Effect of Iron Availability on Induction of Systemic Resistance to Fusarium Wilt of Chickpea by Pseudomonas spp.

PubMed Central

Saikia, Ratul; Srivastava, Alok K.; Singh, Kiran; Lee, Min-Woong

2005-01-01

Selected isolates of Pseudomonas fluorescens (Pf4-92 and PfRsC5) and P. aeruginosa (PaRsG18 and PaRsG27) were examined for growth promotion and induced systemic resistance against Fusarium wilt of chickpea. Significant increase in plant height was observed in Pseudomonas treated plants. However, plant growth was inhibited when isolates of Pseudomonas were used in combination with Fusarium oxysporum f. sp. ciceri (FocRs1). It was also observed that the Pseudomonas spp. was colonized in root of chickpea and significantly suppressed the disease in greenhouse condition. Rock wool bioassay technique was used to study the effect of iron availability on the induction of systemic resistance to Fusarium wilt of chickpea mediated by the Pseudomonas spp. All the isolates of Pseudomonas spp. showed greater disease control in the induced systemic resistance (ISR) bioassay when iron availability in the nutrient solution was low. High performance liquid chromatography (HPLC) analysis indicated that all the bacterial isolates produced more salicylic acid (SA) at low iron (10µM EDDHA) than high iron availability (10µFe3+ EDDHA). Except PaRsG27, all the three isolates produced more pseudobactin at low iron than high iron availability. PMID:24049472

Process to Produce Iron Nanoparticle Lunar Dust Simulant Composite

NASA Technical Reports Server (NTRS)

Hung, Ching-cheh; McNatt, Jeremiah

2010-01-01

A document discusses a method for producing nanophase iron lunar dust composite simulant by heating a mixture of carbon black and current lunar simulant types (mixed oxide including iron oxide) at a high temperature to reduce ionic iron into elemental iron. The product is a chemically modified lunar simulant that can be attracted by a magnet, and has a surface layer with an iron concentration that is increased during the reaction. The iron was found to be -iron and Fe3O4 nanoparticles. The simulant produced with this method contains iron nanoparticles not available previously, and they are stable in ambient air. These nanoparticles can be mass-produced simply.

Comparative metatranscriptomics identifies molecular bases for the physiological responses of phytoplankton to varying iron availability.

PubMed

Marchetti, Adrian; Schruth, David M; Durkin, Colleen A; Parker, Micaela S; Kodner, Robin B; Berthiaume, Chris T; Morales, Rhonda; Allen, Andrew E; Armbrust, E Virginia

2012-02-07

In vast expanses of the oceans, growth of large phytoplankton such as diatoms is limited by iron availability. Diatoms respond almost immediately to the delivery of iron and rapidly compose the majority of phytoplankton biomass. The molecular bases underlying the subsistence of diatoms in iron-poor waters and the plankton community dynamics that follow iron resupply remain largely unknown. Here we use comparative metatranscriptomics to identify changes in gene expression associated with iron-stimulated growth of diatoms and other eukaryotic plankton. A microcosm iron-enrichment experiment using mixed-layer waters from the northeastern Pacific Ocean resulted in increased proportions of diatom transcripts and reduced proportions of transcripts from most other taxa within 98 h after iron addition. Hundreds of diatom genes were differentially expressed in the iron-enriched community compared with the iron-limited community; transcripts of diatom genes required for synthesis of photosynthesis and chlorophyll components, nitrate assimilation and the urea cycle, and synthesis of carbohydrate storage compounds were significantly overrepresented. Transcripts of genes encoding rhodopsins in eukaryotic phytoplankton were significantly underrepresented following iron enrichment, suggesting rhodopsins help cells cope with low-iron conditions. Oceanic diatoms appear to display a distinctive transcriptional response to iron enrichment that allows chemical reduction of available nitrogen and carbon sources along with a continued dependence on iron-free photosynthetic proteins rather than substituting for iron-containing functional equivalents present within their gene repertoire. This ability of diatoms to divert their newly acquired iron toward nitrate assimilation may underlie why diatoms consistently dominate iron enrichments in high-nitrate, low-chlorophyll regions.

Influence of iron availability on nutrient consumption ratio of diatoms in oceanic waters

NASA Astrophysics Data System (ADS)

Takeda, Shigenobu

1998-06-01

The major nutrients (nitrate, phosphate and silicate) needed for phytoplankton growth are abundant in the surface waters of the subarctic Pacific, equatorial Pacific and Southern oceans, but this growth is limited by the availability of iron. Under iron-deficient conditions, phytoplankton exhibit reduced uptake of nitrate and lower cellular levels of carbon, nitrogen and phosphorus. Here I describe seawater and culture experiments which show that iron limitation can also affect the ratio of consumed silicate to nitrate and phosphate. In iron-limited waters from all three of the aforementioned environments, addition of iron to phytoplankton assemblages in incubation bottles halved the silicate:nitrate and silicate:phosphate consumption ratios, in spite of the preferential growth of diatoms (silica-shelled phytoplankton). The nutrient consumption ratios of the phytoplankton assemblage from the Southern Ocean were similar to those of an iron-deficient laboratory culture of Antarctic diatoms, which exhibit increased cellular silicon or decreased cellular nitrogen and phosphorus in response to iron limitation. Iron limitation therefore increases the export of biogenic silicon, relative to nitrogen and phosphorus, from the surface to deeper waters. These findings suggest how the sedimentary records of carbon and silicon deposition in the glacial Southern Ocean can be consistent with the idea that changes in productivity, and thus in drawdown of atmospheric CO2, during the last glaciation were stimulated by changes in iron inputs from atmospheric dust.

Oral exposure to polystyrene nanoparticles affects iron absorption

NASA Astrophysics Data System (ADS)

Mahler, Gretchen J.; Esch, Mandy B.; Tako, Elad; Southard, Teresa L.; Archer, Shivaun D.; Glahn, Raymond P.; Shuler, Michael L.

2012-04-01

The use of engineered nanoparticles in food and pharmaceuticals is expected to increase, but the impact of chronic oral exposure to nanoparticles on human health remains unknown. Here, we show that chronic and acute oral exposure to polystyrene nanoparticles can influence iron uptake and iron transport in an in vitro model of the intestinal epithelium and an in vivo chicken intestinal loop model. Intestinal cells that are exposed to high doses of nanoparticles showed increased iron transport due to nanoparticle disruption of the cell membrane. Chickens acutely exposed to carboxylated particles (50 nm in diameter) had a lower iron absorption than unexposed or chronically exposed birds. Chronic exposure caused remodelling of the intestinal villi, which increased the surface area available for iron absorption. The agreement between the in vitro and in vivo results suggests that our in vitro intestinal epithelium model is potentially useful for toxicology studies.

Iron deficiency anemia in patients with inflammatory bowel disease

PubMed Central

Goldberg, Neil D

2013-01-01

Iron deficiency anemia is the most common form of anemia worldwide, caused by poor iron intake, chronic blood loss, or impaired absorption. Patients with inflammatory bowel disease (IBD) are increasingly likely to have iron deficiency anemia, with an estimated prevalence of 36%–76%. Detection of iron deficiency is problematic as outward signs and symptoms are not always present. Iron deficiency can have a significant impact on a patient’s quality of life, necessitating prompt management and treatment. Effective treatment includes identifying and treating the underlying cause and initiating iron replacement therapy with either oral or intravenous iron. Numerous formulations for oral iron are available, with ferrous fumarate, sulfate, and gluconate being the most commonly prescribed. Available intravenous formulations include iron dextran, iron sucrose, ferric gluconate, and ferumoxytol. Low-molecular weight iron dextran and iron sucrose have been shown to be safe, efficacious, and effective in a host of gastrointestinal disorders. Ferumoxytol is the newest US Food and Drug Administration-approved intravenous iron therapy, indicated for iron deficiency anemia in adults with chronic kidney disease. Ferumoxytol is also being investigated in Phase 3 studies for the treatment of iron deficiency anemia in patients without chronic kidney disease, including subgroups with IBD. A review of the efficacy and safety of iron replacement in IBD, therapeutic considerations, and recommendations for the practicing gastroenterologist are presented. PMID:23766655

Tucum-Do-Cerrado (Bactris setosa Mart.) Consumption Modulates Iron Homeostasis and Prevents Iron-Induced Oxidative Stress in the Rat Liver

PubMed Central

Fustinoni-Reis, Adriana M.; Arruda, Sandra F.; Dourado, Lívia P. S.; da Cunha, Marcela S. B.; Siqueira, Egle M. A.

2016-01-01

This study investigated the effect of tucum-do-cerrado consumption in the oxidative status of iron-supplemented rats. Four groups of rats were treated: Control (AIN-93G), Tuc (AIN-93G added of tucum-do-cerrado), Fe (AIN-93G iron-enriched), or TucFe (AIN-93G with tucum-do-cerrado and iron-enriched) diet, for 30 days. Iron-enriched diet increased serum, liver, spleen, and intestine iron levels; transferrin saturation; liver lipid oxidation; mRNA levels of hepatic Hamp and Bmp6, and Nrf2 in the intestine. Tucum-do-cerrado consumption reduced spleen lipid and protein oxidation; mRNA levels of hepatic Hamp and Ftl, and increased serum antioxidant capacity and hepatic mRNA levels of Bmp6, Hmox1, Nqo1, and Nrf2. TucFe diet consumption abrogated the liver Hamp iron-induced up-regulation, prevented intestinal iron accumulation; hepatic lipid peroxidation; splenic protein damage, and the increase of catalase, glutathione reductase, and glutathione peroxidase activity in some tissues. These results suggest that tucum-do-cerrado protects tissues against oxidative damage, by reducing iron availability in liver and consequently inhibiting liver Hamp expression. PMID:26901220

National Trauma Institute: A National Coordinating Center for Trauma Research Funding

DTIC Science & Technology

2012-10-28

and why anemia does not resolve. Hepcidin, a peptide made in the liver, has recently been identified as the key regulator of iron homeostasis, and...plays a major role in how and why anemia develops. Hepcidin reduces iron availability by: (1) decreased iron absorption across the intestine and (2... iron deficiency . Hepcidin is Page | 11 increased in states of inflammation, and likely plays an important role in the acute inflammation that

Physiology and Pathophysiology of Iron in Hemoglobin-Associated Diseases

PubMed Central

Coates, Thomas D

2016-01-01

Iron overload and iron toxicity, whether because of increased absorption or iron loading from repeated transfusions, can be major causes of morbidity and mortality in a number of chronic anemias. Significant advances have been made in our understanding of iron homeostasis over the past decade. At the same time, advances in magnetic resonance imaging have allowed clinicians to monitor and quantify iron concentrations non-invasively in specific organs. Furthermore, effective iron chelators are now available, including preparations that can be taken orally. This has resulted in substantial improvement in mortality and morbidity for patients with severe chronic iron overload. This paper reviews the key points of iron homeostasis and attempts to place clinical observations in patients with transfusional iron overload in context with the current understanding of iron homeostasis in humans. PMID:24726864

Red blood cell and iron metabolism during space flight

NASA Technical Reports Server (NTRS)

Smith, Scott M.

2002-01-01

Space flight anemia is a widely recognized phenomenon in astronauts. Reduction in circulating red blood cells and plasma volume results in a 10% to 15% decrement in circulatory volume. This effect appears to be a normal physiologic adaptation to weightlessness and results from the removal of newly released blood cells from the circulation. Iron availability increases, and (in the few subjects studied) iron stores increase during long-duration space flight. The consequences of these changes are not fully understood.

Nitrosothiol formation and protection against Fenton chemistry by nitric oxide-induced dinitrosyliron complex formation from anoxia-initiated cellular chelatable iron increase.

PubMed

Li, Qian; Li, Chuanyu; Mahtani, Harry K; Du, Jian; Patel, Aashka R; Lancaster, Jack R

2014-07-18

Dinitrosyliron complexes (DNIC) have been found in a variety of pathological settings associated with (•)NO. However, the iron source of cellular DNIC is unknown. Previous studies on this question using prolonged (•)NO exposure could be misleading due to the movement of intracellular iron among different sources. We here report that brief (•)NO exposure results in only barely detectable DNIC, but levels increase dramatically after 1-2 h of anoxia. This increase is similar quantitatively and temporally with increases in the chelatable iron, and brief (•)NO treatment prevents detection of this anoxia-induced increased chelatable iron by deferoxamine. DNIC formation is so rapid that it is limited by the availability of (•)NO and chelatable iron. We utilize this ability to selectively manipulate cellular chelatable iron levels and provide evidence for two cellular functions of endogenous DNIC formation, protection against anoxia-induced reactive oxygen chemistry from the Fenton reaction and formation by transnitrosation of protein nitrosothiols (RSNO). The levels of RSNO under these high chelatable iron levels are comparable with DNIC levels and suggest that under these conditions, both DNIC and RSNO are the most abundant cellular adducts of (•)NO. © 2014 by The American Society for Biochemistry and Molecular Biology, Inc.

Nitrosothiol Formation and Protection against Fenton Chemistry by Nitric Oxide-induced Dinitrosyliron Complex Formation from Anoxia-initiated Cellular Chelatable Iron Increase*

PubMed Central

Li, Qian; Li, Chuanyu; Mahtani, Harry K.; Du, Jian; Patel, Aashka R.; Lancaster, Jack R.

2014-01-01

Dinitrosyliron complexes (DNIC) have been found in a variety of pathological settings associated with •NO. However, the iron source of cellular DNIC is unknown. Previous studies on this question using prolonged •NO exposure could be misleading due to the movement of intracellular iron among different sources. We here report that brief •NO exposure results in only barely detectable DNIC, but levels increase dramatically after 1–2 h of anoxia. This increase is similar quantitatively and temporally with increases in the chelatable iron, and brief •NO treatment prevents detection of this anoxia-induced increased chelatable iron by deferoxamine. DNIC formation is so rapid that it is limited by the availability of •NO and chelatable iron. We utilize this ability to selectively manipulate cellular chelatable iron levels and provide evidence for two cellular functions of endogenous DNIC formation, protection against anoxia-induced reactive oxygen chemistry from the Fenton reaction and formation by transnitrosation of protein nitrosothiols (RSNO). The levels of RSNO under these high chelatable iron levels are comparable with DNIC levels and suggest that under these conditions, both DNIC and RSNO are the most abundant cellular adducts of •NO. PMID:24891512

Saccharides enhance iron bioavailability to Southern Ocean phytoplankton

PubMed Central

Hassler, Christel S.; Nichols, Carol Mancuso; Butler, Edward C. V.; Boyd, Philip W.

2011-01-01

Iron limits primary productivity in vast regions of the ocean. Given that marine phytoplankton contribute up to 40% of global biological carbon fixation, it is important to understand what parameters control the availability of iron (iron bioavailability) to these organisms. Most studies on iron bioavailability have focused on the role of siderophores; however, eukaryotic phytoplankton do not produce or release siderophores. Here, we report on the pivotal role of saccharides—which may act like an organic ligand—in enhancing iron bioavailability to a Southern Ocean cultured diatom, a prymnesiophyte, as well as to natural populations of eukaryotic phytoplankton. Addition of a monosaccharide (>2 nM of glucuronic acid, GLU) to natural planktonic assemblages from both the polar front and subantarctic zones resulted in an increase in iron bioavailability for eukaryotic phytoplankton, relative to bacterioplankton. The enhanced iron bioavailability observed for several groups of eukaryotic phytoplankton (i.e., cultured and natural populations) using three saccharides, suggests it is a common phenomenon. Increased iron bioavailability resulted from the combination of saccharides forming highly bioavailable organic associations with iron and increasing iron solubility, mainly as colloidal iron. As saccharides are ubiquitous, present at nanomolar to micromolar concentrations, and produced by biota in surface waters, they also satisfy the prerequisites to be important constituents of the poorly defined “ligand soup,” known to weakly bind iron. Our findings point to an additional type of organic ligand, controlling iron bioavailability to eukaryotic phytoplankton—a key unknown in iron biogeochemistry. PMID:21169217

Iron availability, nitrate uptake, and exportable new production in the subarctic Pacific. [phytoplankton population growth support and atmospheric CO2 removal

NASA Technical Reports Server (NTRS)

Banse, Karl

1991-01-01

This paper presents a critique of experimental data and papers by Martin et al. (1989, 1990), who suggested that the phytoplankton growth is iron-limited and that, small additions of iron to large subarctic ocean areas might be a way of removing significant amounts of atmospheric CO2 by increasing phytoplancton growth. Data are presented to show that, in the summer of 1987, the phytoplankton assemblage as a whole was not iron limited, as measured by the bulk removal of nitrate or by the increase of chlorophyll. It is suggested that grazing normally prevents the phytoplankton from reaching concentrations that reduce the iron (and nitrate) to levels that depress division rates drastically.

National Trauma Institute: A National Coordinating Center for Trauma Research Funding

DTIC Science & Technology

2013-10-01

identified as the key regulator of iron homeostasis, and plays a major role in how and why anemia develops. Hepcidin reduces iron availability by: (1...cells. High levels of hepcidin induce a state of functional iron deficiency . Hepcidin is increased in states of inflammation, and likely plays an...elevated in trauma, this will confirm that inability to use iron stores is key to the anemia of trauma. Dr Napolitano suspects that hepcidin will be

Increased iron availability resulting from increased CO2 enhances carbon and nitrogen metabolism in the economical marine red macroalga Pyropia haitanensis (Rhodophyta).

PubMed

Chen, Binbin; Zou, Dinghui; Yang, Yufeng

2017-04-01

Ocean acidification caused by rising CO 2 is predicted to increase the concentrations of dissolved species of Fe(II) and Fe(III), leading to the enhanced photosynthetic carbon sequestration in some algal species. In this study, the carbon and nitrogen metabolism in responses to increased iron availability under two CO 2 levels (390 μL L -1 and 1000 μL L -1 ), were investigated in the maricultivated macroalga Pyropia haitanensis (Rhodophyta). The results showed that, elevated CO 2 increased soluble carbonhydrate (SC) contents, resulting from enhanced photosynthesis and photosynthetic pigment synthesis in this algae, but declined its soluble protein (SP) contents, resulting in increased ratio of SC/SP. This enhanced photosynthesis performance and carbon accumulation was more significant under iron enrichment condition in seawater, with higher iron uptake rate at high CO 2 level. As a key essential biogenic element for algae, Fe-replete functionally contributed to P. haitanensis photosynthesis. Increased SC fundamentally provided carbon skeletons for nitrogen assimilation. The significant increase of carbon and nitrogen assimilation finally contributed to enhanced growth in this alga. This was also intuitively reflected by respiration that provided energy for cellular metabolism and algal growth. We propose that, in the predicted scenario of rising atmospheric CO 2 , P. haitanensis is capable to adjust its physiology by increasing its carbon and nitrogen metabolism to acclimate the acidified seawater, at the background of global climate change and simultaneously increased iron concentration due to decreased pH levels. Copyright © 2017 Elsevier Ltd. All rights reserved.

Growth of Aerobic Ripening Bacteria at the Cheese Surface Is Limited by the Availability of Iron

PubMed Central

Back, Alexandre; Irlinger, Françoise

2012-01-01

The microflora on the surface of smear-ripened cheeses is composed of various species of bacteria and yeasts that contribute to the production of the desired organoleptic properties. The objective of the present study was to show that iron availability is a limiting factor in the growth of typical aerobic ripening bacteria in cheese. For that purpose, we investigated the effect of iron or siderophore addition in model cheeses that were coinoculated with a yeast and a ripening bacterium. Both iron and the siderophore desferrioxamine B stimulated the growth of ripening bacteria belonging to the genera Arthrobacter, Corynebacterium, and Brevibacterium. The extent of stimulation was strain dependent, and generally, the effect of desferrioxamine B was greater than that of iron. Measurements of the expression of genes related to the metabolism of iron by Arthrobacter arilaitensis Re117 by real-time reverse transcription-PCR showed that these genes were transcribed during growth in cheese. The addition of desferrioxamine B increased the expression of two genes encoding iron-siderophore ABC transport binding proteins. The addition of iron decreased the expression of siderophore biosynthesis genes and of part of the genes encoding iron-siderophore ABC transport components. It was concluded that iron availability is a limiting factor in the growth of typical cheese surface bacteria. The selection of strains with efficient iron acquisition systems may be useful for the development of defined-strain surface cultures. Furthermore, the importance of iron metabolism in the microbial ecology of cheeses should be investigated since it may result in positive or negative microbial interactions. PMID:22367081

Increased iron bioavailability from lactic-fermented vegetables is likely an effect of promoting the formation of ferric iron (Fe(3+)).

