[Preparation, properties and physiologic action of the product resulting from association of vitamin C with ferrous and copper salts].
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Ascorbic Acid↗
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[Incidence of hidden iron deficiency in women, especially in pregnancy and puerperium].
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Female↗
Regulation of iron absorption and storage iron turnover.
The regulation of iron supply to plasma was studied in male rate. Repeated exchange transfusions were first carried out with plasma from iron-deficient or iron-loaded animals. There was no recognizable effect on the amount of iron entering the plasma as evidenced by plasma iron concentration or iron absorption by recipient animals. In other studies, iron compounds having different tissue distribution were injected. Subsequent iron release was greater from reticuloendothelial cells than from other iron-loaded tissues. When requirements for transferrin iron were increased by exchange transfusion with high reticulocyte blood, within minutes there was a doubling of the rate of tissue iron donation. It was concluded from these studies that (1) iron turnover in the plasma is primarily determined by the number of tissue receptors for iron, particularly those of the erythron, (2) that the amount of iron supplied by each donor tissue is dependent on the output of other donor tissues, and (3) that a humoral mechanism regulating iron exchange is unlikely in view of the speed of response and magnitude of changes in plasma iron turnover. It is proposed that there is some direct mechanism that determines the movement of iron from donor tissues to unsaturated transferrin binding sites.
Absorption↗
Assessment of iron absorption from ferric trimaltol.
Therapeutic iron compounds have limited absorption and often have side-effects, which limits patient compliance. Iron trimaltol is a novel, stable complex, formed between ferric iron (Fe3+) and maltol (3-hydroxy-2-methyl-4-pyrone), and is effective in the treatment of iron deficiency anaemia with few side-effects. However, the kinetics of iron absorption from ferric trimaltol and the reliability of normal colorimetric analysis in detecting iron absorbed from this complex have not been established. We measured increases in serum iron levels in 12 volunteers following oral challenge with four different pharmaceutical formulations of ferric trimaltol in a double-blind, cross-over, randomized study. The conventional colorimetric method for detecting serum iron was compared with thermal analyses after trichloroacetic acid (TCA) treatment of serum. Measurements of serum iron levels by TCA treatment and thermal analysis closely agreed with measurements by colorimetry. For all formulations, serum iron levels peaked at 90 min with a plateau of at least 5 h [mean (standard deviation) peak absorption 8.3% (6.3%) of ingested dose, n=48]. Absorption of iron, based on peak serum values or area under the serum curve, was not different for the four formulations (n=12 each) and correlated with the individual's iron status, as assessed by serum ferritin values (r = -0.6; P < 0.001). Normal colorimetry is suitable for analysis of serum iron levels following ingestion of ferric trimaltol. There is rapid and sustained absorption of iron from ferric trimaltol and, as with ferrous iron, uptake appears to be controlled through normal mechanisms of iron acquisition that depend upon body iron stores.
Adult↗
Absence of an effect of ferrous sulfate on phenytoin absorption in the rat.
A variety of drugs which bind to iron have significant reductions in absorption when co-administered with iron compounds. The chemical structure of phenytoin indicates that there may be possible binding to iron ions. In vitro experiments were performed to determine whether any binding of iron to phenytoin occurred, and in vivo studies examined the effect of ferrous sulfate on phenytoin absorption in an isolated perfused rat jejunal model of drug absorption. The dose of phenytoin was limited by solubility and represents a human dose of 28 mg on a mg/kg basis for the rat assuming the total dose to be in 10 cm bowel in the rat. The ferrous sulfate doses were chosen to represent 28 and 300 mg doses on a similar basis to phenytoin. There was no significant effect of ferrous sulfate on phenytoin absorption or instability of phenytoin in the presence of ferrous sulfate in the rat. In vitro experiments indicated that little or no phenytoin binding to iron occurred. Results from animal model studies using low doses of phenytoin suggest it is unlikely that there will be a significant reduction in phenytoin absorption during concurrent therapy with iron salts.
Animals↗
The nanophase iron mineral(s) in Mars soil.
