Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0019209 (hepatomegaly)
 5,798 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Both acute and chronic ethanol administration inhibit the secretion of albumin and glycoproteins from the liver. Impairment of posttranslational steps of the secretory process are mainly involved in this secretory defect, although in some instances altered synthesis of the protein moiety may be a factor. Decreased secretion following ethanol administration results in the intrahepatic retention of export proteins. The secretory defect is a consequence of the metabolism of ethanol and is likely mediated via acetaldehyde, although more conclusive proof is still required. The manner by which acetaldehyde impairs the secretory process is unknown, but may be related to its high reactivity with hepatocellular proteins. The specific posttranslational steps or processes involved in the secretory defect are still unclear; however, it appears that the final steps of secretion (post-Golgi events) may be the primary site of impairment. Impaired secretion of proteins from the liver could contribute to altered levels of plasma proteins and hepatomegaly as well as to the liver injury observed in the alcoholic.
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PMID:Effect of ethanol on hepatic secretory proteins. 672 60

Alcohol inhibits the secretion of protein from the liver. Chronic abuse results in intrahepatic accumulation of export-type proteins and decreased plasma levels. These effects appear to be mediated by acetaldehyde, an oxidation product of ethanol. Acetaldehyde is capable of interfering with the assembly of microtubules, a component of the cytoskeleton, the integrity of which is required for normal secretion. Protein retention and cytoskeletal alterations may contribute to manifestations of alcoholic liver disease, such as hepatomegaly, ballooning of the hepatocyte, portal hypertension, and development of Mallory bodies.
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PMID:Effects of alcohol on hepatic transport of proteins. 704 72

The direct toxic effect of alcohol and its metabolite acetaldehyde has been demonstrated both in laboratory animals and in humans. Alterations in the mitochondrial ultrastructure and the dilatation of the sarcoplasmatic reticulum have been shown after an acute infusion of alcohol in the heart. These changes correlate with decreased mitochondrial function, defects in protein synthesis and the occurrence of arrhythmias. The risk of developing alcoholic cardiomyopathy is related to both the mean daily alcohol intake and the duration of drinking, but there is much individual susceptibility to the toxic effect of alcohol. Most patients, in whom alcoholic cardiomyopathy develops, have been drinking over 80 g/d for more than 5 years. The clinical diagnosis of alcoholic cardiomyopathy reflects the coexistence of global myocardial dysfunction in a heavy drinker in whom no other cause for myocardial disease was found. In studies focussing on alcoholic cardiomyopathy the surprising histologic findings in endomyocardial biopsy in about 30% of all cases was myocarditis with a lymphocytic infiltrate in association with myocyte degeneration or focal necrosis. In myocarditis, the network of microtubules and intermediate filaments is also disrupted by the inflammatory reaction which involves resident cells (myocytes, fibroblasts, endothel cells) and systemic cells (granulocytes, macrophages, monocytes, lymphocytes). Changes in the cardiac cytoskeleton and the extracellular matrix may affect contractile function, since the cytoskeleton organizes the intra- and intercellular architecture. After all, in patients with alcohol abuse and myocarditis the immune functioning appears to be compromised. Several studies suggest that heavy drinking alters both lymphocyte and granulocyte production and function. Alcohol consumption per se might harm the immune system. Furthermore, the myocardial damage due to alcohol consumption could initiate autoreactive mechanisms comparable to those in viral or idiopathic myocarditis. Patients with alcohol abuse and myocarditis have a poor prognosis: signs of biventricular failure including tachycardia, hepatomegaly, and peripheral and lung edema are observed. These symptoms are as nonspecific as are various echocardiographic and electrocardiographic changes such as atrial and ventricular arrhythmias which may be associated both with myocarditis, alcoholic cardiomyopathy and acute effects of drinking without hemodynamic alterations. For the management of patients with alcohol abuse the prevention of further alcohol intake is mandatory to reverse the myocardial damage and the unfavorable predisposition for infection. Specific treatment of myocarditis is the second important option, and treatment of heart failure by reducing the size of the dilated heart and alleviating the signs and symptoms of heart failure is a logical third step.
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PMID:[Alcohol and myocarditis]. 880 5

The mechanisms underlying alcoholic liver disease are not completely understood, but lipid accumulation seems to be central to the cause of this disease. The peroxisome proliferator-activated receptor alpha (PPARalpha) plays an important role in the control of lipid homeostasis, metabolism of bioactive molecules, and modulation of inflammatory responses. To investigate the roles of PPARalpha in alcoholic liver injury, wild-type and PPARalpha-null mice were continuously fed a diet containing 4% ethanol, and liver injury was analyzed. PPARalpha-null mice fed ethanol exhibited marked hepatomegaly, hepatic inflammation, cell toxicity, fibrosis, apoptosis, and mitochondrial swelling. Some of these hepatic abnormalities were consistent with those of patients with alcoholic liver injury and were not found in wild-type mice. Next, the molecular mechanisms of ethanol-induced liver injury in PPARalpha-null mice were investigated, and changes related to ethanol and acetaldehyde metabolism, oxidative stress, inflammation, hepatocyte proliferation, fibrosis, and mitochondrial permeability transition activation occurred specifically in PPARalpha-null mice as compared with wild-type mice. In conclusion, these studies suggest a protective role for PPARalpha in alcoholic liver disease. Humans may be more susceptible to liver toxicity induced by ethanol as PPARalpha expression in human liver is considerably lower compared to that of rodents.
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PMID:Peroxisome proliferator-activated receptor alpha protects against alcohol-induced liver damage. 1538 58