bluuebunny/crossref_metadata_2025 huggingface dataset:
Hepatic Triacylglycerol Accumulation Induced by Ethanol and Carbon Tetrachloride: Interactions with Essential Fatty Acids and Prostaglandins
Authors: Cunnane Stephen C
Published: April 2006

Triacylglycerol accumulation in the liver (fatty liver) caused by ethanol or carbon tetrachloride involves interactions with essential fatty acids and prostaglandins. The degree to which the fatty liver develops is dependent on total dietary fat intake. Both ethanol and carbon tetrachloride impair desaturation of linoleic acid and dihomo‐γ‐linolenic acid and this appears to be relevant to the pathogenesis of fatty liver from two points of view. First, low arachidonic acid in liver phospholipids is associated with increased liver triacylglycerol content whether caused by ethanol, carbon tetrachloride, or essential fatty acid deficiency. Second, essential fatty acids including γ‐linolenic acid and arachidonic acid, as well as the prostaglandins, prevent ethanol‐ and carbon tetrachloride‐induced fatty liver. Arachidonic acid and possibly the prostaglandins are therefore likely to be directly involved in lipoprotein and triacylglycerol secretion by the liver.
Effects of Habitual Alcohol Intake and Cigarette Smoking on the Development of Hepatocellular Carcinoma
Authors: Ohnishi Kunihiko , Terabayashi Hidetaka , Unuma Tadao , Takahashi Akira , Okuda Kunio
Published: April 2006

To study the effects of habitual alcohol intake and cigarette smoking on the latency period for the development of hepatocellular carcinoma (HCC), 455 patients with HCC were analyzed with respect to age at diagnosis. They were divided into hepatitis B virus (HBV) positive and negative patients based on HbsAg and high titer anti‐HBc in serum. HBV‐positive and negative HCC patients were further subdivided into four subgroups based on the history of drinking more than one small bottle of Japanese “sake” or its equivalent per day for more than 10 yr and the history of smoking more than one cigarette per day for more than 10 yr. Among HBV‐positive HCC patients, the average age of those with a drinking and a smoking habit (50 ± 10 yr) was younger compared with that of patients with a drinking habit but without a smoking habit (56 ± 14 yr, not significant, NS), of those who were smokers and nondrinkers (55 ± 10 yr, NS) and of those who did not drink nor smoke (59 ± 8 yr, p < 0.005). Among HBV‐negative HCC patients, patients with drinking and smoking habits (57 ± 9 yr) were younger compared with those with a drinking habit without smoking (59 ± 9 yr, NS), those who were smokers and nondrinkers (62 ± 9 yr, p < 0.005), and those who were nondrinkers and nonsmokers (63 ± 12 yr, p < 0.005). These data suggest that habitual alcohol intake may promote the development of HCC if the patients smoke cigarette regardless of the status of HBV seromakers.
Respiratory Responsiveness in Male Alcoholics after Withdrawal
Authors: Lambie David G , Tan Edward T. H. , Johnson Ralph H
Published: April 2006

Peripheral and central chemosensitivity were assessed in eight abstinent male alcoholic patients and in seven healthy normal male subjects. Hypoxic rebreathing (15% O2, 7% CO2) was used to stimulate the peripheral and central chemoreceptors together. Hyperoxic rebreathing (93% O2, 7% CO2) was used to examine the central chemoreceptor response independently of the peripheral chemoreceptors. Minute ventilation was examined in relation to end‐tidal PACO2 under the two conditions. Neither peripheral nor central chemoreceptor responses were signficantly altered in the alcoholic as compared to the control subjects. Abnormal chemoreceptor function is therefore unlikely to be an important factor in the development of abnormal respiratory events during sleep in abstinent alcoholic subjects.
Individual Differences in Behavioral and Subjective Responses to Alcohol
Authors: de Wit H. , Uhlenhuth E. H. , Pierri J. , Johanson C. E.
Published: April 2006

The reinforcing properties and subjective effects of alcohol were assessed in 29 normal volunteers using a seven‐session choice procedure. On the first four sessions, subjects sampled an alcohol (0.5 g/kg) and a placebo beverage twice each. On three subsequent choice sessions, subjects chose the drink they preferred. The number of times they chose alcohol was the measure of its reinforcing properties. On all sessions subjects completed mood questionnaires before and several times after consuming the beverage. Other dependent measures during the experiment included a cognitive performance task, drug liking and identification questionnaires, and breathalyzer alcohol determinations. Demographic and personality data also were obtained. Approximately one‐third of the subjects chose the alcohol‐containing beverage on all three choice sessions, one‐third alternated in their choices of alcohol and placebo, and one‐third consistently chose the placebo. When the subjective effects of alcohol (determined during sampling sessions) were compared across the three choice groups, qualitative differences in response to alcohol were observed. For example, alcohol increased elation and vigor scores in the consistent choosers of alcohol, whereas it decreased scores on these measures in the consistent placebo choosers. Consistent alcohol choosers did not differ from placebo choosers in gender or age but they reported more marijuana use and slightly more alcohol use outside the laboratory. They also scored higher on certain measures of arousal and depression, on the Sensation Seeking Scale and on the Psychopathic State Inventory. The results are discussed in terms of individual differences in vulnerability to excessive use of alcohol.
Hepatic Protein Synthetic Activity in Vivo after Ethanol Administration
Authors: Donohue Terrence M. , Sorrell Michael F , Tuma Dean J
Published: April 2006

