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)

A single iv dose of 15 ml/kg fluosol DA (20%), a perfluorochemical oxygen carrier, caused hepatomegaly and splenomegaly which persisted for at least 3 weeks after drug injection. The peak increase in weight was at 3 days in the spleen (1.7x) and at 14 days in the liver (1.5x). Lung and kidney weights were not altered 1-21 days after administration of fluosol DA. The slopes of the single-dose radiation survival curves for intestinal epithelial cells and spermatogenic stem cells in mice breathing air or oxygen were not significantly altered by the administration of fluosol DA 10 min before irradiation, and the doses to achieve an isoeffect were altered by 1.03 or less. When mice were challenged with iv injected FSa tumor cells 24 h after treatment with fluosol DA, no increase in the number of artificial pulmonary metastases was observed.
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PMID:Acute effects of a perfluorochemical oxygen carrier on normal tissues of the mouse. 408 Sep 82

Chronic consumption of ethanol often results in an increased rate of ethanol metabolism (metabolic tolerance) and in hepatomegaly. However, the extent of these changes is highly variable. We have found that these two phenomena are greatly influenced by age. We studied the effect of age on the development of metabolic tolerance and hepatomegaly and on the increase in hepatic oxygen consumption produced by chronic ethanol administration. The latter has been proposed to contribute to metabolic tolerance to ethanol. Ethanol was administered to female Sprague-Dawley rats with different initial ages (4, 6, 8, 11, and 17 weeks) for a 4-week period in a high-fat liquid diet. Control animals were pair-fed an isocaloric liquid diet in which ethanol was replaced with carbohydrate. Metabolic tolerance and hepatomegaly following chronic ethanol consumption were markedly dependent on the initial age of the animal, with young animals showing the largest increases. Although showing a similar general trend with age, the degree of metabolic tolerance was not linked proportionally with the degree of hepatomegaly. Perfused livers from young rats fed chronically with ethanol showed increases in ethanol metabolism and oxygen consumption, whereas no increase were observed in those from older animals. These findings support the hypothesis that an elevated rate of hepatic oxygen consumption contributes to metabolic tolerance. Total hepatic alcohol dehydrogenase activity was not increased by chronic ethanol consumption in any age group, demonstrating that an increase in the levels of this enzyme is not obligatory for metabolic tolerance.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effect of age on metabolic tolerance and hepatomegaly following chronic ethanol administration. 639 2

In conclusion, the studies presented suggest that two factors commonly occurring in the alcoholic, namely, an increased rate of ethanol metabolism and hepatomegaly, may have important pathogenic implications in alcoholic liver disease. An increased rate of ethanol metabolism is linked to a greater oxygen demand, thus resulting in greater susceptibility to hypoxia in Zone 3 of the liver acinus, a factor which might be responsible for hepatocellular necrosis in alcoholic hepatitis. Propylthiouracil has been shown to have a protective effect against hypoxic necrosis in alcohol-fed animals and has been found to be most effective in accelerating the rate of recovery of alcoholics with active liver disease. On the other hand, hepatocyte expansion in hepatomegaly, in the face of a semi-rigid liver capsule, leads to constriction of extracellular volume and to an increase in intrahepatic and portal pressure. The latter, in turn, could produce a variety of haemodynamic alterations as those found in the alcoholic. To what extent the mechanisms described are responsible for or might add to the myriad of other disturbances observed in alcoholic disease should be further analysed.
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PMID:Hepatocyte demand and substrate supply as factors in the susceptibility to alcoholic liver injury: pathogenesis and prevention. 701 48

Emergencies in pediatric cardiology are heart failure, cyanosis and rhythm disturbances. The signs of heart failure are tachycardia, tachypnea and hepatomegaly. The therapy consists of oxygen, diuretics and digoxin. Occasionally, intubation with mechanical ventilation and intravenous catecholamines are needed. Cyanosis is often the only sign of a severe heart malformation, and prompt hospitalization is mandatory. Oxygen and warm environment is important during transport, correction of a possible metabolic acidosis and prostaglandin infusion are done in the hospital. Beyond the newborn period, so-called cyanotic spells are seen, particularly in tetralogy of Fallot. In supraventricular tachycardia, vagal manoeuvres can be tried first, if not successful, intravenous adenosine or electroconversion will restore sinus rhythm. In the older child, intravenous isoptin can be given. Slow heart rates from total AV block or sinus node affection are treated with atrophic, isuprel or electrical pacing.
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PMID:[Pediatric cardiological emergencies]. 797 84

