Negative iron balance

The selectivity of DFO for iron(ffl) compared with that of DTPA is much greater. The remarkable selectivity of DFO for iron(III) is one of the reasons for its relatively low toxicity. However, even with a selective chelator for iron(III), 

Iron should be coordinated by the chelate in such a manner as to prevent direct access of oxygen and hydrogen peroxide. If this is achieved, then hydroxyl-radical production will be reduced to a minimum. Some iron complexes, for instance ethylenediamine tetra-acetic acid (EDTA) (Fig. 3a), generate hydroxyl radicals efficiently while others such as DFO and the hydroxypyridinones (Fig. 3b) do not. By designing chelators that produce extremely stable complexes, the generation of hydroxyl radicals is further minimized. Such stable complex formation would also reduce the tendency for iron redistribution within the body. 

The membrane permeabilities of the free and complexed ligands also have important implications for their toxicity the lipid solubilities of the iron-free ligand affect the permeability of the blood-brain barrier and may cause CNS toxicity, while the relative solubilities of the free and complexed chelators affect body iron redistribution. 

Further therapeutic benefit can be gained by ensuring that the chelating agent is delivered to target sites at an appropriate concentration, rate and duration. Ideally for maximal chelation, a drug must be present within the body at both a reasonable concentration and length of time to ensure interception of iron from either extracellular or intracellular iron pools. Compounds with short plasma half lives are thus likely to be less effective due to the limited pool of chelatable iron present within the body at any one time. 

Other classes of chelators which have been extensively evaluated as orally active alternatives to DFO are described in the following subsections. 

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Iron is stored in intestinal mucosal cells as ferritin (an iron/protein complex) until needed by the body. Iron deficiency results from acute or chronic blood loss, from insufficient intake during periods of accelerated growth in children, or in heavily menstruating or pregnant women. Therefore it essentially results from a negative iron balance due to depletion of iron stores and inadequate intake, culminating in hypochromic microcytic anemia. Supplementation with ferrous sulfate is required to correct the deficiency. Gastrointestinal disturbances caused by local irritation are the most common adverse effects caused by iron supplements. 

There are several inherited diseases which are associated with the gradual excess accumulation of iron via the gut. Hereditary haemochromatosis is a relatively rare condition in which iron absorption is increased through an unidentified mechanism. This condition usually presents in the fourth or fifth decade of life with the secondary effects of iron overload such as heart failure, liver cirrhosis or sugar diabetes. As the production of red cells is unaffected, the excess iron can be removed slowly by venesecting a unit of blood every week for up to two years. However, in the acute situation, iron chelation may be used to remove toxic low-molecular-weight iron until sufficient negative iron balance has been obtained by venesection. 

Biliary excretion of copper and iron is important. Major losses of iron can be caused by internal bleeding. Thus women during their menstrual periods will be in negative iron balance unless proper nutrition is observed. Blood loss via the gastrointestinal tract, as in ulcers or some forms of cancer, leads quickly to loss of utilizable or stored iron. ... 

Menstrual loss is about 30 mg. period menstruating women may therefore be in negative iron balance. 

The paramount aim of treatment is to reach a negative iron balance. This must be achieved before complications due to the chronic iron overload have their effect on the predisposed organs. The extreme uncontrolled increase in iron absorption is treatable by adjuvant measures, albeit with limited success. 

Before treatment is initiated, the cause of the negative iron balance must be established. Treatment should correct the underlying cause of anemia and improve the iron balance. In general, oral therapy with ferrous salts is... 

Iron deficiency results from prolonged negative iron balance or failure to meet increased physiologic iron need. The speed of iron deficiency development depends on an individuals initial iron stores and balance between iron absorption and loss. Multiple etiologic factors are usually involved. 

The iron-binding agent, 54 inducing a negative iron balance (Breithaupt et al. 1986) also chelated AP . It relieved the inhibitory action of aluminium on parathyroid cells and osteoblasts (Rapoport et al. 1987). However, Cournot-Witmer and Pla-CHOT (1990) showed that in the parathyroid glands of aluminium-intoxicated patients the presence of aluminium deposits neither induced cellular damage or chief cell necrosis nor interfered with the production of parathyroid hormone. In normal... 

