bluuebunny/crossref_metadata_2025 huggingface dataset:
Pituitary‐Adrenal Responses to Morphine and Footshock Stress Are Enhanced following Prenatal Alcohol Exposure
Authors: Nelson Linda R. , Taylor Anna Newman , Lewis James W. , Poland Russell E. , Redei Eva , Branch Berrilyn J.
Published: June 2007

The effect of prenatal ethanol exposure on pituitary‐adrenal function in adult offspring was assessed by measuring cortjcosterone (CS) levels in plasma following exposure to two forms of footshock stress, intermittent and continuous, and after administration of 20 mg/kg of morphine. The footshock experiments were conducted at two time points in the circadian pituitary‐adrenal cycle. Prenatally ethanol‐exposed (E) rats had higher levels of CS than pair‐fed and normal controls following intermittent footshock when tested at the crest of the CS circadian rhythm. However, this difference was not present when intermittent footshock was presented at the trough of the circadian cycle. At either time of day, there were no differences among the prenatal treatment groups in the basal condition or following continuous footshock. In addition, E rats had significantly higher levels of plasma CS than controls following morphine. Plasma adrenocorticotropin (ACTH) levels were measured after intermittent footshock at the crest of the circadian rhythm and were significantly higher in E rats than in controls. These results extend our previous reports of enhanced activation of the hypothalamo‐pituitary‐adrenal axis in response to other stressors as wed as to ethanol in adult rats exposed to ethanol in utero. They also confirm that E rats are differentially hyperresponsive only to intermittent footshock stress, not to continuous footshock, as we had found to be the case when the analgesia induced by these two stressors was the dependent measure.
Chronic Liver Disease in Abusers of Alcohol and Parenteral Drugs: A Report of 204 Consecutive Biopsy‐Proven Cases
Authors: Novick David M. , Stenger Richard J. , Gelb Alvin M. , Most Jeanne , Yancovitz Stanley R. , Kreek Mary Jeanne
Published: June 2007

We studied a consecutive series of 204 patients who were admitted to a hospital for addictive diseases during 40 months and who had a liver biopsy. Parenteral drug abusers (n= 34) were significantly younger than alcohol abusers (n= 23) or abusers of both (n= 147) and had lower levels of serum alkaline phosphatase, total bilirubin, and aspartate aminotransferase than the other two groups. Chronic active hepatitis and chronic persistent hepatitis were more frequent (p < 0.001) in abusers of parenteral drugs alone, whereas cirrhosis was found most often (p < 0.001) in abusers of both alcohol and parenteral drugs. Cirrhosis was present in 10 of 39 (26%) simultaneous abusers of alcohol and parenteral drugs compared with 58 of 96 (60%) alcohol‐abusing former parenteral drug abusers (p < 0.001). Methadone maintenance treatment was not associated with cirrhosis. Thus, methadone‐maintained patients who abuse alcohol and develop cirrhosis should remain in methadone maintenance treatment and receive concomitant alcoholism treatment Also, these data further support the hypothesis that abusers of both alcohol and parenteral drugs have an increased risk of developing cirrhosis.
Oxidation of Ethanol to Acetaldehyde by Bronchopulmonary Washings: Role of Bacteria
Authors: Miyakawa Happei , Baraona Enrique , Chang Jui C. , Lesser Marvin D. , Lieber Charles S.
Published: June 2007

The synergistic effects of tobacco smoking and alcohol consumption on the incidence of upper respiratory cancer may be linked to their common ability to produce acetaldehyde, an irritant and potential mutagen. Since alcohol consumption in most individuals results in very low concentrations of acetaldehyde in the blood, we determined whether bronchopulmonary cellular components are capable of oxidizing ethanol to acetaldehyde. We found that significant production of acetaldehyde occurred in vitro after incubation of human bronchopulmonary washings with 25 mm ethanol. Acetaldehyde production was increased in active smokers and related to microorganisms in the bronchopulmonary tract It was abolished by preincubation of the washings with antibiotics and was reproduced in vitro with Streptococcus pneumoniae. Normal pulmonary cells in bronchopulmonary washings did not produce acetaldehyde from ethanol.
New Instrument Using Gas Sensors for the Quantitative Analysis of Ethanol in Biological Liquids
Authors: Giles H. G. , Rertaud G. E. , Meggiorini S. , Israel Y.
Published: June 2007

A gas sensor was built into an instrument to measure ethanol in biological liquids by determining head space ethanol concentrations without chromatography. The analysis of plasma, urine, and whole blood containing ethanol over the range 20–640 mg/dl determined by this novel instrument is fast (30 sec), accurate (r= 0.99), and precise (coefficients of variation 0.6‐1.8%) when compared with gas chromatography. The addition of alcohol dehydrogenase, 0‐nteotJn‐amide adenine dinucleotide, and semicarbazide to samples allows ethanol to be distinguished from other alcohols. The instrument can be built and operated at modest costs thus allowing its use in multiple settings.
Reduced Sensitivity of Red Blood Cell (Na+, K+)‐ATPase to Ethanol in Vitro in Male Alcoholic Patients: Relationship to Clinical Characteristics
Authors: Swann Alan C. , Reilly Edward , Overall John E.
Published: June 2007