Hepatic protein synthetic activity in vivo was measured by the incorporation of [3H]puromycin into elongating nascent polypeptides of rat liver to form peptidyl‐[3H]puromycin. Our initial experiments showed that saturating doses of [3H]puromycin were achieved at 3‐6 μmol/100 g body weight, and that maximum labeling of nascent polypeptides was obtained 30 min after injection of the labeled precursor. Labeled puromycin was found to be suitable for measuring changes in the status of protein synthesis, since the formation of the peptidyl‐[3H]puromycin was decreased in fasted animals and was increased in rats pretreated with L‐tryptophan. [3H]Puromycin incorporation into polypeptides was then measured after acute ethanol administration as well as after prolonged consumption of ethanol which was administered as part of a liquid diet for 31 days. Acute alcohol treatment caused no significant change in [3H]puromycin incorporation into liver polypeptides. In rats exposed to chronic ethanol feeding, peptidyl‐[3H]puromycin formation, when expressed per mg of protein, was slightly lower compared to pair‐fed controls, but was unchanged compared to chow‐fed animals. When the data were expressed per mg of DNA or per 100 g body wt, no differences in protein synthetic activity were observed among the three groups. These findings indicate that neither acute nor chronic alcohol administration significantly affects protein synthetic activity in rat liver. They further suggest that accumulation of protein in the liver, usually seen after prolonged ethanol consumption, is apparently not reflected by an alteration of hepatic protein synthesis.
Symptoms and Diagnosis of Depression in Alcoholics
Authors: Dorus Walter , Kennedy Josephine , Gibbons Robert D , Ravi Suseela D
Published: April 2006

We examined depressive symptoms, using the Beck Depression Inventory (BDI), in a group of 50 alcoholic patients, diagnosed according to DSM III criteria during active drinking, withdrawal (4 days after their last drink), and abstinence (24 days after their last drink). DSM III diagnoses of major depression were made in 16 (32%) of the patients. The diagnoses were made using the NIMH Diagnostic Interview Schedule (DIS) between the 10th and 24th day after the patients' last drink. Depressive symptoms decreased markedly as the patients progressed from active drinking to abstinence. Alcoholic patients having a diagnosis of major depression had higher BDI scores than those not having a diagnosis of major depression. Analysis of BDI items using a two‐parameter logistic item response model confirmed that the BDI measured depressive symptoms in these alcoholics. We conclude that the BDI is valid for screening for depression in alcoholic patients.
Ethanol Vapor above Skin: Determination by a Gas Sensor Instrument and Relationship with Plasma Concentration
Authors: Giles H.G. , Meggiorini S , Renaud G.E. , Thiessen J.J. , Vidins E.I. , Compton K.V. , Saldivia V , Orrego H , Israel Y
Published: April 2006

Studies with a new instrument show that blood ethanol concentrations in rats and humans can be estimated by measurement of ethanol vapor above the skin. After intravenous bolus administration of ethanol (1 g/kg) to rats a novel device based on the Figaro sensor was placed above the animal's abdomen. Plasma and skin vapor ethanol concentrations, analyzed by gas chromatography and sensor, respectively, declined in parallel (r= 0.96). In healthy human subjects, plasma and skin vapor concentrations, measured on the palm, also declined in parallel after intravenous ethanol infusion (1 hr, 0.5 g/kg), r= 0.99. In 10 alcoholic liver disease outpatients attending clinic in whom plasma ethanol concentrations ranged from 32–304 mg/dl, the correlation of plasma ethanol determined directly by gas chromatography and indirectly by skin vapor analysis was slope = 0.93, intercept = 1.8, r= 0.94. In controlled studies, skin vapor measurements are comparable with breathalyzer determinations; they may be performed in situations where breathalyzer measurements are inconvenient or where continuous monitoring is desirable.
Prenatal Ethanol Exposure Affects Temperature Responses of Adult Rats to Pentobarbital and Diazepam Alone and in Combination with Ethanol
Authors: Taylor Anna Newman , Branch Berrilyn J , Randolph Doris , Hill Mary Ann , Kokka Norio
Published: April 2006

Long‐term effects of prenatal alcohol exposure on body temperature responses to pentobarbital and diazepam and to either drug in combination with ethanol were studied in adult rats who were the offspring of dams fed a 5.0% w/v ethanol‐containing liquid diet during the last 2 weeks of gestation. Adult offspring of pair‐fed and chow‐fed dams served as nutritional and normal controls, respectively. Pentobarbital (6.25–25.0 mg/kg) and diazepam (2.5–10.0 mg/kg) produced significantly greater dose‐related hypothermic responses in females than males. Following either pentobarbital or diazepam administration female prenatally ethanol‐exposed (E) rats responded with a greater fall in body temperature than the controls. Significantly greater hypothermia occurred in both male and female E rats than in controls when ethanol (1.5 g/kg) was administered together with pentobarbital or diazepam. However, the drug combinations did not produce additive effects on body temperature in any prenatal treatment group. Pentobarbital produced acute cross‐tolerance to ethanol while diazepam potentiated ethanol's effect. These studies confirm and extend our previous findings of enhanced hypothermic responses to ethanol in adult rats exposed to ethanol in utero and indicate that maternal alcohol consumption produces long‐term effects on the central thermoregulatory systems of offspring.
Effect of Ethanol on Regional Myocardial Blood Flow and Hemodynamics, before and after Coronary Artery Ligation in Dogs
Authors: Sarma Jonnalagedda S. M. , Venkataraman K. , Samant Dinesh R. , Gadgil Uday
Published: April 2006