A series of surface-modified clays containing nanophase (np) iron oxide/oxyhydroxides of extremely small particle sizes, with total iron contents as high as found in Mars soil, were prepared by iron deposition on the clay surface from ferrous chloride solution. Comprehensive studies of the iron mineralogy in these "Mars-soil analogs" were conducted using chemical extractions, solubility analyses, pH and redox, x ray and electron diffractometry, electron microscopic imaging, specific surface area and particle size determinations, differential thermal analyses, magnetic properties characterization, spectral reflectance, and Viking biology simulation experiments. The clay matrix and the procedure used for synthesis produced nanophase iron oxides containing a certain proportion of divalent iron, which slowly converts to more stable, fully oxidized iron minerals. The clay acted as an effective matrix, both chemically and sterically, preventing the major part of the synthesized iron oxides from ripening, i.e., growing and developing larger crystals. The precipitated iron oxides appear as isodiametric or slightly elongated particles in the size range 1-10 nm, having large specific surface area. The noncrystalline nature of the iron compounds precipitated on the surface of the clay was verified by their complete extractability in oxalate. Lepidocrocite (gamma-FeOOH) was detected by selected area electron diffraction. It is formed from a double iron Fe(II)/Fe(III) hydroxy mineral such as "green rust," or ferrosic hydroxide. Magnetic measurements suggested that lepidocrocite converted to the more stable maghemite (gamma-Fe2O3) by mild heat treatment and then to nanophase hematite (alpha-Fe2O3) by extensive heat treatment. After mild heating, the iron-enriched clay became slightly magnetic, to the extent that it adheres to a hand-held magnet, as was observed with Mars soil. The chemical reactivity of the iron-enriched clays strongly resembles, and offers a plausible mechanism for, the somewhat puzzling observations of the Viking biology experiments. Their unique chemical reactivities are attributed to the combined catalytic effects of the iron oxide/oxyhydroxides and silicate phase surfaces. The reflectance spectrum of the clay-iron preparations in the visible range is generally similar to the reflectance curves of bright regions on Mars. This strengthens the evidence for the predominance of nanophase iron oxides/oxyhydroxides in Mars soil. The mode of formation of these nanophase iron oxides on Mars is still unknown. It is puzzling that despite the long period of time since aqueous weathering took place on Mars, they have not developed from their transitory stage to well-crystallized end-members. The possibility is suggested that these phases represent a continuously on-going, extremely slow weathering process.
Aluminum Silicates↗
Inhibition of growth of the lymphocyte lines by deferoxamine under various iron-supply conditions.
Inhibition of growth of the lymphocyte lines by iron-binding agent deferoxamine under various iron-supply conditions was studied. Three different defined culture media, representing three different iron-supply conditions, were used: (1) ferric citrate (500 microM) medium, (2) transferrin (5 micrograms/ml) medium, and (3) low-iron medium (this medium without any iron compound added contains 0.6 microM contaminative non-transferrin iron). Mouse B cell line PLV-01, human T cell line Jurkat, and human B cell lines Raji and HSCE- were employed. Raji and HSCE- cells are able to grow in low-iron medium but PLV-01 and Jurkat cells do not grow in the medium. For all cell lines tested in ferric citrate medium, a 50% growth inhibition was achieved with 440-500 microM deferoxamine. In transferrin medium, deferoxamine concentrations of 4.4-5.5 microM were required for a 50% inhibition of PLV-01, Jurkat and HSCE- cells. For the same degree of inhibition of Raji cells, 39 microM deferoxamine was required. In the case of low-iron medium, a 50% inhibition of Raji and HSCE- cells was achieved with about 1.4-2.1 microM deferoxamine. The data demonstrate that the sensitivity of the lymphocyte lines to deferoxamine depends on iron-supply conditions. Under the same iron-supply conditions, individual cell lines can exhibit different sensitivity. However, the sensitivity does not correlate with the ability of the cell lines to grow in low-iron medium.
