bluuebunny/crossref_metadata_2025 huggingface dataset:
Helicobacter Pylori, Active Chronic Antral Gastritis, and Gastrointestinal Symptoms in Alcoholics
Authors: Hauge T. , Persson J. , Kjerstadius T.
Published: April 2006

The frequency of Helicobacter pylori (Hp.) infection and active chronic antral gastritis among people with excessive alcohol consumption is not known. A high alcohol intake regularly causes acute gastroduodenitis. In this study, the prevalence of Hp. Infection and active chronic antral gastritis in alcoholics compared with nonalcoholic controls was studied. Further, the frequency of gastrointestinal symptoms was registered. Diagnostic methods for Hp. were compared.

Twenty‐four alcoholics admitted to the hospital for detoxification underwent upper gastrointestinal endoscopy regardless of symptoms. Twelve individuals admitted to upper endoscopy mainly for dyspepsia, with low alcohol consumption and without gross pathology by upper endoscopy, were chosen as controls. Three diagnostic methods for Hp. were used: culture, direct microscopy, and histology.

Hp. infection was found in 7 of the 24 alcoholics (29%) according to culture. In controls, 4 of 12 (33%) had a positive Hp. culture. In the alcoholic group, culture was more sensitive than histology. There was a good correlation between the different diagnostic methods in the control group. Histologically active chronic antral gastritis was found in 6 of the alcoholics (25%) and in 5 of the controls (42%). Five of the 7 Hp.‐positive alcoholics and all of the Hp.‐positive controls had an active chronic antral gastritis.

Hp. infection is not more frequent in alcoholics than in controls. In both groups, there was a good correlation between Hp. infection and histologically, active chronic antral gastritis.
Chronic Ethanol Exposure Inhibits Insulin and IGF‐1 Stimulated Amino Acid Uptake in Cultured Human Placental Trophoblasts
Authors: Karl Peter I. , Fisher Stanley E.
Published: April 2006

Maternal alcohol abuse during pregnancy can lead to abnormalities in fetal development, sometimes manifested as the fetal alcohol syndrome (FAS). Although intrauterine growth retardation is a hallmark of FAS, the pathophysiology is not fully understood. A contributing factor may be altered placental function. In this study, the effect of long‐term exposure to ethanol on subsequent amino acid uptake by the cultured human placental trophoblasts was examined. Both Na+‐dependent and Na+‐independent pathways for AIB uptake were measured. As reported previously, insulin and IGF‐1 enhanced Na+‐dependent AIB uptake. Exposure to ethanol had no effect on basal (nonhormone treated) AIB uptake. However, 72‐hr ethanol pretreatment of trophoblasts inhibited Na+‐dependent AIB uptake under stimulation by insulin or IGF‐1 in the absence of ethanol. Na+‐independent uptake was not affected. Ethanol treatment had no effect on insulin or IGF‐1 binding to cultured trophoblasts. These findings suggest that 72‐hr ethanol treatment in cultured trophoblasts may affect postreceptor signal transduction in the insulin or IGF‐1 pathways. Such changes have implications for the effect of ethanol on normal function of the human placenta, the major interface for maternal/fetal transfer of nutrients.
Stability of [3H]MK‐801 Binding Sites Following Chronic Ethanol Consumption
Authors: Tremwel Margaret F. , Anderson Kevin J. , Hunter Bruce E.
Published: April 2006

Previous work has demonstrated that short periods (1–2 weeks) of exposure to ethanol produce an upregulation of the N‐methyl‐D‐aspartate (NMDA) receptor complex in hippocampus; an alteration that appears to be associated with the development of physical dependence, because a return to control levels occurs over a 24‐ to 48‐hr abstinence period. Prolonged periods of chronic ethanol treatment (CET; 4–8 months of treatment) have been shown to produce severe and permanent alterations in the morphological and functional characteristics of hippocampal pyramidal neurons. Several lines of research have demonstrated that the NMDA receptor complex is involved in excitotoxic cell loss during certain pathological states. On the basis of this evidence, we hypothesized that prolonged ethanol exposure would be accompanied by an enduring increase in NMDA receptors and that NMDA receptor binding in cells surviving CET would be altered. To test this hypothesis, we measured the binding characteristics of the NMDA receptor complex in a variety of brain structures following CET. Animals were fed a nutritionally complete, ethanol‐containing diet for 28 weeks and then allowed a 48‐hr abstinence period. A control group was fed the same diet, except sucrose was isocalorically substituted for ethanol. We first examined the effect of CET on the binding properties of a noncompetitive antagonist to the NMDA receptor channel, [3H]diclozipene ([3H]MK‐801). Next, as an indirect examination of NMDA receptor function, we measured the ability of glutamate to stimulate channel opening and thus [3H]MK‐801 binding. In all brain structures examined, neither the Kd nor the Bmax of [3H]MK‐801 binding to the NMDA receptor was altered following CET. In addition, no effect of treatment was seen on the ability of glutamate to stimulate [3H]MK‐801 binding.
RX FOR HEALTH CARE COSTS:
Authors: Langenbucher James
Published: April 2006

The literature on addictions treatment cost offsets suggests that resolving addictive disorders in the general medical setting will drive down the demand for health care, promote more efficient use of care by both patients and their families, and preserve scarce resources that can be deployed more wisely elsewhere. The demand to reduce waste and trim health care expenditures challenges the historic gulf between general medical practice and the management of addictive behaviors. An example of an addiction treatment technology developed in medical settings for use by medical personnel, brief intervention, is reviewed, with reference to its cost‐saving potential under health care reform.
Magnesium Deficiency in Alcoholism: Possible Contribution to Osteoporosis and Cardiovascular Disease in Alcoholics
Authors: Abbott Lisa , Nadler Jerry , Rude Robert K.
Published: April 2006

