bluuebunny/crossref_metadata_2025 huggingface dataset:
Selective Fetal Malnutrition: Effect of Acute and Chronic Ethanol Exposure upon Rat Placental Na, K‐ATPase Activity
Authors: Fisher Stanley E. , Duffy Lynn , Atkinson Mark
Published: June 2007

Intrauterine growth retardation (IUGR) is characteristic of the fetal alcohol syndrome (FAS). This IUGR is partly due to the toxic effect of ethanol upon placental function, including amino add transport Amino acid transport is dependent, in part, upon Na,K‐ATPase; therefore, plasma membrane activity of Na,K‐ATPase was measured in rat placentas following acute or chronic ethanol exposure. Acute (A) animals were chow fed and gavaged with ethanol on day 20 of gestation and kMed 2 hr later; controls (A‐C) received sucrose. Binge (B) animals were gavaged on gestation days 18 and 19; controls (B‐C) received sucrose. Chronic animals were fed ethanol in a liquid diet containing 2% (CHR‐2%) or 6% (CHR‐6%) ethanol by volume and killed on day 20. Controls (CHR‐2%‐C or CHR‐6%‐C) were isocatoricafy pair fed. Maternal blood ethanol levels were 197.1 ± 29.7 mg/dl (mean ± SE) for A dams and 128.2 ± 15.2 for B (drawn at time of death); 12.6 ± 2.2 for CHR‐2% and 195.0 ± 26.0 for CHR‐6% (drawn weekly and at time of death). Placental weight was increased and fetal weight decreased in the CHR‐6% animals. A, B, and CHR‐2% placental and fetal weights were unaffected. Na,K‐ATPase specific activity was increased in B placentas: B = 134.7 ± 16.5 versus B‐C = 50.0 ± 7.4 nmoi of P1/mg of protein/mm (p < 0.01). Conversely, CHR‐6% treatment diminished enzyme activity: CHR‐6%= 37.0 ± 4.5 versus CHR‐6%‐C = 58.5 ± 4.4 (p < 0.01). The same magnitude of reduction was seen in activity per total membrane fraction per placenta for CHR‐6% treatment It is concluded that chronic, high Mood levels of ethanol lead to diminished placental Na,K‐ATPase activity in the rat which may help to explain the IUGR seen in the FAS.
Alcohol: High Density Lipoproteins, Apolipoproteins
Authors: Cushman Paul , Barboriak Joseph , Kalbfleisch John
Published: June 2007

Plasma lipids, including high density lipoproteins (HDL) components, were studied tn 26 healthy male alcohol abusers. Age‐ and gender‐matched controls denied the use of substances or behaviors associated with increased HDL. On admission to abstinence treatment, the alcohol abusers' total cholesterol and triglycerides were usualy normal. Their HDL‐choiesterol levels were high, and fen to normal within 2 weeks of sobriety. ApoKpoprotein (APO) Al and All were high initialy and also became normal in 2 weeks. APO A I and II to HDL‐choiesterol ratios appeared to change during abstinence, while APO AI/AII did not APO ail, high initially, fell during treatment, but was stM high after 4 weeks of sobriety. Therefore, alcohol seems to affect several components of HDL and these HDL changes move toward normal at different rates. If alcohol is protective against some cardiovascular disease, it remains to be established whether HDL is involved and which HDL component is most important
Ethanol‐Induced Intrauterine Growth Retardation: Correlation with Placental Glucose Transfer
Authors: Snyder Ann K. , Singh Sant P. , Pulten Gordon L.
Published: June 2007

Placental transfer of glucose and alanine analogs was studied at term in ethanol‐fed and control rats. Etnanol was provided as 30% of the caloric intake throughout gestation. Control groups received isocaloric liquid diet without etnanol by pair‐feeding (PF) or ad libitum (AF). On the 22nd day of pregnancy, the rats were injected with a mixture of [3H] 2‐deoxyglucoe and [14C]α‐aittfnoisobutyric acid. The ratios of f etakmatemal plasma radioactivities 1 hr later were used to compare placental transfer between the groups. Mean ± SE body weight of EF fetuses (4.54 ± 0.07 g) was significantly lower than that of PF (4.88 ± 0.06 g) or AF (5.17 ± 0.09 g) fetuses. Maternal etnanol ingestion reduced placental transfer of 2‐deoxyglucose and a‐ami‐noisobutyric acid by 12% and 35%, respectively. Placental transfer of both analogs was not affected in the PF controls. The weight of EF fetuses correlated (p < 0.001) with transfer of 2‐deoxyglucose to the fetus. This relationship was also found in the control groups. Fetal body weight did not show a strong correlation with a‐aminoiso‐butyric acid transfer. Thus, impaired transfer of glucose to the fetus may play a significant role in the growth retardation observed in fetuses of ethanol‐fed rats.
Effects of Acute and Chronic Ethanol Exposure on the Response of Rat Aorta to a Thromboxane Mimic, U46619
Authors: W. Karanian John , Salem Norman
Published: June 2007

