bluuebunny/crossref_metadata_2025 huggingface dataset:
Depletion of Hepatic Glutathione by Ethanol Occurs Independently of Ethanol Metabolism
Authors: Speisky H. , Kera Y. , Penttilä K. E. , Israel Y. , Lindros K. O.
Published: April 2006

The mechanism of ethanol‐induced depletion of hepatic glutathione (GSH) was studied in vivo and in isolated hepatocytes. Neither inhibition of ethanol metabolism with 4–methylpyrazde, nor a 10‐fold elevation of acetaldehyde levels by inhibition of aldehyde dehydrogenase with cyanamide or disulfiram, affected the magnitude of the GSH depletion observed in vivo. The rate of intracellular GSH accumulation by isolated hepatocytes incubated with cysteine or methionine was not inhibited by the addition of 80 mM ethanol. A significantly decreased rate of GSH accumulation was, however, found in hepatocytes isolated from ethanol‐intoxicated animals. Neither the in vivo pretreatment with ethanol nor its in vitro addition to isolated hepatocytes affected the rate of GSH efflux. The results suggest that ethanol itself, rather than its metabolic products, causes depletion of liver GSH, and that events occurring in vivo are required for such an effect to be exerted.
Calcium Status and Calcium‐Regulating Hormones in Alcoholics
Authors: Bjørneboe Gunn‐Elin Aa. , Bjørneboe Anders , Johnsen Jon , Skylv Nina , MD Helge Oftebro , M Gautvik Kaare , Høiseth Arne , Mørland Jørg , Drevon Christian A.
Published: April 2006

To elucidate effects of chronic ethanol consumption on clinical chemical parameters reflecting overall calcium homeostasis 34 hospitalized male alcoholics and 35 age‐matched controls were studied during the winter season. Serum concentrations of 25‐hydroxyvitamin D, and 1,25‐dihydroxyvitamin Ds were reduced by 28% (p < 0.01) and 24% (p < 0.02) among the alcoholics as compared to the controls, respectively. Dietary intake of vitamin D3 did not differ significantly between the groups. The calcium level was below lower limit of reference in nine alcohdics (26%). Serum concentrations of parathyroid hormone and phosphorus were within normal ranges in both groups, and no differences were observed in levels of magnesium, vitamin D‐binding protein, calcitonin, or alkaline phosphatase. In conclusion, it is possible that the activities of enzymes crucial in vitamin D3 metabolism may be altered in alcoholics.
Reductions in Liver Cirrhosis Mortality and Morbidity in Canada: Demographic Differences and Possible Explanations
Authors: Mann Robert E. , Smart Reginald G. , Anglin Lise
Published: April 2006

In Canada, deaths from liver cirrhosis have declined by about 25% since 1974. To gain further insight into the nature of this decline, mortality rates for the years 1974–1984 and morbidity (hospital separation) rates for the years 1974–1980 were examined by age and sex and by province and sex. As well, survey data on drinking practices in Ontario were analyzed. Both mortality and morbidity declined over the time period involved, although variations over provinces, age groups, and sex were observed. The pattern of variations (largest declines in provinces with highest per capita alcohol consumption and in young to middle‐aged males) strongly suggests decreased incidence of alcoholic liver cirrhosis. Among the factors which may be contributing to these declines are: the stabilization and small decreases in per capita consumption of alcohol; consumption pattern changes consistent with observed mortality and morbidity changes; expanded health promotion activities; and increases in the numbers of alcoholics receiving treatment.
Roles of Hormonal and Nutritional Factors in the Regulation of Rat Liver Alcohol Dehydrogenase Activity and Ethanol Elimination Rate in Vivo
Authors: Lakshman M. R. , Chambers Laura L. , Chirtel Stuart J. , Ekarohita Nisa
Published: April 2006

Fasting reduced the liver alcohol dehydrogenase (ADH) activity by 51% (p < 0.001). Insulin, within 2 hr, increased the ADH activity found in fasted animals by 28% (p < 0.02). Insulin administration failed to stimulate the reduced ADH activity in diabetic rats. However, ADH activity in the diabetic‐fed rats decreased by 52‐54% (p < 0.001) compared to normal‐fed rats regardless of whether they were meal‐fed or refed the normal chow. Glucagon blocked by 15% (p < 0.02) the increase in ADH activity associated with refeeding. Furthermore, insulin caused a marginal stimulation of ethanol elimination rate (EER) when administered to fasted rats. All these results imply that insulin and glucagon may not be the only determining factors in the control of liver ADH activity associated with fasting and refeeding.

Meal‐feeding or refeeding a high carbohydrate fat‐free diet compared to the normal chow‐diet caused 29% (p < 0.001) and 36% (p < 0.05) decreases in ADH activity, respectively. Concomitant decreases in EER caused by high carbohydrate fat‐free diet feeding were also observed under identical conditions. These results raise the possibility that the amount and the type of carbohydrate may be crucial in the regulation of ADH and EER. Alternatively, the presence of fat may be important in maintaining the normal level of ADH and EER.
Neonatal and Maternal Hair Zinc Levels in a Nonhuman Primate Model of the Fetal Alcohol Syndrome
Authors: Fisher Stanley E. , Alcock Nancy W. , Amirian James , Altshuler Harold L.
Published: April 2006

