Studies of iron metabolism in children without the use of radioactive isotopes.
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The uptake of [67 Ga]citrate by normal rats of different ages has been compared with the mineral composition of the assayed tissues. Very young animals take up much more 67 Ga than the adults and there seems to be a correlation between the mineral composition (calcium, magnesium and iron) and the radioactivity uptake. The role of those elements and of cellular proliferation in this phenomenon is discussed.
Neutron bombardment (neutron flux, 3 X 10(12) neutrons/cm2/s) of prepared iron tablets containing glycine-iron or iron alone was performed to prepare radioactive tablets to assess the effects of glycine on iron absorption from tableted formulations. No interfering isotopes of sufficient quantity were generated during neutron activation of the iron tablets. Cobalt-60 was the major trace mineral detected and accounted for only 1.3% of the total activity. There may have been trace amounts of zinc-65 or chromium-51 present, but they were not detectable above background radioactivity in the final tablet produced. Iron-59 represented greater than 98% of the radioactivity present in the tablets used in the study. Glycine-containing iron tablets produced dramatically higher amounts of iron in blood and tissues of rabbits (p less than 0.05) than did the same tablet formulations without glycine. The area under the iron blood concentration-time curve over 4 h increased by 67% with glycine added to the formulation over control iron tablets. Iron concentrations in tissues 4 h after iron administration was in the order of blood greater than liver greater than heart greater than kidney greater than muscle.
A successful method for the analytical subcellular fractionation of mouse duodenal mucosa organelles was established. 59Fe(III)-nitrilotriacetate (pH 7.2) was injected into tied-off duodenal segments in vivo and, after 2-20 min, mucosal homogenates were subjected to subcellular fractionation. Radioactivity was recovered in the cytosolic fractions and in the gradient at a density of 1.18-1.20 g/ml. Enhanced iron absorption was achieved by placing the animals in a hypobaric chamber for 3 days. These animals had a higher proportion of particulate 59Fe compared to controls. Homogenisation in sucrose medium containing the selective plasma membrane perturbant digitonin shifted the particulate iron fraction to a higher density region of the gradient indicating a localisation of the iron binding site to the plasma membrane region of the mucosal cells. No significant radioactive iron was observed in the brush-border region of the gradient. Transferrin immunoreactivity was found only in the cytosolic region of the gradient and was not associated with any organelle.
Approximately 2% of iron contained in mouse erythrocytes is transferred into supernatant when haemolysed erythrocytes are precipitated with trichloroacetic acid. The component unprecipitable with trichloroacetic acid is probably bound predominantly to reticulocytes and it is larger the younger is the reticulocyte. Under the conditions of postirradiation suppression of erythropoiesis this component grows strongly and in the phase of overrecovery of erythropoiesis decreases. The numerical values determined in the paper can be used for a correction of the disturbing influence of haemolysis on concentration and radioactivity of plasma iron in the resting state of erythropoiesis, if a preliminary precipitation of a sample with trichloroacetic acid was carried out.
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The content and bioavailability of iron contained in Chilean bread was studied in a random sample from 301 bakeries. A wet digestion procedure followed by a colorimetric method was used. Iron bioavailability was examined in 9 adult women using the extrinsic radioactive tag method. The iron content of bread was 2.4 +/- 0.7 mg/100 g (normally distributed) and 71% of bakeries used wheat flour with adequate iron content. The geometric mean of iron absorption was high (10.5%). Simultaneous ingestion of milk or tea decreased iron absorption by 26 and 35%, respectively. These data suggest that bread represents an important source of iron in the diet of the Chilean population. Iron fortification of bread should be supported and improved nationwide.
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The present experiments were carried out on normal and iron deficient rats which were fed low iron diet and bled several times; the haemoglobin content of blood of normal rats was in the range of 12-14 g/dl, that of iron deficient rats between 6 and 8 g/dl. Iron was administered by a gastric tube and the retention of the radioactively labelled 59Fe-iron compounds was measured on the 6th day after the administration. There is no difference of the absorption of divalent and trivalent iron provided iron is administered in ionized form. This is possible when the iron solution administered is of pH less than 2.5. Since the pH values of gastric juice is in the same order of magnitude, this procedure is hardly to be called unphysiological. The decisive role of pH for the bioavailability of iron ions can be derived from an experiment with cobaltous ions that, in the range of physiological pH values, cannot be hydrolysed. Therefore, no difference of the retention of cobaltous ions was measured regardless whether the solution administered into a tied-off jejunal loop was of pH 2 or 5.5. The administration of either divalent or trivalent iron ions together with food to normal rats is followed by a slight decrease of the amount of iron retained. However, this difference of retention disappears when the ionized iron is administered to fed iron deficient rats.(ABSTRACT TRUNCATED AT 250 WORDS)
BACKGROUND: A large oral dose of iron will reduce the absorption of a subsequent smaller dose of iron in a phenomenon known as mucosal block. Molecular analysis of this process may provide insights into the regulation of intestinal iron absorption. AIMS: To determine the effect of an oral bolus of iron on duodenal expression of molecules associated with intestinal iron transport in rats and to relate this to changes in iron absorption. METHODS: Rats were given an oral dose of iron and duodenal expression of divalent metal transporter 1 (DMT1), Dcytb, Ireg1, and hephaestin (Hp) was determined using the ribonuclease protection assay, western blotting, and immunofluorescence. Iron absorption was measured using radioactive (59)Fe. RESULTS: A decrease in intestinal iron absorption occurred following an oral dose of iron and this was associated with increased enterocyte iron levels, as assessed by iron regulatory protein activity and immunoblotting for ferritin. Reduced absorption was also accompanied by a rapid decrease in expression of the mRNAs encoding the brush border iron transport molecules Dcytb and the iron responsive element (IRE) containing the splice variant of DMT1. No such change was seen in expression of the non-IRE splice variant of DMT1 or the basolateral iron transport molecules Ireg1 and Hp. Similar changes were observed at the protein level. CONCLUSIONS: These data indicate that brush border, but not basolateral, iron transport components are regulated locally by enterocyte iron levels and support the hypothesis that systemic stimuli exert their primary effect on basolateral transport molecules.
