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

To test the hypothesis that the quantities of circulating transferrin receptors are reduced in iron overload, we studied serum transferrin receptors and indirect measures of iron status in 150 subjects from rural Zimbabwe. We found significant inverse correlations between serum concentrations of transferrin receptors and ferritin, the ratio of ferritin to aspartate aminotransferase, and transferrin saturation (r > or = 0.44; P < 0.001). The mean +/- SD concentration of serum transferrin receptors in 23 subjects classified as having iron overload (ferritin > 300 microg/L and transferrin saturation > 60%) was 1.55 +/- 0.61 mg/L, significantly lower than the 2.50 +/- 0.62 mg/L in 75 subjects with normal iron stores (ferritin 20-300 microg/L and transferrin saturation 15-55%; P < 0.0005) and the 2.83 +/- 1.14 mg/L in 8 subjects with iron deficiency (ferritin < 20 microg/L; P = 0.001). In keeping with the regulation of transferrin receptor expression at the cellular level, our findings suggest that serum transferrin receptors are decreased in the presence of iron overload.
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PMID:Serum transferrin receptors are decreased in the presence of iron overload. 955 May 56

Although iron is an essential dietary requirement, the amount absorbed by the body is well regulated and depends on body iron stores and on dietary iron availability. There is very little iron excreted under normal conditions. Iron deficiency is a worldwide problem but iron overload, as seen in the inherited disease, hemochromatosis, is a major cause of morbidity in some Caucasian populations. This is a problem particularly where there is an adequate dietary iron intake and especially in males. A mutation has recently been described in an MHC Class l-like gene (HFE) that encodes for a protein (HFE) of 343 amino acids. The molecule contains a signal sequence peptide-binding region, alpha, and alpha(2) domains, and an immunoglobulinlike alpha(3) domain, in addition to a transmembrane region and a small cytoplasmic tail. It is a candidate gene for hemochromatosis. Several possibilities as to the function of this gene and the corresponding protein have been suggested but none has yet been confirmed. The mutation has been detected by several different groups in 80%-100% of subjects with the disease. However, in one study, 18%-20% of patients with the mutation did not exhibit significant iron overload. The discovery of this gene has important implications for both clinical studies and the elucidation of the pathways of iron metabolism.
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PMID:Hemochromatosis and iron needs. 956 75

A number of factors have been shown to limit the response to recombinant human erythropoietin (r-HuEPO). One major factor appears to be an inadequate iron supply to the bone marrow. Erythropoiesis is dependent upon a continuous supply of iron to the bone marrow. The rate at which iron can be drawn from existing stores may easily limit the rate of delivery for haemoglobin synthesis. This results in 'functional iron deficiency' which is distinct from 'absolute iron deficiency' caused by depletion of iron stores. At present there are three main parameters available to clinicians wishing to monitor iron status in their patients: serum ferritin and transferrin saturation (TFS), which are indirect measurements, and the percentage of hypochromic red cells, which directly reflects marrow iron status. Ferritin levels should be measured before starting r-HuEPO therapy to ensure adequate iron stores (>200 microg/l), and when patients move from the correction phase to the maintenance phase of therapy (have stores become depleted during the correction phase?). In addition, ferritin levels can give an indication of iron overload following excess parenteral iron administration. The TFS represents a balance between iron supply by stores and demand by bone marrow. A saturation below 20% probably indicates iron-deficient erythropoiesis. However, this is an indirect measure of marrow iron supply and wide fluctuations have been observed when determined at different time points. The percentage of hypochromic red blood cells is measured by flow cytometry and a hypochromic subpopulation of more than 10% (normal percentage <2.5%) indicates iron-deficient erythropoiesis. However, not all departments may have access to the required equipment. The aim of iron supplementation is to provide sufficient iron for the correction phase and to replace iron losses (1500-2000 mg/year in haemodialysis patients) during the maintenance phase of r-HuEPO therapy. This amounts to a daily iron need in the range of 5 7 mg, which is well above the normal dietary intake and absorptive capacity of the human intestine. Therefore, there is a need for intravenous iron, in particular when the patient has absolute or functional iron deficiency, is intolerant of oral iron, or is not complying well with the oral regimen.
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PMID:Iron monitoring and supplementation: how do we achieve the best results? 956 84