The effects on regional myocardial blood flows (RMBF) and hemo‐dynamics due to ethanol administered before and after acute coronary artery ligation (CAL) in 18 anesthetized dogs were studied. Ethanol was administered to seven dogs (group I) prior to CAL and to six dogs (group II) after CAL; five dogs (group III, control) received only saline before and after CAL. Uniform blood ethanol levels (180 ± 30 mg/dl) were maintained in groups I and II after initial ethanol administration. In these groups the heart rate and rate‐pressure product (which reflects myocardial oxygen consumption) remained stable, but pulmonary arterial pressures were elevated. Other hemo‐dynamic parameters remained stable in all groups. Ethanol caused a significant transmural increase of RMBF (p < 0.001) in both groups I and II. In group II the increase was significant in both nonischemic and ischemic tissues, with no apparent redistribution of flow among the myocardial layers. The percentage increase of RMBF due to ethanol was highest in group II nonischemic tissue (95–107%) compared to the corresponding ischemic tissue (57–60%) and the group I myocardial tissue (36–47%) prior to CAL (p < 0.001). The observed differences between ethanol pre‐ and posttreatments suggest different interactions between ethanol and catecholamines. The results also confirm that vasodilatory reserve is present in the acutely ischemic myocardium and that the local availability of ethanol is important for coronary vasodilatation.
Adaptation of Lipogenesis and Lipolysis to Dietary Ethanol
Authors: Woollett Laura A. , Baldner‐Shank Glenace L. , Aprahamian Simon , Engen Richard L , Beitz Donald C
Published: April 2006

The effect of dietary ethanol on metabolic fates of glucose and ethanol, and activities of lipoprotein lipase and hormone‐sensitive lipase in several tissues of miniature pigs were determined in vitro. Ethanol and glucose were used at similar rates for fatty acid synthesis in liver and brain and CO2 production in liver. Ethanol was preferred over glucose for fatty acid and CO2 production in ileal mucosal cells. Glucose was the preferred substrate for lipogenesis and oxidation to CO2 in adipose tissue and skeletal muscle, and for oxidation to CO2 in brain. Dietary ethanol decreased glucose and ethanol conversion to fatty acids in ileal mucosa and brain, respectively. Dietary ethanol had no effect on the capacity of liver, adipose tissue, and skeletal muscle to convert either glucose or ethanol to long‐chain fatty acids. The capacity to oxidize ethanol, but not glucose, to CO2 in liver was increased by dietary ethanol. No dietary ethanol effect was observed in other tissues. The capacity for removal of plasma triglycerides (based on lipoprotein lipase activity) tended to increase in adipose tissue and skeletal muscle of pigs fed ethanol. Mobilization of long‐chain fatty acids from adipose tissue (based on hormone‐sensitive lipase activity), triglyceride concentration in plasma, and percentage of lipid in liver remained unchanged when ethanol was fed. Livers of ethanol‐fed pigs, however, were larger than livers of control pigs. Our results indicate that feeding miniature pigs 21–37% of total caloric intake as ethanol causes significant metabolic adaptations of lipid metabolism in liver and ileal mucosa, but not in adipose tissue, skeletal muscle, and brain. The ethanol feeding, however, did not cause fatty livers or hyperlipidemia.
Genetic Influences on Use and Abuse of Alcohol: A Study of 5638 Adult Finnish Twin Brothers
Authors: Kaprio Jaakko , Koskenvuo Markku , Langinvainio Heimo , Romanov Kalle , Sarna Seppo , Rose Richard J
Published: April 2006

To evaluate genetic influences on the use and abuse of alcohol, we compared questionnaire measures of the frequency, quantity, and density of social drinking, and the frequency of alcohol‐induced passouts self‐reported by 879 monozygotic (MZ) and 1940 dizygotic (DZ) pairs of twin brothers, aged 24–49 yr. The measures of frequency, quantity, and density (heavy drinking once or more a month) significantly intercorrelate, and the self‐reported alcohol consumption by this sample is satisfactorily stable and consistent with nationwide sales figures. None of the drinking measures was associated with twin type (zygosity), and only density correlated with age. Similarity of drinking habits among twin brothers was evaluated as a function of their genetic resemblance and age, the frequency of their social contact with one another, and the interactions of these terms. The effects were estimated from hierarchical linear regressions of a double‐entry data matrix from which each twin's drinking was predicted from that of his twin brother, and that pair's age, zygosity, cohabitation status, and frequency of social contact. Significant genetic variance was found for each of the drinking measures with heritability estimates ranging from 0.36 to 0.40. Co‐twins in more frequent social contact with one another reported greater similarity in their use of alcohol, but heritable variance remained after the effects of age and social contact were removed from both mean levels and co‐twin resemblance. Reported frequency of pass‐outs yielded significant, but equivalent, correlations in both MZ and DZ twins and no evidence of genetic influence.
Alcoholic Cerebellar Degeneration Is Not a Dose‐Dependent Phenomenon
Authors: Estrin William J
Published: April 2006

