bluuebunny/crossref_metadata_2025 huggingface dataset:
Behavioral Evaluation of Fetal Alcohol Education for Physicians
Authors: Weiner Lyn , Rosett Henry L. , Edelin Kenneth C.
Published: February 2008

Assessment of clinical behavior has been neglected in evaluating alcohol training for professionals. Inclusion of a systematic drinking history in patient charts provides a sensitive yet simple behavioral marker. At Boston City Hospital, a Ten Question Drinking History (TQOH) was incorporated into a prenatal intake procedure and used to monitor staff behavior. Utilization of the TODH, measured for six time periods, ranged from 92% to 33%. Obstetrical staff was more likely to complete the TQDH when the alcoholism research staff was visible in the clinic and readily available for concultation and referral.
The Effect of Alcohol Ingestion on the Susceptibility of Mice to Viral Infections
Authors: Cotte J. , Forestier F. , Quero A. M. , Bourrinet P. , German A.
Published: February 2008

The influence of acute alcoholization on the evolution of different viral diseases was studied in orally alcoholized mice. Ethanol increased mice susceptibility to encephalomyocarditis and influenza only when it was administered after virus infection. There was no dose‐effect correlation. Vaccinia and Herpes virus infections were not modified by alcoholization. Hypotheses concerning the mechanisms of alcohol action were put forward.
Bleeding and Coagulation Abnormalities in Alcoholic Cirrhotic Liver Disease
Authors: Ragni Margaret V. , Lewis Jessica H. , Spero Joel A. , Hasiba Ute
Published: February 2008

Coagulation profiles were performed in 30 consecutive alcoholic cirrhotic patients without known infection, malignancy, recent surgery, transfusion, or alcoholic intake. Hemorrhagic phenomena were present in 70% and included gastrointestinal bleeding, oozing from venipuncture sites, bruising, and epistaxis. All 30 patients had multiple liver function and coagulation abnormalities, the most frequent of which were increases in F VIII components and decreases in F XI and F VII. Also decreased in half or more of the 30 patients were Fletcher F, F II, F X, prothrombin time (PT), partial thromboplastin time (APTT), thrombin time (TT), repti‐lase time (RT), anti‐thrombin III, and plasminogen. When comparing cirrhotic bleeders with nonbleeders, four parameters were significantly different in those with a bleeding tendency: F VII, anti‐thrombin III, plasminogen, and albumin. The prolonged APTT was associated in four cases with a blocking inhibitor of unknown etiology. The prolonged TT and RT, in the absence of fibrin split products, fibrin monomers, DIC, or shortened euglobulin lysis time in any patient were suggestive of an abnormal fibrinogen, a dysfibrinogen. In three other patients, there was an inhibitor of the TT. Further investigation of the suspected dysfibrinogen in 21 patients by SDS‐polyacrylamide gel electrophoresis revealed that the molecular weights of the Aα, Bβ, and γ polypeptide chains of fibrinogen were not different from normal. Two‐dimensional Immunoelectrophoresis of the suspected dysfibrinogen was similar to normal in 18 of 21 patients, with loss of the initial shoulder in three.
Mechanism for Selective Perivenular Hepatotoxicity of Ethanol
Authors: Jauhonen Pekka , Baraona Enrique , Miyakawa Happei , Lieber Charles S.
Published: February 2008

Chronic alcohol administration to baboons results in perivenular lesions in the liver. To study possible mechanisms, the effect of ethanol on splanchnic oxygen consumption was measured. Acute ethanol administration increased splanchnic oxygen consumption in the control baboons, but the consequences of this effect on oxygenation of the perivenular zones were offset by a concomitant rise in blood flow, resulting in unchanged hepatic venous oxygen tensions. In alcohol‐fed baboons, splanchnic oxygen consumption was not increased, either in the withdrawal state or after ethanol infusion. To study the magnitude of the shift in redox state induced by ethanol in the perivenular zones, we compared the effects of ethanol on the lactate/pyruvate ratio in hepatic venous blood (an approximation of that in perivenular hepatocytes) with the ratio in total liver. Prior to ethanol infusion, the lactate and pyruvate were the same in liver and in hepatic venous blood. By contrast, in all baboons, ethanol produced a much greater rise in the lactate/pyruvate ratio and decreased pyruvate more in hepatic venous blood than in total liver. Moreover, in isolated rat hepatocytes, the ethanoMnduced redox shift was markedly exaggerated by oxygen tensions similar to those found in centrolobular zones. This suggests that the normally low oxygen tensions existing in perivenular zones exaggerate the ethanol‐Induced redox shift, a change which may contribute to the exacerbation of the damage in the perivenular area of the hepatic lobule.
The Effect of Alcoholism in Methadone‐Maintained Persons on Productive Activity: A Randomized Control Trial
Authors: Cohen Murry , Korts David , Hanbury Raymond , Sturiano Victor , Jackson George , Stimmel Barry
Published: February 2008