PubMed

Scheers, Nathalie; Rossander-Hulthen, Lena; Torsdottir, Inga; Sandberg, Ann-Sofie

2016-02-01

Lactic fermentation of foods increases the availability of iron as shown in a number of studies throughout the years. Several explanations have been provided such as decreased content of inhibitory phytate, increased solubility of iron, and increased content of lactic acid in the fermented product. However, to our knowledge, there are no data to support that the bioavailability of iron is affected by lactic fermentation. The objective of the present study was to investigate whether the bioavailability of iron from a vegetable mix was affected by lactic fermentation and to propose a mechanism for such an event, by conducting human and cell (Caco-2, HepG2) studies and iron speciation measurements (voltammetry). We also investigated whether the absorption of zinc was affected by the lactic fermentation. In human subjects, we observed that lactic-fermented vegetables served with both a high-phytate and low-phytate meal increased the absorption of iron, but not zinc. In vitro digested fermented vegetables were able to provoke a greater hepcidin response per ng Fe than fresh vegetables, indicating that Fe in the fermented mixes was more bioavailable, independent on the soluble Fe content. We measured that hydrated Fe(3+) species were increased after the lactic fermentation, while there was no significant change in hydrated Fe(2+). Furthermore, lactate addition to Caco-2 cells did not affect ferritin formation in response to Fe nor did lactate affect the hepcidin response in the Caco-2/HepG2 cell system. The mechanism for the increased bioavailability of iron from lactic-fermented vegetables is likely an effect of the increase in ferric iron (Fe(3+)) species caused by the lactic fermentation. No effect on zinc bioavailability was observed.

Comparative analysis of biofilm formation by Bacillus cereus reference strains and undomesticated food isolates and the effect of free iron.

PubMed

Hayrapetyan, Hasmik; Muller, Lisette; Tempelaars, Marcel; Abee, Tjakko; Nierop Groot, Masja

2015-05-04

Biofilm formation of Bacillus cereus reference strains ATCC 14579 and ATCC 10987 and 21 undomesticated food isolates was studied on polystyrene and stainless steel as contact surfaces. For all strains, the biofilm forming capacity was significantly enhanced when in contact with stainless steel (SS) as a surface as compared to polystyrene (PS). For a selection of strains, the total CFU and spore counts in biofilms were determined and showed a good correlation between CFU counts and total biomass of these biofilms. Sporulation was favoured in the biofilm over the planktonic state. To substantiate whether iron availability could affect B. cereus biofilm formation, the free iron availability was varied in BHI by either the addition of FeCl3 or by depletion of iron with the scavenger 2,2-Bipyridine. Addition of iron resulted in increased air-liquid interface biofilm on polystyrene but not on SS for strain ATCC 10987, while the presence of Bipyridine reduced biofilm formation for both materials. Biofilm formation was restored when excess FeCl3 was added in combination with the scavenger. Further validation of the iron effect for all 23 strains in microtiter plate showed that fourteen strains (including ATCC10987) formed a biofilm on PS. For eight of these strains biofilm formation was enhanced in the presence of added iron and for eleven strains it was reduced when free iron was scavenged. Our results show that stainless steel as a contact material provides more favourable conditions for B. cereus biofilm formation and maturation compared to polystyrene. This effect could possibly be linked to iron availability as we show that free iron availability affects B. cereus biofilm formation. Copyright © 2015 Elsevier B.V. All rights reserved.

Mobilization of Iron by Plant-Borne Coumarins.

PubMed

Tsai, Huei Hsuan; Schmidt, Wolfgang

2017-06-01

Iron is one of the most abundant elements in soils, but its low phytoavailability at high pH restricts plant communities on alkaline soils to taxa that have evolved efficient strategies to increase iron solubility. Recent evidence provides support for a previously underestimated role of root-secreted coumarins in mobilizing iron through reduction and chelation as part of an orchestrated strategy evolved to improve the acquisition of iron from recalcitrant pools. Understanding the mechanisms that tune the production of iron-mobilizing coumarins and their intricate interplay with other biosynthesis pathways could yield clues for deciphering the molecular basis of 'iron efficiency' - the ability of plants to thrive on soils with limited iron availability - and may open avenues for generating iron-fortified crops. Copyright © 2017 Elsevier Ltd. All rights reserved.

Evaluation and treatment of transfusional iron overload in children.

PubMed

Ware, Hannah M; Kwiatkowski, Janet L

2013-12-01

Red blood cell transfusions are increasingly used in the management of various anemias, including thalassemia and sickle cell disease. Because the body lacks physiologic mechanisms for removing excess iron, transfusional iron overload is a common complication in children receiving regular transfusions. Iron chelation is necessary to remove the excess iron that causes injury to the heart, liver, and endocrine organs. Three chelators, deferoxamine, deferasirox, and deferiprone, are currently available in the United States. When choosing a chelator regimen, patients, parents, and providers may consider a variety of factors, including the severity of iron overload, administration schedule, and adverse effect profile. Copyright © 2013 Elsevier Inc. All rights reserved.

Markers of iron deficiency in patients with polycythemia vera receiving ruxolitinib or best available therapy.

PubMed

Verstovsek, Srdan; Harrison, Claire N; Kiladjian, Jean-Jacques; Miller, Carole; Naim, Ahmad B; Paranagama, Dilan C; Habr, Dany; Vannucchi, Alessandro M

2017-05-01

Polycythemia vera (PV) is characterized by erythropoiesis and JAK2-activating mutations, with increased risks of morbidity and mortality. Most patients with PV are iron deficient, and treatment often includes hematocrit control with phlebotomy, which may exacerbate iron deficiency-associated complications. The phase 3 RESPONSE trial evaluated the JAK1/JAK2 inhibitor ruxolitinib (n=110) versus best available therapy (BAT; n=112) in patients with PV who were hydroxyurea-resistant/intolerant. Ruxolitinib was superior to BAT for hematocrit control, reduction in splenomegaly, and blood count normalization. This exploratory analysis, the first to evaluate iron status in a prospective study of patients with PV, investigated ruxolitinib effects on 7 serum iron markers and iron deficiency-related patient-reported outcomes (PRO). Among patients with evidence of baseline iron deficiency, ruxolitinib was associated with normalization of iron marker levels, compared with lesser improvement with BAT. Iron levels remained stable in ruxolitinib patients with normal iron levels at baseline. Regardless of baseline iron status, treatment with ruxolitinib was associated with improvements in concentration problems, cognitive function, dizziness, fatigue, headaches, and inactivity, although improvements were generally greater among patients with baseline iron deficiency. The improvements in iron deficiency markers and PROs observed with ruxolitinib are suggestive of clinical benefits that warrant further exploration. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

Effects of Iron Deficiency on Iron Binding and Internalization into Acidic Vacuoles in Dunaliella salina1[W][OA

PubMed Central

Paz, Yakov; Shimoni, Eyal; Weiss, Meira; Pick, Uri

2007-01-01

Uptake of iron in the halotolerant alga Dunaliella salina is mediated by a transferrin-like protein (TTf), which binds and internalizes Fe3+ ions. Recently, we found that iron deficiency induces a large enhancement of iron binding, which is associated with accumulation of three other plasma membrane proteins that associate with TTf. In this study, we characterized the kinetic properties of iron binding and internalization and identified the site of iron internalization. Iron deficiency induces a 4-fold increase in Fe binding, but only 50% enhancement in the rate of iron uptake and also increases the affinity for iron and bicarbonate, a coligand for iron binding. These results indicate that iron deprivation leads to accumulation and modification of iron-binding sites. Iron uptake in iron-sufficient cells is preceded by an apparent time lag, resulting from prebound iron, which can be eliminated by unloading iron-binding sites. Iron is tightly bound to surface-exposed sites and hardly exchanges with medium iron. All bound iron is subsequently internalized. Accumulation of iron inhibits further iron binding and internalization. The vacuolar inhibitor bafilomycin inhibits iron uptake and internalization. Internalized iron was localized by electron microscopy within vacuolar structures that were identified as acidic vacuoles. Iron internalization is accompanied by endocytosis of surface proteins into these acidic vacuoles. A novel kinetic mechanism for iron uptake is proposed, which includes two pools of bound/compartmentalized iron separated by a rate-limiting internalization stage. The major parameter that is modulated by iron deficiency is the iron-binding capacity. We propose that excessive iron binding in iron-deficient cells serves as a temporary reservoir for iron that is subsequently internalized. This mechanism is particularly suitable for organisms that are exposed to large fluctuations in iron availability. PMID:17513481

Air pollution particles and iron homeostasis | Science ...

EPA Pesticide Factsheets

Background: The mechanism underlying biological effects of particles deposited in the lung has not been defined. Major Conclusions: A disruption in iron homeostasis follows exposure of cells to all particulate matter including air pollution particles. Following endocytosis, functional groups at the surface of retained particle complex iron available in the cell. In response to a reduction in concentrations of requisite iron, a functional deficiency can result intracellularly. Superoxide production by the cell exposed to a particle increases ferrireduction which facilitates import of iron with the objective being the reversal of the metal deficiency. Failure to resolve the functional iron deficiency following cell exposure to particles activates kinases and transcription factors resulting in a release of inflammatory mediators and inflammation. Tissue injury is the end product of this disruption in iron homeostasis initiated by the particle exposure. Elevation of available iron to the cell precludes deficiency of the metal and either diminishes or eliminates biological effects.General Significance: Recognition of the pathway for biological effects after particle exposure to involve a functional deficiency of iron suggests novel therapies such as metal supplementation (e.g. inhaled and oral). In addition, the demonstration of a shared mechanism of biological effects allows understanding the common clinical, physiological, and pathological presentation fol

Derepression of the Azotobacter vinelandii siderophore system, using iron-containing minerals to limit iron repletion.

PubMed Central

Page, W J; Huyer, M

1984-01-01

Azotobacter vinelandii solubilized iron from certain minerals using only dihydroxybenzoic acid, which appeared to be produced constitutively. Solubilization of iron from other minerals required dihydroxybenzoic acid and the siderophore N,N'-bis-(2,3- dihydroxybenzoyl )-L-lysine ( azotochelin ) or these chelators plus the yellow-green fluorescent siderophore azotobactin . In addition to this sequential production of siderophores, cells also demonstrated partial to hyperproduction relative to the iron-limited control. The iron sources which caused partial derepression of the siderophores caused derepression of all the high-molecular-weight iron-repressible outer membrane proteins except a 77,000-molecular-weight protein, which appeared to be coordinated with azotobactin production. Increased siderophore production correlated with increased production of outer membrane proteins with molecular weights of 93,000, 85,000, and 77,000, but an 81,000-molecular-weight iron-repressible protein appeared at a constant level despite the degree of derepression. When iron was readily available, it appeared to complex with a 60,000-molecular-weight protein believed to form a surface layer on the A. vinelandii cell. Images PMID:6233258

Iron-Induced Virulence of Salmonella enterica Serovar Typhimurium at the Intestinal Epithelial Interface Can Be Suppressed by Carvacrol

PubMed Central

Kortman, Guus A. M.; Roelofs, Rian W. H. M.; Swinkels, Dorine W.; de Jonge, Marien I.; Burt, Sara A.

2014-01-01

Oral iron therapy can increase the abundance of bacterial pathogens, e.g., Salmonella spp., in the large intestine of African children. Carvacrol is a natural compound with antimicrobial activity against various intestinal bacterial pathogens, among which is the highly prevalent Salmonella enterica serovar Typhimurium. This study aimed to explore a presumed interaction between carvacrol and bacterial iron handling and to assess the potential of carvacrol in preventing the increase of bacterial pathogenicity during high iron availability. S. Typhimurium was cultured with increasing concentrations of iron and carvacrol to study the effects of these combined interventions on growth, adhesion to intestinal epithelial cells, and iron uptake/influx in both bacterial and epithelial cells. In addition, the ability of carvacrol to remove iron from the high-affinity ligand transferrin and an Fe-dye complex was examined. Carvacrol retarded growth of S. Typhimurium at all iron conditions. Furthermore, iron-induced epithelial adhesion was effectively reduced by carvacrol at high iron concentrations. The reduction of growth and virulence by carvacrol was not paralleled by a change in iron uptake or influx into S. Typhimurium. In contrast, bioavailability of iron for epithelial cells was moderately decreased under these conditions. Further, carvacrol was shown to lack the properties of an iron binding molecule; however, it was able to weaken iron-ligand interactions by which it may possibly interfere with bacterial virulence. In conclusion, our in vitro data suggest that carvacrol has the potential to serve as a novel dietary supplement to prevent pathogenic overgrowth and colonization in the large intestine during oral iron therapy. PMID:24379194

Iron status in pregnant women and women of reproductive age in Europe.

PubMed

Milman, Nils; Taylor, Christine L; Merkel, Joyce; Brannon, Patsy M

2017-12-01

Understanding the iron status in pregnant women in Europe provides a foundation for considering the role of iron screening and supplementation. However, available reports and studies have used different approaches that challenge the devising of overall summaries. Moreover, data on pregnant women are limited, and thus, data on women of reproductive age provide useful background information including baseline iron stores in pregnant women. This review considered data that are available from >15 European countries including national surveys and relevant clinical studies. In European women of reproductive age, median or geometric mean serum ferritin (SF) concentrations were estimated at 26-38 μg/L. Approximately 40-55% of this population had small or depleted iron stores (i.e., SF concentration ≤30 μg/L), and 45-60% of this population had apparently replete iron stores. The prevalence of iron deficiency (ID) and iron deficiency anemia (IDA) was 10-32% and 2-5%, respectively, depending on the cutoffs used. Approximately 20-35% of European women of reproductive age had sufficient iron stores (SF concentration >70 μg/L) to complete a pregnancy without supplementary iron. During pregnancy, European women in controlled supplementation trials who were not receiving iron supplements displayed increasing prevalences of ID and IDA during pregnancy, which peaked in the middle to late third trimester. Available evidence has suggested that, in gestational weeks 32-39, the median or geometric mean SF concentrations were 6-21 μg/L, and prevalences of ID and IDA were 28-85% and 21-35%, respectively. Women who were taking iron supplements had higher iron status and lower prevalences of ID and IDA, which were dependent on the dose of iron and compliance. The data suggest that, in Europe, the iron status of reproductive-aged women varies by region and worsens in pregnancy without iron supplementation. © 2017 American Society for Nutrition.

In Vitro Iron Availability from Insects and Sirloin Beef.

PubMed

Latunde-Dada, Gladys O; Yang, Wenge; Vera Aviles, Mayra

2016-11-09

Interest in the consumption of insects (entomophagy) as an alternative environmentally sustainable source of protein in the diet of humans has recently witnessed a surge. Knowledge of the nutrient composition and, in particular, the bioavailability of minerals from insects is currently sparse. This study evaluated the availability of Fe, Ca, Cu, Mg, Mn, and Zn from four commonly eaten insects and compared these to sirloin beef. Soluble iron from the samples was measured by inductively coupled plasma optical emission spectrometry (ICP-OES). Iron bioavailability was determined using an in vitro simulated peptic-pancreatic digestion, followed by measurement of ferritin (a surrogate marker for iron absorption) in Caco-2 cells. Cricket and sirloin beef had comparably higher levels of Fe, Ca, and Mn than grasshopper, meal, and buffalo worms. However, iron solubility was significantly higher from the insect samples than from beef. The complementation of whole-wheat flour with insect or beef protein resulted in overall decreases in mineral content and iron solubility in the composite mixtures. Collectively, the data show that grasshopper, cricket, and mealworms contain significantly higher chemically available Ca, Cu, Mg, Mn, and Zn than sirloin. However, buffalo worms and sirloin exhibited higher iron bioavailability comparable to that of FeSO 4 . Commonly consumed insect species could be excellent sources of bioavailable iron and could provide the platform for an alternative strategy for increased mineral intake in the diets of humans.

Longitudinal Analysis of the Interaction Between Obesity and Pregnancy on Iron Homeostasis: Role of Hepcidin.

PubMed

Flores-Quijano, María Eugenia; Montalvo-Velarde, Irene; Vital-Reyes, Victor Saul; Rodríguez-Cruz, Maricela; Rendón-Macías, Mario Enrique; López-Alarcón, Mardia

2016-10-01

When pregnancy occurs in obese women, two opposite mechanisms for iron homeostasis concur: increased need for available iron to support erythropoiesis and decreased iron mobilization from diets and stores due to obesity-related inflammation linked to overexpressed hepcidin. Few studies have examined the role of hepcidin on maternal iron homeostasis in the context of obese pregnancy. The aim of the study was to evaluate the combined effect of maternal obesity and pregnancy on hepcidin and maternal iron status while accounting for inflammation and iron supplementation. We conducted a secondary analysis of a cohort of pregnant women recruited from a referral obstetric hospital in Mexico City. Circulating biomarkers of iron status (hepcidin, ferritin [SF], transferrin receptor [sTfR], erythropoietin [EPO]), and inflammation (C-reactive protein [CRP], tumor necrosis factor-[TNF]α, and interleukin-[IL]6) were determined monthly throughout pregnancy. Repeated measures ANOVA and logistic regression models were used for statistics. Twenty-three obese (Ob) and 25 lean (Lc) women were studied. SF and hepcidin declined, and EPO and sTfR increased throughout pregnancy in both groups. sTfR increased more in Ob than in Lc (p = 0.024). The smallest hepcidin decline occurred in iron-supplemented Ob women compared to non-supplemented Lc women (p = 0.022). The risk for iron deficiency at the end of pregnancy was higher for Ob than for Lc (OR = 4.45, 95% CI = 2.07-9.58) after adjusting for iron supplementation and hepcidin concentration. Pre-gestational obesity increases the risk of maternal iron deficiency despite iron supplementation. Overexpressed hepcidin appears to be a potential mechanism. Copyright © 2016 IMSS. Published by Elsevier Inc. All rights reserved.

Quantifying Integrated Proteomic Responses to Iron Stress in the Globally Important Marine Diazotroph Trichodesmium

PubMed Central

Snow, Joseph T.; Polyviou, Despo; Skipp, Paul; Chrismas, Nathan A. M.; Hitchcock, Andrew; Geider, Richard; Moore, C. Mark; Bibby, Thomas S.

2015-01-01

Trichodesmium is a biogeochemically important marine cyanobacterium, responsible for a significant proportion of the annual ‘new’ nitrogen introduced into the global ocean. These non-heterocystous filamentous diazotrophs employ a potentially unique strategy of near-concurrent nitrogen fixation and oxygenic photosynthesis, potentially burdening Trichodesmium with a particularly high iron requirement due to the iron-binding proteins involved in these processes. Iron availability may therefore have a significant influence on the biogeography of Trichodesmium. Previous investigations of molecular responses to iron stress in this keystone marine microbe have largely been targeted. Here a holistic approach was taken using a label-free quantitative proteomics technique (MSE) to reveal a sophisticated multi-faceted proteomic response of Trichodesmium erythraeum IMS101 to iron stress. Increased abundances of proteins known to be involved in acclimation to iron stress and proteins known or predicted to be involved in iron uptake were observed, alongside decreases in the abundances of iron-binding proteins involved in photosynthesis and nitrogen fixation. Preferential loss of proteins with a high iron content contributed to overall reductions of 55–60% in estimated proteomic iron requirements. Changes in the abundances of iron-binding proteins also suggested the potential importance of alternate photosynthetic pathways as Trichodesmium reallocates the limiting resource under iron stress. Trichodesmium therefore displays a significant and integrated proteomic response to iron availability that likely contributes to the ecological success of this species in the ocean. PMID:26562022

Effects of Genotype and Growth Temperature on the Contents of Tannin, Phytate and In Vitro Iron Availability of Sorghum Grains

PubMed Central

Wu, Gangcheng; Johnson, Stuart K.; Bornman, Janet F.; Bennett, Sarita J.; Singh, Vijaya; Simic, Azra; Fang, Zhongxiang

2016-01-01

Background It has been predicted that the global temperature will rise in the future, which means crops including sorghum will likely be grown under higher temperatures, and consequently may affect the nutritional properties. Methods The effects of two growth temperatures (OT, day/night 32/21°C; HT 38/21°C) on tannin, phytate, mineral, and in vitro iron availability of raw and cooked grains (as porridge) of six sorghum genotypes were investigated. Results Tannin content significantly decreased across all sorghum genotypes under high growth temperature (P ≤0.05), while the phytate and mineral contents maintained the same level, increased or decreased significantly, depending on the genotype. The in vitro iron availability in most sorghum genotypes was also significantly reduced under high temperature, except for Ai4, which showed a pronounced increase (P ≤0.05). The cooking process significantly reduced tannin content in all sorghum genotypes (P ≤0.05), while the phytate content and in vitro iron availability were not significantly affected. Conclusions This research provides some new information on sorghum grain nutritional properties when grown under predicted future higher temperatures, which could be important for humans where sorghum grains are consumed as staple food. PMID:26859483

Dietary Iron Fortification Normalizes Fetal Hematology, Hepcidin, and Iron Distribution in a Rat Model of Prenatal Alcohol Exposure.