Magnesium (Mg) deficiency occurs frequently in chronic alcoholism and may contribute to the increased incidence of osteoporosis and cardiovascular disease seen in this population. Mg deficiency is primarily due to renal Mg‐wasting and is exacerbated by dietary Mg deprivation, gastrointestinal losses with diarrhea or vomiting, as well as concomitant use of drugs such as diuretics and aminoglycosides. Osteoporosis is prevalent in the alcoholic population. Mg deficiency may contribute to increased bone loss by its effects on mineral homeostasis. In Mg depletion, there is often hypocalcemia due to impaired parathyroid hormone (PTH) secretion, as well as renal and skeletal resistance to PTH action. Serum concentrations of 1,25‐vitamin D are also low. These changes are seen with even mild degrees of Mg deficiency and may contribute to the metabolic bone disease seen in chronic alcoholics. Hypomagnesemia in alcoholics may also contribute to increased cardiovascular disease by altering platelet function. Mg deficiency has been demonstrated to enhance platelet reactivity. In these studies, Mg was shown to inhibit platelet aggregation against various aggregation agents. Patients with Mg deficiency were shown to have increased platelet aggregation that was normalized with Mg therapy. The antiplatelet effect of Mg may be related to the finding that Mg inhibits the synthesis of thromboxane A2 and 12‐hydroxyeicosatetraenoic acid, eicosanoids thought to be involved in platelet aggregation. Mg also inhibits the thrombin‐induced Ca2+ influx in platelets, as well as stimulates synthesis of prostaglandin l2, the potent antiaggregatory eicosanoid. Therefore, Mg deficiency may increase platelet aggregation and cause increased hypertension and atherosclerotic cardiovascular disease in alcoholics.
Family History of Alcoholism and Childhood Adversity: Joint Effects on Alcohol Consumption and Dependence
Authors: Hill Elizabeth M. , Blow Frederic C. , Young James P. , Singer Kathleen M.
Published: April 2006

Empirical studies provide substantial evidence that having a family history of alcoholism increases the risk of developing alcohol dependence; however, some of this effect may be caused by nonspecific childhood socioeconomic adversity common in families with an alcohol‐dependent parent. In this study, we examine joint effects of family history and childhood adversity within a sample of 509 men and 217 women over age 40. The measures analyzed were included in routine screening assessments for participants in various studies at the University of Michigan Alcohol Research Center. About 60% of the men and 45% of the women were alcohol‐dependent. About 30% reported an alcoholic parent. Degree of family history affected drinking behavior for both men and women. There were also environmental effects on the same measures for both men and women. Childhood socioeconomic adversity was reported more frequently by participants with an alcoholic parent, but adversity effects were also shown for those with a negative family history. The risk of alcohol dependence was additively increased by a positive family history and childhood socioeconomic adversity. The environmental effects identified in this study are promising evidence for nonspecific factors that moderate family history risk for development of alcohol problems.
Comparison of Alcohol Dependence in Subjects from Clinical, Community, and Family Studies
Authors: Bucholz Kathleen K. , Helzer John E. , Shayka Joseph J. , Lewis Collins E.
Published: April 2006

This study contrasts the prevalence of alcohol‐related symptoms, ages of onset of alcoholism milestones, and lifetime prevalence of other psychiatric disorders in three samples of alcohol‐dependent individuals: alcoholics sampled from a variety of clinical settings (not necessarily alcoholism treatment facilities), relatives of alcoholic probands who participated in a Family Study of alcoholism, and alcoholics identified in the St. Louis Epidemiologic Catchment Area survey. Alcohol dependence (with or without abuse) was assessed using DSM‐III diagnostic criteria for all samples. Clinical alcoholics had significantly more lifetime alcohol symptoms than Family Study and Community alcoholics and a significant excess of many alcohol symptoms. Onset information indicated that the three groups were similar in terms of appearance of milestones of alcohol dependence. For females aged 45 or younger, lifetime prevalence of major depression was high in both Clinical and Family Study alcoholics compared with Community alcoholics; male alcoholics from the Community Study had an excess of drug dependence. Findings suggest that, although alcoholics identified in clinical settings may have more severe alcohol dependence, certain types of psychiatric comorbidity are present to a greater degree in other samples of untreated alcoholics.
Clinical Predictors of Alcohol Withdrawal Delirium
Authors: Wetterling T. , Kanitz R.‐D. , Veltrup C. , Driessen M.
Published: April 2006

Up to now, clinical predictors for the course of the alcohol withdrawal syndrome, especially for the occurrence of a delirium, are lacking. Thus, this study was undertaken to examine whether clinical routine investigations at admission before the withdrawal syndrome can reveal factors indicating a higher risk for the development of a delirium. Our results showed that decreased serum electrolyte concentrations (i.e., chloride and potassium), elevated ALT, and γ‐glutamyltransferase serum levels, as well as ataxia and polyneuropathy at the neurological examination, indicate a higher risk for the development of an alcohol withdrawal delirium.
Carbohydrate‐Deficient Transferrin and Other Markers of High Alcohol Consumption: A Study of 502 Patients Admitted Consecutively to a Medical Department
Authors: Bell Helge , Tallaksen Chantal M. E. , Try Kenneth , Haug Egil
Published: April 2006

