SciCombinator

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Concept: Iron deficiency

137

There has been no evidence for the necessity of endoscopy in asymptomatic young men with iron deficiency anemia (IDA). To determine whether endoscopy should be recommended in asymptomatic young men with IDA, we compared the prevalence of gastrointestinal (GI) lesions between young men (< 50 years) with IDA and those without IDA.

Concepts: Hematology, Serum iron, Iron deficiency, Iron, Human iron metabolism, Transferrin, Hemoglobin, Iron deficiency anemia

33

Iron deficiency is a common complication in patients with IBD and oral iron therapy is suggested to exacerbate IBD symptoms. We performed an open-labelled clinical trial to compare the effects of per oral (PO) versus intravenous (IV) iron replacement therapy (IRT).

Concepts: Medical terms, ClinicalTrials.gov, Clinical trial, Effectiveness, Iron deficiency, Iron, Gut flora, Iron supplements

28

The iron regulatory hormone hepcidin responds to both oral and parenteral iron. Here, we hypothesized that the diverse iron trafficking routes may affect the dynamics and kinetics of the hepcidin activation pathway. To address this, C57BL/6 mice were administered an iron-enriched diet or injected i.p. with iron dextran and analyzed over time. After 1 week of dietary loading with carbonyl iron, mice exhibited significant increases in serum iron and transferrin saturation, as well as in hepatic iron, Smad1/5/8 phosphorylation and bone morphogenetic protein 6 (BMP6), and hepcidin mRNAs. Nevertheless, hepcidin expression reached a plateau afterward, possibly due to upregulation of inhibitory Smad7, Id1, and matriptase-2 mRNAs, while hepatic and splenic iron continued to accumulate over 9 weeks. One day following parenteral administration of iron dextran, mice manifested elevated serum and hepatic iron levels and Smad1/5/8 phosphorylation, but no increases in transferrin saturation or BMP6 mRNA. Surprisingly, hepcidin failed to appropriately respond to acute overload with iron dextran, and a delayed (after 5-7 days) hepcidin upregulation correlated with increased transferrin saturation, partial relocation of iron from macrophages to hepatocytes, and induction of BMP6 mRNA. Our data suggest that the physiological hepcidin response is saturable and are consistent with the idea that hepcidin senses exclusively iron compartmentalized within circulating transferrin and/or hepatocytes.

Concepts: Human iron metabolism, Protein, Iron deficiency anemia, Serum iron, Iron metabolism, Iron deficiency, Transferrin, Iron

28

Ferroportin exports iron into plasma from absorptive enterocytes, erythrophagocytosing macrophages, and hepatic stores. The hormone hepcidin controls cellular iron export and plasma iron concentrations by binding to ferroportin and causing its internalization and degradation. We explored the mechanism of hepcidin-induced endocytosis of ferroportin, the key molecular event in systemic iron homeostasis. Hepcidin binding caused rapid ubiquitination of ferroportin in cell lines overexpressing ferroportin and in murine bone marrow-derived macrophages. No hepcidin-dependent ubiquitination was observed in C326S ferroportin mutant which does not bind hepcidin. Substitutions of lysines between residues 229 and 269 in the third cytoplasmic loop of ferroportin prevented hepcidin-dependent ubiquitination and endocytosis of ferroportin, and promoted cellular iron export even in the presence of hepcidin. The human ferroportin mutation K240E, previously associated with clinical iron overload, caused hepcidin resistance in vitro by interfering with ferroportin ubiquitination. Our study demonstrates that ubiquitination is the functionally relevant signal for hepcidin-induced ferroportin endocytosis.

Concepts: Iron deficiency anemia, Iron deficiency, Hepcidin, Ferroportin, Hematology, Cell, Iron metabolism, Human iron metabolism

26

Background: Studies on benefits of intravenous iron therapy among hemodialysis patients with functional iron deficiency anemia have shown conflicting results. We conducted a meta-analysis to assess the efficacy and safety of intravenous iron in this subset of patients. Methods: We searched MEDLINE (through December 2012), the Cochrane Central Register of Controlled Trials and ClinicalTrials.gov for single-arm studies and randomized controlled trials (RCT) that examined the effect of intravenous iron for functional iron deficiency anemia in hemodialysis patients on anemia parameters and markers of oxidative stress and inflammation. Studies of absolute iron deficiency were excluded. Random-effect model meta-analyses were used to compute changes in outcomes of interest. Results: We identified 34 studies (2,658 patients), representing 24 single-arm studies, and 10 parallel-arm RCT. In the analyses of the study arms, intravenous iron therapy resulted in a significant increase in hemoglobin, serum ferritin, transferrin saturation rate, serum iron, reticulocyte hemoglobin content as well as a significant decrease in the percentage of hypochromic erythrocytes and erythropoietin dose. There were significant increases in plasma malonyldialdehyde level and thiobarbituric acid-reactive substances, and a decrease in neutrophil respiratory burst. The analyses of the RCT revealed less robust net changes in these parameters, and there was no increased risk of adverse events including infections, cardiac events and mortality. Conclusions: Intravenous iron therapy for functional iron deficiency anemia in hemodialysis patients improves anemia parameters but exerts some effects on markers of oxidative stress that are of unclear clinical significance. The long-term safety and efficacy of this treatment strategy requires further study. © 2014 S. Karger AG, Basel.

