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

Transferrin receptor (TfR) expression is regulated by iron at the level of mRNA stability through a factor (IRF/IRE-BP) which binds to specific iron-responsive elements (IRE). On the other hand, growth-dependent regulation of TfR expression is generally believed to be transcriptionally controlled. We analyzed the molecular mechanisms that control TfR gene expression at the onset of cell proliferation in vivo during liver regeneration after partial hepatectomy. The amount of TfR mRNA increased considerably after partial hepatectomy while run-on assays did not show significant changes in TfR gene transcription. RNA band-shift assays documented a significant activation of IRF/IRE-BP specific for the faster migrating IRE-protein complex (IRFB). These changes occurred in the absence of modifications of total liver iron concentration but together with a significant decrease of ferritin content. Moreover, when extreme variations of liver iron content were achieved by either chronic iron overload or severe iron deficiency, liver regeneration was unable to influence IRE-binding activity. We conclude that IRF/IRE-BP-mediated post-transcriptional control can fully account for TfR mRNA induction during liver cell proliferation in vivo. IRF/IRE-BP activation in the absence of changes in total tissue iron content might depend either on a drop of iron levels into the regulatory pool or on a relatively iron-independent mechanism specific for the faster migrating complex.
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PMID:Transferrin receptor gene expression during rat liver regeneration. Evidence for post-transcriptional regulation by iron regulatory factorB, a second iron-responsive element-binding protein. 811 90

Anaemia in elderly patients should never be regarded as a normal physiological response to aging. Underlying causes must be investigated and treated in a similar manner to that used in younger adults. In addition to a thorough history and physical examination, basic investigations such as red cell indices and morphology, reticulocyte count, haematinic assays and occasionally bone marrow examination, will detect the underlying pathology in most cases. Anaemia may be classified, according to red blood cell mean corpuscular volume, into microcytic, macrocytic and normocytic types. Anaemia with an absolute reticulocytosis is due either to acute blood loss or haemolysis. Other anaemias, more frequently encountered in elderly patients, are hypoproliferative, and reflect depressed marrow production or impaired erythroid maturation. Examples include anaemia of chronic disease and iron deficiency and, less commonly, megaloblastic anaemia and anaemia due to primary bone marrow failure. The treatment of anaemia should aim to correct the underlying cause of the disorder and/or to improve the quality of the blood, e.g. by haematinic replacement therapy. Recombinant human erythropoietin has revolutionised the treatment of anaemia associated with chronic renal failure, while its role in other anaemias is currently under investigation. Regular blood transfusion may be required for some elderly patients with chronic anaemia. However, the attendant risks of this procedure, such as iron overload and viral hepatitis transmission, must be considered.
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PMID:Identification and treatment of anaemia in older patients. 818 39

Erythropoietin (EPO) is the primary regulator of day-to-day red blood cell production. Secreted by peritubular capillary lining cells in the kidney, EPO circulates in the plasma to interact with target cells in the bone marrow to maintain or stimulate erythropoiesis. The primary target of EPO action is the intermediate-stage erythroid burst-forming unit and the erythroid colony-forming unit (CFU-E). The CFU-E is estimated to have 300 to 400 high-affinity EPO receptors per cell and, in healthy individuals, is the cell with the highest number of receptors in the body. There is some controversy as to whether EPO provides a mitogenic signal to the CFU-E or, rather, prevents programmed cell death (apoptosis). Iron is an essential element for hemoglobin synthesis and its importance has been emphasized in individuals receiving recombinant human erythropoietin (rHuEPO). The administration of rHuEPO to patients with chronic renal failure has resulted in a number of changes in iron metabolism, including the reversal of iron overload as iron is mobilized from storage sites for hemoglobin synthesis. In addition, higher doses of rHuEPO create a state of functional (or relative) iron deficiency that is characterized by a low percent transferrin saturation in the face of adequate iron stores. The value of aggressive iron supplementation in patients receiving rHuEPO has been demonstrated in clinical trials of rHuEPO administration in individuals storing blood for autologous use at the time of surgery.
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PMID:The relationship of erythropoietin and iron metabolism to red blood cell production in humans. 820 25