We examined red Wood ceil (Na+, K+)‐ATPase, its sensitivity to inhi‐brtion by ethanol in vitro, and its relationship to clinical characteristic! and history in 41 newly admitted alcoholic patients and 14 age‐matched healthy controls. Sensitivity to ethanol was significantly lower in the alcoholic patients and correlated negatively with ethanol intake. In addition, sensitivity of enzyme to ethanol was lower ir patients with high agitation‐anxiety ratings and correlated negatively with agitation and anxiety scores on the Brief Psychiatric Rating Scale. There were no relationships between (Na+, K+)‐ATPase measures and depressive symptoms, history of treatment for depression, or family history of depression. These data suggest that tolerance to the effects of ethanol on (Na+, K+)‐ATPase occurs in man and may be related to the severity of ethanol dependence or withdrawal.
Micro Anion Exchange Chromatography of Carbohydrate‐Deficient Transferrin in Serum in Relation to Alcohol Consumption (Swedish Patent8400587–5)
Authors: Stibler Helena , Borg Stefan , Joustra Marius
Published: June 2007

A new simplified and rapid method for detection and quantitation of “carbohydrate‐deficient transferrin” in serum is described. The method is based on isocratk anion exchange chromatography of isotransferrins in disposable microcolumns followed by a double antibody transferrin radioimmune assay. This technique, which separates all transferrin components isoelectric above pH 5.65, showed a very good reproducibility and accuracy with a coefficient of variation between 5 and 9%. 77 alcoholic patients could be dearly separated from 80 healthy “normal consumers” and 33 total abstainers with a specificity of 100% and a sensitivity of 91%. The values were significantly correlated to the amount of alcohol consumed during the latest month, and declined in abstaining alcoholics with a mean biological half‐life of 17 days. Elevated levels occasionally appeared in healthy individuals after daily consumption of 60 g of ethanol during a 10‐day period. In a sample of 187 patients with nonalcohol‐related conditions only 2% false‐positive values were found. This method is suggested as a potential tool for detecting and monitoring alcohol abuse.
Zinc Metabolism in Alcoholic Liver Disease
Authors: McClain Craig J. , Antonow David R. , Cohen Donald A. , Shedlofsky Steven I.
Published: June 2007

Alterations in zinc metabolism or zinc deficiency frequently occur in patients with alcoholic Nver disease. Potential manifestations of zinc deficiency include skin lesions, hypogonadism, impaired night vision, impaired immune function, anorexia, altered protein metabolism, diarrhea, and depressed mental function. Because of the variety of ways in which zinc deficiency may present in alcoholic liver disease, clinicians must maintain a high index of suspicion for this nutrient deficiency when caring for these patients. Not only may zinc deficiency occur with alcoholic liver disease, but there also may be altered zinc metabolism. Recent data from alcoholic hepatitis patients demonstrate increased serum levels of the monokine interieu‐kin 1, which is known to cause hypozincemia and an internal redistribution of zinc. This monokine has a host of metabolic functions other than its effect on mineral metabolism that have relevance for alcoholic liver disease such as fever production, neutrophilia, and muscle catabolism. We suggest that the patient with alcoholic Nver disease frequently has problems with either zinc deficiency or altered zinc metabolism and the potential implications of this are discussed.
Central Cholinergic Correlates of Low Dose Ethanol‐Induced Locomotor Stimulation
Authors: Kochhar Abha , Erickson Cartton K.
Published: June 2007

Brain area levels of acetycholine and choline plus the turnover rate ol acetylcholine were measured in three strains of rats given low, locomotor‐stimulating doses of ethanol. Maudsley reactive (MR/N), Sprague‐Oawley, and randomly bred MR/N (MRrb) rats were killed by microwave irradiation and cholinergic function was measured by gas chromatography/mass spectroscopy methods. The results show that the MR/N strain (2 and 5 months old), which eJtctts enhanced locomotor stimulation after low doses of ethanol, also demonstrates significant increases in cholinergic function at the time of behavioral stimulation. However, after locomotor stimulation, cholinergic parameters returned to normal in these animals. Strains which do not show enhanced locomotor activity after ethanol did not demonstrate significant central cholinergic changes. We conclude that central cholinergic function is related to behavioral stimulation elicited by low doses of ethanol in the MR/N rat strain but not other strains.
Changes in Lipid Composition of Rat Heart Mitochondria after Chronic Ethanol Administration
Authors: Foudin Laurie , Sun Grace Y. , Sun Albert Y.
Published: June 2007

Triacylglycerois and phospholipids of mitochondria from heart ventricular muscle were analyzed following chronic ethanol administration (2 and 10 g/kg of body weight/day) to adult rats for 21 days via intragastric intubation. Triacylgtycerois were elevated 57% in the high ethanol group as compared to controls, but cholesterol level was not altered. Most of the phospholipids, including lysophospho‐Kpids, showed a small increase in level after ethanol administration. However the greatest increase (50%) occurred m ethanotemine plasmalogens. Although smaH changes in the acyt group composition of phosphatidylethanolamines and phosphatidylcholines were observed, the acyt group profile of cardiolipin remained unaltered. K is concluded that myocardial membranes respond to the disordering effects of ethanol by altering the synlhesis of selected lipids more than through altering the phospholipid acyl group composition. Some of these changes may be responsible for altered mitochondrial functions in the myocardium.
Alcoholic Ketosis
Authors: Fulop Milford , Ben‐Ezra Jonathan , Bock Jay
Published: June 2007

