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)

The effects of zileuton, a 5-lipoxygenase inhibitor, on hepatic peroxisomal enzyme activity as well as hepatic drug metabolizing activity in male and female CD-1 mice were assessed after oral administration of the drug (50, 150, or 450 mg/kg/day) for 14 days. The effects were compared to those in mice receiving clofibrate (CLOF;462 mg/kg/day, po) or sodium phenobarbital (PB; 50 mg/kg/day, po). Zileuton pretreatment caused hepatomegaly and elevated liver peroxisomal KCN-insensitive palmitoyl CoA oxidase activity in a dose-dependent manner. However, these changes were marginal (< or = 121% increase), when compared to those elicited by CLOF (approximately 370% increase). In both sexes, zileuton pretreatment also caused a dose-dependent increase in the levels of liver microsomal cytochrome P450 2B and cytochrome P450 4A (CYP4A) proteins, and their associated monoxygenase activity. In the case of CYP4A, the induction of lauric acid 12-hydroxylase activity by zileuton was more pronounced in female (maximal 851% increase) than in male mice (maximal 111% increase). Based on the dose normalized response observed in CD-1 mice, zileuton can be considered a relatively weak inducer of peroxisome enzyme activities (cf.CLOF) and a moderate inducer of cytochromes P450. Moreover, zileuton exhibits characteristics of both a PB- and a CLOF-type hepatic enzyme inducer, especially in the female mice.
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PMID:Hepatic peroxisomal and drug metabolizing activity in CD-1 mice after oral treatment with a novel 5-lipoxygenase inhibitor. 866 44

2-acetyl aminofluorene (AAF) reacts in acidic conditions with nitrous fume yielding N-nitroso-AAF (N-NO-AAF), as previously described, that exerts more toxic and mutagenic effects than its parental compound. In this study, the effect of sodium nitrite (NaNO2) on the tumorigenicity of AAF in rats fed with AAF and NaNO2 was observed. Wistar rats were divided into five groups: group I served as control; group II were treated with NaNO2 (0.3%); group III was given 0.02% AAF alone; groups IV and V received both AAF and NaNO2 (0.2 and 0.3% respectively) in their diet for 12 weeks. At the end of the experiment, all rats in groups III, IV and V developed early stage phenomena of hepatocellular carcinoma, including hepatomegaly with variable-sized foci and neoplastic nodules. Severe damage was observed in the rats treated with AAF and NaNO2. Feeding of AAF (0.02%) for 3 months elevated the levels of c-Fos, c-Jun and c-Myc proteins in the rat livers. The AAF-induced c-Jun, c-Fos and c-Myc expressions were significantly magnified (P < 0.001) by NaNO2. These data confirmed that the strengthening of AAF-induced hepatocarcinogenesis by NaNO2 should be associated with its enhancing effect on the AAF-induced increases in the expressions of c-Jun, c-Fos and c-Myc.
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PMID:Potential effect of sodium nitrite on the expression of nuclear proto-oncogenes during 2-acetyl aminofluorene-induced hepatocarcinogenesis in rats. 946 17

Visceral leishmaniasis is endemic in District Dir, NWFP. We evaluated 10 patients with visceral leishmaniasis at DHQ Hospital Timergara District Dir, N.W.F.P. All patients were in the age range 2 to 10 years. The predominant clinical features in these were chronic fever (10), splenomegaly (10), hepatomegaly (10), weight loss (10) and abdominal distention (5). Lymphadenopathy was absent. Common laboratory abnormalities included anaemia (10), leucopenia (7), thrombocytopenia (10) and hypergammaglobulinaemia (10). Formal Gel test was positive in all patients (100%) and all had positive bone marrow smears for Leishmania Donovani (L.D.) bodies (10). The response to stibogluconate (Glucantime Sodium) therapy was good with a 100 percent cure rate.
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PMID:Visceral leishmaniasis in District Dir, NWFP. 981 85

