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

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.
 ...
PMID:Metal ions and oxygen radical reactions in human inflammatory joint disease. 241 31

Iron-chelating treatment is indicated in all children on prolonged transfusion therapy (i.e., chiefly patients with thalassemia and Blackfan-Diamond anemia). The purpose of iron-chelating treatment is to prevent the development of manifestations of iron overload including cardiac hemosiderosis and insulin-dependent diabetes mellitus (which are two potentially fatal complications), hepatic cirrhosis, hypoparathyroidism, hypothyroidism, and delayed puberty. Deferoxamine is the only effective iron-chelating agent and should be given in a daily dose of 40 mg/kg at initiation of the transfusion program. Administration is by subcutaneous infusions from 8 to 10 hours per day. The goal of iron-chelating treatment is to maintain serum ferritin levels between 500 and 1,000 ng/ml. This long-term treatment is a significant burden for patients and it can be hoped that non-toxic iron-chelating agents, active by mouth, will become available.
 ...
PMID:[Iron chelation in children]. 268 51

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.
 ...
PMID:[Treatment of post-transfusion iron overload by deferoxamine]. 273 4

We treated three children with renal failure and chronic iron overload with intraperitoneal deferoxamine therapy. Each child had an elevated serum ferritin level, a dense liver as measured by computerized tomography (Hounsfield Units) and one had dialysis related porphyria cutanea tarda. Deferoxamine therapy (10 to 17.5 mg/kg) was given in the overnight exchange for three to six months. Prior to therapy, iron was not detected in the dialysate; during the course of therapy, daily dialysate iron removal averaged 5652 micrograms, 2241 micrograms and 4028 micrograms in the three children. The serum ferritin level fell during the course of therapy in two children who were estimated to be in negative iron balance, and was unchanged in the third who was estimated to be in positive iron balance due to frequent transfusions. In 10 children with chronic renal failure, there was a linear correlation (r = 0.855; P less than 0.01) between the serum ferritin and the liver density, suggesting that an increased serum ferritin correlates with hepatic iron content. Interestingly, in each of the three children who received deferoxamine therapy, the liver density increased during therapy regardless of the estimated iron balance and the change in the serum ferritin level. We conclude that intraperitoneal deferoxamine therapy results in substantial iron losses in peritoneal dialysate, can result in negative iron balance but, in this study, did not result in lower liver iron content as measured by density on computerized tomography scan.
 ...
PMID:Intraperitoneal deferoxamine therapy for iron overload in children undergoing CAPD. 277 Jan 13

Serum ferritin and diabetes control were evaluated in 18 White patients with poorly controlled type II (non-insulin-dependent) diabetes who had no known causes of iron-storage disorder. Serum ferritin levels were found to be elevated with normal serum iron and total iron-binding capacity in 9 of the 18 patients studied. Because excess iron, typified by hemochromatosis, is associated with diabetes, and diabetes has been shown to improve after lowering total-body iron load through repeat venesection, I investigated whether regulating elevated ferritin levels could facilitate diabetes control. Deferoxamine (DFO), a known specific chelator of iron, was used because of its capacity to correct excess iron stores. All 9 patients in the high-ferritin diabetic group and 7 of 9 diabetic control subjects with normal serum ferritin levels were given DFO (10 mg/kg i.v.) twice weekly. Diabetic control, fasting glucose, triglyceride, cholesterol, HbA1c, and serum ferritin levels were monitored. Data show that lowering elevated ferritin levels correlated well with diabetes control and improved fasting glucose, triglyceride, and HbA1c in 8 of 9 patients with high ferritin levels. Lowering normal ferritin levels had no effect on diabetes control or on any of the other parameters in the 7 control subjects. This study shows there is a need to study iron metabolism in poorly controlled diabetes and demonstrates the value of DFO in controlling high-ferritin diabetes.
 ...
PMID:Deferoxamine therapy in high-ferritin diabetes. 279 74