Peroxisome proliferators are a structurally diverse group of chemicals. They include fibrate hypolipidaemic drugs, phthalate ester plasticisers, phenoxy acid herbicides, azole antifungal drugs, and perflurinated fatty acids. This presentation will focus on the common pleiotropic responses produced by these compounds including hepatomegaly (hyperplasia and hypertrophy), activation of cell cycle S-phase ploidy changes, cytochrome P4504A1 induction, morphometric/biochemical analysis of peroxisome proliferation and stimulation of growth factors, and oncogene activation. Consideration will also be given to the role of recently described Peroxisome Proliferator Activated Receptor in these diverse hepatic responses. Peroxisome proliferators are uniformly negative in a wide range of genotoxicity tests, but nevertheless are complete carcinogens, particularly in rodent liver. Mechanisms of nonmutagenic carcinogenesis will be discussed including the active oxygen hypothesis involving 8-hydroxydeoxyguanosine adducts and the possibility of peroxisome proliferators promoting preexisting lesions by clonal expansion, eventually resulting in frank tumorigenesis. Finally, a consideration of the risk assessment of peroxisome proliferation to humans will be discussed.
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PMID:Peroxisome proliferators: paradigms and prospects. 839 Jul 28

We demonstrate in this study the cytotoxic effects of inorganic arsenicals, arsenite and arsenate, and organic arsenic compounds, monomethylarsonic acid (MAA), dimethylarsinic acid (DMAA), and trimethylarsine oxide (TMAO), which are metabolites of inorganic arsenicals in human bodies, using murine macrophages in vitro. Inorganic arsenicals, both arsenite and arsenate, are strongly toxic to macrophages, and the concentration that decreased the number of surviving cells to 50% of that in untreated controls (IC50) was 5 or 500 microM, respectively. These inorganic arsenicals mainly caused necrotic cell death with partially apoptotic cell death; about 80% of dead cells were necrotic, and 20% were apoptotic. The inorganic arsenicals also induced marked release of an inflammatory cytokine, tumor necrosis factor alpha (TNF alpha), at cytotoxic doses. This strong cytotoxicity of an inorganic arsenical, arsenite, might be mediated via active oxygen and protease activation because it was inhibited by the addition of some antioxidant reagents, such as superoxide dismutase (SOD), catalase, and GSH, or by a peptide inhibitor of interleukin-1 beta-converting enzyme (ICE). It is likely that these immunotoxic effects of inorganic arsenicals may evoke both immunosuppression and inflammation, and they may be central factors causing carcinogenesis and severe inflammatory responses, such as hepatomegaly and splenomegaly, in chronic arsenicosis patients who daily ingested arsenic-contaminated well water. In contrast, the cytotoxic effects of methylated arsenic compounds were lower than those of inorganic arsenicals. The IC50 value of DMAA was about 5 mM, and MAA and TMAO had no toxicity even at concentrations over 10 mM. Additionally, these methylated chemicals suppressed the TNFalpha release from macrophages. DMAA induced mainly apoptotic cell death in macrophages as indicated by cellular morphological changes, condensed nuclei, terminal deoxynucleotidyltransferase-mediated dUTP-biotin nick end labeling (TUNEL), and DNA fragmentation. However, the cytotoxicity of DMAA might be induced via a different mechanism from that of inorganic arsenicals because it was not abolished by the additions of SOD, catalase, or ICE inhibitor. Conversely, GSH enhanced the toxicity of DMAA. These data suggest that methylation of inorganic arsenicals in mammals plays an important role in suppression of both severe immunosuppression and inflammatory responses caused by inorganic arsenicals.
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PMID:Inorganic and methylated arsenic compounds induce cell death in murine macrophages via different mechanisms. 954 97