The role of zinc deficiency in the etiology of ethanol‐associated fetotoxicity was assessed by measurement of maternal and newborn hair zinc content in a nonhuman primate model of the fetal alcohol syndrome. The model best approximates the human situation for length of gestation and type of placentation, coupled with the ability to control for nutritional factors. All mothers received 110% of their minimum daily caloric requirements as a balanced, nutritionally complete diet, including a minimum of 3.5 mg zinc per day. Over a 2‐year period, maternal hair samples from 17 pregnancies (using 12 females) were obtained at term. There were 16 live, full‐term neonates (nine ethanol exposed and seven control) from whom samples were taken within 1 hr of birth. The ethanol‐exposed infant monkeys had a significantly higher incidence of craniofacial dysmorphology and developmental delay compared to the controls. There was no difference in hair zinc levels between ethanol‐exposed and control animals for either the mothers or the newborns. Neonatal levels were, however, consistently higher than corresponding maternal. Although the findings cannot exclude transient or early gestational zinc deficiency as a factor, they provide further evidence that ethanol (and/or its metabolites) is the proximate toxin in the type of fetal injury seen in the fetal alcohol syndrome.
Carbohydrate‐deficient Transferrin, a Marker for Chronic Alcohol Consumption in Different Ethnic Populations
Authors: Behrens Ursula J. , Worner Theresa M. , Braly Lawrence F. , Schaffner Fenton , Lieber Charles S.
Published: April 2006

Serum levels of carbohydrate‐deficient transferrin (CDT) were determined in a racially mixed population of 107 alcoholics, 18 healthy, nonalcoholic control subjects, 62 abstinent alcoholics, and in 64 Caucasian patients with various nonalcoholic liver diseases. The upper limit of normal CDT levels was 80 mg/liter (2 SD above the mean). CDT values exceeding this level were found in more than 80% of Black, Puerto Rican, and Caucasian alcoholics who had consumed 250 g of alcohol/day for 1 month or longer prior to testing. Puerto Rican alcoholics had higher CDT values than the Black and Caucasian ethnic groups; however, these differences were significant only when compared to the Black population. Of 64 patients with nonalcoholic liver diseases, one individual with chronic active hepatitis (CAH) with an alcohol consumption of 20 g/day, and 10 of 26 subjects with primary biliary cirrhoses (PBC), who claimed to consume either no or only occasional moderate amounts of alcohol, had CDT levels ranging from 81 to 144 mg/liter. Seven of these individuals were in advanced stages of PBC. Total transferrin levels were variable and not significantly different in all subject groups studied. CDT/total transferrin ratios were increased in most patients with abnormal amounts of CDT, and there was a significant correlation between these ratios and CDT levels in all study groups. Serum enzyme parameters as well as red blood cell mean corpuscular volumes did not correlate with CDT values. Our study confirms that CDT is a highly specific marker for chronic alcohol consumption not only in Caucasians but also in other racial populations, although in some patients with PBC, increased levels of serum CDT were observed in the absence of alcohol abuse.
Time Course and Reversibility of Ethanol's Suppressive Effects on Axon Sprouting in the Dentate Gyrus of the Adult Rat
Authors: Lind Marcia D. , Goodlett Charles R. , West James R.
Published: April 2006

Ethanol was administered chronically to adult rats in a liquid diet for 14 days preceding and for 5,7,8,9, or 10 days following the unilateral destruction of the entorhinal cortex. Control groups received a diet of lab chow and water and were sacrificed at comparable survival times. An additional experimental group was given ethanol until 9 days after the lesion, then switched to lab chow and water and sacrificed 1 day later. Coronal sections through the dorsal hippocampal formation were stained and analyzed histochemically for the localization of acetylcholinesterase (AChE). Quantitative measurements of the histochemical patterns in the molecular layer of the dentate gyrus were obtained. Ethanol exposure inhibited the withdrawal of the acetylcholinesterase‐stained septohippocampal fibers and limited the typical lesion‐induced expansion of the pale‐staining commissural/associational zone in the molecular layer of the denervated dentate gyrus. However, abstinence from ethanol for just 24 h released the inhibitory effect on the acetylcholinesterase‐staining fibers, resulting in a significant expansion of the commissural/associational zone.
Psychopathology in Children of Alcoholic and Antisocial Parents
Authors: Earls Felton , Reich Wendy , Jung Kenneth G. , Cloninger C. Robert
Published: April 2006

In this controlled family study the frequency of psychiatric disorder in children of alcoholic parents was found to be higher than in children of nonalcoholic parents. The rate in children of two alcoholic parents was distinctly higher than in those of one alcoholic parent. Comparison was also made between children of antisocial parents (usually coexisting with alcoholism) and children of parents with alcoholism only; no significant differences in the rates of childhood disorder were found between these two groups. Structured diagnostic interviews independently administered to both parents and children between 6 and 17 years old were used to assess psychopathology in the children. The types of disorders in the children of alcoholic parents reflected a mixed diagnostic picture with the reports of both parents and children yielding similar results.
Hepatic Adenosine in Rats Fed Ethanol: Effect of Acute Hyperoxia or Hypoxia
Authors: Miyamoto Kei , French Samuel W.
Published: April 2006