The spasmogenic properties of a stable thromboxane mimic, U46619, were determined in the isolated rat aorta after 1, 4, 8, or 12 hr of acute ethanol exposure in vitro or after 12 days of chronic exposure by inhalation. Acute ethanol exposure (87–822 mm) increased the baseline tension of aortic rings in a concentration‐dependent manner. Moderate concentrations of ethanol (11 and 43 mm) decreased the maximum tensile response of rat aortic rings to U46619 after 8 and 4 hr of exposure, respectively. In contrast, higher ethanol concentrations (87 and 411 mm) did not significantly effect the maximum tensile response to U46619. Ethanol at 822 vm completely inhibited the response to U46619 and this inhibition could be 85% reversed after removal of ethanol. The inhibitory effect of 1.64 Methanol was irreversible. <Sensitivity to U46619 was inversely related to the ethanol concentration (≥43 mm) and incubation time. Similarly, chronic exposure to moderate blood ethanol levels (92–198 mg/100 ml) for 12 days decreased the maximum tensile response whereas high levels did not effect aortic contractility in vitro. Sensitivity of aorta from rats with mean blood ethanol levels ≥92 mg/100 ml decreased at least one order of magnitude. The results suggest that the effect of physiologically tolerable ethanol concentrations on the amplitude of the tensile response to U46619 is Diphasic both during acute exposure in vitro or following a chronic exposure period in vivo and the inhibitory effect on sensitivity for U46619 is both concentration‐ and time‐dependent in the rat aorta preparation.
Dose and Route of Administration Alter the Relative Elimination of Ethanol by Long‐Sleep and Short‐Sleep Mice
Authors: Smoten Andrew , Marks Michael J. , Smoten Toni N. , Collins Allan C.
Published: June 2007

The elimination of ethanol fottowing the intravenous and intraperitoneal administration of five ethanol doses was measured in two mouse lines, the long‐sleep (LS) and short‐sleep (SS), that differ markedly in central nervous system sensitivity to ethanol. Both dose and route of administration affected the relative ethanol elimination in these two mouse Mites. When the ethanol was given Lv., a steady increase in elimination rate was seen in the SS mice as the dose was increased. In the LS mice, consistent changes in rate with dose were not seen. At the lower doses tested, the LS eliminated ethanol more rapidly than did the SS but at higher doses the mouse Kites did not differ. When the ethanol was given i.p., increases in rate with dose were not seen. Rather, the SS elimination rate remained constant as the dose was increased, whereas in the LS a decrease in rate was observed. As consequence, the SS eliminated ethanol more rapidly than did the LS at higher doses. A potential explanation for these results is that ethanol elimination, following the administration of large doses, is affected by both enzymological factors and central nervous system sensitivity to ethanol. The central nervous system factors may be meolated via ethanol‐rnduced hypothermia.
Human Aldehyde Dehydrogenase: Kinetic Identification of the Isozyme for Which Biogenic Aldehydes and Acetaldehyde Compete
Authors: MacKerell Alexander D. , Blatter Erich E. , Pietruszko Regina
Published: June 2007

Michaetis constants and maximal velocities for phenylacetaldehyde (a metabolite of phenylethylamine), 3,4‐dihydroxyphenylacetalde‐hyde (a metabolite of dopamine), 5‐hydroxyindole acetaldehyde (a metabolite of serotonin), and 3,4‐dihydroxyphenylglycolaldehyde (a metabolite of epinephrine and norepinephrine) have been determined for both cytoplasmic (E1) and mitochondrial (E2) isozymes of human liver aldehyde dehydrogenase (EC 1.2.1.3). Kinetic constants with biogenic aldehydes have never been previously determined for individual homogeneous isozymes of aldehyde dehydrogenase from any species. Mathematical treatment of these constants suggests that competition with acetaldehyde during alcohol metabolism would severely inhibit dehydrogenation of biogenic aldehydes with the mitochondrial and not the cytoplasmic isozyme of human liver aldehyde dehydrogenase.
Alcohol Use by Adolescents in Disrupted Families
Authors: Bumside Mary A. , Baer Paul E. , McLaughlin Robert J. , Pokorny Alex D.
Published: June 2007

Alcohol use increases among adults in response to marital disruption and divorce, but data that are available regarding adolescent alcohol use are inconsistent in the light of whether or not families are intact To explore this question we obtained measures of frequency and quantity of alcohol use from 2595 junior and senior high school students, together with information about family intactness and parental alcohol use. Adolescents in single and stepparent families reported more alcohol use than adolescents from intact families, for both frequency and quantity of use. This was the case for boys and for girls, as weH as for junior high school and for senior high school students. Parents in nonintact families also were reported to be using more alcohol than parents in intact families. Adolescent alcohol use was significantly correlated with parental alcohol use. After adjusting adolescent alcohol use for parental alcohol use as a covariate, the finding of greater alcohol use by adolescents in non‐intact families remained.
Equilibration, Distribution, and Elimination of a Single Dose of Intravenous Ethanol in Dogs with Intact Renal Function or Anuria
Authors: Tzamaloukas Antonios H. , Eschbach Robert C. , Jackson Jack E. , Long Debra A.
Published: June 2007

We infused 11 mmol/kg of intravenous ethanol into dogs with either intact renal function (n = 5) or ureteral ligation (n = 7), and studied by frequent blood sampling and by urine collection the time and mode of ethanol equilibration, the elimination parameters, and the comparison of observed equilibrated plasma ethanol levels to levels predicted either by linear or by nonlinear kinetics. Equilibration time was 25 min or less, renal fraction of elimination was less than 5% of total elimination, and both linear (elimination rate) and nonlinear (Vmax, and Km) elimination parameters were not different between dogs with intact renal function and dogs with anuria. Serum sodium concentration did not change throughout the experiments, eliminating the hypothesis that acute ethanol load creates clinically significant temporary osmotic water transfer from the intracellular into the extracellular compartment Distribution volumes of ethanol from linear kinetics were slightly, but not statistically, greater than volumes from nonlinear kinetics. Equilibrated plasma ethanol levels predicted by linear kinetics agreed closely with observed levels greater than 4 mmol/liter, but underestimated observed levels less than 4 mmol/ liter. Equilibrated plasma ethanol levels predicted by nonlinear kinetics agreed with observed levels throughout the range of observed concentrations. The use of linear kinetics to predict blood ethanol levels should be limited to the pseudolinear portion of the blood alcohol curve.
Alcohol Intake and Withdrawal: Effects on Branched Chain Amino Acids and Alanine
Authors: Avogaro Angeto , Cibin Mauro , Croatto Tiziano , Rizzo Alberto , Gallimberti Luigi , Tiengo Antonio
Published: June 2007

