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Biomedical subjects

Y Israel

Publications and source records attributed to Y Israel.

At least 91 records · Page 5Linked to original sources
PubMed1987

Basolateral gamma-glutamyl transferase ectoactivity in rat liver: effects of chronic alcohol consumption.

Chronic alcohol consumption is known to increase hepatic gamma-glutamyl transferase (GGT) activity. The biological significance of this change has, however, remained unknown. Using a recently described methodology which allows the determination of basolateral ectoenzyme GGT activity (Ble-GGT) in perfused rat liver (Speisky et al, 1985), we have investigated the effects of chronic alcohol consumption on Ble-GGT and on its participation in the utilization of circulating glutathione (GSH). Ble-GGT was markedly increased (40-75%) by chronic alcohol consumption. The ecto-activity strongly correlated with total GGT activity, measured in whole liver homogenates from ethanol-fed animals (r = 0.898, p less than 0.001). Ble-GGT was found to catalyze the utilization of significant amounts of circulating GSH (7.4-14.7 nmol/min/100 g B.W.). Chronic ethanol treatment led to marked increases (111%) in the hydrolysis of circulating GSH, which highly correlated (r = 0.958, p less than 0.001) with total liver GGT activity. An increased Ble-GGT activity following chronic alcohol consumption might constitute a mechanism to increase the hepatic availability of GSH precursors.

Alcohol Drinking↗
PubMed1986

Detection of an alcohol specific product in urine of alcoholics.

A simple procedure, using high performance liquid chromatography, was developed to detect and measure in urine an alcohol specific product, "ASP" indicative of chronic alcohol consumption. One day after hospital admission, the average amount of ASP in urine of alcoholics was 17 times higher than that of control subjects and 5 and 2 times higher after 7 and 14 days of abstinence, respectively. Urinary levels of ASP should be of value in the identification of chronic alcoholism.

Alcohol Drinking↗
PubMed1986

Clinical versus laboratory detection of alcohol abuse: the alcohol clinical index.

To determine reliable indicators of alcohol abuse a comprehensive set of clinical and laboratory information was acquired from three groups of subjects with a wide range of drinking histories: 131 outpatients with alcohol problems, 131 social drinkers, and 52 patients from family practice. Findings from clinical examination provided greater diagnostic accuracy than laboratory tests for detecting alcohol abuse. Logistic regression analysis produced an overall accuracy of 85-91% for clinical signs, 84-88% for items from the medical history, and 71-83% for laboratory tests in differentiating the three groups. Further analyses showed 17 clinical signs and 13 medical history items that formed a highly diagnostic instrument (alcohol clinical index) that could be used in clinical practice. A probability of alcohol abuse exceeding 0.90 was found if four or more clinical signs or four or more medical history items from the index were present. Despite recent emphasis on the laboratory diagnosis of alcohol abuse simple clinical measures seem to provide better diagnostic accuracy.

Adult↗
PubMed1986

Monoclonal and polyclonal antibodies against acetaldehyde-containing epitopes in acetaldehyde-protein adducts.

Immunization of mice with acetaldehyde conjugated to human plasma proteins resulted in the production of polyclonal antibodies that reacted with erythrocyte protein-acetaldehyde conjugates, but not with control erythrocyte proteins. Such antibodies recognized erythrocyte protein-acetaldehyde conjugates prepared with 20-100 microM acetaldehyde, concentrations that exist in the blood of alcoholics. The antibodies also recognized acetaldehyde condensation products with synthetic poly-(L-lysine). Immunization with keyhole limpet hemocyanin-acetaldehyde conjugates resulted in antibodies against both plasma protein-acetaldehyde and erythrocyte protein-acetaldehyde conjugates, which did not cross-react with the respective unmodified carrier proteins. Immunization with human erythrocyte protein-acetaldehyde condensates led to the production of antibodies against both the protein moiety as well as the condensate. Monoclonal antibodies with affinities 50 times greater for the condensate than for the carrier protein were produced by hybridization of spleen cells from the immunized mice. Chronic alcohol administration to mice for 45-50 days led to the generation of antibodies that reacted against protein-acetaldehyde conjugates, suggesting that such adducts are formed in vivo and can act as neoantigens. Antibodies against acetaldehyde adducts should be of value in the identification of alcohol consumption and in the study of the biology of the adducts in relation to organ pathology.

Acetaldehyde↗
PubMed1986

New instrument using gas sensors for the quantitative analysis of ethanol in biological liquids.

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, beta-nicotinamide 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.

Alcohol Dehydrogenase↗
PubMed1986

Role of ethanol metabolism in the ethanol-induced increase in splanchnic circulation.

