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Query: UMLS:C0023890 (cirrhosis)
 42,195 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The free proline, free glutamic acid, and total collagen contents of the livers of cirrhotic and noncirrhotic patients were determined. The amounts of free proline in the sera of the patients were also determined. The results indicated that certain metabolic changes occurred in cirrhotic livers of humans that were similar to the metabolic changes observed previously in CCl(4)-induced cirrhosis in the rat. The amount of free proline was coordinate with the increase in total collagen, and both were inversely related to the amount of free glutamic acid. The average proline concentration in sera of cirrhotic patients was not higher than that of non cirrhotic patients, suggesting that the metabolic alteration noted above is a local event in the liver related to fibrogenesis. These and other results suggest that the pool size of free proline may play a prime role in regulation of collagen biosynthesis in liver cirrhosis.
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PMID:The relationship between the free pool of proline and collagen content in human liver cirrhosis. 548 Aug 51

Alcohol is the most significant liver poison. Its degradation takes above all place by the alcohol dehydrogenase and the microsomal alcohol-oxidizing system. In the first step of degradation acetaldehyde develops which in enrichment evokes immediately toxic defects on the mitochondrias of the cells of the liver parenchyma and thus introduces a vicious circle. Furthermore, an increased affection of pharmacometabolites as a sequel of the alcohol-conditioned enzyme induction may lead to a defect. Alcohol influences intermediary metabolic functions: the gluconeogenesis is inhibited, multi-layer disturbances in the lipid metabolism lead to fatty degeneration of the liver. A hyperuricaemia results from overproduction in the liver as well as from decreased renal excretion. The proline formation is increased. Distinct increase of the gamma-GT-activity is an early and relatively specific indicator of the alcoholic liver defect. Morphologic and clinical manifestations are fatty degeneration of the liver, hepatitis based on fatty degeneration of the liver and cirrhosis. Apart from dose and duration of the alcohol intake additional factors require consideration. The author adopts a definite attitude to etiopathogeneis and therapeutic possibilities.
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PMID:[Alcohol and the liver]. 611 57

Carbon tetrachloride inhalation in phenobarbitone treated rats caused a rapid rise in hepatic prolyl hydroxylase activity which was followed by an increase in hepatic collagen and free proline concentrations. Colchicine in a dose of 5 micrograms/day largely prevented the increase in hepatic collagen. This effect was not mediated by impairment of prolyl hydroxylase activity. Colchicine is of potential therapeutic value in preventing the progression of chronic liver disease to cirrhosis.
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PMID:Hepatic collagen synthesis in a rat model of cirrhosis, and its modification by colchicine. 627 60

Plasma amino acid concentrations and plasma glucagon and serum insulin levels were studied in male patients with compensated alcoholic and nonalcoholic liver cirrhosis. Age, nutritional status, and liver function tests were similar in both groups; none of the patients presented hepatic encephalopathy. Plasma valine and leucine concentrations were lower, and tyrosine, higher in alcoholic than nonalcoholic liver cirrhosis. As a result, the molar ratios of branched-chain amino acids (BCAA) to aromatic amino acids (AAA) were reduced markedly in this group. Although correlation coefficients comparing BCAA/AAA ratios and KICG in alcoholic and nonalcoholic liver cirrhosis were similar, a steeper regression line was observed in alcoholics. Plasma glucagon and proline levels were significantly higher in alcoholic than nonalcoholic liver cirrhosis, the former correlated with AAA concentrations only in alcoholic liver cirrhosis, but not with BCAA levels. These results indicated that alcoholic liver cirrhosis presented a more deranged plasma amino acid pattern than nonalcoholic, and the amino acid imbalances, except for depressed BCAA and elevated proline, were derived, in part, from the hyperglucagonemia.
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PMID:Plasma amino acid imbalance in alcoholic liver cirrhosis. 639 76

The mechanisms responsible for the increased hepatic collagen deposition in alcoholic cirrhosis remain unknown. The question of whether ethanol or acetaldehyde has a direct effect on collagen and noncollagen protein production was investigated in human fibroblasts with no detectable activity of alcohol dehydrogenase to distinguish the effects of these metabolites. To eliminate environmental factors, protein production by confluent human skin, fetal and hepatic fibroblasts was studied after three passages. Cells were labeled with [5-3H]proline for 4 hr in the presence of 0.2 mM ascorbate alone or with addition of either ethanol (50 mM) or acetaldehyde (0 to 300 microM). Rates of protein production were calculated from the radioactivities of collagenase-sensitive and collagenase-resistant proteins. Skin fibroblasts from alcoholic individual either with cirrhosis or without liver disease have comparable rates of collagen and noncollagen protein production. Acetaldehyde, in a concentration found in the liver during ethanol abuse, significantly increased collagen production by human skin fibroblasts (up to 140%), fetal fibroblasts (up to 240%) and hepatic fibroblasts (up to 70%) but the addition of ethanol had no significant effect on basal collagen production. The effect of acetaldehyde was dose-related and affected noncollagen protein production in a similar manner. Acetaldehyde did not cause changes in either proline transport or the specific activity of the proline precursor pool. This newly recognized stimulation of collagen production by acetaldehyde may be a possible mechanism of fibrogenesis in alcoholic individuals.
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PMID:Acetaldehyde stimulates collagen and noncollagen protein production by human fibroblasts. 647 53

