Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0023890 (cirrhosis)
 42,195 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A model has been developed for the administration to rats and baboons of ethanol as part of a nutritionally adequate liquid diet. With this regimen, ethanol intake was much higher than with conventional procedures. All animals gained or maintained their body weight, and liver morphology was normal in the controls. Isocaloric substitution of carbohydrate by ethanol (36% of total calories in rats and 50% in baboons) resulted in the production of fatty liver in all animals, while the baboons also developed alcoholic hepatitis and cirrhosis with increased activities of serum glutamic oxaloacetic transaminase. Inebriation and manifestation of dependence on withdrawal of the diet were observed in baboons and quantitated in the rat. Chemical alterations produced by ethanol at the fatty liver stage were characterized by hyperlipemia, striking triglyceride accumulation in the liver, and enhanced activities of microsomal drug metabolizing enzymes, including the microsomal ethanol oxidizing system (MEOS). In showing that all aspects of liver injury observed in alcoholics can be reproduced in animals by the feeding of pure ethanol with an adequate diet, this study incriminates ethanol itself as a cause for the hepatic complications. This new experimental model is proposed as a tool for the study of the pathogenesis and treatment of alcoholic liver injury and dependence.
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PMID:Animal models of ethanol dependence and liver injury in rats and baboons. 94 46

To determine whether ethanol per se affects testosterone metabolism, alcohol was administered to normal male volunteers for periods up to four weeks, resulting in an initial dampening of the episodic bursts of testosterone secretion followed by decreases in both the mean plasma concentration and the production rate of testosterone. The volunteers received adequate nutrition and none lost weight during the study, which tended to exclude a nutritional disturbance as the cause of the decreased testosterone levels. The changes in plasma luteinizing hormone suggested both a central (hypothalamus-pituitary) and gonadal effect of alcohol. In addition, alcohol consumption increased the metabolic clearance rate of testosterone in most subjects studied, probably owing to the combined effects of a decreased plasma binding capacity for the androgen and increased hepatic testosterone A-ring reductase activity. These results indicate that alcohol markedly affects testosterone metabolism independently of cirrhosis or nutritional factors.
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PMID:Effect of alcohol (ethanol) administration on sex-hormone metabolism in normal men. 95 74

Ethanol-1-14C method for the measurement of intrahepatic shunted blood flow was compared with the method of continuous infusion of D-galactose-1-14C. In controls, in chronic hepatitis, and in hepatic cirrhosis, per cent intrahepatic shunt measured by the ethanol-1-14C- method was about a half or one-third of that measured by the D-galactose-1-14C method. Study of radioactivity-dye concentration ratio of the blood sampled from the inferior vena cava showed that per cent intrahepatic shunt was underestimated by the ethanol-1-14C method because of permeability of ethanol-1-14C through the capillaries. In patients with hepatic carcinoma, in whom the carcinomatous tissue was supplied mainly by the hepatic artery, there was no significant difference in per cent intrahepatic shunt between both methods.
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PMID:Measurement of intrahepatic shunted blood flow by ethanol-1-14C method as compared with D-galactose-1-14C method. 96 99

Competitive protein-binding assay of 25-OH-D was developed by the use of specific vitamin D-binding proteins from vitamin D-deficient rat serum. Ether extract of serum sample which was dried and dissolved in ethanol, or standard solution of 25-OH-D3, was incubated with 3H-25-OH-D3 and vitamin D-binding protein for 2 hours at 4degreesC. Free and bound 3H-25-OH-D3 were separated through dextran-coated charcoal. The sensitivity of the assay system was 0.22 ng/tube. Percent cross reaction in the assay was 2.18% in vitamin D3, 0.70% in 1, 25-(OH)2-D3, less than 0.28% in 1alpha-OH-D3, and less than 0.06% in dihydrotachysterol, cholesterol and cortisol. Human serum 25-OH-D is 28.9+/-2.9 ng/ml in 19 normal subjects. Serum 25-OH-D in the old-age group (50-70 years of age) was significantly decreased, compared with that in the young-age group (20-40 years of age). Serum 25-OH-D was significantly decreased in gastrectomized and osteoporotic patients as well as in the patients with liver cirrhosis, in comparison with their age-controls.
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PMID:Effects of age and diseases on human serum 25-hydroxycholecalciferol determined by competitive protein-binding assay. 99 36

This study reproduces in experimental animals the sequential development of all the liver lesions seen in the human alcoholic: in 15 baboons fed ethanol, all developed fatty liver, five progressed to hepatitis, and five had cirrhosis. Maintenance of a nutritionally adequate regimen despite the intake of inebriating amounts of ethanol (50% of total calories) was achieved by incorporation of the ethanol in a totally liquid diet. Upon ethanol withdrawal, signs of physical dependence, such as seizures and tremors, developed. Ultrastructural changes of the mitochondria and the endoplasmic reticulum were already present at the fatty liver stage and persisted throughout the hepatitis and cirrhosis. The lesions were similar to those observed in alcoholics (including the inflammation and the central sclerosis) and differed from the alterations produced by choline and protein defiencies. At the fatty liver stage, some "adaptive" increases in activity of microsomal enzymes [aniline hydroxylase (EC 1.14.14.1) and the microsomal ethanol oxidizing system] were observed, but these tended to disappear with the development of hepatitis and cirrhosis. Fat accumulation was also much more pronounced in the animals with the hepatitis as compared with those with simple fatty liver (an 18-fold compared with 3- to 4-fold increase in liver triglycerides). The demonstration that these lesions can develop despite an adequate diet indicates that in addition to correction of the nutritional status, control of alcohol intake is mandatory for the management of patients with alcoholic liver injury.
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PMID:Sequential production of fatty liver, hepatitis, and cirrhosis in sub-human primates fed ethanol with adequate diets. 105 27