The affects of chronic alcohol consumption on plasma branched chain amino acids and alanine concentrations were evaluated, and basal blood concentrations of these amino acids were determined after chronic ethanol intake and following a withdrawal period in 30 admitted alcoholics. After ethanol intake, alcoholics showed increased branched chain amino acid concentrations; the blood alanine concentrations were depressed after the withdrawal period. To evaluate the effect of ethanol on diurnal variations of these amino acids in the blood, a group of these patients underwent two isocaloric diets with and without wine. The diet with alcohol induced a sustained increase of branched chain amino acids persisting even after the postprandial phase with a decrease of alanine as compared to the diet without
Application of Isoelectric Focusing in Immobilized pH Gradients to the Study of Acetaldehyde‐Modified Hemoglobin
Authors: Gordis Enoch , Herschkopf Sybil
Published: June 2007

We applied the technique of isoelectric focusing (IEF) on immobilized pH gradients (LKB) to determine whether acetaldehyde‐modified hemoglobins (Hb) prepared in vitro with unphysiotogical acetalde‐hyde concentrations have clinical relevance. This technique separates proteins with pi < 0.01 and provides detail about hemoglobins not otherwise separable. We performed two kinds of studies. In one kind of study, we incubated red cells from control subjects with acetaldehyde. Products of these incubations were applied to IEF gels either directly or after reduction with sodium cyanoborohydride. Incubation of red cells with acetaldehyde in 1–150 mm concentration without cyanoborohydride reduction yielded hemoglobin bands of decreasing pi the appearance of which coincided with the disappearance of Hb A and Hb A14. When the products of incubation were reduced with cyanoborohydride before IEF, an additional acidic Hb band appeared which we call the “anodal CNBH band.”

In a second kind of study, we compared IEF patterns of hemoly‐sates from control subjects and alcoholism detoxification patients, without adding acetaldehyde. Again, samples were applied to IEF gels either directly or after reduction with cyanoborohydride. When samples were run on IEF without reduction, no differences were seen between patients and controls. When samples were reduced before IEF, an anodal CNBH band appeared having the same mobility as the band seen after in vitro incubations with acetaldehyde. These bands were often stronger in samples from patients, but not consistently so.

Several experiments, including the use of glycolysis inhibitors, indicated that the anodal CNBH band is an adduct of fructose 1,6‐diphosphate with hemoglobin. We suggest that in millimolar concentrations, acetaldehyde may function as an inhibitor of glycolysis at or below the aldolase step.
Acetaldehyde Causes a Prolongation of the Doubling Time and an Increase in the Modal Volume of Cells in Culture
Authors: Wickramasinghe S. N. , Malik F.
Published: June 2007

The effects of curtailing four human cell lines–Raji, MOLT‐4, WI‐L2, and K562–in the presence of 10–360 μM acetaldehyde for 3–18 days have been investigated. Concentrations of 45–360 μ caused a prolongation of the cell doubling time, and those of 90–360 μM caused an increase in the modal cell volume and in the protein content per cell. The results indicate that relatively low concentrations of acetaldehyde cause an impairment of cell proliferation and an abnormality of cell growth in vitro and support the possibility that ethanol‐derived acetaldehyde may be responsible for some aspects of tissue damage in chronic alcoholics, including the increase in the mean cell volume of erythrocytes. Three of the four cell lines studied showed a reduction and the fourth showed no change in modal cell volume after culture with 100 mM ethanol, suggesting that the macrocytosis of red cells induced by chronic alcoholism is not caused via some direct effect of ethanol on the erythron.
The Effect of Ethanol Intake on Propoxyphene Absorption and Biotransformation in Dogs
Authors: Olsen H. , Aune H. , Lilleaasen P. , Gulliksen M. , Bodd E. , Mwland J.
Published: June 2007

The effect of ethanol (0.5 and 1.0 g/kg) on gastrointestinal absorption and presystemic biotransformation of propoxyphene (4 mg/kg) was studied in dogs in a crossover design. Low ethanol doses (0.5 g/kg) had no effect on the bioavailability of propoxyphene. High ethanol doses (1.0 g/kg) enhanced the bioavailability of orally administered propoxyphene significantly (p < 0.05). With this dose of ethanol, the area under the blood concentration versus time curve (AUC)0–5 h of propoxyphene was approximately 200% of the control value. The level of norpropoxyphene, a major metabolite of propoxyphene, was significantly decreased (p < 0.05) after administration of high ethanol doses. In all blood samples, after propoxyphene administration, an unidentified metabolite of propoxyphene was found, which formation was dose dependentJy inhibited by ethanol.
Effects of Dietary Fat on Alcohol‐Pyrazole Hepatitis in Rats: The Pathogenetic Role of the Nonalcohol Dehydrogenase Pathway in Alcohol‐Induced Hepatic Cell Injury
Authors: Takada Akira , Matsuda Yoshiro , Takase Shujiro
Published: June 2007