In alcohol-induced liver injury, hyperprolinemia has been proposed as a marker of fibrogenesis probably secondary to hyperlactacidemia. However, some studies of plasma proline in alcoholics with cirrhosis have reported normal rather than increased levels. In order to evaluate the frequency of hyperprolinemia in alcoholic liver disease and its relationship to blood lactate, we measured plasma proline levels in 145 subjects including 91 alcoholics with a spectrum of liver disease as well as 22 nonalcoholics with liver injury unrelated to alcohol. We also studied baboons fed alcohol as 50% of total calories for 1 to 4 years. Among alcoholics only 21/91 had elevated proline values. Elevations were most frequent among patients with severe hepatic decompensation (3/8), in patients with alcoholic hepatitis on liver biopsy (5/17), and in those with acute alcohol-related withdrawal, with alcohol still present in the blood (4/9). Patients with liver disease unrelated to alcohol but severe in nature also has elevations in proline (3/3). Only 4/28 patients with cirrhosis due to alcohol had elevated values, and none of the baboons fed alcohol had hyperprolinemia whether withdrawn from alcohol or not. Hyperlactacidemia was associated with hyperprolinemia, but so were depressed serum albumin values and prolongations of the prothrombin time, suggesting a general association with severe liver disease. These results reveal that hyperprolinemia occurs infrequently in patients with alcohol-induced cirrhosis and therefore does not appear to be a sensitive marker of hepatic fibrosis in these patients.
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PMID:Frequency of hyperprolinemia in alcoholic liver cirrhosis: relationship to blood lactate. 670 3

In this work, we studied the changes in human skin collagen occurring in diabetes mellitus and liver cirrhosis. The original methodology, based on the determination of the amino acids proline, 4-hydroxyproline, hydroxylysine, glycine and alanine, allowed us to reveal in skin a change in collagen in diabetes mellitus but none in liver cirrhosis. This biochemical evidence was correlated to the histological investigation. Moreover, diabetes mellitus did not involve any changes in hydroxylation of polypeptidic lysine. This latter observation was in accordance with the accumulation of normal collagen regarding amino acid composition only, and the results suggest a preferential accumulation of collagen type III in skin, in diabetes mellitus.
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PMID:Consequences of diabetes mellitus or liver cirrhosis on total collagen in human skin biopsies. 674 72

In four control subjects and four patients with cirrhosis of the liver a multiple amino acid mixture was infused for 12 h at a constant rate of 68 and 56 mumol alpha-amino N/s, respectively. Before infusion the plasma amino N concentration was 2.4 +/- 0.2 (mean +/- SD) mmol/l in control subjects and 3.5 +/- 0.7 mmol/in patients (P less than 0.025). The concentration of alanine, proline, arginine, tyrosine, and citrulline was significantly increased in the cirrhosis group. 12 h after the infusion began approximately constant amino N concentrations of 11.4 +/- 1.8 mmol/l in controls and 13.7 +/- 3.9 mmol/l in patients were attained, and the urea N synthesis rate was 63 +/- 17 and 44 +/- 8 mumol/s, respectively (P less than 0.05). After correction for loss of amino acids in urine this means that on the average 94 per cent of the N load was recovered as urea. The plasma clearance of infused amino acids, calculated as the ratio between infusion rate and steady state concentration, was 6.0 +/- 1.2 and 4.1 +/- 0.9 ml/s for amino N in the control and cirrhosis group, respectively (P less than 0.025). The clearance of individual amino acids ranged between 2.5 and 28 ml/s. The clearance of most amino acids was decreased in the cirrhosis groups, and of glycine, proline, lysine, threonine, and arginine significantly so (P less than 0.05), reflecting accumulation of amino acids in patients. This indicates that a primary defect in the conversion of amino N in cirrhosis is the reduced urea synthesis.
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PMID:Elimination of infused amino acids from plasma of control subjects and of patients with cirrhosis of the liver. 680 68

It has been reported that the concentration of free proline in the liver can be a limiting factor in the synthesis of hepatic collagen, and there has also been found to be a good correlation between the free proline and the amount of collagen in cirrhotic human livers. Since ethanol retards the breakdown of proline, it might be expected that ethanol-induced liver cirrhosis could be produced by the effect of ethanol on the hepatic proline level. In the present study the hepatic free proline level was increased more than three-fold by the administration of proline-rich diet to the rats used in the experiment. Administration of ethanol to the animals did not further increase the concentration of free proline of the liver. The high free proline level had no effect on the collagen formation, nor on the structure of the liver. It can therefore be assumed that the increased free proline levels observed in cirrhotic livers did not induce an increased collagen accumulation, and are a consequence of an altered proline metabolism.
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PMID:A high hepatic concentration of free proline does not induce collagen synthesis in rat liver. 683 99

Liver biopsy samples from 40 chronic alcoholic patients, including 9 with minimal changes of the liver, 6 with mild hepatic fibrosis, 14 with moderate fibrosis, and 11 with severe fibrosis (cirrhosis) were studied by electron microscopy to assess fibrogenesis in the Disse space and the role of fat-storing cells in this process. In the Disse space of normal liver, collagen fibers are few, and while lipid droplets containing fat-storing cells exist, their rough endoplasmic reticulum (RER) is inconspicuous. In the course of progressive hepatic fibrosis, collagen in the Disse space increased. This was significantly associated with gradual development of RER in fat-storing cells, confirmed by morphometric analysis. It is likely, therefore, that the development of RER in the fat-storing cells is a morphological correlative of their activated fibrogenesis and transformation into fibroblasts. To further clarify this, the rate of collagen synthesis was measured by the method of in vitro incorporation of [3H]proline into collagen in 17 liver biopsy samples from alcoholic patients and compared with the degree of morphological changes of RER in fat-storing cells. In liver samples with well-developed RER in fat-storing cells, a significantly higher rate of collagen synthesis was observed. These results suggest that in alcoholic liver injury, fat-storing cells may play an important role in Disse space fibrogenesis.
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PMID:The role of fat-storing cells in Disse space fibrogenesis in alcoholic liver disease. 686 68


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