An isoform of transferrin, carbohydrate‐deficient transferrin (CDT) is increased in a high percentage of abusing alcoholics and has been found superior in its specificity compared with other biological markers. We used serum CDT as a screening parameter in 502 patients consecutively admitted to our medical department during a 4‐week period. The intake of ethanol during the last 4 weeks was registrated by personal interviews and the mean daily consumption calculated. Serum CDT was measured at admission (CDTect) and compared with γ‐glutamyltranspeptidase (GGT), AST, ALT, and mean corpuscular volume (MCV). Serum CDT detected 18 of 26 (69%) patients who consumed >50 g ethanol daily. The clinical sensitivity of CDT of detection ethanol consumption >50 g daily was 69%, compared with 73%, 50%, 35%, and 52% for increased values of GGT, AST, ALT, and MCV, respectively. Altogether, 38 of 476 patients (8%) with a daily ethanol consumption < 50 g also had increased serum CDT levels. The specificity of CDT was 92%, compared with 75%, 82%, 86%, and 85% for GGT, AST, ALT, and MCV, respectively. In the 60 patients who consumed >10 g ethanol daily, we found a significantly positive correlation between CDT and ethanol consumption (r= 0.52, p < 0.001). A positive correlation was also found between serum transferrin and CDT (r= 0.51, p < 0.001). In conclusion, the specificity of CDT is much higher compared with GGT in detecting alcohol abuse. Some acute and chronic illnesses may increase the serum level of CDT. False‐positive CDT levels may be caused by changes in serum transferrin concentration.
Effects of Moderate Alcohol Consumption During Pregnancy on Child Development at 18 and 42 Months
Authors: Olsen Jørn
Published: April 2006

The aim of this study was to estimate the association between moderate alcohol consumption in pregnancy and child development to the age of 3.5 years. Furthermore, the aim was to compare development indices at 18 and 42 months of age. This study is an extension of the Danish participation in the EuroMac study. In a two‐stage sampling, pregnant women in a well‐defined region (Odense, Denmark) were recruited to a follow‐up study according to their reported drinking habits in the first trimester of pregnancy. All among 2880 pregnant women who reported an alcohol consumption early in pregnancy (12th week of gestation) of at least 5 drinks/week were ascertained (164 women). A similar age and expected time of delivery matched group was selected from the remaining group of pregnant women. Alcohol consumption data were based on self‐reported data, and child development recording was done blindly by two psychologists at 18 and 42 months after birth. Two hundred fifty‐one mother‐child pairs participated in all follow‐up studies. None of the reported levels of alcohol intake was statistically significantly associated with any of the child development indices (including measures of binge drinking). Comparing child development indices at 18 and 42 months did, however, reveal a rather large variation over time for alcohol exposures, as well as nonexposures. A large variation in the outcome measure will tend to mask effects of any exposures, but nevertheless it is unlikely that a low alcohol intake in pregnancy has any substantial impact on child development.
Effects of Fetal Alcohol Exposure on Infant Reaction Time
Authors: Jacobson Sandra W. , Jacobson Joseph L. , Sokol Robert J.
Published: April 2006

Fetal alcohol exposure is associated with slower reaction times (RTs) in children, suggesting an alcohol‐related deficit in “speed of central processing.” This study examined effects of prenatal alcohol exposure on a new paradigm which, for the first time, directly assesses RT in infancy. RT was assessed in 103 Black, inner‐city, 6.5‐montholds born to women recruited prenatally based on alcohol consumption during pregnancy. Maternal drinking was related to longer RTs and to fewer fast responses, after controlling for potential confounders. The incidence of fast performance was reduced in infants whose mothers averaged at least 0.5 oz absolute alcohol/day, indicating an impact at lower levels than those associated with fetal alcohol syndrome. The RT deficits were dose‐dependent and not attributable to maternal depression, intellectual stimulation, prenatal drug exposure, or postpartum maternal drinking. This study provides the first evidence of an alcohol‐related RT deficit in infancy.
Effect of Citalopram on Alcohol Intake in Heavy Drinkers
Authors: Balldin Jan , Berggren Ulf , Engel Jorgen , Eriksson Matts , Hård Ernest , Söderpalm Bo
Published: April 2006

The effect of the selective serotonin reuptake inhibitor citalopram (40 mg daily dose) on alcohol intake was investigated in a doubleblind, placebo‐controlled cross‐over study. Thirty men with heavy alcohol consumption (mean daily alcohol intake 111 ± 51 g pure alcohol) completed the study. After a 2‐week baseline period, subjects were randomly allocated to treatment with either citalopram or placebo for 5 weeks. In the total sample of heavy drinkers, no difference was found between citalopram and placebo treatment in alcohol consumption or days of abstinence. However, the response to citalopram was negatively correlated (ra=–0.67, p < 0.01) with baseline levels of mean daily alcohol intake. Therefore, we divided the total sample into two subgroups with baseline mean daily alcohol intake above and below median (107 g pure alcohol), respectively. In the group with the higher baseline values (138 ± 25 g pure alcohol), citalopram was not different from placebo in reducing the daily alcohol intake, but in subjects with the lower baseline values (85 ± 15 g pure alcohol), citalopram was significantly (p < 0.01) superior to placebo. Consequently, citalopram at the present dose appears capable of reducing alcohol intake only in a subgroup of heavy drinkers with a mean daily consumption of between 60 and 100 g pure alcohol.
Drinking History Is Related to Persistent Blood Pressure Dysregulation in Postwithdrawal Alcoholics
Authors: King Andrea C. , Parsons Oscar A. , Bernardy Nancy C. , Lovallo William R.
Published: April 2006

