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Query: UMLS:C0240066 (iron deficiency)
 7,156 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We measured serum transferrin receptor (sTfR) levels in 22 patients with polycythemia vera and in 26 cases of secondary polycythemia. In our study, raised sTfR levels in both polycythemia groups were related to iron deficiency.
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PMID:Serum transferrin receptor in polycythemia. 983 Aug 13

Anaemia in pregnancy in developing countries continues to be a public health problem of significant proportion. At least 50% of the anaemia has been blamed on iron deficiency. In populations where chronic inflammation and iron deficiency anaemia coexist, the criteria to accurately define iron status are not always clear. Similarly, in pregnancy, with marked physiological changes, cut-off points for biochemical parameters need to be re-examined. In this study we examined the diagnostic accuracy of iron parameters including mean cellular volume (MCV), serum iron, transferrin, total iron binding capacity (TIBC) and its saturation, zinc protoporphyrin (ZPP), ferritin and serum transferrin receptor (TfR) for the assessment of iron status in a population of anaemic pregnant women in Malawi. Stained bone marrow aspirates were used as the standard for comparison. Results show that for the purpose of screening, serum ferritin is the best single indicator of storage iron provided a cut-off point of 30 microg/l is used. A number of other commonly used parameters of iron status were shown to have limited diagnostic accuracy. Logistic regression was used to obtain mathematical models for the prediction of bone marrow iron status using a combination of available parameters.
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PMID:Iron status in pregnant women: which measurements are valid? 985 38

The balance required to maintain appropriate cellular and tissue iron levels has led to the evolution of multiple mechanisms to precisely regulate iron uptake from transferrin and low molecular weight iron chelates. A role for ceruloplasmin (Cp) in vertebrate iron metabolism is suggested by its potent ferroxidase activity catalyzing conversion of Fe2+ to Fe3+, by identification of yeast copper oxidases homologous to Cp that facilitate high affinity iron uptake, and by studies of "aceruloplasminemic" patients who have extensive iron deposits in multiple tissues. We have recently shown that Cp increases iron uptake by cultured HepG2 cells. In this report, we investigated the mechanism by which Cp stimulates cellular iron uptake. Cp stimulated the rate of non-transferrin 55Fe uptake by iron-deficient K562 cells by 2-3-fold, using a transferrin receptor-independent pathway. Induction of Cp-stimulated iron uptake by iron deficiency was blocked by actinomycin D and cycloheximide, consistent with a transcriptionally induced or regulated transporter. Cp-stimulated iron uptake was completely blocked by unlabeled Fe3+ and by other trivalent cations including Al3+, Ga3+, and Cr3+, but not by divalent cations. These results indicate that Cp utilizes a trivalent cation-specific transporter. Cp ferroxidase activity was required for iron uptake as shown by the ineffectiveness of two ferroxidase-deficient Cp preparations, copper-deficient Cp and thiomolybdate-treated Cp. We propose a model in which iron reduction and subsequent re-oxidation by Cp are essential for an iron uptake pathway with high ion specificity.
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PMID:Ceruloplasmin ferroxidase activity stimulates cellular iron uptake by a trivalent cation-specific transport mechanism. 987 59

We undertook this study to evaluate a recently introduced ELISA kit for determining serum transferrin receptor (TfR) concentration (TfR, Ramco Laboratories, Inc.), to produce reference values for healthy adults, and to compare the results with another commercially available reagent system. The mean (SD) recovery of added TfR was 88% (6%). In dilution studies, the ratio between the measured and expected values was 0.98 (0.11). The intra-assay and interassay coefficients of variation were from 5% to 7% and from 6% to 9% in a physiological and a supraphysiological concentration range, respectively, and from 13% to 16% in a subnormal concentration range. In healthy adults between 20 and 60 years of age, we observed no age- or sex-related differences in TfR values. Thus, the same reference interval, 3.0-8.2 mg l(-1), may be used for this population. The correlation between the results obtained with the Ramco TfR test and the Amgen Diagnostics Clinigen test was satisfactory (r=0.79). The Ramco TfR test produced higher values (Tf=0.40 (-0.45-1.25)+1.46 (1.16-1.75)* Clinigen). The number of samples that fell within the same concentration interval with both methods (low, normal or high in relation to the respective reference interval) was only 45% (27/60). The Ramco TfR test had fewer values falsely suggesting iron deficiency than the Clinigen test. Serum TfR methods need to be uniformly standardized.
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PMID:Evaluation of an ELISA test for determination of the serum transferrin receptor. Demonstration of discordance between results obtained with two methods. 989 Mar 39

