Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P02794 (ferritin)
 17,525 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Serogroups of N. meningitidis were characterized as virulent or avirulent according to their capacity to establish meningococcal infection in mice. An agar plate diffusion technique demonstrated that iron had a definite growth-supporting role for both of these meningococcal types. The avirulent strains could use ionic or chelated iron as well as the virulent strains. Iron-reversible growth inhibition occurred to the same extent for both bacterial types in the presence of the synthetic iron-chelating agents Desferal and ethylenediamine-di-orthohydroxy phenylacetic acid. A difference in response was demonstrated for these bacterial types when grown in the presence of various iron-binding proteins from animal body fluids and tissues. The growth of the avirulent strain was inhibited to a greater degree by egg white conalbumin. The humoral iron-binding protein transferrin showed a significant inhibitory capacity only when used in conjunction with bicarbonate. Under conditions of increased iron saturation of this protein, the avirulent strain was inhibited to the furthest extent. In the presence of ferritin, the cellular iron-binding protein, which had been reduced, inhibition of the growth of either strain type did not occur on iron-poor media (less than 5 micrograms/100 ml). However, with the incorporation of iron into the media, the inhibitory effect of the protein became evident. As the concentration of iron increased, the inhibition increased to a certain level and subsequently declined. A substantial difference in the ability of the avirulent type to grow in the presence of reduced horse spleen ferritin was observed. For this microorganism, a correlation appears to exist between the capacity to grow by utilizing the available iron in the presence of reduced ferritin and the ability to establish infection. The host protein ferritin, in the reduced state, apart from simply being a storage protein for iron, can prevent the growth of a procaryotic organism. Our experiments suggest a role for ferritin in the prevention of emningococcal disease. A cehmotherapeutic potential for Desferal is also implied.
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PMID:Inhibition of the growth of Neisseria meningitidis by reduced ferritin and other iron-binding agents. 11 92

The clinical features and therapy of chronic iron overload are reviewed. Chronic iron overload is classified as primary or secondary hemochromatosis. In primary hemochromatosis a genetic defect in iron metabolism results in increased absorption of iron from the gastrointestinal tract. The excess iron in secondary hemochromatosis may be derived from increased gastrointestinal absorption due to ineffective erythropoiesis or from medicinal, dietary, or transfusional sources. Phlebotomy is the treatment of choice in patients with primary hemochromatosis. Iron chelation therapy is indicated in patients who are not candidates for phlebotomy. Deferoxamine mesylate, the only commercially available iron chelator, is usually administered subcutaneously or intravenously over 10-12 hours/day. Serum ferritin concentrations are measured every three to six months to monitor the effectiveness of therapy. The adverse effects of deferoxamine include local skin reactions, ototoxicity, cataracts, growth impairment, and increased susceptibility to infectious organisms. Patient compliance may be compromised by the routes of administration and cost of deferoxamine. Early detection and prompt treatment are necessary to prevent organ damage. Phlebotomy and iron chelation therapy are effective in the treatment of chronic iron overload.
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PMID:Treatment of chronic iron overload. 174 62

The role of ferritin in catalyzing the oxidation of luminol with the production of chemiluminescence was investigated. The effect of pH was compared to its effect on K3Fe(CN)6-catalyzed oxidation and different pH optima were recorded for the two catalysts. The ferrous iron chelator, bipyridyl, enhanced the production of chemiluminescence catalyzed by FeSO4 and ferritin but had little effect on the K3Fe(CN)6-catalyzed reaction. Desferal reduced the level of chemiluminescence in the presence of FeSO4 and ferritin but was a much more effective inhibitor of chemiluminescence catalyzed by K3Fe(CN)6. The hydroxyl radical scavenger, mannitol, had little effect upon light production whereas superoxide dismutase inhibited light production. The addition of antihuman spleen ferritin completely inhibited activity. The catalytic activity of both H and L rich ferritins was affected by iron content. Activity increased until the Fe/protein ratio reached 0.04 micrograms Fe/micrograms protein and then decreased with increasing iron content. Thus activity is controlled by the iron content of the molecule and influenced by its subunit composition as is the uptake of iron into ferritin. These findings suggest that ferroxidation by ferritin is associated with the ability to generate radicals of the nitrogenous base luminol with the production of chemiluminescence. Although activity is greatest at alkaline pH there is significant activity at pH 7.4. Ferritin therefore may be able to generate free radical reactions in vivo with the acidic isoferritin being most active.
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PMID:Luminol peroxidation catalyzed by human isoferritins. 189 51