We evaluated the iron status of 50 Sicilian patients with G6PD deficiency under steady-state conditions and compared our results with those for 50 control patients. We studied haemolysis and iron indices to evaluate the iron balance. These patients could be considered to be at risk of iron overload as a result of increased bone marrow activity. Reticulocytosis and macrocytosis with reduced levels of haptoglobin were found in the G6PD-deficient subjects, both of which are evidence of a moderate haemolysis. Iron status within the normal range, without iron overload or iron deficiency, was found.
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PMID:Low-grade haemolysis and assessment of iron status during the steady state in G6PD-deficient subjects. 823 70

The feeding of diets enriched with (3,5,5-trimethylhexanoyl)ferrocene (TMH-ferrocene) has been shown recently to produce a severe experimental iron overload in rats and has been considered as an adequate animal model for hereditary haemochromatosis in humans. We synthesized three 59Fe-labelled ferrocene compounds with different lipophilic characters (ferrocene, TMH-ferrocene, and 1,1'-bis(3,5,5-trimethylhexanoyl)ferrocene [(TMH)2-ferrocene]) and studied the metabolism of iron from these compounds in comparison with the hydrophilic ferrous sulphate in rats with iron deficiency, and normal and increased iron stores. The bioavailability of iron from TMH-ferrocene (whole body retention, 48% from a 5 mg Fe dose) was twice as high as from ferrocene and six times higher than from (TMH)2-ferrocene and ferrous sulphate. In contrast to the well-known iron salts (ferrous sulphate), the intestinal absorption of TMH-ferrocene iron was independent from the dose (1 or 5 mg Fe) and similar in iron-deficient and iron-loaded rats, indicating that the intestinal absorption of the TMH-ferrocene is not regulated by the body iron stores. After intestinal absorption, TMH-ferrocene iron in the portal blood is transported to the liver independently from transferrin. In contrast to absorbed ferrocene, iron from TMH-ferrocene is almost completely released from the hydrocarbon moiety within the liver. Depending on the body iron stores, TMH-ferrocene iron is then incorporated preferentially into haemoglobin (iron-deficient rats) or added to the iron stores in the liver (iron-loaded rats). A transient storage of the 59Fe-label in fat tissue was observed only from oral ferrocene but not from TMH-ferrocene. Due to the outstandingly high bioavailability of TMH-ferrocene, the chronic feeding of this compound resulted in a fast and progressive iron overload in rats (liver iron: 16.9 mg Fe/g wet weight after 10 weeks of feeding a diet containing 0.5% TMH-ferrocene), and can be regarded as the best characterized and most useful animal model for severe hepatocellular iron overload in humans.
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PMID:Metabolism of iron from (3,5,5-trimethylhexanoyl)ferrocene in rats. A dietary model for severe iron overload. 843 91

We have studied the iron metabolism in nine patients with erythropoietic protoporphyria (EPP) and three patients with sideroblastic anaemia (SA). All, except one EPP patient were iron deficient. The SA patients had a secondary haemochromatosis. The bone marrow aspirates of patients with SA and also three patients with EPP had a high incidence of ring sideroblasts. Ultrastructural examination of the bone marrow consistently showed finely dispersed electron-dense deposits localized in mitochondria of erythroblasts in all patients with EPP and SA. Mitochondrial electron energy-loss spectroscopy (EELS) indicated identical iron compounds in erythroblasts of all EPP and SA patients. These findings indicate that the mitochondrial iron utilization is disturbed in EPP and SA. The observation of mitochondrial iron deposition in erythroblasts in EPP and SA suggests that this failure is not of pathognomonic value for diagnosis of SA, but is apparently the result of an inefficient haem synthesis, in EPP due to a defective ferrochelatase. The mitochondrial iron deposition does not depend on the iron status (iron overload or iron deficiency) of the EPP patient.
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PMID:Accumulation of iron in erythroblasts of patients with erythropoietic protoporphyria. 846 22