Utilization of iron was not affected at levels of 9 to 26g bran/day from corn or wheat (19, 2J0 2 ) or bY 16 g of bran/day (25). Negative balances were observed by Morris and Ellis (21) during the first balance period with daily intakes of 36g bran but not during the second 5-day balance period. However, Simpson et al. (24) found a marked inhibition of non-heme iron absorption from a single test meal which included 6 g of wheat bran. With a diet which provided 35g/day of NDF (neutral detergent fiber from bran bread), iron balances were decreased (26) compared to the 9 or 22g/day intake levels. 

Kelsay and co-workers (27,28) observed no effects on iron balance of including 24g/day of NDF from fruits and vegetables however, negative zinc and copper balances were observed. In a second study (29), lower zinc, but not copper, balances were observed at intakes of 25g NDF/day lower intakes (10, 18g NDF) had no effect. In these studies, the effects of oxalates (from spinach) may have affected mineral balances. In a third study, a combination of consuming spinach every other day plus a daily fiber intake of 26g NDF resulted in increased fecal zinc excretion and negative balances (22) ... 

Negative nitrogen balance may occur in blind people, and the serum protein concentration may be reduced. The serum cholesterol is frequently increased, and bilirubin concentration may also exceed the upper limit of normal. The diurnal variation of serum iron is often lost. 

The unit positive charge on the proton balances the unit negative charge on the electron. In neutral atoms, the number of electrons is exactly equal to the number of protons. In an iron atom (Fe ), there are 26 electrons and just 26 protons. A cation is formed by removing electrons not by adding protons. An ion has one electron less than the neutral atom M . Similarly, an anion M" is formed by adding an electron and not by subtracting a proton from M°. 

Meat products have to be stabilised in some cases, as meat lipids contain no natural antioxidants or only traces of tocopherols. Most muscle foods contain, however, an efficient multi-component antioxidant defence system based on enzymes, but the balance changes adversely on storage. The denaturation of muscle proteins is the main cause of the inbalance as iron may be released from its complexes, catalysing the lipid oxidation. Salting contributes to the negative effects of storage, as it enhances oxidation. Using encapsulated salt eliminates the deleterious effect of sodium chloride. 

Catalytic oxidative dehydrogenation of propane by N20 (ODHP) over Fe-zeolite catalysts represents a potential process for simultaneous functionalization of propane and utilization of N20 waste as an environmentally harmful gas. The assumed structure of highly active Fe-species is presented by iron ions balanced by negative framework charge, mostly populated at low Fe loadings. These isolated Fe sites are able to stabilize the atomic oxygen and prevent its recombination to a molecular form, and facilitate its transfer to a paraffin molecule [1], A major drawback of iron zeolites in ODHP with N20 is their deactivation by accumulated coke, leading to a rapid decrease of the propylene yield. 

The negative sign refers to mineral precipitation instead of dissolution. Such computations are done with PHREEQC (Parkhurst Appelo 1999). An inescapable conclusion of mass balances is that during the weathering of pyritiferous hydrothermally altered rock, iron and silica are precipitated. 

On the mixed electrode of metallic iron immersed in acidic solutions, the anodic and cathodic charge transfer reactions (the anodic transfer of iron ions and the cathodic transfer of electrons) proceed across the electrode interface, at which the anodic ciurent (the positive charge current) is exactly balanced with the cathodic current (the negative charge current) producing thereby zero net current. 

Samples 6 and 7 in table 5.32 are from the Zabargad peridotite (Red Sea) and are representative of the chemistry of upper mantle pyroxenes (Bonatti et al., 1986). The absence of Fe203 in these samples is due to the fact that microprobe analyses do not discriminate the oxidation state of iron, which is thus always expressed as FeO. It must be noted here that the observed stoichiometry (based on four oxygen ions) is quite consistent with the theoretical formula and that no Fe is required to balance the negative charges of oxygen. 

It was first assumed that an inhibitor was produced as a by-product. However, the accuracy with which the initiation rates had to be balanced seemed to demand too great a coincidence if the inhibitor production occurred in a side reaction independent of the initiation reactions. Thus, although possible products which were demonstrably powerful inhibitors of the co-oxidation reaction—e.g., thiolsulfinates—could be postulated, this mechanism was unsatisfactory and did not fully explain the role of iron. Furthermore, diphenyl disulfide, which is a precursor of thiolsul-finate in the presence of hydroperoxide, did not inhibit the reaction. The possibility that the negative term represented a diminishing contribution from a radical-producing process was then studied. 

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