We have previously demonstrated that alcoholics with transitory (< 72 hr) elevations in blood pressure (BP) during withdrawal continue to show residual cardiovascular dysregulation up to 4 weeks of abstinence. The present study replicates and extends these findings. Alcoholic inpatients were divided into three subgroups (ns= 14) based on BP during the first 72 hr of withdrawal: transitory hypertensives (tHTs; BP > 160/95 mm Hg), transitory borderline hypertensives (tBHs; 140/90 BP < 160/95), and normotensives (NTs; all BPs < 140/90). All patients had normal resting pressures after 72 hr of withdrawal. At 3–4 weeks postadmission, the alcoholics and 14 nonalcoholic controls (CONTs) were tested at rest and during a 5‐min handgrip task. The tHTs showed an exaggerated systolic and diastolic BP response to handgrip compared with NTs and CONTs, with tBHs intermediate (ps < 0.05). Drinking history showed the tHTs had the highest reported level of alcohol consumption and severity of withdrawal symptoms (ps < 0.05). Regression analyses indicated that consumption of hard liquor was the variable most predictive of admission BPs; further, parental history of hypertension potentiated this relationship for systolic BP. Age and consumption of nicotine and caffeine were not significant predictors of admission BP. The results suggest a persistent cardiovascular dysregulation in alcoholics showing transient hypertensive withdrawal BPs. These alcoholics may be at increased risk for future alcohol‐related cardiovascular disorder.
Changes in Transaminases Over the Course of a 12‐Week, Double‐Blind Nalmefene Trial in a 38‐Year‐Old Female Subject
Authors: Salvato Fernando R. , Mason Barbara J.
Published: April 2006

A 38‐year‐old female was drinking 30 drinks/week before entering a 12‐week, double‐blind study of nalmetene for the treatment of alcohol dependence. Liver function tests (LFTs) were within normal limits at baseline and week 4, but on week 8, the ALT showed a 7‐fold increase, and the AST showed a 4‐fold increase from baseline. A decision was made to continue study medication based on the patient's positive response to this therapy (i.e., achieving complete abstinence) and no known dose‐dependent association with liver toxicity in over 1300 patients treated with nalmefene for other indications. LFTs were repeated serially to assess the trend of the LFT values. The patient achieved total abstinence over the course of the study period and at the 3‐month posttreatment follow‐up was continuing to maintain these gains from the study program, and her LFTs had returned to normal. A gradual return to normal in ALT and AST, while treatment with nalmefene continued, does not support the role of nalmefene as an hepatotoxin. Relapse to drinking was excluded because of normal values for the γ‐glutamyltransferase, and verification of sobriety by self‐report, significant other, and breathalyzer. A virology panel ruled out the presence of viral hepatitis. Dietary intake before the elevation in LFTs contained elements that have established association with hepatocellular changes. The routine prescription of serial LFTs in alcoholism pharmacotherapy trials may be expected to reveal clinically nonsignificant elevations that could potentially be related to exogenous factors, such as dietary composition and should not be reflexively attributed to medication under investigation and/or drinking.
Studies of the Oxidation of Ethanol to Acetaldehyde by Oxyhemoglobin Using Fluorigenic High‐Performance Liquid Chromatography
Authors: Chen Hui‐Min , Lin Wendy W. , Ferguson Kenneth H. , Scott B. Keyes , Peterson Charles M.
Published: April 2006

We noted a rise in acetaldehyde levels in clinical samples of venous whole blood containing ethanol that did not occur in samples from teetotalers. Experiments were performed to define the mechanism involved in acetaldehyde production. The addition of 0.10% ethanol to whole blood produced an immediate increase in acetaldehyde due to acetaldehyde in the stock solution followed by a subsequent increase that became statistically significant by 48 hr. Separation of blood into components documented that the increase in acetaldehyde was associated with the red cell but not plasma fraction. Incubation of isolated hemoglobin with ethanol produced a rise in acetaldehyde levels. Incubation of oxygenated whole blood with ethanol produced a linear increase in acetaldehyde, whereas nitrogen‐exposed blood produced no increase. The rise of acetaldehyde in the presence of ethanol was dependent on the concentration of oxygenated hemoglobin A0. Addition of inhibitors of catalase, alcohol dehydrogenase, and glycolytic enzymes (aminotriazole, azide, pyrazole, sodium fluoride, sodium citrate, and iodoecetate) did not inhibit the rise of acetaldehyde, but addition of the hemoglobin ligand cyanide abolished the rise in acetaldehyde. Kinetic analysis with oxygenated whole blood plus inhibitors revealed a Km of 2.5 mM and Vmax of 1.42 μM/min. We conclude that oxyhemoglobin contributes to the metabolism of ethanol to acetaldehyde. These findings may explain in part the high levels of acetaldehyde found in red cells compared with plasma. The results also have implications for the optimum storage of blood samples for acetaldehyde analysis.
Effect of Acute and Chronic Alcohol Administration to Rats on the Expression of Interleukin‐6 Cell‐Surface Receptors of Hepatic Parenchymal and Nonparenchymal Cells
Authors: Deaciuc Ion V. , Alappat Julie M. , D'Souza Nympha B.
Published: April 2006