Rats were fed with two different alcohol‐containing (36% of total calories) liquid diets of high fat and low fat (35% and 15% of total calories) with or without 2 mm of pyrazole for 12 weeks. At the 12th week, the serum glutamic oxaloacetic transaminase level was significantly elevated in the alcohol‐pyrazole high fat group, but not in the low fat group. Ballooning and necrotic changes of the hepato‐cytes in the centrolobular area were more prominent in the alcohol‐pyrazole high fat group than in the low fat group and alcohol atone groups, indicating that high fat diet accelerates the development of alcohol‐pyrazole hepatitis. In the alcohol‐pyrazole high fat group, a decrease of hepatic microtubules content and an accumulation of hepatic export proteins in the hepatocytes were found. The protein accumulation was prominent only in the ballooned hepatocytes. Hepatic acetaldehyde levels were significantly higher in the alcohol‐pyrazole high fat group than in the alcohol‐pyrazole tow fat group. These results suggest that the accelerated ethanol metabolism in the nonalcohol dehydrogenase pathway by a high fat diet may play an important role in the development of hepatocybc injuries, by impairing the microtubular function of the hepatocytes.
Study of Dose‐Dependence and Urinary Folate Excretion Produced by Ethanol in Humans and Rats
Authors: McMartin Kenneth E. , Collins Timothy D. , Shiao Cheng Quei , Vidrine Lori , Redetzki Helmut M.
Published: June 2007

Acute ethanol ingestion by human alcoholic subjects produces a marked decrease in serum folate levels within 16 hr. A similar decrease occurs in rats and can be explained by a marked increase in urinary folate excretion following ethanol treatment To assess the effects of acute ethanol ingestion on urinary folate excretion in healthy human volunteers, two studies were carried out at initial ethanol dose levels of 0.8 g/kg and 1.0 g/kg, respectively. Blood ethanol levels peaked at 70 mg/dl in the first study, but in the second study were 100 ± 20 mg/dl through 6 hr. Only in the second study were urinary folate levels significantly increased by ethanol administration, and this 8 hr after ingestion. This increase was accompanied by a decrease in urine volume so that in neither study was the total amount of urinary folate excreted from 0–12 hr increased by ethanol ingestion. Studies with various dose levels of ethanol in rats showed that there was a linear dose‐response relationship between the total urinary folate excretion and the dose of ethanol. Peak urinary ethanol levels also correlated with urinary folate excretion. These results suggest that doses of ethanol larger than 1.0 g/ kg produce increases in urinary folate excretion and that the inability to observe large increases in studies in human subjects is probably related to the limited doses of ethanol chosen.
Pituitary and Thyroid Hormones in Pregnant Alcohol‐Fed Rats and Their Fetuses
Authors: Lee Melvin , Wakabayashi Katsumi
Published: June 2007

The effect of maternal alcohol consumption on serum and pituitary concentrations of hormones was investigated in pregnant rats and their fetuses. Rats were given 20% ethanol in water prior to pregnancy and 30% ethanol in water throughout gestation, with rat chow ad libitum (alcohol group), or water with an equicaloric diet in which com starch was substituted for alcohol (pair‐fed group), or rat chow and water ad libitum (ad libitum control group). Growth hormone (GH), prolactin (Prl), thyroid‐stimulating hormone (TSH), thyroxine (T4), and triiodothyronine (T) were measured in maternal serum, GH, Prl, and TSH in maternal pituitary, and GH, T4, and Ta in fetal serum. Fetuses of alcohol‐fed rats weighed significantly less than fetuses of pair‐fed or ad libitum controls. GH, Prl, and TSH were significantly reduced in the maternal serum of alcohol and pair‐fed rats compared to ad libitum controls, but T4 and Ta did not differ among the three groups. Pituitary GH was reduced in the alcohol‐fed rats, but pituitary Prl and TSH did not differ among the three groups. In the fetuses, neither GH nor T4 differed among the three groups. Fetal Ta was not detectable by this assay. It is suggested that alcohol ingestion affects maternal growth hormone levels, possibly by influencing either the synthesis or the release of the hormone from the pituitary gland. The other hormonal changes may be the result of the reduced food intake, rather than a specific effect of alcohol.
The Influence of Both Drinking and Familial Risk Statuses on Cognitive Functioning of Social Drinkers
Authors: Alterman Arthur I. , Bridges K. Robert , Tarter Ralph E.
Published: June 2007

Problem and nonproblem drinking, college student sons of alcoholics were compared to problem and nonproMem drinking college student sons of nonalcoholic fathers with respect to cognitive functioning. Problem drinkers performed more poorly on two of the four cognitive tasks, Group Embedded Figures and Symbol‐Digit Paired Associates Learning Task, thus supporting earlier findings of cognitive deficits in problem drinking nonalcoholics. Additionally, sons of alcoholics tended to perform more poorly than sons of nonalcoholic* on the Group Embedded Figures Test Cognitive performance was not predicted by any of four measures of impulsive/antisocial personality and behavior‐preadult antisocial behavior, childhood behavior problems, sensation seeking, and the MacAndrew Alcoholism Scale. The findings of the research pointed to the importance of considering both drinking and familial alcoholism risk statuses in studies of the cognitive performance of nonalcoholics. Further implications and limitations of the findings are discussed.
Effects of Ethanol on Gastrointestinal Transit in Mice
Authors: Scroggs Reese , Abaizzo Michael , Advokat Claire
Published: June 2007

The acute effects of ethanol on gastrointestinal transit were studied in mice, intraperitoneal injection of 2 or 3 g of ethanol/kg had a dose‐dependent inhibitory effect on gastrointestinal transit Subcutaneous injection of 4 g of ethanol/kg also inhibited gastrointestinal transit, but this route was less effective than the intraperitoneal route of administration. Further examination of both the time course of inhibition and the weight of the stomach contents suggested that intraperitoneal injections of moderate doses of ethanol did not alter gastric emptying. The data indicated that gastrointestinal transit is inhibited by ethanol and that the most sensitive locus is the small intestine rather than the stomach.
Depression of Iron Uptake from Transferrin by Isolated Hepatocytes in the Presence of Ethanol Is a pH‐Dependent Consequence of Ethanol Metabolism
Authors: Beloqui O. , Nunes R. M. , Blades B. , Berk P. D. , Potter B. J.
Published: June 2007

