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

The optimal regimen of intravenous deferoxamine for iron overload in high-risk homozygous beta-thalassemia is unknown because only short-term follow-up has been described in small patient groups. We report the outcome over a 16-year period of a continuous 24-hour deferoxamine regimen, with dose adjustment for serum ferritin, delivered via 25 indwelling intravenous lines for 17 patients. Treatment indications were cardiac arrhythmias, left ventricular dysfunction, gross iron overload, and intolerability of subcutaneous deferoxamine. Cardiac arrhythmias were reversed in 6 of 6 patients, and the left ventricular ejection fraction improved in 7 of 9 patients from a mean (+/- SEM) of 36 +/- 2% to 49 +/- 3% (P =.002, n = 9). The serum ferritin fell in a biphasic manner from a pretherapy mean of 6281 +/- 562 microg/L to 3736 +/- 466 microg/L (P =.001), falling rapidly and proportionally to the pretreatment ferritin (r(2) = 0.99) for values >3000 microg/L but falling less rapidly below this value (at 133 +/- 22 microg/L/mo). The principal catheter-related complications were infection and thromboembolism (1. 15 and 0.48 per 1000 catheter days, respectively), rates similar to other patient groups. Only one case of reversible deferoxamine toxicity was observed (retinal) when the therapeutic index was briefly exceeded. An actuarial survival of 61% at 13 years with no treatment-related mortality provides evidence of the value of this protocol. (Blood. 2000;95:1229-1236)
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PMID:Long-term outcome of continuous 24-hour deferoxamine infusion via indwelling intravenous catheters in high-risk beta-thalassemia. 1066 95

Anemia management in hemodialysis patients continues to evolve, and recently, greater emphasis has been placed on the wider use of intravenous iron to maintain adequate iron levels. This survey provides scarcely available yet potentially useful information on the clinical treatment of anemia in a large cohort of hemodialysis patients. The erythropoietin and iron administration details and pertinent laboratory measurements from 1,639 patients were analyzed for the month of December, 1998. A standardized protocol had been used in that erythropoietin was begun at a total weekly dose of 150 U/kg IV or 100 U/kg subcutaneously and was then adjusted to maintain a hematocrit (Hct) of 33-36%. Iron supplements, oral, IV, or both, were administered to maintain percent transferrin saturation (TSAT) at 20-30% and/or a serum ferritin of 100-500 ng/ml. No intravenous iron was administered if the ferritin was more than 500 ng/ml. Although 82% of patients were on iron supplementation and, among them, 58% were on IV iron, the percentage of patients with TSAT >20, i.e., bioavailable iron, was only 51%. The serum ferritin was high at 498 +/- 10 ng/ml (mean +/- SEM) and 88% and 10% of patients had serum ferritin >100 and >1,000 ng/ml, respectively, suggestive of sequestration of part of the infused iron. Erythropoietin was administered to 96% of patients, 99.5% by IV route. The latter was consistent with the US dialysis population at large but in variance with DOQI preference for the subcutaneous route. The target Hct range of 33-36 was found in 33%, with a mean Hct of 34.0 +/- 0.12. When the data were reanalyzed by excluding patients who had not been receiving erythropoietin and had not been on dialysis for at least 3 months, the percentage of patients achieving the target Hct increased to 37%. Paired analysis of 875 patients present in 1996 and 1998 showed that, although there was a marked increase in the use of IV iron, the improvement in anemia was modest, and there was evidence for increased iron accumulation. In summary, this 1998 survey on the clinical practice of anemia management in a large hemodialysis population indicates that there is a marked increase in need-based IV iron usage that was associated with modest improvement in anemia and evidence for increased iron storage. A maintenance iron dosing protocol with smaller doses of iron, such as 25 mg of iron dextran per hemodialysis, may make bioavailable iron continuously present for erythropoiesis, yet may reduce the chance for iron catalyzed lipid peroxidation and tissue iron deposition.
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PMID:Anemia and iron target realization in 1998: clinical management of anemia in 1,639 patients on hemodialysis. 1157 28

Endoscopy is indicated for the evaluation of unexplained iron deficiency to rule out neoplasia. Iron deficiency is common in postgastrectomy patients. The endoscopic yield for significant pathology in these patients is unknown but is expected to be lower than for other iron-deficient groups. A retrospective case-control study with 2:1 matching was performed comparing iron-deficient patients (ferritin < or = 50 microg/liter) having prior Billroth I or Billroth II gastrectomy to matched iron-deficient controls with normal gastric anatomy. There were 52 postgastrectomy patients and 113 controls. There were no significant differences between postgastrectomy patient and controls in age, gender ratio, or laboratory test results, with the exception of MCV (88.9 +/- -1.1 vs 86.0 +/- -0.8, mean +/- SEM, P = 0.048) There were no significant differences in the prevalence of upper gastrointestinal pathology (24.5% vs 29.2%), large (>1 cm) colon polyps (8.3% vs 5.2%), or the presence of any adenomatous colon polyp (28.6% vs 18.9%). There were no malignancies. In conclusion, prevalence of clinically significant pathology is similar for postgastrectomy and nonpostgastrectomy iron-deficient patients. Endoscopic evaluation of iron deficiency should not differ in postgastrectomy patients.
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PMID:Endoscopic evaluation of patients with partial gastrectomy and iron deficiency. 1191 53