Animals↗
Oral iron absorption test in patients on CAPD: comparison of ferrous sulfate and a polysaccharide ferric complex.
We prospectively compared the absorption of ferrous sulfate to that of a polysaccharide ferric complex (Niferex) in 5 healthy controls and 7 stable patients on continuous ambulatory peritoneal dialysis (CAPD). All study subjects received an equivalent of 150 mg of elemental iron of either preparation, in a random fashion. After a baseline fasting serum iron level was obtained, the serum iron concentration was measured at 2 h in the control group and at 2 and 4 h in the CAPD patients. One to 2 months later, all study subjects received the alternative iron compound and were studied in an identical manner. A significant rise in serum iron was only observed in the healthy subjects after the ingestion of ferrous sulfate and not Niferex (ferrous sulfate 102 +/- (SE) 9 vs. 142 +/- 7 Mg/dl, p = 0.0005; Niferex 96 +/- (SE) 10 vs. 102 +/- 12 mg/dl; baseline vs. 2 h, respectively). The absorption of both compounds was poor in the patients on CAPD, with the 2- and 4-hour serum iron levels not significantly higher than the baseline values (ferrous sulfate 73 +/- 7 vs. 107 +/- 21 vs. 109 +/- 21 mg/dl, p = NS; Niferex 57 +/- 11 vs. 65 +/- 14 vs. 60 +/- 11 mg/dl, p = NS; baseline vs. 2 vs. 4 h, respectively). Our data suggest that the absorption of both ferrous sulfate and ferric polysaccharide complex is poor in patients on CAPD.
Administration, Oral↗
Utilization of iron gallate and other organic iron complexes by bacteria from water supplies.
The degradation of four soluble organic iron compounds by bacteria isolated from surface waters and the precipitation of iron from these complexes by the isolates was studied. All eight isolates brought about the precipitation of iron when grown on ferric ammonium citrate agar. Three isolates were able to degrade ferric malonate, and three others degraded ferric malate with iron precipitation. Only three isolates, two strains of Pseudomonas and one of Moraxella, were able to degrade gallic acid when this was supplied as the sole carbon source. One strain of Pseudomonas was found to be active in degrading ferric gallate. Electron microscopy of cells of this bacterium after growth in ferric gallate as the sole carbon source yielded results indicating uniform deposition of the iron on or in the bacterial cells. Seven of the isolates could degrade the iron gallate complex if supplied with additional carbon in the form of yeast extract.
Alcaligenes↗
Iron supplementation.
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.
Anemia, Iron-Deficiency↗
New approaches for designing and evaluating food fortification programs.
Historically, food fortification programs were often undertaken with little attention to issues such as micronutrient bioavailability, optimal levels of addition, or efficacy or to monitoring impact on nutritional status, health, and human function. Several developments in recent years have enabled substantial progress to be made in the design and evaluation of fortification programs. The methodology for estimating the prevalence of inadequate nutrient intakes in a population and tolerable upper intake levels has been established and can be used as the basis for estimating desirable amounts of nutrient addition. More attention is being paid to assessing the bioavailability of nutrients (especially minerals) using stable and radioactive isotopes, and bioavailability of iron compounds can be estimated from changes in total body iron calculated from the ratio of transferrin receptors to serum ferritin. Procedures for quality control of the fortification process have been established. New approaches to monitoring the impact of fortification over time include assessment of liver retinol stores using retinol isotope dilution. In summary, the design and evaluation of food fortification programs now requires a series of formative research procedures on the part of nutritionists, which were not often expected or conducted in the past.
Biological Availability↗
Attitudes to prescribing iron supplements in general practice.
In response to a postal questionnaire general practitioners in the Southampton and New Forest area indicated a considerable understanding of the principles of iron prescribing and use of laboratory tests to determine iron deficiency. Many respondents, however, chose slow release and compound iron preparations as first treatments for iron deficiency. The role of parenteral iron appeared to be poorly understood. The use of and response to laboratory investigations for iron deficiency were generally appropriate, but many practitioners probably do not check for a response to oral iron sufficiently early during treatment or stop prescribing supplements before iron stores have been replenished. There is scope for further education in the biology and management of iron deficiency in general practice.