Eleven alcoholics with cerebellar degeneration (eight with computerized tomography confirmation of cerebellar atrophy) were matched with nonataxic alcoholics and nonalcoholics. There were no laboratory or physiological markers for ataxia, including hemoglobin A1a+b, red blood cell transketolase, liver function enzymes, and measures of reaction time and hand‐eye coordination. Acetaldehyde‐modified hemoglobin levels (as hemoglobin A1a+b) did not, as previously reported, distinguish between alcoholics and nonalcoholics. There was 24% less annual alcohol consumption in ataxic alcoholics compared with nonataxic alcoholics, 9% less lifetime consumption in ataxic alcoholics, and 33% less maximal daily intake. The finding that ataxic alcoholics do not have higher alcohol consumption than nonataxic alcoholics suggests that alcoholic cerebellar degeneration is not a dose‐dependent phenomenon, and that alcoholics with cerebellar degeneration may have an idiosyncratic sensitivity to the neuronal effects of alcohol.
Influence of Family Alcoholism History on Alcohol Metabolism, Sensitivity, and Tolerance
Authors: Nagoshi Craig T , Wilson James R
Published: April 2006

As part of the Colorado Alcohol Research on Twins and Adoptees (CARTA), 35 subjects who reported having an alcoholic parent or sibling [family alcoholism history positive (FHP)] were matched with 35 controls [family alcoholism history negative (FHN)]. All subjects were tested three times on a battery of physiological, motor, and cognitive performance tasks before the ingestion of alcohol, then were tested three more times over a 3‐hr period during which their blood alcohol concentration (BAG) was brought up to and maintained at about 0.10 g/dl by an initial large dose of ethanol and subsequent topping doses. FHP subjects scored significantly lower than FHN subjects on the Raven's Progressive Matrices and on some of the cognitive tasks before alcohol ingestion. FHP and FHN subjects, however, did not significantly differ in absorption and clearance of alcohol or in sensitivity and acute tolerance scores calculated on the repeated measures. Contrary to expectations, FHP subjects perceived themselves as being more impaired by alcohol than FHN subjects, and there was little evidence to suggest that they were less sensitive to variations in BAC.
Brain Impairment in Social Drinkers? No Cause for Concern
Authors: Bowden Stephen C
Published: April 2006

Correlations between measures of alcohol consumption and cognitive test scores have been interpreted to reflect a chronic toxic effect of ethanol on brain function in light to moderate social drinkers. However, the data indicate that there is little support across research groups for any specific relationship and, at best, the effect of alcohol consumption accounts for only a small proportion of variance. Consideration of test validity suggests that the principal measure of ability used in this research is not capable of elucidating cerebral deficit. Further, the pattern of observed correlations is not consistent with the assumption that the putative effects of social drinking involve deficits less severe but similar in type to those seen in chronic alcoholics. Instead, an association between innate ability, demographic variables, and drinking behavior in the general population is the most parsimonious explanation of all the data.
Alcohol Use among Drug Abusers: Treatment Outcomes in a Therapeutic Community
Authors: De Leon George
Published: April 2006

Male and female dropouts and graduates (N = 248) from a traditional drug‐free therapeutic community were followed 2 years after treatment. A 4‐hr face‐to‐face interview traced the social adjustment one year pre‐, through all years posttreatment. Results showed that (a) success (no crime and no opioid and/or no use of nonopioid primary drug) was maintained through 2 years of follow‐up by 34% of the dropouts and 68% of the graduates; (b) success rates were highest among opioid abusers and the lowest among primary alcohol abusers; (c) among the latter, however, abstinence rates were significantly increased and daily use of alcohol significantly decreased as did criminal involvement; (d) among the opioid abstinent group, alcohol use increased posttreatment but heavy drinking was not prominent indicating no significant shift in substance dependency. Overall, the therapeutic community appears most effective for opioid abusers but has a clear impact on a considerable number of those primarily involved with alcohol and other substance use.
Differences among Five Main Forms of Serum Transferrin
Authors: Petrén Sven , Vesterberg Olof , Jörnvall Hans
Published: April 2006

Five forms of human serum transferrin with different isoelectric points were purified by isoelectric focusing in agarose gels. They constitute a set of main transferrin forms in serum of healthy individuals. Their relative proportions are changed in serum from alcoholic individuals, where the more basic of these forms are increased. Tryptic peptides of all forms were compared by high performance liquid chromatography (HPLC) patterns (fingerprint analysis). Two major differences were detected between corresponding tryptic peptides of the five transferrin forms. Some minor differences were also noticed. The corresponding peptides were purified from the main form and analyzed for total composition and amino acid sequence. The peptides with the major differences between the forms were found to be the two with the glycosylation attachment at positions 413 and 611. A minor peptide difference between the transferrin forms contains a product that is explained by incomplete stoichiometry in cleavage of the peptide bond at positions 217–218. Successive loss of sialic acid is compatible with the presence of different transferrin forms, and our results indicate that the main differences between the serum transferrin forms from healthy and alcoholic individuals are in successive changes of the carbohydrate chains attached at positions 413 and 611.
Auditory Brainstem Potentials in Sons of Alcoholic Fathers
Authors: Begleiter Henri , Porjesz Bernice , Bihari Bernard
Published: April 2006

With the use of event‐related brain potentials we have observed sensory as well as cognitive deficits in abstinent alcoholics. By recording auditory brainstem potentials (BSP) from abstinent alcoholics we demonstrated significant delays in brainstem transmission time. We have also reported that P3 amplitudes are significantly reduced in abstinent alcoholics compared to control subjects.