Rats were treated with alcohol either acutely (continuous, 7‐hr intravenous infusion; blood alcohol levels ∼35 mM) or chronically (liquid diet, 12–14 weeks). Three hr before killing, the animals received Gram‐negative bacterial lipopolysaccharide (LPS) or saline. Hepatocytes, Kupffer cells, and liver sinusoidal endothelial cells were isolated by liver collagenase perfusion and centrifugal elutriation, and used for measurements of recombinant human [125I]interleukin‐6 binding. Dissociation constant (Kd) and the amount of cell‐surface receptors (Bmax) were measured on whole cells, at 4°C. Two binding sites were detected on all three cell types: high‐affinity (Kd1, from 20 to 125 PM) and low‐affinity (Kd2, from 0.2 to 2 nM), with low Bmax (Bmax from 0.4 to 12 fmol/106 cells) and high Bmax (Bmax2, from 10 to 210 fmol/106 cells). Hepatocytes displayed an 8‐fold higher binding capacity for high‐affinity sites (Bmax1) than the other two cell types. Acute ethanol treatment induced the following significant changes in the binding parameters: a decrease in Kd1 for hepatocytes and Kupffer cells, an increase in Bmax2 for hepatocytes, and a decrease in Bmax1 for Kupffer cells. Although the control (nonalcoholic) liquid diet per se completely suppressed the high‐affinity binding sites, alcohol‐containing diet induced only one change: a significant increase in Kd2 for hepatocytes. No changes in the binding parameters were seen after LPS administration to the chronically treated group. In the acute group, LPS mimicked alcohol action on hepatocyte binding parameters. Alcohol blunted LPS effects. No changes were observed in the cytokine binding to Kupffer cells after LPS injection. The results show that alcohol alters interleukin‐6 cell‐surface receptor properties and receptor amount on hepatocytes and Kupffer cells. By demonstrating the presence of interleukin‐6 receptors on non‐parenchymal liver cells, our data also suggest that these cells may be involved in an autocrine loop‐like response, which could be a target for alcohol action on the liver.
Purification and Characterization of Helicobacter pylori Alcohol Dehydrogenase
Authors: Kaihovaara Pertti , Salmela Katja S. , Roine Risto P. , Kosunen Timo U. , Salaspuro Mikko
Published: April 2006

Alcohol dehydrogenase of Helicobacter pylori (HPADH) was purified from the soluble fraction of cultured bacteria (strain NCTC 11637) by anion exchange and affinity chromatography. On sodium dodecyl sulfate‐polyacrylamide gel electrophoresis, the 160‐fold purified enzyme displayed one protein band with a mobility that corresponded to an M, of 38,000. Although HPADH was capable of utilizing both NADP and NAD as cofactors in alcohol oxidation, it showed a strong preference for NADP over NAD. Kinetic studies revealed a Km value of 26 mM and a kct value of 530 min−1 for ethanol/active site at 37°C in 0.1 M potassium phosphate buffer (pH 7.4). The enzyme was considerably more active toward primary aliphatic alcohols than secondary alcohols. The Km and kct values decreased as the chain length of the alcohol increased. Benzyl alcohol was a 100 times better substrate than ethanol in terms of kct/Km values. At neutral pH, HPADH was more effective in aldehyde reduction than in alcohol oxidation. Because of its high specific activity for ethanol (14 units mg−1) under physiological conditions, HPADH can also effectively produce acetaldehyde at higher ethanol levels. This reversed function of HPADH and the production of toxic and reactive acetaldehyde could account for at least some of the gastrointestinal morbidity associated with H. pylori infection.
Ethanol Increases Hepatocyte Water Volume
Authors: Wondergem Robert , Davis Janet
Published: April 2006

Mouse hepatocytes respond to osmotic stress with adaptive changes in transmembrane potential, Vm, such that hypotonic stress hyperpolarizes cells and hypertonic stress depolarizes them. These changes in Vm provide electromotive force for redistribution of ions such as CI−, and this comprises part of the mechanism of hepatocyte volume regulation. We conducted the present study to determine whether ethanol administered in vitro to mouse liver slices increases hepatocyte water volume, and whether this swelling triggers adaptive changes in the Vm. Cells in mouse liver slices were loaded with tetramethylammonium ion (TMA). Changes in hepatocyte water volume were computed from measurements with Ion sensitive micro‐electrodes of changes in intracellular activity of TMA (a1TMA) that resulted from water fluxes. Ethanol (70 mM) increased hepatocyte water volume Immediately, and this peaked at 17% by 7 to 8 min, by which time a plateau was reached. Liver slices also were obtained from mice treated 12 hr prior with 4‐methylpyrazole (4 mM). The effect of ethanol on their hepatocyte water volume was identical to that from untreated mice, except that the onset and peak were delayed 2 min. Hepatocyte Vm showed no differences between control or ethanol‐treated cells during the course of volume changes. In contrast, hyposmotic stress, created by dropping external osmolality 50 mosm, increased Vm from –30 mV to –46 mV. Ethanol did not inhibit this osmotic stress‐induced hyperpolarization, except partially at high concentrations of 257 mM or greater. We infer that ethanol‐induced swelling of hepatocytes differs from that resulting from hyposmotic stress. Cellular events associated with increased activity of intracellular water most likely trigger the hyperpolarization of Vm that accompanies the latter. We conclude, therefore, that ethanol‐induced swelling occurs without change in cell water activity. This may result from the retention of macromolecules by ethanol in cells that constitutively secrete protein.
Magnitude, Origin, and Implications of the Discrepancy between Blood Ethanol Concentrations of Tail Vein and Arterial Blood of the Rat
Authors: Levitt Michael D. , Furne Julie , DeMaster Eugene G.
Published: April 2006

