Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P17174 (aspartate aminotransferase)
 14,872 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The effect of the pyoverdin Pf (an iron chelating agent isolated and purified from Pseudomonas fluorescens CCM 2798) was studied on iron overloaded rat hepatocyte cultures. Iron overload was obtained by addition of 5-80 microM ferric nitrilotriacetate to the culture medium. Twenty-four hours after iron treatment, a significant increase in aspartate aminotransferase and lactate dehydrogenase in the culture medium was observed. This corresponded to intracellular decrease in the activity of these two enzymes and correlated with a decrease in albumin secretion and an increase in total free malondialdehyde production. The iron toxicity was inhibited by desferrioxamine B. Pyoverdin Pf added to the hepatocyte cultures served as an effective agent to prevent iron toxicity induced in overload. The observed effect of the pyoverdin Pf was as potent as that of desferrioxamine B.
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PMID:Inhibition of iron overload toxicity in rat hepatocyte cultures by pyoverdin Pf, the siderophore of Pseudomonas fluorescens. 156 81

Eighty patients with chronic viral hepatitis were screened for evidence of iron overload. Elevated serum iron values were noted in 36% of cases; serum ferritin values were above normal in 30% of men and 8% of women. Twenty-eight additional patients with chronic hepatitis for whom liver tissue was available for determination of iron content were evaluated to study the significance of iron overload in association with chronic hepatitis. Although 46% had elevated serum iron, ferritin, or transferrin-saturation levels, the hepatic iron concentration was elevated in only four cases, and the hepatic iron index was in the range for hereditary hemochromatosis (greater than 2.0) in only two of these. Serum aspartate aminotransferase activities correlated with serum ferritin levels in these patients, suggesting that ferritin and iron levels were increased in serum because of their release from hepatocellular stores associated with necrosis. Thus, in patients with chronic hepatitis in whom hereditary hemochromatosis is suspected, a liver biopsy should be performed with quantitation of hepatic iron and calculation of the hepatic iron index to confirm the diagnosis.
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PMID:Measurements of iron status in patients with chronic hepatitis. 842 15

To define an iron overload index independent of liver cell damage, the mean annual levels of alanine aspartate transaminase (ALAT) and serum ferritin and their ratios were determined. Ferritin/ALAT ratio values were compared between two groups of patients with acute or chronic hepatitis without iron overload, and one group of thalassaemic patients with iron overload. The two groups without iron overload exhibited ferritin/ALAT ratio values of 2 and 1.2 respectively; a ratio value higher than 10 was always observed in those patients with iron overload. The ferritin/ALAT ratio is correlated with the degree of iron overload. This ratio increases in regularly-transfused patients without chelation treatment. It generally remains stable or decreases after initiation of iron chelation therapy. The ferritin/ALAT ratio thus appears useful in the follow-up of patients subjected to a long-term transfusional treatment particularly when acute or chronic liver cell damage may interfere with iron overload by increasing serum ferritin values.
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PMID:Use of the ferritin/alanine aspartate transaminase ratio as an iron overload marker independent of liver cell damage. 261 15

Liver biopsies were performed on 51 regularly transfused patients with beta thalassaemia, age range 5-36 (mean 18.6) years, who had received regular subcutaneous desferrioxamine (DFX) treatment for periods between one and eight years (40 for eight years). The biopsy specimens were examined by light microscopy and immunofluorescence for hepatitis B virus surface and core antigens (HBsAg and HBcAg), and the iron content was determined chemically. The results were compared with serum ferritin concentration and aspartate transaminase (AST) activity and with hepatitis B virus serology. Biopsy specimens, in which chemical liver iron had been determined in 12, were also available from 17 patients. Mean serum ferritin (+/- SD) had fallen from 5885 (3245) micrograms/l to 1638 (976) micrograms/l in 36 patients after eight years' chelation, while mean (+/- SD) liver iron concentration had fallen from 2945 (900) micrograms/100 mg dry weight to 857 (435) micrograms/100 mg dry weight in 12 of them. All biopsy specimens examined were negative for HBs and HBc antigens. The presence of histological features of hepatitis was associated with increased liver iron content, increased fibrosis, and with progression of fibrosis between the two biopsies. Procollagen III peptide was assayed in 28 patients but did not correlate with the degree of hepatitis, fibrosis, or with chemical liver iron content. We conclude that with regular subcutaneous DFX, mean concentrations of serum ferritin and liver iron are maintained in these patients at about five and 10 times the normal value, respectively, and that progression of liver damage is more likely to be due to viral hepatitis, presumably related to the parenterally transmitted non-A, non-B agents than to iron overload.
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PMID:Iron state and hepatic disease in patients with thalassaemia major, treated with long term subcutaneous desferrioxamine. 312 79

