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)

Genetic (hereditary) hemochromatosis is probably the most common autosomal recessive disorder found in white Americans, of whom about 5/1,000 (0.5 percent) are homozygous for the associated gene. The hemochromatosis gene is probably located close to the HLA-A locus on the short arm of chromosome 6. Homozygous individuals may develop severe and potentially lethal hemochromatosis, especially after age 39. Hereditary hemochromatosis involves an increased rate of iron absorption from the gut with subsequent progressive storage of iron in soft organs of the body. Excess iron storage eventually produces pituitary, pancreatic, cardiac, and liver dysfunction and death may result from cardiac arrhythmias, congestive heart failure, and/or hepatic failure or cancer. Early diagnosis can prevent these excess iron-induced problems. Iron overload owing to HLA-linked hereditary hemochromatosis can be distinguished from other causes of hemochromatosis by liver biopsies and interpretations. Patients at risk for genetic hemochromatosis should be screened, identified, and treated as early as age 20 to prevent or minimize the deadly complications of hemochromatosis. Population screening should include measurements of serum iron concentration, total iron binding capacity (TIBC), percent saturation of transferrin, and serum ferritin concentrations. Family members of hereditary hemochromatosis patients are at increased risk and should be tested. Screening, identification and early treatment (phlebotomies, sometimes in combination with the use of Desferal or other iron-chelating agents) may help prevent or reduce iron-related organ damage and premature deaths. Early diagnosis and treatment will reduce the population of aging individuals with severe, complicated hemochromatosis and dramatically reduce medical costs (billions of U.S. dollars per annum) associated with the management of this disease.
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PMID:Hereditary hemochromatosis. 978 32

We designed a study to obtain follow-up on behavioral aspects of compliance with home deferoxamine administration, explore social factors that might influence compliance, and evaluate the effectiveness of a pilot intervention program for patients with thalassemia or sickle cell disease who were receiving chronic transfusion therapy. Thirty-one patients between the ages of 6 and 21 years and their primary caregivers were administered a 24-hour recall Interview about home care. Fifteen went on to participate in a Desferal Day Camp, which combined educational strategies with peer support. Behavioral measures of treatment adherence were similar for most patients with sickle cell disease and thalassemia. Patient compliance with days of deferoxamine administration at follow-up was associated with initial compliance, perceived support, and patient and caregiver knowledge. Increased sharing of responsibilities for home care by patients and caregivers and caregiver knowledge were associated with lower ferritin and liver iron levels. A subsample of 3 patients who were extremely noncompliant with days of deferoxamine administration was examined separately; these patients were found to be moderately compliant with the number of hours and amount of deferoxamine administered and to share fewer home care tasks with primary caregivers. Participation in Desferal Day Camp did not result in increases in knowledge or peer support, suggesting that future interventions should focus on family support and on improving self-regulatory skills. The crucial role of collaboration among patients, families, and health care providers in developing interventions to enhance adherence was emphasized.
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PMID:Improving adherence with deferoxamine regimens for patients receiving chronic transfusion therapy. 1120 66

The differential ferrioxamine test is a simple method for the measurement of chelation of body iron by desferrioxamine. A single six-hour specimen of urine is obtained after intravenous Desferal, accompanied by (59)Fe-ferrioxamine. Two values are measured: F(d), the excretion of ferrioxamine derived from body iron by chelation, and F(ex), the proportion of ferrioxamine excreted from a known intravenous dose. The data enables F(v), chelation of iron in vivo, to be calculated by simple proportion. Desferrioxamine chelation proceeds for about half an hour after injection. The results in normal subjects, in cases with known high iron stores, and in cases of iron-deficiency anaemia are described. High, normal, and low body iron states have been differentiated. F(v) values in the higher ranges obtained in iron-storage diseases and in haemolytic states are differentiated by the pattern of excretion, high F(d) values and low F(ex) values respectively. IT IS SUGGESTED THAT THERE ARE TWO MAIN SOURCES OF CHELATABLE BODY IRON: as ferritin-haemosiderin and as iron newly released from haem in a more readily chelatable form. The significance of variable chelation susceptibility in iron metabolism is briefly discussed. It is suggested that variable chelatability of different sources of body iron may explain the preferential utilization of iron released from red cells or absorbed from the intestine, rather than storage iron, in the biosynthesis of haem.
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PMID:DIFFERENTIAL FERRIOXAMINE TEST FOR MEASURING CHELATABLE BODY IRON. 1424 11