Reports are scanty regarding kala-azar in children in Nepal. In this communication we document 20 children diagnosed to have kala-azar who were admitted and treated at B. P. Koirala Institute of Health Sciences, Dharan, Nepal. The children were between 2 and 14 years old. The duration of illness varied between 12 days and 24 months with a majority (65 per cent) of children being ill for less than 6 months. Hepatomegaly and splenomegaly were seen in 95 and 90 per cent of cases respectively. Splenomegaly was not found in two (10 per cent) children. Anaemia, leucopenia, and thrombocytopenia were seen in 95, 60, and 75 per cent of children respectively. Amastigotes of Leishmania donovani (LD bodies) were demonstrated in Giemsa-stained smears of bone marrow aspirates in 16 (80 per cent) children. All the children responded to treatment with sodium stibogluconate. No mortality was observed. This study emphasizes the importance of kala-azar in children in endemic areas of eastern Nepal.
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PMID:Clinical and laboratory study of kala-azar in children in Nepal. 1034 3

To examine the effect on cell population in hepatocytes of phenobarbital (PB) and other barbiturates, PB, allobarbital (ALB), barbital sodium (BS) and barbituric acid (BA) were given orally to male rats for 7 consecutive days. Although there was no apparent change in non-promoting BA, hepatomegaly was induced by PB, BS and ALB, which are promoters of hepatocarcinogenesis. In PB- and BS-treated livers, hepatomegaly was attributable to hepatocyte proliferation and enzyme induction. In ALB-treated liver, it was attributable to enzyme induction. The level of cell proliferation was reduced to less than the control values following withdrawal of PB, ALB and BS. It seemed that the degree of suppression of cell proliferation following withdrawal of these compounds correlated to the degree of cell proliferation (PB>BS>ALB) during treatment. In PB-treated liver, apoptosis was induced during treatment, serving to eliminate the excess of hepatocytes. This suggests that short-term administration of PB neither induced suppression of apoptosis nor disturbed homeostasis of hepatocyte populations.
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PMID:Apoptosis and cell proliferation in rat hepatocytes induced by barbiturates. 1067 85

A retrospective study was undertaken of 33 children with visceral leishmaniasis admitted to Sultan Qaboos University Hospital (SQUH), Oman between 1993 and 1999. The aim was to study the epidemiological and clinical characteristics of visceral leishmaniasis in children in Oman. All presented with fever, anaemia and splenomegaly. Hepatomegaly and lymphadenopathy were present in 88% and 39% of children, respectively. All had iron deficiency anaemia. Hypertriglyceridaemia is a new observation. Diagnosis in all cases was confirmed by histological demonstration of Leishmania amastigotes in bone marrrow (32 subjects) or splenic aspirate (one subject). All children were treated with sodium stibogluconate, 14 needed blood transfusion or blood products and all but two responded well. There were two deaths from associated complications (6% mortality).
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PMID:Visceral leishmaniasis in Omani children: a review. 1147 Dec 61

We describe an elderly case of idiopathic dilatation of the right atrium in which right-sided heart failure was exacerbated by drug-induced bradyarrhythmia. An 84-year-old man, who had a 10-year history of episodic edema, was treated with proscillaridin and verapamil hydrochloride at another hospital. He had experienced a poor appetite and general malaise 2 months previously, and exertional dyspnea 10 days previously. On admission, he had jugular venous dilatation, systemic edema, and hepatomegaly. On auscultation, a third heart sound originating from the right ventricle and systolic murmur of tricuspid regurgitation were heard. An admission electrocardiogram showed an atrial standstill and junctional escape rhythm with a QRS rate of 31 beats/minute. Chest roentgenogram revealed a bilateral pleural effusion and cardiomegaly with a cardiothoracic ratio of 76%, but no pulmonary congestion. Echocardiogram disclosed idiopathic dilatation of the right atrium and secondary tricuspid regurgitation. He was given a diagnosis of right-sided heart failure due to idiopathic dilatation of the right atrium exacerbated by bradyarrhythmia, which was suspected to derive from the side effects of proscillaridin and verapamil hydrochloride. Thus, these agents were withheld. In addition, the patient reduced sodium intake and was treated with diuretics and beta-adrenergic agonist. Thereafter, right-sided heart failure markedly improved. At the time of the last follow-up 16 months after discharge, he felt well.
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PMID:[An elderly case of idiopathic dilatation of the right atrium in which right-sided heart failure was exacerbated by drug-induced bradyarrhythmia]. 1152 70

