bluuebunny/crossref_metadata_2025 huggingface dataset:
The Effect of Age on Ethanol Metabolism and on the Hypothermic and Hypnotic Responses to Ethanol in the Fischer 344 Rat
Authors: Ott Janet F. , Hunter Bruce E. , Walker Don W.
Published: February 2008

The hypothesis that the central nervous system (CNS) of aged rats is more sensitive to acute ethanol effects was examined by measuring ethanol elimination rates, and the hypothermic and hypnotic responses to ethanol In four age groups (3,12, 21, and 30 months) of Fischer 344 rats. Following a 2.5 g/kg Intraperftoneal dose of ethanol, rectal temperature and blood ethanol concentration (BEC) were measured at regular intervals for 8 hr. The 30‐month group's hypothermic response to ethanol was equivalent to the 3‐month group's despite lower peak BEC. Response to a hypnotic dose (3.0 g/kg) of ethanol was evaluated by measuring the time for regain of righting reflex (RORR) and the BEC at RORR. The 3‐month group slept for a shorter time, and awoke at a higher BEC, than the 12‐ or 21‐month groups. The response of the 30‐month group was more complex. Although this group had the lowest BEC at RORR, their sleep time was equivalent to the 3‐month group. The shortened sleep time of the 30‐month group Is consistent with the observation of significantly lower peak BEC and higher metabolic rate (calculated from Widmark r values) in this group. Thus, aged rats of the Fischer 344 strain may be more sensitive to acute ethanol, but these CNS effects may be partially offset by enhanced ethanol disposition at older ages.
Ethanol Oxidation by Hydroxyl Radicals: Role of Iron Chelates, Superoxide, and Hydrogen Peroxide
Authors: Feierman Dennis E. , Winston Gary W. , Cederbaum Arthur I.
Published: February 2008

Oxygen‐derived free radicals such as the hydroxyl radical (OH) have been shown to mediate the oxidation of ethanol by a variety of oxy radical‐generating systems. Among these are microsomal electron transport systems (both intact and purified, reconstituted systems), the coupled oxidation of hypoxanthine or xanthine by xanthine oxidase, and the model ironascorbate system. The sequence of reactions leading to the oxy radical‐dependent oxidation of ethanol as was as other hydroxyl radical‐scavenging agents by these various systems is believed to proceed through the formation of a common intermediate, namely, hydrogen peroxide (H2O2), after disrmitation of the superoxide anion radical (O2−). The presence of iron, especially chelated iron, greatly enhances the production of OH by serving as an oxidant for O2− or a reductant for H2O2 Experiments were carried out to evaluate the role of iron, the chelating agent, 02−, and H2O2 in the oxidation of ethanol by a variety of in vitro systems (chemical, enzymatic, and intact membrane bound) that can produce oxy radicals via different mechanisms. The generation of OH by aN the systems studied was sensitive to catalase, which indicates that H1O2 is the precursor of OH. Superoxide radical appears to be the reducing agent in the hypoxanthine‐xanthine oxidase system, indicating an iron‐catalyzed Haber‐Weiss reaction. In the ascorbate, reductase, and microsomal systems, superoxide radical does not appear to be the reducing agent However, superoxide radical probably is the precursor of H*0. While iron plays an important role in the production of OH by the various systems, the effect of iron depends on the nature of the iron chelate. For example, ferric‐EDTA is always stimulatory, whereas desferoxamine is always inhibitory. Certain iron chelates work in one system but not in another. In the reductase‐dependent systems, only those iron chelates that stimulated NADPH oxidation stimulated OH scavenger and ethanol oxidation. These data suggest that the ability of iron to promote OH production and ethanol metabolism depends on the nature of the system which must take into account the reductant, the chelating agent, and the OH scavenger employed. Hence, the role of iron as a mediator of oxidative processes is complex, and further studies will be required in order to understand the role of iron and, in particular, physmlogicalry relevant iron chelates in promoting lipid peroxidation and the production of oxy radicals, and the interaction of ethanol with oxygen radicals derived from various systems.
Hypertension Associated with Alcohol Withdrawal: Assessment of Mechanisms and Complications
Authors: Clark Luther T. , Friedman Howard S.
Published: February 2008

Two hundred and fifty‐six consecutive alcoholics admitted for detoxification, but not having delirium tremens, were evaluated for hypertension. Thirty‐three per cent (84) of the alcoholics had a blood pressure ≥ 160/95 mm Hg on or within 72 hr of admission. In 71% (60 of 84) of alcoholics with hypertension, pressure elevation was transitory, whereas 29% (24 of 84) required therapy. After 4 to 5 days of abstinence, alcoholics with transitory hypertension, whose blood pressure was no longer elevated, had a larger increment of pressure (p amp;lt; 0.001) with a cold pressor test than did normotensive alcoholics. Hypertensive alcoholics were older and tended to use greater amounts of alcohol, but their liver enzymes, alcohol levels on admission, and serum magnesium concentrations did not distinguish them from normotensive alcoholics. Basal plasma renin activity and epinephrine were elevated in both hypertensive and normotensive alcoholics, whereas plasma norepinephrine was normal. Although plasma renin activity (4.08 ± 0.9 vs. 2.88 ± 0.4 ng/ml/hr) and epinephrine (138 ± 17 vs. 108 ± 28 pg/ml) were higher in alcoholics with hypertension than in normotensive alcoholics, differences were not significant. However, elevated plasma epinephrine was found in 86% of alcoholics with hypertension, whereas only 44% of normotensive subjects had elevations (x2= 5.49; p = 0.01). Although alcoholics with hypertension demonstrated an exaggerated catecholamine response with the cold pressor test, these changes per se did not explain the elevations in blood pressure. Thus, a transitory, reactive form of hypertension associated with increased catecholamines and vascular hyperresponsiveness is present in alcoholics.
Differential Effect of Ethanol Consumption on Hamster Liver Microsomal Electron Transport Systems
Authors: McCoy G. David , Lobel Peter , DeMarco George J.
Published: February 2008