The level of adenosine was measured in monthly biopsied livers from rats fed ethanol and a high fat/low protein diet in order to test a hypothesis that hepatic adenosine is increased due to enhanced breakdown of adenine nucleotides in which ATP and total adenylate pool were decreased by chronic ethanol feeding. The ethanol‐fed rats showed a significantly higher average level of adenosine compared to the pair‐fed controls. When investigated monthly, however, adenosine in ethanol‐fed rats increased only after the decrease in ATP had stabilized and AMP remained unchanged, indicating that these changes were not temporarily related. The average percentage of change in adenosine after acute hyperoxia or hypoxia were variable both in ethanol‐fed and pair‐fed rats. There was a tendency for a positive correlation between the percentage of change of adenosine and AMP after hyperoxia regardless of ethanol feeding. A negative correlation between the percentage of change of adenosine and energy charge, and a positive correlation between the percentage of change of adenosine and AMP were seen after hypoxia regardless of ethanol feeding. Adenosine levels changed rapidly In response to changes in systemic of pO2 in both the ethanolfed and control rats, indicating that the liver maintained its normal response to the changes in energy state. The results indicate that chronic ethanol feeding does increase the level of adenosine in the liver and that this level remains responsive to acute changes in pO2. It is speculated that the increase in adenosine observed after 2 months of ethanol feeding may explain why the adenine nucleotides stop falling since portal blood flow may be increased in response to the elevated adenosine level thus compensating for the centrilobular hypoxia caused by ethanol stimulated increase in O2 consumption by the liver.
Changes in Carbohydrate‐Deficient Transferrin Levels after Alcohol Withdrawal
Authors: Behrens Ursula J. , Worner Theresa M. , Lieber Charles S.
Published: April 2006

Sequential serum levels of carbohydrate‐deficient transferrin (CDT) were determined in 72 alcoholics at various intervals during detoxification. Before treatment, 57 patients (79%) had increased CDT values (Group A), whereas in 15 individuals (21%) (Group B), CDT levels were within the normal range. In 51 Group A patients, CDT decreased progressively after cessation of alcohol intake (half‐life, 16 ± 5 days), but fluctuated and remained abnormal in the remaining six. Nine Group B patients maintained normal CDT values throughout the follow‐up period, but slightly or moderately increased levels were recorded on one occasion in the other six Group B subjects. Patients whose CDT levels had reached normal values after treatment, showed a recurrent increase in CDT after a relapse. γ‐Glutamyl trensferase activities, which were elevated in 56% of Group A and in 80% of Group B alcoholics, showed a decrease after cessation of alcohol consumption in most patients with initially elevated values (Group A, 30 of 32; Group B, 10 of 12). Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) activities, as well as mean corpuscular volumes (MCV) were normal in the majority of patients. CDT/total transferrin ratios correlated positively with CDT levels. CDT proved to be the most sensitive marker for chronic alcoholism (79%), whereas GOT activity levels were more useful only in patients with normal CDT levels before alcohol withdrawal. In the assessment of treatment outcome, the combination of CDT and GGT as markers yielded a sensitivity of 95%.
What Schedule‐Induced Polydipsia Can Tell Us About Alcoholism
Authors: Falk John L. , Tang Maisy
Published: April 2006

An animal model of chronic and excessive voluntary (unforced) alcohol ingestion is presented in which, by drinking, animals produce repeated, substantial elevations in blood ethanol concentration and develop physical dependence. The overindulgence is elective in that ethanol is chosen in preference to certain other fluid‐ingestive alternatives. Beside the usual demonstrations of acutely compromised motor performance, tolerance development, cross‐tolerance, etc., the model demonstrates that the consequences of even short, but continued, daily drinking episodes results in the disruption of reinforced behavior that occurs later in the day when blood ethanol is absent (impaired general functioning). The conditions which induce the ethanol overindulgence can generate a variety of behavioral excesses which places alcoholism in a context of environmentally determined malfunctions that are subject to therapeutic change by altering situational parameters. Efficacious experiments utilizing therapeutic and preventive strategies are described that may serve as suggestions for corresponding human alcoholism intervention strategies.
Genetic Tools in the Study of Drug Self‐administration
Authors: George Frank R.
Published: April 2006

Recent studies have shown that large genetic differences exist in the extent to which orally delivered ethanol will come to serve as a positive reinforcer under operantly defined conditions. In addition, these studies suggest that a significant correlation exists between results from two‐bottle choice studies of ethanol drinking and operant self‐administration studies of ethanol functioning as a reinforcer. The present paper reports further genetic influences on ethanol self‐administration which were found using Long Sleep and Short Sleep mice, bred selectively for high and low duration of loss of the righting reflex in responses to ethanol, respectively. It was possible to establish ethanol as a reinforcer in Long Sleep mice but not in Short Sleep mice. These results indicate that neurosensitivity to ethanol may determine the absolute amount of ethanol consumption but is not highly related to the ability of ethanol to serve as a positive reinforcer. In addition, this paper presents genetic correlations which indicate that (a) ethanol preference and self‐administration are highly correlated across genotype; (b) sensitivity to ethanol and self‐administration of this drug are not highly genetically correlated; (c) ethanol is not self‐administered in operant studies solely for its caloric value; and (d) there exist important genetic determinants of drug reinforced behavior.
Effect of Disulfiram on Canine Liver Aldehyde Dehydrogenase Activity: In Vivo Inactivation in a Nonrodent Animal Model
Authors: Sanny Charles G. , Mahoney Andrew J. , Kilmore Mearl A. , Rymas Kimberlee
Published: April 2006

Dogs were used as nonrodent animal models to study the in vivo effects of disulfiram on hepatic aldehyde dehydrogenase (ALDH) activity. Dogs were treated with disulfiram either intraperitoneally or orally (100 mg/kg/day for 2 days followed by 40 mg/kg/day for 3 days). Liver biopsies from control and treated animals were fractionated by differential centrifugation and the subcellular fractions were analyzed for ALDH activity. Significantly less activity was observed in cell homogenates from treated animals (20–50% of control activity per gram of liver). The majority of loss in activity was accounted for by a decrease in ALDH activity in the soluble fraction of the cell (12–30% of control activity) and in the mitochondrial fraction (23–30% of control activity). Activities at both high (5 mM) and low (50 μM) acetaldehyde concentrations were affected. The subcellular distribution of ALDH activity and in vivo inhibition by disulfiram in dogs is different from that reported for rats.
Neuropsychological Performance of Young Nondrinkers, Social Drinkers, and Long‐ and Short‐Term Sober Alcoholics
Authors: Emmerson R. Y. , Dustman R. E. , Heil J. , Shearer D. E.
Published: April 2006