We prospectively studied 23 episodes of suspected alcoholic ketosis in order to team whether there was objective evidence of the patients having stopped drinking ethanol a few days before admission, and of being starved. Eight patients had moderate ketosis (plasma 3‐hydroxybutyrate 4.1–7.8 mmot/liter); seven patients had mild ketosis (2–4 mmol/liter); and eight had little or no ketosis (less than 2 mmd/ liter). The latter eight patients had mainly lactic acidosis (plasma lactate 2.0–13.3 mmol/liter). Most of the ketotic patients did not have ethanol detected in their blood. The presence of starvation was supported by the finding of subnormal plasma triiodothyronine levels (less than 90 /μg/dl) in six of seven ketotic patients (average 60 μg/dl for ad seven). The ketotic patients usually had low‐normal plasma insulin levels (3‐ 16 μU/ml), as is common in starvation. Our findings support the previously undocumented belief that most patients with alcoholic ketosis did stop drinking ethanol some time before admission, and that starvation is a major pathogenetic factor in the disorder.
Assessment of the Development of Tolerance to Ethanol Using Multiple Measures
Authors: Pohorecky L. A. , Brick J. , Carpenter J. A.
Published: June 2007

Development of tolerance to ethanol was examined using a motor coordination test, startle response, and rectal temperature in rats chronically treated with ethanol (8–11 g/kg/day), equicaloric dextrin maltose (DM) or water. A 2.0 g/kg test dose resulted in 92, 48, and 2.7% depression from baseline of motor coordination test performance, startle response, and rectal temperature, respectively, on the first test day. There was complete tolerance to the hypothermic effect of this dose of ethanol on the 9th day of treatment while 17 days of treatment were required to achieve total tolerance on dowel test but still did not produce full tolerance on the startle response. Measurement of blood ethanol concentration indicated no significant changes in the rate of ethanol disappearance. Therefore the observed decrease in sensitivity to ethanol represents functional tolerance. These results indicate tolerance to ethanol develops at different rates depending on the measures employed to evaluate it.
Alcohol Dehydrogenase Isozymes in Baboons: Tissue Distribution, Catalytic Properties, and Variant Phenotypes in Liver, Kidney, Stomach, and Testis
Authors: Holmes Roger S. , Courtney Yolanda Reed , VandeBerg John L.
Published: June 2007

Isoelectric focusing and cellulose acetate electrophoresis were used to examine the multiplicity, tissue distribution, and variability of alcohol dehydrogenase (AOH) among baboons, a primate species used as a model for research on alcohol metabolism and alcohol‐induced liver pathology. Five major AOH isozymes were resolved and distinguished on the basis of their isoelectric points, tissue distributions, relative activities with alcohol substrates, and sensitivities to inhibition with 4‐methyt pyrazote. ADH‐1 and ADH‐2 exhibited class I kinetic properties and were observed in high activity in kidney and liver extracts, respectively. ADH‐3 showed class II kinetic properties, exhibiting high activity in stomach extracts, and was widely distributed in extracts of other baboon tissues, including kidney, esophagus, heart, testis, brain, and male sex accessory tissues. ADH‐4 also showed class II ADH properties but was found only in liver (similar to human “x‐ADH”). ADH‐5 exhibited class III AOH kinetic properties, being inactive with ethanol up to 0.5 M (similar to human “x‐ADH”) and was distributed widely in baboon tissue extracts. Major activity variation was observed for liver ADH‐4 between different animals. An electrophoretic variant for ADH‐3 was observed for the enzyme in stomach, kidney, and testis extracts, and activity variation existed for this isozyme in kidney extracts. It is apparent that baboon ADH shares a number of features with the human ADH phenotype; however, several species‐specific differences were observed, particularly for the liver and kidney class I isozymes and for stomach ADH.
Reinterpretation of the Pharmacokinetic Mechanism of Oral Benzodiazepine Ethanol Interaction
Authors: Guthrie Sally K. , Lane Elizabeth A.
Published: June 2007

Previously published studies investigating the oral benzodiazepine ethanol interaction have utilized a single dose of ethanol, a single dose of oral benzodiazepine, and measured plasma benzodiazepine concentration over varying time periods. Most studies reported an increase or no change in benzodiazepine plasma concentrations following ethanol administation, which the investigators usually ascribed to an ethanoi‐induced increase in the benzodiazepine absorption rate constant However, ethanol decreases the hepatic clearance of benzodiazepines that are biotransformed via the P450 enzyme system and this effect was not taken into account in evaluation of the results of these studies. Computer simulations have been used to investigate possible mechanisms of the oral benzodiazepine‐ethanol interaction. The effects of a constant or transient decrease in clearance and an increase or decrease in absorption rate constant upon maximum concentration, time of maximum concentration, and area under the benzodiazepine plasma concentration curve (AUC) have been examined. A transient 75% decrease in benzodiazepine clearance resulted in a 13.6% increase in AUC (0–36 hr), a 3.4% increase in Cmax and a 5.7% increase in tmax These changes are qualitatively consistent with, but quantitatively shy, of those observed in most studies. Consequently, an effect of ethanol upon benzodiazepine absorption must still be considered.
Ethanol Oxidation and Toxicity: Role of Alcohol P‐450 Oxygenase
Authors: Koop Dennis R. , Coon Minor J.
Published: June 2007

The isolation and characterization of ethanol‐inducible rabbit Nver microsomal cytochrome P‐450, termed P‐450 3a or P‐450ALC, has provided definitive evidence for the role of this enzyme in alcohol oxidation. From findings on the distribution, substrate specificity, and mechanism of action of P‐450ALC we have suggested “alcohol P‐450 oxygenase” as a more biochemically accurate name than “microsomal ethanol‐oxidizing system.” The present review is concerned with studies in this and other laboratories on activities and inducers associated with this versatile enzyme. Numerous xenobiot‐ics, including alcohols and ketones, nitrosamines, aromatic compounds, and halogenated afkanes, alkenes, and ethers, are known to undergo increased microsomal metabolism after chronic exposure of various species to ethanol. Diverse compounds and treatments may induce P‐450ALC, including the administration of ten or more chemically different compounds, fasting, or the diabetic state. Whether a common mechanism of induction is involved is unknown at this time. As direct evidence that P‐450ALC catalyzes numerous metabolic reactions, the purified rabbit enzyme has been used in a reconstituted system to demonstrate various metabolic transformations, including the oxidation of various alcohols, acetone, acetol, p‐nitrophenol, and aniline, the dealkylation of substituted nitrosamines, the reductive dechlorination of carbon tetrachloride, carbon tetra‐chloride‐induced lipid peroxidation, and acetaminophen activation to form the glutathione conjugate.
The Effect of Ethanol on the β‐Oxidation of Fatty Acids
Authors: Grunnet Niels , Kondrup Jens
Published: June 2007