Although the neurophysiological deficits observed in abstinent alcoholics are presumed to be alcohol‐related effects, it is possible that some of these deficits may exist prior to alcohol exposure, and may be present in subjects at high risk for alcoholism. We have recently observed significantly reduced P3 components in young sons of alcoholics similar to those observed in abstinent alcoholics. In the present study, we examined auditory BSPs in young boys at high risk for alcoholism and matched controls. We found no statistically significant difference in brainstem transmission time between high risk individuals and matched control subjects. These findings suggest that while some brain deficits observed in abstinent alcoholics may antecede the development of alcoholism (P3) and may represent a predisposing factor, other deficits (BSP) appear to be the consequence of alcohol and/or nutritional‐related effects.
Chronic Ethanol Consumption Affects Filipin‐Cholesterol Complexes and Intramembranous Particles of Synaptosomes of Rat Brain Cortex
Authors: Renau‐Piqueras Jaime , Miragall Fernando , Marques Amparo , Baguena‐Cervellera Rafael , Guerri Consuelo
Published: April 2006

To assess the effect of ethanol on the planar distribution of cholesterol as well as on the surface architecture of presynaptic terminals of rats, synaptosomes isolated from cerebral cortex of rats chronically exposed to alcohol were incubated with filipin, a cytochemical marker for β‐hydroxycholesterol, and analyzed using both conventional (qualitative and quantitative) and freeze‐fracture electron microscopy. Synaptosomes incubated in the absence of filipin were used as cytochemical controls. Biochemical determination indicates a 12% increase of cholesterol in synaptosomal membranes from alcohol treated rats. This increase was confirmed by a significant increment in the number of filipin‐cholesterol complexes.

Synaptosomes of treated rats showed a reduction in the total number of synaptic vesicles (SV) as well as a decrease in the density and total number of intramembranous particles (IMP) per synaptosome. In control rats, most synaptosomal IMP were distributed in clusters whereas in those of rats exposed to alcohol they were distributed at random. These changes in distribution of IMP were also observed in presynaptic terminals analyzed “in situ.” These findings indicate that ethanol acts on the presynaptic terminals. The variations in cholesterol content as well as in the density and distribution of IMP appear to be related to alcohol‐induced changes in the physicochemical properties of components of the synaptosomal membrane.
Association between Alcoholism and Increased Hepatic Iron Stores
Authors: Irving Michael G. , Halliday June W. , Powell Lawrie W.
Published: April 2006

Although alcoholic liver disease is often associated with some increase in hepatic iron stores, it is now established that when gross iron overload is present, this is due to genetic hemochromatosis. Furthermore, there appears to be a critical iron concentration necessary for the induction of hepatic fibrosis. Lipid peroxidation induced by ethanol and/or iron would appear to play a major role in hepatic damage in both humans and experimental animals. Although the exact mechanism(s) of induction of lipid peroxidation by ethanol and iron remains to be elucidated, both toxins can exert a synergistic effect upon hepatic lipid peroxidation. Iron overload has also been shown to stimulate directly hepatocyte and hepatic procollagen mRNA expression, which is further stimulated by ethanol. The observed synergism between iron and alcohol with respect to both hepatic lipid peroxidation and collagen biosynthesis offers a possible explanation of the apparent early onset of fibrosis and cirrhosis in patients with iron overload who have an excessive alcohol intake.
α‐2‐Adrenoceptor Function in Alcohol Withdrawal: A Pilot Study of the Effects of IV Clonidine in Alcoholics and Normals
Authors: Nutt David , Glue Paul , Molyneux Stephen , Clark Earl
Published: April 2006

Central α‐adrenoceptor function was studied in seven withdrawing alcoholics and compared with seven normal controls using the clonidine challenge test The alcoholic group had significantly elevated basal levels of Mood pressure and plasma 3‐methoxy‐4‐hydroxyphenyl glycol. The percentage of fall in Mood pressure produced by clonidine was blunted in the alcoholics. There was disruption of the neuroendocrine effects of clonidine on growth hormone release. Physiological indices of withdrawal, in particular plasma 3‐methoxy‐4‐hydroxyphenyl glycol and blood pressure correlated with measures of previous withdrawal experiences, supporting the idea that kindling might occur with repeated episodes of withdrawal.
Alcoholics Committed to Treatment: A Prospective Long‐Term Study of Behavioral Characteristics, Mortality, and Social Adjustment
Authors: Berglund Mats
Published: April 2006

Three hundred eighty‐three alcoholics, who had at least once been ordered supervision or compulsory treatment at an institution for alcoholics by the Temperance Board, were compared with 383 other alcoholics matched for age and sex. All the alcoholics were first admitted to the Department of Psychiatry, University Hospital, Lund, during the years 1949 to 1969 and followed up until January 1, 1981. They were systematically rated concerning symptoms and etiological factors at first admission. According to a stepwise logistic regression analysis, the following initial symptoms were positively associated with later compulsory treatment: slight cerebral dysfunction/personality change, antisociality/criminality, and impaired social and work performance. Social pressure/responsibility/conflict, slight depression, and continuous drinking were positively associated with the controls. There were 168 deaths in the compulsory treatment group and 124 in the control group (p < 0.01). The excess deaths in the compulsory treatment group were mainly caused by accidents, poisoning, and violence (21 cases) and sudden cardiac death (10 cases), while there were no differences concerning alcohol‐related neoplasms and liver cirrhosis. The compulsory treatment group had a worse long‐term social adjustment. The findings indicate that compulsory treatment was related to behavioral patterns showing a stability over time, supporting the validity of subclassification of alcoholics using social data.
Genetically Determined Response of Hepatic Aldehyde Dehydrogenase Activity to Ethanol Exposures May Be Associated with Alcohol Sensitivity in Mouse Genotypes
Authors: Wei V. L. , Singh S. M.
Published: April 2006