Neuropsychological performance of 23–42‐year‐old males with diverse drinking histories was assessed. Comparisons were made among nondrinkers, social drinkers, short‐term sober (<30 days) alcoholics and long‐term sober (>30 days) alcoholics. Results of these comparisons provided little support for the notion that neurotoxic effects of chronic alcohol consumption are directly related to cognitive impairment. Instead, these results suggested that performance differences among the groups were more closely related to subclinical withdrawal symptoms or native ability than to long‐term alcohol consumption. Because none of the dependent measures was related to length of abstinence, and because Wechsler's Adult Intelligence Scale‐R Vocabulary differences among groups paralleled neuropsychological test performance differences, it is suggested that differences among groups may reflect differences in native ability. In addition, there were no differences between social drinkers and nondrinkers, nor were there any significant correlations among drinking variables and performance of social drinkers, providing further evidence against a direct relationship between alcohol consumption and cognitive performance.
Hyperresponsiveness to Stress: Differential Effects of Prenatal Ethanol on Males and Females
Authors: Weinberg Joanne
Published: April 2006

In this study we investigated the hypothesis that pituitary‐adrenal response inhibition is compromised in animals prenatally exposed to ethanol. In the first experiment, we examined whether opportunity to perform a consummatory response reduces the adrenocortical response to a novel test cage. Animals were water deprived for 24 hr and tested in one of three conditions: (a) removed from home cage, blood sample obtained immediately; (b) placed into empty novel cage, blood sample obtained 30 min later; (c) placed into novel cage with water available, blood sample obtained 30 min later. All animals showed an increase in corticoids over basal levels following 24‐hr water deprivation, and placement into a novel cage produced a further significant increase in corticosterone. Opportunity to drink reduced the corticosterone response to novelty for all males. However, fetal ethanol‐exposed females showed significantly less attenuation of their corticosterone response to novelty than both pair‐fed and control females. In the second experiment, we examined adrenocortical habituation to a stressful stimulus. Animals were restrained in plastic tubes which restricted movement, and blood samples were obtained following 30 or 60 min of restraint. All animals showed significant corticoid elevations at 30 min. Males showed no change in corticoids from 30 to 60 min while both pair‐fed and control females showed a corticoid decrease at 60 min. Fetal ethanol‐exposed females, however, showed no significant corticoid decrease at 60 min. These data support the hypothesis that behavioral or psychological variables are less effective in inhibiting or attenuating the pituitary‐adrenal response to stress in animals prenatally exposed to ethanol than in controls, and suggest that females may be more vulnerable to these effects of ethanol than males.
Mechanism and Regulation of Ethanol Elimination in Humans: Intermolecular Hydrogen Transfer and Oxidoreduction in Vivo
Authors: Cronholm Tomas , Jones A. Wayne , Skagerberg Stefan
Published: April 2006

Ethanol metabolism was studied in four healthy volunteers by intravenous infusion of a mixture of [1, 1‐2H2]ethanol (1.0 mmol/kg) and [2,2,2‐2H3]ethanol (1.0 mmol/kg) followed by blood sampling at 10‐min intervals. The concentrations of ethanols labeled with 1, 2, 3, and 4 deuterium atoms were determined by gas chromatography/mass spectrometry of the 3,5‐dinitrobenzoates. During the first 30 min mono‐ and tetradeuteriated molecules appeared rapidly, which indicates that a fraction of the ethanol was formed from acetaldehyde by exchange. This fraction was calculated to be 38–58% and the hydrogen incorporated during the reduction was mainly (63–82%) derived from C‐1 of ethanol, indicating slow exchange of enzyme‐bound NADH. After 30 min the elimination followed first‐order kinetics with t1/2 of 18–31 min and with a small primary isotope effect (1.05–1.11). This indicates almost complete removal of ethanol from blood passing through the liver when the concentration is low (below 1 mM). The results indicate that as long as hepatic blood flow is not limiting, the rate of alcohol dehydrogenase‐catalyzed elimination of a small dose of ethanol in vivo is limited by the dissociation of NADH from the enzyme and by the rates of oxidation of acetaldehyde and reoxidation of NADH.
One‐Month Repeatability of Emotional Responses to Alcohol
Authors: Nagoshi Craig T. , Wilson James R.
Published: April 2006

Thirty‐four subjects in the Colorado Alcohol Research on Twins and Adoptees (CARTA) were brought back between 30 to 60 days after their initial testing to be retested on all the CARTA procedures. As before, subjects were given a dose of ethanol (0.8 g/kg) calculated to bring their blood alcohol concentration (BAC) to near 0.10 g/dl. Additional doses were given at the end of each of the next 2 hr to maintain their BAC near peak for approximately 3 hr. During both testings, subjects' self‐reports of their emotional responses and perceived intoxication following alcohol dosing were only minimally correlated with their alcohol metabolism parameters and reported average level of alcohol use. Repeatabilities (test‐retest correlations) for subjects' self‐reports of positive affect and of intoxication following alcohol dosing were consistently high, in contrast to earlier reports of minimal repeatabilities for alcohol metabolism and responses to alcohol on physiological, motor coordination, reaction time, and perceptual speed measures. Tester ratings of the subjects' levels of intoxication were also moderately stable between the two testings.
Judgments of “Normal” and “Problem” Alcohol Use as Related to Reported Alcohol Consumption
Authors: Danko George P. , Johnson Ronald C. , Nagoshi Craig T. , Yuen Sylvia H. L. , Gidley Jane E. , Ahn Melinda
Published: April 2006