The effect of alcoholism on indices of productive activity was determined in a prospective, randomized, and controlled study of alcoholism in narcotic addicts undergoing methadone maintenance (MM) therapy. Indices of productive activity included: percentage of persons engaged in productive activities; number of days worked per quarter; number of arrests per quarter; number of hospitalizations; and days of hospitalizations per quarter. Baseline as well as longitudinal data were obtained on operative alcoholics (OA), inactive alcoholics (IA), and nonalcoholics (NA). OA patients were subsequently randomized to a control group or groups receiving either abstinence‐oriented insight group therapy or controlled drinking‐oriented behavioral modification group therapy. The retention rate in MM of OA versus NA during the 29‐month clinical phase of the study did not differ significantly. Similarly, no significance was reported with respect to any index of productive activity. Indices of productive activity in OA undergoing treatment as compared to those randomized to the control group also did not reveal any significant differences. The compliance of OA in seeking and maintaining therapy for their alcoholism, however, was sufficiently poor so that any conclusions concerning the effectiveness of therapy on indices of productive activity should be viewed cautiously.
The Ability of a Self‐Administered Alcohol Screening Test (mSAAST) to Detect Future Excessive Alcohol Consumption in Persons on Methadone Maintenance
Authors: Stimmel Barry , Sturiano Victor , Cohen Murry , Korts David , Hanbury Raymond , Jackson George
Published: February 2008

A modified Self‐Administered Alcoholism Screening Test (mSAAST) was prospectively administered to 625 narcotic addicts participating in a randomized clinical control trial to study its effectiveness in detecting future excessive alcohol consumption. At entry into the study, of 105 patients categorized as active alcoholics, 84 (80%) obtained a positive score on the mSAAST. of 77 patients initially identified as being at risk for developing alcoholism (potential alcoholics) by mSAAST scores, 31 (40%) subsequently developed characteristics of excessive alcohol consumption. Of the 321 patients classified as nonalcoholic by history as well as mSAAST score, a significantly lesser proportion (15%) developed characteristics of excessive alcohol consumption (p<0.001). These findings suggest the mSAAST to be a useful adjunctive indicator of persons at risk of developing excessive consumption of alcohol. It is probable that the usefulness of the mSAAST extends beyond narcotic‐dependent populations and may be of value in identifying the potential for excessive alcohol consumption in other populations.
Thiocyanate and Drinking during Pregnancy
Authors: Bottoms Sidney F. , Judge Nancy E. , Kuhnert Paul M. , Sokol Robert J.
Published: February 2008

Alcohol appears to have a relatively direct effect in decreasing fetal growth; however, it also appears that other factors associated with alcohol consumption may also contribute to lowered birthweight. Three studies have suggested that beverage source of alcohol may be a determinant of decreased intrauterine growth and that beer may have a comparatively greater effect than wine and liquor. Since beer is reported to contain thiocyanate (SCN), a substance which has been implicated as a determinant of fetal growth retardation in relation to cigarette smoking, we studied maternal and fetal serum SCN levels in 82 pregnancies. After controlling for maternal characteristics, gestational age, and tobacco and marijuana use, the quantity of beer consumed was found to have a significant positive correlation with fetal serum SCN (p < 0.005). Consumption of other types of alcoholic beverages was not significantly associated with elevated fetal serum SCN, although the numbers of wine and liquor drinkers in this study were limited. Further research is warranted to explore the possibility that the correlation of beer consumption with increased SCN might provide at least one explanation for the reported linkage of diminished fetal growth and beer drinking.
Maternal Drinking Behavior and Decreased Intrauterine Growth
Authors: Kuzma Jan W. , Sokol Robert J.
Published: February 2008

Reduced intrauterine growth has been a widely observed effect of maternal alcohol use during pregnancy in both animals and humans, although results in studies of humans have been inconsistent. The goal of this prospective study was to evaluate the relative importance of volume, frequency, and beverage source of alcohol as determinants of infant birthweight, while adjusting for other known determinants using multivariate techniques. In a sample of 5,093 maternal‐infant pairs, 44 potential determinants of intrauterine growth were evaluated. The frequency of beer drinking, controlled for wine drinking, liquor drinking, and other variables, was found to contribute independently to a reduction of intrauterine growth, as measured by birth‐weight adjusted for gestational age. Of the variables explored, 11, including cigarette smoking and caffeine intake, were found to contribute significantly (R2= 32%; p < 0.001) to the variance. The effect of beer drinking was most apparent in the most frequently drinking 3% of gravidas. These results appear to confirm a previous suggestion that heavy beer drinking during pregnancy is related to decreased intrauterine growth, but should be interpreted cautiously since there are several alternative explanations for the finding. Thus, these results suggest several areas for further investigation.
Interaction of Apomorphine and Amantadine with Ethanol in Men
Authors: PharmD Ronald L. Alkana , Parker Elizabeth S. , Malcolm Richard D. , Cohen Harry B. , Birch Herman , Noble Ernest P.
Published: February 2008

Male moderate drinkers (n = 12) drank ethanol (0.8 g/ kg) and then ingested one of the following: apomorphine (5 mg), amantadine (200 mg), or placebo. Subjects were tested on a battery of physiological and behavioral measures using a double‐blind, within‐subjects, crossover design. Postethanol ingestion of apomorphine significantly increased ethanol's effect on 3 out of the 8 measures employed (divided attention, objective and subjective inebriation ratings) without significantly altering blood ethanol concentrations or the rate of blood ethanol decline. There was no indication that apomorphine antagonized ethanol's effects. In contrast to reports indicating that amantadine antagonized ethanol depression in rodents, amantadine did not significantly alter the degree of ethanol intoxication in humans. The increase in intoxication induced by apomorphine supports suggestions that dopaminergic systems may be involved in mediating ethanol intoxication and that the sobering effect of catecholamine‐augmenting drugs results from noradrenergic, rather than combined noradrenergic and dopaminergic, stimulation. Further studies are necessary to elucidate the role of pre‐ and postsynaptic dopaminergic receptors in mediating these effects.
Acute Effects of Ethanol on Biosynthesis and Glycosylation of IgGl(k) Antibody Molecules in Cultured P3/X63‐Ag8 Myeloma Cells
Authors: Eaton Leslie C. , Ingram Lonnie O.
Published: February 2008