In Parkinson's disease (PD) and its neurotoxin-induced models, 6-hydroxydopamine (6-OHDA) and N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), significant accumulation of iron occurs in the substantia nigra pars compacta. The iron is thought to be in a labile pool, unbound to ferritin, and is thought to have a pivotal role to induce oxidative stress-dependent neurodegeneration of dopamine neurons via Fenton chemistry. The consequence of this is its interaction with H(2)O(2) to generate the most reactive radical oxygen species, the hydroxyl radical. This scenario is supported by studies in both human and neurotoxin-induced parkinsonism showing that disposition of H(2)O(2) is compromised via depletion of glutathione (GSH), the rate-limiting cofactor of glutathione peroxide, the major enzyme source to dispose H(2)O(2) as water in the brain. Further, radical scavengers have been shown to prevent the neurotoxic action of the above neurotoxins and depletion of GSH. However, our group was the first to demonstrate that the prototype iron chelator, desferal, is a potent neuroprotective agent in the 6-OHDA model. We have extended these studies and examined the neuroprotective effect of intracerebraventricular (ICV) pretreatment with the prototype iron chelator, desferal (1.3, 13, 134 mg), on ICV induced 6-OHDA (250 micro g) lesion of striatal dopamine neurons. Desferal alone at the doses studied did not affect striatal tyrosine hydroxylase (TH) activity or dopamine (DA) metabolism. All three pretreatment (30 min) doses of desferal prevented the fall in striatal and frontal cortex DA, dihydroxyphenylacetic acid, and homovalinic acid, as well as the left and right striatum TH activity and DA turnover resulting from 6-OHDA lesion of dopaminergic neurons. A concentration bell-shaped neuroprotective effect of desferal was observed in the striatum, with 13 micro g being the most effective. Neither desferal nor 6-OHDA affected striatal serotonin, 5-hydroxyindole acetic acid, or noradrenaline. Desferal also protected against 6-OHDA-induced deficit in locomotor activity, rearing, and exploratory behavior (sniffing) in a novel environment. Since the lowest neuroprotective dose (1.3 micro g) of desferal was 200 times less than 6-OHDA, its neuroprotective activity may not be attributed to interference with the neurotoxin activity, but rather iron chelation. These studies led us to develop novel brain-permeable iron chelators, the VK-28 series, with iron chelating and neuroprotective activity similar to desferal for ironing iron out from PD and other neurodegenerative diseases, such as Alzheimer's disease, Friedreich's ataxia, and Huntington's disease.
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PMID:Ironing iron out in Parkinson's disease and other neurodegenerative diseases with iron chelators: a lesson from 6-hydroxydopamine and iron chelators, desferal and VK-28. 1510 75

Pores regulate access between ferric-oxy biomineral inside and reductants/chelators outside the ferritin protein nanocage to control iron demineralization rates. The pore helix/loop/helix motifs that are contributed by three subunits unfold independently of the protein cage, as observed by crystallography, Fe removal rates, and CD spectroscopy. Pore unfolding is induced in wild type ferritin by increased temperature or urea (1-10 mM), a physiological urea range, 0.1 mM guanidine, or mutation of conserved pore amino acids. A peptide selected for ferritin pore binding from a combinatorial, heptapeptide library increased the rate of Fe demineralization 3-fold (p<0.001), similarly to a mutation that unfolded the pores. Conjugating the peptide to Desferal (desferrioxamine B mesylate), a chelator in therapeutic use, increased the rates to 8-fold (p<0.001). A second pore binding peptide had the opposite effect and decreased the rate of Fe demineralization 60% (p<0.001). The peptides could have pharmacological uses and may model regulators of ferritin demineralization rates in vivo or peptide regulators of gated pores in membranes. The results emphasize that small peptides can exploit the structural plasticity of protein pores to modulate function.
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PMID:Peptides selected for the protein nanocage pores change the rate of iron recovery from the ferritin mineral. 1778 67

Myelodysplastic syndrome (MDS) is composed of a diverse spectrum of hematopoietic stem cell malignancies characterized by ineffective blood cell production. Many MDS patients are dependent on red blood cell (RBC) transfusions for symptomatic management of refractory anemia. Iron overload ensues when the iron acquired from transfused RBCs exceeds body storage capacity, thereby raising the risk for end organ damage. This is of greatest concern in patients with lower-risk MDS whose expected survival is measured in years. Transfusion dependence is associated with shorter survival and an increased risk for progression to acute myeloid leukemia (AML) in transfusion-dependent patients. Application of recent advances in the treatment of MDS can reduce or eliminate the need for transfusions, thus minimizing the risk of iron overload. Case control studies, prospective surveys, and phase II studies indicate that iron chelation therapy reduces iron load as measured by changes in serum ferritin and may prolong overall survival. Iron chelation strategies include oral agents such as deferasirox (Exjade, Novartis Pharmaceuticals Corp, East Hanover, NJ), deferiprone (Ferriprox, Apotex Europe BV, Leiden, the Netherlands) and, for those patients who are intolerant of or for whom oral therapy is ineffective, parenteral administration of deferoxamine (Desferal, Novartis). This review presents the data related to iron overload in MDS, including its prevalence, diagnosis, clinical impact, and management.
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PMID:Iron overload in myelodysplastic syndromes: diagnosis and management. 2012 80


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