The rat is widely used as an animal model for experiments involving ethanol, and alcohol concentrations in blood obtained from the tail routinely are used to monitor ethanol exposure and metabolism. The present study demonstrates that during periods of rising and declining ethanol levels, the alcohol concentrations in tail vein blood lags far behind that of arterial, jugular, or femoral vein blood. As a result, tail vein ethanol concentrations markedly underestimate the concentration in arterial blood and rapidly perfused tissue during periods of increasing body ethanol, whereas the reverse is true as body ethanol declines. This discrepancy, which appeared to result from the low blood perfusion:tissue water ratio in the tail, disappeared when the tail was heated to 37°C. Compared with arterial blood, alcohol measurements performed on tail vein blood yielded a much higher apparent Km for ethanol clearance and a somewhat lower estimate of ethanol reaching the peripheral circulation. We conclude that, for a variety of studies, analyses of arterialized blood from the heated tail should yield a more accurate and reproducible measure of ethanol exposure and/or metabolism than does the conventional collection from the unheated tail.
Prenatal Alcohol Exposure Alters the Hypothalamic‐Pituitary‐Adrenal Axis Response of Immature Offspring to Interleukin‐1: Is Nitric Oxide Involved?
Authors: Lee Soon , Rivier Catherine
Published: April 2006

We have previously shown that following prenatal alcohol exposure, immature offspring showed blunted ACTH released in response to the peripheral administration of interleukin‐1β (IL‐1β). The present studies were conducted to investigate the role of changes in corticosteroid feedback (measured by altered adrenal responses to ACTH), corticotropin‐releasing factor (CRF) content of the median eminence (ME), and the influence of endogenous nitric oxide (NO). The injection of several doses of ACTH failed to indicate measurable differences between the corticosterone responses of offspring born to dams fed ad libitum [control (C)], pair‐fed (PF), or fed alcohol [ethanol (EtOH) = E]. CRF content in the ME, taken as an index of the amount of releasable peptide, showed a small, but statistically significant, decrease following prenatal alcohol exposure. A comparable change, however, was also noted in PF rats. As expected, the subcutaneous injection of IL‐1β (0.5 μg/kg) induced smaller increases in plasma ACTH levels of E than C pups. The response of PF animals was intermediate between that of E and C rats. Finally, we observed that inhibition of NO formation by the administration of the arginine derivative Lwnitro‐L‐arginine‐methylester significantly augmented ACTH secretion in all three experimental groups, and reversed the decreased corticotrophs' response to IL‐1β caused by prenatal alcohol.

Taken together, our results suggest that the ability of prenatal alcohol exposure to alter ACTH released by immature pups in response to blood‐borne IL‐1β is probably not mediated through changes in adrenal responsiveness. We propose, on the other hand, that endogenous NO levels may be increased by the prenatal treatment, thereby interfering with the release of peptides from nerve terminals in the ME.
Ganglioside GM1 Reduces Fetal Alcohol Effects in Rat Pups Exposed to Ethanol In Utero
Authors: Hungund Basalingappa L. , Ross Donald C. , Gokhale Vinayak S.
Published: April 2006

We have investigated the effect of in utero ethanol exposure and ganglioside GM1 pretreatment on the endogenous ganglioside profile of the rat fetal brain. Prenatal ethanol exposure on gestation day (GD) 7 and GD8 and/or GD13 and GD14 leads to a very significant increase in the ganglioside GM1 content in at least 50% of the pup brains when assayed on GD20. This treatment protocol also results in significant decrease in the content of polysialogangliosides GD1a, GT1b, and GQ1b. GM1 treatment of pregnant dams before ethanol administration prevented this alteration in pup brain ganglioside profile. Ganglioside GM1 pretreatment appears to block the cellular membrane changes associated with fetal alcohol effects and thereby minimizes alterations in brain maturation and associated behavioral dysfunction.
Vapor Phase Exposure to Acetaldehyde Generated from Ethanol Inhibits Bovine Bronchial Epithelial Cell Ciliary Motility
Authors: Sisson J. H. , Tuma D. J.
Published: April 2006

Acetaldehyde is a toxic product of the oxidation of ethanol and is known to induce slowing of ciliary motility in airway epithelium. Alcohol ingestion results in high exhaled breath concentrations of ethanol where lung microsomes and upper airway bacterial flora are capable of metabolizing it to acetaldehyde. Because acetaldehyde is very volatile, we hypothesized that the production and release of acetaldehyde vapor into the airway may result in ciliary slowing or ciliastasis. To test this hypothesis, ciliated bovine bronchial airway epithelial cells were maintained on collagen‐coated dishes for 48 hr before coincubation with a separate dish containing control or test mixtures. In this arrangement, the ciliated cells were exposed only to the volatile components of the separate dish. The separate dish contained ethanol, acetaldehyde, or an acetaldehyde‐generating system (AGS) that consisted of ethanol + glucose + glucose oxidase + catalase. This mixture was placed next to the ciliated cells within in a transparent sealed chamber. Ciliary motility was recorded at room temperature by video microscopy, and ciliary beat frequency was determined using computerized frequency spectrum analysis. Exposure to the AGS resulted in time‐and concentration‐dependent ciliary slowing with complete ciliastasis, with as low as 20 mM ethanol in the AGS. Direct vapor phase exposure to acetaldehyde alone served as a positive control and also resulted in time‐dependent ciliary slowing with complete ciliastasis reached by 4 hr. The AGS‐induced ciliastasis was reached 2 hr later than with acetaldehyde alone. When cells were pretreated with cyanamide, which is known to block acetaldehyde dehydrogenase, the time to ciliastasis was decreased by 10–30 min compared with untreated cells. We conclude that acetaldehyde generated from ethanol is capable of inducing ciliastasis at concentrations of ethanol frequently encountered during drinking. In addition, our results suggest that ciliated airway epithelial cells have acetaldehyde dehydrogenase‐like activity that may be protective against aldehyde‐induced airway injury.
Genetic Polymorphism and Activities of Human Colon Alcohol and Aldehyde Dehydrogenases: No Gender and Age Differences
Authors: Yin Shih‐Jiun , Liao Chin‐Shya , Lee Ye‐Chan , Wu Chew‐Wun , Jao Shu‐Wen
Published: April 2006

Alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH) isoenzyme patterns from 69 (men, 47; women, 22) surgical colon mucosal specimens were identified by agarose isoelectric focusing. γ‐ADH was found to be the predominant form in the mucosa, whereas only β‐ADH was detectable in the muscle layer. ALDH1, ALDH2, and ALDH3 were detectable in the mucosa, with cytosolic ALDH1 being the major form. At pH 7.5, the ADH activities in the colon mucosae with the homozygous phenotype (exhibiting γ1γ1) and the heterozygous phenotype (exhibiting γ1γ1, γ1γ2, γ2γ2) were determined to be 183 ± 13 and 156 ± 30 nmol/min/g tissue, respectively. The ALDH activities in the ALDH2‐active and ALDH2‐inactive phenotypes were determined to be 40.2 ± 2.3 and 34.6 ± 2.0 nmol/min/g tissue, respectively. The lack of significant difference in the ALDH activities between these two phenotypic groups can be attributed to the very low expression of the mitochondrial ALDH2 in the colon mucosa. No significant differences in the ADH or the ALDH activities were found between the men and women studied and between the three age groups (20–40, 49–70, and 72–83 years). The ascending, transverse, descending, and sigmoid colons exhibited similar ADH and ALDH activities. The isoenzyme patterns of ADH and ALDH remained unaltered in colon carcinomas, except that a significant reduction of the enzyme activities was found in the cancer tissue as compared with the adjacent normal portions. it is concluded that human colon mucose exhibits significant amounts of ethanol‐ and acetaldehyde‐oxidizing activities.
Differences between Alcohol‐Preferring (AA) and Alcohol‐Avoiding (ANA) Rats in the Prodynorphin and Proenkephalin Systems
Authors: Nylander Ingrid , Hyytiä Petri , Forsander Olof , Terenius Lars
Published: April 2006

The motivation to drink alcohol and the eventual risk of becoming addicted are in part genetically determined. Because opioid peptides are considered central to motivated behaviors, we have analyzed opioid peptides in relevant areas of the brain of two outbred lines of rats: the alcohol‐preferring [Alko Alcohol (AA)] line who voluntarily drink alcohol and the alcohol‐avoiding [Alko Non‐Alcohol (ANA)] line with negligible intake. (Met)enkephalinArg6Phe7 (MEAP) was measured as a marker of proenkephalin, and dynorphin A, dynorphin B, and (Leu)enkephalinArg6 as markers of the prodynorphin system. The major line differences and effects of alcohol intake were observed in mesolimbic brain areas. The mesolimbic dopamine pathway, which projects from the ventral tegmental area (VTA) to the nucleus accumbens, is central in the reward system. Basal levels of MEAP and dynorphin peptides were low in the nucleus accumbens of AA rats, whereas (Leu)enkephalinArg6 levels were lower in the VTA of these rats. Alcohol drinking caused MEAP levels in the accumbens to rise, but had no effect on prodynorphin peptides. Opioids also influence the nigrostriatal dopamine pathway. However, this study showed no significant differences for any peptide between rat lines, or effect of alcohol intake, in either substantia nigra or striatum, except for a decrease of nigral and striatal (Leu)enkephalinArg6 levels in alcohol‐drinking AA rats. Large line differences were observed in the pituitary gland. AA rats had high basal levels of MEAP, which became even higher after voluntary alcohol consumption for 4 weeks, and low levels of dynorphin peptides, not affected by alcohol drinking. In summary, there are differences in baseline and drinking‐induced opioid peptide levels between the rat lines. First, the AA rats have lower dynorphin levels in the nucleus accumbens, which may increase the sensitivity to the reinforcing effects of dopamine. Second, the AA rats who have lower MEAP levels in the nucleus accumbens, respond by an increase on alcohol intake, which may strengthen the motivation to continue alcohol drinking. Thus, there is a possible relationship between differences in opioid peptide levels and differences in the motivation to drink alcohol between these two lines of rats.
Alteration of Copolymer‐Specific Humoral and Cell Mediated Immune Responses by Ethanol
Authors: Waltenbaugh Carl , Mikszta John , Ward Howard , Hsiung Linda
Published: April 2006

Excessive alcohol consumption represents a major human health threat. The frequency and severity of infections in alcoholics is often pronounced, suggesting impaired immune function in these patients. The precise effect of ethanol on cells of the immune system is poorly understood. We have previously shown that synthetic copolymers of L‐amino acids, GT and GAT, are powerful tools for clarifying the role of regulatory T‐cells in both cell‐mediated and humoral immunity in inbred mouse strains. We asked whether these same antigens would have application to a murine model of ethanol consumption. In this study, female mice were placed on a nutritionally complete liquid diet containing 35% ethanol‐derived calories. As control, mice either were placed on a liquid control diet that isocalorically substitutes sucrose for ethanol or remained on a solid diet consisting of standard laboratory chow and water ad libitum. Our data show that the liquid ethanol diet severely inhibits two measures of cell‐mediated immunity, the ability of responder B6 mice to make an anti‐GAT delayed hypersensitivity and GAT‐specific T‐cell proliferative responses as compared with pair‐fed liquid control diet or solid diet controls. On the contrary, this liquid ethanol diet does not significantly impair humoral immunity; it allows nonresponder C57BL/6 or C3H/HeN mice to respond in vivo to GT immunization. These findings suggested to us that the effect of ethanol may occur prior to antigenic stimulation, and this was confirmed by in vitro immunization.
Modification of Lymphocyte Subsets in the Intestinal‐Associated Immune System and Thymus by Chronic Ethanol Consumption
Authors: Lopez Maria C. , Huang Dennis S. , Borgs Peter , Wang Yuejian , Watson Ronald Ross
Published: April 2006