Protein synthesis in cultured P3/X63‐Ag8 mouse myeloma cells was inhibited by acute exposure to ethanol. However, the synthesis of IgGl antibody, as a percentage of total protein synthesis, increased slightly. Experiments using actinomycin 0 suggest that the overall inhibition of protein synthesis by ethanol occurs at the translational level. Following an L‐[35S]methiomne pulse, cultured P3/X63‐Ag8 cells contained one light antibody polypeptide and two heavy antibody polypeptides. One of these heavy chains was shown to be the unglycosylated precursor of the other, mature molecule. Only the glycosylated polypeptide is a normal constituent of secreted IgGl antibody. The glycosylation of the immature heavy chains occurred more rapidly during a 1‐hr isotopic pulse in cells exposed to ethanol (0.1 v/v % and above), than in unexposed control cells. The observed effects of ethanol on antibody glycosylation may be related to the increased susceptibility of alcoholic patients to infections. Ethanol may also affect the synthesis of other glycoproteins in myeloma cells and other tissues.
Circadian Patterns of Plasma Cortisol and Testosterone in Chronic Male Alcoholics
Authors: Bertello Pierdomenico , Agrimonti Fulvio , Gurioli Lorenzo , Frairia Roberto , Fornaro Daniela , Angeli Alberto
Published: February 2008

Twelve alcoholic men (28–55 yr) presenting hypogonadal features but without overt liver failure were hospitalized and examined still consuming alcohol regularly. Sleep was approximately from 2200 to 0600; three equicaloric meals were served at 0700, 1200, and 1800. Blood samples were drawn at 4‐hr intervals throughout a 24‐hr span starting from 0800. Measured levels of Cortisol and testosterone were then analyzed by rhythmometric procedures in order to estimate parameters of the circadian oscillation such as mesor, amplitude, and acrophase, and the relevant confidence limits. Data were compared to those obtained in a matched group of 20 healthy controls. With regard to Cortisol, the rhythmometric analyses allowed the demonstration of a normally synchronized circadian rhythm substantially superimposable in alcoholics and controls. With regard to testosterone, the results were compatible with a significant circadian oscillation only in the control group. Alcoholics did show ample inter‐individual variability of plasma testosterone levels, but the apparent lack of the circadian rhythm was independent of the steroid concentration. These data extend previous observations and are consistent with the occurrence of important abnormalities in the circadian pattern of plasma testosterone in chronic male alcoholics prior to liver failure.
Relationship of Alcoholic Hyperlipidemia to the Feed‐Back Regulation of Hepatic Cholesterol Synthesis by Chylomicron Remnants
Authors: Lakshmanan M. R. , Ezekiel Mildred
Published: February 2008

Pairfeeding of ethanol liquid diet for 6 weeks to male Wistar rats resulted in defective extrahepatic as well as hepatic catabolism of rat lymph chylomicrons. Based upon the exponential decay curves of the chylomicrons in the blood compartment it was concluded that chronic ethanol feeding caused 30 and 67% decreases in the rate of degradation of the triacylglycerol and cholesterol moieties, respectively. As a consequence, abnormal chylomicron remnants accumulated in chronic ethanol‐fed but not in control animals. These abnormal remnants were not as efficient as the normal remnants in causing the feedback inhibition of cholesterol synthesis in hepatocytes from normal meal‐fed rats. Furthermore, the hepatocytes from chronic ethanol‐fed animals exhibited defective feedback regulation of cholesterol synthesis by normal chylomicron remnants. The net result of all these abnormalities caused by chronic ethanol feeding would be the delayed clearance of triacylglycerol‐rich lipoproteins from the blood compartment and enhanced synthesis and secretion of the triacylglycerol‐rich lipoproteins by the liver.
Four Year MMPI Changes in Abstinent and Drinking Alcoholics
Authors: Pettinati Helen M. , Sugerman A. Arthur , Maurer Helen S.
Published: February 2008

Alcoholic patients completed the Minnesota Multiphasic Personality Inventory (MMPI) while hospitalized for treatment and again after 4 years of follow‐up. Those who remained abstinent and functioned well in the community for the 4‐yr period were characterized during treatment by a significant elevation on the Depression (D) scale which decreased to normal ranges at follow‐up. Those who continued to drink periodically over the 4‐yr period had initial peaks on Psychopathy (Pd) and Hypomania (Ma) which were still elevated at follow‐up. An intermediate group who were usually abstinent during the 4‐yr period but had occasional relapses showed elevations on D and Pd during treatment with return to normal levels at follow‐up.
Behavioral Effects of Ethanol in Animals: Age Differences and Age Changes
Authors: Wood W. Gibson , Armbrecht H. James
Published: February 2008

Ethanol‐induced behavior is related to the age of the organism. This relationship has been shown for several different kinds of measures, e.g., voluntary consumption of ethanol, effects of acute and chronic administration of ethanol. The usefulness of studies concerned with voluntary ethanol consumption and aging is questioned. Usually, causal mechanisms are not determined and blood ethanol levels are not measured in these animal studies.

Both acute and chronic studies have shown that old animals are more sensitive to the effects of ethanol as compared to young animals. This effect has been reported in studies employing a number of different methods of administering ethanol, e.g., injection, inhalation, liquid diet. Age‐related effects in response to short‐term administration of ethanol have been observed for measures such as loss of the righting reflex, general motor activity, hypothermia, and withdrawal signs. Long‐term administration of ethanol has been found to affect brain chemistry, performance, and life span. Explanations for the effects of ethanol among different age groups include differences in the rate of metabolism of ethanol, the percentage of body water and lean body mass, and changes in central nervous system sensitivity.