Iron regulatory proteins (IRP)-1 and 2 are cytoplasmic mRNA-binding proteins that control intracellular iron homeostasis by regulating the translation of ferritin mRNA and stability of transferrin receptor mRNA in an iron-dependent fashion. Although structurally and functionally similar, the two IRP are different in their mode of regulation, pattern of tissue expression and modulation by multiple factors, such as bioradicals. In the present study RNA bandshift assays demonstrated that IRP-2, but not IRP-1, activity was higher in cultured cells than in tissues. Increased expression of IRP-2 in cell lines was not related to immortalization and differentiation but seemed associated to cell proliferation, although not closely dependent on cell growth rate. As a growing cell consumes more iron than its quiescent counterpart, we assessed the iron status of cell lines and found that ferritin content was lower than in tissues. Analysis of IRP activity in cell lines supplemented with heme or non-heme iron and in livers of iron-loaded and iron-deficient rats indicated that IRP-2 responds more promptly than IRP-1 to modulations of iron content. We propose that enhanced IRP-2 activity in cultured cells could be due to a proliferation-dependent, relative iron deficiency that is sensed first by IRP-2.
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PMID:Preferential activation of iron regulatory protein-2 in cell lines as a result of higher sensitivity to iron. 991 7

Transferrin receptor is a key protein for the cellular uptake of transferrin iron. The highest number of transferrin receptors is on the surface of erythroblasts. The released iron is used for hemoglobinosynthesis. Regulation occurs at mRNA level depending on the intracellular iron concentration. The synthesis of ferritin and transferrin receptor are regulated in an opposite manner. Serum transferrin receptor is a truncated monomeric form of the cellular receptor. Most of the circulating receptors come from erythroid marrow precursors. Its level mirrors the total tissue receptor mass, it depends on the rate of erythropoiesis and on the iron status. Serum transferrin receptor is easily measured by Elisa methods but the lack of standardization triggers large differences in the results. Unlike ferritin, the concentration of serum transferrin receptors is unaffected in inflammatory diseases, infections, malignancies or cytolysis. In these conditions its measurement is particularly valuable for assessing an associated iron deficiency. It is a very useful tool for the diagnosis of different causes of anemia. In chronic renal failure serum transferrin receptor can predict whether patients will respond to rHu EPO therapy.
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PMID:[The transferrin receptor: its role in iron metabolism and its diagnosis utility]. 992 Sep 62

In haemodialysis (HD) patients, functional iron deficiency frequently appears due to recombinant human erythropoietin (r-HuEPO) treatment. However, the diagnosis of iron deficiency is not always easy in such patients. Recent studies have shown that the serum transferrin receptor (s-TfR) level is a sensitive, quantitative measure of tissue iron deficiency. In this study, we examined the changes in s-TfR levels in patients with iron deficiency anaemia due to r-HuEPO treatment. We compared s-TfR levels of 24 patients with i.v. administered r-HuEPO (50-70 U/kg/dose) at the end of each dialysis session (three times a week) and diagnosed as having iron deficiency anaemia by routine laboratory methods (ferritin <50 microg/l and transferrin saturation <16%) with s-TfR levels of 32 patients not receiving r-HuEPO and without iron deficiency anaemia. Also, 40 healthy volunteer subjects were included in the study as a control group. Serum ferritin and transferrin receptor levels were measured with ELISAs using monoclonal reagents. There were no differences between the two groups with and without iron deficiency anaemia with respect to mean age, body weight, haemodialysis duration, haemoglobin and serum creatinine levels (p>0.05). For s-TfR levels, while no difference was present between the control and the non-iron deficiency groups (p>0.05), the iron deficiency group had higher s-TfR values than those of both the control and non-iron deficiency groups (p<0.001). Besides, there was an inverse correlation between haemoglobin and s-TfR levels in patients with iron deficiency anaemia (r = -0.85, p<0.0001). We conclude that the measurement of s-TfR levels may be useful in the diagnosis of functional iron deficiency in haemodialysis patients receiving r-HuEPO.
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PMID:The importance of serum transferrin receptor level in the diagnosis of functional iron deficiency due to recombinant human erythropoietin treatment in haemodialysis patients. 993 12

