve for sucrose was shifted two orders of magnitude to the right of the ethanol curve. Temporal response patterns during control sessions for both reinforcers were characterized by initial high rates that terminated after approximately 10 min. VTA injections of quinpirole dose dependently delayed the onset of the first response and the initial high rate period, and resulted in an early termination of responding following onset. These data support the hypothesis that dopamine activity in the VTA is involved in the regulation of ethanol‐reinforced responding in a manner similar to that of other reinforcers.
Alcohol and Aldehyde Dehydrogenases in Human Esophagus: Comparison With the Stomach Enzyme Activities
Authors: Yin Shih‐Jiun , Chou Fang‐Ju , Chao Shu‐Feng , Tsai Sho‐Feng , Liao Chin‐Shya , Wang Sung‐Ling , Wu Chew‐Wun , Lee Shih‐Chun
Published: April 2006

Alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH) isoenzymes from surgical esophageal and gastric mucosa were compared by agarose isoelectric focusing. Two prominent ADH forms, designated μ1 (equivalent to the recently reported μ‐form) and μ2, were expressed in all the 15 esophagus specimens studied, whereas only four of seven examined gastric specimens exhibited a weak to moderately strong μ1‐ADH activity band on the isoelectric focusing gels. pl values of the esophageal μ1‐ADH and μ2‐ADH, and the liver π‐ADH were determined to be 8.61, 8.13, and 8.90, respectively. μ‐ADHs exhibited high Km for ethanol (12 mM) and low sensitivity to 4‐methylpyrazole inhibition. ALDH3 (BB form) and ALDH1 were the major high‐ and low‐Km aldehyde dehydrogenase in the esophagus, respectively. The ADH and ALDH activities were determined at pH 7.5 to be 751 ± 78 and 29.9 ± 3.0 nmol/min/g tissue, respectively (measured at 500 mM ethanol or at 200 μM acetaldehyde; mean ±sem; N = 15). The esophageal ADH activity was approximately 4‐fold and the ALDH activity 20% that of the stomach enzyme. Because the presence of high activity and high Kmμ‐ADHs as well as low‐activity ALDH1 were found in human esophageal mucosa, it is suggested that there may exist an accumulation of intracellular acetaldehyde during alcohol ingestion. This reactive and toxic metabolite may be involved in the pathogenesis of alcohol‐induced esophageal disorders.
Potential Role of 5HT1C and/or 5HT2 Receptors in the Mianserin‐Induced Prevention of Anxiogenic Behaviors Occurring During Ethanol Withdrawal
Authors: Lal Harbans , Prather Paul L. , Rezazadeh S. Mehdi
Published: April 2006

A single dose of mianserin (a 5HT1C/5HT2 antagonist), administered 1 hr, 48 hr, or 7 days before testing, was evaluated for its efficacy in alleviating or preventing the occurrence of anxiogenic behaviors observed during ethanol withdrawal. Other behavioral experiments using selected drug interactions were conducted to examine whether the effect of mianserin was related to a long‐term modification of 5‐hydroxy‐tryptamine (5HT) receptor function. Rats were fed a liquid diet containing 4.5% ethanol for 4 days. They were tested on the elevated plus‐maze (EPM) 12 hr (acute withdrawal) and 5 days (protracted withdrawal) after the last ethanol dose. Ethanol withdrawal induced a pattern of “anxiogenic” behavior that consisted of reduced activity (total entries) and a reduced proportion of open arm activity. Mianserin, injected as a single dose given either 1 hr (0.16‐5 mg/kg, ip) before testing or given (20 mg/kg, ip) on the morning of the 3rd day of ethanol administration, i.e., 48 hr and 7 days before testing, dose‐dependently prevented or reversed the ethanol withdrawal induced reduction in open‐arm activity. In contrast, the 5HT1C/5HT2 receptor agonist (±)‐1‐(2,5‐dimethoxy‐4‐iodophenyl)‐2‐amino‐propane HCI (DOI) did not affect behaviors in the EPM in ethanolnaive rats, nor in those undergoing ethanol withdrawal. However, although there was a marked tolerance to DOI‐induced body shakes (a measure of 5HT2 function) during withdrawal, DOI reversed the action of mianserin in the EPM. The 5HT1 receptor agonist, 5HT2 receptor antagonist 1‐naphthyl‐piperazine (1‐NP) reduced open‐arm activity in ethanol‐naive rats and this action was enhanced during withdrawal. 1‐NP reversed the effect of mianserin pretreatment and during ethanol withdrawal the dose‐response curve of 1‐NP was shifted to the left. The behavioral data indicated a reduced efficacy of 5HT2 receptors during ethanol withdrawal while anxiogenic behaviors are present, whereas stimulation of 5HT1C receptors appears anxiogenic. These data support the hypothesis that mianserin may alleviate withdrawal anxiety by direct blockade or down‐regulation of 5HT1C receptors.
Role of Noradrenergic Innervation of Brown Adipose Tissue in Thermoregulatory Deficits Following Prenatal Alcohol Exposure
Authors: Zimmerberg Betty , Carson Elizabeth A. , Kaplan Lawrence J. , Zuniga Jorge A. , True Robert C.
Published: April 2006