The study of the relationship between the effects of ethanol and aging is relatively new. The most obvious conclusion that can be made from a review of the literature is that much more work needs to be done. Greater attention needs to be given to the theoretical and methodological issues associated with aging research.
Cognitive Patterns Resembling Premature Aging in Male Social Drinkers
Authors: Parker Elizabeth S. , Parker Douglas A. , Brody Jacob A. , Schoenberg Ronald
Published: February 2008

In two samples of employed men (ns of 102 and 496), the amount of alcohol typically consumed per drinking occasion was significantly associated with decreased sober abstraction performance. Age was also significantly related to reduced abstraction scores. An increase of one drink in the quantity of alcohol typically consumed was associated with an average reduction in abstraction performance equivalent to 3.7 more yr of age in one sample and 2.4 more yr of age in the other sample.
Adult Rat Hepatocytes in Primary Culture. VII. Proliferative and Functional Properties of Cells from Ethanol‐Intoxicated Animals: Evidence for a Reversible Albumin ‘Production Defect’
Authors: Lad Pushkaraj J. , Shier W. Thomas , Skelly Harold , de Hemptinne Bernard , Leffert Hyam L.
Published: February 2008

Properties of long‐term cultures of hepatocytes isolated from nutritionally maintained adult rats treated in vivo for 8–12 days with ethanol to achieve blood levels of 200–220 mg ethanol/dl (experimental group) and from isocalorically maintained mock‐treated (control) rats were compared. Two kinds of treatment protocols were used: intragastric intubation or inhalation chambers. Similar results were observed with cultured cells obtained from either protocol.

Hepatocytes in ‘monolayers’ from both animal groups showed unimpaired proliferative responses with respect to (a) cell multiplication and DNA synthesis rates during an asynchronous 12‐day growth cycle and (b) proliferogenic peptides [insulin, glucagon, and epidermal growth factor (EGF)] that reinitiate DNA synthesis parasynchronously during late stationary phase (days 12–13). Quantitative differences in [3H]leucine uptake into total proteins (cellular plus ‘secreted’) were not detected during the growth cycle. However, during stationary phase (days 8–12), 25%‐75% less [3H]leucine‐labeled albumin was released into culture fluids by hepatocytes from experimental livers than by hepatocytes from control livers. More pronounced differences were seen when albumin in the same culture fluids was measured by radioimmunoassay in contrast to measurements of [3H]leucine‐labeled albumin in these fluids. The defect was reversible since it was not seen in stationary‐phase hepatocyte cultures prepared from rats withdrawn more than 7 days from ethanol treatment whose blood alcohol levels had fallen to 0 mg ethanol/dl.

These findings are consistent with the hypothesis that, with respect to albumin production by hepatocytes, chronic ethanol exposure induces a specific but reversible ‘defect’. Because this defect is not seen in short‐term hepatocyte cultures, long‐term cultures should facilitate attempts to understand the molecular and cellular causes of this functional impairment.
Ethanol‐Induced Stimulation of Hepatic Ornithine Decarboxylase Activity in the Rat
Authors: Murty Challakonda N. , Hornseth Ruth , Verney Ethel , Sidransky Herschel
Published: February 2008

The effect of a single feeding of ethanol on hepatic ornithine decarboxylase (ODC) activity in rats was investigated. Ethanol (7.5 g/kg body weight) was tube‐fed to overnight‐fasted rats as a 50% (v/v) solution in water 1, 2, 3, 4, 8, 12, or 24 hr before sacrifice. The levels of ODC activity in the livers were assayed in vitro by measuring the release of 14C02 from 0L‐1‐14C‐ornithine. Hepatic ODC activities were significantly stimulated by ethanol (7.5 g/kg body weight) beginning at 1 hr and reaching a peak at 4 hr (more than a 16‐fold increase over zero time controls). Single feedings of varying doses of ethanol (2.5, 5.0, or 7.5 g/kg body weight) to overnight‐fasted rats 3 hr before sacrifice also exhibited significant increases (3 to 13‐fold) in the hepatic ODC activities. In vitro 14C‐leucir>e incorporation into protein using hepatic microsomes of ethanol‐treated rats was decreased in comparison with that of controls. The ethanoMnduced stimulation of hepatic ODC activity was not abolished by pretreatment with pyrazoie, an inhibitor of ethanol metabolism. However, the stimulation of hepatic ODC activity by ethanol was suppressed by actinomycin D or cycloheximide, indicating that the enhancement is attributable to the synthesis of new enzyme protein. Furthermore, abolition of the stimulation of hepatic ODC activity due to ethanol by prior adrenalectomy suggests that the induced increase is probably mediated through stimulation of adrenal hormones. These studies demonstrate that a single dose of ethanol per os can significantly enhance in the rat the activity of hepatic ODC, a key enzyyme in the biosynthesis of polyamines, and that the effect is indirect, via adrenal hormones.
Evidence of a Toxic Effect of Ethanol on Bone in Rats
Authors: Peng Tai‐Chan , Gamer Sanford C. , Frye Gerald D. , Crenshaw Miles A.
Published: February 2008