Incubation of freshly isolated rat hepatocytes with highly purified radiolabeled rat transferrin in weakly buffered medium in the presence of 10 mM ethanol resulted in a marked diminution of iron uptake by these cells, associated with a greater pH depression than in ethanol‐free control studies. This effect on iron uptake persisted, even when the cells were preincubated for 90 min with ethanol before the addition of transferrin. Increasing the buffering capacity of the system or the addition of a metabolic inhibitor of alcohol dehydrogenase (4‐methylpyrazole) returned iron uptake to control values. Acetaktehyde, acetate, lactate (products of ethanol metabolism), and 3‐butanol (an alcohol not metabolized by alcohol dehydrogenase) had no influence on iron uptake. Further investigation of iron uptake over the pH range 6–8.5 revealed a marked dependency of iron uptake on the extracellular pH. Leucine incorporation into cell protein was also found to be pH dependent ft is suggested that, in the light of current understanding of transferrin recycling by other cell types, the disturbances of iron homeostasis observed in alcoholics can be partially accounted for by alterations in their acid‐base metabolism.
Effects of Acute Ethanol Administration on Neocortical Inhibition
Authors: Ruttedge Lester T. , Chi Shu‐lng , Sutter Mark A.
Published: June 2007

The hypothesis that acutely administered ethanol could interfere with neocortical recurrent inhibition (Rl) was supported. The large surface negative wave in response to antidromic stimulation of the cerebral peduncle represents a summation of inhibitory postsynaptic potentials, a measure of Rl. In acute experiments on adult rats, blood alcohol levels of less than about 120 mg/100 ml slightly facilitated the surface negative wave. Higher blood alcohol levels always blocked the surface negative response. Stimulation of the somatosensory thalamic relay nudei produced a cortical response on which ethanol had a moderate blocking effect Conditioning‐test procedures revealed that cerebral peduncle stimulation strongly blocked the thalamocortical (test) response, especially after ethanol, but thalamic stimulation (conditioning) had no effect upon the surface negative wave. This demonstrates a differential effect on the two cortical processes. Cortical Rl seems to be especially sensitive to blood alcohol level, but the function of cortical Rl is complex. By way of acting on Rl, ethanol likely affects control of sensory input and cortical sensory organization as well as selectivity and magnitude of motor discharge.
Prolonged Feeding of Ethanol to the Young Growing Guinea Pig. III. Effect on the Synthesis of the Myocardial Contractile Proteins
Authors: Schreiber Sidney S. , Reff Francine , Evans Carole D. , Rothschild Marcus A. , Oratz Murray
Published: June 2007

Prolonged ingestion of ethanol may lead to a cardiomyopathy, and studies in the experimental animal have demonstrated alterations in protein metabolism. These changes include depression of protein synthesis with acetakfehyde in the acute experiment, in vitro, and after chronic ethanol ingestion in vivo. The present studies were initiated to see if the inhibition of protein synthesis following prolonged ethanol ingestion involved myocardial contractile proteins. Newly weaned guinea pigs, weighing 350 g, were placed on a regimen of normal laboratory diet with 10% ethanol in the drinking water. Calorie‐matched controls, drinking dextromaltose in the water, were simultaneously run. After 40 weeks of ingesting 10% ethanol in the drinking water, hearts from growing guinea pigs were removed and synthesis of myocardial contractile proteins (myosin heavy chains, light chains (LC1 LC2), actin, and tropomyosin) assayed in vitro with 3H‐labeled amino adds. With aging, there was a decrease in the rates of synthesis of all the contractile proteins. After 40 weeks of ethanol ingestion, the synthetic rates of myosin heavy and light chains and tropomyosin were the same as in calorie‐matched controls, but the synthetic rate of actin was significantly decreased by 20% (p < 0.01). This decrease in actin synthesis may be the first indication of ultimate inhibition of synthesis of all the contractile proteins which may lead to myofibrillar disorganization and vacuolization reported after chronic ethanol ingestion.
Mechanisms of Vitamin Deficiencies in Alcoholism
Authors: Hoyumpa Anastacio M.
Published: June 2007

Chronic alcoholic patients are frequently deficient in one or more vitamins. The deficiencies commonly involve folate, vitamin B* thiamine, and vitamin A. Although inadequate dietary intake is a major cause of the vitamin deficiency, other possible mechanisms may also be involved. Alcoholism can affect the absorption, storage, metabolism, and activation of many of these vitamins. Possible factors which cause alterations in the absorption, storage, and metabolism of these vitamins are discussed. Suggestions for management of vitamin deficiencies in chronic alcoholics are also discussed.
Alcoholism Diagnoses for Convicted Drinking Drivers Referred for Alcoholism Evaluation
Authors: Miller Brenda A. , Whitney Robert , Washousky Richard
Published: June 2007

The types and extent of alcohol‐related problems were determined for a sample of 461 convicted drinking drivers who were referred to an alcoholism treatment facility for evaluation and possible treatment Using responses to questionnaire and structured interview questions on alcohol‐related problems, DSM III diagnoses are constructed; approximately three‐quarters of the sample are diagnosed with sufficient severity for a DSM III diagnosis of abuse or dependence.

