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)

Proline metabolism was prospectively evaluated in patients with surgical sepsis, cirrhosis, and elective surgical procedures. Significant correlations were found in the septic patients. Proline levels were an excellent indicator of mortality and correlated positively with lactate levels. Lactate and proline were inversely related to total peripheral resistance and oxygen consumption. In septic patients who expired: the metabolites involved in the hepatic pathways of proline degradation were elevated in proportion to proline; lactate, glutamate and proline were directly related to pyruvate; lactate/pyruvate ratios were constant; proline, glutamate, ammonia, ornithine, lactate and pyruvate levels were inversely proportional to oxygen consumption and total peripheral resistance. The primary defects in sepsis seem to be metabolic; there are very strong correlations in time between physiology and metabolism; the metabolic abnormality seems to be a progressive energy-fuel deficit, possibly from a progressive inhibition of substrate entry into the Krebs cycle.
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PMID:Proline metabolism in sepsis, cirrhosis and general surgery. The peripheral energy deficit. 11 5

Significant liver disease including fatty metamorphosis, alcoholic hepatitis, cirrhosis, and hepatoma occur in two thirds of subjects who consume alcoholic beverages in sufficient quantities to interfere with work and social responsibilities; this is of major importance in the rapidly escalating morbidity and mortality from alcoholism. Chronic alcoholics should be routinely evaluated for the presence of altered liver function and structure. Clearance of indocyanine green using dichromatic ear densitometry and computer and analysis provides a simple and sensitive method for mass screening of such patients. Clinical studies of lymphocyte reactivity to purified alcoholic hyaline may be valuable in recognizing alcoholic hepatitis, the precursor of cirrhosis. Ethanol toxicity, malnutrition and constitutional factors contribute to the development of hepatic fibrosis and cirrhosis in alcoholics. Ethanol and/or acetaldehyde and the supernatant from lymphocytes stimulated by alcoholic hyaline cause a significant increase in the incorporation of proline into collagen of the damaged liver. Abstinence and correction of nutrient deficits are the cornerstones of treatment for alcoholic liver disease; a daily meal and dietary supplements should be provided for those with liver injury who continue to imbibe. Alcoholics with progressive liver disease despite supportive therapy may be aided by pharmacologic agents which suppress immunologic response and reduce fibrogenesis.
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PMID:Liver disease of the alcoholic. 16 41

As part of a double-blind, randomized, controlled trial to evaluate the effect of colchicine on liver cirrhosis, 43 cirrhotic patients were assigned to either a placebo (20 patients) or a colchicine (23 patients) treatment group. Colchicine 1 mg and an indistinguishable placebo were administered orally on a daily dose 5 days a week. In the colchicine group, 12 were males and 11 females, while in the control group 13 were males and 7 females. The time elapsed between diagnosis and inclusion in the study was 14.1 mo for the controls and 14.5 mo for the patients on colchicine. Mortality related to the liver disease occurred in 4 patients on colchicine and 8 patients on placebo. Although the probability of surviving in the colchicine group was greater than that of the placebo, the difference did not reach statistically significant levels. Of the colchicine-treated patients, in three a remarkable decrease in liver fibrosis was observed in serial biopsies. In two other patients, carcinoma of the liver developed. Six of the survivors on colchicine have improved clinically, noticing disappearance of ascites and edema, as well as a decrease in the size of the spleen. All the survivors on placebo continue to show clinical deterioration. In contrast to the usual drop of serum albumin seen in the cirrhotic patients, those receiving colchicine increased and maintained their serum albumin levels throughout the study. Serum proline values were elevated only in the alcohol cirrhotic patients. Serum alkaline phosphatase increased only in those patients receiving colchicine. The results indicate that in some cases, liver fibrosis could be modified by treatment with antifibrotic drugs. The use of colchicine at present should remain within controlled studies.
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PMID:Treatment of cirrhosis with colchicine. A double-blind randomized trial. 37 54

The relation between availability of free amino acids and development of cirrhosis in rat liver has been experimentally evaluated. Levels of free glycine and proline were found to increase when animals are treated with phenobarbital and carbon tetrachloride. This increase is concomitant with increase in collagen and loss of activity of enzymes responsible for degradation of amino acids. It is concluded that elevated levels of proline observed in the serum of cirrhotic patients may be a consequence, rather than a cause, of collagen accumulation in the liver.
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PMID:Cirrhosis and the synthesis of proline and glycine in rat liver. 53 2

Adult human liver biopsies were cultured from normal, alcoholic hepatitis, chronic active hepatitis, fibrosis plus alcoholic hepatitis (active cirrhosis), inactive cirrhosis, and drug hepatitis. The synthesis of collagen was estimated in cultures from 58 livers by measuring the conversion of [(14)C]proline to the [(14)C]hydroxyproline of collagen; that of glycosaminoglycans in cultures from 57 livers by the incorporation of [(3)H]acetate and (35)SO(4) into glycosaminoglycans (GAG). The synthesis of procollagen was increased only in cultures from alcoholic hepatitis, both in the pulse medium (P < 0.05) and in the chase medium (P < 0.02). The synthesis of insoluble collagen was increased in cultures from chronic (active) hepatitis (P < 0.01), fibrosis plus alcoholic hepatitis (active cirrhosis) (P < 0.001), and inactive cirrhosis (P < 0.05). Essentially all radioactive GAG was soluble in culture media. The predominant GAG were chondroitin-4 or -6-SO(4). The synthesis of GAG was increased only in cultures from fibrosis plus alcoholic hepatitis (active cirrhosis) both in the pulse medium (P < 0.01) and chase medium (P < 0.001). The data indicate that in the absence of immuno-competent cells or their secretory products, tissue cultures from livers showing biopsy evidence of active fibrosis in vivo may demonstrate increased synthesis of collagen and GAG in vitro. Increased (soluble) procollagen synthesis in cultures from alcoholic hepatitis was not associated with histologically demonstrable overt hepatic fibrosis in vivo, nor was it associated with increased GAG synthesis in vitro. No significant difference was demonstrable in collagen or GAG synthesis in paired cultures which contained either 300 mg/dl ethanol or 3.75 mg/dl methylprednisolone compared to their respective controls.
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PMID:The rate of synthesis of glycosaminoglycans and collagen by fibroblasts cultured from adult human liver biopsies. 87 75