Activated phagocytic cells produce superoxide (O2-) and hydrogen peroxide (H2O2); their production is important in bacterial killing by neutrophils and has been implicated in tissue damage by activated phagocytes. H2O2 and O2- are poorly reactive in aqueous solution and their damaging actions may be related to formation of more reactive species from them. One such species is hydroxyl radical (OH.), formed from H2O2 in the presence of iron- or copper-ion catalysts. A major determinant of the cytotoxicity of O2- and H2O2 is thus the availability and location of metal-ion catalysts of OH. formation. Hydroxyl radical is an initiator of lipid peroxidation. Iron promoters of OH. production present in vivo include ferritin, and loosely bound iron complexes detectable by the 'bleomycin assay'. The chelating agent Desferal (desferrioxamine B methanesulphonate) prevents iron-dependent formation of OH. and protects against phagocyte-dependent tissue injury in several animal models of human disease. The use of Desferal for human treatment should be approached with caution, because preliminary results upon human rheumatoid patients have revealed side effects. It is proposed that OH. radical is a major damaging agent in the inflamed rheumatoid joint and that its formation is facilitated by the release of iron from transferrin, which can be achieved at the low pH present in the micro-environment created by adherent activated phagocytic cells. It is further proposed that one function of lactoferrin is to protect against iron-dependent radical reactions rather than to act as a catalyst of OH. production.
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PMID:Metal ions and oxygen radical reactions in human inflammatory joint disease. 241 31

Iron chelation therapy must be associated with the regular blood transfusions required for thalassaemia and other chronic anemias. We report here a study concerning 4 groups of patients, aged 6 to 28, regularly transfused at Necker Enfants-Malades hospital: a) 20 with thalassaemia major; b) 6 with thalassaemia intermedia; c) 2 with sickle cell disease and d) 2 with Blackfan-Diamond syndrome. The transfusion regimen consisting of monthly or quarterly transfusions varied as a function of the groups. Desferal was used in all patients. The dosage and the route of administration (IV, IM, SC) were adapted to the amount of iron transfused and to the nature of the disease. The serum ferritin level was considered as the indicator of the iron overload. Comparisons were established between the quantities of iron transfused, ferritin levels, and parameters such as dosage, route of administration and compliance to Desferal. During the period of study 3 patients died from cardiac failure due to transfusional hemosiderosis. Endocrine complications (diabetes 2 cases, hypocalcemia 3 cases, hypothyroidism 1 case and delayed puberty 7 cases) were observed. This high incidence of complications induced by post-transfusional iron overload has recently prompted us to improve the quality of chelation therapy through the use of the services of a specialized center where patients as well as their families can be trained more adequately in home care and self-treatment.
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PMID:[Treatment of post-transfusion iron overload by deferoxamine]. 273 4