Cells of Escherichia coli K-12 could grow aerobically at an iron concentration as low as 0.05 micrometer without any of the known iron ionophores present. The growth rate increased between 0.05 and 2 micrometer iron. Supplementation with the iron ligands ferrichrome and citrate resulted in optimal growth already at 0.05 micrometer iron. Under certain conditions iron uptake preceded growth of cells by more than an hour. During logarithmic growth the rate of iron uptake matched the growth rate. The radioactive tracer method revealed a cellular iron content of 4 nmol/mg dry weight. After consumption of the iron in the medium cells continued to grow with high rate for 1-2 generations. The iron uptake activity was increased during iron starvation.
Iron uptake and magnetite (Fe3O4) crystal formation could be studied in the microaerophilic magnetic bacterium Magnetospirillum gryphiswaldense by using a radioactive tracer method for iron transport and a differential light-scattering technique for magnetism. Magnetite formation occurred only in a narrow range of low oxygen concentration, i.e., 2 to 7 microM O2 at 30 degrees C. Magnetic cells stored up to 2% iron as magnetite crystals in intracytoplasmic vesicles. This extraordinary uptake of iron was coupled tightly to the biomineralization of up to 60 magnetite crystals with diameters of 42 to 45 nm.
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Paramagnetic complexes of manganese(II), iron(III), and gadolinium(III) with many ligands appear to undergo ligand substitution in vivo, producing biodistribution data similar to the hydrated metal ions. To identify ligands likely to be valuable in the preparation of paramagnetic contrast agents, a series of aminopolycarboxylate complexes with stability constants increasing in the order iminodiacetic acid (IDA) less than nitrilotriacetic acid (NTA) less than EDTA less than CDTA less than or equal to DTPA was prepared with 54Mn(II), 59Fe(III), and 153Gd(III) at both tracer and carrier levels. Biodistribution studies in mice suggested that complexes remained unchanged in vivo if their stability constants (K1) were approximately greater than 10(16) for Mn(II) and Gd(III) and greater than 10(22) for Fe(III) complexes at tracer levels. Metal complexes with added carrier appeared to be effectively more stable in vivo, possibly due to dissociation and saturation of metal-binding sites. To avoid the accumulation of metal ions in tissues, new paramagnetic contrast agents containing these metal ions will require stability constants equal to or greater than those identified here.
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In iron overload, non-transferrin-bound iron (NTBI) is found in plasma and is rapidly removed by hepatocytes. Some of this NTBI is excreted into bile. Biliary excretion of NTBI, in the form of an iron-deferiprone chelate, is greatly increased by deferiprone, an iron chelator. The aim of this study was to test whether biliary iron as such or as an iron-deferiprone chelate (both originating from plasma NTBI) is absorbed from the intestine and re-secreted into bile. In healthy biliary fistula (donor) rats, biliary 55Fe originating from plasma NTBI was obtained by injecting Fe citrate (to saturate transferrin) followed by 55Fe. This biliary 55Fe was infused into the duodenum of (recipient) rats whose transferrin was saturated or unsaturated. Similar experiments were performed using iron-overloaded (donor) rats given deferiprone, followed by infusion of the biliary 55Fe-deferiprone chelate into iron-overloaded (recipient) rats. The results show that in healthy (recipient) rats, duodenal infusion of 55Fe from NTBI was followed by increased plasma 55Fe when transferrin was unsaturated, or by biliary excretion of 55Fe when transferrin was saturated, indicating intestinal absorption of 55Fe. In iron-overloaded rats, neither plasma nor bile became radioactive, indicating no intestinal absorption of iron from the deferiprone chelate. We conclude that biliary iron, originating from NTBI, is absorbed from the intestine, and undergoes enterohepatic circulation if transferrin is saturated. In iron-overloaded rats, biliary iron originating from plasma NTBI and present as an iron-deferiprone chelate in bile is not absorbed.
This paper describes a method of quantitatively assaying the bioavailability of orally administered iron in order to promote haemoglobin synthesis in iron deficiency anaemia. The non-radioactive tracer substance 54Fe was employed. An experimental iron deficiency model was tested in 18 healthy male volunteers. The trial design made it possible to assess intestinal absorption and efficacy of iron substitution. The iron deficiency was experimentally induced by weekly phlebotomy. Two commercially available iron preparations with different rates of iron release were investigated at a dosage of 150 and 160 mg Fe2+ daily, respectively. In the first seven days of treatment, both preparations were administered in 54Fe-labelled form. Afterwards, iron substitution was given with the commercially available preparations. Measurements were made of erythrocyte utilization of 54Fe and plasma iron tolerance curves at the beginning of the periods in which the 54Fe-labelled product and the commercially available preparation were administered, and of haemoglobin and serum ferritin concentration curves over three months. The mean utilization of the iron administered was virtually identical for the two preparations (23 and 22%, respectively). Likewise, there was no difference with respect to the average daily increase in haemoglobin concentration in the blood (1.5 g 1-1). There was also no significant difference with respect to serum ferritin concentration curves. In contrast, the two preparations differed markedly with respect to the plasma iron tolerance curves. This suggests that evaluation of plasma iron tolerance curves alone is not suitable for comparative assessment of the therapeutic value of orally administered iron preparations.