The application of radiolabeled fatty acids to measurements of fatty add oxidation is discussed and a method for measuring the rate of β‐oxidation and of acetyt‐CoA oxidation to CO2 is described. In hepatocytes from starved or fed rats, ethanol inhibited total /?‐oxidation in the presence of 1.3 mm palmitate by 22% and 25%, respectively. If changes in the specific radioactivity of acetyl‐CoA were not corrected for, the effect of ethanol would have been overestimated by 15% and underestimated by 15% in hepatocytes from fed and starved rats, respectively. In perfused liver from fed rats, inhibition by ethanol of total β‐oxidation in the presence of 1 mm palmitate was 35%. The rate of β‐oxidation in the absence of ethanol was underestimated by 65% if proper corrections were not applied. Inhibition of the tricarboxylic acid cycle by ethanol was 57% and 72% in hepatocytes from starved and fed rats, respectively. Pyrazoie titration experiments demonstrated a correlation between changes in the mitochondrial NADH/NAD+ ratio and both inhibition of the tricarboxylic acid cycle and inhibition of the β‐oxidation pathway. The concentration of acetoacetyl‐CoA is suggested as an additional regulatory factor of the β‐oxidation pathway. The ethanol‐induced accumulation of triacylglycerol as a consequence of the inhibition of the β‐oxidation pathway is estimated to represent a 10% increase in the cellular triacylglycerol pool/hr/g of wet weight Hence its chemical determination requires experiments of several hours duration. Primary cultures of hepatocytes have been shown to be a useful experimental system for studies of the ethanol‐induced triacylglycerol accumulation.
The Deuterium Isotope Effect on Ethanol Metabolism in Perfused Rat Liver: Effect of Reversed Perfusion on Ethanol and Oxygen Uptake
Authors: Lundquist F. , Quistorff B. , Iversen H.
Published: June 2007

Livers from rats fasted for 24 hr were subjected to nonrecirculating perfusion with Krebs‐Ringer bicarbonate solution containing 10 mm ethanol. The deuterium isotope effect was measured using (1‐R)‐[1‐14C, 1‐2H]ethanol. A value of 2.57 ± 0.09 (SO) was obtained independent of the direction of perfusion. Oxygen uptake and ethanol metab‐olism in contrast were significantly increased when reverse perfusion (i.e., from vena cava to vena portae) was used. The magnitude of the isotope effect indicates that contribution from microsomal ethanol‐oxidizing system if this is the only supplementary system is 9.8% under the experimental conditions. At high ethanol concentrations, the contribution would approach 18%. Equal activities of microsomal ethanol‐oxidizing system and catalase under the experimental conditions would mean that both contribute 7.3% of the total ethanol metabolism. At high ethanol concentrations (80 mm), how‐ever, catalase will be 6.8% and microsomal ethanol‐oxidizing system is calculated to 13.3%. Preliminary experiments with rats pretreated with phenobarbital showed no change in the isotope effect or in the rate of ethanol metabolism, but a 40–50% increase in oxygen consumption. The acetaldehyde concentration in the effluent medium was below 1 μM.
The Effects of Chronic Ethanol Consumption on Carcinogen Metabolism and on O6‐Methylguanine Transferase‐Mediated Repair of Alkylated DNA
Authors: Garro Anthony J. , Espina Noel , Farinati Fabio , Salvagnini Mario
Published: June 2007

This article presents a review and update of recent experiments conducted in collaboration with Dr. C. S. Lieber on mechanisms underlying the increased cancer risk associated with alcohol abuse. Ethanol has been found to be a potent inducer of microsomal enzymes involved in carcinogen metabolism in a variety of rat tissues including liver, esophagus, lungs, and intestines. In some of these tissues, ethanol's inductive effect on microsomal cytochrome P‐450 enzyme activity may result in enhanced levels of electrophilic metabolites of procarcinogens which are not readily detoxified. In addition, chronic ethanol feeding has been found to depress the activity of O6‐methylguanine transferase, an enzyme involved in the repair of carcinogen‐induced DNA alkylation. The effects of ethanol on carcinogen metabolism and on DNA repair would be expected to enhance the initiation phase of chemically induced cancers.
In Vivo Effects of Disulfiram and Cyanamide on Canine Liver Aldehyde Dehydrogenase Isoenzymes as Detected by High‐Performance (Pressure) Liquid Chromatography
Authors: Sanny Charles G. , Rymas Kimberlee
Published: June 2007

