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)

Significance of the antibody to alcohol altered hepatocyte plasma membrane (AAHM) was studied in various types of alcoholic liver diseases (ALD). AAHM was detected in the sera that were collected within 3 months of alcohol abstinence from patients with various types of ALD, with higher frequency in alcoholic hepatitis and cirrhosis. Serum acetaldehyde, gamma-globulin fraction, immunoglobulin A and G were higher in patients positive for AAHM, though the levels of GOT, GPT, mGOT were indifferent of the existence of AAHM. Histologically, hepatocyte ballooning and pericellular fibrosis were frequently seen in patients positive for AAHM, but close relationship between the extent of necrosis and existence of AAHM was not observed. These findings suggest that the occurrence of AAHM is closely related with the functional and morphological changes of the hepatocyte induced by acetaldehyde but not with hepatocyte necrosis.
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PMID:[Study of the antibody to alcohol altered hepatocyte plasma membrane in alcoholic patients]. 222 84

The effects of acute ethanol challenge on serum glycoprotein concentrations in man were studied. Serum levels of haptoglobin, alpha-2-macroglobulin and pre-albumin were measured fasting and 6 hr after oral ethanol 0.75 g/kg body weight in 8 healthy controls, 13 patients with alcoholic liver disease and 13 with non-alcoholic-related liver damage, both patient groups being further subdivided into those with and without cirrhosis. Basal levels of haptoglobin were significantly higher in non-cirrhotic alcoholics than controls and pre-albumin levels were lower in non-alcohol-related cirrhotic liver disease. In response to ethanol challenge, no consistent change was observed in any group, nor was there any significant difference between groups. There was, however, a significant correlation (r = 0.53, P less than 0.005) between the percentage changes in haptoglobin and alpha-2-macroglobulin. In 16 subjects (2 controls, 8 alcoholics and 6 non-alcoholics) blood levels of ethanol and acetaldehyde were measured serially: there was no relationship between the peak or mean concentration and the glycoprotein response. This study does not substantiate other reports which claimed to be able to predict the severity and reversibility of alcoholic liver disease on the basis of the serum glycoprotein response to ethanol: ethanol challenge with measurement of serum glycoproteins cannot substitute for proper histological assessment.
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PMID:Effect of ethanol challenge on serum glycoproteins in alcoholic and non-alcoholic liver disease. 244 17

Acetaldehyde, a product of ethanol oxidation which forms adducts with proteins, has been incriminated in the pathogenesis of alcoholic liver injury. High serum antibody titers against acetaldehyde-protein adducts have been found not only in alcoholics but also in patients with nonalcoholic liver disease, suggesting a contribution of acetaldehyde derived from sources other than exogenous ethanol. To investigate the effect of liver injury on the removal and the production of acetaldehyde, we produced fibrosis and cirrhosis (by chronic administration of carbon tetrachloride) and fatty liver (with very small doses of dimethylnitrosamine) in rats. Endogenous blood acetaldehyde levels increased by 38% in rats with severe liver injury (p less than 0.005), but not significantly in rats with fatty liver. However, an i.v. load of threonine (a physiological source of acetaldehyde), in amounts equivalent to the daily intake of this amino acid, increased blood and hepatic acetaldehyde levels in the rats with both types of liver injury more than in controls. Threonine dehydrogenase and dehydratase activities, involved in the major pathways for threonine degradation in mitochondria and cytosol, respectively, were markedly decreased in rats with liver injury with a resulting increase in hepatic threonine concentration. Moreover, the threonine aldolase activity, which splits threonine into glycine and acetaldehyde, remained unaffected or even slightly increased. Liver injury was also associated with impaired mitochondrial functions, including a 10 to 23% decrease in acetaldehyde oxidation (depending upon the severity of the lesions). As a consequence, administration of ethanol (an exogenous source of acetaldehyde) resulted in striking elevations in the levels of acetaldehyde in carbon tetrachloride-treated rats.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:High levels of acetaldehyde in nonalcoholic liver injury after threonine or ethanol administration. 251 Nov 35

The authors describe the correlations between chronic alcoholism and cirrhosis known not only from clinical observations but also from retrospective assessment of liver biopsy. However, the mechanism of hepatocellular injury by ethanol remains still unclear. It seems that three hypotheses prevail presently: 1) acetaldehyde which is a product of ethanol oxidation in the liver forms with certain biogenic amines alkaloids of the type of salsolinol causing cirrhosis, 2) ethanol or/and acetaldehyde catalyse the development of free radicals which may induce liver damage through lipid peroxides etc, 3) acetaldehyde formed during ethanol oxidation is released into blood or tissue fluids where it binds to albumins with formation of cytotoxic complexes leading to cirrhosis.
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PMID:[Various biochemical mechanisms of alcoholic liver cirrhosis]. 261 99