Concepts: Iron deficiency, Serum iron, Iron, Randomized controlled trial, Transferrin, Hemoglobin, Anemia, Iron deficiency anemia

18

Hearing loss in the US adult population is linked to hospitalization, poorer self-reported health, hypertension, diabetes, and tobacco use. Because iron deficiency anemia (IDA) is a common and easily correctable condition, further understanding of the association between IDA and all types of hearing loss in a population of US adults may help to open new possibilities for early identification and appropriate treatment.

Concepts: Biology, Serum iron, Iron deficiency, Iron, Human iron metabolism, Transferrin, Hemoglobin, Iron deficiency anemia

18

Iron is a functional component of oxygen transport and energy production in humans and therefore is a critically important micronutrient for sport and exercise performance. Athletes, particularly female athletes participating in endurance sport, are at increased risk of compromised iron status due to heightened iron losses through menstruation and exercise-induced mechanisms associated with endurance activity. Conventionally oral iron supplementation is used in prevention or/and treatment of iron deficiency. However, this approach has been criticised because of the side effects and increased risk of iron toxicity associated with the use of supplements. Thus, more recently there has been a growing interest in using dietary modification rather than the use of supplements to improve iron status of athletes. Dietary iron treatment methods include the prescription of an iron-rich diet, or/and haem iron-based diet, dietary advice counselling and inclusion of novel iron-rich products into the daily diet. Although studies using dietary modification are still scarce, current literature suggests that dietary iron interventions can assist in maintaining iron status in female athletes, especially during intensive training and competition. Future research should focus on the most efficient method(s) of dietary modification for improvement of iron status and whether these approaches can have a favourable impact on sports and exercise performance.

Concepts: Improve, Iron deficiency, Hemoglobin, Human iron metabolism, Iron, Heme, Iron supplements, Human

17

To investigate the influence of daily oral iron supplementation on changes in hemoglobin mass (Hbmass) and iron parameters after 2-4 weeks of moderate altitude exposure.

Concepts: Parameter, Iron deficiency, Iron, Anemia, Iron deficiency anemia, Iron supplements, Ferritin

15

Regulation of iron metabolism and innate immunity are tightly interlinked. The acute phase response to infection and inflammation induces alterations in iron homeostasis that reduce iron supplies to pathogens. The iron-hormone hepcidin is activated by such stimuli causing degradation of the iron exporter ferroportin and reduced iron release from macrophages, suggesting that hepcidin is the crucial effector of inflammatory hypoferremia. Here we report the discovery of an acute inflammatory condition that is mediated by Toll-like receptor (TLR) 2 and TLR6 and which induces hypoferremia in mice injected with TLR ligands. Stimulation of TLR2/TLR6 triggers profound decreases in ferroportin mRNA and protein expression in bone marrow-derived macrophages, liver and spleen of mice without changing hepcidin expression. Furthermore, C326S ferroportin mutant mice with a disrupted hepcidin/ferroportin regulatory circuitry respond to injection of the TLR2/6 ligands FSL1 or PAM3CSK4 by ferroportin down regulation and a reduction of serum iron levels. Our findings challenge the prevailing role of hepcidin in hypoferremia and suggest that rapid hepcidin-independent ferroportin down regulation in the major sites of iron recycling may represent a first line response to restrict iron access for numerous pathogens.

Concepts: Hepcidin, Ferroportin, Iron deficiency anemia, Iron metabolism, Iron deficiency, Iron, Human iron metabolism, Immune system

12

The prevalence of iron deficiency (ID) among non-pregnant, reproductive-age US women significantly exceeds rates among males. In clinical practice ID screening relies on hemoglobin, a late-stage indicator of ID. As a single, low-cost laboratory test to diagnose ID before anemia develops is lacking, the study objective was to improve ID screening by identifying risk factors among non-anemic, iron-deficient reproductive age women.

Concepts: Medical statistics, Transferrin, Female, Heme, Iron deficiency, Iron, Hemoglobin, Iron deficiency anemia