PubMed

Huebner, Shane M; Helfrich, Kaylee K; Saini, Nipun; Blohowiak, Sharon E; Cheng, Adrienne A; Kling, Pamela J; Smith, Susan M

2018-06-01

Prenatal alcohol exposure (PAE) causes neurodevelopmental disability. Clinical and animal studies show gestational iron deficiency (ID) exacerbates PAE's behavioral and growth deficits. In rat, PAE manifests an inability to establish iron homeostasis, increasing hepcidin (maternal and fetal), and fetal liver iron while decreasing brain iron and promoting anemia. Here, we hypothesize dietary iron fortification during pregnancy may mitigate alcohol's disruption of fetal iron homeostasis. Pregnant Long-Evans rats, fed iron-sufficient (100 ppm iron) or iron-fortified (IF; 500 ppm iron) diets, received either 5 g/kg alcohol (PAE) or isocaloric maltodextrin daily on gestational days (GD) 13.5 through 19.5. Maternal and fetal outcomes were evaluated on GD20.5. PAE reduced mean fetal weight (p < 0.001) regardless of maternal iron status, suggesting iron fortification did not improve fetal growth. Both PAE (p < 0.01) and IF (p = 0.035) increased fetal liver iron. In fetal brain, PAE (p = 0.015) affected total (p < 0.001) and nonheme iron (p < 0.001) such that iron fortification normalized (p = 0.99) the alcohol-mediated reductions in brain iron and nonheme iron. Iron fortification also improved fetal hematologic indices in PAE including hemoglobin, hematocrit, and mean cell volume (ps<0.001). Iron fortification also normalized hepcidin expression in alcohol-exposed maternal and fetal liver. Neither diet nor PAE affected transferrin (Tf) and ferritin (FTN) content in fetal liver, nor Tf or transferrin receptor in fetal brain. However, IF-PAE fetal brains trended to less FTN content (p = 0.074), suggesting greater availability of nonstorage iron. In PAE, hepcidin levels were linearly related to increased liver iron stores and decreased red blood cell count and brain iron. Maternal oral iron fortification mitigated PAE's disruption of fetal iron homeostasis and improved brain iron content, hematologic indices, and hepcidin production in this rat PAE model. Clinical studies show maternal ID substantially enhances fetal vulnerability to PAE, and our work supports increased maternal dietary iron intake may improve fetal iron status in alcohol-exposed pregnancies. Copyright © 2018 by the Research Society on Alcoholism.

Iron deficiency: new insights into diagnosis and treatment.

PubMed

Camaschella, Clara

2015-01-01

Iron deficiency and iron deficiency anemia are common conditions worldwide affecting especially children and young women. In developing countries, iron deficiency is caused by poor iron intake and/or parasitic infection, whereas vegetarian dietary choices, poor iron absorption, and chronic blood loss are common causes in high-income countries. Erythropoiesis stimulating agents can result in functional iron deficiency for erythropoiesis even when stores are iron-replete. Diagnosis of iron deficiency is straightforward, except when it occurs in the context of inflammatory disorders. Oral iron salts correct absolute iron deficiency in most patients, because low hepcidin levels facilitate iron absorption. Unfortunately frequent side effects limit oral iron efficacy. Intravenous iron is increasingly utilized, because currently available preparations allow rapid normalization of total body iron even with a single infusion and are effective also in functional iron deficiency and in iron deficiency associated with inflammatory disorders. The evidence is accumulating that these preparations are safe and effective. However, long-term safety issues of high doses of iron need to be further explored. © 2015 by The American Society of Hematology. All rights reserved.

Iron homeostatis and oxidative stress in idiopathic pulmonary alveolar proteinosis: a case-control study

EPA Science Inventory

ABSTRACT: BACKGROUND: Lung injury caused by both inhaled dusts and infectious agents depends on increased availability of iron and metal-catalyzed oxidative stress. Because inhaled particles, such as silica, and certain infections can cause secondary pulmonary alveolar proteinosi...

An online calculator for marine phytoplankton iron culturing experiments.

PubMed

Rivers, Adam R; Rose, Andrew L; Webb, Eric A

2013-10-01

Laboratory experiments with iron offer important insight into the physiology of marine phytoplankton and the biogeochemical cycles they influence. These experiments often rely on chelators to buffer the concentration of available iron, but the buffer can fail when cell density increases, causing the concentration of that iron to drop rapidly. To more easily determine the point when the iron concentration falls, we developed an online calculator to estimate the maximum phytoplankton density that a growth medium can support. The results of the calculator were compared to the numerical simulations of a Fe-limited culture of the diatom Thalassiosira weissflogii (Grunow) Fryxell and Hasle. Modeling reveals that the assumptions behind thermodynamic estimates of unchelated Fe concentration can fail before easily perceptible changes in growth rate, potentially causing physiological changes that could alter the conclusions of culture experiments. The calculator is available at http://www.marsci.uga.edu/fidoplankter. © 2013 Phycological Society of America.

In vitro dissolution profile of two commercially available iron preparations.

PubMed

Patrício, José P H; Santos, Cristina; Cerdeira, Rui

2012-03-01

Current scientific evidence indicates that anemia in pregnancy, regardless of severity, is associated with an increased risk of maternal and fetal mortality. There is little published information about the bioavailability and bioequivalence of formulations containing both iron and folic acid. However, in vitro dissolution studies can provide important information on the likely relative bioavailability of various formulations. The objective of our study was to compare the in vitro dissolution of two similar commercially available formulations of iron- and folic acid-containing supplements, Folifer® (Bialport - Produtos Farmacêuticos, S.A., Portugal) and Ferroliver® (SM Pharma c.a., Venezuela), in order to determine the in vitro availability of their iron content. Folifer® and Ferroliver® were chosen because they contained similar amounts of elemental iron. The amount of iron released from each tablet was evaluated over a 4-hour period in three dissolution media replicating gastric or intestinal juices with pH values ranging from 1.5 to 6.9. The samples were then titrated with a solution of cerium ammonium sulfate in order to calculate the amount of iron released in each specific pH condition. The percentage of dissolved iron was calculated as a cumulative frequency, using the percentage of dissolved iron at all timepoints. The dissolution similarity between the two commercially available formulations was evaluated using the &U0192;(2) statistic formula. During a 4-hour dissolution test, Folifer® released 59.4 mg of iron compared with 48.5 mg released by Ferroliver®. The value obtained for the similarity factor, an indicator of likely bioequivalence, was 41. These data suggest that Folifer® releases more iron than Ferroliver®, and that the two formulations are not equivalent in vitro. The superior dissolution of ferrous sulfate with Folifer® compared with ferrous fumarate in Ferroliver® might be responsible for the observed difference.

[Iron deficiency in ND-CKD: from diagnosis to treatment].

PubMed

Liberti, Maria Elena; Garofalo, Carlo; Sagliocca, Adelia; Borrelli, Silvio; Conte, Giuseppe; De Nicola, Luca; Minutolo, Roberto

2017-09-28

In non-dialysis-chronic kidney disease (CKD), iron deficiency is a frequent nutritional disorder due to either the greater tendency to occult gastrointestinal bleeding or to the chronic inflammatory state resulting in a reduced intestinal iron reabsorption through an increased synthesis of hepcidin. These phenomenon are responsible for a negative iron balance that compromises erythropoiesis and contributes to the pathogenesis of anemia in CKD. Several laboratory tests are now available to allow an adequate diagnosis of iron deficiency. Among the new parameters, the percentage of hypochromic red cells (% HYPO) and the reticulocyte hemoglobin content (CHr) are now considered as the most specific markers for diagnosing iron-deficiency erythropoiesis. Unfortunately, their implementation in clinical practice is limited by the scarce availability. In non-dialyzed CKD , subjects intolerant or non-responsive to oral iron therapy, can be effectively treated with novel intravenous iron preparations, such as iron carboxymaltose, that allow a complete and rapid correction of iron deficient anemia. Furthermore, this iron compound is associated with lower rate of adverse effects since the carbohydrate shell (carboxymaltose) is more stable than gluconate and saccarate thus reducing the release of free iron in the bloodstream. Of note, the possibility of administering this drug at high doses and reduced frequency decreases the risk of infusion reactions. Finally, a substantial economic saving mainly dependent on a reduction in indirect costs represents a further advantage in the use of iron carboxymaltose in this population. Copyright by Società Italiana di Nefrologia SIN, Rome, Italy.

Haemophilus Responses to Nutritional Immunity: Epigenetic and Morphological Contribution to Biofilm Architecture, Invasion, Persistence and Disease Severity

PubMed Central

Szelestey, Blake R.; Heimlich, Derek R.; Raffel, Forrest K.; Justice, Sheryl S.; Mason, Kevin M.

2013-01-01

In an effort to suppress microbial outgrowth, the host sequesters essential nutrients in a process termed nutritional immunity. However, inflammatory responses to bacterial insult can restore nutritional resources. Given that nutrient availability modulates virulence factor production and biofilm formation by other bacterial species, we hypothesized that fluctuations in heme-iron availability, particularly at privileged sites, would similarly influence Haemophilus biofilm formation and pathogenesis. Thus, we cultured Haemophilus through sequential heme-iron deplete and heme-iron replete media to determine the effect of transient depletion of internal stores of heme-iron on multiple pathogenic phenotypes. We observed that prior heme-iron restriction potentiates biofilm changes for at least 72 hours that include increased peak height and architectural complexity as compared to biofilms initiated from heme-iron replete bacteria, suggesting a mechanism for epigenetic responses that participate in the changes observed. Additionally, in a co-infection model for human otitis media, heme-iron restricted Haemophilus, although accounting for only 10% of the inoculum (90% heme-iron replete), represented up to 99% of the organisms recovered at 4 days. These data indicate that fluctuations in heme-iron availability promote a survival advantage during disease. Filamentation mediated by a SulA-related ortholog was required for optimal biofilm peak height and persistence during experimental otitis media. Moreover, severity of disease in response to heme-iron restricted Haemophilus was reduced as evidenced by lack of mucosal destruction, decreased erythema, hemorrhagic foci and vasodilatation. Transient restriction of heme-iron also promoted productive invasion events leading to the development of intracellular bacterial communities. Taken together, these data suggest that nutritional immunity, may, in fact, foster long-term phenotypic changes that better equip bacteria for survival at infectious sites. PMID:24130500

Update of a comparative analysis of cost minimization following the introduction of newly available intravenous iron therapies in hospital practice

PubMed Central

Bhandari, Sunil

2011-01-01

Background The clinical need to be able to administer high doses of intravenous iron conveniently as a rapid infusion has been addressed by the recent introduction of ferric carboxymaltose and subsequently iron isomaltoside 1000. Neither requires a test dose. The maximum dose of ferric carboxymaltose is 1000 mg. The maximum dose of iron isomaltoside 1000 is based on 20 mg/kg body weight without a specified ceiling dose, thereby increasing the scope of being able to achieve total iron repletion with a single infusion. This ability to give high doses of iron is important in the context of managing iron deficiency anemia, which is associated with a number of clinical conditions where demands for iron are high. It is also an important component of the strategy as an alternative to blood transfusion. Affordability is a key issue for health services. Recent price changes affecting iron sucrose and ferric carboxymaltose, plus modifications to the manufacturers’ prescribing information, have provoked this update. Methods This study is a comparative analysis of the costs of acquiring and administering the newly available intravenous iron formulations against standard treatments in the hospital setting. The costs include the medication, nursing costs, equipment, and patient transportation. Three dosage levels (600 mg, 1000 mg, and 1600 mg) are considered. Results and conclusion The traditional standard treatments, blood and iron sucrose, cost more than the alternative intravenous iron preparations across the dose spectrum and sensitivities. Low molecular weight iron dextran is the least expensive option at the 1600 mg dose level but has the caveat of a prolonged administration time and requirement for a test dose. At 600 mg and 1000 mg dose levels, both iron isomaltoside 1000 and ferric carboxymaltose are more economical than low molecular weight iron dextran. Iron isomaltoside 1000 is less expensive than ferric carboxymaltose at all dose levels. Newly available iron preparations appear to be clinically promising, cost effective, and practical alternatives to current standards of iron repletion. PMID:22241947

Experimental oral iron administration: Histological investigations and expressions of iron handling proteins in rat retina with aging.

PubMed

Kumar, Pankaj; Nag, Tapas Chandra; Jha, Kumar Abhiram; Dey, Sanjay Kumar; Kathpalia, Poorti; Maurya, Meenakshi; Gupta, Chandan Lal; Bhatia, Jagriti; Roy, Tara Sankar; Wadhwa, Shashi

2017-12-01

Iron is implicated in age-related macular degeneration (AMD). The aim of this study was to see if long-term, experimental iron administration with aging modifies retinal and choroidal structures and expressions of iron handling proteins, to understand some aspects of iron homeostasis. Male Wistar rats were fed with ferrous sulphate heptahydrate (500mg/kg body weight/week, oral; elemental iron availability: 20%) from 2 months of age onward until they were 19.5 month-old. At 8, 14 and 20 months of age, they were sacrificed and serum and retinal iron levels were detected by HPLC. Oxidative stress was analyzed by TBARS method. The retinas were examined for cell death (TUNEL), histology (electron microscopy) and the expressions of transferrin, transferrin receptor-1 [TFR-1], H- and L-ferritin. In control animals, at any age, there was no difference in the serum and retinal iron levels, but the latter increased significantly in 14- and 20 month-old iron-fed rats, indicating that retinal iron accumulation proceeds with progression of aging (>14 months). The serum and retinal TBARS levels increased significantly with progression of aging in experimental but not in control rats. There was significant damage to choriocapillaris, accumulation of phagosomes in retinal pigment epithelium and increased incidence of TUNEL+ cells in outer nuclear layer and vacuolation in inner nuclear layer (INL) of 20 month-aged experimental rats, compared to those in age-matched controls. Vacuolations in INL could indicate a long-term effect of iron accumulation in the inner retina. These events paralleled the increased expression of ferritins and transferrin and a decrease in the expression of TFR-1 in iron-fed rats with aging, thereby maintaining iron homeostasis in the retina. As some of these changes mimic with those happening in eyes with AMD, this model can be utilized to understand iron-induced pathophysiological changes in AMD. Copyright © 2017 Elsevier B.V. All rights reserved.

MFehi adipose tissue macrophages compensate for tissue iron pertubations in mice.

PubMed

Hubler, Merla J; Erikson, Keith M; Kennedy, Arion J; Hasty, Alyssa H

2018-05-16

Resident adipose tissue macrophages (ATMs) play multiple roles to maintain tissue homeostasis, such as removing excess FFAs and regulation of extracellular matrix. The phagocytic nature and oxidative resiliency of macrophages not only allows them to function as innate immune cells but also to respond to specific tissue needs, such as iron homeostasis. MFe hi ATMs are a subtype of resident ATMs that we recently identified to have twice the intracellular iron content as other ATMs and elevated expression of iron handling genes. While studies have demonstrated iron homeostasis is important for adipocyte health, little is known about how MFe hi ATMs may respond to and influence AT iron availability. Two methodologies were used to address this question - dietary iron supplementation and intraperitoneal iron injection. Upon exposure to high dietary iron, MFe hi ATMs accumulated excess iron, while the iron content of MFe lo ATMs and adipocytes remained unchanged. In this model of chronic iron excess, MFe hi ATMs exhibited increased expression of genes involved in iron storage. In the injection model, MFe hi ATMs incorporated high levels of iron and adipocytes were spared iron overload. This acute model of iron overload was associated with increased numbers of MFe hi ATMs; 17% could be attributed to monocyte recruitment and 83% to MFe lo ATM incorporation into the MFe hi pool. The MFe hi ATM population maintained its low inflammatory profile and iron cycling expression profile. These studies expand the field's understanding of ATMs and confirm that they can respond as a tissue iron sink in models of iron overload.

Involvement of cytosolic and mitochondrial iron in iron overload cardiomyopathy: an update.

PubMed

Gordan, Richard; Wongjaikam, Suwakon; Gwathmey, Judith K; Chattipakorn, Nipon; Chattipakorn, Siriporn C; Xie, Lai-Hua

2018-04-19

Iron overload cardiomyopathy (IOC) is a major cause of death in patients with diseases associated with chronic anemia such as thalassemia or sickle cell disease after chronic blood transfusions. Associated with iron overload conditions, there is excess free iron that enters cardiomyocytes through both L- and T-type calcium channels thereby resulting in increased reactive oxygen species being generated via Haber-Weiss and Fenton reactions. It is thought that an increase in reactive oxygen species contributes to high morbidity and mortality rates. Recent studies have, however, suggested that it is iron overload in mitochondria that contributes to cellular oxidative stress, mitochondrial damage, cardiac arrhythmias, as well as the development of cardiomyopathy. Iron chelators, antioxidants, and/or calcium channel blockers have been demonstrated to prevent and ameliorate cardiac dysfunction in animal models as well as in patients suffering from cardiac iron overload. Hence, either a mono-therapy or combination therapies with any of the aforementioned agents may serve as a novel treatment in iron-overload patients in the near future. In the present article, we review the mechanisms of cytosolic and/or mitochondrial iron load in the heart which may contribute synergistically or independently to the development of iron-associated cardiomyopathy. We also review available as well as potential future novel treatments.

Green Tea Polyphenols Require the Mitochondrial Iron Transporter, mitoferrin, for Lifespan Extension in Drosophila melanogaster

PubMed Central

Lopez, Terry E.; Pham, Hoang M.; Nguyen, Benjamin V.; Tahmasian, Yerazik; Ramsden, Shannon; Coskun, Volkan; Schriner, Samuel E.; Jafari, Mahtab

2016-01-01

Green tea has been found to increase the lifespan of various experimental animal models including the fruit fly, Drosophila melanogaster. High in polyphenolic content, green tea has been shown to reduce oxidative stress in part by its ability to bind free iron, a micronutrient that is both essential for and toxic to all living organisms. Due to green tea’s iron-binding properties, we questioned whether green tea acts to increase the lifespan of the fruit fly by modulating iron regulators, specifically, mitoferrin, a mitochondrial iron transporter, and transferrin, found in the hemolymph of flies. Publicly available hypomorph mutants for these iron-regulators were utilized to investigate the effect of green tea on lifespan and fertility. We identified that green tea could not increase the lifespan of mitoferrin mutants but did rescue the reduced male fertility phenotype. The effect of green tea on transferrin mutant lifespan and fertility were comparable to w1118 flies, as observed in our previous studies, in which green tea increased male fly lifespan and reduced male fertility. Expression levels in both w1118 flies and mutant flies, supplemented with green tea, showed an up-regulation of mitoferrin but not transferrin. Total body and mitochondrial iron levels were significantly reduced by green tea supplementation in w1118 and mitoferrin mutants but not transferrin mutant flies. Our results demonstrate that green tea may act to increase the lifespan of Drosophila in part by the regulation of mitoferrin and reduction of mitochondrial iron. PMID:27696504

Effect of a nutrition education program and diet modification in Beninese adolescent girls suffering from mild iron deficiency anemia.

PubMed

Alaofé, Halimatou; Zee, John; Dossa, Romain; O'Brien, Huguette Turgeon

2009-01-01

A 26-week nutrition intervention, including 4 weeks of nutrition education, combined with an increase in the content and bioavailability of dietary iron for 22 weeks was carried out in 34 intervention and 34 control adolescent girls suffering from mild iron deficiency anemia (IDA). In post-intervention, hemoglobin and serum ferritin were significantly higher in the intervention group, whereas the incidence of IDA was significantly lower in the intervention group compared to the control group. Nutrition knowledge scores were significantly higher in intervention girls compared to control girls. Dietary changes to improve available dietary iron can reduce iron deficiency anemia.

New insights into iron deficiency and iron deficiency anemia.

PubMed

Camaschella, Clara

2017-07-01

Recent advances in iron metabolism have stimulated new interest in iron deficiency (ID) and its anemia (IDA), common conditions worldwide. Absolute ID/IDA, i.e. the decrease of total body iron, is easily diagnosed based on decreased levels of serum ferritin and transferrin saturation. Relative lack of iron in specific organs/tissues, and IDA in the context of inflammatory disorders, are diagnosed based on arbitrary cut offs of ferritin and transferrin saturation and/or marker combination (as the soluble transferrin receptor/ferritin index) in an appropriate clinical context. Most ID patients are candidate to traditional treatment with oral iron salts, while high hepcidin levels block their absorption in inflammatory disorders. New iron preparations and new treatment modalities are available: high-dose intravenous iron compounds are becoming popular and indications to their use are increasing, although long-term side effects remain to be evaluated. Copyright © 2017 Elsevier Ltd. All rights reserved.

Oral sucrosomial iron versus intravenous iron in anemic cancer patients without iron deficiency receiving darbepoetin alfa: a pilot study.