Tibiae from rats treated chronically for 12 days with enough ethanol to induce physical dependence were found to have an increased incidence of fracture during dissection and cleaning (7 of 12 or 58%) compared to control animals (1 of 12 or 8%). The site of the fractures, the proximal end of the tibia, showed an increased opacity to X‐rays, and the dried bones were distinctly darker in appearance than similarly prepared control bones. The effects noted in our study suggest that the rat model could be useful for the study of the mechanisms by which alcohol affects bone growth, remodeling, and strength. These studies might shed new light on the pathogenesis of increased bone fragility in alcoholics.
Evaluation of the Role of Acetaldehyde in the Actions of Ethanol on Gluconeogenesis by Comparison with the Effects of Crotonol and Crotonaldehyde
Authors: Cederbaum Arthur I. , Dicker Elisa
Published: February 2008

Liver cells from fasted rats oxidized ethanol and crotonol at identical rates. Ethanol and crotonol increased the cytosolic lactate/pyruvate ratio to the same extent, however only ethanol increased the mitochondrial B‐hydroxybutyrate/acetoacetate ratio. The rate of oxidation of crotonaldehyde by liver cells was 30% to 50% of the rate of oxidation of acetaldehyde. Cyanam‐ide, which is especially inhibitory towards the low Km mitochondrial aldehyde dehydrogenase, inhibited the oxidation of acetaldehyde to a greater extent than it inhibited the oxidation of crotonaldehyde. Acetaldehyde, but not crotonaldehyde, increased the B‐hydrox‐ybutyrate/acetoacetate ratio; both aldehydes produced some increase in the lactate/pyruvate ratio. Consequently, differences between the effects of ethanol and crotonol on the mitochondrial redox state may relate to differences between the metabolism of their respective aldehydes.

Intact mitochondria oxidized crotonaldehyde at about 10% the rate found with acetaldehyde. In deox‐ychoiate‐disrupted mitochondria, in the presence of external NAD+, crotonaldehyde was oxidized at rates less than one‐fourth the rate found with acetaldehyde. Cyanamide inhibited the oxidation of acetaldehyde to a greater extent than the oxidation of crotonaldehyde. These results suggest that crotonaldehyde is a poor substrate for the low Km mitochondrial aldehyde dehydrogenase.

In isolated hepatocytes, acetaldehyde stimulated glucose production from pyruvate, but inhibited gluconeogenesis from glycerol, xylitol, and sorbitol. Crotonaldehyde had no effect on glucose production from these substrates, indicating that the effects of acetaldehyde were due to the metabolism of acetaldehyde in the mitochondria. Ethanol stimulated glucose production from pyruvate, whereas crotonol was without effect. The stimulation by ethanol, and the lack of effect by crotonol, appears to be due to changes in the mitochondrial redox state produced as a consequence of the further oxidation of acetaldehyde, but not crotonaldehyde. Crotonol and ethanol inhibited glucose production from glycerol, xylitol, and sorbitol, suggesting that changes in the cytosolic redox state play the major role in the effect of the alcohols on glucose production from these substrates. However, the inhibition by ethanol was consistently 10% to 15% greater than the inhibition by crotonol, suggesting that acetaldehyde contributes to the effects of ethanol. These differences between ethanol and crotonol are consistent with a role for acetaldehyde metabolism in the actions of ethanol. Crotonol may be a useful aid in determining the mechanism whereby ethanol alters henatic functions.
Alcohol Causes a Fatty Pancreas. A Rat Model of Ethanol‐Induced Pancreatic Steatosis
Authors: Wilson J. S. , Colley P. W. , Sosula L. , Pirola R. C. , Chapman B. A. , Somer J. B.
Published: February 2008

To develop an animal model of alcoholic pancreatic steatosis, female Wistar rats were pair fed liquid diets, containing ethanol as 36% of calories or an isocaloric amount of carbohydrate for 3 weeks. Electron microscopic examination showed lipid vesicles localized principally at the bases of pancreatic acinar cells in the ethanol‐fed rats. Ethanol feeding significantly increased pancreatic content of cholesteryl ester without changing levels of other lipids. Ethanol feeding enhanced labeled acetate, palmitate, oleate, and lino‐leate incorporation into cholesteryl ester. Therefore, increased esterification of cholesterol may, in part, explain the observed accumulation of cholesteryl ester.
The Human Blood Platelet as a Model for Studying Interactions of Ethanol with Membrane Lipids
Authors: Fenn Christopher G. , Littleton John M.
Published: February 2008

The effect of ethanol on human blood platelet aggregation is generally inhibitory, but aggregation caused by arachidonic acid is either unaffected or potentiated by ethanol. Of the other aggrega‐tory agents tested, the calcium ionophore A23187, collagen, and thrombin were most inhibited by ethanol. These results suggest that in the case of collagen and ionophore A23187 ethanol may act to inhibit aggregation at some point between the rise in cytosolic calcium and the cleavage of membrane phospholipids associated with the platelet release reaction. A similar spectrum of inhibition was produced by the incorporation of unsaturated fats into the platelet or by reduction of divalent cations by addition of EDTA to the external medium. Platelets in which unsaturated fats were incorporated were less susceptible to inhibition by ethanol than those into which saturated fats had been incorporated.
Alcohol and the Opiate Receptor
Authors: Levine Allen S. , Hess Sheryl , Morley John E.
Published: February 2008

A number of in vivo studies have suggested that alcohol and the opiates may be integrally related in the brain. In this study we report that 0.1, 0.2, and 0.4% ethanol significantly increases the density of binding sites for [3H]naloxone in isolated brain membranes.
Aromatization of Androstenedione by Microsomes from the Human Placenta after Gestational Alcohol Consumption
Authors: Sheean Leon A.
Published: February 2008