In this study we report the effect on splanchnic hemodynamics of acute oral ethanol at doses ranging from 0.25 to 4.0 g/kg body wt. Flows were determined by use of a radioactive microsphere technique. Ethanol was found to increase portal blood flow by 23-57%. In awake rats this increase reached a plateau at the 0.5 g/kg dose. In ketamine-anesthetized rats, the increase was observed only at doses of 3.0 g/kg or more, with the response at doses of 0.5, 1.0, and 2.0 g/kg being suppressed by ketamine. Inhibition of alcohol dehydrogenase by intra-arterial administration of 4-methylpyrazole resulted in suppression of the liver blood flow increase after ethanol was administered to awake animals. Ethanol in the range of doses studied did not result in changes in blood glucagon levels. Rats fed ethanol-containing diets for 4 wk and withdrawn for 18 h had the same response to acute oral ethanol as did naive rats. It is suggested that ethanol metabolism mediates the effects of ethanol on splanchnic blood flow. An increase in splanchnic blood flow when concurrent with an increase in liver O2 consumption induced by ethanol might protect the liver from hypoxic damage.

Animals↗
PubMed1985

Inhibitory effect of propylthiouracil on the development of metabolic tolerance to ethanol.

Chronic ethanol administration (4-5 weeks) to female spontaneously hypertensive (SH) rats led to a marked increase in the rate of ethanol metabolism. This was accompanied by an increase in hepatic alcohol dehydrogenase (ADH) and by an increase in the rate of oxygen consumption in perfused livers of these animals. Treatment with the antithyroid drug 6-n-propyl-2-thiouracil (PTU) during the last 9 days (40 mg/kg/day) of the chronic administration of ethanol reduced hepatic oxygen consumption, resulting in a net diminution of the metabolic tolerance to ethanol, despite a further elevation in ADH activity. In these animals, microsomal ethanol-oxidizing system (MEOS) activity was not affected by chronic ethanol administration or by treatment with PTU. Data strongly suggest that in the female SH rat all the metabolic tolerance to ethanol proceeds via the ADH pathway, and that the increase in hepatic oxygen consumption is more important in the development of metabolic tolerance to ethanol than the increased ADH levels.

Alcohol Dehydrogenase↗
PubMed1985

Increased loss and decreased synthesis of hepatic glutathione after acute ethanol administration. Turnover studies.

The effect of acute ethanol administration on rates of synthesis and utilization of hepatic glutathione (GSH) was studied in rats after a pulse of [35S]cysteine. A 35% decrease in hepatic GSH content 5h after administration of 4 g of ethanol/kg body wt. was accompanied by a 33% increase in the rate of GSH utilization. The decrease occurred without increases in hepatic oxidized glutathione (GSSG) or in the GSH/GSSG ratio. The rate of non-enzymic condensation of GSH with acetaldehyde could account for only 6% of the rate of hepatic GSH disappearance. The increased loss of [35S]GSH induced by ethanol was not accompanied by an increased turnover; rather, a 30% inhibition of GSH synthesis balanced the increased rate of loss, leaving the turnover rate unchanged. The rate of acetaldehyde condensation with cysteine in vitro occurred at about one-third of the rate of GSH loss in ethanol-treated animals. However, ethanol induced only a minor decrease in liver cysteine content, which did not precede, but followed, the decrease in GSH. The characteristics of 2-methylthiazolidine-4-carboxylic acid, the condensation product between acetaldehyde and cysteine, were studied and methodologies were developed to determine its presence in tissues. It was not found in the liver of ethanol-treated animals. Ethanol administration led to a marked increase (47%) in plasma GSH in the post-hepatic inferior vena cava, but not in its pre-hepatic segment. Data suggest that an increased loss of GSH from the liver constitutes an important mechanism for the decrease in GSH induced by ethanol. In addition, an inhibition of GSH synthesis is observed.

Acetaldehyde↗
PubMed1985

Pattern of alcohol use associated with self-identified problem drinking.

To estimate the pattern and level of alcohol consumption leading to problem drinking, the drinking histories of 70 early stage problem drinkers were examined. An average consumption of four drinks (54 g/ethanol), on an average of three days/week, was the pattern that best separated the phase when patients were problem free from the phase when their drinking led to problems.

Adolescent↗
PubMed1985

Lack of changes in diene conjugate levels following ethanol induced glutathione depletion or hepatic necrosis.

Acute administration of 5 g/kg ethanol resulted in a 35% reduction of glutathione levels but not in increases in lipoperoxidation as measured by diene conjugate levels in mitochondria or in microsomes. Administration of diethylmaleate which markedly decreased glutathione levels by 85% did not render the livers susceptible to lipoperoxidation after ethanol administration. Chronic alcohol administration did not result in detectable changes in diene conjugates with respect to isocaloric sucrose treatment. Liver necrosis when induced by anemia in rats chronically treated with ethanol was not accompanied by increases in diene conjugate levels.