PubMed

Mafodda, Antonino; Giuffrida, D; Prestifilippo, A; Azzarello, D; Giannicola, R; Mare, M; Maisano, R

2017-09-01

Erythropoiesis-stimulating agents (ESAs) are often used in treatment of patients with chemotherapy-induced anemia. Many studies have demonstrated an improved hemoglobin (Hb) response when ESA is combined with intravenous iron supplementation and a higher effectiveness of intravenous iron over traditional oral iron formulations. A new formulation of oral sucrosomial iron featuring an increased bioavailability compared to traditional oral formulations has recently become available and could provide a valid alternative to those by intravenous (IV) route. Our study evaluated the performance of sucrosomial iron versus intravenous iron in increasing hemoglobin in anemic cancer patients receiving chemotherapy and darbepoetin alfa, as well as safety, need of transfusion, and quality of life (QoL). The present study considered a cohort of 64 patients with chemotherapy-related anemia (Hb >8 g/dL <10 g/dL) and no absolute or functional iron deficiency, scheduled to receive chemotherapy and darbepoetin. All patients received darbepoetin alfa 500 mcg once every 3 weeks and were randomly assigned to receive 8 weeks of IV ferric gluconate 125 mg weekly or oral sucrosomial iron 30 mg daily. The primary endpoint was to demonstrate the performance of oral sucrosomial iron in improving Hb response, compared to intravenous iron. The Hb response was defined as the Hb increase ≥2 g/dL from baseline or the attainment Hb ≥ 12 g/dL. There was no difference in the Hb response rate between the two treatment arms. Seventy one percent of patients treated with IV iron achieved an erythropoietic response, compared to 70% of patients treated with oral iron. By conventional criteria, this difference is considered to be not statistically significant. There were also no differences in the proportion of patients requiring red blood cell transfusions and changes in QoL. Sucrosomial oral iron was better tolerated. In cancer patients with chemotherapy-related anemia receiving darbepoetin alfa, sucrosomial oral iron provides similar increase in Hb levels and Hb response, with higher tolerability without the risks or side effects of IV iron.

Factors influencing the dissolved iron input by river water to the open ocean

NASA Astrophysics Data System (ADS)

Krachler, R.; Jirsa, F.; Ayromlou, S.

The influence of natural metal chelators on the bio-available iron input to the ocean by river water was studied. Ferrous and ferric ions present as suspended colloidal particles maintaining the semblance of a dissolved load are coagulated and settled as their freshwater carrier is mixed with seawater at the continental boundary. However, we might argue that different iron-binding colloids become sequentially destabilized in meeting progressively increasing salinities. By use of a 59Fe tracer method, the partitioning of the iron load from the suspended and dissolved mobile fraction to storage in the sediments was measured with high accuracy in mixtures of natural river water with artificial sea water. The results show a characteristic sequence of sedimentation. Various colloids of different stability are removed from a water of increasing salinity, such as it is the case in the transition from a river water to the open sea. However, the iron transport capacities of the investigated river waters differed greatly. A mountainous river in the Austrian Alps would add only about 5% of its dissolved Fe load, that is about 2.0 µg L-1 Fe, to coastal waters. A small tributary draining a sphagnum peat-bog, which acts as a source of refractory low-molecular-weight fulvic acids to the river water, would add approximately 20% of its original Fe load, that is up to 480 µg L-1 Fe to the ocean's bio-available iron pool. This points to a natural mechanism of ocean iron fertilization by terrigenous fulvic-iron complexes originating from weathering processes occurring in the soils upstream.

Factors influencing the dissolved iron input by river water to the open ocean

NASA Astrophysics Data System (ADS)

Krachler, R.; Jirsa, F.; Ayromlou, S.

2005-05-01

The influence of natural metal chelators on the bio-available iron input to the ocean by river water was studied. Ferrous and ferric ions present as suspended colloidal particles maintaining the semblance of a dissolved load are coagulated and settled as their freshwater carrier is mixed with seawater at the continental boundary. However, we might argue that different iron-binding colloids become sequentially destabilized in meeting progressively increasing salinities. By use of a 59Fe tracer method, the partitioning of the iron load from the suspended and dissolved mobile fraction to storage in the sediments was measured with high accuracy in mixtures of natural river water with artificial sea water. The results show a characteristic sequence of sedimentation. Various colloids of different stability are removed from a water of increasing salinity, such as it is the case in the transition from a river water to the open sea. However, the iron transport capacities of the investigated river waters differed greatly. A mountainous river in the Austrian Alps would add only about 5% of its dissolved Fe load, that is about 2.0 µg L-1 Fe, to coastal waters. A small tributary draining a sphagnum peat-bog, which acts as a source of refractory low-molecular-weight fulvic acids to the river water, would add approximately 20% of its original Fe load, that is up to 480 µg L-1 Fe to the ocean's bio-available iron pool. This points to a natural mechanism of ocean iron fertilization by terrigenous fulvic-iron complexes originating from weathering processes occurring in the soils upstream.

Menopause increases the iron storage protein ferritin in skin.

PubMed

Pelle, Edward; Jian, Jinlong; Zhang, Qi; Muizzuddin, Neelam; Yang, Qing; Dai, Jisen; Maes, Daniel; Pernodet, Nadine; Yarosh, Daniel B; Frenkel, Krystyna; Huang, Xi

2013-01-01

Menstruation and desquamation are important routes for humans to excrete iron. Because menstruation is no longer available in postmenopausal women, in the present study, we examined whether iron accumulates more in postmenopausal skin than in premenopausal skin. Skin biopsy samples were obtained from six pre- and six postmenopausal Caucasian women. Iron levels in the form of ferritin were 42% higher, but vascular endothelial growth factor and total antioxidant capacity were 45% and 34% lower in postmenopausal skin (58.8 ± 1.3 years old) than in premenopausal skin (41.6 ± 1.7 years old), respectively. Moreover, in vitro cultured normal human epidermal keratinocytes had surprisingly high levels of ferritin when compared to immortalized human breast epithelial MCF-10A cells or human liver HepG2 cancer cells. Our results indicate that skin is a cellular repository of iron and that menopause increases iron in skin and, thus, may contribute to the manifestation of accelerated skin aging and photo aging after menopause.

Magnetic resonance imaging measurement of iron overload

PubMed Central

Wood, John C.

2010-01-01

Purpose of review To highlight recent advances in magnetic resonance imaging estimation of somatic iron overload. This review will discuss the need and principles of magnetic resonance imaging-based iron measurements, the validation of liver and cardiac iron measurements, and the key institutional requirements for implementation. Recent findings Magnetic resonance imaging assessment of liver and cardiac iron has achieved critical levels of availability, utility, and validity to serve as the primary endpoint of clinical trials. Calibration curves for the magnetic resonance imaging parameters R2 and R2* (or their reciprocals, T2 and T2*) have been developed for the liver and the heart. Interscanner variability for these techniques has proven to be on the order of 5–7%. Summary Magnetic resonance imaging assessment of tissue iron is becoming increasingly important in the management of transfusional iron load because it is noninvasive, relatively widely available and offers a window into presymptomatic organ dysfunction. The techniques are highly reproducible within and across machines and have been chemically validated in the liver and the heart. These techniques will become the standard of care as industry begins to support the acquisition and postprocessing software. PMID:17414205

Effect of adherent bacteria and bacterial extracellular polymers upon assimilation by Macoma balthica of sediment-bound Cd, Zn and Ag

USGS Publications Warehouse

Harvey, Ronald W.; Luoma, Samuel N.

1985-01-01

Effects of adherent bacteria and bacterial extracellular polymer (exopolymer) upon uptake of particle-bound Cd, Zn and Ag by the deposit-feeding clam Macoma balthica were studied in the laboratory. Amorphous iron oxyhydroxide and unaltered and alkaline-extracted sediments were used as model particulates in separate, controlled deposit-feeding experiments. In general, amounts of metal taken up from ingested particles varied dramatically with the nature of the particle surface. Ingestion of contaminated iron oxide particles did not contribute to overall uptake of Cd and Ag in feeding clams, but accounted for 89 to 99% of total Zn uptake. Exopolymer adsorbed on iron oxide particles caused an increase in the biological availability of particle-bound metals in the order Ag>Cd>Zn, whereas adherent bacteria up to 3.2 X 1011 g-1 had no effect upon amounts of metal taken up from ingested particulates. At the higher Cd and Ag concentrations employed (3.6 X 10-7M), feeding rates declined with increasing amounts of iron oxide-bound exopolymer, suggesting behavioral avoidance due to increased metal availability. Much of the Cd (57 %) taken up by clams feeding on unaltered estuarine sediments originated from particulates, even though particle/solute distribution of Cd (86%) was similar to that in experiments with iron oxide particles. Uptake of Cd from alkalineextracted sediments was insignificant, as it was from unamended iron oxide. However, addition of exopolymer (10 mgg-1 sediment) caused a restoration nn bioavailability of sediment-bound Cd.

Iron for Africa—Report of an Expert Workshop

PubMed Central

Mwangi, Martin N.; Phiri, Kamija S.; Abkari, Abdelhak; Gbané, Mory; Bourdet-Sicard, Raphaelle; Braesco, Véronique Azaïs; Zimmermann, Michael B.; Prentice, Andrew M.

2017-01-01

Scientific experts from nine countries gathered to share their views and experience around iron interventions in Africa. Inappropriate eating habits, infections and parasitism are responsible for significant prevalence of iron deficiency, but reliable and country-comparable prevalence estimates are lacking: improvements in biomarkers and cut-offs values adapted to context of use are needed. Benefits of iron interventions on growth and development are indisputable and outweigh risks, which exist in populations with a high infectious burden. Indeed, pathogen growth may increase with enhanced available iron, calling for caution and preventive measures where malaria or other infections are prevalent. Most African countries programmatically fortify flour and supplement pregnant women, while iron deficiency in young children is rather addressed at individual level. Coverage and efficacy could improve through increased access for target populations, raised awareness and lower cost. More bioavailable iron forms, helping to decrease iron dose, or prebiotics, which both may lower risk of infections are attractive opportunities for Africa. Fortifying specific food products could be a relevant route, adapted to local context and needs of population groups while providing education and training. More globally, partnerships involving various stakeholders are encouraged, that could tackle all aspects of the issue. PMID:28587263

Co-precipitation of phosphate and iron limits mitochondrial phosphate availability in Saccharomyces cerevisiae lacking the yeast frataxin homologue (YFH1).

PubMed

Seguin, Alexandra; Santos, Renata; Pain, Debkumar; Dancis, Andrew; Camadro, Jean-Michel; Lesuisse, Emmanuel

2011-02-25

Saccharomyces cerevisiae cells lacking the yeast frataxin homologue (Δyfh1) accumulate iron in the mitochondria in the form of nanoparticles of ferric phosphate. The phosphate content of Δyfh1 mitochondria was higher than that of wild-type mitochondria, but the proportion of mitochondrial phosphate that was soluble was much lower in Δyfh1 cells. The rates of phosphate and iron uptake in vitro by isolated mitochondria were higher for Δyfh1 than wild-type mitochondria, and a significant proportion of the phosphate and iron rapidly became insoluble in the mitochondrial matrix, suggesting co-precipitation of these species after oxidation of iron by oxygen. Increasing the amount of phosphate in the medium decreased the amount of iron accumulated by Δyfh1 cells and improved their growth in an iron-dependent manner, and this effect was mostly transcriptional. Overexpressing the major mitochondrial phosphate carrier, MIR1, slightly increased the concentration of soluble mitochondrial phosphate and significantly improved various mitochondrial functions (cytochromes, [Fe-S] clusters, and respiration) in Δyfh1 cells. We conclude that in Δyfh1 cells, soluble phosphate is limiting, due to its co-precipitation with iron.

Transfusion of stored blood impairs host defenses against Gram-negative pathogens in mice.

PubMed

Prestia, Kevin; Bandyopadhyay, Sheila; Slate, Andrea; Francis, Richard O; Francis, Kevin P; Spitalnik, Steven L; Fidock, David A; Brittenham, Gary M; Hod, Eldad A

2014-11-01

Although human red blood cell (RBC) units may be refrigerator stored for up to 42 days, transfusion of older RBCs acutely delivers a large bolus of iron to mononuclear phagocytes. Similarly, iron dextran circulates in plasma for hours to days and is progressively cleared by mononuclear phagocytes, which return iron to plasma. Finally, malaria infection continuously delivers iron to macrophages by intra- and extravascular hemolysis. Studies suggest that iron administration increases infectious risk. To assess the effects of increased iron availability on susceptibility to infection, we infected mice with model Gram-negative intracellular or extracellular pathogens (Salmonella typhimurium or Escherichia coli, respectively), accompanied by RBC transfusion, iron dextran administration, or malarial coinfection. In our mouse models, transfusion of older RBCs exacerbates infection with both Gram-negative pathogens. Although iron dextran exacerbates E. coli infection to a similar extent as transfusion of corresponding amounts of iron, higher iron doses are required to produce comparable effects with S. typhimurium. Coinfection of mice with Plasmodium yoelii and S. typhimurium produces overwhelming Salmonella sepsis. Finally, treating mice with antibiotics abrogates the enhancing effect on E. coli infection of both older RBC transfusion and iron dextran administration. Transfusion of older RBCs exacerbates Gram-negative infection to a similar extent as malaria coinfection or iron dextran administration. Appropriate antibiotic therapy abrogates the effect of older RBC transfusions on infection with E. coli. Iron delivery to macrophages may be an underappreciated mechanism mediating, at least some, adverse effects of RBC transfusions. © 2014 AABB.

Posttranslational stability of the heme biosynthetic enzyme ferrochelatase is dependent on iron availability and intact iron-sulfur cluster assembly machinery

PubMed Central

Crooks, Daniel R.; Ghosh, Manik C.; Haller, Ronald G.; Tong, Wing-Hang

2010-01-01

Mammalian ferrochelatase, the terminal enzyme in the heme biosynthetic pathway, possesses an iron-sulfur [2Fe-2S] cluster that does not participate in catalysis. We investigated ferrochelatase expression in iron-deficient erythropoietic tissues of mice lacking iron regulatory protein 2, in iron-deficient murine erythroleukemia cells, and in human patients with ISCU myopathy. Ferrochelatase activity and protein levels were dramatically decreased in Irp2−/− spleens, whereas ferrochelatase mRNA levels were increased, demonstrating posttranscriptional regulation of ferrochelatase in vivo. Translation of ferrochelatase mRNA was unchanged in iron-depleted murine erythroleukemia cells, and the stability of mature ferrochelatase protein was also unaffected. However, the stability of newly formed ferrochelatase protein was dramatically decreased during iron deficiency. Ferrochelatase was also severely depleted in muscle biopsies and cultured myoblasts from patients with ISCU myopathy, a disease caused by deficiency of a scaffold protein required for Fe-S cluster assembly. Together, these data suggest that decreased Fe-S cluster availability because of cellular iron depletion or impaired Fe-S cluster assembly causes reduced maturation and stabilization of apo-ferrochelatase, providing a direct link between Fe-S biogenesis and completion of heme biosynthesis. We propose that decreased heme biosynthesis resulting from impaired Fe-S cluster assembly can contribute to the pathogenesis of diseases caused by defective Fe-S cluster biogenesis. PMID:19965627

Impact of Microcystis aeruginosa Exudate on the Formation and Reactivity of Iron Oxide Particles Following Fe(II) and Fe(III) Addition.

PubMed

Garg, Shikha; Wang, Kai; Waite, T David

2017-05-16

Impact of the organic exudate secreted by a toxic strain of Microcystis aeruginosa on the formation, aggregation, and reactivity of iron oxides that are formed on addition of Fe(II) and Fe(III) salts to a solution of the exudate is investigated in this study. The exudate has a stabilizing effect on the particles formed with decreased aggregation rate and increased critical coagulant concentration required for diffusion-limited aggregation to occur. These results suggest that the presence of algal exudates from Microcystis aeruginosa may significantly influence particle aggregation both in natural water bodies where Fe(II) oxidation results in oxide formation and in water treatment where Fe(III) salts are commonly added to aid particle growth and contaminant capture. The exudate also affects the reactivity of iron oxide particles formed with exudate coated particles undergoing faster dissolution than bare iron oxide particles. This has implications to iron availability, especially where algae procure iron via dissolution of iron oxide particles as a result of either reaction with reducing moieties, light-mediated ligand to metal charge transfer and/or reaction with siderophores. The increased reactivity of exudate coated particles is attributed, for the most part, to the smaller size of these particles, higher surface area and increased accessibility of surface sites.

Metabolic changes of iron uptake in N(2)-fixing common bean nodules during iron deficiency.

PubMed

Slatni, Tarek; Vigani, Gianpiero; Salah, Imen Ben; Kouas, Saber; Dell'Orto, Marta; Gouia, Houda; Zocchi, Graziano; Abdelly, Chedly

2011-08-01

Iron is an important nutrient in N(2)-fixing legume nodules. The demand for this micronutrient increases during the symbiosis establishment, where the metal is utilized for the synthesis of various iron-containing proteins in both the plant and the bacteroid. Unfortunately, in spite of its importance, iron is poorly available to plant uptake since its solubility is very low when in its oxidized form Fe(III). In the present study, the effect of iron deficiency on the activity of some proteins involved in Strategy I response, such as Fe-chelate reductase (FC-R), H(+)-ATPase, and phosphoenolpyruvate carboxylase (PEPC) and the protein level of iron regulated transporter (IRT1) and H(+)-ATPase proteins has been investigated in both roots and nodules of a tolerant (Flamingo) and a susceptible (Coco blanc) cultivar of common bean plants. The main results of this study show that the symbiotic tolerance of Flamingo can be ascribed to a greater increase in the FC-R and H(+)-ATPase activities in both roots and nodules, leading to a more efficient Fe supply to nodulating tissues. The strong increase in PEPC activity and organic acid content, in the Flamingo root nodules, suggests that under iron deficiency nodules can modify their metabolism in order to sustain those activities necessary to acquire Fe directly from the soil solution. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

POTENTIAL IMPACT ON BLOOD AVAILABILITY AND DONOR IRON STATUS OF CHANGES TO DONOR HEMOGLOBIN CUTOFF AND INTERDONATION INTERVALS

PubMed Central

Spencer, Bryan R.; Johnson, Bryce; Wright, David J.; Kleinman, Steven; Glynn, Simone A.; Cable, Ritchard G.

2016-01-01

BACKGROUND A minimum male hemoglobin (Hb) of 13.0 g/dL will become an FDA requirement in May 2016. In addition, extending whole blood (WB) interdonation intervals (IDIs) beyond 8 weeks has been considered in order to reduce iron depletion in repeat blood donors. This study estimates the impact these changes might have on blood availability and donor iron status. STUDY DESIGN AND METHODS Six blood centers participating in REDS-II collected information on all donation visits from 2006–09. Simulations were developed from these data using a multi-stage approach that first sought to adequately reproduce the patterns of donor return, Hb and ferritin levels, and outcomes of a donor’s visit (successful single or double RBC donation, deferral for low Hb) observed in REDS-II datasets. Modified simulations were used to predict the potential impact on the blood supply and donor iron status under different Hb cutoff and IDI qualification criteria. RESULTS More than 10% of WB donations might require replacement under many simulated scenarios. Longer IDIs would reduce the proportion of donors with iron depletion, but 80% of these donors may remain iron-depleted if minimal IDIs increased to 12 or 16 weeks. CONCLUSION Higher Hb cutoffs and longer IDIs are predicted to have a potentially large impact on collections but only a modest impact on donor iron depletion. Efforts to address iron depletion should be targeted to at-risk donors, such as iron supplementation programs for frequent donors, and policy makers should try to avoid broadly restrictive donation requirements that could substantially reduce blood availability. PMID:27237451

