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)

The hepatic activities and the isoenzyme patterns of both alcohol dehydrogenase and aldehyde dehydrogenase have been studied in 60 alcoholics with varying degrees of liver damage (from normal tissue or minimal changes to cirrhosis with alcoholic hepatitis) and in 24 nonalcoholics with chronic hepatitis or cirrhosis in order to ascertain their association with liver damage. In alcoholics both alcohol dehydrogenase and low-Km aldehyde dehydrogenase activities decreased proportionally with the severity of liver disease. In contrast, in nonalcoholics, there was a reduction of low-Km aldehyde dehydrogenase activity related to the severity of liver injury, but alcohol dehydrogenase was similar in patients with chronic hepatitis and nonalcoholic cirrhosis. There were no significant changes in total and high-Km aldehyde dehydrogenase activities among the different histologic groups studied, although the lowest activities were observed in patients with more severe liver injury. The prevalence of atypical alcohol dehydrogenase was similar in alcoholic (6.6%) and in nonalcoholic (8.3%) liver disease. All patients exhibited isoenzyme aldehyde dehydrogenase II, whereas isoenzyme I was not detected in 39.5% of the alcoholic patients and in 9.5% of those with nonalcoholic liver disease. The lack of aldehyde dehydrogenase I was observed in cases with the lowest enzymatic activities. These results suggest that the decrease of alcohol and aldehyde dehydrogenase activities in alcoholics is not a primary defect and, therefore, their decrease is secondary to liver damage. It is speculated that the diminution of alcohol dehydrogenase, found particularly in alcoholics, could be due to centrilobular cell necrosis.
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PMID:Influence of liver disease on hepatic alcohol and aldehyde dehydrogenases. 275 31

The occurrence of hepatic cirrhosis with ascites and diabetes insipidus in the same patient is described. The stimulability of residual vasopressin was confirmed by water deprival and the partial vasopressin deficit by the administration of dDAVP. Water loading test referred to the possibility of suppression of residual vasopressin. Studying the specific renal functions in diets of different sodium content following the administration of dDAVP and diuretics, the diuretic without adding ADH was found to be the best therapy for these patients. Reviewing the literature the authors are taking into consideration the difficulties of differential diagnostics and the mechanisms which may explain the inhibiting effect of the liver disease on the polyuria associated with diabetes insipidus.
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PMID:[Partial diabetes insipidus and ascitic liver cirrhosis in a patient]. 279 88

1. Liver biopsies were performed in healthy control subjects and in subjects with alcoholic and non-alcoholic liver disease in order to examine alcohol dehydrogenase (ADH; EC 1.1.1.1) and aldehyde dehydrogenase [ALDH; aldehyde dehydrogenase (NAD+); EC 1.2.1.3] activities. Erythrocyte ALDH and ethanol metabolism were also investigated in the same subjects. 2. Fifteen per cent of the subjects studied (seven of 48 subjects tested) presented atypical ADH activity, characterized by elevated activity at pH 7.4 or 8.8 compared with that found in subjects with the usual ADH form. However, the ethanol elimination curves obtained in two subjects with atypical ADH were indistinguishable from the kinetics of the group with normal ADH. Subjects displaying atypical ADH activity showed normal liver and erythrocyte ALDH activities. 3. Considering only the subjects with the normal ADH form, hepatic ADH activity was unaltered in subjects with non-alcoholic liver disease (chronic hepatitis or cirrhosis) and in those with alcoholic steatosis. Subjects with alcoholic hepatitis or alcoholic cirrhosis showed a lower ADH activity compared with the healthy control group. 4. In spite of the changes detected in subjects with alcoholic liver disease, curves of blood ethanol concentration after oral administration of 0.4 g of ethanol/kg were indistinguishable between the alcoholic hepatitis group and the control group. 5. Hepatic ALDH activity, assayed at 300 mumol/l acetaldehyde, was found to be diminished in all liver pathologies investigated, regardless of their aetiology. Nevertheless, erythrocyte ALDH activity was not modified in subjects with non-alcoholic or alcoholic liver disease. As a result of these findings, no relationship was found between hepatic and erythrocyte ALDH.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effect of liver disorders on ethanol elimination and alcohol and aldehyde dehydrogenase activities in liver and erythrocytes. 292 May 34

The effects of polyunsaturated fatty acids (phosphatidylcholine) on renal function in healthy subjects and in patients with chronic renal failure, with liver cirrhosis, and with heart failure were studied. The drug was administered at 3.5 mg/kg i.v. (Linoleic acid 1.24 mg/kg). In all cases, the administration of the drug caused an increased excretion of sodium and especially of water with a reduction in basal urinary hypertonicity. The polyuria was caused by the higher glomerular filtration rate not being counterbalanced by an increase in tubular water reabsorption. The water reabsorption was mostly anisosmotic. The presence of urinary hypertonicity excluded an inhibition of ADH secretion by this drug. The sodium excretion was probably caused by an increase of the glomerular filtration rate whereas no significant changes in the tubular reabsorption of sodium were seen. We found a significant (p 0.05) increase in PGE2 urinary excretion after phosphatidylcholine administration. Lysine - acetylsalicylate injection after phosphatidylcholine, in other trials in the same patients, prevented the effects previously reported. Therefore we suggest that the effects of this drug are mediated by an increased availability of renal prostaglandins.
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PMID:Effects of polyunsaturated fatty acids and prostaglandin synthesis on renal function. 308 1