We examined the efficacy of long-term subcutaneous deferoxamine therapy in the prevention of iron-related cardiac disease in patients with thalassemia major who began treatment after the age of 10 years. Of 36 such patients without preexisting cardiac disease, 19 did not comply with the program of chelation therapy. Over the course of treatment (1977 to 1983) serum ferritin and aspartate aminotransferase levels fell in the compliant group, from mean values (+/- S.D.) of 4765 +/- 2610 to 2950 +/- 1850 ng per milliliter and 58.1 +/- 22 IU to 30 +/- 20 IU per liter, respectively (P less than 0.05), but rose in the noncompliant group, from 5000 +/- 2316 to 6040 +/- 2550 ng per milliliter and 56.6 +/- 20 to 90 +/- 35 IU per liter, respectively. Only one patient in the compliant group acquired cardiac disease and died of fulminant congestive heart failure. In contrast, 12 noncompliant patients acquired cardiac disease, and 7 died. In addition, the mean age of the compliant population (18.9 +/- 4.5 years) now approaches the mean age of acquisition of cardiac disease in the noncompliant group (19 +/- 4.3). These data demonstrate that compliance with treatment with deferoxamine may protect patients from cardiac disease induced by iron overload.
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PMID:Prevention of cardiac disease by subcutaneous deferoxamine in patients with thalassemia major. 400 Jan 98

In this study maximum urinary iron elimination with continuous desferrioxamine subcutaneous infusion was obtained in thalassemia major patients with chronic persistent or active hepatitis with lower doses (60 mg/kg) than those necessary in patients without hepatitis (80 mg/kg). Since dose-response curves were highly variable the treatment schedule should be tailored to the individual needs of each patient. Both groups may achieve iron balance but chronic hepatitis patients have more frequently a net urinary iron excretion. In patients with chronic hepatitis no correlation was found between serum ferritin levels or serum ferritin/aspartate aminotransferase ratios and transfusional iron overload while serum ferritin/aspartate aminotransferase ratios were seen to be correlated with liver iron stores.
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PMID:Iron chelation in transfusion-dependent thalassemia with chronic hepatitis. 680 Feb 2

The protective effect of the hydroxypyridin-4-ones (CP20 and CP94) was studied on iron-loaded rat and human hepatocytes; desferrioxamine B was used as a chelator reference. Iron load was achieved by addition of 5 up to 50 microM iron citrate to the culture medium. One day after iron treatment, an increase in lactate dehydrogenase, aspartate aminotransferase, alanine aminotransferase and malondialdehyde extracellular concentrations was measured in rat and human hepatocyte cultures. This enzyme release and the increase in free extracellular malondialdehyde were observed with 5 microM iron and high levels were obtained with 50 microM. The bidentate chelators CP20 and CP94 (150 microM) appeared to be as effective as the hexadentate chelator desferrioxamine (50 microM) in the protection of rat and human hepatocytes against the toxic effect of iron load achieved by culturing the cells for 1 day in the presence of 50 microM iron citrate. In rat and human hepatocytes cultured for 1 day in the presence of 1 microM 55Fe-50 microM iron citrate plus CP20, CP94 or desferrioxamine B, a decrease of iron uptake by the cells was observed. When the hepatocytes were cultured for 1 day in the presence of 1 microM 55Fe-50 microM iron citrate and then for a further day in the presence of CP20, CP94 or desferrioxamine B but not iron, the chelators decreased the intracellular iron level, indicating their iron releasing effect from the loaded cells. The observed effects of the hydroxypyridin-4-ones CP20 and CP94 were as potent as the effect of desferrioxamine B. This study presents new data favoring the potential clinical interest of this new class of chelating agents in the treatment of human iron overload.
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PMID:Inhibition of iron toxicity in rat and human hepatocyte cultures by the hydroxypyridin-4-ones CP20 and CP94. 749 88

