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)

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

A 12-year-old girl with congenital dyserythropoietic anemia, type I, was diagnosed as having hemochromatosis. Deferoxamine was given subcutaneously for 14 months. Iron overload, as measured by liver iron and serum ferritin levels, was reduced substantially, liver function tests improved, and hepatomegaly decreased. Toxicity was negligible.
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PMID:Use of subcutaneous deferoxamine in a child with hemochromatosis associated with congenital dyserythropoietic anemia, type I. 707 63

The effects of various iron-containing compounds on the responses of human peripheral lymphocytes to phytohemagglutinin (PHA) and pokeweed mitogen (PWM) were studied in serum-free medium supplemented with bovine serum albumin. Hemoglobin, transferrin and ferritin enhanced the incorporation of 3H-thymidine into DNA after PHA-stimulation of lymphocytes, while hemin, iron metal powder, ferrous sulfate, chromium powder, and zinc sulfate have little effect. The response to PWM, measured by plaque formation, was enhanced only by transferrin. Desferrioxamine, a chelating agent specific for ferric iron, completely removed these augmentative effects. The results indicate that iron-containing proteins influenced the responses of lymphocytes to stimulation by PHA and PWM in serum-free medium.
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PMID:Iron-containing proteins augment responses of human lymphocytes to phytohemagglutinin and pokeweek mitogen in serum-free medium. 711 53

During acute viral hepatitis, disturbances in iron metabolism occur. To obtain more insight into this, DFO and DTPA induced urinary iron excretion was studied during acute viral hepatitis. It was found that liver cell damage enhances iron excretion, in proportion to the extent of liver cell disintegration: a highly significant correlation was shown between the DFO as well as DTPA induced urinary iron excretion, and the SGPT. Also, a correlation existed between sideruria and the serum iron level, as well as with the serum bilirubin concentration, provided the test was performed within 10 days after the onset of the jaundice. It is suggested that during liver cell damage, iron, which is liberated during ferritin catabolism, forming a transit pool within the hepatocyte and/or at the cell membrane, is the immediate source of iron donation to DFO and/or DTPA. The practical importance for interpretation of iron mobilisation tests is pointed out.
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PMID:Iron mobilisation with chelating agents during acute viral hepatitis. 717 6

The release of iron from horse spleen ferritin by the chelating agents desferrioxamine B, rhodotorulic acid, 2,3-dihydroxybenzoate, 2,2'-bipyridyl and pyridine-2-aldehyde-2-pyridyl hydrazone (Paphy) has been studied in vitro. Ferritin prepared by classical procedures involving thermal denaturation releases its iron less effectively than ferritin isolated by a modified procedure that avoids this step. Desferrioxamine B and rhodotorulic acid are the most effective in releasing iron from both preparations of ferritin. When FMN is added, iron release by desferrioxamine B, rhodotorulic acid, and 2,3-dihydroxybenzoate was effectively blocked, whereas both bipyridyl and Paphy showed a marked simulation. A substantial increase in iron release was also observed for bipyridyl and Paphy with ascorbate; a less important increase was noted for rhodotorulic acid. EDTA exerted a marked inhibition of iron release from ferritin with rhodotorulic acid, 2,3-dihydroxybenzoate, bipyridyl, and Paphy. The effects of citrate and oxalate on iron release by the chelators was small. The effect of the concentration of flavin on iron release from ferritin by bipyridyl and desferrioxamine B have been studied. Desferrioxamine is unable to mobilize FeII from ferritin following reduction by reduced FMN, whereas bipyridyl can rapidly complex the ferrous iron. The results are discussed in the context of our current concepts of storage iron mobilization in the treatment of iron overload.
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PMID:Iron mobilization from ferritin by chelating agents. 719 39

The A. compare the values of serum ferritin and Desferrioxamine (DFO)-induced sideruria on 73 patients affected by different diseases. The results may be divided into three groups: a first one concerning patients with low serum ferritin and low DFO-induced sideruria, a second one of patients with normal serum ferritin and normal DFO-induced sideruria; in the third group of patients the A. found high values of serum ferritin and high or normal values of DFO-induced sideruria. The different behaviour observed in this III group of patients mostly affected by malignancy may be ascribed, in all those cases with high ferritin and normal sideruria, to a direct production of isoferritins by cancer cells.
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PMID:[Comparison between serum ferritin and induced sideruria in the diagnosis of disorders of iron metabolism]. 729 Apr 73