Oral iron supplements for children in malaria-endemic areas

PubMed Central

Neuberger, Ami; Okebe, Joseph; Yahav, Dafna; Paul, Mical

2016-01-01

Background Iron-deficiency anaemia is common during childhood. Iron administration has been claimed to increase the risk of malaria. Objectives To evaluate the effects and safety of iron supplementation, with or without folic acid, in children living in areas with hyperendemic or holoendemic malaria transmission. Search methods We searched the Cochrane Infectious Diseases Group Specialized Register; the Cochrane Central Register of Controlled Trials (CENTRAL), published in the Cochrane Library, MEDLINE (up to August 2015) and LILACS (up to February 2015). We also checked the metaRegister of Controlled Trials (mRCT) and World Health Organization International Clinical Trials Registry Platform (WHO ICTRP) up to February 2015. We contacted the primary investigators of all included trials, ongoing trials, and those awaiting assessment to ask for unpublished data and further trials. We scanned references of included trials, pertinent reviews, and previous meta-analyses for additional references. Selection criteria We included individually randomized controlled trials (RCTs) and cluster RCTs conducted in hyperendemic and holoendemic malaria regions or that reported on any malaria-related outcomes that included children younger than 18 years of age. We included trials that compared orally administered iron, iron with folic acid, and iron with antimalarial treatment versus placebo or no treatment. We included trials of iron supplementation or fortification interventions if they provided at least 80% of the Recommended Dietary Allowance (RDA) for prevention of anaemia by age. Antihelminthics could be administered to either group, and micronutrients had to be administered equally to both groups. Data collection and analysis The primary outcomes were clinical malaria, severe malaria, and death from any cause. We assessed the risk of bias in included trials with domain-based evaluation and assessed the quality of the evidence using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. We performed a fixed-effect meta-analysis for all outcomes and random-effects meta-analysis for hematological outcomes, and adjusted analyses for cluster RCTs. We based the subgroup analyses for anaemia at baseline, age, and malaria prevention or management services on trial-level data. Main results Thirty-five trials (31,955 children) met the inclusion criteria. Overall, iron does not cause an excess of clinical malaria (risk ratio (RR) 0.93, 95% confidence intervals (CI) 0.87 to 1.00; 14 trials, 7168 children, high quality evidence). Iron probably does not cause an excess of clinical malaria in both populations where anaemia is common and those in which anaemia is uncommon. In areas where there are prevention and management services for malaria, iron (with or without folic acid) may reduce clinical malaria (RR 0.91, 95% CI 0.84 to 0.97; seven trials, 5586 participants, low quality evidence), while in areas where such services are unavailable, iron (with or without folic acid) may increase the incidence of malaria, although the lower CIs indicate no difference (RR 1.16, 95% CI 1.02 to 1.31; nine trials, 19,086 participants, low quality evidence). Iron supplementation does not cause an excess of severe malaria (RR 0.90, 95% CI 0.81 to 0.98; 6 trials, 3421 children, high quality evidence). We did not observe any differences for deaths (control event rate 1%, low quality evidence). Iron and antimalarial treatment reduced clinical malaria (RR 0.54, 95% CI 0.43 to 0.67; three trials, 728 children, high quality evidence). Overall, iron resulted in fewer anaemic children at follow up, and the end average change in haemoglobin from base line was higher with iron. Authors' conclusions Iron treatment does not increase the risk of clinical malaria when regular malaria prevention or management services are provided. Where resources are limited, iron can be administered without screening for anaemia or for iron deficiency, as long as malaria prevention or management services are provided efficiently. PLAIN LANGUAGE SUMMARY Iron supplements for children living in malaria-endemic countries Why the review is important Children living in malarial areas commonly develop anaemia. Long-term anaemia is thought to delay a child's development and make children more likely to get infections. In areas where anaemia is common, health providers may give iron to prevent anaemia, but there is a concern amongst researchers that this may increase the risk of malaria. It is thought that the iron tablets will increase iron levels in the blood, and this will promote the growth of the Plasmodium parasite that causes malaria. We aimed to assess the effects of oral iron supplementation in children living in countries where malaria is common. Main findings of the review Cochrane researchers searched the available evidence up to 30 August 2015 and included 35 trials (31,955 children). Iron did not increase the risk of malaria, indicated by fever and the presence of parasites in the blood (high quality evidence). There was no increased risk of death among children treated with iron, although the quality of the evidence for this was low. Among children treated with iron, there was no increased risk of severe malaria (high quality evidence). Although it is hypothesized that iron supplementation might harm children who do not have anaemia living in malarial areas, there is probably no increased risk for malaria in these children (moderate quality evidence). In areas where health services are sufficient to help prevent and treat malaria, giving iron supplements (with or without folic acid) may reduce clinical malaria. In areas where these services are not available, iron supplementation (with or without folic acid) may increase the number of children with clinical malaria (low quality evidence). Overall, iron resulted in fewer anaemic children at follow up, and the end average change in haemoglobin from base line was higher with iron. Conclusions Our conclusions are that iron supplementation does not adversely affect children living in malaria-endemic areas. Based on our review, routine iron supplementation should not be withheld from children living in countries where malaria is prevalent and malaria management services are available. PMID:26921618

The effect of feeding a low iron diet prior to and during gestation on fetal and maternal iron homeostasis in two strains of rat

PubMed Central

2013-01-01

Background Iron deficiency anaemia during pregnancy is a global problem, with short and long term consequences for maternal and child health. Animal models have demonstrated that the developing fetus is vulnerable to maternal iron restriction, impacting on postnatal metabolic and blood pressure regulation. Whilst long-term outcomes are similar across different models, the commonality in mechanistic events across models is unknown. This study examined the impact of iron deficiency on maternal and fetal iron homeostasis in two strains of rat. Methods Wistar (n=20) and Rowett Hooded Lister (RHL, n=19) rats were fed a control or low iron diet for 4 weeks prior to and during pregnancy. Tissues were collected at day 21 of gestation for analysis of iron content and mRNA/protein expression of regulatory proteins and transporters. Results A reduction in maternal liver iron content in response to the low iron diet was associated with upregulation of transferrin receptor expression and a reduction in hepcidin expression in the liver of both strains, which would be expected to promote increased iron absorption across the gut and increased turnover of iron in the liver. Placental expression of transferrin and DMT1+IRE were also upregulated, indicating adaptive responses to ensure availability of iron to the fetus. There were considerable differences in hepatic maternal and fetal iron content between strains. The higher quantity of iron present in livers from Wistar rats was not explained by differences in expression of intestinal iron transporters, and may instead reflect greater materno-fetal transfer in RHL rats as indicated by increased expression of placental iron transporters in this strain. Conclusions Our findings demonstrate substantial differences in iron homeostasis between two strains of rat during pregnancy, with variable impact of iron deficiency on the fetus. Whilst common developmental processes and pathways have been observed across different models of nutrient restriction during pregnancy, this study demonstrates differences in maternal adaptation which may impact on the trajectory of the programmed response. PMID:23635304

Inadequate erythroid response to hypoxia in cystic fibrosis.

PubMed

Vichinsky, E P; Pennathur-Das, R; Nickerson, B; Minor, M; Kleman, K; Higashino, S; Lubin, B

1984-07-01

An increase in hemoglobin concentration characterizes the normal compensatory response to chronic tissue hypoxia. We observed no such increase in 42 chronically hypoxic patients with cystic fibrosis, in whom the mean concentration was 12.6 gm/dl; one third of the patients were anemic. Compared with patients with cyanotic heart disease, patients with cystic fibrosis did not have a compensatory increase in P50 or 2,3-diphosphoglycerate. Despite anemia, erythropoietin levels in patients with cystic fibrosis were not significantly different from normal control values. The growth of colony-forming units-erythroid in patients with cystic fibrosis was similar to that in control subjects, and there was no inhibition of growth with the addition of autologous serum. Erythropoietin sensitivity, determined by measuring the CFUe dose response curve, was normal in both patients and controls. Results of iron studies were consistent with iron deficiency in the majority of patients. Impaired absorption of iron was observed in six of 13 iron-deficient patients with cystic fibrosis. An inverse correlation between erythrocyte sedimentation rate and peak serum iron was obtained during the iron absorption study. Eight patients who underwent a therapeutic trial of iron demonstrated a 1.8 gm/dl rise in hemoglobin concentration. Two patients with previously documented iron malabsorption responded to parenteral iron therapy after failure to respond to oral supplementation. These studies demonstrate that patients with cystic fibrosis not only have an impaired erythroid response to hypoxia, but are frequently anemic. Their inadequate erythroid response to hypoxia results in part from disturbances in erythropoietin regulation and iron availability.

Iron uptake controls the generation of Leishmania infective forms through regulation of ROS levels

PubMed Central

Mittra, Bidyottam; Cortez, Mauro; Haydock, Andrew; Ramasamy, Gowthaman; Myler, Peter J.

2013-01-01

During its life cycle, Leishmania undergoes extreme environmental changes, alternating between insect vectors and vertebrate hosts. Elevated temperature and decreased pH, conditions encountered after macrophage invasion, can induce axenic differentiation of avirulent promastigotes into virulent amastigotes. Here we show that iron uptake is a major trigger for the differentiation of Leishmania amazonensis amastigotes, independently of temperature and pH changes. We found that iron depletion from the culture medium triggered expression of the ferrous iron transporter LIT1 (Leishmania iron transporter 1), an increase in iron content of the parasites, growth arrest, and differentiation of wild-type (WT) promastigotes into infective amastigotes. In contrast, LIT1-null promastigotes showed reduced intracellular iron content and sustained growth in iron-poor media, followed by cell death. LIT1 up-regulation also increased iron superoxide dismutase (FeSOD) activity in WT but not in LIT1-null parasites. Notably, the superoxide-generating drug menadione or H2O2 was sufficient to trigger differentiation of WT promastigotes into fully infective amastigotes. LIT1-null promastigotes accumulated superoxide radicals and initiated amastigote differentiation after exposure to H2O2 but not to menadione. Our results reveal a novel role for FeSOD activity and reactive oxygen species in orchestrating the differentiation of virulent Leishmania amastigotes in a process regulated by iron availability. PMID:23382545

Iron-Hepcidin Dysmetabolism, Anemia and Renal Hypoxia, Inflammation and Fibrosis in the Remnant Kidney Rat Model

PubMed Central

Garrido, Patrícia; Ribeiro, Sandra; Fernandes, João; Vala, Helena; Bronze-da-Rocha, Elsa; Rocha-Pereira, Petronila; Belo, Luís; Costa, Elísio; Santos-Silva, Alice; Reis, Flávio

2015-01-01

Anemia is a common complication of chronic kidney disease (CKD) that develops early and its severity increases as renal function declines. It is mainly due to a reduced production of erythropoietin (EPO) by the kidneys; however, there are evidences that iron metabolism disturbances increase as CKD progresses. Our aim was to study the mechanisms underlying the development of anemia of CKD, as well as renal damage, in the remnant kidney rat model of CKD induced by 5/6 nephrectomy. This model of CKD presented a sustained degree of renal dysfunction, with mild and advanced glomerular and tubulointerstitial lesions. Anemia developed 3 weeks after nephrectomy and persisted throughout the protocol. The remnant kidney was still able to produce EPO and the liver showed an increased EPO gene expression. In spite of the increased EPO blood levels, anemia persisted and was linked to low serum iron and transferrin levels, while serum interleukin (IL)-6 and high sensitivity C-reactive protein (hs-CRP) levels showed the absence of systemic inflammation. The increased expression of duodenal ferroportin favours iron absorption; however, serum iron is reduced which might be due to iron leakage through advanced kidney lesions, as showed by tubular iron accumulation. Our data suggest that the persistence of anemia may result from disturbances in iron metabolism and by an altered activity/function of EPO as a result of kidney cell damage and a local inflammatory milieu, as showed by the increased gene expression of different inflammatory proteins in the remnant kidney. In addition, this anemia and the associated kidney hypoxia favour the development of fibrosis, angiogenesis and inflammation that may underlie a resistance to EPO stimuli and reduced iron availability. These findings might contribute to open new windows to identify putative therapeutic targets for this condition, as well as for recombinant human EPO (rHuEPO) resistance, which occurs in a considerable percentage of CKD patients. PMID:25867633

Effect of ammonium and nitrate on ferric chelate reductase and nitrate reductase in Vaccinium species.

PubMed

Poonnachit, U; Darnell, R

2004-04-01

Most Vaccinium species have strict soil requirements for optimal growth, requiring low pH, high iron availability and nitrogen primarily in the ammonium form. These soils are limited and are often located near wetlands. Vaccinium arboreum is a wild species adapted to a wide range of soils, including high pH, low iron, and nitrate-containing soils. This broader soil adaptation in V. arboreum may be related to increased efficiency of iron or nitrate uptake compared with the cultivated Vaccinium species. Nitrate, ammonium and iron uptake, and nitrate reductase (NR) and ferric chelate reductase (FCR) activities were compared in two Vaccinium species grown hydroponically in either nitrate or ammonia, with or without iron. The species studied were the wild V. arboreum and the cultivated V. corymbosum interspecific hybrid, which exhibits the strict soil requirements of most Vaccinium species. Ammonium uptake was significantly greater than nitrate uptake in both species, while nitrate uptake was greater in the wild species, V. arboreum, compared with the cultivated species, V. corymbosum. The increased nitrate uptake in V. arboreum was correlated with increased root NR activity compared with V. corymbosum. The lower nitrate uptake in V. corymbosum was reflected in decreased plant dry weight in this species compared with V. arboreum. Root FCR activity increased significantly in V. corymbosum grown under iron-deficient conditions, compared with the same species grown under iron-sufficient conditions or with V. arboreum grown under either iron condition. V. arboreum appears to be more efficient in acquiring nitrate compared with V. corymbosum, possibly due to increased NR activity and this may partially explain the wider soil adaptation of V. arboreum.

Long-term trends in dissolved iron and DOC concentration linked to nitrate depletion in riparian soils

NASA Astrophysics Data System (ADS)

Musolff, Andreas; Selle, Benny; Fleckenstein, Jan H.; Oosterwoud, Marieke R.; Tittel, Jörg

2016-04-01

The instream concentrations of dissolved organic carbon (DOC) are rising in many catchments of the northern hemisphere. Elevated concentrations of DOC, mainly in the form of colored humic components, increase efforts and costs of drinking water purification. In this study, we evaluated a long-term dataset of 110 catchments draining into German drinking water reservoirs in order to assess sources of DOC and drivers of a potential long-term change. The average DOC concentrations across the wide range of different catchments were found to be well explained by the catchment's topographic wetness index. Higher wetness indices were connected to higher average DOC concentrations, which implies that catchments with shallow topography and pronounced riparian wetlands mobilize more DOC. Overall, 37% of the investigated catchments showed a significant long-term increase in DOC concentrations, while 22% exhibited significant negative trends. Moreover, we found that increasing trends in DOC were positively correlated to trends in dissolved iron concentrations at pH≤6 due to remobilization of DOC previously sorbed to iron minerals. Both, increasing trends in DOC and dissolve iron were found to be connected to decreasing trends and low concentrations of nitrate (below ~6 mg/L). This was especially observed in forested catchments where atmospheric N-depositions were the major source for nitrate availability. In these catchments, we also found long-term increases of phosphate concentrations. Therefore, we argue that dissolved iron, DOC and phosphate were jointly released under iron-reducing conditions when nitrate as a competing electron acceptor was too low in concentrations to prevent the microbial iron reduction. In contrast, we could not explain the observed increasing trends in DOC, iron and phosphate concentrations by the long-term trends of pH, sulfate or precipitation. Altogether this study gives strong evidence that both, source and long-term increases in DOC are primarily controlled by riparian wetland soils within the catchments. Here, the achievement of a long-term reduction in nitrogen deposition may in turn lead to a more pronounced iron reduction and a subsequent release of DOC and other iron-bound substances such as phosphate.

Dietary strategies for improving iron status: balancing safety and efficacy

PubMed Central

Mendoza, Yery A.; Pereira, Dora; Cerami, Carla; Wegmuller, Rita; Constable, Anne; Spieldenner, Jörg

2017-01-01

In light of evidence that high-dose iron supplements lead to a range of adverse events in low-income settings, the safety and efficacy of lower doses of iron provided through biological or industrial fortification of foodstuffs is reviewed. First, strategies for point-of-manufacture chemical fortification are compared with biofortification achieved through plant breeding. Recent insights into the mechanisms of human iron absorption and regulation, the mechanisms by which iron can promote malaria and bacterial infections, and the role of iron in modifying the gut microbiota are summarized. There is strong evidence that supplemental iron given in nonphysiological amounts can increase the risk of bacterial and protozoal infections (especially malaria), but the use of lower quantities of iron provided within a food matrix, ie, fortified food, should be safer in most cases and represents a more logical strategy for a sustained reduction of the risk of deficiency by providing the best balance of risk and benefits. Further research into iron compounds that would minimize the availability of unabsorbed iron to the gut microbiota is warranted. PMID:27974599

Upregulation of transferrin receptor-1 induces cholangiocarcinoma progression via induction of labile iron pool.

PubMed

Jamnongkan, Wassana; Thanan, Raynoo; Techasen, Anchalee; Namwat, Nisana; Loilome, Watcharin; Intarawichian, Piyapharom; Titapun, Attapol; Yongvanit, Puangrat

2017-07-01

Labile iron pool is a cellular source of ions available for Fenton reactions resulting in oxidative stress. Living organisms avoid an excess of free irons by a tight control of iron homeostasis. We investigated the altered expression of iron regulatory proteins and iron discrimination in the development of liver fluke-associated cholangiocarcinoma. Additionally, the levels of labile iron pool and the functions of transferrin receptor-1 on cholangiocarcinoma development were also identified. Iron deposition was determined using the Prussian blue staining method in human cholangiocarcinoma tissues. We investigated the alteration of iron regulatory proteins including transferrin, transferrin receptor-1, ferritin, ferroportin, hepcidin, and divalent metal transporter-1 in cholangiocarcinoma tissues using immunohistochemistry. The clinicopathological data of cholangiocarcinoma patients and the expressions of proteins were analyzed. Moreover, the level of intracellular labile iron pool in cholangiocarcinoma cell lines was identified by the RhoNox-1 staining method. We further demonstrated transferrin receptor-1 functions on cell proliferation and migration upon small interfering RNA for human transferrin receptor 1 transfection. Results show that Iron was strongly stained in tumor tissues, whereas negative staining was observed in normal bile ducts of healthy donors. Interestingly, high iron accumulation was significantly correlated with poor prognosis of cholangiocarcinoma patients. The expressions of iron regulatory proteins in human cholangiocarcinoma tissues and normal liver from cadaveric donors revealed that transferrin receptor-1 expression was increased in the cancer cells of cholangiocarcinoma tissues when compared with the adjacent normal bile ducts and was significantly correlated with cholangiocarcinoma metastasis. Labile iron pool level and transferrin receptor-1 expression were significantly increased in KKU-214 and KKU-213 when compared with cholangiocyte cells (MMNK1). Additionally, the suppression of transferrin receptor-1 expression significantly decreased intracellular labile iron pool, cholangiocarcinoma migration, and cell proliferation when compared with control media and control small interfering RNA. In Conclusion, high expression of transferrin receptor-1 resulting in iron uptake contributes to increase in the labile iron pool which plays roles in cholangiocarcinoma progression with aggressive clinical outcomes.

Anti-TNF-Mediated Modulation of Prohepcidin Improves Iron Availability in Inflammatory Bowel Disease, in an IL-6-Mediated Fashion.

PubMed

Cavallaro, Flaminia; Duca, Lorena; Pisani, Laura Francesca; Rigolini, Roberta; Spina, Luisa; Tontini, Gian Eugenio; Munizio, Nadia; Costa, Elena; Cappellini, Maria Domenica; Vecchi, Maurizio; Pastorelli, Luca

2017-01-01

Background. Anaemia is common in inflammatory bowel disease (IBD), frequently resulting from a combination of iron deficiency and of anaemia of chronic disease (ACD). ACD is characterized by macrophage iron retention induced by proinflammatory cytokines. Hepcidin is the master inducer of iron accumulation during ACD, and its production is mainly regulated by IL-6 and the novel erythroid hormone erythroferrone (ERFE). This study evaluates whether anti-TNF monoclonal antibodies therapy modurates hepcidin production and the levels of its main regulators, leading to a restoration of iron homeostasis. Methods. Sera were collected from 21 IBD patients, before each anti-TNF administration, for the first 6 weeks of therapy. Prohepcidin, erythropoietin, erythroferrone, C reactive protein, interleukin-6, iron markers, and haemoglobin levels were measured and clinical activity indexes were evaluated. Results. Serum prohepcidin, IL-6, CRP, and ferritin were significantly reduced after 6-week treatment; an increase in serum iron and total transferrin was observed. No changes in the EPO-ERFE axis were found. Remarkably, haemoglobin was significantly increased. Conclusions. Anti-TNF therapy improves iron metabolism and, subsequently, anaemia in IBD. This effect appears to be related to the modulation of the cytokine network and specifically IL-6 leading to a relevant decrease of hepcidin, a master regulator of ACD.

Nitric Oxide Improves Internal Iron Availability in Plants1

PubMed Central

Graziano, Magdalena; Beligni, María Verónica; Lamattina, Lorenzo

2002-01-01

Iron deficiency impairs chlorophyll biosynthesis and chloroplast development. In leaves, most of the iron must cross several biological membranes to reach the chloroplast. The components involved in the complex internal iron transport are largely unknown. Nitric oxide (NO), a bioactive free radical, can react with transition metals to form metal-nitrosyl complexes. Sodium nitroprusside, an NO donor, completely prevented leaf interveinal chlorosis in maize (Zea mays) plants growing with an iron concentration as low as 10 μm Fe-EDTA in the nutrient solution. S-Nitroso-N-acetylpenicillamine, another NO donor, as well as gaseous NO supply in a translucent chamber were also able to revert the iron deficiency symptoms. A specific NO scavenger, 2-(4-carboxy-phenyl)-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide, blocked the effect of the NO donors. The effect of NO treatment on the photosynthetic apparatus of iron-deficient plants was also studied. Electron micrographs of mesophyll cells from iron-deficient maize plants revealed plastids with few photosynthetic lamellae and rudimentary grana. In contrast, in NO-treated maize plants, mesophyll chloroplast appeared completely developed. NO treatment did not increase iron content in plant organs, when expressed in a fresh matter basis, suggesting that root iron uptake was not enhanced. NO scavengers 2-(4-carboxy-phenyl)-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide and methylene blue promoted interveinal chlorosis in iron-replete maize plants (growing in 250 μm Fe-EDTA). Even though results support a role for endogenous NO in iron nutrition, experiments did not establish an essential role. NO was also able to revert the chlorotic phenotype of the iron-inefficient maize mutants yellow stripe1 and yellow stripe3, both impaired in the iron uptake mechanisms. All together, these results support a biological action of NO on the availability and/or delivery of metabolically active iron within the plant. PMID:12481068

The effect of CO2 availability on the growth, iron oxidation and CO2-fixation rates of pure cultures of Leptospirillum ferriphilum and Acidithiobacillus ferrooxidans.