Tissue iron loading in hypotransferrinaemic (hpx/hpx) mice was investigated as a model for genetic (primary) haemochromatosis. Iron loading of liver preceded that in the pancreas and heart. One-year-old hpx/hpx mice showed iron staining in exocrine pancreas, liver parenchymal cells, and cardiac and intestinal smooth muscle cells. Iron-loaded macrophages were observed in all these tissues. Islets of Langerhans, biliary epithelial cells, and spleen were iron-free. The pancreas was fibrotic with massive macrophage infiltration and loss of secretory epithelium. Liver showed evidence of chronic inflammatory infiltration with increased collagen fibres in the parenchymal region but no cirrhosis. Serum aspartate aminotransferase activity and plasma glucose were increased in hpx/hpx compared with wild-type mice. Heavy iron loading with haemosiderin deposition in the liver could be demonstrated in hpx/hpx mice from 6 weeks of age. Heterozygous hypotransferrinaemic mice showed minor increases in liver iron stores at 6-12 weeks, but not at 1 year of age. Serum ferritin levels in heterozygous mice were also increased at 6-8 weeks of age. It was concluded that 1-year-old hpx/hpx mice showed evidence of liver and pancreatic damage secondary to tissue iron overload. The iron loading pattern and tissue damage showed some features which were distinct from those observed in haemochromatosis.
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PMID:Tissue iron loading and histopathological changes in hypotransferrinaemic mice. 827 72

Biochemical evidence of iron overload (transferrin saturation greater than 60% and/or serum ferritin concentration greater than 1000 micrograms/L) was observed in 16% of patients admitted to an alcohol withdrawal unit. No subjects in an age and sex matched control group showed such biochemical changes. Whilst changes in serum ferritin concentration closely correlated with aspartate aminotransferase activity and could be explained by alcohol induced liver damage, the increased transferrin saturation was not similarly explained. In nine patients withdrawal of alcohol resulted in a decrease in transferrin saturation and serum ferritin, the former due to a reduction in serum iron concentration. In patients with high alcohol intake biochemical measures of iron status may be misleading and a decrease in both transferrin saturation and serum ferritin concentration after withdrawal of alcohol may help to rule out the possible diagnosis of hereditary haemochromatosis.
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PMID:Assessment of iron status in association with excess alcohol consumption. 857 83

To test the hypothesis that the quantities of circulating transferrin receptors are reduced in iron overload, we studied serum transferrin receptors and indirect measures of iron status in 150 subjects from rural Zimbabwe. We found significant inverse correlations between serum concentrations of transferrin receptors and ferritin, the ratio of ferritin to aspartate aminotransferase, and transferrin saturation (r > or = 0.44; P < 0.001). The mean +/- SD concentration of serum transferrin receptors in 23 subjects classified as having iron overload (ferritin > 300 microg/L and transferrin saturation > 60%) was 1.55 +/- 0.61 mg/L, significantly lower than the 2.50 +/- 0.62 mg/L in 75 subjects with normal iron stores (ferritin 20-300 microg/L and transferrin saturation 15-55%; P < 0.0005) and the 2.83 +/- 1.14 mg/L in 8 subjects with iron deficiency (ferritin < 20 microg/L; P = 0.001). In keeping with the regulation of transferrin receptor expression at the cellular level, our findings suggest that serum transferrin receptors are decreased in the presence of iron overload.
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PMID:Serum transferrin receptors are decreased in the presence of iron overload. 955 May 56


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