Visceral leishmaniasis, or kala-azar, is a chronic disease caused by Leishmania donovani, Leishmania chagasi or Leishmania infantum. The disease is transmitted through the bite of a species of sandfly of the genus Phlebotomus, releasing amastigote parasites that invade various organs of the body and eventually result in such conditions as anemia, splenomegaly and hepatomegaly. Although no vaccine exists for the disease, diagnostic techniques based not only on pathological tests, but more sophisticated detectors such as polymerase chain reaction, enzyme-linked immunosorbent assay, latex agglutination and immunochromatographic strip testing have been developed. Traditional treatment for the disease consists of two pentavalent antimonial drugs, sodium stibogluconate and meglumine antimoniate, but the growing resistance to these drugs has compelled scientists to search for new efficient compounds. (c) 2002 Prous Science. All rights reserved.
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PMID:Visceral Leishmaniasis: Clinical Features, Pathology, Diagnosis and Chemotherapeutic Developments. 1267 77

The Children's Cancer Group (CCG) 1952 clinical trial for children with standard-risk acute lymphoblastic leukemia (SR-ALL) compared intrathecal (IT) methotrexate (MTX) with IT triples (ITT) (MTX, cytarabine, and hydrocortisone sodium succinate [HSS]) as presymptomatic central nervous system (CNS) treatment. Following remission induction, 1018 patients were randomized to receive IT MTX and 1009 ITT. Multivariate analysis identified male sex, hepatomegaly, CNS-2 status, and age younger than 2 or older than 6 years as significant predictors of isolated CNS (iCNS) relapse. The 6-year cumulative incidence estimates of iCNS relapse are 3.4% +/- 1.0% for ITT and 5.9% +/- 1.2% for IT MTX; P = .004. Significantly more relapses occurred in bone marrow (BM) and testicles with ITT than IT MTX, particularly among patients with T-cell phenotype or day 14 BM aspirate containing 5% to 25% blasts. Thus, the estimated 6-year event-free survivals (EFS) with ITT or IT MTX are equivalent at 80.7% +/- 1.9% and 82.5% +/- 1.8%, respectively (P = .3). Because the salvage rate after BM relapse is inferior to that after CNS relapse, the 6-year overall survival (OS) for ITT is 90.3% +/- 1.5% versus 94.4% +/- 1.1% for IT MTX (P = .01). It appears that ITT improves presymptomatic CNS treatment but does not improve overall outcome.
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PMID:Intrathecal triple therapy decreases central nervous system relapse but fails to improve event-free survival when compared with intrathecal methotrexate: results of the Children's Cancer Group (CCG) 1952 study for standard-risk acute lymphoblastic leukemia, reported by the Children's Oncology Group. 1660 69

Sulfate plays an essential role in human growth and development, and its circulating levels are maintained by the renal Na+-SO42- cotransporter, NaS1. We previously generated a NaS1 knockout (Nas1-/-) mouse, an animal model for hyposulfatemia, that exhibits reduced growth and liver abnormalities including hepatomegaly. In this study, we investigated the hepatic gene expression profile of Nas1-/- mice using oligonucleotide microarrays. The mRNA expression levels of 92 genes with known functional roles in metabolism, cell signaling, cell defense, immune response, cell structure, transcription, or protein synthesis were increased (n = 51) or decreased (n = 41) in Nas1-/- mice when compared with Nas1+/+ mice. The most upregulated transcript levels in Nas1-/- mice were found for the sulfotransferase genes, Sult3a1 (approximately 500% increase) and Sult2a2 (100% increase), whereas the metallothionein-1 gene, Mt1, was among the most downregulated genes (70% decrease). Several genes involved in lipid and cholesterol metabolism, including Scd1, Acly, Gpam, Elov16, Acsl5, Mvd, Insig1, and Apoa4, were found to be upregulated (> or = 30% increase) in Nas1-/- mice. In addition, Nas1-/- mice exhibited increased levels of hepatic lipid (approximately 16% increase), serum cholesterol (approximately 20% increase), and low-density lipoprotein (approximately 100% increase) and reduced hepatic glycogen (approximately 50% decrease) levels. In conclusion, these data suggest an altered lipid and cholesterol metabolism in the hyposulfatemic Nas1-/- mouse and provide new insights into the metabolic state of the liver in Nas1-/- mice.
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PMID:Transcriptional profile reveals altered hepatic lipid and cholesterol metabolism in hyposulfatemic NaS1 null mice. 1662 89


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