X-Prolyl dipeptidyl-aminopeptidase (no EC no. assigned) activity in normal and pathological human sera was assayed with several newly synthesized X-proline p-nitroanilides as chromogenic substrates. Normal values for 88 healthy subjects (15 to 81 years old), with glycylproline p-nitroanilide as substrate at pH 8.7, were 54.9 +/- 1.5 (SE) (range, 25.7 - 96.0) mumol/min per liter of serum at 37 degrees C. The results suggest that the enzyme activities with all X-proline p-nitroanilides were increased in patients with hepatitis and decreased in patients with gastric cancer. On Sephadex G-200 column chromatography, normal human sera showed a single peak of enzyme activity with glycylproline p-nitroanilide as the substrate, which coincided with the peak with glycylproline beta-naphthylamide but was different from the peaks with leucine beta-naphthylamide. Sera from patients with hepatitis or liver cirrhosis showed an increase in the normal peak and the appearance of another new peak with glycylproline p-nitroanilide as substrate.
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PMID:X-Prolyl dipeptidyl-aminopeptidase activity, with X-proline p-nitroanilides as substrates, in normal and pathological human sera. 94 33

Serum free proline and free hydroxyproline were determined in 71 patients with liver disease and in 62 control subjects. The group with liver disease included 60 patients with liver cirrhosis and 11 with chronic active liver disease. Forty-five of the cirrhotic patients were alcoholics, 9 of which were studied during an episode of alcoholic hepatitis. The control group consisted of 24 healthy volunteers, 19 primary malnourished patients, and 19 severely ill patients without liver disease. The values obtained in normal subjects were quite constant; no differences related to sex or age were detected. In patients with malnutrition, and especially in severely ill patients, the proline values were always below the normal limit. Patients with nonalcoholic cirrhosis or chronic active liver disease had serum proline and hydroxyproline values similar to those of normal subjects. However, the patients with alcoholic liver cirrhosis had proline and hydroxyproline values significantly higher than the normal group. Furthermore, in patients with alcoholic hepatitis the serum free proline values were significantly higher than in the other groups. The results suggest that alcohol might have a direct effect on proline metabolism or facilitate its release from the liver cell.
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PMID:Serum free proline and free hydroxyproline in patients with chronic liver disease. 112 2

In an attempt to study the collagen formation in the liver occurring in association with obstructive jaundice, the authors carried out an experiment with liver slices from common bile duct-ligated rats. Hepatic collagen was fractionated into the neutral soluble, acid soluble and insoluble fractions, and the hydroxyproline synthesis rate of each fraction was measured using 14C-proline. Determination was also made for hexosamine content in the same liver tissue. The hydroxyproline content of hepatic collagen increased as biliary obstruction was prolonged, particularly from the 4th week, which is the transitional period of liver histology into biliary cirrhosis. The hexosamine content of hepatic collagen showed a similar tendency. The neutral soluble, acid soluble and insoluble collagen fractions all increased as biliary obstruction was prolonged. The collagenosynthetic activity of the neutral soluble fraction, attained a peak in 1 to 2 weeks of biliary obstruction, which indicates that collagen fibers are formed actively in the early stage of jaundice, although there is only a slight increase in the absolute amount of fibers developed then. Serum monoamine oxidase level tended to be parallel to collagenosynthetic activity but not to collagen content.
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PMID:Biochemical study of fibrosis in the rat liver in biliary obstruction. 115 83

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

Rats drank ethanol, on the average 1.20 g/100 g body weight, for various periods up to nearly 300 days. Experimental variables included a high-fat, low-protein diet, administration of additional ethanol by stomach tube, and CCl4 injections instead of ethanol. Growth was retarded by all the variables, especially by the high-fat, low-protein diet. The specific histological finding in the ethanol groups was the presence of Mallory bodies. Significant increase in total liver lipids was caused by ethanol, and rapid fat accumulation, inflammatory changes, and even fibrosis and cirrhosis by the high-fat, low-protein diet and the CCl4 injections. Ethanol raised the concentrations of collagen and soluble protein in the liver; the collagen content was increased also by the high-fat, low-protein diet and the CCl4 injections. The incorporation of proline to collagen was stimulated in incubated liver slices from both ethanol-treated and high-fat, low-protein-fed rats. These treatments also increased the concentration of free proline in the liver, thus augmenting the protein synthesis in fibroblasts.
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PMID:Effect of long-term administration of ethanol to the rat: lipids, collagen and other proteins, and Mallory bodies in the liver. 120 62


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