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Biomedical subjects

Y Israel

Publications and source records attributed to Y Israel.

At least 109 records · Page 6Linked to original sources
PubMed1983

Calcium requirement for anoxic liver cell injury.

There is disagreement as to whether Ca2+ entrance into the cell constitutes a final common pathway in cell death by a variety of injurious conditions. Pre-necrotic lesions and leakage of lactate dehydrogenase were induced both in isolated perfused rat livers and in freshly isolated hepatocytes by short exposure to anoxic conditions. Removal of Ca2+ from the media markedly reduced cell damage induced by anoxia in the perfused liver preparation but not in freshly isolated hepatocytes. Data obtained support the hypothesis that Ca2+ ions play a role in the process of cell death in intact preparations and possibly in vivo, and suggest that mechanism of cell necrosis may be different in the perfused liver than in freshly isolated suspended hepatocytes.

Animals↗
PubMed1982

The swift increase in alcohol metabolism. Inhibition by propylthiouracil.

Administration of a single large dose of ethanol (5 g/kg) to rats elevates the rates of ethanol metabolism and of oxygen consumption in perfused livers in 2-3 hr. Pretreatment with the antithyroid drug propylthiouracil (PTU) for 10 days abolished both of these effects. Under all treatment conditions studied (controls; PTU-pretreatment; acute ethanol treatment; PTU-pretreated + acute ethanol treatment),, a significant correlation between ethanol metabolism and oxygen consumption was observed (r = 0.86). It is concluded that a normal thyroidal state is required to evoKe the swift increase in alcohol metabolism (SIAM) and an elevation of oxygen consumption.

Animals↗
PubMed1982

Alcohol-induced hepatomegaly: pathogenesis and role in the production of portal hypertension.

Hepatomegaly after chronic alcohol consumption results from an increase in cell size and not in cell number. About 50--60% of the increase in liver weight is accounted for by an increase in intracellular water, while extracellular water remains constant. Therefore, a substantial reduction in the ratio of extracellular to intracellular water occurs. Intracellular potassium can osmotically account for 40--50% of the excess water retained in the hepatocytes. It is proposed that an increase in hepatocyte size after chronic alcohol consumption compresses vascular-sinusoidal pathways. This results, after a threshold in cell size is exceeded, in increased intrahepatic and portal pressure. Possible factors responsible for the threshold are proposed. By applying the concept that animal cells act as osmometers, a new in vitro model has been developed to study the relationship between cell enlargement and portal pressure. In this model, the existence of a threshold and the generation of portal hypertension associated with hepatocyte enlargement have been demonstrated. In humans with alcoholic liver disease, a threshold in hepatocyte size enlargement (1600--1700 micrometer 2) before pressures were increased was also observed. In these patients, a strong correlation was also found between hepatocyte size and intrahepatic pressure. The same correlation occurs regardless of the presence or absence of cirrhosis, therefore suggesting that a major determinant of portal hypertension in cirrhosis is cell size and not the existence of nodules of fibrous septa. The higher portal pressures found in cirrhotics may be explained by the fact that these patients have larger hepatocytes.

Animals↗
PubMed1981

Early identification of alcohol abuse: 2: Clinical and laboratory indicators.

Despite awareness of the wide variety of clinical and laboratory abnormalities associated with alcohol abuse, drinking problems often remain undetected in hospital and in general medical practice. The diagnosis of alcohol abuse has been emphasized repeatedly in the literature but far less attention has been paid to indicators that would permit detection of excessive drinking at a stage when intervention might be more effective and less costly. The search for indicators of early alcohol abuse is complicated since many of the medical sequelae of alcoholism are nonspecific and may only be manifested after a number of years of excessive drinking. Part 2 of this two-part series considers various clinical and laboratory features related to alcohol abuse and highlights items that are potentially more sensitive for detecting early stages of problem drinking. Use by physicians of a composite profile of both biomedical and psychosocial indicators of excessive alcohol consumption is recommended for early identification of this problem.

Alcoholism↗
PubMed1981

Early identification of alcohol abuse: 1. Critical issues and psychosocial indicators for a composite index.