To investigate whether disordered immune function, as shown by abnormalities in lymphokine production, is present in alcoholic liver disease, interleukin-1 and interleukin-2 activity were assayed in a group of patients with acute alcoholic hepatitis in the absence of underlying cirrhosis, and a group of patients with inactive alcoholic cirrhosis. Activities of both IL-1 and IL-2 in alcoholic hepatitis were similar to those of normal individuals, although in abstinent patients with alcoholic cirrhosis, IL-1 activity was increased and IL-2 activity decreased. Lymphocyte transformation in response to PHA in patients with alcoholic hepatitis was significantly impaired when compared with normal controls, and addition of exogenous IL-2 did not correct this impaired response over a wide range of concentrations of both PHA and IL-2. These observations suggest the underlying defects in cell mediated immunity in acute alcoholic hepatitis, as assessed by blast transformation, could be fundamentally different from those of alcoholic cirrhosis and could be secondary to the metabolic effects of acetaldehyde or altered redox potentials on the behaviour of proliferating cells.
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PMID:Contrasts in interleukin-1 and interleukin-2 activity in alcoholic hepatitis and cirrhosis. 262 42

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

We recently presented preliminary data indicating the presence of antibodies against acetaldehyde adducts in sera of over 70% of alcoholic patients. To assess the respective roles of liver disease and alcohol consumption as well as the specificity of this immune response, 141 patients in various stages of alcoholic and nonalcoholic liver diseases were tested by a hemagglutination assay. Sixty-three (73%) of 86 alcoholics had antibody titers above control levels (p less than 0.0001). Alcohol consumption of these individuals was significantly higher (p less than 0.001) than that of those alcoholics with normal titers. Twenty-two patients (39%) with nonalcoholic liver diseases also had elevated levels of antibodies against acetaldehyde adducts (p less than 0.0005); of these, 8 had primary biliary cirrhosis (7 in Stages III and IV), 9 had chronic active hepatitis (6 with cirrhosis) and 5 had acute (virus- or drug-induced) hepatitis. Antibody titers did not correlate with levels of transaminase or alkaline phosphatase activity, nor with bilirubin, and albumin. However, in 52 alcoholics and in nonalcoholic patients with biopsy-confirmed liver disease, the highest titers were seen in the more advanced stages of liver damage. Thus, in addition to alcohol consumption, severity of liver disease may play a role in the appearance of circulating antibodies against acetaldehyde adducts.
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PMID:The role of alcoholism and liver disease in the appearance of serum antibodies against acetaldehyde adducts. 337 72

It is now possible to pinpoint the biochemical processes responsible for liver damage in alcoholics and to monitor detoxication from a biological point of view. Cirrhosis of the liver is a direct consequence of chronic alcoholism in 60-80 % of cases, and most alcoholics, after several years of drinking, cannot escape the ravages of alcohol, although it is not yet known why a small proportion are not affected biochemically. Psychological deterioration can be explained biochemically, due to the neurotoxic effects of acetaldehyde, formed by alcohol but 20-30 times more toxic, which acts on catecholamines and serotonin with, inter alia, depressant, habit-forming, hallucinogenic and convulsive properties. Hepatic symptoms depend on the stage the alcholic has reached - acute, subacute or the chronic and final stage of cirrhosis of the liver, and include disturbances of transaminases, gamma-GT, serum proteins, immunoglobulins, specific proteins, lipids (including very interestingly an increase in cholesterol-HDL which needs to be investigated further) and hematic changes with FDP and thrombocytes affected, and often anaemia.
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PMID:[Biological profile of liver damage in alcoholics (author's transl)]. 611 Mar 11

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

Ther are several main mechanisms that allow us to understand a number of the hepatic and metabolic effects of ethanol. Ethanol is oxidized in the liver to two products (hydrogen and acetaldehyde), to which many of the effects of ethanol can be attributed. The hydrogen generated alters the redox state, and though this effect is attenuated after chronic ethanol consumption, it may still be sufficient to explain alterations in lipid metabolism, possibly increased collagen deposition, and, under special circumstances, depression of protein synthesis. Acetaldehyde impairs microtubules, decreases protein secretion, and causes protein retention and ballooning of the hepatocyte. Acetaldehyde exerts toxicity also with regard to other key cellular functions, particularly in the mitochondria, and it may promote peroxidation of the cellular membranes. It is noteworthy that after chronic consumption of ethanol, there is increased acetaldehyde, in part because of decreased disposition in the mitochondria and partly because of induction of an alternative pathway of ethanol metabolism, namely the microsomal ethanol-oxidizing system. Indeed, this MEOS increases in activity after chronic ethanol consumption, with cross induction and acceleration of the metabolism of other drugs and increased lipoprotein production with hyperlipemia. There is also increased microsomal activation of hepatotoxic compounds (including drugs and possibly vitamin A). Fibrosis and cirrhosis can develop despite an associated adequate diet and even in the absence of alcoholic hepatitis. They are preceded by myofibroblasts and fibroblast proliferation. What eventually causes the increased number of myofibroblasts and promotes fibrosis is unclear, nor do we know the relative role of hepatocytes or mesenchymal cells in the process of fibroplasis. Possibly selective roles in this process of specific nutritional factors remain to be elucidated.
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PMID:Alcohol, protein nutrition, and liver injury. 634 74


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