Human placental microsomes were used to evaluate rates of andre stenedione aromatiration from patients selected for gestational alcohol consumption. After term delivery, kinetic comparisons of specific activity and Michaelis constants of reduced pyridine nucleotide cotactors were determined. The data failed to indicate a significant alcohol effect on these enzymatic parameters.
Nonlinear Pharmacokinetics of Ethanol Elimination in Long Sleep and Short Sleep Mice
Authors: Gilliam David M. , Bloedow Duane C. , Collins Allan C.
Published: February 2008

Pharmacokinetic studies of ethanol elimination in humans and dogs have suggested that elimination from the blood can be best described through the application of MichaelikMenten enzyme kinetics. In an attempt to extend the application of the Michaelis‐Menten model to ethanol elimination in mice, we measured elimination rates using serial blood samples obtained from the long sleep (Ls) and short sleep (SS) selected mouse lines following a bolus, intravenous ethanol infusion. A comparison was made between elimination rates as predicted by Widmark's linear model and by the nonlinear Michaelis‐Menten model. Volume of distribution was also determined for each mouse line.

Ethanol elimination in these mice conformed to the nonlinear model. Significantly greater Vmax and Km values were obtained for the SS mice than for the LS; however, no significant difference in linear elimination rates was found between lines. The LS mice exhibited a significantly greater volume of distribution than did the SS. The Michaelis‐Menten model predicts that SS ethanol metabolism should be greater than LS metabolism at blood ethanol concentrations greater than 120 mg%. The results support the suggestion that ethanol elimination can be best described by Michaelis‐Menten kinetics. Line differences in ethanol elimination may have resulted from changes in the doses used to select these mice and/or the induction of specific ethanol metabolizing systems.
ALCOHOL AND ENDOCRINE SYSTEMS INTERACTION—PART II Biochemical Mechanisms That Contribute to Alcohol‐Induced Hypogonadism in the Male
Authors: Chiao Yu‐Bin , Thiel David H. Van
Published: February 2008

An overview of the biochemical mechanisms known to contribute to alcoholinduced Leydig cell failure is presented, along with results of studies performed both in vitro and in vivo. The data obtained in animals and in various in vitro model systems is discussed in terms of its application to the clinical situation.
Determinants of Blood Acetaldehyde Level during Ethanol Oxidation in Chronic Alcoholics
Authors: Nuutinen Hannu , Lindros Kai O. , Salaspuro Mikko
Published: February 2008

We analyzed the blood alcohol and acetaldehyde concentrations in nine alcoholics and four healthy nonalcoholic controls during and after an intravenous infusion of a high and a low dose of alcohol. In the alcoholics, the mean rates of plasma ethanol disappearance were significantly higher than in nonalcoholic controls. In the control subjects, the blood acetaldehyde levels were, in general, below the detection limit (<0.5 #μm), but in sharp contrast to this, an elevated blood acetaldehyde during ethanol infusion was found in 6/9 alcoholics. Peak blood acetaldehyde values were higher after the high than the low dose of alcohol. Fructose infusion significantly enhanced the rate of plasma ethanol disappearance both in controls and in alcoholics, and this was usually associated with a significant elevation of blood acetaldehyde level. The maximal specific activities (expressed as milliunits/mg of protein) of alcohol, lactate, and aldehyde dehydrogenases in liver were significantly lower in alcoholics than in controls. Even more importantly, the peak blood acetaldehyde correlated negatively with the activity of hepatic “low‐Km” aldehyde dehydrogenase. Our results suggest that the main reason for blood acetaldehyde elevation seen in these chronic alcoholics is their impaired capacity to metabolize acetaldehyde. This may be further accentuated by the increased rate of ethanol oxidation.
Effect of Ethanol on Alkaline Phosphatase Activity in HeLa Cells
Authors: Goz Barry , BS A. Chester Stowe. , Townsend Alan J.
Published: February 2008

Incubation of HeLa cells with 10–80 mM ethanol, caused a dosedependent decrease in alkaline phosphatase specific activity. With 80 mM ethand, the decrease became apparent after 24–48 hr Incubation. The same dosedependent effect was observed with the nonmetabolizable alcohol t‐butanol. The effect of ethanol was not due to toxicity as the cells continued to replicate for weeks In the presence of ethanol and was reversible. There were no differences in the Km values of alkaline phosphatase in crude extracts or rolubilized enzyme prepared either from control or 80 mM ethanoltreated cells. Hydrocortisone and choline chlorlde, which by themselves Increase alkaline phosphatase specific activity, altered the effect of ethanol on alkaline phosphatase. In the presence of either 1 μm hydrocortisone or 40 mM choline chlorlde, neither 10 nor 20 mM ethanol decreased alkaline phosphatase specific activity.
Factors Affecting Outcome of Depressive Symptoms in Alcoholics
Authors: Nakamura Michiko M. , Overall John E. , Hollister Leo E. , Radcliffe Edgard
Published: February 2008

Eighty‐eight patients consecutively admitted to an alcohol treatment program were studied to determine the amount of depressive symptoms on entry to the program and after 4 weeks ot treatment. The degree of symptoms was in turn related to various aspects of their drinking behavior. Twenty‐two of the patients were classified as having moderate to marked depressive symptoms, 40 had mild symptoms, and 26 had no significant symptoms at the time of entry into the program. Factors in drinking behavior that best characterized those wlth moderate to marked symptoms were addiction, sleep disturbance, hangover incapacitation, loss of control, neurological signs, and organicity/toxicity. At the end of treatment, only four patlents could actually be diagnosed as depressed, while 12 had mild residual symptoms and 72 no longer had significant symp toms. The one factor that clearly distinguished those patlents with residual depressive symptoms was the use of drinking for social facilitation. For such individuals, bars and drinking were the focus of social life.