Mice (Mus musculus) from four genetic strains (BALB/c, C57BL/6J, 12Q/ReJ, and SW) and their F, hybrids (SWxBALB/c, C57BL/6JWxBALB/c, and C57BL/6Jx129/ReJ) were used to evaluate the effect of ethanol on the activity of the two primary enzymes, alcohol dehydrogenase (ADH; E.C.1.1.1.1) and aldehyde dehydrogenase (ALDH; E.C. 1.2.1.3), of alcohol metabolism. Three week‐old male mice (12–16 g) were placed on liquid diet (5% ethanol) while a weight‐matched littermate control was fed isocaloric maltose‐dextrin in place of ethanol. Animals were sacrificed after 3 weeks and the liver and stomach were excised for biochemical analysis. Although the ethanol feeding did not influence the stomach ADH and ALDH activity levels, these enzymes in the liver were affected. The liver ADH activity was depressed to varying degrees in all mouse genotypes studied. Also, the ethanol feeding altered the liver‐ALDH activity, which was highly variable and genotype specific. The mice of C57BL/6J and F, C57BL/GJxBALB/c, both relatively resistant genotypes, exhibited significant increase in liver ALDH‐(cytosolic and whole liver homogenate) activity. The response in the other genotypes were not significantly different from their matched controls. The relative resistance of the C57BL/6J strain may be associated with the increase in liver ALDH activity which is expected to facilitate the elimination of acteladehyde, the toxic metabolite. The results from the selected F1 crosses indicate a multigene system regulating the inducibility of the liver ALDH. The relative sensitivity of different genotypes may be attributed to inducibility components regulating the liver enzyme activity, particularty liver ALDH following challenges with ethanol. These observations may offer a new approach in explaining extensive variability in response to alcohols in most populations.
Effects of Prenatal Alcohol Exposure on the Sexually Dimorphic Nucleus of the Preoptic Area of the Hypothalamus in Male and Female Rats
Authors: Barron Susan , Tiernan Suzannah Bliss , Riley Edward P.
Published: April 2006

Prenatal alcohol exposure can produce a variety of behavioral and physiological alterations, including changes in sexually dimorphic behaviors. It has been proposed that alcohol alters these behaviors by altering prenatal androgen and/or other steroid levels. This study was designed to examine the effects of prenatal alcohol exposure on a sexually dimorphic neuroanatomical structure, namely, the sexually dimorphic nucleus of the preoptic area of the hypothalamus (SDN‐POA). This nucleus is larger in males than females and is sensitive to perinatal sex steroid exposure. The SDN‐POA was examined in 70–80‐day‐old male and female rats whose mothers received on days 6–20 of pregnancy either a liquid diet containing 35% ethanol‐derived calories (EDC) or a 0% EDC isocaloric pair‐fed liquid diet. An ad libitum lab chow control group was also included (LC). Both volume and average cell size of the SDN‐POA were markedly smaller in alcohol‐exposed males relative to 0% EDC and LC controls. In contrast, prenatal alcohol exposure did not appear to affect SDN‐POA volume or cell size in females. Prenatal alcohol exposure did not significantly alter the volume of a nearby nucleus, the nucleus of the anterior commissure, in either sex. These findings support the hypothesis that prenatal alcohol exposure alters sexual differentiation in males, perhaps by altering some aspect of the prenatal androgen environment. The absence of any effect in 35% EDC females suggests that males and females may be differentially sensitive to alcohol's effects on this nucleus.
Angiotensin Converting Enzyme Inhibitors: Animal Experiments Suggest a New Pharmacological Treatment for Alcohol Abuse in Humans
Authors: Spinosa G. , Perlanski E. , Leenen F. H. H. , Stewart R. B. , Grupp L. A.
Published: April 2006

The prevalence of heavy alcohol consumption is a major problem of increasing proportions throughout the world. Although alcohol sensitizing drugs and more recently serotonin uptake inhibitors are drug interventions with some following, their long term beneficial consequences have yet to be demonstrated. In recent years, we have demonstrated that manipulating activity in the renin‐angiotensin system will dramatically alter voluntary alcohol consumption in rats. Based on these findings, the present study evaluated the ability of a class of drugs known as the angiotensin converting enzyme inhibitors to reduce voluntary alcohol drinking in laboratory animals. These drugs prevent the conversion of angiotensin I to angiotensin II. They have been licensed for use in Europe and North America and are indicated in the treatment of hypertension. Our experiments showed that both captopril (Capoten, Squibb) and enalapril (Vasotec, Merck Sharpe & Dohme) can reduce alcohol drinking in both normotensive and hypertensive animals regardless of whether the pattern of intake is in a bout or of a less exaggerated nature. Furthermore, this change in alcohol intake can occur without concomitant changes in blood pressure, plasma renin activity, overall fluid balance, or the distribution and metabolism of alcohol. Taken together these findings suggest that the angiotensin converting enzyme inhibitors should be evaluated in a clinical setting for they may prove to be a useful new treatment or treatment adjunct for alcohol abuse in humans.
Pharmacokinetics of Ethanol in the Guinea Pig
Authors: Litvin Judith , Switzer Boyd R.
Published: April 2006