The effect of 28‐day ethanol consumption on hamster liver microsomal electron transport systems and associated enzymatic activities has been examined. Microsomes isolated from ethanol‐consum‐ing hamsters showed increased levels of cytochrome P‐450 and NADPH supported enzymatic activities. In contrast, reductions in the amount of cytochrome bs and the NADH‐supported rate of stearoyl‐CoA desaturase were observed. NADH‐cytochrome c reductase was decreased while a small increase in NAOH‐ferricyanide reductase was observed. These data suggest that decreased stearoyl‐CoA desaturase activity is the result of lowered cytochrome bs levels in microsomes isolated from ethanol‐consuming hamsters.
Alcoholism and Affective Disorder
Authors: Bedi Ashok R. , Halikas James A.
Published: February 2008

From January to November 1980, 421 consecutive new patient admissions to a large alcohol treatment facility were interviewed and diagnosed using the Affective Disorder Section of the Research Diagnostic Criteria. The patient population was divided into two groups based on the presence of an affective disorder diagnosis. The groups identified at the highest risk for concurrent affective disorder among alcoholic inpatients were females ages 20 through 30 and not presently married individuals. Implications of these findings are further discussed.
Sensitivity of Individual Erythrocyte Membrane Phospholipids to Changes in Fatty Acid Composition in Chronic Alcoholic Patients
Authors: Droitte Philippe La , Lamboeuf Yves , Blanquat Georges de Saint , Bezaury Jean‐Pierre
Published: February 2008

The erythrocyte membrane levels of total phospholipids and cholesterol and the fatty acid composition of individual groups of phospholipids (phosphatjdylethanolamine, phosphatidylserine plus phospha‐tidylinositol, and phosphatidylcholine) were studied in 10 patients admitted for ethanol detoxification and in 14 control subjects. The fatty acid composition of the patient phospholipids was modified but the level of cholesterol and the level of phospholipids remained unchanged. The fatty acid changes were mainly confined to phosphatidylcholine. The modifications concerned the levels of the oc‐tadecenoic acids (18:1) which rose (p < 0.01), and linoleic acid (18:2) which fell (p < 0.05). These results suggest that chronic ethanol ingestion may perturb the cell membrane organization with, in consequence, possible effects on cell morphology and functions.
Cerebral Dysfunction in Alcoholism Related to Mortality and Long Term Social Adjustment
Authors: Berglund Mats
Published: February 2008

All 1312 first‐admitted alcoholics at the Department of Psychiatry, University Hospital, Lund (120 women) during1949–1969 were followed until December 31,1980. There were 537 deaths. All patients had been rated at discharge with a multidimensional rating scale including signs of cerebral dysfunction. Thirty‐three per cent of the total patient group had signs of cerebral dysfunction, increasing with age up to 64% in those over 50 years. Men younger than 50 years with brain dysfunction had a higher mortality caused by alcohol‐related physical disorders in relationship to violent deaths compared with the others. The main finding in those over the age of 50 was the increased number of deaths caused by circulatory disorder in the brain dysfunction group. The social prognosis was similar in all groups. It is suggested that a continuous and heavy drinking pattern in the young dysfunctional group and an accelerated aging in the old dysfunctional group could explain the differences found.
Psychological Correlates of Drinking Behavior in Social Drinker College Students
Authors: Jones‐Saumty D. J. , Zeiner A. R.
Published: February 2008

Psychological adjustment, cognitive functioning, and drinking behaviors have been shown to discriminate between alcoholic and control populations. Few data exist on the discriminatory power ol such measures among social drinkers differing on alcohol intake level. The purpose of this study was to assess the relationship between alcohol consumption and psychological/cognitive functioning in a group of social drinker college students made up of equal numbers of mates and females, matched on age and education, and varying on amount of alcohol consumed per drinking episode. Results indicate no relationship between alcohol consumption and cognitive functioning in this group of social drinkers. Drinking and psychological profiles of heavy social drinkers were very similar to those of diagnosed alcoholics and very dissimilar to light social drinkers. Such a finding suggests that these types of profiles may have predictive value for identifying at‐risk social drinkers in the general population.
An Animal Model for Low Dose Ethanol‐Induced Locomotor Stimulation: Behavioral Characteristics
Authors: Erickson C. K. , Kochhar A.
Published: February 2008

The present paper describes a rat strain, Maudsley reactive (MR/N), which dramatically and reliably shows enhanced locomotor stimulation in an openfield apparatus after low doses of ethanol. Other strains, Sprague‐Dawley and Wistar inbred, do not show stimulation, whereas Maudsley nonreactive rats show a less dramatic and variable response to ethanol, compared to the MR/N strain. Female MR/ N rats show greater stimulation than male MR/N rats, and the response it dose‐, age‐, and apparatus‐related. We conclude that low dose ethanol‐induced locomotor stimulation in the MR/N rat strain could be a valuable rodent model for studying central neurochemical correlates of alcohol intoxication.
Persistence of Depression in Detoxified Alcoholics
Authors: Overall John E. , Reilly Edward L. , Kelley James T. , Hdlister Leo E.
Published: February 2008