The favorable course of depressive symptoms in alcoholics soon after they stop drinking suggests that they are more likely the consequence of drlnking than the cause of it. The fact that patients who drink primarily to facilitate social aspects of their lives were the most likely to have residual symptoms suggests that treatment of such indlvlduals should involve development of alternative mechanisms of social interaction.
Ethanol Ingestion and Polyunsaturated Fatty Acids: Effects on the Acyl‐CoA Desaturases
Authors: Wang Danny L. , Reitz Ronald C.
Published: February 2008

The ingestion of ethanol results in altered compositions of the polyenoic fatty acids in a varlety of liver and brain membranes. A possible cause for these alterations in hepatic endoplasmic reticu‐lum membranes has been studied by measuring the Δ9, Δ6, and Δ5acyl‐CoA desaturase activities in hepatic microsomes from chronically or acutely treated rats. Chronically, ethanol decreased all three enzyme activities with the following order of sensitlvlty: Δ8(65%), Δ9(54%), and Δ5(46%). The short‐term study indicated that all three desaturase activities were affected after 1 day of ethanol feeding. NADPH‐ and NADHsytochrome c reductase activitles were found to be reduced in chronically treated rats, and the NADH‐cytochrome c reductase was decreased in the acutely treated. However, these reduced enzyme activities could not account for the decrease in desaturase activities due to the very marked differences between the specific activities of these enzymes compared to the desaturase. Thus, we conclude that changes in membrane polyenoic fatty acid composition can be the result of ethanol‐induced decreases in the terminal desaturase enzymes.
Alcohol Use and Iron Status in Pregnant Women
Authors: Streissguth Ann Pytkowicz , Barr Helen M. , Labbe Robert F. , Smith James R. , Darby Betty L. , Smith Nathan J. , Martin Donald C. , Doan Roscius N.
Published: February 2008

Iron status, assessed by ferritin (ng/ml), transferrin saturation (YO), and hemoglobin (g/100 ml), was examined in a sample of 1398 women from blood samples drawn at their first prenatal visit and in 712 of these women later at their 32‐week prenatal visit. Self‐reported alcohol use (average ounces of absolute alcohol consumed per day around the time of conception) was not systematically related to iron status. Furthermore, the proportion of iron‐depleted or anemic women did not vary according to different levels of alcohol use. An exception is noted in a small group of nine very heavy drinkers, reporting eight or more drinks per day, who, at 32 weeks gestation, had a higher proportion of iron depletion but not anemia.

It was concluded that at least in a sample of primarily middle class women receiving good prenatal care, iron depletion and/or anemia probably do not explain the alcohol‐related adverse pregnancy outcomes that have been reported previously. Nevertheless, results from several very heavy drinkers suggest that the iron status of pregnant alcoholic women should be investigated further.
New Inhibitors of Alcohol Dehydrogenase: Studies in Vivo and in Vitro in the Rat
Authors: Delmas Catherine , Blanquat Georges de Saint , Freudenreich Charles , Bielimann Jean‐FranCois
Published: February 2008

Two compounds bearing an amide group, pbutoxyphenyl acetamide (BPA) and N‐(p‐butoxybenzyl)formamide (BBF) were studied as inhibitors of alcohol dehydrogenase (ADH) and their action compared with that of 4‐methyl‐pyrazole (4‐MP), a known Inhibitor of this enzyme. In vitro studies on pure horse liver ADH showed that BPA and BBF were noncompetitive inhibitors with respect to ethanol and that their K, vaiues were 22 and 0.14 pm, respectively. The apparent K, values of BPA and BBF for rat liver ADH were found to be 90 and 2.3. pm, respectively (noncompetitive inhibition). Several in vivo experiments were carried out in the rat. Administration intraperitoneaily of the substances (480 μmol/kg) 1 hr before intra‐peritoneal injection of alcohol (2 g/kg body weight) led to a significant decrease in ethanol catabollsm. Injection of the substances at 460 pmol/kg brought about a decrease in rat liver ADH activity, but the activity of mitochondrial aldehyde dehydrogenase was only decreased in animals treated with BBF.
Tyrosine Hydroxylase Activity in the Brain and Adrenal Gland of Rats Following Chronic Administration of Ethanol
Authors: Masserano Joseph M. , Takimoto Glenn S. , Weiner Norman
Published: February 2008

The effects of chronic ethanol administration and ethanol withdrawal on the activity of tyrosine hydroxylase were examined in the adrenal gland and six brain regions, Including the frontal cortex, hippocampus, locus coeruleus, striatum, substantia nigra, and hy‐pothalamus. Ethanol was administered to rats by oral intubation every 8 hr for 48 hr in amounts based upon their state of intoxication. One hr after the last intubation, tyrosine hydroxylase activity was not aigniflcantly dlfferent from control values In either the adrenal gland or brain. Forty hr following the last ethanol intubation, tyrosine hydroxylase activity was significantly increased above control values in both the adrenal gland and locus coeruleus. Tyrosine hydroxylase activity in the remalning five brain areas was unaffected by ethanol treatment. lmmunotitratlon studies Indicate that the increases in tyrosine hydroxylase activity found in the adrenal gland and locus coeruleus 40 hr after ethanol administration were due to an increase in enzyme protein. These data indlcate that hlgh blood ethanol concentratlons maintained over a short period of time (48 hr) do not affect adrenal gland or brain tyrosine hydroxylase activity. However, withdrawal from ethanol following 48 hr of treatment does produce an increase in tyroslne hydroxylase activity in the adrenal gland and locus coeruleus, similar to that seen following other stresses.
Impaired Ethanol Metabolism with Advancing Age
Authors: Hahn Henry K. J. , Burch Robert E.
Published: February 2008