Congenital aortic stenosis accounts for about 5% of cardiac malformations recognized in childhood. It belongs to the category of acyanotic congenital heart disease. These lesions produce a load on the heart because of left ventricular outflow tract obstruction. Severe aortic stenosis in the newborn period (critical aortic stenosis) presents with signs of left sided heart failure (pulmonary edema, poor perfusion), right sided heart failure (hepatomegaly, peripheral edema) and may progress rapidly to total circulatory collapse. We present a case of an infant with critical aortic stenosis presenting with cyanosis, who was entirely dependent on ductal patency for systemic output. When oxygen was given, the ductus started to close, with a worsening of the left sided output and subsequent acidosis. With the right to left shunt across the ductus, the baby was cyanotic and dependent on prostaglandin to keep the ductus open. There was minimal flow across the aortic valve because of the stenosis and extremely poor left ventricular function prior to surgery. After relief of the aortic valvular obstruction, there was finally good antegrade flow across the aortic valve, terminating cyanosis.
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PMID:One day old infant with acyanotic congenital heart disease: critical aortic stenosis. 1056 81

The liver can precisely regulate its growth and mass. Surgical resection of hepatic lobes or hepatocyte loss caused by viral or chemical injury triggers hepatocyte replication while enlarged liver mass is corrected by apoptosis. Hepatocytes have a great replicative capacity and are capable of repopulating the liver. However, "stem-like" cells proliferate when hepatocyte replication is blocked or delayed. Detailed studies of the mechanisms that regulate liver growth have been done in animals subjected to partial hepatectomy or chemical injury. Substantial progress has been achieved using appropriate transgenic and knockout mouse models for this work. Gene expression in the regenerating liver can be divided into several phases, starting with expression of a large number of immediate early genes. Hepatocytes need to be primed before they can fully respond to the growth factors HGF (Hepatocyte Growth Factor), TGFalpha (Transforming Growth Factor Alpha), and EGF (Epidermal Growth Factor) in vitro. Priming requires the cytokines TNF and IL-6 in addition to other agents that prevent cytotoxicity. Reactive Oxygen Species and glutathione content can determine whether the TNF effect on hepatocytes is proliferative or apoptotic. At least four transcription factors, NFkappaB, STAT3 (which are strongly induced by TNF), AP-1 and C/EBPbeta play major roles in the initiation of liver regeneration. In addition, extensive remodeling of the hepatic extracellular matrix occurs shortly after partial hepatectomy. Progression through the cell cycle beyond the initiation phase requires growth factors. The expression of Cyclin D1 probably establishes the stage at which replication becomes growth factor-independent and autonomous. Knowledge about the mechanisms of liver regeneration can now be applied to correct clinical problems caused by deficient liver growth.
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PMID:Liver regeneration. 1072 91

Liver enlargement and hepatocyte proliferation, normal responses in wild-type (WT) mice infected with the parasitic helminth Schistosoma mansoni, were found to be severely impaired in infected IL-4(-/-) mice. Compared with WT mice, increased levels of O(2)(-), NO, and the more highly reactive ONOO(-) were detected in the liver and produced by lesional cells isolated from liver granulomas of infected IL-4(-/-) mice. Concurrently, antioxidant defenses in the liver, specifically catalase levels, diminished dramatically during the course of infection in these animals. This contrasted to the situation in infected WT mice, where catalase levels remained as high as those in normal mice. Actual levels of reactive oxygen and nitrogen intermediates in the livers of infected IL-4(-/-) animals are thus likely to be considerably higher than those in the livers of infected WT mice. To determine whether these changes contributed to the development of the more severe disease that characterizes infection in the IL-4(-/-) animals, we treated infected IL-4(-/-) mice with uric acid, a potent scavenger of ONOO(-). This resulted in significantly increased hepatocyte proliferation, decreased morbidity, and prolonged survival. Taken together, these data indicate that IL-4 is playing a protective role during schistosomiasis by controlling the tight regulation of the generation of reactive oxygen and nitrogen intermediates in the liver.
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PMID:IL-4 plays a crucial role in regulating oxidative damage in the liver during schistosomiasis. 1116 Feb 38

A young trauma patient developed severe adult respiratory distress syndrome (ARDS), right heart failure, hepatic congestion and an extreme hepatomegaly but no hepatic failure. The patient needed 100% oxygen during ventilatory support for 80 days and was weaned from the ventilator after more than 100 days. The hepatomegaly gradually disappeared. Four months after the injury, the anatomical shape of the lungs, heart and liver were normalized. This case illustrates that severe ARDS may cause right heart failure and extreme hepatomegaly due to venous congestion in the liver and spleen, but without hepatic failure.
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PMID:Severe ARDS may cause right heart failure with extreme hepatomegaly but without hepatic failure. 1213 50


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