Methods for analysis of aldehyde dehydrogenase isoenzymes using high‐performance (pressure) liquid chromatography (HPLC) were used to determine in vivo effects of disulfiram and cyanamide on canine liver aldehyde dehydrogenase (ALDH) isoenzymes. Liver ALDH isoenzymes from control and disulfiram‐ or cyanamide‐treated dogs were separated by ion‐exchange HPLC, and enzyme activity was detected using a postcolumn reactor. Two major peaks of ALDH activity (peaks I and II) were detected. Varying the composition of the reaction column reagents resulted in alterations in the elution profiles consistent with the kinetic properties of individual isoenzymes (i.e., ALDH IB in peak I and ALDH IIB in peak II), including estimates of the Km for acetaldehyde and the effects of magnesium ions on ALDH activity. Disulfiram treatment decreased both peaks depending on disulfiram dose and length of treatment, with peak I being more sensitive to inactivation than peak II. Reagents containing MgCI: (1 mM) decreased peak I and increased peak II compared with EDTA (1 mM) for samples from both control and disulfiramtreated animals. These data are consistent with the assignment of the disulfiram‐sensitive isoenzyme (ALDH IB) to peak I and the isoenzyme stimulated by magnesium ions (ALDH IIB) to peak II. In vivo cyanamide treatment produced similar decreases in both peaks to a maximum decrease of ‐30% of control depending on cyanamide dose. Peak I, however, was more sensitive than peak II to in vitro inactivation by cyanamide, which suggests that cytosolic ALDH in the dog (in contrast to other mammals) is more sensitive to inactivation than mitochondrial ALDH.
Ethanol‐Induced Modulation of Cytokine Production by Splenocytes during Murine Retrovirus Infection CausingMurine AIDS
Authors: Wang Yuejian , Huang Dennis S. , Giger Paul T. , Watson Ronald R.
Published: June 2007

Ethanoi (ETOH) consumption has been associated with general suppression of the immune response, resulting in increased susceptibility to infection. Chronic dietary ETOH consumption may be one of the cofactors accelerating development of human acquired immune deficiency syndrome (AIDS) after retrovirus infection. Chronic dietary ETOH [5% (v/v)] in the Lieber‐DeCarli liquid diet was fed female C57BL/6 mice inoculated with LP‐BM5 retrovirus causing murine AIDS for 11 weeks. Because cytokines are key regulators of humoral and cellular immunity, their production by concanavalin A (ConA) and lipopolysaccharide (LPS)‐induced splenocytes was measured by ELISA methods. Decreased levels of interleukin (IL)‐2 caused by retrovirus infection remained unchanged. Elevated levels of IL‐5 and IL‐6 produced in vitro by ConA‐stimulated spleen cells during retrovirus infection were significantly further increased by dietary ETOH. Elevated IL‐4 due to retroviral infection were not affected by dietary ETOH. Increased production of IL‐10 induced by retrovirus infection, however, was significantly reduced by dietary ETOH, whereas decreased release of interferon‐r induced by retrovirus infection was significantly enhanced. Elevated levels of tumor necrosis factor‐a produced by LPS‐stimulated splenocytes from retrovirus infected mice were significantly further increased by dietary ETOH, whereas levels of IL‐6 by LPS‐stimulated splenocytes were not affected. Suppressed T‐cell proliferation caused by retrovirus infection was significantly reduced further by dietary ETOH. However, no effect of dietary ETOH was observed on decreased B‐cell proliferation by retrovirus infection. These results suggest that dietary ETOH aggravates progression of immune dysfunction leading to AIDS, because dietary ETOH modifies production of immunological regulatory cytokines.
Neuroscience Research: How Has It Contributed to Our Understanding of Alcohol Abuse and Alcoholism? A Review
Authors: Hunt Walter A.
Published: June 2007

Alcohol abuse and alcoholism are the greatest substance abuse problems in the United States today and contribute to numerous medical and social problems. To deal with many of these problems, an understanding of how alcohol acts on the brain is extremely important. Advances in neuroscience research have provided significant clues about where and how alcohol works on the brain. Alcohol clearly acts on membrane function, altering such processes as ion movements and neurotransmitter interactions with their receptors. Although these alcohol‐induced alterations are presumed to relate to changes in behavior, this has not been clearly established. However, alcohol research is on the threshold of making a giant leap forward in our understanding the etiology of alcoholism.
Protective Effect of Liv.52 on Alcohol‐Induced Fetotoxicity
Authors: Gopumadhavan S. , Jagadeesh S. , Chauhan B. L. , Kulkarni R. D.
Published: June 2007

The adverse effects of maternal alcohol consumption on the development of the fetus are well known. The adverse effects of ethanol on the liver are now believed to be due to acetaldehyde formed as an intermediate metabolite of ethanol. Liv.52 has been shown to bring about faster elimination of acetaldehyde from the body and thus prevent alcoholic liver damage. Other toxic effects of alcohol may also be due to acetaldehyde and may be prevented by Liv.52. In this study, rats were given 20% (v/v) ethanol in drinking water, during the gestation period, and the effect on maternal body weight and fetal outcome was noted. The protective effect of Liv.52 administration during the gestation period was studied. The results show that ethanol ingestion caused a decrease in gestational weight gain, total fetal weight, and number of live fetuses. There were increases in resorptions. Liv.52 administration reduced the deleterious effects of ethanol. The concentration of acetaldehyde in the amniotic fluid of ethanol‐consuming animals was 0.727 μg/ml. Liv.52 administration lowered it to 0.244 μg/ml. The protective effect of Liv.52 could be due to the rapid elimination of acetaldehyde.
Liver Transplantation for Alcoholic Liver Disease: Survival of Patients Transplanted with Alcoholic Hepatitis Plus Cirrhosis as Compared with Those with Cirrhosis Alone
Authors: Bonet Harry , Manez Rafael , Kramer David , Wright Harlan I. , Gavaler Judith S. , Baddour Nahed , Van Thiel David H.
Published: June 2007