Chronic consumption of ethanol by pregnant and nonpregnant guinea pigs for 8 weeks at doses of 1.2 or 1.6 g/kg body weight twice daily affected pregnancy outcome and changed the pharmacokinetics of ethanol elimination. Ethanol treatment as compared to that of isocaloric sucrose decreased maternal weight, and decreased both the litter size and the number of liveborn offspring. Total litter weight was significantly decreased with the low ethanol dose (12% alcohol‐derived energy). During pregnancy, low and high doses produced peak blood ethanol concentrations (BEC) of 89 ± 8 mg/dl (mean ± SE) and 125 ± 6 mg/dl, respectively. At the high dose, peak BEC decreased dramatically (about 30%) in both pregnant and nonpregnant animals from treatment weeks 0 to 4; thereafter peak BEC remained depressed up to 8 weeks of treatment, which occurred with a concomitant increased volume of ethanol distribution. With both doses, rates of ethanol elimination and Michaelis‐Menten's Vm values were significantly lower among pregnant as compared with nonpregnant guinea pigs during 8 weeks of treatment. These data suggest that the guinea pig can be a valuable animal model to study the effects of low ethanol doses on fetal growth, the adaptation of peak BEC with duration of treatment and the lower rate of ethanol elimination in pregnancy.
Brain CT Changes in Alcoholics: Effects of Age and Alcohol Consumption
Authors: Pfefferbaum Adolf , Rosenbloom Margaret , Crusan Kathryn , Jernigan Terry L.
Published: April 2006

A computerized tomographic (CT) brain scan and assessments of lifetime alcohol consumption, body size, and cognitive performance were performed in 37 male alcoholics, aged 26–62 years. Hematocrit and mean corpuscular volume (MCV) were also measured. CT data were analyzed using a semiautomated scoring system yielding measures of percentage of fluid at the ventricles and cortical sulci. Normative brain CT data from 57 community controls spanning the adult age range allowed Z‐score assessment of deviation from age norms for each alcoholic. Across the entire group, alcoholics had significantly enlarged ventricles and sulci for their age. Enlargement at both sites correlated significantly with lifetime alcohol consumption. Sulcal enlargement in alcoholics was found across all ages. In contrast, ventricular enlargement was apparent only in older alcoholics and became increasingly exaggerated with age. Measures of body sire, hematocrit, and MCV correlated with ventricular but not sulcal enlargement, suggesting that nutritional factors play a role in ventricular enlargement. Associations between neuropsychological performance and CT changes or alcohol consumption were less pronounced and at times counterintuitive. The findings support a modest dose‐effect relationship between ethanol exposure and changes in brain morphology, and suggest that ventricles and sulci show a different time course of response. The role of nutritional status needs to be more closely investigated.
Neuropsychological Performance and Treatment Outcome in Male Alcoholics
Authors: Eckardt Michael J. , Rawlings Robert R. , Graubard Barry I. , Faden Vivian , Martin Peter R. , Gottschalk Louis A.
Published: April 2006

Commonly used neuropsychological tests were administered to 91 detoxified alcoholics at the beginning of treatment. Statistically significant relationships were observed between test scores and post treatment consumption determined 8 months after completing treatment for 72 patients. The results varied depending upon the particular measure of posttreatment consumption evaluated and the type of statistical analysis used. The most consistent relationships were often counter to the notion that increased neuropsychological performance is correlated with a more favorable treatment outcome. Neuropsychological evaluation is of limited clinical utility in predicting posttreatment alcohol consumption.
Multivariate Diallel Analysis of Ethanol Withdrawal Symptoms in Mice
Authors: Corley Robin , Allen Darrel
Published: April 2006

Mice from five highly inbred strains were crossed in a complete diallel design. Five hundred and fifty‐five offspring were given a liquid diet containing ethanol as their sole food source for 9 days in an attempt to induce dependence. At 6 hr postwithdrawal on day 10, the mice were given a battery of physiological and behavioral measures designed to assess the symptoms of withdrawal. Littermate data were aggregated separately by sex and the aggregate litter mean data was employed in a multivariate extension of Hayman's diallel analysis. Hypothesis sums of squares and cross‐products were tested against pooled‐within‐cell sums of squares and crossproducts using Wilk's λ as a criterion. For each sex, a highly significant additive effect was found, with some evidence for dominance effects as well, suggesting the raw materials are present for successful genetic selection, There was some evidence for dominance effects as well, but no evidence for maternal and other reciprocal effects was found for the set of seven measures. Composites derived from the additive and general dominance hypotheses correlation matrices and error correlation matrix were compared with a composite index currently being used in a multivariate selection study of ethanol dependence. Total ethanol consumption during the exposure period was positively correlated with low dependence between strains, and negatively correlated with measures of low dependence within cells.
Drinking Patterns and Problems Associated with Injury Status in Emergency Room Admissions
Authors: Cherpitel Cheryl J. Stephens
Published: April 2006

A study of emergency room admissions at San Francisco General Hospital was undertaken to analyze the association of drinking patterns and problems with injury status. A 20% probability sample of patients admitted to the emergency room around‐the‐clock over a 60‐day period was interviewed. Interviews were completed on 75% of those sampled (N= 1896). Of these, 29% (N= 555) were admitted to the emergency room for injuries, with drinkers more likely than abstainers to be admitted for injuries. Differences were found in the quantity and frequency of usual drinking and frequency of drunkenness for type and cause of injury and for prior alcohol‐related accidents. Little difference was found between the injured and noninjured on social consequences of drinking or experiences associated with alcohol dependence and loss of control over drinking. Both injured and noninjured in this population reported much higher rates of frequent heavy drinking and alcohol‐related problems than that found in the general population which may have masked additional associations of drinking patterns and problems with injury status.
Alcohol‐induced Enhancement of Intestinal γ‐Glutamyl Transpeptidase Activity in Rats and Humans: A Possible Role in Increased Serum γ‐Glutamyl Transpeptidase Activity in Alcoholics
Authors: Ishii Hirornasa , Watanabe Yoko , Okuno Furnio , Takagi Toshikazu , Munakata Yoshio , Miura Soichiro , Shigeta Yohsuke , Tsuchiya Masaharu
Published: April 2006