Although many alcoholics appear depressed upon entry into an alcoholism treatment program, the depressive features tend to disappear in most cases after only a few weeks of sobriety in an appropriate treatment setting. This report is concerned with understanding factors that mediate for persistence of depression in some detoxified alcoholics. Among four relatively independent aspects of alcohol‐related behavior measured by the Drinking Behavior Interview, only one factor, that related to disruption in close personal relationships, was found to correlate significantly with level of self‐reported depression at the end of a 4‐week treatment program. These results and those from a previous study are discussed in terms of the loss of social support
Application of a High Performance Liquid Chromatography Method for Screening of Aldehyde Dehydrogenase Isozyme Deficiency in Hair Roots from Different Ethnic Groups
Authors: Tottmar Olof , Nilsson Goran , Spuhler Karen P. , Petersen Dennis , Little Roger , Deitrich Richard A.
Published: February 2008

A sensitive high performance liquid chromatography method has been used to measure aldehyde dehydrogenase (ALDH) activity in hair roots from Caucasian and Japanese subjects. Kinetic studies confirmed previous isoelectric focusing results that hair roots from Caucasians have two forms of ALDH, one low K. form and another high Km form, white hair roots from Japanese individuals who show a flushing reaction after ethanol intake lack, or have low activity of, the low Km form. By taking the ratio of the activities measured at a low (3 μm) and a high (75 μM) concentration of the substrate (3,4‐dihydroxyphenylacetaldehyde), a suitable index for ALDH deficiency was obtained. The ratio varied between 1.6 and 3.5 for Caucasians and between 7 and 23 for Japanese flushers, and it was 2.5 for a Japanese nonflusher. The current method allows a more quantitative and qualitative assessment of the ALDH isozyme pattern in hair roots than that obtained with the isoelectric focusing technique.
Perception of Pregnancy and Social Support as Predictors of Alcohol Consumption during Pregnancy
Authors: Stephens Cheryl J.
Published: February 2008

Although an association between alcohol consumption during pregnancy and adverse fetal outcomes has been well documented, variables related to alcohol consumption during pregnancy have remained neglected. Since pregnancy has been considered a time of crisis and stress for pregnant women, this study sought to determine the association of perceptions of pregnancy and social support to alcohol consumption during pregnancy. The 311 Southern metropolitan prenatal patients sampled were interviewed twice during pregnancy. Perception of pregnancy was not found to be correlated with either social support or alcohol consumption during pregnancy. Social support was significantly associated with decreased alcohol consumption during pregnancy. Using standard multiple regressions, two components of social support, general support and pregnancy support, were found to be working in opposite directions prior to pregnancy, with general support showing a positive association with alcohol consumption. Only pregnancy support continued to account for a significant amount of the variance in alcohol consumption during the first 4 months of pregnancy. Pregnancy support, additionally, showed a significant negative association with high maximum drinking (consuming five or more drinks on occasion) prior to pregnancy. These findings suggest that social support may be an important predictor of alcohol consumption both prior to and during pregnancy and merits further investigation.
Effects of in Utero Exposure to Alcohol upon Male Rats
Authors: Udani Mahendra , Parker Stephen , Gavater Judith , Thiel David H. Van
Published: February 2008

Ethanol ingestion by pregnant women can result in the development of the fetal alcohol syndrome in their progeny. To investigate the late consequences of maternal ethanol ingestion upon male progeny, pregnant dams were administered ethanol‐containing liquid diets from the 12th day of gestation to 10 days postpartum and their male progeny were compared to those of offspring obtained from dams isocalorically fed a liquid diet without alcohol in which Dextri‐MaKose isocalorically replaced the ethanol of the ethanol‐containing diet and those of dams fed a standard rat chow ad libitum. A significant decrease in body weight at birth (p < 0.0001), at weaning, and at 55 days of age (postpuberty) (p < 0.005) was found for the in utero ethanol‐exposed animals as compared to that of the animals obtained from the two control groups. Anogenital distances and indices (measures of masculinity) in the male progeny were reduced (p < 0.001) on days 1 and 5 in the alcohol‐exposed animals as compared to those of the two control groups. Testes and prostate‐seminal vesicle weights of the alcohol‐exposed animals were reduced on day 55 (p < 0.05) and again on day 110 (p < 0.01) as compared to those of the two control groups. Similarly, serum testosterone and luteinizing hormone levels were reduced significantly on day 55 (p < 0.05) in the alcohol‐exposed animals but not in the controls. No difference was noted at 110 days of age in testosterone and LH (luteinizing hormone) levels between the various groups. However, sexual motivation and performance were reduced in the alcohol‐exposed animals as compared to that of the two control groups. These data suggest that in utero alcohol exposure of male rats results in less phenotypic masculinization at birth and reduced growth of the testes, prostate, and seminal vesicles, a delayed attainment of adult levels of tetosterone and LH, and abnormalities of adult sexual behavior.
Pup‐Induced Maternal Behavior in Adult and Juvenile Rats Exposed to Alcohol Prenatally
Authors: Barron Susan , Riley Edward P.
Published: February 2008