Genetic haemochromatosis is a common iron overload disorder of unknown aetiology. To characterize the defect of iron metabolism responsible for this disease, this study localized and semi-quantified the mRNA and protein expression of transferrin, transferrin receptor and ferritin in the liver and duodenum of patients with genetic haemochromatosis. Biopsies were obtained from iron-loaded non-cirrhotic patients with genetic haemochromatotic and control patients with normal iron stores. Additional duodenal biopsies were obtained from patients with iron deficiency. Immunohistochemical and in situ hybridization analysis for transferrin, transferrin receptor and ferritin was performed. Hepatic transferrin, transferrin receptor and ferritin protein expression was localized predominantly to hepatocytes and was increased in patients with genetic haemochromatosis when compared with normal controls. Interestingly, hepatic ferritin mRNA expression was not increased in these same patients. In the genetic haemochromatotic duodenum, ferritin mRNA and protein was localized mainly to crypt and villus epithelial cells and the level of expression was decreased compared with normal controls, but similar to iron deficiency. Duodenal transferrin receptor mRNA and protein levels colocalized to epithelial cells of the crypt and villus were similar to normal controls. Early in the course of genetic haemochromatosis and before the onset of hepatic fibrosis, transferrin receptor-mediated iron uptake by hepatocytes contributes to hepatic iron overload. Increased hepatic ferritin expression suggests this is the major iron storage protein. While persisting duodenal transferrin receptor expression may be a normal response to increased body iron stores in patients with genetic haemochromatosis, decreased duodenal ferritin levels suggest that duodenal mucosa is regulated as if the patient were iron deficient.
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PMID:Cellular expression and regulation of iron transport and storage proteins in genetic haemochromatosis. 971 7

Iron deficiency and iron overload disorders are common in clinical practice. Both can result from perturbations in the flux of iron across the absorptive intestinal enterocyte. Until recently iron transport has been poorly understood. In 1997 two independent cloning strategies identified Nramp2 (DCT1) as the first mammalian transmembrane iron transporter. In this review we discuss evidence that Nramp-related proteins play essential roles in metal homeostasis and host defense.
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PMID:Mammalian iron transport: an unexpected link between metal homeostasis and host defense. 985 35

Iron deficiency affects approx. 20% of the world population. Due to predominantly vegetarian diets that reduce the bioavailability of food iron drastically, deficiency states are most widely distributed in developing countries. In addition, iron demand is increased by blood losses and by fast growth which increases the risk of iron deficiency in infants, young adolescents, and in menstruating and pregnant women. The symptoms of iron deficiency include impaired physical and intellectual performance. Iron supplementation may help to break the vicious cycle between inadequate nutrition and poverty. Fortification programs have to consider social and health aspects, including provision against iron overload. Excess iron stores may promote cancer and increase the cardiovascular risk, though the latter is a subject of current debate. The best approach to control such risks is individual iron supplementation geared to the demand by adequate laboratory controls. However, this approach is too costly for general application in developing countries. Food-iron fortification has successfully reduced iron deficiency in many trials and, in comparison, is much cheaper. As iron deficiency is widely distributed in most developing countries, the risk of inducing iron overload in the general population is low. Genetically determined diseases that may lead to siderosis, such as hereditary haemochromatosis or thalassaemia major, show a limited geographic and ethnic distribution. Such subgroups can be largely avoided by targeting food-iron fortification to infants, young adolescents, or pregnant women. Food vehicle and iron compound have to be matched in order to optimise iron bioavailability and to avoid rancidity in food, spoiling its taste and odour. The fortification of salt, sugar and spice mixtures or of bakery products with a short shelf-life are valid approaches to this end. Alternatively, haem iron can be used to fortify cereal-based food staples in developing countries such as tortillas or chappaties. Thus, a variety of options is available to solve the technical problems of food iron fortification. However, optimal solutions have to be tailored to the individual situation in each country.
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PMID:Iron supplementation. 985 25

Interest in including screening for hemochromatosis in the routine medical care of adults has grown in recent years. In March 1997, at a meeting on iron overload at the Centers for Disease Control and Prevention, the directors of four hemochromatosis screening programs described the major challenges that they faced and the lessons that they learned in implementing their programs. Seven issues were consistently described as important challenges: 1) changes in case definitions of hemochromatosis, 2) selection of screening threshold values and identification of false-positive cases, 3) variability and lack of standardization in screening test measurements, 4) physician education, 5) informed consent and concerns about medical and genetic discrimination, 6) patient compliance with screening and therapy, and 7) incidental detection of iron deficiency. The two programs that have been completed report a prevalence of iron overload from hemochromatosis of 4.2 to 4.5 per 1000 persons screened; this is consistent with findings in the recent literature. All programs report that screening is feasible and propose that hemochromatosis be defined by repeated elevated serum transferrin saturation values(with or without DNA test results) rather than by the clinical outcome of excessive iron in tissue. The goal of screening programs is to diagnose iron status disorders, particularly hemochromatosis, before they lead to iron overload and chronic disease states. Further research is needed on the ability of genetic and phenotypic tests to predict the clinical expression of hemochromatosis. The experiences outlined in this report highlight practical issues that need to be addressed when iron status screening for hemochromatosis is implemented. It is hoped that this information will facilitate similar efforts in other health care settings.
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PMID:Screening for hemochromatosis in primary care settings. 986 49