Traditional approaches to the medical management of alcohol-related disorders have met with limited success in altering the prevalence of alcohol abuse. Evidence suggests that identifying early those who drink to excess and intervening with low-cost educational and motivational programs could significantly reduce the prevalence of alcohol-related disabilities. However, physicians must take systematic steps to detect alcohol abuse. Part 1 of this two-part series discusses the need for early identification of individuals who drink to excess and the factors that may either facilitate or hinder the development of effective programs for detecting alcohol abuse. A profile is given of important psychosocial indicators of alcohol abuse, including the classic signs of alcohol abuse, the early manifestations of heavy drinking, the predisposing or high-risk factors for alcohol abuse, and the precipitating events and correlated habits of excessive drinking.

Alcoholism↗
PubMed1981

Low-molecular-weight polyethylene glycol as a probe of gastrointestinal permeability after alcohol ingestion.

Gastrointestinal permeability has been assessed previously by the excretion of PEG-400, which consists of inert molecules that are neither degraded nor metabolized and are excreted intact in the urine. We report here the effects of alcohol on gastrointestinal permeability using PEG-400. Ten grams of PEG-400 dissolved in 60 ml of water were given to 12 intoxicated alcoholics (mean blood alcohol: 2406 mg/liter). The mean urinary excretion of PEG-400 in the following 6 hr was 3.75 +/- 0.3 g SEM. When repeated after sobering up (mean elapsed time: 45 hr), all except one subject showed a decrease in PEG-400 excretion (mean: 2.08 +/- 0.2 g) (P less than 0.001). Similar experiments were conducted in two series with 12 normal controls. (1) In 7 subjects the administration on consecutive days of (a) PEG-400 (10 g) alone, (b) 10.2 g (0.42 mol) of ethanol plus PEG-400 (10 g), (c) PEG-400 (10 g) alone, and (d) PEG-400 (10 g) plus a diuretic (40 mg furosemide) resulted in the following values of PEG-400 excretion in urine: (a) 2.12 +/- 0.3 g; (b) 3.5 +/- 0.3 g, P less than 0.005; (c) 2.02 +/- 0.4, NS; and (d) 2.2 +/- 0.2 g, NS. (2) In the second experiment (5 subjects) the administration on subsequent days of (a) PEG-400 (10 g) + 0.42 mol of urea; (b) PEG-400 (10 g) + 19.2 g ethanol; (c) PEG-400 (10 g) + 0.42 mol of urea resulted also, as in the previous experiment, in increased urinary excretion of PEG-400 after the solution (b) containing ethanol (P less than 0.001). Peak serum levels of PEG-400 were (a) 0.094 +/- 0.01 g/liter; (b) 0.152 +/- 0.02 g/liter (P less than 0.05); and (c) 0.095 +/- 0.01 (P less than 0.05). The ratio of urea--creatinine clearance and urinary volumes were the same in the three periods. Therefore, PEG-400 excretion was not related to changes in urinary clearance or in volume, since the furosemide increased the volume but not PEG-400 excretion. It is concluded that ethanol increases the permeability of the gastrointestinal tract as measured by the PEG-400 test, both in chronic alcoholics during intoxication and in nonalcoholics after a small dose of ethanol. The permeability alteration is transient once ethanol ingestion stops.

Adult↗
PubMed1981

Effects of ethanol on hepatic blood flow in the rat.

Hepatic blood flow measured by indocyanine green clearance was studied in rats after an acute intoxicating dose of ethanol (2 g/kg) or after chronic ethanol administration by feeding with alcohol liquid diets. Acute intoxication to normal animals did not modify hepatic blood flow. In chronically alcohol-fed rats, hepatic blood flow was significantly decreased when measured after 15 hr of abstinence. If ethanol was not withdrawn and an acute dose of ethanol was given before the indocyanine green clearance, a decreased hepatic blood flow was not observed. It is suggested that the reduction of hepatic blood flow in recently abstinent chronically alcohol-treated animals is related to the withdrawal syndrome.