Self‐reported consumption levels and drinking/driving incidents increase as the level of the alcohol problem increases; persons in the Alcohol Abuse category are heavier consumers and drive more frequentfy after drinking than are persons who are not diagnosed by the DSM III as having an alcohol problem. Persons in the Alcohol Dependence category are heavier consumers than either the Alcohol Abuse or Undiagnosed Problem categories and report more drinking/ driving incidents.

The DSM III provides useful subcategories of convicted drinking drivers referred for alcoholism evaluation and distinguishes groups differing in quantity, frequency, and self‐reported DWI measures, independent of basic demographics. These analyses suggest that drinking/driving countermeasures should include intervention efforts to address alcohol‐related problems. Serious alcohol problems exist among some drinking drivers, and drinking/driving incidents are more frequent among these individuals.
Electrophysiological Effects of Monoamine‐Derived Aldehydes on Single Neurons in Neocortex and Cerebellum in Rats
Authors: Palmer Michael R. , Tottmar Olof , Dettrich Richard A.
Published: June 2007

The electrophysiological effects of aldehydes derived from several monoamines were studied on single neurons m the cerebellum and neocortex of rats. The aldehydes derived from dopamine (3,4‐dihy‐droxyphenylacetaldehyde) and serotonin (5‐hydroxy‐3‐acetalde‐hyde) were prepared as stable disutfite complexes, from which free aldehydes were extracted. Serotonin and S‐hydroxy‐3‐acetaMehyde caused pronounced depression of firing rates both of cerebellar Purkinje neurons and neurons in prefrontal cortex. When locally applied from muHibarrel micropipettes by pressure ejection, 5‐hy‐droxy‐3‐acetaldehyde was twice as potent in the neocortex as in the cerebellum, and was equipotent with serotonin in both brain areas. The aldehyde of tryptamine also caused depressions of neuronal activity in cerebellum, but only at 5‐fold higher doses than were effective for 5‐hydroxy‐3‐acetaldehyde. 3,4‐Dihydroxyphen‐ylacetaldehyde was without effect in prefrontal cortex, but had mixed responses in the cerebellum. The results show that monoamine‐derived aldehydes are physiologically active. It is possible that changes in the steady state level of these aldehydes caused by drugs such as ethanol and barbiturates might influence the electrophysiological properties of neurons in the central nervous system.
Clonal Response to Ethanol of Proliferating Rat Hepatoma Cells in Vitro
Authors: Cook Robert T. , Martin Gail S.
Published: June 2007

We have grown HTC cefls (ascites variant of Morris hepatoma 7288c) Hi spinner cultures in the presence of various concentrations of ethanol, both in short‐term incubations and in chronically exposed cultures. In short‐term exposures cell proliferation is decreased in a dose‐related fashion, falling to approximately 25% of control values at 35 mM ethanol. tot reted cultures maintained at ethanol concentrations gradually increased to 17 mM, there is an initial decrease in proliferation followed by stabilization. Comparison of the growth patterns of ceHs chronically exposed to ethanol with the growth patterns of unctoned naive ceHs suggests the presence of both ethanol‐sensitive and ‐resistant HTC cell clones. Preliminary cloning experiments have been successful in demonstrating that HTC clones do exist which have widely varying responses to ethanol. Clones have been isolated which are growth‐inhibited by low concentrations of ethanol whereas others are resistant or even stimulated in the same concentration range. The critical differences between ethanol‐sensitive and ‐resistant HTC cells are currently unknown, but the general phenomenon of clonal selection during chronic ethanol exposure is of interest in the pathogenesis of alcohol‐related diseases.
The Effect of 5,5‘‐Dithiobis(l‐methyItetrazole) on Cytoplasmic Aldehyde Dehydrogenase and Its Implications for Cephalosporin‐Alcohol Reactions
Authors: Kitson Trevor M.
Published: June 2007

Cephalosporin antibiotics with a 1‐methyttetrazofe‐5‐thio side chain have the ability to cause an unpleasant flushing reaction if they are taken some time before the drinking of alcohol. It is proposed that the explanation for this is that the side chain becomes liberated In vivo and oxidized to 5,5dithiobis(1‐methyttetrazole) or to a mixed disulfide analogue which then inactivates aldehyde dehydrogenase. Support for this proposal is given by the results below concerning the interaction in vitro between the disulfides and sheep Hver cytoplasmic aldehyde dehydrogenase. 5,5Dithiobis(1‐methy!tetrazo!e) has a rapid and pronounced macthratory effect, very similar in many ways (though not identical) to that of disulfiram, to which K has a structural similarity. (Disulfiram is widely used therapeutically to deter alcoholics from drinking.) 1‐Methyl‐5‐methytthiotetrazole (which is a simple model of the antibiotics) and the free 1‐methyfte‐trazole‐5‐thiol have no effect on the enzyme in vitro,> but methyl 5‐(1‐methyftetrazoiyl) disulfide is a potent inactivator, this also supports the proposed pathway.
Disulfiram‐Ethanol Reaction in the Rat. 1. Blood Alcohol, Acetaldehyde, and Liver Aldehyde Dehydrogenase Relationships
Authors: Jensen J. Chris , Faiman Morris D.
Published: June 2007