PubMed

Bryan, C G; Davis-Belmar, C S; van Wyk, N; Fraser, M K; Dew, D; Rautenbach, G F; Harrison, S T L

2012-07-01

Understanding how bioleaching systems respond to the availability of CO(2) is essential to developing operating conditions that select for optimum microbial performance. Therefore, the effect of inlet gas and associated dissolved CO(2) concentration on the growth, iron oxidation and CO(2) -fixation rates of pure cultures of Acidithiobacillus ferrooxidans and Leptospirillum ferriphilum was investigated in a batch stirred tank system. The minimum inlet CO(2) concentrations required to promote the growth of At. ferrooxidans and L. ferriphilum were 25 and 70 ppm, respectively, and corresponded to dissolved CO(2) concentrations of 0.71 and 1.57 µM (at 30°C and 37°C, respectively). An actively growing culture of L. ferriphilum was able to maintain growth at inlet CO(2) concentrations less than 30 ppm (0.31-0.45 µM in solution). The highest total new cell production and maximum specific growth rates from the stationary phase inocula were observed with CO(2) inlet concentrations less than that of air. In contrast, the amount of CO(2) fixed per new cell produced increased with increasing inlet CO(2) concentrations above 100 ppm. Where inlet gas CO(2) concentrations were increased above that of air the additional CO(2) was consumed by the organisms but did not lead to increased cell production or significantly increase performance in terms of iron oxidation. It is proposed that At. ferrooxidans has two CO(2) uptake mechanisms, a high affinity system operating at low available CO(2) concentrations, which is subject to substrate inhibition and a low affinity system operating at higher available CO(2) concentrations. L. ferriphilum has a single uptake system characterised by a moderate CO(2) affinity. At. ferrooxidans performed better than L. ferriphilum at lower CO(2) availabilities, and was less affected by CO(2) starvation. Finally, the results demonstrate the limitations of using CO(2) uptake or ferrous iron oxidation data as indirect measures of cell growth and performance across varying physiological conditions. Copyright © 2012 Wiley Periodicals, Inc.

A Rice Phenolic Efflux Transporter Is Essential for Solubilizing Precipitated Apoplasmic Iron in the Plant Stele*

PubMed Central

Ishimaru, Yasuhiro; Kakei, Yusuke; Shimo, Hugo; Bashir, Khurram; Sato, Yutaka; Sato, Yuki; Uozumi, Nobuyuki; Nakanishi, Hiromi; Nishizawa, Naoko K.

2011-01-01

Iron deficiency is one of the major agricultural problems, as 30% of the arable land of the world is too alkaline for optimal crop production, rendering plants short of available iron despite its abundance. To take up apoplasmic precipitated iron, plants secrete phenolics such as protocatechuic acid (PCA) and caffeic acid. The molecular pathways and genes of iron uptake strategies are already characterized, whereas the molecular mechanisms of phenolics synthesis and secretion have not been clarified, and no phenolics efflux transporters have been identified in plants yet. Here we describe the identification of a phenolics efflux transporter in rice. We identified a cadmium-accumulating rice mutant in which the amount of PCA and caffeic acid in the xylem sap was dramatically reduced and hence named it phenolics efflux zero 1 (pez1). PEZ1 localized to the plasma membrane and transported PCA when expressed in Xenopus laevis oocytes. PEZ1 localized mainly in the stele of roots. In the roots of pez1, precipitated apoplasmic iron increased. The growth of PEZ1 overexpression lines was severely restricted, and these lines accumulated more iron as a result of the high solubilization of precipitated apoplasmic iron in the stele. We show that PEZ1 is responsible for an increase of PCA concentration in the xylem sap and is essential for the utilization of apoplasmic precipitated iron in the stele. PMID:21602276

Considerations and challenges in defining optimal iron utilization in hemodialysis.

PubMed

Charytan, David M; Pai, Amy Barton; Chan, Christopher T; Coyne, Daniel W; Hung, Adriana M; Kovesdy, Csaba P; Fishbane, Steven

2015-06-01

Trials raising concerns about erythropoiesis-stimulating agents, revisions to their labeling, and changes to practice guidelines and dialysis payment systems have provided strong stimuli to decrease erythropoiesis-stimulating agent use and increase intravenous iron administration in recent years. These factors have been associated with a rise in iron utilization, particularly among hemodialysis patients, and an unprecedented increase in serum ferritin concentrations. The mean serum ferritin concentration among United States dialysis patients in 2013 exceeded 800 ng/ml, with 18% of patients exceeding 1200 ng/ml. Although these changes are broad based, the wisdom of these practices is uncertain. Herein, we examine influences on and trends in intravenous iron utilization and assess the clinical trial, epidemiologic, and experimental evidence relevant to its safety and efficacy in the setting of maintenance dialysis. These data suggest a potential for harm from increasing use of parenteral iron in dialysis-dependent patients. In the absence of well powered, randomized clinical trials, available evidence will remain inadequate for making reliable conclusions about the effect of a ubiquitous therapy on mortality or other outcomes of importance to dialysis patients. Nephrology stakeholders have an urgent obligation to initiate well designed investigations of intravenous iron in order to ensure the safety of the dialysis population. Copyright © 2015 by the American Society of Nephrology.

Acidic processing of mineral dust iron by anthropogenic compounds over the north Pacific Ocean

NASA Astrophysics Data System (ADS)

Solmon, F.; Chuang, P. Y.; Meskhidze, N.; Chen, Y.

2009-01-01

Atmospheric processing of mineral aerosol by anthropogenic pollutants may be an important process by which insoluble iron can be transformed into soluble forms and become available to oceanic biota. Observations of the soluble iron fraction in atmospheric aerosol exhibit large variability, which is poorly represented in models. In this study, we implemented a dust iron dissolution scheme in a global chemistry transport model (GEOS-Chem). The model is applied over the North Pacific Ocean during April 2001, a period when concentrations of dust and pollution within the east Asia outflow were high. Simulated fields of many key chemical constituents compare reasonably well with available observations, although some discrepancies are identified and discussed. In our simulations, the production of soluble iron varies temporally and regionally depending on pollution-to-dust ratio, primarily due to strong buffering by calcite. Overall, we show that the chemical processing mechanism produces significant amounts of dissolved iron reaching and being deposited in remote regions of the Pacific basin, with some seasonal variability. Simulated enhancements in particulate soluble iron fraction range from 0.5% to 6%, which is consistent with the observations. According to our simulations, ˜30% to 70% of particulate soluble iron over the North Pacific Ocean basin can be attributed to atmospheric processing. On the basis of April 2001 monthly simulations, sensitivity tests suggest that doubling SO2 emissions can induce a significant increase (13% on average, up to 40% during specific events) in dissolved iron production and deposition to the remote Pacific. We roughly estimate that half of the primary productivity induced by iron deposition in a north Pacific high-nutrient low-chlorophyll region is due to soluble iron derived from anthropogenic chemical processing of Asian aerosol.

Management of inflammatory bowel disease-related anemia and iron deficiency with specific reference to the role of intravenous iron in current practice.

PubMed

Stein, Jürgen; Aksan, Ayşegül; Farrag, Karima; Dignass, Axel; Radeke, Heinfried H

2017-11-01

Anemia is a common extraintestinal manifestation in patients with inflammatory bowel disease, impacting disease prognosis, morbidity, hospitalization rates and time lost from work. While iron deficiency anemia and anemia of chronic inflammation predominate, combinations of hematimetric and biochemical markers facilitate the diagnosis and targeted therapy of other etiologies according to their underlying pathophysiological causes. Intravenous iron replacement is currently recommended in IBD patients with moderate to severe anemia or intolerance to oral iron. Areas covered: This review examines the impact, pathophysiology and diagnostics of iron deficiency and anemia, compares the characteristics and safety profiles of available oral and intravenous iron preparations, and highlights issues which require consideration in decision making for therapy administration and monitoring. Expert opinion: Modern intravenous iron formulations have been shown to be safe and effective in IBD patients, allowing rapid anemia correction and repletion of iron stores. While traditional oral iron preparations are associated with increased inflammation, negative effects on the microbiome, and poor tolerance and compliance, first clinical trial data indicate that newer oral compounds such as ferric maltol and sucrosomial iron offer improved tolerability and may thus offer a viable alternative for the future.

Staphylococcus aureus Redirects Central Metabolism to Increase Iron Availability

PubMed Central

Pishchany, Gleb; Whitwell, Corbin W; Torres, Victor J; Skaar, Eric P

2006-01-01

Staphylococcus aureus pathogenesis is significantly influenced by the iron status of the host. However, the regulatory impact of host iron sources on S. aureus gene expression remains unknown. In this study, we combine multivariable difference gel electrophoresis and mass spectrometry with multivariate statistical analyses to systematically cluster cellular protein response across distinct iron-exposure conditions. Quadruplicate samples were simultaneously analyzed for alterations in protein abundance and/or post-translational modification state in response to environmental (iron chelation, hemin treatment) or genetic (Δfur) alterations in bacterial iron exposure. We identified 120 proteins representing several coordinated biochemical pathways that are affected by changes in iron-exposure status. Highlighted in these experiments is the identification of the heme-regulated transport system (HrtAB), a novel transport system which plays a critical role in staphylococcal heme metabolism. Further, we show that regulated overproduction of acidic end-products brought on by iron starvation decreases local pH resulting in the release of iron from the host iron-sequestering protein transferrin. These findings reveal novel strategies used by S. aureus to acquire scarce nutrients in the hostile host environment and begin to define the iron and heme-dependent regulons of S. aureus. PMID:16933993

The glacial iron cycle from source to export

NASA Astrophysics Data System (ADS)

Hawkings, J.; Wadham, J. L.; Tranter, M.; Raiswell, R.; Benning, L. G.; Statham, P. J.; Tedstone, A. J.; Nienow, P. W.; Telling, J.; Bagshaw, E.; Simmons, S. L.

2014-12-01

Nutrient availability limits primary production in large sectors of the world's oceans. Iron is the major limiting nutrient in around one third of the oceanic euphotic zone, most significantly in the Southern Ocean proximal to Antarctica. In these areas the availability of bioavailable iron can influence the amount of primary production, and thus the strength of the biological pump and associated carbon drawdown from the atmosphere. Despite experiencing widespread iron limitation, the Polar oceans are among the most productive on Earth. Due to the extreme cold, remoteness and their perceived "stasis", ice sheets have previously been though of as insignificant in global biogeochemical cycles. However, large marine algal blooms have been observed in iron-limited areas where glacial influence is large, and it is possible that these areas are stimulated by glacial bioavailable iron input. Here we discuss the importance of the Greenland and Antarctic ice sheets in the global iron cycle. Using field collected trace element data, bulk meltwater chemistry and mineralogical analysis, including photomicrographs, EELS and XANES, we present, for the first time, a conceptual model of the glacial iron cycle from source to export. Using this data we discuss the sources of iron in glacial meltwater, transportation and alteration through the glacial system, and subsequent export to downstream environments. Data collected in 2012 and 2013 from two different Greenlandic glacial catchments are shown, with the most detailed breakdown of iron speciation and concentrations in glacial areas yet reported. Furthermore, the first data from Greenlandic icebergs is presented, allowing meltwater-derived and iceberg-derived iron export to be compared, and the influence of both in marine productivity to be estimated. Using our conceptual model and flux estimates from our dataset, glacial iron delivery in both the northern and southern hemisphere is discussed. Finally, we compare our flux estimates to other major iron sources to the polar regions such as aeolian dust, and discuss potential implications of increased melting of the ice sheets on the global iron cycle in the future.

Iron in Neisseria meningitidis: minimum requirements, effects of limitation, and characteristics of uptake.

PubMed Central

Archibald, F S; DeVoe, I W

1978-01-01

A simple defined medium (neisseria defined medium) was devised that does not require iron extraction to produce iron-limited growth of Neisseria meningitidis (SDIC). Comparison of this medium to Mueller-Hinton broth and agar showed nearly identical growth rates and yields. The defined medium was used in batch cultures to determine the disappearance of iron from the medium and its uptake by cells. To avoid a number of problems inherent in batch culture, continuous culture, in which iron and dissolved oxygen were varied independently, was used. Most of the cellular iron was found to be nonheme and associated with the particulate fraction in sonically disrupted cells. Nonheme and catalase-heme iron were reduced by iron starvation far more than cytochromes b and c and N,N,N',N'-tetramethylphenylenediamine-oxidase. The respiration rate and efficiency also decreased under iron limitation, whereas generation times increased. The iron-starved meningococcus took up iron by an energy-independent system operating in the first minute after an iron pulse and a slower energy-dependent system inhibited by respiratory poisons and an uncoupler. The energy-dependent system showed saturation kinetics and was stimulated nearly fourfold by iron privation. In addition, to determine the availability to the meningococcus of the iron in selected compounds, a sensitive assay was devised in which an iron-limited continuous culture was pulsed with the iron-containing compound. PMID:101516

Synthetic and natural iron chelators: therapeutic potential and clinical use

PubMed Central

Hatcher, Heather C; Singh, Ravi N; Torti, Frank M; Torti, Suzy V

2013-01-01

Iron-chelation therapy has its origins in the treatment of iron-overload syndromes. For many years, the standard for this purpose has been deferoxamine. Recently, considerable progress has been made in identifying synthetic chelators with improved pharmacologic properties relative to deferoxamine. Most notable are deferasirox (Exjade®) and deferiprone (Ferriprox®), which are now available clinically. In addition to treatment of iron overload, there is an emerging role for iron chelators in the treatment of diseases characterized by oxidative stress, including cardiovascular disease, atherosclerosis, neurodegenerative diseases and cancer. While iron is not regarded as the underlying cause of these diseases, it does play an important role in disease progression, either through promotion of cellular growth and proliferation or through participation in redox reactions that catalyze the formation of reactive oxygen species and increase oxidative stress. Thus, iron chelators may be of therapeutic benefit in many of these conditions. Phytochemicals, many of which bind iron, may also owe some of their beneficial properties to iron chelation. This review will focus on the advances in iron-chelation therapy for the treatment of iron-overload disease and cancer, as well as neurodegenerative and chronic inflammatory diseases. Established and novel iron chelators will be discussed, as well as the emerging role of dietary plant polyphenols that effectively modulate iron biochemistry. PMID:21425984

TLc-A, the leading nanochelating-based nanochelator, reduces iron overload in vitro and in vivo.

PubMed

Kalanaky, Somayeh; Hafizi, Maryam; Safari, Sepideh; Mousavizadeh, Kazem; Kabiri, Mahboubeh; Farsinejad, Alireza; Fakharzadeh, Saideh; Nazaran, Mohammad Hassan

2016-03-01

Iron chelation therapy is an effective approach to the treatment of iron overload conditions, in which iron builds up to toxic levels in the body and may cause organ damage. Treatments using deferoxamine, deferasirox and deferiprone have been introduced and despite their disadvantages, they remain the first-line therapeutics in iron chelation therapy. Our study aimed to compare the effectiveness of the iron chelation agent TLc-A, a nano chelator synthetized based on the novel nanochelating technology, with deferoxamine. We found that TLc-A reduced iron overload in Caco2 cell line more efficiently than deferoxamine. In rats with iron overload, very low concentrations of TLc-A lowered serum iron level after only three injections of the nanochelator, while deferoxamine was unable to reduce iron level after the same number of injections. Compared with deferoxamine, TLc-A significantly increased urinary iron excretion and reduced hepatic iron content. The toxicity study showed that the intraperitoneal median lethal dose for TLc-A was at least two times higher than that for deferoxamine. In conclusion, our in vitro and in vivo studies indicate that the novel nano chelator compound, TLc-A, offers superior performance in iron reduction than the commercially available and widely used deferoxamine.

Prenatal Alcohol Exposure Alters Fetal Iron Distribution and Elevates Hepatic Hepcidin in a Rat Model of Fetal Alcohol Spectrum Disorders123

PubMed Central

Huebner, Shane M; Blohowiak, Sharon E; Kling, Pamela J; Smith, Susan M

2016-01-01

Background: Prenatal alcohol exposure (PAE) causes neurodevelopmental disabilities, and gestational iron deficiency (ID) selectively worsens learning and neuroanatomical and growth impairments in PAE. It is unknown why ID worsens outcomes in alcohol-exposed offspring. Objective: We hypothesized that PAE alters maternal-fetal iron distribution or its regulation. Methods: Nulliparous, 10-wk-old, Long-Evans rats were mated and then fed iron-sufficient (100 mg Fe/kg) or iron-deficient (≤4 mg Fe/kg) diets. On gestational days 13.5–19.5, dams received either 5.0 g ethanol/kg body weight (PAE) or isocaloric maltodextrin by oral gavage. On gestational day 20.5, maternal and fetal clinical blood counts, tissue mineral and iron transport protein concentrations, and hepatic hepcidin mRNA expression were determined. Results: In fetal brain and liver (P < 0.001) and in maternal liver (P < 0.005), ID decreased iron (total and nonheme) and ferritin content by nearly 200%. PAE reduced fetal bodyweight (P < 0.001) and interacted with ID (P < 0.001) to reduce it by an additional 20%. Independent of maternal iron status, PAE increased fetal liver iron (30–60%, P < 0.001) and decreased brain iron content (total and nonheme, 15–20%, P ≤ 0.050). ID-PAE brains had lower ferritin, transferrin, and transferrin receptor content (P ≤ 0.002) than ID-maltodextrin brains. PAE reduced fetal hematocrit, hemoglobin, and red blood cell numbers (P < 0.003) independently of iron status. Unexpectedly, and also independent of iron status, PAE increased maternal and fetal hepatic hepcidin mRNA expression >300% (P < 0.001). Conclusions: PAE altered fetal iron distribution independent of maternal iron status in rats. The elevated iron content of fetal liver suggests that PAE may have limited iron availability for fetal erythropoiesis and brain development. Altered fetal iron distribution may partly explain why maternal ID substantially worsens growth and behavioral outcomes in PAE. PMID:27146918

Regulation of the Vibrio vulnificus hupA gene by temperature alteration and cyclic AMP receptor protein and evaluation of its role in virulence.

PubMed

Oh, Man Hwan; Lee, Sung Min; Lee, Dong Hwan; Choi, Sang Ho

2009-03-01

Availability of free iron is extremely limited in the mammalian host, and the acquisition of iron in the host is essential for successful infection by pathogenic bacteria. Expression of many genes involved in acquiring iron is regulated in response to the level of iron availability, and iron regulation is mediated by Fur. In this study, cellular levels of Vibrio vulnificus HupA, a heme receptor protein, and the hupA transcript were found to increase in cells grown at 40 degrees C compared to cells grown at 30 degrees C. The results suggested that change in growth temperature, in addition to iron availability, is an environmental cue controlling the expression of the hupA gene. The influence of global regulatory proteins on the expression of hupA was examined, and the cyclic AMP receptor protein (CRP) was found to activate the expression of hupA at the transcriptional level. CRP exerts its effects by directly binding to DNA upstream of the hupA promoter P(hupA), and a CRP binding site, centered at 174 bp upstream of the transcription start site, was identified by a DNase I protection assay. Finally, a hupA mutant showed reduced virulence in mice and in tissue cultures, in which growth of the hupA mutant was impaired, indicating that HupA of V. vulnificus is essential for survival and multiplication during infection.

Regulation of the Vibrio vulnificus hupA Gene by Temperature Alteration and Cyclic AMP Receptor Protein and Evaluation of Its Role in Virulence▿

PubMed Central

Oh, Man Hwan; Lee, Sung Min; Lee, Dong Hwan; Choi, Sang Ho

2009-01-01

Availability of free iron is extremely limited in the mammalian host, and the acquisition of iron in the host is essential for successful infection by pathogenic bacteria. Expression of many genes involved in acquiring iron is regulated in response to the level of iron availability, and iron regulation is mediated by Fur. In this study, cellular levels of Vibrio vulnificus HupA, a heme receptor protein, and the hupA transcript were found to increase in cells grown at 40°C compared to cells grown at 30°C. The results suggested that change in growth temperature, in addition to iron availability, is an environmental cue controlling the expression of the hupA gene. The influence of global regulatory proteins on the expression of hupA was examined, and the cyclic AMP receptor protein (CRP) was found to activate the expression of hupA at the transcriptional level. CRP exerts its effects by directly binding to DNA upstream of the hupA promoter PhupA, and a CRP binding site, centered at 174 bp upstream of the transcription start site, was identified by a DNase I protection assay. Finally, a hupA mutant showed reduced virulence in mice and in tissue cultures, in which growth of the hupA mutant was impaired, indicating that HupA of V. vulnificus is essential for survival and multiplication during infection. PMID:19139193

Effects of long-term weekly iron and folic acid supplementation on lower genital tract infection - a double blind, randomised controlled trial in Burkina Faso.