The effects of prenatal alcohol exposure on pup‐induced maternal behaviors were examined in virgin rats whose mothers consumed liquid diets containing either 35 or 0% ethanol‐derived‐calories (EDC) on days6–20 of gestation. A pair‐feeding procedure was utilized to control for reduced caloric intake and, in addition, an ad libitum lab chow group was included to control for possible liquid diet effects. The results from experiments 1 and 2 revealed a sexually differential effect on this behavior in adult virgins exposed to alcohol in utero. Adult 35% EDC females showed a variety of deficits in maternal behaviors relative to controls; however, males with similar prenatal treatment appeared unaffected. In experiment 3, both 35% EDC male and female juveniles displayed altered maternal behaviors relative to controls. These results demonstrate yet another behavior sensitive to prenatal alcohol exposure. Prenatal hormonal alterations occurring as a consequence of maternal alcohol consumption may be a mechanism by which this long term behavioral effect is observed. This hypothesis and the importance of future research in this relatively new area of fetal alcohol studies are discussed.
Indomethacin Pretreatment Blocks the Effects of High Concentrations of Ethanol
Authors: Collins Allan C. , Gilliam David M. , Miner Lucinda L.
Published: February 2008

Previous reports from our laboratory have indicated that the responses to ethanol following intraperitoneal (i.p.) injection increase as the concentration of the ethanol solution increases. We have also presented evidence which indicates that pretreatment with drugs such as indomethacin (a prostaglandin synthetase inhibitor) decreases the response of mice to ethanol injected i.p. The results reported here corroborate our earlier findings in that the sleep time response of C57BL and DBA mice was greater following injection with a 40% (w/v) ethanol solution than that seen following i.p. injection with a 20% (w/v) ethanol solution. The increase in sleep time does not appear to be due to alterations in the rates of absorption or elimination of ethanol. Pretreatment with indomethacin reduced sleep time in those animals injected with the 40% solution but was without effect in the animals injected with the 20% solution. Both C57BL and DBA mice pretreated with indomethacin exhibited an increase in waking blood and brain ethanol, an indicant of altered central nervous system sensitivity. In addition, both DBA and C57BL mice exhibited an increase in the linear rate of ethanol elimination if pretreated with indomethacin before injection with the 40% ethanol solution. Indomethacin did not affect ethanol elimination rates of animals injected with the 20% ethanol solution. These data indicate that high concentrations of ethanol when injected into the peritoneal cavity promote the production of prostaglandins which serve to enhance the behavioral response to ethanol. This enhancement may be due to altered pharmacokinetics as well as central nervous system effects.
Association between Low Plasma Tryptophan and Blackouts in Male Alcoholic Patients
Authors: Branchey L. , Branchey M. , Zucker D. , Shaw S. , Lieber C. S.
Published: February 2008

Alcohol has been observed to alter various aspects of memory function. Some of the most extreme forms of memory impairment experienced by alcoholics are blackouts. There are at present very few data on the biological mechanisms underlying alcohol‐related memory impairment A variety of mechanisms including the cholinergic and catecholaminergic systems have been implicated in learning and memory. More recently, however, the importance of the serotonergic system in memory function has been demonstrated. We investigated whether patients with a history of blackouts had lower plasma levels of the serotonin precursor tryptophan than patients without such a history. Tryptophan values were significantly lower in patients who had experienced blackouts than in patients who had not No significant differences between the two group of patients were observed for other amino adds sharing with tryptophan the same transport carrier into the brain. Drinking history variables did not differentiate among the two patient groups. Our data suggest that a decrease in plasma tryptophan (and concomitant lowered brain serotonin) could increase the vulnerability of certain individuals to manifestations of various aspects of memory impairment mdudrng one of its most extreme forms, the blackout
The Antagonistic Placebo Response to Alcohol Cues
Authors: Newlin David B.
Published: February 2008

The classical conditioning model of drug tolerance makes a strong prediction of an antagonistic placebo response, or a placebo response that is opposite in direction to the effect of alcohol. In an initial experiment, 85 normal social drinkers consumed near beer (0% alcohol) while autonomic measures were recorded continuously. Subjects who reported mild intoxication (n= 11) showed a significant decrease in heart rate from predrinking baseline compared to subjects who did not report intoxication (n= 57). In a replication study with a suitable control group, subjects who received near beer and reported mild intoxication (n= 8) showed a significant heart rate and electrodermal response opposite in direction to the autonomic effects of alcohol compared to a control group that received a soft drink (n= 10). The antagonist placebo response challenges current conceptualizations of placebo responding, and has implications for classical conditioning theories of alcoholism.
Binding Properties of Glycosylated Albumin and Acetaldehyde Albumin
Authors: Karp Warren B. , Kinsley Michael , Subramanyam S. B. , Robertson Alex F.
Published: February 2008

Glucose and acetaldehyde react covalently with albumin to form the post‐translationally modified group of proteins, the glycosylated albumins and the acetaldehyde albumins, respectively. This study contrasts the binding ability of a major acetaldehyde albumin fraction synthesized in vitro with glycosylated albumin. A microdialysis rate method, using either [34C]monoacetyidiaminodiphenyl sulfone (MADDS), a deputy ligand for bilirubin, or [34C]diazepam, was employed to evaluate binding at these two sites. Our results indicate that prolonged exposure of purified human serum albumin to acetaldehyde results in a major acetaldehyde albumin fraction that lacks the ability to bind MADDS and diazepam. This fraction migrates identically to albumin on SDS polyacrylamide gel electrophoresis, but exhibits microheterogeneity with a more acidic pi band as seen on analytical isoelectric focusing. We suggest that altered drug binding in alcoholics may be partially explained by altered binding ability of acetaldehyde albumins.
Prostaglandin Synthesis Inhibitors Block Alcohol‐Induced Fetal Hypoplasia
Authors: Pennington Sam , Allen Zebetta , Runion Jane , Farmer Pam , Rowland Lisa , Kalmus Gerhard
Published: February 2008