Alcoholic Intoxication↗
PubMed1981

Hepatocyte demand and substrate supply as factors in the susceptibility to alcoholic liver injury: pathogenesis and prevention.

In conclusion, the studies presented suggest that two factors commonly occurring in the alcoholic, namely, an increased rate of ethanol metabolism and hepatomegaly, may have important pathogenic implications in alcoholic liver disease. An increased rate of ethanol metabolism is linked to a greater oxygen demand, thus resulting in greater susceptibility to hypoxia in Zone 3 of the liver acinus, a factor which might be responsible for hepatocellular necrosis in alcoholic hepatitis. Propylthiouracil has been shown to have a protective effect against hypoxic necrosis in alcohol-fed animals and has been found to be most effective in accelerating the rate of recovery of alcoholics with active liver disease. On the other hand, hepatocyte expansion in hepatomegaly, in the face of a semi-rigid liver capsule, leads to constriction of extracellular volume and to an increase in intrahepatic and portal pressure. The latter, in turn, could produce a variety of haemodynamic alterations as those found in the alcoholic. To what extent the mechanisms described are responsible for or might add to the myriad of other disturbances observed in alcoholic disease should be further analysed.

Animals↗
PubMed1981

Correlation of intrahepatic pressure with collagen in the Disse space and hepatomegaly in humans and in the rat.

In 70 alcoholic patients the amount of collagen in the space of Disse was compared, using an electron microscopic graded score, to the height of the intrahepatic pressure. A highly significant correlation was found between the amount of collagen and intrahepatic pressure in the group as a whole (r = 0.84; p < 10(-6)), as well as in subgroups of 30 alcoholic patients with normal livers or steatosis (r = 0.83; p < 10(-6)), 9 patients with alcoholic hepatitis (r = 0.81; p < 0.01), and 31 with cirrhosis (r = 0.86; p < 10(-6)). A nonparametric correlational analysis for the complete group also showed a significant relationship (rho = 0.85; p < 10(-6)) between collagen scores and intrahepatic pressure. In 60 patients hepatocyte surface area was measured in the biopsies. In these, hepatocyte surface area significantly correlated with intrahepatic pressure (r = 0.68; p < 10(-7)). No correlation was found between intrahepatic pressure and fat, alcoholic hyalin, or terminal hepatic vein sclerosis. Only with necrosis (r = 0.38; p < 0.001) and inflammation (r = 0.29; p < 0.05) was there a significant relationship with intrahepatic pressure. Chronic ethanol administration for 4 wk in liquid diets to young Wistar rats produced a 50% hepatomegaly due to an increase in hepatocyte size. Intrahepatic pressure in the rats receiving alcohol (19.3 +/- 2.3 mmHg) was significantly higher than in the controls on sucrose (10.4 +/- 0.9 mmHg) (p < 0.01). A highly significant correlation was found between hepatocyte surface area and intrahepatic pressure (r = 0.70; p < 0.005). There was no increase in collagen in the Disse space in these animals. Therefore, hepatomegaly in the absence of an increase in collagen in the Disse space may result in increased intrahepatic pressure. These studies may indicate a sequence of events: hepatomegaly, portal hypertension, and collagenization in the Disse space, which could occur in alcoholic liver disease.

Alcoholism↗
PubMed1981

Long-term ethanol administration and short- and long-term liver regeneration after partial hepatectomy.