Clinical Laboratory Techniques↗
Iron balance in hemodialysis patients.
Iron deficiency is a frequent complication in chronically hemodialyzed patients because of the significant blood losses associated with this technique. Quantitating iron stores (by marrow examination or serum iron and total iron-binding capacity) on a repetitive basis had been difficult or unreliable, often resulting in failure to recognize iron deficiency superimposed on the existing anemia of chronic renal failure, or overtreating, which can lead to iron excess. Use of the serum ferritin allows easier quantitation of iron stores and, when measured serially in dialysis patients, can predict the emergence of iron deficiency. There was no correlation between serum ferritin levels and serum iron, total iron-binding capacity, or percent transferrin saturation. Iron absorption studies show that food iron absorption is physiologic, increasing when the serum ferritin is below 30 ng/ml, decreasing when more than 300 ng/ml. Treatment of iron deficiency with oral iron compounds increases serum ferritin levels and usually can maintain iron balance.
Ferritins↗
The role of vitamin C in iron absorption.
Iron requirements remain the same despite the current lower energy requirement. This means that more iron must be absorbed per unit energy. A higher bioavailability of the dietary iron can be achieved by increasing the content of food components enhancing iron absorption (ascorbic acid, meat/fish) or by decreasing the content of inhibitors (e.g., phytates, tannins). The latter is not feasible considering the recent and reasonable trend toward increasing the intake of dietary fibre. The key role of ascorbic acid for the absorption of dietary nonheme iron is generally accepted. The reasons for its action are twofold: (1) the prevention of the formation of insoluble and unabsorbable iron compounds and (2) the reduction of ferric to ferrous iron, which seems to be a requirement for the uptake of iron into the mucosal cells.
Ascorbic Acid↗
Biogeochemistry of the compost bioreactor components of a composite acid mine drainage passive remediation system.
The compost bioreactor ("anaerobic cell") components of three composite passive remediation systems constructed to treat acid mine drainage (AMD) at the former Wheal Jane tin mine, Cornwall, UK were studied over a period of 16 months. While there was some amelioration of the preprocessed AMD in each of the three compost bioreactors, as evidenced by pH increase and decrease in metal concentrations, only one of the cells showed effective removal of the two dominant heavy metals (iron and zinc) present. With two of the compost bioreactors, concentrations of soluble (ferrous) iron draining the cells were significantly greater than those entering the reactors, indicating that there was net mobilisation (by reductive dissolution) of colloidal and/or solid-phase ferric iron compounds within the cells. Soluble sulfide was also detected in waters draining all three compost bioreactors which was rapidly oxidised, in contrast to ferrous iron. Oxidation and hydrolysis of iron, together with sulfide oxidation, resulted in reacidification of processed AMD downstream of the compost bioreactors in two of the passive treatment systems. The dominant cultivatable microorganism in waters draining the compost bioreactors was identified, via analysis of its 16S rRNA gene, as a Thiomonas sp. and was capable of accelerating the dissimilatory oxidation of both ferrous iron and reduced sulfur compounds. Sulfate-reducing bacteria (SRB) were also detected, although only in the bioreactor that was performing well were these present in significant numbers. This particular compost bioreactor had been shut down for 10 months prior to the monitoring period due to operational problems. This unforeseen event appears to have allowed more successful development of AMD-tolerant and other microbial populations with critical roles in AMD bioremediation, including neutrophilic SRB (nSRB), in this compost bioreactor than in the other two, where the throughput of AMD was not interrupted. This study has revealed new insights into the operation of compost bioreactors used to remediate mine waters and has shown that, when operated under appropriate conditions, they can be highly efficient at generating alkalinity and removing metals from extremely acidic, metal-rich AMD.
Biochemistry↗
Phosphorus reduction in a shallow hypereutrophic reservoir by in-lake dosage of ferrous iron.