Alcohol‐induced growth retardation is a fetal effect consistently associated with maternal ethanol consumption. In humans, those infants whose mothers consume even a limited amount of ethanol during pregnancy have a significant incidence of growth inhibition. The molecular mechanism responsible for this growth deficiency is unknown, and prevention depends on maternal abstinence during pregnancy. The data reported here suggest that ethanol‐mediated increases in tissue prostaglandin (PG) E levels (PGE1 plus PGE2) are correlated with the growth retardation. Further, simultaneous administration of PG synthesis inhibitors with the alcohol blocks the rise in tissue PG levels and protects against the alcohol‐induced hypoplasia.
Erythrocyte Aldehyde Dehydrogenase and Disulfiram‐Like Side Effects of Hypoglycemics and Antianginals
Authors: Towell John , Garthwaite Thomas , Wang Richard
Published: February 2008

Disurfiram‐like responses to various drug therapies are caused by elevated ethnot‐derived blood acetatdehyde concentrations resulting from drug‐induced inhibition of aldehyde dehydrogenase enzymes. We have found that the nitrate ester antianginal drugs, isosorbide dinitrate and nitroglycerin, are potent inhibitors of human erythrocyte aldehyde dehydrogenase. To further characterize this drug‐induced enzyme inhibition, erythrocyte aldehyde dehydrogenase activities were measured in patients undergoing therapy with nitrate ester antianginals (isosorbide dinitrate and nitroglycerin) and sulfonylurea hypoglycemics (chlorpropamide and tolazamide). The erythrocyte enzyme was decreased by approximately 25% in sutfonyturea‐treated patients, whereas in the nitrate ester‐treated patients, an 88% inhibition was observed. The minimal enzyme inhibition in the suWonyturea‐treatsd group was unexpected because these therapies have weil‐documented disurnram‐like side effects. This weak inhibition contrasted with the severe inhibition observed in the nitrate ester‐treated group where the disutfiram‐like side effects are not considered a serious clinical problem. This apparent anomaly was attributed to differences in inhibition of the erythrocyte and liver aldehyde dehydrogenase by the parent drugs and their hepatic metabolites.
Cultural Influences and Alcoholism: A Study of Puerto Ricans
Authors: Fernandez‐Pol Blanca , Bluestone Harvey , Morales Gertrude , Mizruchi Mark
Published: February 2008

Some reports in the literature suggest a correlation between acceptance of traditional Latin American family values and alcoholism in Hispanic males. To examine the effects of traditional values on alcoholism, the authors surveyed 151 lower‐class Puerto Rican alcoholics (126 males and 25 females), using a scale to measure Hispanic‐American family values. The scores of these patients were compared with those of 116 lower‐class Puerto Rican nonalcoholics (45 males and 71 females). A path model was constructed with alcoholism as the dependent variable, the Traditional Scale scores as an intervening variable, and demographic variables which may also influence alcoholism (such as sex, age, years of residence in the United States, education, and English ability) as independent variables. Overall, the findings show that traditionalism is a significant predictor of alcoholism, both directly and as an intervening variable in the relation between sex and alcoholism, and education and alcoholism. However, sex and years of residence in the United States were both stronger direct predictors of alcoholism than was traditionalism. These results support the hypothesis that the manifestations of alcoholism in lower‐class Puerto Ricans are influenced by cultural attitudes.
Neonatal Neurobehavioral Characteristics as Correlates of Maternal Alcohol Use during Gestation
Authors: Cotes Claire D. , Smith Iris , Fernhoff Paul M. , Fatek Arthur
Published: February 2008

To determine the neurobehavioral consequences of alcohol use during drrferent periods in gestation, we compared the behavior of 103 neonates bom to women who: (1) drank a mean of 12 ounces of absolute alcohol per week throughout pregnancy; (2) drank a mean of 14 ounces of absolute alcohol and were otherwise comparable to the first group but stopped drinking in the second trimester, and (3) never drank at afl during pregnancy. Low socioeconomic status, predominantly black women applying for prenatal care at a large inner crry hospital were recruited in the second trimester of pregnancy, and those reporting alcohol use were advised to stop drinking. Neurobehavioral evaluation with the Brazetton Neonatal Behavioral Assessment Scale was conducted at 3 days postnatal age. As a group, infants exposed to alcohol at any time during gestation were found to have significant alterations in reflexive behavior, less mature motor behavior, and an increased activity level in comparison to unexposed infants. Infants whose mothers stopped drinking in the second trimester were superior to those whose mothers continued to drink throughout pregnancy in observed state control, need for stimulation, motor tone, tremulousness, and asymmetries in reflexive behavior. These results indicate that characteristic damage does occur to the central nervous system of a fetus exposed to alcohol throughout pregnancy, and that exposure during only the early part of pregnancy also seems to have measurable effects. Multivariate analysis indicated that neither amount of alcohol used per week nor cigarette use contributed significantly to these effects on infant behavior.
Increased Blood Acetate: A New Laboratory Marker of Alcoholism and Heavy Drinking
Authors: Korri Ulla‐Mari , Nuutinen Hannu , Salaspuro Mikko
Published: February 2008

