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

The most common alpha-thalassemia in Southeast Asian or Southern Chinese populations is the (--SEA) double alpha-globin deletion. Couples heterozygous for (--SEA) have 25% risk for hydrops fetalis from loss of all four alpha-globin genes. The (--SEA) deletion spares the embryonic zeta-globin genes and causes traces of zeta-peptide to persist throughout life. A colorimetric monoclonal anti-zeta antibody test for raised zeta-peptide has detected the (--SEA) deletion in liquid blood samples, but not deletions of the entire alpha-globin region with loss of the zeta-globin genes. Eluates from dried blood spots had the same anti-zeta antibody color reaction as whole blood, even after storage at 4 degrees C for up to 77 days. The anti-zeta antibody test was positive in 24 of 91 microcytic samples (mean corpuscular hemoglobin < 24 pg), including four with iron deficiency; it was negative in 26 provisionally diagnosed alpha-thalassemia-1 heterozygotes and all 32 nonmicrocytic samples. Southern blot analysis and a specific SEA-polymerase chain reaction test confirmed that 18 anti-zeta antibody-positive samples and 1 anti-zeta antibody-negative sample had the (--SEA) deletion. Two anti-zeta antibody-negative microcytic samples had the (--Fil) total alpha-globin region deletion, 2 had single alpha-gene deletions, 22 others may also have had a total alpha-region deletion. Hence specificity was very high and sensitivity was 95%. The anti-zeta antibody test can detect the (--SEA) deletion in dried blood samples, even after prolonged storage. This simple inexpensive test can conveniently screen samples collected at a distance from a central laboratory.
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PMID:Anti-zeta antibody screening for alpha-thalassemia using dried filter paper blood. 819 21

Both iron deficiency and malaria are common in much of sub-Saharan Africa, and the interaction between these conditions is complex. To investigate the association between nutritional iron status, immunoglobulins, and clinical Plasmodium falciparum malaria, we determined the incidence of malaria in a cohort of children between the ages of 8 months and 8 years who were living on the Kenyan coast. Biochemical iron status and malaria-specific immune responses were determined during 2 cross-sectional surveys. We found that the incidence of clinical malaria was significantly lower among iron-deficient children (incidence-rate ratio [IRR], 0.70; 95% confidence interval [CI], 0.51-0.99; P<.05), that the incidence of malaria was significantly associated with plasma ferritin concentration (IRR for log ferritin concentration, 1.48; 95% CI, 1.01-2.17; P<.05), and that iron status was strongly associated with a range of malaria-specific immunoglobulins. We conclude that iron deficiency was associated with protection from mild clinical malaria in our cohort of children in coastal Kenya and discuss possible mechanisms for this protection.
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PMID:Iron deficiency and malaria among children living on the coast of Kenya. 1565 90

New parameters correlated with the hemoglobin content in reticulocytes (RET-Y) and in red blood cells (RBC-Y) have been suggested as helpful in diagnosing iron deficiency anemia. We have studied RET-Y and RBC-Y indices in two groups of patients with microcytosis to verify if these parameters could be used to differentiate iron deficiency anemia from beta-thalassemia minor. Blood samples from 33 iron-deficient patients, 25 beta-thalassemic minor patients and 50 normal individuals were analyzed on a Sysmex XE-2100 instrument. A significant difference was observed in reticulocyte counting and immature reticulocyte fraction between iron deficiency anemia and beta-thalassemia minor groups, but not in RBC-X and RET-Y parameters. Reticulocyte counting was higher in beta-thalassemia minor and the immature reticulocyte fraction was higher in severe iron deficiency anemia. The ratio RET-Y/mean cell volume was tested and was significantly different when beta-thalassemia minor was compared with mild and severe iron deficiency anemia, and showed better performance than the Mentzer ratio and the Green and King function. A great overlap of RET-Y and RBC-Y individual values was observed in both groups of microcytic anemias; we conclude that these new indices may be used with caution as indicative of iron deficiency, mainly in populations where beta-thalassemia minor is frequent.
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PMID:Measurement of reticulocyte and red blood cell indices in patients with iron deficiency anemia and beta-thalassemia minor. 1584 16