We obtained alcohol use data and judgments of individual (“What do you think?”) and cultural (“What do people in general think?”) norms for normal and problem quantity and frequency of alcohol use, as well as ratings of whether particular alcohol‐related behaviors indicated a drinking problem, from 928 adult respondents who were members of Hawaii's five major racial/ethnic groups [Chinese, European (Caucasian), Filipino, Hawaiian/Part‐Hawaiian, and Japanese ancestry]. As compared with older survey data (but consonant with recent survey data), Hawaiians have substantially increased in alcohol use, as have Filipinos (if they drink at all; a high proportion are abstainers), and to a lesser extent, Japanese. Chinese remain very low in alcohol use, while Caucasians have relatively decreased in use.

Alcohol use norms (especially of own judged normal use) vary across sexes and ethnic groups and are predictors of consumption both within and across groups. Family resemblances are substantial with regard to alcohol use category (present users, former drinkers, abstainers). Among present users, family resemblances are often significant with regard to amount used; resemblances are more substantial between mothers and offspring than between spouses or between fathers and offspring. There were small but significant ethnic group differences in the number of specific behaviors judged to be indicative of a drinking problem, with the groups reporting the highest mean alcohol consumption (Caucasians and Hawaiians/Part Hawaiians) also indicating more behaviors, particularly pathological as opposed to celebratory behaviors, as being problematic. Abstainers judged more celebratory behaviors as being problematic compared with low and high quantity‐frequency users of alcohol, but both abstainers and low alcohol users judged more pathological behaviors as being problematic than the high use group. These results were discussed in terms of cultural norms and individual expectations of alcohol effects.
Effect of Ethanol on the in Vitro Sulfation of Salivary Mucin
Authors: Slomiany Bronislaw L. , Liau Yun H. , Zalesna Grazyna , Slomiany Amalia
Published: April 2006

In vitro sulfation of mucus glycoprotein by sulfotransferase from rat submandibular salivary gland and the effect of ethanol on this enzyme activity was investigated. Subcellular fractionation studies revealed that the enzyme which catalyzes the transfer of sulfate ester group from 3′‐phosphoadenosine‐5′‐phosphosulfate to submandibular gland mucus glycoprotein is associated with Golgi‐rich membrane fraction. The sulfotransferase enzyme exhibited optimum activity at pH 6.8 in the presence of 0.5% Triton X‐100, 4 mM MgCl2, and 25 mM NaF. The enzyme was equally capable of sulfation of the desulfated intact as well as proteolytically degraded desulfated glycoprotein preparations, whereas the acceptor capacity of the intact mucus glycoprotein was 70% lower. The submandibular gland sulfotransferase activity was inhibited by ethanol. The rate of inhibition of mucus glycoprotein sulfation was proportional to the concentration of ethanol up to 0.4 M, at which concentration a 39% reduction in the sulfotransferase activity occurred. The apparent Km value of the enzyme for salivary mucus glycoprotein was 11.1 μM, and the K1 in the presence of ethanol was 0.93 M. The synthesized 35S‐labeled glycoprotein gave on CsCl equilibrium density gradient centrifugation 35S‐labeled peak which coincided with that of the glycoprotein. Alkaline borohydride treatment of this glycoprotein led to the liberation of the label into the acidic oligosaccharide alditol fraction. As the inhibition by ethanol of sulfotransferase enzyme occurred below its isosmotic concentration to plasma, the observed effect could also be detrimental to salivary mucus glycoprotein sulfation in vivo.
Degradation of Aliphatic Alcohols by Human Liver Alcohol Dehydrogenase: Effect of Ethanol and Pharmacokinetic Implications
Authors: Ehrig Torsten , Bohren Kurt Max , Wermuth Bendicht , von Wartburg Jean‐Pierre
Published: April 2006

We have investigated the oxidation of low molecular weight aliphatic alcohols by Class I, II, and III alcohol dehydrogenases (ADH) isolated from human liver. These alcohols are generally present as byproducts of alcoholic beverages and referred to as alcoholic congeners. At concentrations corresponding to those in the blood after ingestion of alcoholic drinks (10–100 μM), the oxidation of propanol‐1, isobutanol, 2‐methylbutanol‐1, and 3‐methylbutanol‐1 was mediated mainly by the isoenzymes of class I ADH, whereas butanol‐1 was metabolized by Class I and II ADH. Class III ADH showed no activity with any of the alcohols at concentrations up to 100 μM. Lineweaver‐Burk plots of the Class I ADH‐catalyzed oxidation of all the congeners tested were linear in the pharmacokinetically relevant concentration range between 10 and 100 μM. Ethanol at concentrations found in the blood after moderate drinking (2.5–10 mM) caused a concentration‐dependent inhibition of the congener oxidation. The experimentally determined kinetic constants were used to simulate the pharmacokinetics of propanol‐1 metabolism in a multicompartment model system which accounts for first‐pass elimination. The results suggest, in agreement with reported data from drinking experiments, that congener alcohols undergo considerable metabolism during the first liver passage, the extent of the first‐pass metabolism depending on the ethanol dose.
Some Aspects of Antioxidant Status in Blood from Alcoholics
Authors: Bjørneboe Gunn‐Elin Aa. , Johnsen Jon , Bjørneboe Anders , Marklund Stefan L , Skylv Nina , Høiseth Arne , Bache‐Wiig Jon‐Erik , Mørland Jørg , Drevon Christian A.
Published: April 2006