Blood acetate concentration of 51 intoxicated patients was measured and compared to conventional laboratory markers of chronic alcoholism. Mean blood acetate concentration of 23 chronic alcoholics and 17 heavy drinkers was stgrtrftcarrtty (p < 0.0005) higher than that of 53 nonalcoholic volunteers or 11 occasional drinkers. Blood acetate level was completely independent of blood ethanol concentration ranging from 0.20 to 2.90 promiNe. Blood acetate was elevated in 65% of both chronic alcoholics and heavy drinkers. Gammaghita‐myttransferase was abnormal only in 35%, aspartate aminotransferase in 21% and mean corpuscular volume in 12% of heavy drinkers. Combination (acetate + gammaglutamyttransferase) correctly detected 87% of alcoholics and 71% of heavy drinkers. During ethanol oxidation the upper normal limit of blood acetate is 0.75 mn The specificity of increased blood acetate is as high as 92%. Increased blood acetate is indicative for metabolic tolerance to alcohol and it may be so far the most sensitive and specific laboratory marker of chronic alcoholism and heavy drinking.
The Nitrefazole‐Ethanol Interaction in Man: Cardiovascular Responses and the Accumulation of Acetaldehyde and Catecholamines
Authors: Suokas Antti , Kupari Markku , Pettersson Jouko , Lindros Kai
Published: February 2008

The cardiovascular effects of ethanol ingestion after pretreatment with a new antialcohol drug, nitrefazole (2‐methy1‐4‐nrlro‐1‐(4‐nitro‐pfienyl)tmidazote, AMmol) were studied. Left ventricular function was examined by echocardiography and systolic time intervals in six healthy Finnish male volunteers who ingested 0.15‐0.25 g of ethanol/ kg, 24 hr after an 800 or 1600‐mg peroral dose of nitrefazole. After ethanol ingestion, accumulation of acetaldehyde in blood (25–150 /IM) was accompanied by a 1.5‐2‐foW increase in plasma noradrenaline, a 3–10‐foM increase in plasma adrenaline, and a 0.5‐2.0oC rise hi skin temperature. Heart rate increased by 70% and cardiac output by 107%. Diastolic blood pressure decreased by 30% and peripheral vascular resistance by 54%. Election fraction and maximum circumferential fiber‐shortening velocity increased by 26 and 71%, respectively; the pre‐ejection period/ejection time ratio decreased by 46%. An apparent vasovagal collapse was noticed in two nrirefazoietreated subjects after ethanol ingestion, and a third subject experienced a fainting attack shortly after the experiment Thus, in subjects pretreated with nitrefazole, ingestion of rather small amounts of ethanol results in marked accumulation of acetaldehyde apparently due to aldehyde dehydrogenase inhibition. This causes elevation of plasma catecholamines and intense enhancement of cardiac performance. The marked cardiovascular changes demonstrate the potency of nitrefazole, suggesting that, particularly with alcoholics with occult myocardial diseases, its interaction with ethanol may be even more hazardous than that produced by other antialcohol drugs.
Alcohol Withdrawal: Effects of Clonidine Treatment on Sympathetic Activity, the Renin‐Aldosterone System, and Clinical Symptoms
Authors: Manhem Per , Nilsson Lars Hakan , Moberg Ann‐Louise , Wadstein Jan , Hbkfelt Bemt
Published: February 2008

Twenty male alcoholics with alcohol withdrawal syndrome were randomized to receive either oral clonidine (3–600 μg, six hourty) or oral chlormethiazole (500–1000 mg, six hourty) for 4 days. All subjects were also given oral caroamazepine (200 mg, 12 hourly) throughout the study. Nine subjects given clonidine and eight given chlormethiazole completed the study. Clonidine was as effective as chlormethiazole in suppressing the symptoms and signs of alcohol withdrawal. However, plasma catecholamines, blood pressure, and pulse rate feH more rapidly and to a greater extent during clonidine than following chlormethiazole, findings which could have therapeutic implications, tt is suggested that activation of brain noradrenergic neurons constitutes a common denominator in the pathophysiology of several withdrawal syndromes.
Lowering of Blood Acetaldehyde but Not Ethanol Concentrations by Pantethine following Alcohol Ingestion: Different Effects in Flushing and Nonflushing Subjects
Authors: Watanabe Akiharu , Hobara Norio , Kobayashi Michio , Nakatsukasa Harushige , Nagashima Hideo
Published: February 2008

A rise in Mood acetaldehyde concentration* foftowmg alcohol ingestion was significantly inhibited when healthy nonflushing sutojecti were administered a clinical dose of pantethine oraty. However, similar findings were not observed in flushing (alcohol‐sensitive) subjects lacking hepatic low Km aldehyde dehydrogenase (ALOH). The blood ethanol concentrations were not altered by this treatment in either flushing or nonflushing subjects. Acetaldehyde (45 μM) added in vitro to whole blood and plasma obtained 1 hr after pantethine administration disappeared as the incubation continued similarly as with blood and plasma obtained prior to pantethine treatment Pantethine‐related metabolites, such as taurine, pantetheine, coenzyme A, and pantothenate, activated ALOH in vitro. Hepatic acetaldehyde levels following ethanol loading of rats treated with pantethine were much lower than in untreated rats. The pantethine action observed only in nonflushing subjects might be due to an accelerated oxidation of acetaldehyde by the activation of low Km ALOH by pantethine‐related metabolites formed in the liver.
The Effects of Ethanol on Mucociliary Clearance
Authors: Leitch Gordon J. , Frid Leon H. , Phoenix Debbie
Published: February 2008

