We report the successful infusion of molten salt mixtures containing LiCl-KCl, NaCl, and NaCl-CaCl.sub.2 with UCl.sub.3 via reaction of U metal with iron chlorides (FeCl.sub.2 and FeCl.sub.3). ...Reaction in LiCl-KCl and NaCl-CaCl.sub.2 resulted in a yield of 93% and 96.7% using FeCl.sub.2 at 500 and 600 °C, respectively. Reaction to form NaCl-UCl.sub.3 at 850 °C had a yield of 70.6%. Volatilization of the oxidant may explain low yields. Reaction with the more volatile FeCl.sub.3 in NaCl-CaCl.sub.2 at 600 °C resulted in 80.7% yield. Open circuit potential measurements were made and yielded values consistent with very high selectivity for UCl.sub.3 rather than UCl.sub.4.
Prevention of iron deficiency in African children is a public health priority. Current WHO/FAO estimations of iron requirements are derived from factorial estimates based on healthy, iron-sufficient ...“model” children using data derived mainly from adults.
In this study, we aimed to quantify iron absorption, loss, and balance in apparently healthy 5- to 7-y-old children living in rural Africa.
We directly measured long-term iron absorption and iron loss in a 2-y observational study in Malawian children (n = 48) using a novel stable iron isotope method.
Of the 36 children with height-for-age and weight-for-age z scores ≥−2, 13 (36%) were iron deficient (soluble transferrin receptor >8.3 mg/L) and 23 were iron sufficient. Iron-deficient children weighed more than iron-sufficient children mean difference (95% CI): +2.1 (1.4, 2.7) kg; P = 0.01. Mean iron losses did not differ significantly between iron-deficient and iron-sufficient children and were comparable to WHO/FAO median estimates of 19 µg/(d × kg). In iron-sufficient children, median (95% CI) dietary iron absorption was 32 (28, 34) µg/(d × kg), comparable to WHO/FAO-estimated median requirements of 32 µg/(d × kg). In iron-deficient children, absorption of 28 (25, 30) µg/(d × kg) was not increased to correct their iron deficit, likely because of a lack of bioavailable dietary iron. Twelve children (25%) were undernourished (underweight, stunted, or both).
Our results suggest that WHO/FAO iron requirements are adequate for healthy iron-sufficient children in this rural area of Malawi, but iron-deficient children require additional bioavailable iron to correct their iron deficit.
Iron deficiency anemia (IDA) is the most prevalent and treatable form of anemia worldwide. The clinical management of patients with IDA requires a comprehensive understanding of the many etiologies ...that can lead to iron deficiency including pregnancy, blood loss, renal disease, heavy menstrual bleeding, inflammatory bowel disease, bariatric surgery, or extremely rare genetic disorders. The treatment landscape for many causes of IDA is currently shifting toward more abundant use of intravenous (IV) iron due to its effectiveness and improved formulations that decrease the likelihood of adverse effects. IV iron has found applications beyond treatment of IDA, and there is accruing data about its efficacy in patients with heart failure, restless leg syndrome, fatigue, and prevention of acute mountain sickness. This review provides a framework to diagnose, manage, and treat patients presenting with IDA and discusses other conditions that benefit from iron supplementation.
Healthy, term, breastfed infants usually have adequate iron stores that, together with the small amount of iron that is contributed by breast milk, make them iron sufficient until ≥6 mo of age. The ...appropriate concentration of iron in infant formula to achieve iron sufficiency is more controversial. Infants who are fed formula with varying concentrations of iron generally achieve sufficiency with iron concentrations of 2 mg/L (i.e., with iron status that is similar to that of breastfed infants at 6 mo of age). Regardless of the feeding choice, infants' capacity to regulate iron homeostasis is important but less well understood than the regulation of iron absorption in adults, which is inverse to iron status and strongly upregulated or downregulated. Infants who were given daily iron drops compared with a placebo from 4 to 6 mo of age had similar increases in hemoglobin concentrations. In addition, isotope studies have shown no difference in iron absorption between infants with high or low hemoglobin concentrations at 6 mo of age. Together, these findings suggest a lack of homeostatic regulation of iron homeostasis in young infants. However, at 9 mo of age, homeostatic regulatory capacity has developed although, to our knowledge, its extent is not known. Studies in suckling rat pups showed similar results with no capacity to regulate iron homeostasis at 10 d of age when fully nursing, but such capacity occurred at 20 d of age when pups were partially weaned. The major iron transporters in the small intestine divalent metal-ion transporter 1 (DMT1) and ferroportin were not affected by pup iron status at 10 d of age but were strongly affected by iron status at 20 d of age. Thus, mechanisms that regulate iron homeostasis are developed at the time of weaning. Overall, studies in human infants and experimental animals suggest that iron homeostasis is absent or limited early in infancy largely because of a lack of regulation of the iron transporters DMT1 and ferroportin.