Desferrioxamine (DFX) alone (40-50 mg/kg/d s.c. over 8-12 h, five times weekly) was compared with combined DFX twice weekly and deferiprone (75 mg/kg/d) over 12 months in previously poorly chelated thalassaemia patients. Serum ferritin fell from 5506 +/- 635 microg/l (mean +/- SEM) to 3998 +/- 604 microg/l (P < 0.001; n = 14) in the DFX group and from 4153 +/- 517 microg/l to 2805 +/- 327 microg/l in the combined group (P < 0.01; n = 11). Deferiprone plus DFX produced a greater mean urine iron excretion (1.01 mg/kg/24 h) than iron intake from blood transfusion in each patient. Main side-effects were skin reactions (DFX alone), nausea and arthralgia (combined therapy). As chelation therapy, the combined protocol was as effective as DFX five times weekly.
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PMID:Comparison between desferrioxamine and combined therapy with desferrioxamine and deferiprone in iron overloaded thalassaemia patients. 1267 Mar 52

It is well established that Fe and ceruloplasmin interact in animals and in in vitro models. However, Fe-mediated regulation of ceruloplasmin has never been investigated in humans. In an observational study, 53 pregnant women aged 19-39 yr (29.8 +/- 0.7 yr, mean +/- SEM) were recruited at the Aberdeen Antenatal Clinic, Aberdeen Maternity Hospital, UK. All requirements for local ethical committees were followed. Venous blood samples were taken from each woman at 34 wk gestation for measurement of Fe status and ceruloplasmin. Various parameters were used to test for Fe status. The most sensitive one appeared to be soluble transferrin receptor, which increased with parity. In the population studied, there was no relationship between hemoglobin or ferritin and serum ceruloplasmin. However, using soluble transferrin receptor (sTfR) levels, we were able to demonstrate an inverse linear relationship (r = 0.37, p = 0.021, n = 41) between Fe status and ceruloplasmin. Fe supplementation, number of previous pregnancies, and smoking habits did not affect this relationship. Our data support in vitro results showing regulation of ceruloplasmin by Fe and also suggest that the interactions between Fe and ceruloplasmin should be considered when Fe supplementation is given.
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PMID:Interrelations between ceruloplasmin and Fe status during human pregnancy. 1505 95

Persistent levels of plasma nontransferrin bound iron (NTBI) have been associated with tissue iron overload and toxicity. We characterized NTBI's susceptibility to deferoxamine (directly chelatable iron [DCI]) and redox activity (labile plasma iron [LPI]) during the course of long-term, continuous L1 (deferiprone) treatment of patients with hemoglobin E disease and beta-thalassemia (n = 17). In 97% of serum samples (n = 267), the LPI levels were more than 0.4 microM (mean +/- SEM, 3.1 +/- 0.2 microM) and the percent transferrin (Tf) saturation more than 85 (111 +/- 6), whereas only in 4% of sera were the LPI levels more than 0.4 microM for Tf saturation less than 85%. Daily administration of L1 (50 mg/kg) for 13 to 17 months caused both LPI and DCI to decrease from respective initial 5.1 +/- 0.5 and 5.4 +/- 0.6 microM to steady mean levels of 2.18 +/- 0.24 and 2.81 +/- 0.14 microM. The steady lowest levels of LPI and DCI were attained after 6 to 8 months, with a half time (t(1/2)) of 2 to 3 months. Serum ferritin and red cell membrane-associated iron followed a similar course but attained steady basal levels only after 10 to 12 months of continuous treatment, with a t(1/2) of 5 to 7 months. These studies indicate that LPI and DCI can serve as early indicators of iron overload and as measures for the effectiveness of iron chelation in reducing potentially toxic iron in the plasma.
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PMID:Labile plasma iron (LPI) as an indicator of chelatable plasma redox activity in iron-overloaded beta-thalassemia/HbE patients treated with an oral chelator. 1515 64