Mucociliary clearance by the in vitro frog palate can be used as a model to study such clearance by mammalian lung. Frog palates bathed in Ringer's solution exhibited a constant mucociliary clearance rate for over 2 hr. When the bathing solution was exchanged for one containing ethanol, the mucociliary clearance rate was de‐tectabty inhibited by 300 mg/100 ml (mg%) ethanol and significantly inhibited by 400 (50%) and 500 mg% (67%) ethanol. At a concentration of 500 but not 200 mg%, ethanol significantly increased both the amount and the apparent viscosity of the frog palate mucus secreted in 1 hr. Mucus removed from palates bathed in Ringer's solution containing 500 mg% ethanol had no effect on the mucociliary clearance of palates bathed in Ringer's solution alone, and mucus from palates bathed in Ringer's solution alone failed to restore the mucociliary clearance of palates bathed in Ringer's solution containing 500 mg% ethanol. These results suggest that while mucus secretion and rheology are affected by ethanol, such changes in palate mucus do not account for the ethanoi‐induced inhibition of mucociliary clearance, but rather that the inhibition is the result of a ciliotoxic action of ethanol. Prior exposure of palates to histamine significantly attenuated the inhibitory effect of 500 mg% ethanol on mucociliary clearance, while 200 mg% ethanol significantly potentiated the inhibitory effect of dopamine. It is concluded that the neurohumoral environment of the ciliated epithelium in part determines the effect a given concentration of ethanol will have on mucociliary clearance.
Effects of Ethanol on Reproduction and Arterial Hypertension in Spontaneously Hypertensive and Normotensive Rats: a Preliminary Communication
Authors: Mankes Russell F. , LeFevre Rene , Fieseher James , Santiago Anthony , Benitz Karl‐Fredrick , Lyon Robert
Published: February 2008

Ethanol consumption and spontaneous (essential) hypertension are important fetal and maternal risk factors. Alone, they contribute to embryopathy (fetal alcohol syndrome) or maternal organ pathology and fetal loss in hypertensive pregnancies. Combined, the effects of ethanol consumption on the progress of a hypertensive pregnancy have not been adequately investigated. In the present study, groups of O‐A strain genetic hypertensive (SHR: groups 1 and 2) and Wistar‐Kyoto normotensive (WKY: groups 3 and 4) pregnant rats were given 20 ml/kg of distiMed water by gavage to serve as controls [groups 1 (SHR) and 3 (WKY)] or 3.2 g/kg of ethanol [groups 2 (SHR) and 4 (WKY)] from days 6 to 15 of gestation. During acctmation, hypertension developed in SHR rats (WKY pressures were 105 to 114 mm Hg; SHR pressures were 137 to 148 mm Hg). From day 6 to 15 of gestation, ethanoi‐consummg rats (groups 2 and 4) had higher arterial pressures than controls (groups 1 and 3). Pregnant SHR rats given ethanol did not experience a prebirthing hypotension. On gestabon day 20, most offspring (84%, group 2; 86%, group 4) of alcoholic dams were dead or malformed. Intrauterine growth retardation occurred in group 4. Hydrocephalus, microphthalmia, and mild hydronephrosis and hydroureter were common in live offspring of group 2 dams. Hydronephrosis and hydroureter were increased in group 4 pups. Variant cranial ossification was noted in group 2 and 4 pups. These preliminary data suggest an altered hypertensive response during pregnancy in alcohol‐consuming rats and confirm the embryopathic effects of relatively high levels of ethanol consumed during the critical period of organogenesis in two additional strains of rats.
Ethanol Tolerance of Cerebellar Purkinje Neurons from Selectively Outbred Mouse Lines: in Vivo and in Vitro Electrophysiological Investigations
Authors: Palmer Michael R. , Basile Anthony S. , Proctor William R. , Baker Rodney C. , Dunwiddie Thomas V.
Published: February 2008

The electrophysiological activity of cerebellar Purkinje neurons was characterized in long sleep (LS: ethanol sensitive) and short sleep (SS: ethanol insensitive) mice made tolerant to ethanol. After 1 to 4 weeks of feeding on a liquid ethanol diet, mice of both lines were less sensitive to the sedative and ataxic effects of parenteral ethanol than were controls. In addition, cerebellar Purkinje cells in ethanol‐fed LS and SS mice were less responsive than the controls to the depressant effects of ethanol applied via bath perfusion in vitro and via local pressure ejection application in vivo. Tolerance to the electrophysiological effects of ethanol were already apparent after 7 to 9 days on the ethanol diet, and the degree of tolerance did not increase significantly in either mouse line fed ethanol for an additional 1–3 weeks. Finally, the differences in ethanol sensitivities of naive mice (LS >> SS) were maintained following the development of tolerance. We conclude that tolerance to both the cellular and behavioral depressant effects of ethanol can be observed after chronic feeding with ethanol in LS and SS mice, and that there are no significant differences in the degree of tolerance developed by these mice. In addition, our data suggest that the inherited differences in ethanol sensitivity between LS and SS mice, and the changes in ethanol sensitivity which occur in these mice with chronic exposure to this depressant agent, are mediated by different mechanisms.
Importance of plant physical cues in host acceptance for oviposition by Busseola fusca
Authors: Calatayud P.‐A. , Ahuya P.O. , Wanjoya A. , Le Rü B. , Silvain J.‐F. , Frérot B.
Published: February 2008