Animals↗
PubMed1984

Hypermetabolic state and hypoxic liver damage.

The concept of a hypermetabolic state to explain metabolic tolerance to ethanol grew from the recognition that the rate of alcohol metabolism is, in general, limited by the rate at which mitochondria can reoxidize reducing equivalents and thus by the rate at which oxygen can be consumed by the liver. This relationship appears to be most important in conditions in which the alcohol dehydrogenase (ADH)/QO2 ratio is high and is not in conflict with observations suggesting that ADH can, under certain conditions, constitute a rate-determining step for ethanol metabolism in rodents. Liver preparations from animals fed alcohol chronically, in which an increase in ethanol metabolism is shown, consume oxygen at higher rates. This effect, concerning which there is discrepancy among investigators, depends on the type of preparation. Thyroid hormones play a permissive role in the development of the hypermetabolic state, while increased circulating levels of these hormones are not required. Antithyroid drugs inhibit both metabolic tolerance in vivo and the hypermetabolic state. While the hypermetabolic state requires an increased ATP utilization in the form of an adenosine triphosphatase, or an inhibition of ATP synthesis, the different mechanisms proposed for such an effect do not quantitatively account for the increases in oxygen consumption. In humans and animals chronically exposed to ethanol, but withdrawn, oxygen tensions in blood leaving the liver are significantly reduced. In some situations, low oxygen tensions in zone 3 of the hepatic acinus can reach critical hypoxic levels and may lead to cell necrosis. Studies in which the effectiveness of propylthiouracil is tested in human alcoholic hepatitis are discussed.

Adenosine Triphosphate↗
PubMed1984

Identification of alcohol abuse using laboratory tests and a history of trauma.

In a study involving 68 ambulatory patients with known alcohol problems and 68 social drinkers matched for age and sex, a questionnaire about the patients' history of trauma identified 7 out of 10 subjects with drinking problems. In contrast, abnormal values for gamma-glutamyl transferase, mean corpuscular volume, or high-density lipoproteins had only moderate sensitivity (26% to 40%) for identifying alcohol problems but excellent specificity (88% to 99%) for ruling out cases. Similar rates of sensitivity and specificity were found among 61 family practice patients. Diagnostic accuracy was improved by combining tests results, using computer-based logistic regression analysis. This study suggests that a brief questionnaire on history of trauma is valuable for the earlier detection of problem drinking in ambulatory populations, in contrast to laboratory tests, which appear to have high sensitivity only with more chronic alcoholics.

Adult↗
PubMed1983

On the characteristics of alcohol-induced liver enlargement and its possible hemodynamic consequences.

Chronic consumption of alcohol leads to an increase in liver weight, primarily due to an increase in hepatocyte volume. About 50-60% of such an increase is due to an increase in intracellular water. Accumulation of intracellular K+ osmotically accounts for about one half of the increase in intracellular water, while an increase in soluble proteins plays only a minor role in such an increase in cell volume. The increase in intracellular water is accompanied by a relative reduction in water in the extracellular space, probably due to compression of the extracellular volume by the enlarged hepatocytes. It is suggested that such an increase in hepatocyte size, with an attending reduction of the extracellular volume, results in an increased resistance to blood flow through the liver and thus in an increase in portal pressure. In alcoholics, portal and intrahepatic pressure correlate with cell size both in cirrhotics (r = 0.79) and in non-cirrhotics (r = 0.74), thus suggesting that cell enlargement plays a major role in the production of portal hypertension in the alcoholic.

Alcoholism↗
PubMed1983

Variation in mortality from ischemic heart disease in relation to alcohol and milk consumption.

A simple correlation analysis of data for 19 Western countries confirmed previously reported findings that the rate of mortality from ischemic heart disease (IHD) varies inversely with total alcohol consumption and positively with the consumption of unfermented milk proteins. However, when milk protein consumption was held constant in a multiple-partial correlation analysis, the association between total alcohol consumption and the IHD mortality rate was reduced to non-significance. In contrast, when alcohol consumption was held constant there was little effect on the high correlation between the mortality rate and the consumption of milk proteins. Multiple regression analysis confirmed the importance of the milk factor over alcoholic beverages as a determinant of variation in IHD mortality rates. It was concluded that the inverse association between alcohol consumption and IHD mortality, observed in international comparisons, is probably largely an artifact of a negative association between alcohol and milk consumption. An hypothesis is offered respecting the component of milk which might be responsible for its apparent atherogenicity.

Alcohol Drinking↗