16 chronic haemodialysis patients (group I), with non-microcytic anaemia (mean haemoglobin 7.2 g/dl, SD 1.0, range 5.8-9.8), moderate aluminium overload (serum aluminium 44 micrograms/l, SD 16, range 21-74), and normal or high iron stores (ferritin 800 micrograms/l SD 464, range 34-2013) were treated with intravenous desferrioxamine 1 g at the end of each dialysis for six months. 8 patients with similar characteristics served as controls (group II). After six months group I showed a rise in haemoglobin to 9.1 (SD 2.5) g/dl and a decrease in blood transfusion requirements, both significant, whereas group II showed no changes. Other significant changes observed in group I, but not group II, were a rise in reticulocytes and in red cell creatine and a fall in red cell protoporphyrin and serum ferritin. Ferritin decreased more in the patients whose anaemia improved. Minor increases in serum aluminium in group I did not differ from those in the control group. Desferrioxamine may benefit the anaemia of chronic haemodialysis patients through improvement of erythropoiesis. The effect seems not to be related to chelation of a heavy aluminium overload.
 ...
PMID:Improvement in the erythropoiesis of chronic haemodialysis patients with desferrioxamine. 289 66

Increased 59Fe excretion was observed following the intragastric and intraperitoneal administration of 1-ethyl- and 1-methyl-2-methyl-3-hydroxypyrid-4-ones in normal and iron-loaded, 59Fe-labelled mice, respectively. Administration of these chelators and desferrioxamine parenterally or intragastrically to an iron-loaded rabbit caused no increase in Cu, Zn, Ca or Mg urinary excretion. Iron mobilisation was also observed following the incubation of the chelators with ferritin and haemosiderin but not with haemoglobin. Desferrioxamine under the same conditions caused methaemoglobin formation.
 ...
PMID:Orally active alpha-ketohydroxypyridine iron chelators: effects on iron and other metal mobilisations. 312 Apr 74

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)
 ...
PMID:Management of iron overload in dialysis patients. 329 89

The major diseases of iron metabolism are iron deficiency anaemia, which could be treated using Fe2+ or Fe3+ salt supplements, and iron overload, which could arise either from an increased gastrointestinal absorption of iron or from recurrent blood transfusions. While the former form of iron overload could be treated by phlebotomy the latter requires the use of a chelator. Desferrioxamine is the only clinically available chelator for the treatment of iron overload but its use worldwide is limited because it is expensive and orally inactive. Several alpha-ketohydroxy heteroaromatic chelators have been synthesised and tested for their iron binding properties at physiological pH. The synthetic route involves the benzylation of the hydroxyl group of maltol using benzyl chloride, the conversion of the benzylated maltol to the 1-alkyl benzylated pyridine derivative by introducing the corresponding alkylamine in alkaline conditions and the cleavage of the benzyl group in acid to form the 1-alkyl-2-methyl-3-hydroxypyrid-4-one. All the chelators are water soluble and stable at a wide range of pH, forming stable, water soluble, coloured iron complexes with a molar ratio of approximately 3 chelator: 1 iron at pH 7.4 and lower molar ratio of chelators to iron complexes at acidic pH. When the 1-methyl, 1-ethyl and 1-propyl, -2-methyl-3-hydroxypyrid-4-ones were mixed at pH 7.4 with transferrin, ferritin and haemosiderin substantial amounts of iron were released.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:New synthetic approach and iron chelating studies of 1-alkyl-2-methyl-3-hydroxypyrid-4-ones. 343 80

In order to study the role of excessive synovial iron sequestration in the production of anemia in rheumatoid arthritis (RA), the antianemic efficacy and anti-inflammatory effect of desferrioxamine administered in a short-term treatment (14 days), were evaluated in 10 patients suffering from classic or definite RA and hyposideremic anemia. Treatment with desferrioxamine showed an elevated urinary iron excretion, a significant increase of serum iron, UIBC and hemoglobin, and a marked progressive decrease of serum ferritin. A moderate improvement of the pain intensity, morning stiffness and Ritchie's index was also observed. The results obtained suggest that excessive reticuloendothelial iron deposits occur in RA and that the iron uptake can be an important factor in the production of anemia. Desferrioxamine seems to be useful in the treatment of patients suffering from RA and anemia, in order to release iron from synovial tissue, reduce the inflammatory process and improve anemia, changing an anemia which is typically resistant to the martial therapy into an iron-sensitive anemia.
 ...
PMID:Antianemic and potential anti-inflammatory activity of desferrioxamine: possible usefulness in rheumatoid arthritis. 351 95


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>