PubMed

Brabin, Loretta; Roberts, Stephen A; Gies, Sabine; Nelson, Andrew; Diallo, Salou; Stewart, Christopher J; Kazienga, Adama; Birtles, Julia; Ouedraogo, Sayouba; Claeys, Yves; Tinto, Halidou; d'Alessandro, Umberto; Faragher, E Brian; Brabin, Bernard

2017-11-23

Provision of routine iron supplements to prevent anaemia could increase the risk for lower genital tract infections as virulence of some pathogens depends on iron availability. This trial in Burkina Faso assessed whether weekly periconceptional iron supplementation increased the risk of lower genital tract infection in young non-pregnant and pregnant women. Genital tract infections were assessed within a double blind, controlled, non-inferiority trial of malaria risk among nulliparous women, randomised to receive either iron and folic acid or folic acid alone, weekly, under direct observation for 18 months. Women conceiving during this period entered the pregnancy cohort. End assessment (FIN) for women remaining non-pregnant was at 18 months. For the pregnancy cohort, end assessment was at the first scheduled antenatal visit (ANC1). Infection markers included Nugent scores for abnormal flora and bacterial vaginosis (BV), T. vaginalis PCR, vaginal microbiota, reported signs and symptoms, and antibiotic and anti-fungal prescriptions. Iron biomarkers were assessed at baseline, FIN and ANC1. Analysis compared outcomes by intention to treat and in iron replete/deficient categories. A total of 1954 women (mean 16.8 years) were followed and 478 (24.5%) became pregnant. Median supplement adherence was 79% (IQR 59-90%). Baseline BV prevalence was 12.3%. At FIN and ANC1 prevalence was 12.8% and 7.0%, respectively (P < 0.011). T. vaginalis prevalence was 4.9% at FIN and 12.9% at ANC1 (P < 0.001). BV and T. vaginalis prevalence and microbiota profiles did not differ at trial end-points. Iron-supplemented non-pregnant women received more antibiotic treatments for non-genital infections (P = 0.014; mainly gastrointestinal infections (P = 0.005), anti-fungal treatments for genital infections (P = 0.014) and analgesics (P = 0.008). Weekly iron did not significantly reduce iron deficiency prevalence. At baseline, iron-deficient women were more likely to have normal vaginal flora (P = 0.016). Periconceptional weekly iron supplementation of young women did not increase the risk of lower genital tract infections but did increase general morbidity in the non-pregnant cohort. Unabsorbed gut iron due to malaria could induce enteric infections, accounting for the increased administration of antibiotics and antifungals in the iron-supplemented arm. This finding reinforces concerns about routine iron supplementation in highly malarious areas. Trial registration number NCT01210040 . Registered with Clinicaltrials.gov on 27 September 2010.

Iron dosing in kidney disease: inconsistency of evidence and clinical practice

PubMed Central

Gaweda, Adam E.; Ginzburg, Yelena Z.; Chait, Yossi; Germain, Michael J.; Aronoff, George R.; Rachmilewitz, Eliezer

2015-01-01

The management of anemia in patients with chronic kidney disease (CKD) is difficult. The availability of erythropoiesis-stimulating agents (ESAs) has increased treatment options for previously transfusion-requiring patients, but the recent evidence of ESA side effects has prompted the search for complementary or alternative approaches. Next to ESA, parenteral iron supplementation is the second main form of anemia treatment. However, as of now, no systematic approach has been proposed to balance the concurrent administration of both agents according to individual patient's needs. Furthermore, the potential risks of excessive iron dosing remain a topic of controversy. How, when and whether to monitor CKD patients for potential iron overload remain to be elucidated. This review addresses the question of risk and benefit of iron administration in CKD, highlights the evidence supporting current practice, provides an overview of standard and potential new markers of iron status and outlines a new pharmacometric approach to physiologically compatible individualized dosing of ESA and iron in CKD patients. PMID:24821751

Advantages and disadvantages of an iron-rich diet.

PubMed

Hallberg, L

2002-03-01

A review by invitation about advantages and disadvantages of an iron-rich diet by analyzing physiological iron requirements, dietary factors influencing iron absorption and the regulatory systems available to control iron absorption according to needs. The control to prevent iron deficiency is good but not perfect, as observed in previously described studies on relationships between individual iron requirements and the probability of iron deficiency developing in relation to diet. The control to prevent iron overload seems to be perfect except in the few subjects being homozygotes for hereditary hemochromatosis. A diet rich in easily available iron is important for covering basal iron losses, menstrual iron losses and the high iron requirements for growth from infancy to adolescence and for pregnancy.

Using iron fertilizer to control Cd accumulation in rice plants: a new promising technology.

PubMed

Shao, GuoSheng; Chen, MingXue; Wang, DanYing; Xu, ChunMei; Mou, RenXiang; Cao, ZhaoYun; Zhang, XiuFu

2008-03-01

Effects of two kinds of iron fertilizer, FeSO4 and EDTA.Na2Fe were studied on cadmium accumulation in rice plants with two rice genotypes, Zhongzao 22 and Zhongjiazao 02, with soil culture systems. The results showed that application of iron fertilizers could hardly make adverse effects on plant growth and rice grain yield. Soil application of EDTA.Na2Fe significantly reduced the Cd accumulation in rice roots, shoots and rice grain. Cd concentration in white rice of both rice genotypes in the treatment of soil application of EDTA.Na2Fe was much lower than 0.2 mg/kg, the maximal Cd permission concentration in cereal crop foods in State standard. However, soil application of FeSO4 or foliar application of FeSO4 or EDTA.Na2Fe resulted in the significant increase of Cd accumulation in rice plants including rice grain compared with the control. The results also showed iron fertilizers increased the concentration of iron, copper and manganese element in rice grain and also affected zinc concentration in plants. It may be a new promising way to regulate Cd accumulation in rice grain in rice production through soil application of EDTA.Na2Fe fertilizers to maintain higher content of available iron and ferrous iron in soils.

Ferric Citrate Reduces Intravenous Iron and Erythropoiesis-Stimulating Agent Use in ESRD

PubMed Central

Jalal, Diana I.; Greco, Barbara A.; Umeukeje, Ebele M.; Reisin, Efrain; Manley, John; Zeig, Steven; Negoi, Dana G.; Hiremath, Anand N.; Blumenthal, Samuel S.; Sika, Mohammed; Niecestro, Robert; Koury, Mark J.; Ma, Khe-Ni; Greene, Tom; Lewis, Julia B.; Dwyer, Jamie P.

2015-01-01

Ferric citrate (FC) is a phosphate binder with shown efficacy and additional effects on iron stores and use of intravenous (iv) iron and erythropoiesis-stimulating agents (ESAs). We provide detailed analyses of changes in iron/hematologic parameters and iv iron/ESA use at time points throughout the active control period of a phase 3 international randomized clinical trial. In all, 441 subjects were randomized (292 to FC and 149 to sevelamer carbonate and/or calcium acetate [active control (AC)]) and followed for 52 weeks. Subjects on FC had increased ferritin and transferrin saturation (TSAT) levels compared with subjects on AC by week 12 (change in ferritin, 114.1±29.35 ng/ml; P<0.001; change in TSAT, 8.62%±1.57%; P<0.001). Change in TSAT plateaued at this point, whereas change in ferritin increased through week 24, remaining relatively stable thereafter. Subjects on FC needed less iv iron compared with subjects on AC over 52 weeks (median [interquartile range] dose=12.9 [1.0–28.9] versus 26.8 [13.4–47.6] mg/wk; P<0.001), and the percentage of subjects not requiring iv iron was higher with FC (P<0.001). Cumulative ESA over 52 weeks was lower with FC than AC (median [interquartile range] dose=5303 [2023–9695] versus 6954 [2664–12,375] units/wk; P=0.04). Overall, 90.3% of subjects on FC and 89.3% of subjects on AC experienced adverse events. In conclusion, treatment with FC as a phosphate binder results in increased iron parameters apparent after 12 weeks and reduces iv iron and ESA use while maintaining hemoglobin over 52 weeks, with a safety profile similar to that of available binders. PMID:25736045

Perioperative anemia management in colorectal cancer patients: A pragmatic approach

PubMed Central

Muñoz, Manuel; Gómez-Ramírez, Susana; Martín-Montañez, Elisa; Auerbach, Michael

2014-01-01

Anemia, usually due to iron deficiency, is highly prevalent among patients with colorectal cancer. Inflammatory cytokines lead to iron restricted erythropoiesis further decreasing iron availability and impairing iron utilization. Preoperative anemia predicts for decreased survival. Allogeneic blood transfusion is widely used to correct anemia and is associated with poorer surgical outcomes, increased post-operative nosocomial infections, longer hospital stays, increased rates of cancer recurrence and perioperative venous thromboembolism. Infections are more likely to occur in those with low preoperative serum ferritin level compared to those with normal levels. A multidisciplinary, multimodal, individualized strategy, collectively termed Patient Blood Management, minimizes or eliminates allogeneic blood transfusion. This includes restrictive transfusion policy, thromboprophylaxis and anemia management to improve outcomes. Normalization of preoperative hemoglobin levels is a World Health Organization recommendation. Iron repletion should be routinely ordered when indicated. Oral iron is poorly tolerated with low adherence based on published evidence. Intravenous iron is safe and effective but is frequently avoided due to misinformation and misinterpretation concerning the incidence and clinical nature of minor infusion reactions. Serious adverse events with intravenous iron are extremely rare. Newer formulations allow complete replacement dosing in 15-60 min markedly facilitating care. Erythropoiesis stimulating agents may improve response rates. A multidisciplinary, multimodal, individualized strategy, collectively termed Patient Blood Management used to minimize or eliminate allogeneic blood transfusion is indicated to improve outcomes. PMID:24587673

Clinical consequences of iron overload in patients with myelodysplastic syndromes: the case for iron chelation therapy.

PubMed

Shammo, Jamile M; Komrokji, Rami S

2018-06-14

Patients with myelodysplastic syndromes (MDS) are at increased risk of iron overload due to ineffective erythropoiesis and chronic transfusion therapy. The clinical consequences of iron overload include cardiac and/or hepatic failure, endocrinopathies, and infection risk. Areas covered: Iron chelation therapy (ICT) can help remove excess iron and ultimately reduce the clinical consequences of iron overload. The authors reviewed recent (last five years) English-language articles from PubMed on the topic of iron overload-related complications and the use of ICT (primarily deferasirox) to improve outcomes in patients with MDS. Expert Commentary: While a benefit of ICT has been more firmly established in other transfusion-dependent conditions such as thalassemia, its role in reducing iron overload in MDS remains controversial due to the lack of prospective controlled data demonstrating a survival benefit. Orally administered chelation agents (e.g., deferasirox), are now available, and observational and/or retrospective data support a survival benefit of using ICT in MDS. The placebo-controlled TELESTO trial (NCT00940602) is currently examining the use of deferasirox in MDS patients with iron overload, and is evaluating specifically whether use of ICT to alleviate iron overload can also reduce iron overload-related complications in MDS and improve survival.

Comparative response to single or divided doses of parenteral iron for functional iron deficiency in hemodialysis patients receiving erythropoietin (EPO).

PubMed

Saltissi, D; Sauvage, D; Westhuyzen, J

1998-01-01

EPO treatment rapidly corrects anemia in patients with end-stage renal failure treated with hemodialysis, as long as sufficient iron is available. Absolute and relative (to demand) iron deficiency blunts the erythropoietic response and parenteral iron is frequently required during the course of therapy to restore EPO efficacy. Since the optimum time course of iron administration to restore EPO response in the short term is unknown, we compared three protocols of i.v. iron dextran administration in apparent functionally iron-deficient HD patients on oral iron therapy (hemoglobin < 10.0 g/dl plus ferritin < 100 micrograms/l and/or transferrin saturation < 20%). Intravenous iron (Imferon; Fisons Pty Ltd.) was given either as a single 600 mg dose (n = 15, Group I) or in divided doses of 100 mg administered on 6 successive dialyses (n = 14, Group II) or weekly for 6 weeks (n = 14, Group III). Response was monitored for 8 weeks. No adverse effects were observed. Collectively, mean hemoglobin increased (p < 0.01) by 0.4-0.5 g/dl plateauing at 4 weeks (between group comparison, p = 0.92). Mean ferritin concentrations changed with time (p < 0.01), peaking at 2 weeks in Groups I and II and at 4 weeks in Group III. Mean transferrin saturation levels also increased during the study (p < 0.001). The between group comparisons for the trends in iron indices were significant (p < 0.01 and 0.05 respectively). As there were no clinically significant differences in hemoglobin response at 4 weeks, single dose iron infusion would seem to be the most expedient in the short term, however frequent small doses are similarly effective.

Hydrogen sulphide improves adaptation of Zea mays seedlings to iron deficiency

PubMed Central

Chen, Juan; Wu, Fei-Hua; Shang, Yu-Ting; Wang, Wen-Hua; Hu, Wen-Jun; Simon, Martin; Liu, Xiang; Shangguan, Zhou-Ping; Zheng, Hai-Lei

2015-01-01

Hydrogen sulphide (H2S) is emerging as a potential molecule involved in physiological regulation in plants. However, whether H2S regulates iron-shortage responses in plants is largely unknown. Here, the role of H2S in modulating iron availability in maize (Zea mays L. cv Canner) seedlings grown in iron-deficient culture solution is reported. The main results are as follows: Firstly, NaHS, a donor of H2S, completely prevented leaf interveinal chlorosis in maize seedlings grown in iron-deficient culture solution. Secondly, electron micrographs of mesophyll cells from iron-deficient maize seedlings revealed plastids with few photosynthetic lamellae and rudimentary grana. On the contrary, mesophyll chloroplasts appeared completely developed in H2S-treated maize seedlings. Thirdly, H2S treatment increased iron accumulation in maize seedlings by changing the expression levels of iron homeostasis- and sulphur metabolism-related genes. Fourthly, phytosiderophore (PS) accumulation and secretion were enhanced by H2S treatment in seedlings grown in iron-deficient solution. Indeed, the gene expression of ferric-phytosiderophore transporter (ZmYS1) was specifically induced by iron deficiency in maize leaves and roots, whereas their abundance was decreased by NaHS treatment. Lastly, H2S significantly enhanced photosynthesis through promoting the protein expression of ribulose-1,5-bisphosphate carboxylase large subunit (RuBISCO LSU) and phosphoenolpyruvate carboxylase (PEPC) and the expression of genes encoding RuBISCO large subunit (RBCL), small subunit (RBCS), D1 protein (psbA), and PEPC in maize seedlings grown in iron-deficient solution. These results indicate that H2S is closely related to iron uptake, transport, and accumulation, and consequently increases chlorophyll biosynthesis, chloroplast development, and photosynthesis in plants. PMID:26208645

Hydrogen sulphide improves adaptation of Zea mays seedlings to iron deficiency.

PubMed

Chen, Juan; Wu, Fei-Hua; Shang, Yu-Ting; Wang, Wen-Hua; Hu, Wen-Jun; Simon, Martin; Liu, Xiang; Shangguan, Zhou-Ping; Zheng, Hai-Lei

2015-11-01

Hydrogen sulphide (H2S) is emerging as a potential molecule involved in physiological regulation in plants. However, whether H2S regulates iron-shortage responses in plants is largely unknown. Here, the role of H2S in modulating iron availability in maize (Zea mays L. cv Canner) seedlings grown in iron-deficient culture solution is reported. The main results are as follows: Firstly, NaHS, a donor of H2S, completely prevented leaf interveinal chlorosis in maize seedlings grown in iron-deficient culture solution. Secondly, electron micrographs of mesophyll cells from iron-deficient maize seedlings revealed plastids with few photosynthetic lamellae and rudimentary grana. On the contrary, mesophyll chloroplasts appeared completely developed in H2S-treated maize seedlings. Thirdly, H2S treatment increased iron accumulation in maize seedlings by changing the expression levels of iron homeostasis- and sulphur metabolism-related genes. Fourthly, phytosiderophore (PS) accumulation and secretion were enhanced by H2S treatment in seedlings grown in iron-deficient solution. Indeed, the gene expression of ferric-phytosiderophore transporter (ZmYS1) was specifically induced by iron deficiency in maize leaves and roots, whereas their abundance was decreased by NaHS treatment. Lastly, H2S significantly enhanced photosynthesis through promoting the protein expression of ribulose-1,5-bisphosphate carboxylase large subunit (RuBISCO LSU) and phosphoenolpyruvate carboxylase (PEPC) and the expression of genes encoding RuBISCO large subunit (RBCL), small subunit (RBCS), D1 protein (psbA), and PEPC in maize seedlings grown in iron-deficient solution. These results indicate that H2S is closely related to iron uptake, transport, and accumulation, and consequently increases chlorophyll biosynthesis, chloroplast development, and photosynthesis in plants. © The Author 2015. Published by Oxford University Press on behalf of the Society for Experimental Biology.

Rethinking Iron Regulation and Assessment in Iron Deficiency, Anemia of Chronic Disease, and Obesity: Introducing Hepcidin

PubMed Central

Tussing-Humphreys, Lisa; Pustacioglu, Cenk; Nemeth, Elizabeta; Braunschweig, Carol

2012-01-01

Adequate iron availability is essential to human development and overall health. Iron is a key component of oxygen-carrying proteins, has a pivotal role in cellular metabolism, and is essential to cell growth and differentiation. Inadequate dietary iron intake, chronic and acute inflammatory conditions, and obesity are each associated with alterations in iron homeostasis. Tight regulation of iron is necessary because iron is highly toxic and human beings can only excrete small amounts through sweat, skin and enterocyte sloughing, and fecal and menstrual blood loss. Hepcidin, a small peptide hormone produced mainly by the liver, acts as the key regulator of systemic iron homeostasis. Hepcidin controls movement of iron into plasma by regulating the activity of the sole known iron exporter ferroportin-1. Downregulation of the ferroportin-1 exporter results in sequestration of iron within intestinal enterocytes, hepatocytes, and iron-storing macrophages reducing iron bioavailability. Hepcidin expression is increased by higher body iron levels and inflammation and decreased by anemia and hypoxia. Importantly, existing data illustrate that hepcidin may play a significant role in the development of several iron-related disorders, including the anemia of chronic disease and the iron dysregulation observed in obesity. Therefore, the purpose of this article is to discuss iron regulation, with specific emphasis on systemic regulation by hepcidin, and examine the role of hepcidin within several disease states, including iron deficiency, anemia of chronic disease, and obesity. The relationship between obesity and iron depletion and the clinical assessment of iron status will also be reviewed. PMID:22717199

Analysis of the global ocean sampling (GOS) project for trends in iron uptake by surface ocean microbes.

PubMed

Toulza, Eve; Tagliabue, Alessandro; Blain, Stéphane; Piganeau, Gwenael

2012-01-01

Microbial metagenomes are DNA samples of the most abundant, and therefore most successful organisms at the sampling time and location for a given cell size range. The study of microbial communities via their DNA content has revolutionized our understanding of microbial ecology and evolution. Iron availability is a critical resource that limits microbial communities' growth in many oceanic areas. Here, we built a database of 2319 sequences, corresponding to 140 gene families of iron metabolism with a large phylogenetic spread, to explore the microbial strategies of iron acquisition in the ocean's bacterial community. We estimate iron metabolism strategies from metagenome gene content and investigate whether their prevalence varies with dissolved iron concentrations obtained from a biogeochemical model. We show significant quantitative and qualitative variations in iron metabolism pathways, with a higher proportion of iron metabolism genes in low iron environments. We found a striking difference between coastal and open ocean sites regarding Fe(2+) versus Fe(3+) uptake gene prevalence. We also show that non-specific siderophore uptake increases in low iron open ocean environments, suggesting bacteria may acquire iron from natural siderophore-like organic complexes. Despite the lack of knowledge of iron uptake mechanisms in most marine microorganisms, our approach provides insights into how the iron metabolic pathways of microbial communities may vary with seawater iron concentrations.

Climatically sensitive transfer of iron to maritime Antarctic ecosystems by surface runoff

NASA Astrophysics Data System (ADS)

Hodson, Andy; Nowak, Aga; Sabacka, Marie; Jungblut, Anne; Navarro, Francisco; Pearce, David; Ávila-Jiménez, María Luisa; Convey, Peter; Vieira, Gonçalo

2017-02-01

Iron supplied by glacial weathering results in pronounced hotspots of biological production in an otherwise iron-limited Southern Ocean Ecosystem. However, glacial iron inputs are thought to be dominated by icebergs. Here we show that surface runoff from three island groups of the maritime Antarctic exports more filterable (<0.45 μm) iron (6-81 kg km-2 a-1) than icebergs (0.0-1.2 kg km-2 a-1). Glacier-fed streams also export more acid-soluble iron (27.0-18,500 kg km-2 a-1) associated with suspended sediment than icebergs (0-241 kg km-2 a-1). Significant fluxes of filterable and sediment-derived iron (1-10 Gg a-1 and 100-1,000 Gg a-1, respectively) are therefore likely to be delivered by runoff from the Antarctic continent. Although estuarine removal processes will greatly reduce their availability to coastal ecosystems, our results clearly indicate that riverine iron fluxes need to be accounted for as the volume of Antarctic melt increases in response to 21st century climate change.

Evidence that stainable bone marrow iron following parenteral iron therapy does not correlate with serum iron studies and may not represent readily available storage iron.