Modification of the mucosa‐associated intestinal immune system of female C57BL/6 mice was studied during consumption of the Lieber‐DeCarli diet supplemented with 5% v/v ethanol or laboratory chow with ethanol (20% w/v) in the drinking water. All groups received ethanol for 11 weeks. Mice fed the Lieber‐DeCarli diet had fewer CD8+ cells/villus than the chow‐fed controls. Mice that received ethanol in the drinking water had fewer IgA‐containing cells and CDB+ cells than controls. There were no differences in the number of cells in the mesenteric lymph nodes between ethanol‐treated mice and their respective controls. Nevertheless, chow‐fed control mice had more cells than those fed the Lieber‐DeCarli control diet. Although no differences were detected in the percentages of CD4+, CD8+, LECAM‐1+, and LECAM‐1+ CD4+ cells, there was a decrease in the percentage of LECAM‐1+ CD8+ cells in ethanol‐fed mice when compared with their Lieber‐DeCarli controls. Mice receiving ethanol in the drinking water showed alterations in the CD4 CD45RC subsets and in the CD8 CD45RC subsets. Similar results were observed in mice receiving Lieber‐DeCarli diets alone or supplemented with ethanol. The low dose, chronic exposure of dietary ethanol in the Lieber‐DeCarli‐fed mice did not significantly affect the numbers of various thymocyte subsets. But, a decrease in the percentage of CD4‐ CD8+ cells was observed in the thymus of mice receiving ethanol in the drinking water. Chronic ethanol consumption caused significant decreases in the number of CD8+ and IgA+ cells in the intestinal lamina propria, important in mucosal immune defenses.
Effects of Alcohol on Blastocyst Implantation and Fecundity in the Rat
Authors: Mitchell J. A.
Published: April 2006

The effects of alcohol on blastocyst implantation and fecundity were determined. Pregnant rats (insemination = day 1) received vehicle only (water), or alcohol (2 or 4 g/kg body weight) daily by feeding tube on days 1–4 and the time of implantation determined on day 5 or fecundity assessed on day 19. Implantation sites were rendered visible by the blue‐reaction; fecundity was expressed as the ratio of live fetuses to total implantations. The time course of blastocyst implantation was advanced by alcohol (2 g/kg dose). At 1000 hr, 1.9 vs. 0.9 blastocysts had implanted in treated vs. controls. By 1200 hr, 66 vs. 17% of blastocysts had implanted and by 1500 hr 90 vs. 52% had implanted in the 2 g/kg dose group vs. controls. Blastocyst implantation was not consistently advanced by the 4 g/kg dose of alcohol. The total number of blastocysts ultimately implanting did not differ between groups (control: 7:0 ± 0.9; 2 g:7.3 ± 0.9; 4 g:7.1 ± 0.5 sites/cornu at 1800 hr). Fecundity did not differ markedly between control and the 2 g/kg dose group (97 vs. 96%, respectively), but was reduced in the 4 g/kg dose group (58%). The results indicate that daily administration of alcohol (2 g/kg body weight) during the preimplantation period (days 1–4) advances the time course of blastocyst implantation without reducing fecundity.
Maternal Ethanol Consumption: Effects on G Proteins and Second Messengers in Brain Regions of Offspring
Authors: Druse Mary J. , Tajuddin Nuzhath F. , Eshed Maya , Gillespie Roberta
Published: April 2006

Previous work in this and other laboratories has demonstrated that in utero ethanol exposure adversely affects the development of the serotonergic, dopaminergic, cholinergic, and other neurotransmitter systems. In several of these systems, receptor number is significantly altered. To determine whether the altered number of two G protein‐linked receptors is reflected in changes in cell function, we examined dopamine‐stimulated adenylate cyclase in the striatum and cortex and carbachol‐stimulated phosphoinositide (PI) hydrolysis in the cortex. Serotonin‐stimulated cortical PI hydrolysis was assessed for comparison. We also studied G proteins that link adenylate cyclase and other second messenger systems to their receptors. The G proteins that were analyzed include the α‐subunits for Ga, Go, G11, G12, and G13. G proteins were analyzed in the cortex and cortical regions, as well as in the brain stem.

The results of these experiments demonstrated that dopaminestimulated adenylate cyclase activity was comparable in the striatum of 5‐ and 19‐day offspring of control and ethanol‐fed rats and in the motor cortex of 19‐day offspring. We also found that carbachol‐ and serotonin‐stimulated hydrolysis of cortical phosphoinositides was unchanged in ethanol‐exposed offspring on gestational day 19, and on postnatal days 5 and 19. G protein content was examined by Western blot analysis, using antibodies directed against the α‐subunits of Ga, Go, and the G11/G12 and G13/Go combinations. These investigations indicated that, with two minor exceptions (∼10% change in the proteins detected by antibodies against the α‐subunits of the G11/G12 and G13/Go combinations), there were no significant differences in the content of any of the G proteins analyzed.