Haemodialysis patients with iron overload sometimes develop resistance to erythropoietin therapy due to 'functional iron deficiency'. It is known that this resistance may be overcome by iron supplementation; however, the latter could worsen haemosiderosis. Therefore, we treated four iron-overloaded haemodialysis patients who had developed relative resistance to erythropoietin (among whom three had features of 'functional iron deficiency') with ascorbic acid (500 mg intravenously after haemodialysis, 1-3 times a week). The erythropoietin doses were voluntarily kept unchanged during the study. After a latency of 2-4 weeks, haematocrit and haemoglobin had increased respectively from 26.5 +/- 0.7 to 32.7 +/- 0.4 vol% and from 8.8 +/- 0.3 to 10.8 +/- 0.2 g/dl (means +/- SEM, P < 0.001). While serum ferritin remained unchanged, transferrin saturation increased from 27 +/- 7 to 54 +/- 12% (P < 0.05), suggesting that ascorbic acid supplementation had allowed mobilization of iron from tissue burdens. In one patient, haematocrit declined after withdrawal of vitamin C and increased again after rechallenge. Also, ascorbate supplementation was continued after the study in two patients and allowed the erythropoietin doses to be decreased, 8 and 11 weeks, respectively, after the start of the trial. When a control group of seven patients with normal iron status and without resistance to erythropoietin were challenged in the same manner with ascorbate, no elevation of haematocrit or transferrin saturation was noted. We conclude that ascorbate supplementation may circumvent resistance to erythropoietin that sometimes occurs in iron-overloaded patients, in particular, in the setting of 'functional iron deficiency'.
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PMID:Resistance to erythropoietin in iron-overloaded haemodialysis patients can be overcome by ascorbic acid administration. 852 94

There are two major disturbances of iron balance: iron deficiency and iron overload. Iron-deficiency anemia is a major problem in developing countries and affects between 500 million and 600 million people worldwide. While iron overload is much less prevalent, it has a number of major pathologic sequelae and there have been recent suggestions that even modest increases in the body's iron stores may have pathologic associations. To understand the ways in which iron balance can be disturbed, it is necessary to have an understanding of how losses from the body are matched by the absorption of iron in different dietary settings as well as the limits of this regulatory control.
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PMID:Overview and mechanisms of iron regulation. 857 6

Regulation of iron balance is of particular interest, especially iron absorption, cellular iron metabolism and transferrin-transferrin receptor in hematopoiesis. Recent advances in molecular and cell biology have helped to reveal the mysteries of cellular iron metabolism concerning mRNA encoding ferritin and transferrin receptor synthesis. The physiology of transferrin and transferrin receptor is applied in the evaluation of erythropoiesis, i.e., erythron transferrin uptake in ferrokinetics and measurement of serum transferrin receptor. In iron absorption, much of the key mechanism remains unknown. The importance of iron metabolism in human beings is discussed in traditional areas of iron deficiency and nutrition. Iron overload is a new clinical problem to be solved in hemochromatosis or in relation to ischemic heart disease.
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PMID:Overview of iron metabolism. 858 65

Iron deficiency may develop in hemodialysis patients, especially when erythropoietin is given. The role of iron deficiency in the anemia of predialysis chronic renal failure (CRF), however, is much less clear. We have intravenously (IV) administered iron as ferric saccharate in a total dose of 200 mg elemental iron monthly for 5 months to 33 CRF patients who remained anemic despite oral iron supplementation and who had no laboratory signs of iron overload. None was receiving erythropoietin therapy. In 22 of the patients there was an increase in the hematocrit values by the end of the study. These patients were considered responders to intravenous iron (IV Fe) therapy. In 11 patients the iron administration was not associated with improvement of the anemia (nonresponders). Before onset of the IV Fe therapy there were no differences between the responders and nonresponders with regard to degree of anemia, serum ferritin, iron saturation, renal function, or blood pressure. One additional patient was excluded from the study because of a mild reaction during an IV test dose before the study. No worsening of kidney function and no other side effects were noted. In four patients (three responders and one nonresponder) the control of blood pressure necessitated antihypertensive drug therapy adjustment. In conclusion, IV Fe supplementation in two thirds of anemic CRF patients not receiving dialysis resulted in a significant improvement of the anemia, thus avoiding the necessity of erythropoietin or blood administration. This could be achieved by increasing the plasma ferritin levels to 200 to 400 microns/L and/or increasing the iron saturation to 25% to 35%. Intravenous ferric saccharate appears to be a safe and effective method of administering iron for the correction of anemia in CRF patients not receiving dialysis.
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PMID:Intravenous iron supplementation for the treatment of the anemia of moderate to severe chronic renal failure patients not receiving dialysis. 865 99


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