Studies were carried out to determine whether the disuifiram‐ethanol reaction (DER) in the rat could be correlated with blood acetaldehyde, ethanol, and liver aldehyde dehydrogenase (ALOH) inhibition. Both hypothermia and hypotension were used as indices of the DER. Female Sprague‐Dawley rats were given disulfiram (DSF) (100 mg/ kg, i.p.) and low and high liver ALDH determined. No effect on high Km ALOH was found. Inhibition of low K. ALOH was dependent on DSF pretreatment time, with significant inhibition observed at 6, 8, and 12 hr following DSF. in rats receiving ethanol only, maximal blood ethanol was reached within 120 min. Blood acetaldehyde was almost undetectable. No change in rat core temperature was observed. In rats pretreated with DSF (100 mg/kg, i.p.) 8 hr before ethanol challenge (1 g/kg, i.p.), a marked increase in Mood acetaldehyde was found and remained elevated throughout the temperature and blood pressure monitoring period. Blood ethanol reached a maximum within 90 min and then declined. Maximal hypothermia and hypotension occurred 120 min after ethanol. The administration of the dopamine receptor blocker pimozide (0.5 mg/kg, i.p.) 60 mm before ethanol challenge, attenuated the hypothermia and hypotension. Pimozide was effective when given either 60 min before ethanol or 30 min after ethanol. The onset and duration of hypothermia and hypotension during the DER appears to follow the rise and faU of blood ethanol but not blood acetaldehyde. It is concluded that in the rat, although DSF inhibited low Km ALDH and increased blood acetaldehyde, the severity of the DER was not related to Mood acetaldehyde, but appears to temporally correlate with Mood ethanol, and that brain dopamine and the dopamine receptor may be implicated in the DER.
The Effects of Physostigmine on Open‐Field Behavior in Rats Exposed to Alcohol Prenatally
Authors: Riley Edward P. , Barron Susan , Driscoll Cynthia D. , Hamlin Robert T.
Published: June 2007

The present study examined the effects of physostigmine, a chofin‐esterase inhibitor, on activity in young rats whose mothers consumed isocaloric liquid diets containing 35% or 0% ethand‐derived calories on days 6–20 of pregnancy. A pair‐feeding procedure was utilized and an ad libitum lab chow group was included. Physostigmine was administered to 18‐day‐oM offspring on 3 consecutive days with activity measures recorded for 30 mm each day. Injections of physostigmine produced significant reductions in activity in alcohol‐exposed offspring relative to control groups. These results provide support for a functional cholinergic deficit in offspring exposed to alcohol in utero and may have relevant clinical implications in the treatment of atterrtional deficit disorder which can occur following prenatal alcohol exposure.
Alcohol Use Patterns of First‐Year Medical Students: II. Psychosocial Characteristics Associated with Drinking Level
Authors: Clark David C. , Daugherty Steven R. , Zeldow Peter B. , Eckenfels Edward J. , Silverman Cathy M.
Published: June 2007

Psychosocial characteristics that identified first‐year medical students who drank more or less alcohol than their peers were examined. Subjects were 116 freshman medical students (96% of one class) who completed questionnaires about alcohol use, mood, personality, social relationships, and parental alcohol abuse on the first day of school, and 106 (88% of the class) who responded to the same questionnaires in April of the first year. Heavier drinking students (i.e., the upper 25% of the sample) were more likely to be male and single, to have drunk heavily prior to medical school, to come from larger social networks which include fewer relatives, and to demonstrate a lower interpersonal orientation. Mood, academic performance, and parental alcohol abuse were not associated with drinking level. The heaviest drinkers in this sample appear to be precisely those individuals who are most impervious to peer or other social influences.
Low‐Level Hyperbaric Antagonism of Ethanol‐Induced Locomotor Depression in C57BL/6J Mice: Dose Response
Authors: Bejanian M. , Jones B. L. , Alkana R. L.
Published: June 2007

This study characterized the antagonistic effects of hyperbaric exposure on the dose‐response curve for ethanol‐induced depression of locomotor activity. Drug‐naive, male C57BL/6 mice were injected intraperitoneally with saline, 1.5, 2.0, 2.5, or 3.0 g/kg ethanol, and were exposed to 1 atmosphere absolute (ATA) air or 12 ATA helium‐oxygen gas mixtures (heliox) at temperatures that offset the hypothermic effects of ethanol and helium. Locomotor activity was measured 10‐30 min after injection. In addition, the effects of exposure to 12 ATA heliox on blood ethanol concentrations were tested in a separate group of mice injected with 2.5 g/kg ethanol. Ethanol produced a dose‐dependent depression of locomotor activity beginning at 2.0 g/kg. Exposure to 12 ATA heliox completely antagonized the locomotor depressant effects of 2.0 and 2.5 g/kg ethanol and partially blocked the effects of 3.0 g/kg. Activity in mice given 1.5 g/ kg ethanol was not significantly affected at 1 ATA air, but was significantly increased at 12 ATA heliox. Low‐level hyperbaric exposure shifted the ethanol dose‐response curve to the right with a resultant increase in the ED50 of ethanol for locomotor depression from 2.6 to 3.3 g/kg. Exposure to 12 ATA heliox did not alter blood ethanol concentrations in mice injected with 2.5 g/kg ethanol. These findings with 12 ATA heliox present key new evidence for the hypothesis that low‐level hyperbaric exposure acts directly, with a pattern analogous to a competitive, mechanistic antagonist of ethanol.
Acute Interactions Between Cytokines and Alcohol on ACTH and Corticosterone Secretion in the Rat
Authors: Rivier Catherine
Published: June 2007

Possible interactions between alcohol (EtOH) and interleukins (ILs) were studied in intact and adrenalectomized (ADX) rats. In intact animals, administration of 0.3 or 0.65 g EtOH/kg 30 min to 4 hr earlier did not cause measurable changes in plasma adrenocorticotropic hormone (ACTH) levels measured immediately before acute intravenous injection of IL‐1β or endotoxin [lipopolysaccharide (LPS)], and did not interfere with the ability of either treatments to increase ACTH secretion. Administration of 1.5 g EtOH/kg, on the other hand, resulted in elevated plasma ACTH and corticosterone 30 min later, and significantly decreased the magnitude of the ACTH response to IL‐1β in both intact and ADX rats. When administered 4 hr before the cytokine, however, 1.5 g EtOH/kg did not alter the responsiveness of the hypothalamic‐pituitary‐adrenal (HPA) axis to IL‐1/3. Studies of the reverse paradigm were conducted in rats injected with LPS, a means of increasing endogenous IL‐1 levels. Intraperitoneal administration of alcohol 4 hr later resulted in measurably blunted ACTH release by intact rats, but not ADX animals.