From January 1986 through December 1991, a total of 221 patients with alcoholic liver disease received liver transplantation. In 147 of these cases, complete pretransplant histopathologic, demographic, and laboratory data (minimum of CBC, AST, ALT, total bilirubin, albumin, and prothrombin time) were available for review. Forty‐five (30%) of the 147 recipients had alcoholic hepatitis plus cirrhosis (AH), whereas 70% had cirrhosis (CIRR) alone. Age and sex were similar in the subgroups, but the patients with CIRR had a greater AST/ALT ratio, longer protime, and lower platelet count (all p < 0.01). Coexistent hepatitis B (4.7%) or hepatitis C (4.1%) was similar in both groups. Current survival is 80% for patients with AH and 84% for those with CIRR (NS). Overall, survivors were younger (43.4 ±1.7 years) than nonsurvivors (53.6 ± 3.2) (p < 0.01), an age influence that was significant in the CIRR group (p <; 0.01) but not in the AH group. Inexplicably, the AST/ALT ratio was greater in AH survivors (1.5 ± 0.2) than it was in nonsurvivors (0.4 ± 0.1) (p < 0.01). In patients with CIRR, the platelet count was greater in survivors (252 ± 29 vs. 86 + 11 ± 109cells/liter).

The data support the clinical impression that patients with chronic decompensated cirrhosis referred for liver transplantation had more severe complications of their liver disease than did those with AH. Survival in both subgroups was similar, but overall the survivors are nearly a decade younger than the nonsurvivors. Because the diagnosis of AH implies a briefer period of alcohol abstention, it was interesting to note that liver transplantation could be accomplished as successfully with AH as with CIRR.
Invasive molluscs in the diet of Pterodoras granulosus (Valenciennes, 1821) (Pisces, Doradidae) in the Upper Paraná River floodplain, Brazil
Authors: Cantanhêde G. , Hahn N. S. , Gubiani É. A. , Fugi R.
Published: June 2007

Abstract –  Diet composition of Pterodoras granulosus was investigated from June 2004 to June 2005 in the Upper Paraná River floodplain, following invasion by two mollusc species Corbicula fluminea and Limnoperna fortunei. Stomach and intestinal contents analysis showed spatial differences in the diet composition. In the Baía River, P. granulosus diet consisted mainly of C. fluminea, whereas plant items dominated in the Ivinheima River, and L. fortunei was the most important food in the Paraná River. There was little selectivity in shell length consumed. In spite of C. fluminea being a larger mollusc, L. fortunei appears to be energetically more profitable because its shell is more fragile and is rapidly opened and digested. A considerable amount of closed shells of C. fluminea at the end of the digestive tract points to a possible role of P. granulosus as a mollusc disperser.
Life‐history variation in relation to nest site abundance in males of the freshwater goby Tridentiger brevispinis
Authors: Takahashi Daisuke
Published: June 2007

Abstract –  Age at maturity in males of the freshwater goby Tridentiger brevispinis, a species with exclusive paternal care, was investigated in two populations in Lake Biwa, Japan, that differed markedly in nest site abundance. At Ohmi‐maiko, where nest sites were scarce, most males matured at age 3, and mean body size of males guarding eggs in nests was larger than that of males sampled randomly (including both guarding and nonguarding males) in the population. Conversely, at Minamihama, where nest sites were abundant, many males matured at age 1, and there was no difference in body size between guarding males and males collected randomly. The slope of regression lines between body size of the guarding male and the number of eggs in his nest was greater in Ohmi‐maiko than in Minamihama. These results suggest that the shortage of nest sites enhances reproductive success in larger males, probably through male–male competition for nest sites and female mate choice for larger males. I conclude that in nest spawners, the availability of nest sites should strongly affect life‐history traits of males through sexual selection.
Egg Yolk Protein and Egg Yolk Phosvitin Inhibit Calcium, Magnesium, and Iron Absorptions in Rats
Authors: Ishikawa S.‐I. , Tamaki S. , Arihara K. , Itoh M.
Published: June 2007

ABSTRACT:  Egg yolk decreases the absorption of iron. The effects of egg yolk protein and egg yolk phosvitin on the absorption of calcium, magnesium, and iron were investigated by in vivo studies. Male Wistar rats were fed purified diets containing casein, soy protein, or egg yolk protein for 14 d. The apparent absorptions of calcium, magnesium, and iron in the rats fed the yolk protein‐based diet were lower than those in rats fed the casein‐ and soy protein‐based diets. The apparent phosphorus absorption and the apparent protein digestibility in the yolk protein group were lower than those in the casein and soy protein groups. In the feces of the yolk protein group, serine comprised more than 30% of the amino acids. The addition of egg yolk phosvitin to the casein diets at levels of 1% and 2% (w/w) produced effects on calcium and magnesium absorptions similar to those produced by the diet containing yolk protein. The tricine sodium dodecyl sulfate‐polyacrylamide gel electrophoresis (SDS‐PAGE) pattern suggested that phosphopeptide fragments having molecular masses of 28, 22, and 15 kDa were evident in the contents of the small intestine of the rats fed phosvitin diets. These results indicate that yolk protein, when compared with casein and soy protein, decreases calcium and magnesium absorption via the resistance of phosvitin to proteolytic action.
Characterization and Selection of Autochthonous Lactic Acid Bacteria Isolated from Traditional Iberian Dry‐Fermented Salchichón and Chorizo Sausages
Authors: Benito M.J. , Martín A. , Aranda E. , Pérez‐Nevado F. , Ruiz‐Moyano S. , Córdoba M.G.
Published: June 2007