It is a well‐known phenomenon that serum γ glutamyltranspeptidase (γ‐GTP, EC 2.3.2.2.) activity is increased after chronic consumption of ethanol, and γ‐GTP has been, therefore, widely used as a sensitive marker for detection of alcoholism and its related liver disease. However, the precise mechanisms whereby the chronic ethanol consumption leads to an increase in serum γ‐GTP activity are not fully understood. In the present study, we investigated the relationship between the intestinal and serum γ‐GTP activities after chronic ethanol consumption both in rats and humans.

Chronic ethanol feeding to rats resulted in a significant increase in serum γ‐GTP activity associated with a significant increment of the intestinal γ‐GTP activity. The histochemical staining of γ‐GTP in the mucosa of the small intestine of these animals demonstrated enhanced γ‐GTP activity at the microvilli of the brush border membrane, lamina propria of the mucosa, and endoplasmic reticulum of the intestinal epithelial cell. The augmented activity in the lamina propria was mainly localized at the submucosal lymphatics. Histology of the small intestine of human alcoholics was, more or less, similar to those observed in alcoholic rats.

We further investigated the γ‐GTP activity in the mesenteric lymph using the animal model of lymphorrhea, and found that the γ‐GTP activity was increased by 83% when expressed per unit of lymph in the ethanol‐fed rat, accompanied by a marked decrease of serum γ‐GTP activity, suggesting a close relationship between the serum and the intestinal γ‐GTP via the lymphatic channel. In conclusion, an increased serum γ‐GTP activity, which is frequently observed in alcoholics, may, at least in part, originate from the enhanced activity of the intestinal γ‐GTP.
Interaction between Ethanol and Stress on ACTH and β‐Endorphin Secretion
Authors: Rivier Catherine , Vale Wylie
Published: April 2006

The intraperitoneal infusion of ethanol (EtoH) (1 g/hr/kg body weight for 3 hr) to intact rats blunted the secretion of adrenocorticotropic hormone (ACTH) and β‐endorphin induced by a subsequent 10‐min exposure to mild, inescapable electroshocks (1.5 mA; 2 sec; four shocks/min) or by corticotropin‐releasing factor (CRF). Conversely, administration of the shocks for 3 hr diminished the pituitary response to an acute i.p. injection of EtoH. While we have previously shown (Rivier C, Vale W Endocrinology 121:1320–1328, 1987) that prolonged stress induces a loss of pituitary responsiveness due to the depletion of pituitary ACTH stores, the infusion of EtoH did not cause statistically significant changes in pituitary ACTH content. In adrenalectomized rats, the infusion of EtoH caused an elevation of ACTH plasma levels that was significantly (p≤ 0.01) larger than intact animals. These rats also showed a blunted pituitary response to the acute injection of CRF, possibly because they were already secreting ACTH at a maximal rate. These results support the hypothesis that CRF, stress, and alcohol do not potentiate each other on pituitary ACTH and β‐endorphin secretion.
Effects of Long‐Term Ethanol Inhalation on the Immune and Hematopoietic Systems of the Rat
Authors: Marietta Cheryl A. , Jerrells Thomas R. , Meagher Richard C. , Karanian John W. , Weight Forrest F. , Eckardt Michael J.
Published: April 2006

An inhalation method of ethanol administration was used to study the effects of 14 day, of ethanol administration on the immune and hematopoietic systems of the rat. A decrease in cellularity was found in the spleen, thymus, and bone marrow of ethanol‐treated rats. Although the red blood cell count, white blood cell count, and hemoglobin concentration were not significantly different between treatment and control groups, treatment with ethanol altered the relative proportion of lymphocytes and polymorphonuclear leukocytes in the peripheral blood. The granulocyte‐macrophage progenitor cells in the bone marrow were unaffected by ethanol treatment, but a significant decline in the number of erythroid progenitor cells warn noted in ethanol‐treated rats. Splenic lymphocytes, although fewer in number in the ethanol‐treated rats, showed no significant difference in ability to proliferate when stimulated by nonspecific mitogens
P300 and the Risk for Alcoholism: Family History, Task Difficulty, and Gender
Authors: Polich John , Burns Tim , Bloom Floyd E.
Published: April 2006

P300 event‐related brain potentials (ERPs) were obtained from 20 pairs of male and 20 pairs of female undergraduate subjects. One member of each pair reported having a father who was alcoholic (FHP), the other reported no known alcoholic biological relative (FHN). Pair members were matched on age, height, weight, grade point average, and personal drinking history. Three auditory tasks which differed in stimulus discrimination difficulty were presented to each subject. All tasks employed 20% target and 80% standard tones with the subject required to move their index finger whenever a target stimulus was detected. No significant differences in P300 amplitude or latency were obtained between the family history subject groups, although female FHP subjects tended to have smaller P300 amplitudes than their FHN counterparts. P300 amplitude decreased with increases in the amount of self‐reported alcohol consumed for FHP subjects but significantly so only for the most difficult task situation. The results suggest that the relationship between the P300 ERP and the inheritability of alcoholism is not yet clear and may be subject to modulation by task requirements, population differences, and subject sex.