Ethanol metabolism as a function of age was assessed in male Sprague‐Dawley rats. The ethanol metabolic rates decreased linearly with advancing age. It was also observed that a linear decrease in hepatic alcohol dehydrogenase activity occurred as a function of age. The decreased enzyme activity could be the biochemical mechanism underlying changes in ethanol metabolism. Impaired ethanol metabolism may produce increased pharmacologic effects in older subjects due to increased blood ethanol levels.
Alcohol Use, Negative Mood States, and Menstrual Cycle Phases
Authors: Sutker Patricia B. , Libet Julian M. , Allain Albert N. , Randall Carrie L.
Published: February 2008

This study investigated the hypothesis that alcohol consumption patterns among normally menstrually cycling women would be influenced by increased negative mood states and phase of the menstrual cycle. A timeseries, within‐groups design was used to allow for comparisons among normally cycling women, women maintained on oral contraceptives, and men. Thirty‐two adults recorded daily estimates of ongoing behaviors in the areas mentioned for two menstrual cycles or equivalent periods. Radioimmunoassay and temperature data were used to confirm ovulation and to define ovulatory, premenstrual, and menstrual phases. Estimates of anxiety, depression, and hostility were highly intercorrelated, but negative moods were not significantly related to frequency/amount of alcohol consumption. However, normally cycling women reported significantly more negative moods, more frequent drinking to relieve tension/depression, and more frequent solitary drinking at menstruation. These relationships were not observed among oral contraceptive women or men. Collected among psychologically robust, working subjects of high intelligence, these data provide estimates of baseline functioning for future studies exploring the progression of pathological alcohol use patterns among women.
Evaluation of the Differential in Vivo Toxic Effects of Ethanol and Acetaldehyde on the Hypothalamic‐Pituitary‐Gonadal Axis Using 4‐Methylpyrazole
Authors: Gavaler Judith S. , Gay Vernon , Egler Kimberly , Thiel David H. Van
Published: February 2008

4‐Methylpyrarole (4‐MP) blocks ethanol (ETOH) oxidation by inhibiting alcohol dehydrogenase (ADH). Because ADH has been identified and shown to be active in the testes, we examined the effect of ETOH + 4‐MP in the ETOH‐fed rat model. Weanling rats were divided Into four groups of 15 rats each and fed a liquid diet: group I received ETOH (5% v/v) + 4‐MP (1.34 mM); group II was pair‐fed the diet containing only 4‐MP and isocalorically matched to group I; group III received ETOH dlet; and group IV was pair‐fed isocaiorically to match group III. Using two‐way analysis of variance for nonorthogonal data, the results were analyzed to examine both ETOH and 4‐MP as the main treatment and to test for interaction. Both ETOH and 4‐MP produced significant main treatment effects with significant interaction on liver/body ratio, testes weight expressed as per cent of normal, and plasma luteiniring hormone levels, and without interaction on plasma testosterone concentrations.
Concentration‐Dependent Effects of Ethanol in Long‐Sleep and Short‐Sleep Mice
Authors: Gilliarn David M. , Collins Allan C.
Published: February 2008

It has been observed that responses to ethanol may be altered by varying the injection concentration while keeping the dose constant, but these concentration‐dependent effects have not been well characterized. The results of the study reported here indicate that the long‐sleep (LS) and short‐sleep (SS) mice, selectively bred for ethanol‐induced narcosis at a concentration of 30% v/v, may have been selected in large part for the concentration‐dependent peripheral toxic effects of ethanol rather than ethanol's direct effects on the central nervous system. The study was designed to assess sleep time and waking blood ethanol concentration (BEC), hypothermia, and the linear decline in BEC in LS mice following an intraperitoneal injection of 3.8 g/kg of ethanol in concentrations of 190.0, 237.5, 292.3, or 380.0 mg/ml, and in SS mice following an intraperitoneal injection of 4.1 g/kg of ethanol in concentrations of 205.0, 256.2, 315.4, or 410.0 mg/ml. LS sleep time increased as a function of concentration, and mice injected with 380.0 mg/ml never regained the righting reflex. Waking BECs were significantly different for LS mice injected with the 190.0 and 292.3 mg/ml concentrations. For the SS mice, marginally significant differences were found among sleep times, and none of the animals injected with the 410.0 mg/ml regained the righting reflex. The lack of significant concentration‐dependent differences in SS waking BECs is attributable to extreme variability in the BECs of mice injected with the 315.4 mg/ml concentration. Both the LS and SS mice showed a concentration‐dependent decrease in body temperature, with the greatest temperature change observed at the highest concentrations. Maximum temperature depression occurred at 120 to 150 min postinjection in the LS mice and at 60 to 90 min postinjection in the SS. Only SS mice injected with the 205.0 or 256.2 mg/ml concentrations reethanolgained control temperature levels. The linear decline in BEC was faster at lower concentrations than at higher concentrations for LS mice. The declines in BEC for SS mice were not found to vary as a function of concentration. Concentration‐dependent differences in sleep time and hypothermia may not be due to differences in circulating levels of ethanol, but rather to slower elimination rates and/or enhanced depressant effects on peripheral organ systems. The present study supports the notion that the LS mice are more sensitive to the peripherally mediated concentration‐dependent effects of ethanol than are the SS mice. The systemic toxic effects of high ethanol concentrations may be more important in determining narcosis than previously suspected.