Alcohol intakes and dietary habits of 304 alcoholic, hospitalized patients were evaluated. There were 195 patients with hepatic cirrhosis, 40 precirrhotics, and 69 noncirrhotics. Alcohol contributed 50% to 58% of total calories. Two thirds of the patients drank excessively for more than 20 years. There were no statistically significant differences between the three groups in the duration or degree of alcohol excess. Dietary intakes were assessed for a period of at least two years before the presenting illness. Noncirrhotics had higher food caloric intakes and higher protein intakes than the cirrhotics (P less than .05). The findings suggest that dietary factors may be involved in the pathogenesis of the disease.
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PMID:Alcohol and dietary factors in cirrhosis. An epidemiological study of 304 alcoholic patients. 115 66

Percutaneous liver biopsies obtained from patients with a history of chronic alcoholism and normal liver, fatty liver, alcoholic hepatitis, or active cirrhosis were incubated with tritiated proline to determine the pattern of collagen biosynthesis in these conditions. Incorporation of labeled proline and hydroxyproline into salt-soluble and insoluble fractions of collagen was evaluated by radiochemical analysis and tissue localization documented by autoradiography. Biopsy specimens of alcoholic hepatitis and cirrhosis exhibit a significant increase in the amount of radioactive proline and hydroxyproline in salt-soluble and insoluble collagen. Marked accumulation of radioactivity occurred over bile ducts, fibroblasts, and collagen fibers in the portal area and over hepatocytes, fibroblasts, and collagen fibers in the centrilobular area. Fatty liver is associated with an increase in uptake of proline and hydroxyproline in the salt-soluble fraction of collagem; silver grains appear in the periphery of fat-laden cells and in areas of focal inflammation. Digestion by collagenase indicates that labeling over fibroblasts and collagen reflects active synthesis, whereas, entry of proline into the cell protein pool is responsible for accumulation of radioactivity in other sites. In vitro ethanol causes a significant increase in the incorporation of proline and hydroxyproline into collagen in biopsy specimens of alcoholic hepatitis or active cirrhosis, but has no effect on collagen synthesis by normal or fatty liver.
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PMID:Collagen biosynthesis in liver disease of the alcoholic. 117 Feb 67

Zinc deficiency is a concomitant of both alcoholism and cirrhosis, as indicated by plasma and tissue measurements in man. The intracellular sites of zinc distribution, the site-specific nature of alcohol/cirrhosis-related depletion, and the alcohol exposure-zinc depletion time function have not been reported. Spague-Dawley rats (16) at 5 to 6 weeks were given normal chow and 20 per cent ethanol as sole water source. Control animals (14) had tap water. In rats killed at 2, 5, 9, and 14 weeks, zinc levels were measured by atomic absorption spectroscopy in plasma (p); muscle tissue (MT), cell sap (MCS) cell sap-free (MCSF), and mitochondria (MM); liver tissue (LT), cell sap (MCS), cell sap-free fraction (LCSF), And mitochondria (LM). Control zinc levels were stable in all tissues over the 14-week study; p = 108, plus or minus 10 mug per 100 ml., MT = 125 plus or minus 18, MCS = 30.3 plus or minus 3, MCSF = 70 plus or minus 6, MM = 209 plus or minus 17, LT = 198 plus or minus 29, LCS = 125 plus or minus 11.0, LCSF = 79.5 plus or minus 11.2, and LM = 291 plus or minus 30 mug per gram of dry tissue. Ethanol-fed rats showed marked decrease in all liver zinc fractions from the earliest (2 weeks) time, with the greatest depletion in LM to 35 per cent of control. MT and p zinc showed monotonic gradual declines at the rate of 3 per cent per week, becoming statistically different from control at 9 weeks in both tissues. Normal weight gain occurred in control animals: alcohol rats gained 52 per cent of control to 5 weeks, and showed no subsequent gain, weighing 62 per cent of control levels at 14 weeks. Liver mitochondria contain the highest zinc concentration, and are most rapidly depleted. MT and p declines follow hepatic zinc loss.
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PMID:Distribution of zinc in skeletal muscle and liver tissue in normal and dietary controlled alcoholic rats. 117 Feb 68

Malnutrition is common among alcoholics because alcohol displaces protein-, vitamin-, and mineral-containing foods in the diet, and chronic alcohol consumption results in maldigestion and malabsorption of essential nutrients. In addition, alcohol exerts direct toxic effects on both the liver and gut, resulting in structural alterations in the intestine and the development of fatty liver, alcoholic hepatitis, and cirrhosis. Liver injury is preceded by an adaptive phase characterized by accelerated metabolism of drugs (including ethanol), and hyperlipemia, secondary to hypertrophy and hyperactivity of the smooth endoplasmic reticulum. Side effects include enhanced hepatotoxicity of CCI4 and possibly energy wastage. Alcoholics should not be led to beleive that correction or prevention of nutritional deficiency will prevent liver damage in the face of continued alcohol abuse.
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PMID:Alcohol and malnutrition in the pathogenesis of liver disease.. 117 54

The constant failure to produce a liver cirrhosis that can be ascribed to alcohol in the rat promoted the present study in guinea-pigs. The animals were given 40 per cent of calories as ethanol during 8 months. However, no alcoholic hepatitis or cirrhosis developed. Triglycerides and cholesterol increased in the liver and in serum. The persistance of liver triglyceride increase in spite of a rather low fat content of the diet is in contrast to experiences in the rat. A slight depression of coagulation factors II, VII, X and XI was observed in the ethanol-fed animals.
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PMID:Effects on lipids, coagulation factors and liver histology of long-term ethanol administration to guinea-pigs. 117 46


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