Iron deficiency is prevalent in children worldwide. Programmes of presumptive therapy, mass supplementation and food fortification have been introduced in many countries. The continuing unresolved debate over the interaction of iron and infection in the clinical setting indicates the need for firm guidelines for these practices. Iron overload is associated with increased susceptibility to certain infections, although the exact mechanisms may vary with the main pathology. Iron treatment has been associated with acute exacerbations of infection, in particular malaria. In Papua New Guinea parenteral iron was associated with increased rates of malaria and increased morbidity due to respiratory disease in infants but not in school children. Several subsequent studies in Africa using oral iron showed deleterious effects. In most instances cited, immunity was compromised, and therapeutic doses of oral iron were used. Knowledge of malarial endemicity, immunity with respect to age and the prevalence of haemoglobinopathies is important in planning interventions. A fine balance needs to be struck in the timing and dose of oral iron if informed recommendations are to be made. In parallel with supplementation studies, the effects of iron chelation on infection are being reported increasingly. Such therapy is clearly protective against malaria and some other infections but may predispose to fungal and Yersinia infections.
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PMID:Iron and infection in the tropics: paediatric clinical correlates. 987 73

Iron is essential for many cellular functions; consequently, disturbances of iron homeostasis, leading to either iron deficiency or iron overload, can have significant clinical consequences. Despite the clinical prevalence of these disorders, the mechanism by which dietary iron is absorbed into the body is poorly understood. We have identified a key component in intestinal iron transport by study of the sex-linked anaemia (sla) mouse, which has a block in intestinal iron transport. Mice carrying the sla mutation develop moderate to severe microcytic hypochromic anaemia. Although these mice take up iron from the intestinal lumen into mature epithelial cells normally, the subsequent exit of iron into the circulation is diminished. As a result, iron accumulates in enterocytes and is lost during turnover of the intestinal epithelium. Biochemical studies have failed to identify the underlying difference between sla and normal mice, therefore, we used a genetic approach to identify the gene mutant in sla mice. We describe here a novel gene, Heph, encoding a transmembrane-bound ceruloplasmin homologue that is mutant in the sla mouse and highly expressed in intestine. We suggest that the hephaestin protein is a multicopper ferroxidase necessary for iron egress from intestinal enterocytes into the circulation and that it is an important link between copper and iron metabolism in mammals.
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PMID:Hephaestin, a ceruloplasmin homologue implicated in intestinal iron transport, is defective in the sla mouse. 998 72

Carbohydrate-deficient transferrin (CDT), a microheterogeneous form of serum transferrin (Tf), has been proposed as the most reliable marker of chronic alcohol consumption, although unexplained false-positive and -negative results have been reported. We investigated whether body iron influenced CDT serum levels by studying alcohol abusers with or without iron overload and nonabusers with iron deficiency or iron overload caused by genetic hemochromatosis (GH). In alcohol abusers, CDT was significantly lower in the presence of iron overload than in the absence (24.6 +/- 16.5 U/L vs. 33.3 +/- 11.7 U/L; P <.01), with false-negative results almost exclusively in patients with iron overload. Similarly, in nonabusers with GH, CDT was lower than in normal controls (9.6 +/- 2. 2 U/L vs. 15.7 +/- 3.3 U/L; P <.0001), whereas, patients with iron deficiency anemia had significantly higher levels than controls (28. 1 +/- 5.8 U/L vs. 15.7 +/- 3.3 U/L; P <.0001). In nonabusers, iron supplementation therapy significantly decreased CDT levels in patients with iron deficiency anemia (33.7 +/- 6.6 U/L vs. 21.7 +/- 5.2 U/L; P =.0007), while iron-depletion treatment significantly increased CDT levels in patients with GH (9.7 +/- 2.0 U/L vs. 14.7 +/- 4.0 U/L; P =.001). Alcohol abusers had a significant relationship between liver iron concentration (LIC) and the reciprocal of CDT (r =.65; P <.0001), while in nonabusers, there was a significant correlation between Tf and CDT (r =.72; P <.0001). In conclusion, CDT serum levels are markedly affected by the patient's iron status, with iron overload reducing its sensitivity in alcohol abusers and iron deficiency its specificity in nonabusers. CDT can be considered a reliable marker of alcohol abuse only when iron stores are normal.
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PMID:Carbohydrate-deficient transferrin, a sensitive marker of chronic alcohol abuse, is highly influenced by body iron. 1005 65


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