The effect of ethanol consumption on serum concentration of α‐tocopherol, erythrocyte activities of superoxide dismutase, glutathione peroxidase, and catalase were studied in 34 male alcoholics and 35 age‐matched controls. Serum concentration of α‐tocopherol was 30% lower in the alcoholics as compared to the controls (p < 0.001). No significant difference was found in erythrocyte activities of Cu‐Zn‐containing superoxide dismutase, glutathione peroxidase, or catalase between the groups. Of the 12 alcoholics with subnormal serum α‐tocopherol, 50% had concomitant neurological clinical scores and cerebellar atrophy, and their neurological scores were significantly higher (82%) than for alcoholics with normal α‐tocopherol levels (p < 0.03). However, no significant correlation was observed between levels of α‐tocopherol and neurological clinical scores or cerebellar atrophy. When entering the study, alcoholics and controls were each randomized into two separate groups, receiving vitamin E supplementation (100 mg/day) or placebo capsules for 10 days, respectively. In the four subgroups, α‐tocopherol levels increased only in alcoholics receiving vitamin E supplementation (23%) (p < 0.001). The reduced serum levels of α‐tocopherol in alcoholics may be normalized by vitamin E supplementation.
Suggestive Evidence of Genetic Linkage between Alcoholism and the MNS Blood Group
Authors: Hill Shirley Y. , Aston Christopher , Rabin Bruce
Published: April 2006

Thirty nuclear families ascertained through an alcoholic proband were studied using segregation and linkage analyses. Linkage was investigated between a putative alcoholism susceptibility (AS) gene and six blood group markers: ABO, Rhesus, Duffy, Kidd, Kell, and MNS. Evidence is presented suggestive of linkage between susceptibility to alcoholism and the MNS blood group.
Prenatal Brain Malformations following Acute Ethanol Exposure in the Rat
Authors: Kotkoskie Lois A. , Norton Stata
Published: April 2006

Morphology of the cerebral cortex was studied in fetuses on gestational Day 21 following oral administration of several doses of ethanol (for total doses of 10,15, or 18 g/kg) to pregnant rats on gestational Days 14 and 15, a critical period for the development of the cerebral cortex. All doses of ethanol were associated with a reduction in maternal weight gain, fetal body weight, and placental weight. Only the high dose of ethanol (total dose 18 g/kg) caused significant fetal cortical thinning. Acute exposure of pregnant rats to ethanol produced dose‐dependent malformations of the cerebral cortex and hippocampus in fetuses. On gestational Day 21, the 18 g/kg group contained fetuses with severely disorganized cortical architecture, heterotopias of the cerebral cortex, pia and choroid plexus, and status verrucosus deformis. Fetuses from the 10 g/kg group had less severe malformations, such as disorganization of layers of cortical neurons and dentate granule cells while fetuses from the 15 g/kg group had a mixture of severe and minor malformations. This study demonstrates that acute ethanol exposure during a critical period of development in rats can result in brain malformations similar to those reported in human fetuses and neonates from alcoholic mothers.
Maintenance of Alcohol Dehydrogenase Activity in Long‐Term Culture of Hepatocytes from Female Rat
Authors: Grunnet Niels , Vind Constance , Dich John
Published: April 2006

Conditions for maintaining the activity of alcohol dehydrogenase in cultures of hepatocytes isolated from female rats were studied. The activity of alcohol dehydrogenase in freshly isolated cells was 1.7 U/mg DNA. When cultured, the activity declined 20% after one day of culture, irrespective of the culture conditions. In a conventional medium with 5mm glucose the activity after one week of culture was only 30% of that initially measured in culture. Addition of 25 mm glucose or a high concentration of amino acids delayed the decrease. When these compounds were added together it was possible to maintain the initial activity for one week, but the activity declined during the following week. Addition of growth hormone had no effect during the first week of culture but abolished the fall during the second week. The initial metabolism of ethanol was 0.65 μmol/min × mg DNA and declined to two‐thirds during the 2 weeks of culture.
Cognitive Ability and Drinking Behavior in a National Sample of Young Adults
Authors: Windle Michael , Blane Howard T.
Published: April 2006

The role of verbal intelligence (VI) as an antecedent and moderator of alcohol‐related problems was investigated for a national sample of young adults. A measure of VI was used to predict alcohol related behavior 5 years later. Results indicated that lower VI was associated with lower risk for drinking per se. Lower VI was also associated with higher risk for alcohol‐related problems among those who drink. These findings were robust across gender, age, and to a large extent across different areas of alcohol related problems. Cognitive‐behavioral functions associated with intelligence, such as social judgement, social inference, and social skills, are proposed as possible moderators of the relationship between intelligence and alcohol‐related problems.
Is Clonidine Useful in the Treatment of Alcohol Withdrawal?
Authors: Robinson B. J. , Robinson G. M. , Maling T. J. B. , Johnson R. H.
Published: April 2006