We conclude that when prior alcohol administration does not result in elevated ACTH levels at the time of IL‐1 injection, no alteration in the HPA axis' response to the cytokine is observed. As we have shown in other experiments that circulating levels of corticosterone were temporarily increased by all doses of alcohol used in the present study, these results suggest that steroid feedback did not play a major role in modulating the ability of IL‐1β to activate the HPA axis. In contrast, prior exposure to endotoxin 4 hr earlier blunted the subsequent effect of an acute injection of alcohol. This effect was probably mediated through corticosteroid feedback, because it was absent in ADX rats. Thus the order in which alcohol and cytokines are administered, and/or the time frame that separates the two treatments, appears to be important in determining whether these stimuli can influence each other's ability to activate the HPA axis.
Diminution of Biological Reactivity of Ethanol by Changing the Solution Structure by Weak Ultrasonication
Authors: Haseba Takeshi , Matsushita Kazuhiro , Asakura Toshihiro , Kameyama Kouji , Tamaki Takeshi , Okouchi Shoichi , Watanabe Tokinori , Uedaira Hisashi
Published: June 2007

The weak ultrasonication (40 kHz, 12 mW, 1 week) of ethanol solutions was found to reduce stimulation of the senses of smell and taste by the ethanol on the basis of blind tests with an aqueous ethanol solution (33.0% w/v) and an immature distilled spirit (25.0% v/v). Experiments on mice also demonstrated that a treated aqueous ethanol solution had a weaker depressant effect on the central nervous system, as evaluated by the relative frequency with which mice regained the righting reflex at a dose of either 4.0 or 4.5 g/kg (p < 0.05 or p < 0.01, respectively) and by the reduction in rectal temperature at a dose of 5.0 g/kg (p < 0.05) soon after ethanol administration.

Analyses of both the ethanol concentration by head‐space gas chromatography and the free radicals by electron spin resonance spectrometer failed to reveal any chemical changes in aqueous ethanol solutions subjected to weak ultrasonication. However, measurement of the spin‐lattice relaxation time (7'i) of the 2H of water molecules by 2H‐NMR showed that the treatment slightly accelerated the thermal motion of water molecules in the solutions. Treated solutions were also found to have a slightly higher density than untreated ones. These physical data demonstrate that weak ultrasonication induces a structural change, such as a more compact and homogeneous structure by changing the microdynamic behavior of the solution. These biological and physical studies suggest that only a slight structural change in an ethanol solution induces a marked change in the biological reactivity of ethanol without any chemical modification of the solution itself.
Ethanol‐Induced Changes in Astrocyte Gene Expression during Rat Central Nervous System Development
Authors: Fletcher Tara L. , Shain William
Published: June 2007

Disruption of spatial and temporal patterns of gene expression in cells of the developing brain could result in abnormal development. We report that briefly exposing neonatal rats to a moderate dose of ethanol on postnatal days 5 through 7 caused a large, specific increase in glial fibrillary acidic protein (GFAP) mRNA and GFAP. Astrocytes of the cerebral cortex were apparently more sensitive to this effect of ethanol than astrocytes in several other brain regions. As a first step in the characterization of an in vitro model of ethanol's effect on GFAP gene expression, ethanol was added to the media of primary cultures of cortical astrocytes in a pattern of exposure and at concentrations equal to pups' peak blood levels. This resulted in an increase in GFAP mRNA whose magnitude and specificity mirrored that observed in the animal model. Together, these results suggest that even brief exposure to ethanol can alter gene expression in astrocytes, and forms the foundation for further characterization of an in vitro model that may be used to determine the mechanism of this effect.
Effect of Exposure to an Alcohol Diet for 10 Days on the Ability of Interleukin‐1β to Release ACTH and Corticosterone in the Adult Ovariectomized Female Rat
Authors: Lee Soon , Rivier Catherine
Published: June 2007

Adult ovariectomized female rats were fed an alcohol diet for 10 days. Animals fed ad libitum, or fed an isocaloric diet (pair‐fed), were also included in all experiments. The intravenous injection of interleukin‐β caused dose‐related increases in plasma adrenocorticotropic hormone (ACTH) levels in all three groups of rats. However, alcohol‐fed animals showed a significant blunting of their ACTH, but not corticosterone response, in comparison with rats fed ad libitum or pair‐fed. In contrast, corticotropin‐releasing factor (CRF) injection caused overall statistically comparable ACTH secretory rates in all animals, although small differences were observed in some cases. Exposure to mild electroshocks for 30 min significantly increased ACTH values in all animals, but alcohol‐fed rats again showed blunted release. In this paradigm, pair‐fed animals exhibited a response that was intermediate between that of the ad libitum and alcohol‐fed groups.

We conclude that chronic alcohol consumption decreases the response of the hypothalamic‐pituitary axis to cytokines and mild footshocks. This suggests that the activity of both CRF nerve terminals in the median eminence, and of CRF perikarya in the hypothalamus, is inhibited by this treatment, although pituitary responsiveness to CRF appears unchanged.