A method of loading macrophages from normal and inflammatory mouse peritoneal exudates with 59Fe using 59Fe, 125I-transferrin-antitransferrin immune complexes is described and the subsequent release of iron and degraded transferrin to the incubation medium has been studied. Release of iron occurred more rapidly from resident macrophages than from thioglycollate broth-induced (stimulated) macrophages, but degradation of the 125I-transferrin in the immune complexes was faster in stimulated cells. A small percentage of the iron released was in the form of ferritin. Desferrioxamine (1 mM) increased the release of iron from both stimulated and resident macrophages, the effect being proportionally greater in the stimulated cells. Ascorbic acid (1 mM) had no effect on the release of iron, nor did the addition of apotransferrin (1 mg/ml) to the culture medium. These results support the concept of a blockade of iron release by reticuloendothelial cells in states of inflammation, and suggest that it may be a primary cause of the anaemia of chronic disease.
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PMID:Release of iron by resident and stimulated mouse peritoneal macrophages following ingestion and degradation of transferrin-antitransferrin immune complexes. 731 89

The instability of oncogenic mRNA such as c-fos mRNA is controlled in cis by sequences present in both the coding and the 3' untranslated regions (3'UTR). The latter contains AU-rich elements (ARE) which, depending on the cellular context, mediate either their rapid degradation or inhibit their translation. These observations, along with the known increase of the life spans of many unstable mRNA promoted by inhibitors of protein synthesis, raise the possibility that both processes are linked. To investigate further the putative involvement of translation in both coding region and ARE-mediated rapid decay of c-fos mRNA, we designed an expression vector based on the use of the ferritin mRNA iron regulatory element (IRE). The latter structure links translation to intracellular iron concentration when inserted at the proper location within the 5'UTR. Rapid degradation of a beta-globin/c-fos 3'UTR construct was prevented by Desferrioxamine, an iron chelator, and facilitated by ferric ammonium citrate or hemin, while stability of other mRNAs not containing the IRE or the ARE were unchanged. The same conclusion was reached when the stability of a c-fos mRNA devoid of ARE was assessed in function of iron availability.
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PMID:c-fos mRNA instability determinants present within both the coding and the 3' non coding region link the degradation of this mRNA to its translation. 747 33

Desferrioxamine (DFO) is the most important drug in the treatment of thalassemia major and other hematological diseases requiring regular transfusion. It eliminates excessive ferritin by building up chelate complexes. Different mechanisms of possible DFO toxicity are induction of oxidation, damage of the blood-retina barrier, or reduction in other metalloions (Cu2+, Zn2+). The objective of the present study was to evaluate the ocular side effects of DFO treatment. We prospectively examined 17 patients aged 5 to 25 years, all of them treated with DFO. Visual acuity, pupillary reaction, anterior segment, lens and fundus were checked. If possible, visual fields, color vision, dark adaptation, stereoscopic vision, and contrast sensitivity were investigated. Lens opacities were found in 41% (7/17), changes in the retinal pigment epithelium in 35% (6/17), tortuosity of retinal vessels in 24% (4/17), dilation and sheathing of the retinal vessels in 18% (3/17), defects in color vision in 29% (5/17), and abnormal dark adaptation in 18% (3/17) of the patients. The oculotoxicity of DFO is dose-dependent. Major side effects like depression of the visual acuity are partially reversible after discontinuing the therapy. Regular ophthalmological check-ups are therefore necessary.
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PMID:[Ocular findings in Desferal therapy]. 771 74

In summary, it has been shown that orally administered HBED causes enhanced excretion of iron in all of the thalassemia major patients studied and that both urinary and stool iron are increased in the process. Increasing the dose from 40 to 80 mg/kg divided t.i.d. caused iron balance to increase from 38% to 50%. While this is significantly less than that expected based on our preclinical studies in animals, the potential usefulness of this chelator has been demonstrated. Efforts to increase its oral bioavailability are now in progress. Lending further support to the effort is the fact that no evidence of toxicity has been observed in the studies performed to date and that negative iron balance was achieved in the one thalassemia intermedia patient studied. The results also reinforce the conclusion that DFO causes the excretion of substantially more iron than would be predicted by an assessment of serum ferritin levels or past compliance with chelation therapy. In patients with thalassemia major, serum ferritin levels relate more to tissue damage than to body iron load. Effective chelation therapy can diminish the former much faster than it can remove storage iron. Hence, in cases of iron overload, aggressive chelation therapy should not be tapered off until a significant reduction in iron excretion can be demonstrated. Routine measurements of urinary iron excretion should now be considered essential in the management of beta-thalassemia. Finally, two more patients with thalassemia intermedia will be studied in an effort to substantiate that net negative iron balance can be achieved in this subgroup of patients. We also plan to study several transfused patients in whom the dose of HBED will be increased to 120 mg/kg divided t.i.d. While the chances of achieving net negative iron balance in these patients seems remote, we hope to further demonstrate the safety of this drug with an eye toward the development of an effective prodrug.
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PMID:Results from a phase I clinical trial of HBED. 788 41


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