The aims of this study were to diagnose iron-restricted erythropoiesis (functional iron deficiency) in patients with classic iron deficiency (ID), anemia of chronic disease (ACD) and the combined state of ID/ACD with the use of two hematological methods for the measurement of reticulocyte hemoglobinization. In comparison, the biochemical markers of iron status were determined. We studied 474 anemic patients admitted to hospital with a broad spectrum of diseases. We measured indicators of reticulocyte hemoglobinization. CHr was determined on an Advia 120 hematology analyzer. A Sysmex XE-2100 hematology analyzer was used to determine RET-Y, the forward scatter of fluorescence-labeled reticulocytes, which can also be expressed as the reticulocyte hemoglobin equivalent (RET-H(e)), as well as RBC-Y, the forward scatter of fluorescence-labeled erythrocytes, which can be expressed as the erythrocyte hemoglobin equivalent. Ferritin, soluble transferrin receptor (sTfR) and the sTfR/log ferritin ratio (sTfR-F index) were used as biochemical markers. The comparison of RET-Y with CHr demonstrated an excellent curvilinear relationship between the two parameters. The normal reference range for Ret-Y was 1630-1860 arbitrary units (AU); mathematical transformation to RET-H(e) gave a range of 28.2-35.7 pg. Correlations of biochemical iron markers with RET-H(e) were as weak as with CHr in patients with ACD and acute phase response. In a diagnostic plot to identify iron status, RET-H(e) could replace CHr without any loss of sensitivity or specificity. Patient mismatch analysis between RET-H(e) and CHr in the diagnostic plot demonstrated agreement for 449 of 474 patients (94.4%). Patient specific anemia mismatches were 2.9-6.2%. According to our results, the indicators of reticulocyte hemoglobinization, RET-H(e) and CHr, measure the same phenomenon. RET-H(e) is as valuable as CHr for the diagnosis of iron-restricted erythropoiesis. The combination of RET-H(e) and the sTfR-F index in a diagnostic plot offers an attractive tool for the evaluation of iron status and identification of the progression of ID.
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PMID:Reticulocyte hemoglobin measurement--comparison of two methods in the diagnosis of iron-restricted erythropoiesis. 1623 85

Neurological development and functioning are adversely affected by iron deficiency in early life. Iron-deficient rats are known to have elevations in extracellular DA and NE, suggesting alterations in reuptake of these monoamines. To explore possible mechanisms by which cellular iron concentrations may alter NE transporter functioning, we utilized NET expressing PC12 cells and iron-deficient rats to explore the relationship between NET protein and mRNA expression patterns and iron concentrations. Treatment of PC12 with the iron chelator, desferrioxamine mesylate (DFO, 50 microM for 24 h), significantly decreased [3H] NE uptake by more than 35% with no apparent change in Km. PC12 cells exposed to increasing concentrations of DFO (25-100 microM) exhibited a dose response decrease in [3H] NE uptake within 24 h (38-73% of control) that paralleled a decrease in cellular NET protein content. Inhibition of protein synthesis with cycloheximide resulted in NET disappearance rates from DFO-treated cells greatly exceeding the rate of loss from control cells. RT-PCR analysis revealed only a modest decrease in NET mRNA levels. Rat brain locus ceruleus and thalamus NET mRNA levels were also only modestly decreased (10-15%) despite a 40% reduction in regional brain iron. In contrast, NET proteins levels in thalamus and locus ceruleus were strongly affected by regional iron deficiency with high correlations with iron concentrations (r > 0.94 and r > 0.80 respectively). The present findings demonstrate that NET protein concentrations and functioning are dramatically reduced with iron deficiency; the modest effect on mRNA levels suggests a stronger influence on NET trafficking and degradation than on protein synthesis.
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PMID:Cellular iron concentrations directly affect the expression levels of norepinephrine transporter in PC12 cells and rat brain tissue. 1665 Aug 37

Calcium and iron play dual roles in neuronal function: they are both essential but when present in excess they cause neuronal damage and may even induce neuronal death. Calcium signals are required for synaptic plasticity, a neuronal process that entails gene expression and which is presumably the cellular counterpart of cognitive brain functions such as learning and memory. Neuronal activity generates cytoplasmic and nuclear calcium signals that in turn stimulate pathways that promote the transcription of genes known to participate in synaptic plasticity. In addition, evidence discussed in this article shows that iron deficiency causes learning and memory impairments that persist following iron repletion, indicating that iron is necessary for normal development of cognitive functions. Recent results from our group indicate that iron is required for long-term potentiation in hippocampal CA1 neurons and that iron stimulates ryanodine receptor-mediated calcium release through ROS produced via the Fenton reaction leading to stimulation of the ERK signaling pathway. These combined results support a coordinated action between iron and calcium in synaptic plasticity and raise the possibility that elevated iron levels may contribute to neuronal degeneration through excessive intracellular calcium increase caused by iron-induced oxidative stress.
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PMID:Calcium, iron and neuronal function. 1750 66

We studied the effect of iron deficiency, i.e., 24-h preincubation in iron-free medium, and the effect of high level of non-transferrin iron, i.e., the preincubation in ferric citrate medium containing 500 microM ferric citrate, on the expression of DMT1, Dcytb, ferroportin, hephaestin, and ceruloplasmin in various functional types of human cells. The expression of these proteins potentially involved in non-transferrin iron transport across cell membranes was tested on mRNA level by quantitative real-time PCR as well as on protein level by western blot analysis in Caco-2 (colorectal carcinoma), K562 (erythroleukemia), and HEP-G2 (hepatocellular carcinoma) cells. We found that changes in non-transferrin iron availability, i.e., iron deficiency and high level of non-transferrin iron, affect the expression of tested proteins in a cell type-specific manner. We also demonstrated that changes in the expression on mRNA level do not often correlate with relevant changes on protein level.
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PMID:Differing expression of genes involved in non-transferrin iron transport across plasma membrane in various cell types under iron deficiency and excess. 1883 May 67