A beryllium (Be)-ferritin adduct containing 270 pm of Be stimulated proliferation of bronchoalveolar lavage (BAL) lymphocytes from subjects with chronic beryllium disease (CBD) at concentrations 5-6 logs lower than the amounts of beryllium sulfate (BeSO4) needed to induce proliferation. We observed increased apoptotic CBD BAL macrophages after exposure to both BeSO4 (50 +/- 6%, mean +/- SEM, P <0.05 versus unstimulated controls) and Be-ferritin (40 +/- 2%), whereas only 2.0 +/- 0.2% of BAL lymphocytes underwent activation-induced cell death. Be-ferritin also induced apoptosis in BAL macrophages from subjects with Be sensitization (25 +/- 3%) and in the H36.12j hybrid macrophage cell line (15 +/- 2%). Be-ferritin induced lung macrophage CD95 (Fas) expression and the activation of intracellular caspase-3, -8 and -9. Thus, lung macrophages take up Be-ferritin, delivering physiologically relevant levels of Be that promote Be antigen presentation and macrophage apoptosis. Be-ferritin thereby serves as a "Trojan Horse," triggering proliferation of Be-ferritin-specific CBD BAL T cells. We hypothesize that Be-ferritin exposure may result in persistent antigen exposure inducing Be-specific T cell clonal expansion and T cell helper type 1-type cytokine production and potentially explains the chronicity of CBD and its development years after environmental Be exposure has ceased.
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PMID:Beryllium-ferritin: lymphocyte proliferation and macrophage apoptosis in chronic beryllium disease. 1525 86

Commercial elemental iron powders (electrolytic and reduced iron), as well as heme iron supplements, were tested for efficacy in improving the iron status of women. In a randomized, double-blind trial, 51 women with moderate to low iron stores received daily for 12 wk: 1) placebo, 2) 5 mg iron as heme iron or 50 mg iron as 3) electrolytic iron, 4) reduced iron, or 5) FeSO(4). Treatments were provided in 2 capsules (heme carrier) and 3 wheat rolls (other iron sources). Differences in iron status, food nonheme iron absorption, and fecal properties were evaluated. Body iron, assessed from the serum transferrin receptor:ferritin ratio, increased significantly more in subjects administered FeSO(4) (127 +/- 29 mg; mean +/- SEM) and electrolytic (115 +/- 37 mg), but not the reduced (74 +/- 32 mg) or heme (65 +/- 26 mg) iron forms, compared with those given placebo (2 +/- 19 mg). Based on body iron determinations, retention of the added iron was estimated as 3.0, 2.7, 1.8, and 15.5%, in the 4 iron-treated groups, respectively. Iron treatments did not affect food iron absorption. The 50 mg/d iron treatments increased fecal iron and free radical-generating capacity in vitro, but did not affect fecal water cytotoxicity. In subjects administered FeSO(4), fecal water content was increased slightly but significantly more than in the placebo group. In conclusion, electrolytic iron was approximately 86% as efficacious as FeSO(4) for improving body iron, but the power of this study was insufficient to detect any efficacy of the reduced or heme iron within 12 wk. With modification, this methodology of testing higher levels of food fortification for several weeks in healthy women with low iron stores has the potential for economically assessing the efficiency of iron compounds to improve iron status.
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PMID:Electrolytic iron or ferrous sulfate increase body iron in women with moderate to low iron stores. 1731 50

Properties of ferritin, immobilized on dithiobis (N-succinimydyl propionate) (DTSP)-covered gold electrode, in 3-morpholino propanesulfonic acid buffer were investigated by AFM and FE-SEM. Electrochemical properties the ferritin was measured by a cyclic volatammetry. When the potentials of 0.2, 0.34, and 1.0V vs. Ag/AgCl were applied for 15h for the ferritin immobilization, the electrode potential of Fe(II)/Fe(III) in ferritin changed to negative values. Negative electrode potential shift of Fe(II)/Fe(III) in ferritin with respect to the applied potential could be attributed to the stabilized ferritin on DTSP-covered gold electrode. From AFM and SEM images, it was proven that ferritins fixed at below 0.34V were clusters in several micrometer and those fixed at higher applied potential than OCV were finely distributed particles in several tens of nanometer.
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PMID:Immobilization and characterization of ferritin on gold electrode. 1934 94

Transfusional iron overload associated with thalassemia leads to the appearance of non-transferrin-bound iron (NTBI) in blood that is toxic and causes morbidity and mortality via tissue damage. Hence, a highly sensitive and accurate assay of NTBI, with broad clinical application in both diagnosis and validation of treatment regimens for iron overload, is important. An assay based on iron chelation by a high-affinity siderophore, azotobactin, has been developed. The steps consist of blocking of native apotransferrin iron binding sites, mobilization of NTBI, ultrafiltration of all serum proteins, and finally the addition of the probe, which has a chromophore that fluoresces at 490 nm. Binding of Fe3+ to azotobactin quenches the fluorescence in a concentration-dependent manner. Measured NTBI levels in 63 sera ranged from 0.07 to 3.24 microM (0.375+/-0.028 microM [means+/-SEM]). It correlated well with serum iron and percentage transferrin saturation but not with serum ferritin. Pearson's correlation coefficients were found to be 0.6074 (P<0.0001) and 0.6102 (P<0.0001) for percentage transferrin saturation and total serum iron, respectively. The low values are due to the patients being under regular chelation therapy even prior to sampling, indicating that the method is sensitive to very low levels of NTBI, allowing a much lower detection limit than the available methods.
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PMID:Fluorescence assay of non-transferrin-bound iron in thalassemic sera using bacterial siderophore. 1963 91


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