Iron-sulfur (Fe/S) clusters are essential protein cofactors crucial for many cellular functions including DNA maintenance, protein translation, and energy conversion. De novo Fe/S cluster synthesis ...occurs on the mitochondrial scaffold protein ISCU and requires cysteine desulfurase NFS1, ferredoxin, frataxin, and the small factors ISD11 and ACP (acyl carrier protein). Both the mechanism of Fe/S cluster synthesis and function of ISD11-ACP are poorly understood. Here, we present crystal structures of three different NFS1-ISD11-ACP complexes with and without ISCU, and we use SAXS analyses to define the 3D architecture of the complete mitochondrial Fe/S cluster biosynthetic complex. Our structural and biochemical studies provide mechanistic insights into Fe/S cluster synthesis at the catalytic center defined by the active-site Cys of NFS1 and conserved Cys, Asp, and His residues of ISCU. We assign specific regulatory rather than catalytic roles to ISD11-ACP that link Fe/S cluster synthesis with mitochondrial lipid synthesis and cellular energy status.
Iron deficiency (ID) before the age of 3 y can lead to long-term neurological deficits despite prompt diagnosis of ID anemia (IDA) by screening of hemoglobin concentrations followed by iron ...treatment. Furthermore, pre- or nonanemic ID alters neurobehavioral function and is 3 times more common than IDA in toddlers. Given the global prevalence of ID and the enormous societal cost of developmental disabilities across the life span, better methods are needed to detect the risk of inadequate concentrations of iron for brain development (i.e., brain tissue ID) before dysfunction occurs and to monitor its amelioration after diagnosis and treatment. The current screening and treatment strategy for IDA fails to achieve this goal for 3 reasons. First, anemia is the final state in iron depletion. Thus, the developing brain is already iron deficient when IDA is diagnosed owing to the prioritization of available iron to red blood cells over all other tissues during negative iron balance in development. Second, brain ID, independently of IDA, is responsible for long-term neurological deficits. Thus, starting iron treatment after the onset of IDA is less effective than prevention. Multiple studies in humans and animal models show that post hoc treatment strategies do not reliably prevent ID-induced neurological deficits. Third, most currently used indexes of ID are population statistical cutoffs for either hematologic or iron status but are not bioindicators of brain ID and brain dysfunction in children. Furthermore, their relation to brain iron status is not known. To protect the developing brain, there is a need to generate serum measures that index brain dysfunction in the preanemic stage of ID, assess the ability of standard iron indicators to detect ID-induced brain dysfunction, and evaluate the efficacy of early iron treatment in preventing ID-induced brain dysfunction.
Cellular iron homeostasis is maintained by iron regulatory proteins 1 and 2 (IRP1 and IRP2). IRPs bind to iron-responsive elements (IREs) located in the untranslated regions of mRNAs encoding protein ...involved in iron uptake, storage, utilization and export. Over the past decade, significant progress has been made in understanding how IRPs are regulated by iron-dependent and iron-independent mechanisms and the pathological consequences of IRP2 deficiency in mice. The identification of novel IREs involved in diverse cellular pathways has revealed that the IRP–IRE network extends to processes other than iron homeostasis. A mechanistic understanding of IRP regulation will likely yield important insights into the basis of disorders of iron metabolism. This article is part of a Special Issue entitled: Cell Biology of Metals.
► IRP1 and IRP2 are the principal regulators of mammalian cellular iron homeostasis. ► IRPs bind to iron-responsive elements (IREs) located in the untranslated regions of mRNAs involved in iron uptake, storage, utilization and export. ► IRPs are post-translationally regulated by iron and reactive oxygen and nitrogen species. ► The identification of novel IREs reveals the presence of an expanded IRP–IRE network beyond cellular iron homeostasis. ► IRP deficiency in mice disrupts iron homeostasis and leads to hematological, neurodegenerative and metabolic disorders.
Iron deficiency is the most prevalent nutritional deficiency, affecting more than 30% of the total world's population. It is a major public health problem in many countries around the world. Over the ...years various methods have been used with an effort to try and control iron-deficiency anemia. However, there has only been a marginal reduction in the global prevalence of anemia. Why is this so? Iron and zinc are essential trace elements for humans. These metals influence the transport and absorption of one another across the enterocytes and hepatocytes, due to similar ionic properties. This paper describes the structure and roles of major iron and zinc transport proteins, clarifies iron-zinc interactions at these sites, and provides a model for the mechanism of these interactions both at the local and systemic level. This review provides evidence that much of the massive extent of iron deficiency anemia in the world may be due to an underlying deficiency of zinc. It explains the reasons for predominance of cellular zinc status in determination of iron/zinc interactions and for the first time thoroughly explains mechanisms by which zinc brings about these changes.
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