Hereditary hemochromatosis (HH) is a common autosomal recessive disorder characterized by tissue iron deposition secondary to excessive dietary iron absorption. We recently reported that HFE, the protein defective in HH, was physically associated with the transferrin receptor (TfR) in duodenal crypt cells and proposed that mutations in HFE attenuate the uptake of transferrin-bound iron from plasma by duodenal crypt cells, leading to up-regulation of transporters for dietary iron. Here, we tested the hypothesis that HFE-/- mice have increased duodenal expression of the divalent metal transporter (DMT1). By 4 weeks of age, the HFE-/- mice demonstrated iron loading when compared with HFE+/+ littermates, with elevated transferrin saturations (68.4% vs. 49.8%) and elevated liver iron concentrations (985 micrograms vs. 381 micrograms). By using Northern blot analyses, we quantitated duodenal expression of both classes of DMT1 transcripts: one containing an iron responsive element (IRE), called DMT1(IRE), and one containing no IRE, called DMT1(non-IRE). The positive control for DMT1 up-regulation was a murine model of dietary iron deficiency that demonstrated greatly increased levels of duodenal DMT1(IRE) mRNA. HFE-/- mice also demonstrated an increase in duodenal DMT1(IRE) mRNA (average 7.7-fold), despite their elevated transferrin saturation and hepatic iron content. Duodenal expression of DMT1(non-IRE) was not increased, nor was hepatic expression of DMT1 increased. These data support the model for HH in which HFE mutations lead to inappropriately low crypt cell iron, with resultant stabilization of DMT1(IRE) mRNA, up-regulation of DMT1, and increased absorption of dietary iron.
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PMID:Mechanism of increased iron absorption in murine model of hereditary hemochromatosis: increased duodenal expression of the iron transporter DMT1. 1007 51

Iron is essential for oxidation-reduction catalysis and bioenergetics, but unless appropriately shielded, iron plays a key role in the formation of toxic oxygen radicals that can attack all biological molecules. Hence, specialized molecules for the acquisition, transport (transferrin), and storage (ferritin) of iron in a soluble nontoxic form have evolved. Delivery of iron to most cells, probably including those of the kidney, occurs following the binding of transferrin to transferrin receptors on the cell membrane. The transferrin-receptor complexes are then internalized by endocytosis, and iron is released from transferrin by a process involving endosomal acidification. Cellular iron storage and uptake are coordinately regulated post-transcriptionally by cytoplasmic factors, iron-regulatory proteins 1 and 2 (IRP-1 and IRP-2). Under conditions of limited iron supply, IRP binding to iron-responsive elements (present in 5' untranslated region of ferritin mRNA and 3' untranslated region of transferrin receptor mRNA) blocks ferritin mRNA translation and stabilizes transferrin receptor mRNA. The opposite scenario develops when iron in the transit pool is plentiful. Moreover, IRP activities/levels can be affected by various forms of "oxidative stress" and nitric oxide. The kidney also requires iron for metabolic processes, and it is likely that iron deficiency or excess can cause disturbed function of kidney cells. Transferrin receptors are not evenly distributed throughout the kidney, and there is a cortical-to-medullary gradient in heme biosynthesis, with greatest activity in the cortex and least in the medulla. This suggests that there are unique iron/heme metabolism features in some kidney cells, but the specific aspects of iron and heme metabolism in the kidney are yet to be explained.
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PMID:Cellular iron metabolism. 1008 80

Iron plays an essential role in a spectrum of metabolic processes. Cellular iron uptake is facilitated by transferrin receptor (TfR)-mediated endocytosis. In recent years more insight has been obtained in TfR physiology and the regulation of cellular iron homeostasis. The synthesis of TfR and the iron storage protein ferritin is regulated reciprocally at the post-transcriptional level according to the cellular iron status. As a result of externalization of TfR during the endocytic cycle, a soluble form of TfR can be detected in serum. The serum TfR (sTfR) level is closely related to erythroid TfR turnover and the prime determinants of the sTfR concentration are cellular iron demands and erythroid proliferation rate. In the absence of a hyperplastic erythropoiesis the sTfR level is a sensitive parameter of early tissue iron deficiency. The entire spectrum of body iron status can be assessed by measurement of serum ferritin and sTfR levels, with ferritin as marker of tissue iron stores and sTfR as index of tissue iron needs. The sTfR may be a promising tool to detect iron deficiency in inflammatory states and in the anaemia of chronic disease as its concentration is, in contrast to ferritin levels, not influenced by the acute phase response. Determination of sTfR levels may also improve assessment of body iron stores during pregnancy and in neonates. Finally, the sTfR may be a useful parameter to monitor erythropoiesis in various clinical settings, for instance in the prediction of the haematological response to erythropoietin treatment. However, standardization of the sTfR assay, with definition of reference and pathological ranges, is necessary for the definitive introduction of the sTfR as major parameter of iron metabolism.
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PMID:Structure, function and clinical significance of transferrin receptors. 1009 72


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