In Bautzen Reservoir (Germany), a technique of internally dosing iron compounds in combination with a local water column destratification was developed in order to control Microcystis blooms. In this paper, experimental results concerning the phosphorus (P) precipitation by iron application are reported. First, preliminary studies were conducted serving the choice of an appropriate precipitant. Subsequently, a whole-lake experiment was carried out. Fe2+ salts displayed a delayed oxidation and flocculation behaviour when injected into an ascending water jet. Nevertheless, the efficiency of soluble reactive phosphorus (SRP) elimination was equal to experiments with Fe3 + compounds both in laboratory and field experiments. During Fe2+ application, a large P-binding potential remained during the horizontal spreading of the treated water, since the proportion of the dissolved iron fraction near the dosage point was still high. Thus, measurements at a greater distance from the dosage point revealed higher amounts of P eliminated by Fe2+ than by Fe3+ dosage. Compared to the preceding year 1995, during the treatment periods in May-August 1996 and 1997 the SRP contents in the whole water body dropped by 72% and 54%, respectively, while the total phosphorus contents dropped by 45% at each period. We conclude that in-lake dosage of Fe2+ is an appropriate method to reduce the P loading of hypereutrophic reservoirs.
Chemical Precipitation↗
Chloroquine induces human macrophage killing of Histoplasma capsulatum by limiting the availability of intracellular iron and is therapeutic in a murine model of histoplasmosis.
We investigated the role of intracellular iron on the capacity of Histoplasma capsulatum (Hc) yeasts to multiply within human macrophages (Mphi). Coculture of Hc-infected Mphi with the iron chelator deferoxamine suppressed the growth of yeasts in a concentration-dependent manner. The effect of deferoxamine was reversed by iron-saturated transferrin (holotransferrin) but not by iron-free transferrin (apotransferrin). Chloroquine, which prevents release of iron from transferrin by raising endocytic and lysosomal pH, induced human Mphi to kill Hc. The effect of chloroquine was reversed by iron nitriloacetate, an iron compound that is soluble at neutral to alkaline pH, but not by holotransferrin, which releases iron only in an acidic environment. Chloroquine (40-120 mg/kg) given intraperitoneally for 6 d to Hc-infected C57BL/6 mice significantly reduced the growth of Hc in a dose-dependent manner. At 120 mg/kg there was a 17- and 15-fold reduction (P < 0.01) in CFU in spleens and livers, respectively. The therapeutic effect of chloroquine also correlated with the length of treatment. As little as 2 d of chloroquine therapy (120 mg/kg), when started at day 5 after infection, reduced CFU in the spleen by 50%. Treatment with chloroquine for 10 d after a lethal inoculum of Hc protected six of nine mice; all control mice were dead by day 11 (P = 0.009). This study demonstrates that: (a) iron is of critical importance to the survival and multiplication of Hc yeasts in human Mphi; (b) in vitro, chloroquine induces Mphi killing of Hc yeasts by restricting the availability of intracellular iron; and (c) in vivo, chloroquine significantly reduces the number of organisms in the spleens and livers of Hc-infected mice and can protect mice from a lethal inoculum of Hc yeasts. Thus, chloroquine may be effective in the treatment of active histoplasmosis and also may be useful in preventing relapse of histoplasmosis in patients with acquired immunodeficiency syndromes.
Animals↗
Differential loss of enzyme activity by vitC and iron containing proteins.
Our earlier studies showed that rabbit muscle phosphoglucomutase was irreversibly inactivated by exposure to a mixture of vitamin C, FeCl3 and O2. The enzyme lost about 70% of its phosphate (V.V. Desphande and J.G. Joshi, J. Biol. Chem. 260, 754-764, 1985). The present report shows that several other iron proteins can substitute for FeCl3 to a varying degree. The rate of inactivation by FeCl3 greater than ferritin greater than hemoglobin = hemerythrin greater than transferrin = ferridoxin = vitamin C. These iron compounds also produced dephosphoenzyme but did not dephosphorylate ATP, ADP, AMP or phospholipids.
Animals↗