ABSTRACT:  A total of 192 lactic acid bacteria were isolated from 2 types of naturally fermented dry sausages at 3 different stages of the ripening process in order to select the most suitable strains as starter cultures in dry‐cured sausage manufacture according to their technological characteristics such as glucose fermentation, lactic and acetic acid production, and proteolytic, lipolytic, and antimicrobial activities. Identification of the isolates revealed that 31.2% were Pediococcus pentosaceus, 26.9%Lactococcus lactis, 18.6%Pediococcus acidilactici, 17%Lactobacillus brevis, and sporadic isolates of Leuconostoc mesenteroides, Lactobacillus plantarum, and Lactobacillus curvatus. Most of the strains did not produce gas from glucose and showed the capacity to produce lactic acid rapidly. Some 25% of the strains were able to degrade tributyrin (esterase activity), but none showed lipolytic activity against olive oil and pork fat. Only 3 strains of P. acidilactici showed weak proteolytic activity against myofibrillar or sarcoplasmic proteins. Also, the same strains showed antimicrobial activity against Listeria monocytogenes. Nine strains with the best properties were preselected and tested for biogenic amine production. The results showed that two of the strains, identified as P. acidilactici by polymerase chain reaction, had the potential to be further tested as starter cultures in pilot processing of Iberian sausages.
Dependence of Fructooligosaccharide Content on Activity of Fructooligosaccharide‐Metabolizing Enzymes in Yacon (Smallanthus sonchifolius) Tuberous Roots during Storage
Authors: Narai‐Kanayama A. , Tokita N. , Aso K.
Published: June 2007

ABSTRACT:  Tuberous roots of yacon (Smallanthus sonchifolius) accumulate about 10%, on a fresh weight basis, of inulin‐type fructooligosacharides (FOSs), known as a food ingredient with various healthy benefits. However, we have a great difficulty to ensure these benefits because FOSs with a lower degree of polymerization (DP) decreased remarkably, and fructose increased when the tuberous roots were stored after harvesting even under previously recommended storage conditions of low temperature with high humidity. In the present study, to elucidate the involvement of FOS‐metabolizing enzymes in FOS reduction during storage at 90% relative humidity and 8°C, we extracted a crude protein from yacon tuberous roots and measured the activities of invertase (β‐fructofuranosidase, EC 3.2.1.26), sucrose:sucrose 1‐fructosyltransferase (1‐SST, EC 2.4.1.99), fructan:fructan 1‐fructosyltransferase (1‐FFT, EC 2.4.1.100), and fructan 1‐exohydrolase (1‐FEH, EC 3.2.1.80). The enzyme activities acting on sucrose, both invertase and 1‐SST, were weakened after storage for a month. In addition, the activity of 1‐FEH acting on short FOSs such as 1‐kestose (GF2) and 1‐nystose (GF3) was higher than that of 1‐FFT. These results suggest that the continuous decline in FOSs of low DP during storage was dependent mainly on the 1‐FEH activity. On the other hand, FOSs with a DP of ≥ 9 only slightly decreased in stored yacon tuberous roots during storage, though distinct 1‐FEH activity was observed in vitro toward a high‐DP inulin‐type substrate, indicating that highly polymerized FOSs content was unlikely to be closely connected with the 1‐FEH activity.
Combined Effects of Hydrostatic Pressure, Temperature, and pH on the Inactivation of Spores of Clostridium perfringens Type A and Clostridium sporogenes in Buffer Solutions
Authors: Paredes‐Sabja D. , Gonzalez M. , Sarker M.R. , Torres J.A.
Published: June 2007

ABSTRACT:  To develop a spore inactivation strategy, the effect of 15‐min hydrostatic pressure treatments (550 and 650 MPa) at 55 and 75 °C in citric acid buffer (4.75 and 6.5 pH) on spores of 5 isolates of Clostridium perfringens type A carrying the gene that encodes the C. perfringens enterotoxin (cpe) on the chromosome (C‐cpe), 4 isolates carrying the cpe gene on a plasmid (P‐cpe), and 2 strains of C. sporogenes were investigated. Treatments at 650 MPa, 75 °C and pH 6.5 were moderately effective against spores of P‐cpe (approximately 3.7 decimal reduction, DR) and C. sporogenes (approximately 2.1 DR) but not for C‐cpe (approximately 1.0 DR) spores. Treatments at pH 4.75 were moderately effective against spores of P‐cpe (approximately 3.2 DR) and C. sporogenes (approximately 2.5 DR) but not of C‐cpe (approximately 1.2 DR) when combined with 550 MPa at 75 °C. However, when pressure was raised to 650 MPa under the same conditions, high inactivation of P‐cpe (approximately 5.1 DR) and C. sporogenes (approximately 5.8 DR) spores and moderate inactivation of C‐cpe (approximately 2.8 DR) spores were observed. Further advances in high‐pressure treatment strategies to inactivate spores of cpe‐positive C. perfringens type A and C. sporogenes more efficiently are needed.
Phosphatidylinositol 4,5‐bisphosphate regulates inspiratory burst activity in the neonatal mouse preBötzinger complex
Authors: Crowder Erin A. , Saha Margaret S. , Pace Ryland W. , Zhang Honglu , Prestwich Glenn D. , Del Negro Christopher A.
Published: June 2007