Plant and surrogate stems exhibiting specific combinations of physical cues were used to determine which plant‐related stimuli influence the oviposition of Busseola fusca (Fuller) (Lepidoptera: Noctuidae). The number of eggs and egg batches laid per female increased with an increase in diameter of both natural and artificial stems. Direct observations of the oviposition behaviour (walking, antennating, and sweeping with the ovipositor) indicated that the female moths preferred oviposition supports with a large diameter and non‐pubescent or smooth surfaces over pubescent or rough ones. Pubescence and rough surfaces significantly affected the behavioural steps leading to oviposition by interfering with the ovipositor sweep process necessary to find a suitable oviposition site. Furthermore, more eggs and egg batches were laid on soft than rigid supports. The rigidity of the support affected the proper insertion of the ovipositor for egg deposition. Our results underline the importance of physical stimuli in B. fusca's choice of an oviposition site, which may facilitate the identification of potential host plants or preferred oviposition sites on a plant for this species.
Swimming performance of wild and F1‐hatchery‐reared Atlantic salmon (Salmo salar) and brown trout (Salmo trutta) smolts
Authors: Pedersen L.‐F. , Koed A. , Malte H.
Published: February 2008

Abstract –  The swimming performance of wild and hatchery‐reared smolts of two salmonid species was investigated. Wild Atlantic salmon smolts (WS) and brown trout smolts (WT) of equal size were caught in fish traps during migration. Hatchery‐reared smolts of both species (HS and HT for salmon and trout respectively) were first generation offspring from wild broodstock. The swimming performance of individual smolts from the four groups (WS, HS, WT, HT) was tested three consecutive times using a swimming flume with water flowing at a start rate of 0.16 m·s−1 and a constant acceleration rate of 0.167 cm·s−2 (10 cm·s−1·min−1). Wild caught smolts of both species performed significantly better than those reared in hatchery conditions. The WS group were observed to maintain an average swimming speed (Uburst) that was 30% faster than the HS group, whereas the wild trout smolts were superior to HT by approximately 25%. Repeated measures revealed species‐specific exhaustion patterns. Brown trout smolts maintained consecutive Uburst indicating significant stamina compared with Atlantic salmon smolts that were found to be exhausted by the initial trial.
Quality of Life Improvements in Dialysis Patients Receiving Darbepoetin Alfa
Authors: Fukuhara Shunichi , Akizawa Tadao , Morita Satoshi , Koshikawa Shozo ,   the KRN321 A08 Study Group
Published: February 2008

Abstract:  Short‐acting hematopoietic agents can improve the quality of life (QOL) of hemodialysis patients, but questions remain regarding the domains of QOL affected, the relative importance of initial and final hemoglobin (Hb) concentrations, and the use of long‐acting hematopoietic agents. We measured Hb concentrations and QOL in 487 hemodialysis patients who were switched from treatment with recombinant human erythropoietin to treatment with darbepoetin alfa. QOL was measured with the Japanese‐language version of the SF‐36, at the start of therapy with darbepoetin alfa and again 7–14 weeks later. We examined changes in QOL over time in the group as a whole, and in subgroups stratified by the change in Hb concentration. We also studied relationships between the final Hb concentration achieved and the magnitude of change in QOL. QOL scores increased significantly in all SF‐36 domains except Social Functioning. The greatest increases were in vitality and in the two role‐functioning domains. The magnitude of the increase in Hb concentration was related to the magnitude of the increase in QOL for only one subscale: Vitality. Patients with higher final Hb concentrations also had greater increases in Vitality scores. Hematopoiesis induced by darbepoetin alfa is associated with increased vitality and may also be associated with improved role functioning. Vitality increased significantly only in those patients with the greatest increases in Hb concentration and in those with higher final Hb concentrations.
EFFECT OF BIFIDOBACTERIUM BREVE ON THE GROWTH OF ENTEROBACTER SAKAZAKII IN REHYDRATED INFANT MILK FORMULA
Authors: OSAILI T.M. , SHAKER R.R. , AYYASH M.M. , HOLLEY R.A.
Published: February 2008

The effect of Bifidobacterium breve on the survival and growth of Enterobacter sakazakii in rehydrated infant milk formula stored at 4–45C was studied. A commercial culture of B. breve and a five‐strain cocktail E. sakazakii were mixed with rehydrated formula and stored up to 8 h. The populations of B. breve and E. sakazakii at each storage time/temperature were determined. There was a two‐way interactive effect between B. breve numbers and temperature on the number of E. sakazakii in the rehydrated formula at 3–8 h of storage. E. sakazakii did not grow in the rehydrated formula at 4C. At 12 and 20C, the numbers of E. sakazakii in the presence of B. breve were lower than those in the formula without B. breve at 8 h of storage, and at 45C, when the bacteria were combined, a similar result was obtained at 6‐ and 8‐h storage. The presence of B. breve in the formula appeared to enhance the growth of E. sakazakii at 37C in the rehydrated formula stored at 2–8 h. Other more competitive inhibitory probiotic cultures would be more appropriate to control E. sakazakii growth in unrefrigerated rehydrated milk‐based formula.

PRACTICAL APPLICATIONS

Results obtained showed that the probiotic organisms Bifidobacterium breve did not reduce Enterobacter sakazakii levels in rehydrated infant formula if held >2 h at >30C. At 37C, B. breve stimulated the growth of the pathogen after 2 h. Choice of probiotic bacteria for inclusion in these products to improve infant gut microflora should be based on their neutral or negative influence on E. sakazakii survival/growth to reduce the risk to health associated with the contamination of these products during manufacture.