The purpose of this study was to determine whether long-term ethanol consumption affects the long-term regeneration of the liver after partial hepatectomy and to study whether the metabolic demands imposed on the liver by the regenerative process accentuate liver damage produced in the liver by ethanol. Animals fed alcohol (35% of total calories) in liquid diets over time were partially hepatectomized (68% removal) and then were given ethanol-containing diets until complete liver restitution. They were studied at 24 hr and at 7 and 14 days. At these times, prior and continued ethanol administration did not result in changes in total DNA restituted, percent of cells undergoing mitosis, or incorporation of 3H-thymidine into DNA as determined chemically and by autoradiography. After partial hepatectomy, ethanol-fed animals showed a reduction in both DNA and proteins per gram of liver. However, these effects were the result of the hepatomegaly induced by ethanol and were also observed in sham-operated animals fed the diets containing ethanol. An apparent decrease in percent restitution of live weight was observed at 24 hr after hepatectomy in the ethanol-fed animals. However, this was caused by a marked increase in hepatocyte size in the controls, which matched the already enlarged hepatocytes in the ethanol-fed animals. Partial hepatectomy was found to transiently increase the lipid content of the livers in control animals. In ethanol-fed animals partial hepatectomy resulted in markedly fatty livers, as observed both histologically and chemically, which exceeded these abnormalities in alcohol-fed sham-operated rats. In conclusion, long-term ethanol consumption prior to partial hepatectomy and continuous ethanol consumption after the operation did not affect negatively the complete restitution of the liver when compared with controls.

Animals↗
PubMed1980

Modulation of alcohol dehydrogenase and ethanol metabolism by sex hormones in the spontaneously hypertensive rat. Effect of chronic ethanol administration.

In young (4-week-old) male and female spontaneously hypertensive (SH) rats, ethanol metabolic rate in vivo and hepatic alcohol dehydrogenase activity in vitro are high and not different in the two sexes. In males, ethanol metabolic rate falls markedly between 4 and 10 weeks of age, which coincides with the time of development of sexual maturity in the rat. Alcohol dehydrogenase activity is also markedly diminished in the male SH rat and correlates well with the changes in ethanol metabolism. There is virtually no influence of age on ethanol metabolic rate and alcohol dehydrogenase activity in the female SH rat. Castration of male SH rats prevents the marked decrease in ethanol metabolic rate and alcohol dehydrogenase activity, whereas ovariectomy has no effect on these parameters in female SH rats. Chronic administration of testosterone to castrated male SH rats and to female SH rats decreases ethanol metabolic rate and alcohol dehydrogenase activity to values similar to those found in mature males. Chronic administration of oestradiol-17beta to male SH rats results in marked stimulation of ethanol metabolic rate and alcohol dehydrogenase activity to values similar to those found in female SH rats. Chronic administration of ethanol to male SH rats from 4 to 11 weeks of age prevents the marked age-dependent decreases in ethanol metabolic rate and alcohol dehydrogenase activity, but has virtually no effect in castrated rats. In the intoxicated chronically ethanol-fed male SH rats, serum testosterone concentrations are significantly depressed. In vitro, testosterone has no effect on hepatic alcohol dehydrogenase activity of young male and female SH rats. In conclusion, in the male SH rat, ethanol metabolic rate appears to be limited by alcohol dehydrogenase activity and is modulated by testosterone. Testosterone has an inhibitory effect and oestradiol has a testosterone-dependent stimulatory effect on alcohol dehydrogenase activity and ethanol metabolic rate in these animals.

Age Factors↗
PubMed1980

Enhancement of noradrenaline-induced metabolic coronary dilatation by ethanol.

Isolated perfused rat hearts receiving noradrenaline as a cardiostimulatory agent show the characteristic metabolic coronary dilatations which correlate with the inotropic effect elicited by noradrenaline. Addition of ethanol (20-400 mg/dl) to the perfusion fluid produced a concentration-dependent enhancement of the metabolic coronary dilatation. The latter was increased by 50% at about 125 mg ethanol/dl. Since the inotropic responses to noradrenaline were not affected by ethanol it is suggested that alcohol produces an alteration in the system that normally adapts the coronary flow to an increased cardiac performance. The effect of ethanol was fully reversible; removal of alcohol from the perfusion fluid restored the metabolic coronary dilatation in response to noradrenaline to control values. At high concentrations, 200-400 mg/dl, ethanol produced a small but significant reduction in contractility of the myocardium (11.1 +/- 2.4%). At these concentrations ethanol enhanced the noradrenaline induced metabolic coronary dilatation by about 100%. These data indicate that ethanol at concentrations that are commonly found in blood in vivo may be beneficial in facilitating the coronary reactions during cardiac exertion. However cardiodepressant effects, particularly at higher concentrations, must also be considered.

Animals↗