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Query: UNIPROT:P02794 (ferritin)
 17,525 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Hemochromatosis is a syndrome which, when fully expressed, is manifested by melanoderma , diabetes mellitus, and liver cirrhosis, with iron overload involving parenchymal and reticuloendothelial cells in many organ systems. This clinical presentation may arise as a consequence of either hereditary or acquired abnormalities of iron overload, although the mechanisms are quite different. In hereditary hemochromatosis (also known as primary, or idiopathic, hemochromatosis), increased intestinal iron absorption leads to excessive accumulations of iron, throughout the body, particularly in parenchymal cells. In secondary forms of iron overload including transfusional hemosiderosis, alcoholic cirrhosis, thalassemia, sideroblastic anemia, and porphyria cutanea tarda, iron accumulates in the reticuloendothelial system initially, but with increasing amounts of total body iron, excessive iron deposits eventually accumulate in parenchymal cells throughout the body producing a picture indistinguishable from hereditary hemochromatosis. In this article, the course, prognosis, and therapy of iron overload will be reviewed in detail. Clinical and experimental data concerning the pathogenesis of the different forms of iron overload will be examined critically. In particular, information relating to possible abnormalities of reticuloendothelial function, intestinal mucosal iron transport, and alterations in serum and tissue isoferritin patterns in hereditary hemochromatosis will be analyzed, and possible directions for future research will be suggested. The mode of inheritance and linkage with the major histocompatibility (HLA) complex will be discussed. Theories on the pathogenesis of tissue damage by excess iron will be evaluated. Methods for measuring the extent of iron overload in clinical practice will be described, including measurements of serum iron, serum ferritin, iron absorption, cobalt excretion, desferrioxamine excretion, liver biopsy and tissue iron determinations, and HLA typing. Finally, unresolved problems in the understanding of the disease process, diagnosis, and therapy will be delineated.
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PMID:Iron overload disorders: natural history, pathogenesis, diagnosis, and therapy. 637 41

The effects of slow subcutaneous (s.c.) infusions of desferrioxamine (Desferal: DF) on iron metabolism and excretion were studied in 6 thalassaemia major patients in the course of a ferrokinetic study with 59Fe as a label; s.c. DF infusions were performed every 4th day starting 4 days after that of the 59Fe injection. Serum iron and total iron binding capacity (TIBC) increased after s.c. infusion, whereas serum ferritin levels remained unchanged. 59Fe urinary specific activity decreased in all subjects from the first to subsequent infusions, whereas faecal specific activity remained almost constant throughout the experiment. These data support the hypothesis that iron reaching RE cells concentrates initially in a readily chelatable pool from which then it moves to a larger and not readily chelatable pool, whereas iron reaching parenchymal hepatic cells remains permanently available to chelant.
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PMID:A study of the mechanisms and sites of action of desferrioxamine in thalassaemia major. 642 Oct 46

Basic ferritin (liver-type) was measured in erythrocytes of subjects with alpha- and beta-thalassemia trait, thalassemia intermedia and Cooley's disease, and compared with normals and patients with abnormal iron metabolism without erythrocyte metabolic defect (iron deficiency anemia and idiopathic hemochromatosis). In all the thalassemic syndromes considered, erythrocyte ferritin was significantly higher than in normals (p less than 0.001) and increased progressively with the increasing 'severity' of the thalassemic disorder. In both thalassemic and non-thalassemic subjects, erythrocyte ferritin levels were related to body iron status, but in the thalassemic group, the increased erythrocyte ferritin values seemed also to be closely related to the intracellular metabolic abnormality. The severity of the defect in globin chain synthesis seemed to play an important role in determining ferritin accumulation in red cells of thalassemic subjects.
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PMID:Erythrocyte ferritin in thalassemia syndromes. 642 38

Thyroid function was investigated by a TRH test in 24 clinically prepubertal children, 3-15 years old with beta-thalassaemia major; in 7 of them the test was repeated once and in 2 twice at intervals of at least 12 months. Basal T4, T3, TBG and TSH levels and the TSH levels during a TRH test were determined and correlated with age and serum ferritin levels. Basal serum T4, T3 and TBG levels were lower and serum TSH levels were higher during the test and in the basal state in thalassaemia major children than in control children. These results show a compensated sub-clinical primary hypothyroidism. The transversal study did not show any significant correlation between the hormonal parameters studied and chronological age or serum ferritin levels. In contrast, the longitudinal study showed a significant correlation between pituitary-thyroidal axis function and siderosis (positive correlations between the variations of TSH levels as delta, peak, 30 and 45 min values and the variations of serum ferritin levels). The thyroid impairment seems not to be correlated with serum ferritin levels in the transversal study because of the presence of an individual different sensitivity of the gland to the iron overload. The ferritin dependence of this impairment is shown only by longitudinal studies where individual differences in sensitivity of the gland are absent.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Endocrine involvement in children with beta-thalassaemia major. Transverse and longitudinal studies. I. Pituitary-thyroidal axis function and its correlation with serum ferritin levels. 643 70