The development of thermoregulation in newborns is delayed by prenatal alcohol exposure in an animal model of moderate maternal drinking. Newborn mammals generate heat primarily via nonshivering thermogenesis in brown adlpose tissue (BAT), which is activated by the sympathetic nervous system. In this study, the effects of prenatal alcohol exposure on the development of the sympathetic innervation of BAT was investigated by assessing the concentration of norepinephrine (NE) in interscapular BAT. Pregnant dams were given either a liquid diet with 35% of the calories derived from alcohol, a liquid diet without alcohol to control for any effects of the liquid diet administration, or ad libitum food and water. Interscapular brown adipose tissue was excised from 5‐, 10‐, and 20‐day‐old male and female offspring. At 5 days of age, alcohol‐exposed pups had significantly lower NE concentrations than did pups in either control group. However, 20‐day‐old alcohol‐exposed pups had significantly higher NE concentrations than either control group. These results suggest a delay in the development of the sympathetic activation of BAT thermogenesis, followed by a compensatory overactivation. These findings may have important implications for understanding the mechanisms underlying thermoregulatory deficits seen after prenatal alcohol exposure. In addition, these results suggest that maternal alcohol consumption may increase the risk of sudden infant death syndrome, which has been linked to inappropriate BAT thermogenesis.
Chronic Cadmium Exposure Attenuates Ethanol‐Induced Hypoalgesia in the Adult Rat
Authors: Burkey Robert T. , Nation Jack R. , Grover Cathy A. , Bratton Gerald D.
Published: April 2006

Adult male rats were exposed to a diet containing either 100 ppm added cadmium (Cadmium‐Diet), or a control diet containing no added chemicals (Control‐Diet) for 67 days prior to pain reactivity testing using a tail‐flick procedure. Rats were placed in restraining tubes for a 20‐min acclimation period, then baseline tail‐flick latencies in response to a radiant heat source were measured. Subsequently, half the animals from each group were serially injected intraperitoneally with either 0.5, 1.0, 1.5, or 2.0 g/kg body weight of a 20% v/v ethanol solution, and the other half of the animals were injected with an equivalent volume of saline. Tail‐flick latencies were reassessed at 20‐min intervals over the next 2 hr. Results indicated dose‐dependent ethanol‐induced hypoalgesia in the Control‐Diet animals for the two highest doses, but ethanol‐induced hypoalgesia was evident only at the highest dose for the Cadmium‐Diet animals. Further, the magnitude of this hypoaigesic effect was significantly lower for the Cadmium‐Diet animals than the Control‐Diet animals at the 2.0 g/kg dose. Results are discussed in terms of an attenuation of the pharmacological properties of ethanol by cadmium.
The Alcohol Beverage Warning Label: When Did Knowledge Increase?
Authors: Hankin Janet R. , Sloan James J. , Firestone Ira J. , Ager Joel W. , Sokol Robert J. , Martier Susan S. , Townsend Joyce
Published: April 2006

This article presents data on the awareness of the alcohol beverage warning label among a sample of 5,169 inner city African‐American gravidas seeking prenatal care. While the label law was implemented in November 1989, a significant increase in knowledge of the label did not occur until March 1990. Women who predominantly consumed wine coolers and beer, and those under age 30 were more likely to know about the label than their counterparts.
Dietary Carbohydrate Accelerates Ethanol Elimination, But Does Not Alter Hepatic Alcohol Dehydrogenase
Authors: Keegan Andrew , Batey Robert
Published: April 2006

In naive animals the rate of ethanol elimination is dependent on the hepatic alcohol dehydrogenase activity. Carbohydrates have been shown to modify ethanol metabolism by a mechanism that has not been determined. In this study, adult female rats, fed chow diets supplemented with fructose or glucose in their drinking water for 10 days demonstrated significantly greater ethanol elimination rates (4.85 ± 0.28 and 4.92 ± 1.5 μm ethanol/min/g liver, respectively) than rats receiving water (3.65 ± 0.29). The hepatic alcohol dehydrogenase activity of the fructose (1687 ± 101 nm ethanol/min/g liver) and the glucose (1832 ± 15)‐supplemented rats were not significantly different from that of control rats (1845 ± 160). Dietary carbohydrate supplementation, therefore, enhanced ethanol elimination, but did not alter the activity of alcohol dehydrogenase. Thus the changes in the ethanol elimination rate following carbohydrate loading were not the consequence of an alteration in hepatic alcohol dehydrogenase.
Alcohol and Murine Acquired Immunodeficiency Syndrome Suppression of Resistance to Cryptosporidium parvum Infection during Modulation of Cytokine Production
Authors: Alak John I. B. , Shahbazian Masoud , Huang Dennis S. , Wang Yuejian , Darban Hamid , Jenkins Edward M. , Watson Ronald R.
Published: April 2006