Mutations leading to abrogation of matriptase-2 proteolytic activity in humans are associated with an iron-refractory iron deficiency anemia (IRIDA) due to elevated hepcidin levels. Here we describe two novel heterozygous mutations within the matriptase-2 (TMPRSS6) gene of monozygotic twin girls exhibiting an IRIDA phenotype. The first is the frameshift mutation (P686fs) caused by the insertion of the four nucleotides CCCC in exon 16 (2172_2173insCCCC) that is predicted to terminate translation before the catalytic serine. The second mutation is the di-nucleotide substitution c.467C>A and c.468C>T in exon 3 that causes the missense mutation A118D in the SEA domain of the extracellular stem region of matriptase-2. Functional analysis of both variant matriptase-2 proteases has revealed that they lead to ineffective suppression of hepcidin transcription. We also demonstrate that the A118D SEA domain mutation causes an intra-molecular structural imbalance that impairs matriptase-2 activation. Collectively, these results extend the pattern of TMPRSS6 mutations associated with IRIDA and functionally demonstrate that mutations affecting protease regions other than the catalytic domain may have a profound impact in the regulatory role of matriptase-2 during iron deficiency.
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PMID:Matriptase-2 mutations in iron-refractory iron deficiency anemia patients provide new insights into protease activation mechanisms. 1959 82

The evaluation of iron status in dialysis patients provides information essential to the planning of adequate recombinant human erythropoietin treatment. The cellular iron status of the patients can be determined from the recently available measurement of reticulocyte hemoglobin equivalent (RET-He). RET-He is measured on the basis of automated fluorescent flow cytometry which in the reticulocyte channel, using a polymethine dye, also measures the mean value of the forward light scatter intensity of mature red blood cells and reticulocytes. These values equate with reticulocyte hemoglobin content. In this study, to clarify the accuracy of RET-He in diagnosing iron deficiency in dialysis patients, we initially compared RET-He with such iron parameters as serum ferritin levels, transferrin saturation and content of reticulocyte hemoglobin (CHr) which has been established as indicators of functional iron deficiency. Secondly, we investigated the changes in RET-He during iron supplementation for iron-deficient patients to determine whether this marker is a prospective and reliable indicator of iron sufficiency. The participants in this study were 217 haemodialysis patients. Iron deficiency was defined as havsing a transferrin saturation (TSAT) < 20% or serum ferritin < 100 ng/ml. Conventional parameters of red blood cells and RET-He were measured by on a XE-2100 automated blood cell counter (Sysmex). CHr was measured on an ADVIA120 autoanalyser (Siemens). RET-He mean value was 32.4 pg and good correlation (r = 0.858) between RET-He and CHr is obtained in dialysis patients. Receiver operating characteristic curve analysis revealed, values of the area was 0.776 and at a cutoff value of 33.0 pg, a sensitivity of 74.3% and a specificity of 64.9%, were achieved. Iron supplements given to the patients with low TSAT or ferritin, RET-He responded within 2 weeks, and this seemed to be a potential advantage of using RET-He in the estimation of iron status. RET-He is a new parameter, equivalent value to CHr, and is easily measurable on the widely spread and popular blood cell counter and is a sensitive and specific marker of iron status in dialysis patients.
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PMID:Usefulness of measuring reticulocyte hemoglobin equivalent in the management of haemodialysis patients with iron deficiency. 1962 2

We evaluated the usefulness of RET-Y and RBC-Y in distinguishing functional iron deficiency from iron-deficiency anaemia (IDA) in patients with anaemia of inflammation (AI). Sixty healthy blood donors constituted the control group. We studied RET-Y and RBC-Y in 115 patients with hypochromic/microcytic anaemia. Of these 42 patients had uncomplicated IDA and 73 had AI. The AI patients were further subdivided into AI with IDA and AI with functional IDA based on soluble transferrin receptor (sTfR) levels. The mean RBC-Y and RET-Y values in iron-deficient patients were 122.4 and 119.8, respectively, which were significantly lower than the control (P < 0.001). The mean level of RET-Y in patients with AI associated with IDA was 149.3 and this level in AI patients with functional iron deficiency was 147.4. RET-Y levels in both subgroups of AI patients were significantly lower than control but no significant difference was observed between the two subgroups. Similar findings were observed for RBC-Y. Receiver operating characteristic analysis also showed lower specificity for RBC-Y and RET-Y compared with that of sTfR and its log ferritin ratio (F-index). RET-Y and RBC-Y are useful in the diagnosis of simple IDA but have limited utility in the diagnosis of IDA with AI.
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PMID:RET-Y and RBC-Y in the diagnosis of iron deficiency associated with anaemia of inflammation. 2010 66


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