Malonyldialdehyde, a product of membrane lipid peroxidation, was measured in the platelets of 16 normal subjects after stimulation with a variety of aggregating and stimulating agents. Nethylmaleimide and hydrogen peroxide generated the largest amounts of malonyldialdehyde. These agents were used to stimulate platelets from 11 patients with thalassaemia major suffering from iron overload due to repeated transfusion. Mean malonyldialdehyde concentrations were the same in normal subjects as in thalassaemic patients, but high concentrations were recorded in patients with severe iron overload. There was a highly significant correlation between malonyldialdehyde and serum ferritin concentrations in all thalassaemic patients. Platelet derived malonyldialdehyde may be a useful test of continuing membrane damage in patients with iron overload.
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PMID:Platelet derived malonyldialdehyde production in patients with thalassaemia major. 647 Jan 82

To determine the therapeutic effect of long-term, intensive iron chelation therapy, we studied liver iron content and histology in four children with thalassaemia major during 52-83 months of intensive therapy with desferrioxamine. The initial biopsies obtained prior to or within 21 months after beginning chelation therapy had Grade IV iron staining, with heavy iron deposition present in parenchymal and reticuloendothelial cells. Subsequent biopsies, obtained when serum ferritin levels had fallen to 71-246 micrograms/l, contained Grade 0 or Grade I stainable iron. Little or no iron was present in parenchymal or reticuloendothelial cells. The liver iron concentration, measured by magnetic susceptibility, returned to normal or nearly normal levels. Hepatic fibrosis did not progress during treatment with desferrioxamine. These findings demonstrate that intensive and sustained chelation therapy with desferrioxamine will remove excessive liver iron and preserve hepatocellular structure.
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PMID:Depletion of excessive liver iron stores with desferrioxamine. 647 38

Increased iron storage represents a characteristic condition in patients with beta zero-thalassaemia intermedia. Iron overload is an important factor in cellular damage. Recent studies have shown an enhanced lysosomal fragility due to increased iron storage. 13 patients with beta-thalassaemia intermedia, aged 17-44 years, were studied. Both serum ferritin and serum N-acetyl-beta-D-glucosaminidase levels were evaluated in all subjects studied. A significant linear correlation (P less than 0.05) between serum ferritin and serum N-acetyl-beta-D-glucosaminidase levels were found.
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PMID:Iron overload and lysosomal stability in beta zero-thalassaemia intermedia and trait: correlation between serum ferritin and serum N-acetyl-beta-D-glucosaminidase levels. 650 27

In a group of young patients with thalassaemia and iron overload treated by subcutaneous infusions of desferrioxamine we have found a number of minor alterations in retinal function. The incidence of such changes is not related to drug dosage or to ferritin level but to abnormality of the extended glucose tolerance test.
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PMID:Ocular changes in patients undergoing long-term desferrioxamine treatment. 650 7

Body iron status, as measured by serum ferritin, was studied in 101 adult Chinese thalassaemic patients, 46 males and 55 females. Thirty of them had mild disease (beta thalassaemia trait), 56 disease of intermediate severity (haemoglobin H disease) and 15 severe disease (homozygous beta thalassaemia, Hb E-beta thalassaemia and delta beta-beta thalassaemia). The extent of iron overload correlated with the severity of disease. In severe thalassaemia, iron overload occurred early in life and was independent of multiple transfusions. While significant impairment of left ventricular function was present in only one of six patients studied, evidence of decreased pituitary (especially gonadotrophic) function was observed in six out of seven. Hypocalcaemia, probably due to hypoparathyroidism, was seen in one.
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PMID:Iron overload in thalassaemic patients in Hong Kong. 651 14

Up until recently in clinical practice suspected hemochromatosis with a pathological iron-screening test (plasma iron, percentage transferrin saturation, serum ferritin, desferrioxamine-induced urinary iron excretion) made a liver biopsy necessary. Today, as a first step, the density of the liver parenchyma can be measured by means of computed tomography. Normal findings obviate the need for laparoscopy. Since the late forties weekly or twice weekly phlebotomy has been the sole form of treatment for manifest idiopathic hemochromatosis. In the mid-sixties the hopes placed in chelating substances (desferrioxamine) were not fulfilled, because the plasma half-life (only 7-10 minutes) of this drug was too short. Even with several daily injections only a small amount of iron was removed from the body tissue (10-25 mg daily urinary iron excretion). The introduction of portable infusion pumps in the late seventies offered us a new possibility of administering desferrioxamine by subcutaneous injection (Propper et al., 1976). Until that time such treatment was successfully used only in the field of pediatrics to treat secondary transfusion hemochromatosis in thalassemia. In one case of idiopathic hemochromatosis with severe organic involvement (right heart failure, repeated esophageal hemorrhage and bronzed diabetes) we had to achieve rapid iron elimination, and for this purpose we used continuous long-term desferrioxamine administration by means of a portable infusion pump (Autosyringe) in addition to phlebotomy. Since, particularly in the critical initial phase of treatment when heart failure was always threatening, great care had to be exercised in the use of phlebotomy, iron removal was achieved largely by desferrioxamine administration (daily up to 240 mg iron elimination in urine and stools).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:New diagnostic and therapeutic possibilities in manifest idiopathic hemochromatosis. 651 41


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