The comparative efficacy of clonidine and chlormethiazole has been examined in the management of acute alcohol withdrawal. A double blind randomized study was conducted in consecutive patients admitted to a hospital detoxification unit. Patients were assessed regularly by a standard alcohol withdrawal rating‐scale. Thirty‐two patients received either clonidine or chlormethiazole in reducing dosages over 96 hr. All the patients receiving chlormethiazole had uneventful withdrawals. However, eight patients treated with clonidine were withdrawn from the trial due to hallucinations (two), seizures (two), symptomatic orthostatic hypotension (three) or drowsiness (one), indicating that clonidine is less effective than chlormethiazole in the prevention of the major manifestations of alcohol withdrawal.
Time‐dependent Effects of Alcohol on the Hypothalamic‐Hypophyseal‐Testicular Function in the Rat
Authors: Esquifino A. I. , Mateos A. , Agrasal C. , Martin I. , Canovas J. M. , Fermoso J.
Published: April 2006

Adult male rats were followed throughout ethanol administration, in order to examine the time‐dependent effects of ethanol on the hypothalamic‐pituitary‐gonadal axis. The results indicate that there is an increase in plasma prolactin levels together with a reduction in basal plasma luteinizing hormone (LH) levels, which are evident from the beginning of the intoxication period. An exaggerated response of LH to luteinizing hormone‐releasing hormone was also evident from 2nd week on, in ethanol‐treated rats. Basal and human chorionic gonadotropin‐stimulated plasma testosterone levels were decreased in alcohol‐treated as compared to control rats, at all time points studied. In addition, plasma estradiol levels were increased in ethanol‐fed rats. These data suggest a direct suppressive effect of ethanol on LH release in the beginning of the intoxication period. Subsequent elevations of plasma estradiol and prolactin levels may have contributed to the maintenance of hypogonadism at the end of the intoxication period.
Effect of Chronic Ethanol Consumption on the Content of α‐Tocopherol in Subcellular Fractions of Rat Liver
Authors: Hagen Bente F. , Bjørneboe Anders , Bjørneboe Gunn‐Elin Aa. , Drevon Christian A.
Published: April 2006

The effects of long‐term administration of ethanol (35% of total energy for 6–8 weeks) on the distribution and concentration of α‐tocopherol in subcellular fractions of rat liver have been studied. Marker enzymes were measured in all fractions. The highest concentration of α‐tocopherol was found in the light mitochondrial fraction both in ethanol‐fed and control rats, 754 ± 104 and 1127 ± 126 pmol/mg protein, respectively. The microsomal, heavy mitochondrial, and nuclear fractions also had high concentrations of α‐tocopherol, whereas the cytosolic fraction contained minor amounts. In the light mitochondrial fraction we found the highest concentration of a‐tocopherol in lysosomes, whereas small amounts were detected in peroxisomes. In the microsomal fraction the highest concentration was found in the Golgi apparatus. The content of α‐tocopherol in the light mitochondrial fraction was reduced by 33% (p < 0.02) in the ethanol‐fed group as compared to the controls. In the other fractions no significant differences between the two groups were obsetved. Long term administration of ethanol promoted, however, a further enrichment of α‐tocopherol (178% higher than controls) in the Golgi apparatus, possibly due to reduced secretion of very low density lipoprotein‐associated α‐tocopherol.
Impaired Hepatic Elimination of Paranitrophenol and Its Metabolites in the Rat following Chronic Ethanol Pretreatment
Authors: Mitchell M. C. , Hall S. D. , Schenker S. , Branch R. A.
Published: April 2006

Chronic ethanol feeding has been shown to enhance hepatic microsomal drug oxidation in humans and in laboratory animals. However, the effects of chronic ethanol administration on drug conjugation are less conclusive. We have studied the effects of chronic ethanol feeding on (a) the conjugation and elimination of p‐nitrophenol (PNP) by the isolated perfused rat liver, (b) the formation of PNP glucuronide by hepatic microsomal PNP‐glucuronyltransferase in vitro and (c) the hepatic content of UDP‐glucuronic acid (UDPGA). PNP elimination from the isolated perfused rat liver was best described as a combination of parallel saturable and first‐order processes. Ethanol pretreatment did not influence the former but resulted in a 48% reduction in the rate of elimination by the latter. This was associated with a significant reduction in recovery of PNP‐glucuronide from bile, but no change in concentrations of PNP glucuronide or sulfate in perfusate. Michaelis constants and Vmax for PNP‐glucuronyltransferase in native and solubilized microsomes and UDPGA concentrations in liver were not influenced by ethanol pretreatment. These results suggest that chronic ethanol treatment reduces PNP elimination in the intact liver primarily via a reduction in the biliary excretion of PNP glucuronide without altering glucuronidation per se.
Effects of Chronic Ethanol Consumption on Carcinogen Activating and Detoxifying Systems in Rat Upper Alimentary Tract Tissue
Authors: Farinati F. , Lieber C. S. , Garro A. J.
Published: April 2006

The effect of chronic ethanol consumption on enzyme systems directly involved in carcinogen activation and detoxification were studied in rat upper alimentary tract tissue. Microsomal cytochrome P‐450 (P‐450) levels and glutathione levels as well as glutathione transferase and UDP‐glucuronic acid transferase (UDPGT) activities were measured in mucosa scraped from esophagus, forestomach and glandular stomach of rats which had been pair‐fed ethanol or dextrimaltose‐containing diets. Esophageal and forestomach P‐450 levels were increased in the ethanol‐fed rats. The ethanol diet also produced a small but significant increase in esophageal glutathione transferase levels. Glutathione levels and UDPGT activity were unaffected. Since P‐450 is directly involved in the activation of many chemical carcinogens, these results are consistent with the hypothesis that the increase in upper alimentary tract cancer risk associated with alcohol abuse is due, at least in part, to ethanol's altering the balance between carcinogen activation and detoxification.
Thyrotropin‐releasing Hormone Antagonism of Ethanol Inebriation
Authors: Knutsen Håvar , Dolva Lars Øystein , Skrede Sverre , Bjørklund Roald , Mørland Jørg
Published: April 2006

The effect of ethanol [1 g/kg per orally (p.o.) during 1 hr] after thyrotropin‐releasing hormone (TRH) pretreatment (five doses of 20 mg p.o. during 30 hr preceeding ethanol intake) was studied in a placebo‐controlled, double‐blind design in 11 healthy subjects. Computerized reaction tests measuring errors and reaction time, as well as clinical testing and a self evaluation (modified Osgood test) were performed before, 75, 150, and 225 min after ethanol intake.