Acquired hemosiderosis resulting from massive iron deposits in various organs, including heart, liver, and pancreas, may lead to architectural and functional disturbances of these organs. Even though iron overload can occur in nonuremic as well as in uremic individuals, the dialysis patient is at particular risk for developing hemosiderosis. Many dialysis patients receive exogenous iron from either oral iron therapy or blood transfusions. In addition, these patients seem to be at high risk for retaining iron. A diagnosis of excess iron deposition should be considered if the patient has unexplained cardiomyopathy, hepatic cirrhosis, proximal myopathy, diabetes mellitus, arthropathy, or immune dysfunction such as listeriosis. Several techniques are available for determining iron overload. Diagnostic tests include measuring serum ferritin levels, staining bone marrow preparations for excess iron, measuring tissue hemosiderin concentrations, magnetic resonance imaging, and the deferoxamine (DFO; Desferal) "challenge test." The simplest treatment for iron overload in nonuremic patients is removal of iron by venesection. However, in patients in whom venesection is not feasible, the chelating agent DFO can effectively remove excess iron. In the dialysis patient, DFO therapy can be combined with either dialysis or hemoperfusion to remove the iron-DFO complex that would otherwise be removed by the kidney. DFO therapy in the nondialyzed individual has proven to be successful, but before treatment, the benefits of the treatment must be weighed against possible adverse side effects such as cataracts, changes in color vision, and anaphylaxis. In the dialysis patient, indications for iron removal are less clearly defined.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Management of iron overload in dialysis patients. 329 89

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

Several reports have suggested that iron deficiency might explain "sports anemia" especially in long distance runners. The present study was made to further study the iron metabolism in runners as the proposed cause of "sports anemia" is abstruse considering the good iron nutrition in these athletes. Based on a screening of 43 elite male runners, using bone marrow hemosiderin, serum ferritin and transferrin saturation, two groups of subjects were selected for a very extensive study on iron metabolism. In group 1 (n = 5) iron depletion was suggested in at least one of the screening studies. In group 2 (n = 7) at least one test strongly indicated good iron repletion. This experimental design was chosen to obtain two groups with similar body composition and exercise load but different iron metabolism. The studies comprised determinations of red cell and plasma volumes, plasma iron turnover and red cell incorporation of radioiron, red cell indices, plasma iron and transferrin, red cell protoporphyrin, serum ferritin, serum haptoglobin, urinary iron losses, iron absorption, bone marrow hemosiderin, dietary intake of energy and nutrients and a Desferal test. Pooling the results together it was obvious that none of the subjects were truly iron-deficient. A few occasional findings suggesting low iron stores cannot be satisfactorily explained and indicate that further studies are needed.
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PMID:Iron metabolism and "sports anemia". I. A study of several iron parameters in elite runners with differences in iron status. 649 74

In seven patients with hemochromatosis, arthropathy was an early symptom, or first clinical symptom, of the hemochromatosis. In all seven patients, serum iron, transferrin saturation, and parameters of storage iron (serum ferritin, Desferal-test) were clearly elevated. In 5 patients hemochromatosis was associated with the HLA loci A3 and B7. Bone scan proved a sensitive detection method for hemochromatosis arthropathy. In one case joint involvement was detected by bone scan prior to clinical symptoms. Parameters of iron metabolism correlated well with other organ manifestations of hemochromatosis. In contrast, joint involvement did not correlate with parameters of iron metabolism or severity of hemosiderosis of other organs, and was not relieved by phlebotomy. These 7 cases confirm that joint symptoms can be an early or leading symptom of hemochromatosis, can lead to early therapy and thereby prevent major organ damage. It remains undecided, however, whether the arthropathy is a consequence of iron storage or an independent disease which is genetically associated with hemochromatosis.
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PMID:[Arthropathy as an early symptom of hemochromatosis. Overview of the literature and 7 case reports]. 672 20

Subcutaneous infusions of Desferal (DF) rarely induce negative iron balance in thalassemia major patients less than 6 years old. In nonsplenectomized patients the requirements for blood transfusions increase slightly. Urinary iron excretion decreases during the first days following a blood transfusion. An average of 5.8 mg/day equivalent to 30% of the total iron excretion is eliminated with the feces after subcutaneous infusions of DF. Serum ferritin does not decrease significantly after 18-24 months of therapy. The effectiveness of long-term therapy progressively increases in the splenectomized patients, while it decreases appreciably in the course of the treatment in the nonsplenectomized ones.
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PMID:Intensive iron chelation therapy in beta-thalassemia major: some effects on iron metabolism and blood transfusion dependence. 681 66


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