Neurons of the preBötzinger complex (preBötC) form local excitatory networks and synchronously discharge bursts of action potentials during the inspiratory phase of respiratory network activity. Synaptic input periodically evokes a Ca2+‐activated non‐specific cation current (ICAN) postsynaptically to generate 10–30 mV transient depolarizations, dubbed inspiratory drive potentials, which underlie inspiratory bursts. The molecular identity ofICANand its regulation by intracellular signalling mechanisms during inspiratory drive potential generation remains unknown. Here we show that mRNAs coding for two members of the transient receptor potential (TRP) family of ion channels, namely TRPM4 and TRPM5, are expressed within the preBötC region of neonatal mice. Hypothesizing that the phosphoinositides maintaining TRPM4 and TRPM5 channel sensitivity to Ca2+may similarly influenceICANand thus regulate inspiratory drive potentials, we manipulated intracellular phosphatidylinositol 4,5‐bisphosphate (PIP2) and measured its effect on preBötC neurons in the context of ongoing respiratory‐related rhythms in slice preparations. Consistent with the involvement of TRPM4 and TRPM5, excess PIP2augmented the inspiratory drive potential and diminution of PIP2reduced it; sensitivity to flufenamic acid (FFA) suggested that these effects of PIP2wereICANmediated. Inositol 1,4,5‐trisphosphate (IP3), the product of PIP2hydrolysis, ordinarily causes IP3receptor‐mediatedICANactivation. Simultaneously increasing PIP2while blocking IP3receptors intracellularly counteracted the reduction in the inspiratory drive potential that normally resulted from IP3receptor blockade. We propose that PIP2protectsICANfrom rundown by interacting directly with underlying ion channels and preventing desensitization, which may enhance the robustness of respiratory rhythm.
Enhanced expression of three monocarboxylate transporter isoforms in the brain of obese mice
Authors: Pierre Karin , Parent Annabelle , Jayet Pierre‐Yves , Halestrap Andrew P. , Scherrer Urs , Pellerin Luc
Published: June 2007

Monocarboxylate transporters (MCTs) are membrane carriers for lactate and ketone bodies. Three isoforms, MCT1, MCT2 and MCT4, have been described in the central nervous system but little information is available about the regulation of their expression in relation to altered metabolic and/or nutritional conditions. We show here that brains of mice fed on a high fat diet (HFD) up to 12 weeks as well as brains of genetically obese (ob/ob) or diabetic (db/db) mice exhibit an increase of MCT1, MCT2 and MCT4 expression as compared to brains of control mice fed a standard diet. Enhanced expression of each transporter was visible throughout the brain but most prominently in the cortex and in the hippocampus. Using immunohistochemistry, we observed that neurons (expressing mainly MCT2 but also sometimes low levels of MCT1 under normal conditions) were immunolabelled for all three transporters in HFD mice as well as in ob/ob and db/db mice. At the subcellular level, changes were most remarkable in neuronal cell bodies. Western blotting performed on brain structure extracts allowed us to confirm quantitatively the enhancement of MCT1 and MCT2 expression. Our data demonstrate that the expression of cerebral MCT isoforms can be modulated by alterations of peripheral metabolism, suggesting that the adult brain is sensitive and adapts to new metabolic states. This observation could be relevant in the context of obesity development and its consequences for brain function.
Dynamic Modeling of a Monopropellant-Based Chemofluidic Actuation System
Authors: Gulati Navneet , Barth Eric J.
Published: June 2007

This paper presents a dynamic model of a monopropellant-based chemofluidic power supply and actuation system. The proposed power supply and actuation system, as presented in prior works, is motivated by the current lack of a viable system that can provide adequate energetic autonomy to human-scale power-comparable untethered robotic systems. As such, the dynamic modeling presented herein is from an energetic standpoint by considering the power and energy exchanged and stored in the basic constituents of the system. Two design configurations of the actuation system are presented and both are modeled. A first-principle based lumped-parameter model characterizing reaction dynamics, hydraulic flow dynamics, pneumatic flow dynamics, and compressible gas dynamics is developed for purposes of control design. Experimental results are presented that validate the model.
Mixed Sky-Hook and ADD: Approaching the Filtering Limits of a Semi-Active Suspension
Authors: Savaresi Sergio M. , Spelta Cristiano
Published: June 2007

The problem considered in this paper is the design and analysis of control strategies for semiactive suspensions in road vehicles. The most commonly used control algorithm is the well-known sky-hook (SH) damping. Recently, a new control approach named acceleration driven damping (ADD) has been developed, using optimal-control theory. It has been shown that SH and ADD have complementary characteristics: SH provides large benefits around the body resonance; otherwise performs similarly to a passive suspension; instead, ADD provides large benefits beyond the body resonance. The first goal of this paper is to show that—in their specific frequency domains—SH and ADD provide quasi-optimal performances, namely, that it is impossible to achieve (with the same semi-active shock-absorber) better performances. This result has been obtained using the framework of the optimal predictive control, assuming full knowledge of the disturbance. This result is very interesting since it provides a lower-bound to semi-active suspension performances. The second goal of the paper is to develop a control algorithm which is able to mix the SH and ADD performances. This algorithm is surprisingly simple and provides quasi-optimal performances.
Dynamic-Deflection Tire Modeling for Low-Speed Vehicle Lateral Dynamics
Authors: Koo Shiang-Lung , Tan Han-Shue
Published: June 2007

Vehicle lateral dynamics depends heavily on the tire characteristics. Accordingly, a number of tire models were developed to capture the tire behaviors. Among them, the empirical tire models, generally obtained through lab tests, are commonly used in vehicle dynamics and control analyses. However, the empirical models often do not reflect the actual dynamic interactions between tire and vehicle under real operational environments, especially at low vehicle speeds. This paper proposes a dynamic-deflection tire model, which can be incorporated with any conventional vehicle model to accurately predict the resonant mode in the vehicle yaw motion as well as steering lag behavior at low speeds. A snowblower was tested as an example and the data gathered verified the predictions from the improved vehicle lateral model. The simulation results show that these often-ignored characteristics can significantly impact the steering control designs for vehicle lane-keeping maneuvers at low speeds.