The effects of inoculation of LP‐BM5 murine leukemia retrovirus and chronic ethanol (5% v/v) ingestion on immunomodulation and Cryptosporidium parvum infection in C57BL/6 female mice were evaluated. The intestinal mucosae of retrovirally immunosuppressed animals were heavily colonized by Cryptosporidium parasites, and oocysts shedding in the feces persisted throughout the duration of the study. Mortality was exacerbated by murine retrovirus infection alone and exacerbated with concomitant chronic alcohol feeding (42.8 and 69.4%). Chronic ethanol ingestion decreased production of interferon‐γ and soluble interleukin‐2 receptor released in supernatants of splenocytes when stimulated with concanavalin A, compared with the control group. Decreased production of interferon‐γ and interleukin‐2 receptor was further exacerbated due to retrovirus infection. Tumor necrosis factor production by splenocytes stimulated with lipopolysaccharide, however, was significantly increased because of retrovirus infection. LP‐BM5 retrovirus infection alone as well as with concomitant ethanol feeding altered cytokine production, which might have led to immunodeficiency. These changes may help explain the enhanced persistence of Cryptosporidiosis.
Cholecystokinin and Bombesin Inhibit Ethanol and Food Intake in Rats Selectively Bred for Ethanol Sensitivity
Authors: Kulkosky Paul J. , Clayborne Yvonna J. , Sandoval Susan L.
Published: April 2006

Cholecystokinin octapeptide (CCK‐8) and bombesin tetradecapeptide (BBS‐14) are brain‐gut neuropeptides shown to inhibit intake and choice of alcohol solutions and foods in a variety of species. Recently, Draski and colleagues selectively bred strains descended from N/Nih outbred Norway rats that differ in sleep time after injection of ethanol. The intake of 5% w/v ethanol, food, and water was measured in these rats with high, low, and control alcohol sensitivity (HAS, US, and CAS), after intraperitoneal injection of randomized sequences of doses of CCK‐8 or BBS‐14 (0–8 μg/kg). During baseline adaptation to water deprivation‐induced consumption of alcohol, LAS rats consumed reliably more ethanol than HAS or CAS rats. Injection of CCK‐8 or BBS‐14 significantly and equivalently suppressed intake of ethanol and food at 30 min after presentation in each group of rats. Water intake and food intake at 30–60 min following alcohol access was not affected by prior injection of either neuropeptide. Large differences in alcohol neurosensitivity (HAS > CAS > LAS) were observed in these rats' resting behavior for 1 hr after intraperitoneal injection of 1 g/kg of ethanol. These selectively bred alcohol neurosensitivity differences cannot be explained by corresponding differences in sensitivity to the inhibitory behavioral effects of CCK‐8 or BBS‐14. However, differences in alcohol intake and resting behavior do correspond to artificially selected sensitivities to ethanol's hypnotic effect.
Ethanol‐Induced Changes in Peripheral Blood and Splenic Natural Killer Cells
Authors: Blank Sally E. , Pfister Linda J. , Gallucci Randle M. , Meadows Gary G.
Published: April 2006

Previous work demonstrated that splenic natural killer (NK) cell cytolytic activity was suppressed in ethanol‐consuming mice within 1 week and for as long as 10 weeks concurrent with ethanol intake. However, it is unknown if suppression of NK cell activity with ethanol consumption results from regional losses in NK cells. The present experiments were designed to examine the effect of ethanol on the percentage and total number of NK cells in the spleen and blood. Data indicate that, after 4 weeks of ethanol intake, NK cell activity of peripheral blood lymphocytes was also suppressed (50% of controls). With short‐term (2‐week) exposure, the percentage of NK cells in the blood and the spleen remained relatively constant. In the spleen, changes in the number of NK cells reflected generalized fluctuations in lymphocyte numbers rather than variation in the percentage of NK cells. NK cells were most sensitive to the effects of ethanol during long‐term (8‐week) ethanol intake, as demonstrated by significant reductions in the total percentage of NK 1.1+ cells in the blood, and the LGL‐1+ subset in the blood and spleen.

These results provide insight into the mechanism of NK modulation by ethanol. Because NK cells were not selectively depleted after 2–4 weeks of ethanol intake, loss of cytolytically active NK cells cannot explain the suppression of in vitro cytolytic activity of cells from ethanol‐consuming mice. However, with prolonged ethanol intake (8 weeks), the depletion of NK cells, specifically the LGL‐1+ subset, may contribute to the overall suppression of NK cell cytolytic function.