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

A method has been developed for simultaneous analysis of alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH) isoenzymes in small (2.5 mg) liver biopsy cores by starch gel electrophoresis. All the currently recognized hepatic isoenzymes coded by ADH1, ADH2, ADH3 and ADH4 can be detected as can the five ALDH isoenzymes. Using this technique we have investigated the isoenzyme composition of liver samples from English and Chinese subjects and a group of chronic alcoholics. Pronounced racial differences in frequency of ADH2 and ALDH phenotypes were found--only 2 (4%) of English controls had the "atypical" ADH2 variant whereas this was present in 42 (84%) of Chinese subjects, and whereas all the English subjects had the rapidly migrating mitochondrial isoenzyme of ALDH, this was absent in 27 (54%) of Chinese. No differences in ADH or ALDH phenotype were seen in the chronic alcoholics, all of whom were of English origin, compared with the English controls, but there was a reduction in overall ALDH activity and particularly in the mitochondrial isoenzyme in those with cirrhosis. The reduction in ALDH activity is probably acquired; by limiting acetaldehyde oxidation it could be responsible for the rapid deterioration in liver function in patients who continue drinking excessively.
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PMID:Hepatic ADH and ALDH isoenzymes in different racial groups and in chronic alcoholism. 635 65

Although an impairment in renal water excretion is a commonly encountered clinical problem in cirrhotic patients, the mechanisms responsible for this abnormality are uncertain. ADH levels are elevated in some patients with decompensated cirrhosis, but a causal relationship between these levels and impaired water excretion has not been established. Since in normal man, water immersion to the neck (NI) results in a preferential central hypervolemia (CV), without plasma compositional change, and a resultant suppression of AVP, we designed the present study to determine if the diuretic response of cirrhotic patients to NI is mediated by a decrease in AVP. 17 cirrhotic patients with ascites were studied following 14 h of dehydration on two occasions: during a seated control study (C) and during 4 h of NI. AVP, determined by RIA, was measured every 30 min. 12 of the 17 patients manifested a diuresis that equalled or exceeded that documented in normal hydropenic subjects during immersion. NI did not alter mean AVP as compared with either the pre-study hour or those of the corresponding control study. Furthermore, peak V and CH2O varied independently of prestudy AVP (r = -0.116), mean change in AVP (r = -0.060), as well as nadir AVP levels (r = -0.122). The demonstration of a diuresis in some of the subjects, occurring without concomitant suppression of plasma AVP, suggests that ADH may constitute a permissive rather than pivotal factor in the impaired water excretion of many patients with advanced liver disease.
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PMID:Relationship between plasma arginine vasopressin and renal water handling in decompensated cirrhosis. 637 13

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

Hepatic ethanol metabolism in the liver from carbon tetrachloride (CCl4)- treated animals was studied using non-recirculating hemoglobin-free liver perfusion system. CCl4-administration decreased ethanol uptake by the liver to 56% and 30% of the control values following the acute (24 hrs. after treatment) and chronic (8-12 weeks) treatments, respectively. In addition, 4 mM fructose, a well-known agent to increase ethanol metabolism in the liver, did not increase the hepatic uptake of ethanol in CCl4-treated livers. Hepatic alcohol dehydrogenase activity was not changed following acute and chronic CCl4 treatments. The lactate/pyruvate (cytosolic NADH/NAD) ratio as well as beta-hydroxybutyrate/acetoacetate (mitochondrial NADH/NAD) ratio significantly increased, whereas both hepatic oxygen uptake and oxidation of NADH in mitochondria remarkably decreased in parallel with the magnitude of liver injury induced by CCl4. Histological studies revealed that the liver had centrilobular coagulative necrosis with fatty droplet formations at acute phase, while bridging fibrosis between central and portal areas and the pattern of cirrhosis with conspicuous changes in the mitochondria were seen at chronic phase. These data indicate that CCl4-treatment significantly reduces hepatic ethanol metabolism via the inhibition of reoxidation of NADH, a rate limiting step of ethanol metabolism in the liver.
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PMID:Alteration of hepatic ethanol metabolism in CCL4-intoxicated rats: analysis using isolated liver perfusion system. 676 60

Vitamin A and zinc metabolism are affected both by ethanol and by hepatic cirrhosis. Ethanol causes abnormal dark adaptation by acting as a competitive inhibitor with retinol for alcohol dehydrogenase in the eye. In animals oral ethanol intake results in increased losses of zinc by the urinary and fecal routes. Vitamin A malnutrition in cirrhotics may be caused by poor diet, malabsorption, decreased hepatic vitamin A uptake, and decreased hepatic storage capacity for vitamin A. In some cirrhotic patients zinc deficiency and or protein deficiency may limit the ability to respond to vitamin A. Combined vitamin A and zinc deficiencies are common in cirrhotics and either may result in abnormal dark adaptation or impaired taste and smell. The interaction of these two micro-nutrients must be kept in mind by the clinician caring for alcoholic or alcoholic cirrhotic patients.
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PMID:Vitamin A and zinc metabolism in alcoholism. 700 92


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