TRH treatment did not influence blood ethanol concentrations. The effect of ethanol to produce errors was substantially reduced in all three reaction tests after TRH treatment compared to placebo treatment. The reaction times were slightly increased in simple and four choice reaction tests and up to 20% increased in a complex test in the TRH‐ethanol situation compared to the placebo‐ethanol situation. The effects caused by ethanol were also significantly reduced in three clinical tests and in two subjective tests of inebriation by TRH treatment compared to placebo treatment.

In conclusion the study demonstrated that several acute effects of ethanol intake in humans were reduced by TRH pretreatment which did not interfere with the blood ethanol concentration versus time curve.
Underreporting of Alcohol Use in Pregnancy: Relationship to Alcohol Problem History
Authors: Morrow‐Tlucak Mary , Emhart Claire B. , Sokol Robert J. , Martier Susan , Ager Joel
Published: April 2006

Assessment of alcohol‐related fetal risk is complicated by difficulties in assessing alcohol exposure. We previously described considerable underreporting of alcohol use during pregnancy, particularly among problem drinkers. This report is of the relationship between severity of drinking problems and the magnitude of underreporting. Pregnant disadvantaged women responded to the Michigan Alcoholism Screening Test (MAST) at the first antenatal visit and provided self‐report data regarding alcohol use at each antenatal visit. Five years later, 238 of these women again provided self‐report information about drinking during the target pregnancy. Underreporting was defined as a positive difference between the indices computed from the retrospective and the in‐pregnancy data. The relationship of underreporting to the MAST score was highly significant and indicated a 20‐fold increase in underreporting from the lowest to highest MAST score. However, the marked individual variability seen in this relationship indicates that while the MAST may be a better indicator of risk than self‐reports of drinking, it is also not sufficient for the purpose. Further work examining other measures and techniques for obtaining drinking information is indicated.
Ethanol‐induced Hydrolysis of Brain Sialoglycoconjugates in the Rat: Effect pf Sialic Acid in Antagonizing Ethanol Intoxication
Authors: Cherian L. , Mathew J. , Klemm W.R.
Published: April 2006

Several reports indicate that acute ethanol promotes the cleavage of brain sialoglycoconjugates (SGC). We attempted to confirm this effect by monitoring cleavage of sialic acid (SA) that had been radiolabeled by pretreatment with the specific precursor of SA, N‐[3H]acetyl‐d‐mannosamine, injected intracerebroventricuhrly into rats 20 h prior to ethanol injection (2 or 3 g/kg, given four times in a simulated “binge drinking” protocol).

Analysis of the residual labeled material revealed a significant reduction of radiolabel (p < 0.01), as compared to saline controls. A dose of 3 g/kg diminished the total labeled SGC by half. Brain sialidase activity was not affected by the ethanol treatment.

Since ethanol intoxication is associated with enhanced SA cleavage, one hypothesis needing testing is that loss of SA might help to cause intoxication. If so, pretreatment with SA might antagonize intoxication, presumably by offsetting loss due to cleavage of SA. Consistent with our earlier results, we found that when sialic acid was given i.p. (25 mg/kg), 1, 6, or 24 h prior to ethanol injection (4 g/kg, i.p.), the sleep time was reduced by 35‐40% and the performance on rotorod was significantly enhanced (p < 0.01). When ethanol was replaced by pentobarbital (40 mg/kg), the sleep time was increased (∼30%) at 6 h after injection with either 25 or 100 mg/kg sialic acid, whereas at the 24 h postinjection it was decreased (∼20%) at both doses. The results suggest that sialic acid is a key component in mediating ethanol effects and perhaps also, in a different way, anesthetic effects.
T Lymphocyte Populations in Fetal Alcohol Syndrome
Authors: Ewald Sandra J
Published: April 2006

There are reports that fetal alcohol syndrome (FAS) is associated with immune deficiency or DiGeorge syndrome. To investigate the effect of prenatal alcohol exposure on the immune system, we used a mouse model of FAS in which C57BL/6J female mice were fed a complete liquid diet containing 25% ethanol‐derived calories (EDC) from gestational day (g.d.) 1 to 18. Thymus cell numbers were markedly reduced in 18‐day fetuses exposed to ethanol. Thymocytes from fetuses from the 25% EDC diet group and from pair‐fed and ad‐libitum control diet groups were compared by flow cytometry for expression of T cell differentiation antigens. The proportions of L3T4‐and Lyt‐2 positive thymus cells were significantly reduced in alcohol‐exposed fetuses compared to controls; however, the number of Thy‐1‐positive cells did not differ among any of the groups. Six‐day old neonates exposed prenatally to ethanol from g.d. 1 to 13 had thymus and spleen T cell populations similar to those of controls in almost all cases, indicating a “catch‐up” of T cell numbers in most animals. Spleen T cell function, assessed by response to Concanavalin A (Con A), or Con A plus T cell growth factors, was somewhat depressed in ethanol‐exposed 6‐day pups.