PubMed

Thomason, Ronald W; Almiski, Muhamad S

2009-04-01

We recently reported that parenteral iron therapy is associated with a characteristic pattern of iron staining on bone marrow aspirate smears. We now present clinical information from 6 patients who received parenteral iron and, at one or more points in follow-up, were found to have low or borderline low serum ferritin levels and/or serum iron levels, even though marrow aspirate smears revealed abundant stainable iron in the pattern characteristic of prior parenteral iron therapy. We conclude that stainable iron seen in this pattern does not correlate with serum iron studies and may not represent functionally available storage iron. This pattern of iron staining should not be used as evidence to withhold further iron therapy in patients who otherwise continue to have features of iron deficiency anemia.

Interaction between sulfur and lead in toxicity, iron plaque formation and lead accumulation in rice plant.

PubMed

Yang, Junxing; Liu, Zhiyan; Wan, Xiaoming; Zheng, Guodi; Yang, Jun; Zhang, Hanzhi; Guo, Lin; Wang, Xuedong; Zhou, Xiaoyong; Guo, Qingjun; Xu, Ruixiang; Zhou, Guangdong; Peters, Marc; Zhu, Guangxu; Wei, Rongfei; Tian, Liyan; Han, Xiaokun

2016-06-01

Human activities have resulted in lead and sulfur accumulation in paddy soils in parts of southern China. A combined soil-sand pot experiment was conducted to investigate the influence of S supply on iron plaque formation and Pb accumulation in rice (Oryza sativa L.) under two Pb levels (0 and 600 mg kg(-1)), combined with four S concentrations (0, 30, 60, and 120 mg kg(-1)). Results showed that S supply significantly decreased Pb accumulation in straw and grains of rice. This result may be attributed to the enhancement of Fe plaque formation, decrease of Pb availability in soil, and increase of reduced glutathione (GSH) in rice leaves. Moderate S supply (30 mg kg(-1)) significantly increased Fe plaque formation on the root surface and in the rhizosphere, whereas excessive S supply (60 and 120 mg kg(-1)) significantly decreased the amounts of iron plaque on the root surface. Sulfur supply significantly enhanced the GSH contents in leaves of rice plants under Pb treatment. With excessive S application, the rice root acted as a more effective barrier to Pb accumulation compared with iron plaque. Excessive S supply may result in a higher monosulfide toxicity and decreased iron plaque formation on the root surface during flooded conditions. However, excessive S supply could effectively decrease Pb availability in soils and reduce Pb accumulation in rice plants. Copyright © 2016 Elsevier Inc. All rights reserved.

Personalised iron supply for prophylaxis and treatment of pregnant women as a way to ensure normal iron levels in their breast milk.

PubMed

Marin, G H; Mestorino, N; Errecalde, J; Huber, B; Uriarte, A; Orchuela, J

2012-02-22

Because the characteristics of all body fluids depends on patient's health status, is it possible that disadvantaged and socially vulnerable mothers may have lower amounts of iron in their breast milk, and that their babies receive lower content of the mineral for their normal growth and development. Assuring a preventive treatment of the mother might solve this problem. To demonstrate breast milk iron content from disadvantaged mothers and impact of personalized iron supplementation program. cross-sectional study. Breast milk samples were obtained for ferritin analysis. Health's services usually provides free folic acid and iron treatment however, treatment compliance is low. Patients were random in two groups: "A: Controls" that had free iron tablets available from Health Centre; and "B: Intervention" group where patients accepted to be periodically contacted at home by health's team for personalized iron dispensation. 360 patients were included. Profilaxis and treatment compliance were 100% and 97,6% for B group while for "Control" one was 63% and 34%(p0.0001). Higher breast milk iron levels were detected in Intervention's mothers compared with control's patients (p0.007). Personalized iron prophylaxis and treatment increased breast milk iron levels. Public health policy must ensure iron dispensation for each underserved mother in order to reduce children problems associate to iron deficiency during the first year of their life.

Erythropoietic response to oral iron in patients with nondialysis-dependent chronic kidney disease in the FIND-CKD trial
.

PubMed

Macdougall, Iain C; Bock, Andreas H; Carrera, Fernando; Eckardt, Kai-Uwe; Gaillard, Carlo; Wyck, David Van; Meier, Yvonne; Larroque, Sylvain; Perrin, Amandine; Roger, Simon D

2017-12-01

To evaluate erythropoietic response rates to oral iron over time in iron-deficient anemic patients with nondialysis-dependent chronic kidney disease (ND-CKD). FIND-CKD was a 1-year, randomized, multicenter trial of iron therapy in patients with ND-CKD, anemia, and iron deficiency, without erythropoiesis-stimulating agent (ESA) therapy. Patients with active infection or C-reactive protein > 20 mg/L were excluded. In this post-hoc analysis, response was defined as ≥ 1 g/dL increase in hemoglobin (Hb) from baseline, before initiation of alternative anemia therapy (i.e., ESA, transfusion, or intravenous iron). 308 patients received oral iron (200 mg elemental iron/day). Mean (SD) Hb at baseline was 10.4 (0.7) g/dL. At week 4, Hb data were available from 292 patients without alternative anemia therapy: 63/292 (21.6%) showed a response. Among the 229 nonresponders at week 4, 48.8% showed a cumulative response on ≥ 1 occasion by week 52 (11.1%, 19.9%, 25.9%, and 28.7% had a response at weeks 8, 12, 24, and 52, respectively), and 27.9% had received alternative iron therapy by week 52. Baseline levels of Hb, ferritin, and transferrin saturation were lower in responders than in nonresponders. Neither concomitant medication nor adherence (as assessed by medication count) was substantially different between early responders and nonresponders. Four weeks after starting oral iron therapy, only 21.6% of anemic patients with ND-CKD and iron deficiency showed an Hb increase of at least 1 g/dL. Among early nonresponders, < 30% responded at any subsequent time point. Earlier consideration of alternative therapy could improve anemia management in this population.
.

Siderophore-promoted dissolution of smectite by fluorescent Pseudomonas.

PubMed

Ferret, Claire; Sterckeman, Thibault; Cornu, Jean-Yves; Gangloff, Sophie; Schalk, Isabelle J; Geoffroy, Valérie A

2014-10-01

Siderophores are organic chelators produced by microorganisms to fulfil their iron requirements. Siderophore-promoted dissolution of iron-bearing minerals has been clearly documented for some siderophores, but few studies have addressed metabolizing siderophore-producing bacteria. We investigated iron acquisition from clays by fluorescent Pseudomonads, bacteria that are ubiquitous in the environment. We focused on the interactions between smectite and Pseudomonas aeruginosa, a bacterium producing two structurally different siderophores: pyoverdine and pyochelin. The presence of smectite in iron-limited growth media promoted planktonic growth of P. aeruginosa and biofilm surrounding the smectite aggregates. Chemical analysis of the culture media indicated increases in the dissolved silicon, iron and aluminium concentrations following smectite supplementation. The use of P. aeruginosa mutants unable to produce either one or both of the two siderophores indicated that pyoverdine, the siderophore with the higher affinity for iron, was involved in iron and aluminium solubilization by the wild-type strain. However, in the absence of pyoverdine, pyochelin was also able to solubilize iron but with a twofold lower efficiency. In conclusion, pyoverdine and pyochelin, two structurally different siderophores, can solubilize structural iron from smectite and thereby make it available for bacterial growth.

Paramagnetic iron-doped hydroxyapatite nanoparticles with improved metal sorption properties. A bioorganic substrates-mediated synthesis.

PubMed

Mercado, D Fabio; Magnacca, Giuliana; Malandrino, Mery; Rubert, Aldo; Montoneri, Enzo; Celi, Luisella; Bianco Prevot, Alessandra; Gonzalez, Mónica C

2014-03-26

This paper describes the synthesis of paramegnetic iron-containing hydroxyapatite nanoparticles and their increased Cu(2+) sorbent capacity when using Ca(2+) complexes of soluble bioorganic substrates from urban wastes as synthesis precursors. A thorough characterization of the particles by TEM, XRD, FTIR spectroscopy, specific surface area, TGA, XPS, and DLS indicates that loss of crystallinity, a higher specific area, an increased surface oxygen content, and formation of surface iron phases strongly enhance Cu(2+) adsorption capacity of hydroxyapatite-based materials. However, the major effect of the surface and morphologycal modifications is the size diminution of the aggregates formed in aqueous solutions leading to an increased effective surface available for Cu(2+) adsorption. Maximum sorption values of 550-850 mg Cu(2+) per gram of particles suspended in an aqueous solution at pH 7 were determined, almost 10 times the maximum values observed for hydroxyapatite nanoparticles suspensions under the same conditions.

Rapid assay for microbially reducible ferric iron in aquatic sediments

USGS Publications Warehouse

Lovely, Derek R.; Philips , Elizabeth J.P.

1987-01-01

The availability of ferric iron for microbial reduction as directly determined by the activity of iron-reducing organisms was compared with its availability as determined by a newly developed chemical assay for microbially reducible iron. The chemical assay was based on the reduction of poorly crystalline ferric iron by hydroxylamine under acidic conditions. There was a strong correlation between the extent to which hydroxylamine could reduce various synthetic ferric iron forms and the susceptibility of the iron to microbial reduction in an enrichment culture of iron-reducing organisms. When sediments that contained hydroxylamine-reducible ferric iron were incubated under anaerobic conditions, ferrous iron accumulated as the concentration of hydroxylamine-reducible ferric iron declined over time. Ferrous iron production stopped as soon as the hydroxylamine-reducible ferric iron was depleted. In anaerobic incubations of reduced sediments that did not contain hydroxylamine-reducible ferric iron, there was no microbial iron reduction, even though the sediments contained high concentrations of oxalate-extractable ferric iron. A correspondence between the presence of hydroxylamine-reducible ferric iron and the extent of ferric iron reduction in anaerobic incubations was observed in sediments from an aquifer and in fresh- and brackish-water sediments from the Potomac River estuary. The assay is a significant improvement over previously described procedures for the determination of hydroxylamine-reducible ferric iron because it provides a correction for the high concentrations of solid ferrous iron which may also be extracted from sediments with acid. This is a rapid, simple technique to determine whether ferric iron is available for microbial reduction.

Regulation of iron transport systems in Enterobacteriaceae in response to oxygen and iron availability.

PubMed

Carpenter, Chandra; Payne, Shelley M

2014-04-01

Iron is an essential nutrient for most bacteria. Depending on the oxygen available in the surrounding environment, iron is found in two distinct forms: ferrous (Fe(II)) or ferric (Fe(III)). Bacteria utilize different transport systems for the uptake of the two different forms of iron. In oxic growth conditions, iron is found in its insoluble, ferric form, and in anoxic growth conditions iron is found in its soluble, ferrous form. Enterobacteriaceae have adapted to transporting the two forms of iron by utilizing the global, oxygen-sensing regulators, ArcA and Fnr to regulate iron transport genes in response to oxygen. Copyright © 2014 Elsevier Inc. All rights reserved.

Antarctic iron meteorites: An unexpectedly high proportion of falls of unusual interest

NASA Technical Reports Server (NTRS)

Clarke, R. S., Jr.

1986-01-01

The inhabited and explored areas of Earth have contributed 725 iron meteorites, accounting for 28% of the 2611 authenticated meteorites known of all types. Observed fall statistics give a much different view of relative abundance. The 42 historic iron meteorite falls spanning 230 years suggests a frequency of one fall per 5.6 years and represents only 4.9% of the total 853 known falls. Antarctic iron meteorite recoveries offer promise of providing a new perspective on the influx problem. At least 42 iron meteorite specimens were found during the last 25 years by various field teams working in Antarctica. Most of these specimens were not described in detail, but the available data indicates that 21 separate falls are represented, 50% of the number of recovered specimens. Twelve of the 21 falls were both structurally classified and placed into chemical groups. They are listed in order of increasing structural complexity and/or Ni content.

Microstructure of bentonite in iron ore green pellets.

PubMed

Bhuiyan, Iftekhar U; Mouzon, Johanne; Schröppel, Birgit; Kaech, Andres; Dobryden, Illia; Forsmo, Seija P E; Hedlund, Jonas

2014-02-01

Sodium-activated calcium bentonite is used as a binder in iron ore pellets and is known to increase strength of both wet and dry iron ore green pellets. In this article, the microstructure of bentonite in magnetite pellets is revealed for the first time using scanning electron microscopy. The microstructure of bentonite in wet and dry iron ore pellets, as well as in distilled water, was imaged by various imaging techniques (e.g., imaging at low voltage with monochromatic and decelerated beam or low loss backscattered electrons) and cryogenic methods (i.e., high pressure freezing and plunge freezing in liquid ethane). In wet iron ore green pellets, clay tactoids (stacks of parallel primary clay platelets) were very well dispersed and formed a voluminous network occupying the space available between mineral particles. When the pellet was dried, bentonite was drawn to the contact points between the particles and formed solid bridges, which impart strength to the solid compact.

Iron fertilisation of the ocean through major volcanic eruptions. A case study of the Kasatochi eruption 2008

NASA Astrophysics Data System (ADS)

Lindenthal, A.; Langmann, B.; Hort, M.; Hoshyaripour, G.; Paetsch, J.; Lorkowski, I.

2012-04-01

Until recently it was more or less common sense that once volcanic ash enters the ocean it simply deposits into the sediments without any further impact on ocean biochemistry. This view has been notably revised after the eruption of Kasatochi volcano in 2008. During the eruption significant amounts of ash were deposited into oceanic NE Pacific. The NE Pacific is known as a high-nutrient-low-chlorophyll (HNLC) region where algae growth is limited by the bio-available, i.e. soluble iron. These bio-available iron salts residing on the volcanic ash are most likely formed by gas-ash/aerosol interactions inside the volcanic plume. The physico-chemical mechanisms behind the processes contributing to bio-available iron production in volcanic plumes, however, are still poorly constrained. As the eruption occurred in early August, the atmospheric and oceanic conditions were favourable to generate a massive phytoplankton bloom as was observed by satellite instruments and in-situ measurements. Here we investigate this event with the marine biogeochemical model ECOHAM, which is a regional scale three-dimensional ocean biogeochemistry model, coupled to the hydrodynamic model HAMSON. It has been successfully applied mainly over the NW European continental shelf area where iron limitation does not play a role. For applications of this model to the eruption of Kasatochi volcano, an iron cycle model has been implemented, which considers the influence of iron addition to the euphotic zone on diatoms, flagellates, and carbon dioxide concentrations. This model-approach assumes that all dissolved iron in the first meters of seawater is bio-available for phytoplankton uptake. It describes the limitation of phytoplankton growth rates by iron in addition to the limitation by the macro-nutrients nitrogen, phosphate and silicate as well as by light. The surface ocean iron input associated with the eruption of Kasatochi volcano has been determined by an atmospheric-aerosol model to be on the order of 4.5-6x1011kg (ash volume of 0.23-0.3km3). This amount of volcanic ash is consistent with estimates from 1D eruption column models. ECOHAM model results show that volcanic ash can stimulate algae blooms in surface ocean waters in HNLC regions like the NE Pacific. Soluble iron released from volcanic ash acts as a key micro nutrient for phytoplankton growth, especially for diatoms. Model results have been verified with measurements of station Papa (50°N, 145°W). Here a deposition of bio-available iron of 968 micromol Fe/m2 into the surface ocean between Aug. 8-11 lead to an increase in the primary production of chlorophyll in the upper 10m of the ocean of 3.7mg Chl/m3. Following the ash deposition the CO2 partial pressure at station Papa dropped by about 40microatm, which compares well with the 50microatm drop observed in our model calculations.

Haemoglobin variants, iron status and anaemia in Sri Lankan adolescents with low red cell indices: A cross sectional survey.

PubMed

Rodrigo, Rexan; Allen, Angela; Manampreri, Aresha; Perera, Luxman; Fisher, Christopher A; Allen, Stephen; Weatherall, David J; Premawardhena, Anuja

2018-07-01

Iron deficiency complicates the use of red cell indices to screen for carriers of haemoglobin variants in many populations. In a cross sectional survey of 7526 secondary school students from 25 districts of Sri Lanka, 1963 (26.0%) students had low red cell indices. Iron deficiency, identified by low serum ferritin, was the major identifiable cause occurring in 550/1806 (30.5%) students. Low red cell indices occurred in iron-replete students with alpha-thalassaemia including those with single alpha-globin gene deletions. Anaemia and low red cell indices were also common in beta-thalassaemia trait. An unexpected finding was that low red cell indices occurred in 713 iron-replete students with a normal haemoglobin genotype. It is common practice to prescribe iron supplements to individuals with low red cell indices. Since low red cell indices were a feature of all forms of α thalassaemia and also of iron deficiency, in areas where both conditions are common, such as Sri Lanka, it is imperative to differentiate between the two, to allow targeted administration of iron supplements and avoid the possible deleterious effects of increased iron availability in iron replete individuals with low red cell indices due to other causes such as α thalassaemia. Copyright © 2018 Elsevier Inc. All rights reserved.

Self-assembled monolayers of n-alkanethiols suppress hydrogen evolution and increase the efficiency of rechargeable iron battery electrodes.

PubMed

Malkhandi, Souradip; Yang, Bo; Manohar, Aswin K; Prakash, G K Surya; Narayanan, S R

2013-01-09

Iron-based rechargeable batteries, because of their low cost, eco-friendliness, and durability, are extremely attractive for large-scale energy storage. A principal challenge in the deployment of these batteries is their relatively low electrical efficiency. The low efficiency is due to parasitic hydrogen evolution that occurs on the iron electrode during charging and idle stand. In this study, we demonstrate for the first time that linear alkanethiols are very effective in suppressing hydrogen evolution on alkaline iron battery electrodes. The alkanethiols form self-assembled monolayers on the iron electrodes. The degree of suppression of hydrogen evolution by the alkanethiols was found to be greater than 90%, and the effectiveness of the alkanethiol increased with the chain length. Through steady-state potentiostatic polarization studies and impedance measurements on high-purity iron disk electrodes, we show that the self-assembly of alkanethiols suppressed the parasitic reaction by reducing the interfacial area available for the electrochemical reaction. We have modeled the effect of chain length of the alkanethiol on the surface coverage, charge-transfer resistance, and double-layer capacitance of the interface using a simple model that also yields a value for the interchain interaction energy. We have verified the improvement in charging efficiency resulting from the use of the alkanethiols in practical rechargeable iron battery electrodes. The results of battery tests indicate that alkanethiols yield among the highest faradaic efficiencies reported for the rechargeable iron electrodes, enabling the prospect of a large-scale energy storage solution based on low-cost iron-based rechargeable batteries.

Choice of High-Dose Intravenous Iron Preparation Determines Hypophosphatemia Risk

PubMed Central

Schaefer, Benedikt; Würtinger, Philipp; Finkenstedt, Armin; Braithwaite, Vickie; Viveiros, André; Effenberger, Maria; Sulzbacher, Irene; Moschen, Alexander; Griesmacher, Andrea; Tilg, Herbert; Vogel, Wolfgang; Zoller, Heinz

2016-01-01

Background Ferric carboxymaltose (FCM) and iron isomaltoside 1000 (IIM) are increasingly used because they allow correction of severe iron deficiency in a single infusion. A transient decrease in serum phosphate concentrations is a frequent side effect of FCM. Aim To characterize this adverse event and search for its predictors in a gastroenterology clinic patient cohort. Methods Electronic medical records of patients attending the University Hospital of Innsbruck were searched for the keywords ferric carboxymaltose or iron isomaltoside. Eighty-one patients with documented administration of FCM or IIM with plasma phosphate concentrations before and after treatment were included. Results The prevalence of hypophosphatemia (<0.8 mmol/L) increased from 11% to 32.1% after treatment with i.v. iron. The hypophosphatemia risk was greater after FCM (45.5%) compared with IIM (4%). Severe hypophosphatemia (<0.6 mmol/L) occurred exclusively after FCM (32.7%). The odds for hypophosphatemia after i.v. iron treatment were independently determined by baseline phosphate and the choice of i.v. iron preparation (FCM vs. IIM—OR = 20.8; 95% CI, 2.6–166; p = 0.004). The median time with hypophosphatemia was 41 days, but prolonged hypophosphatemia of ≥ 2 months was documented in 13 of 17 patients in whom follow-up was available. A significant increase in the phosphaturic hormone intact FGF-23 in hypophosphatemic patients shows that this adverse event is caused by FCM-induced hormone dysregulation. Conclusion Treatment with FCM is associated with a high risk of developing severe and prolonged hypophosphatemia and should therefore be monitored. Hypophosphatemia risk appears to be substantially lower with IIM. PMID:27907058

Choice of High-Dose Intravenous Iron Preparation Determines Hypophosphatemia Risk.

PubMed

Schaefer, Benedikt; Würtinger, Philipp; Finkenstedt, Armin; Braithwaite, Vickie; Viveiros, André; Effenberger, Maria; Sulzbacher, Irene; Moschen, Alexander; Griesmacher, Andrea; Tilg, Herbert; Vogel, Wolfgang; Zoller, Heinz

2016-01-01

Ferric carboxymaltose (FCM) and iron isomaltoside 1000 (IIM) are increasingly used because they allow correction of severe iron deficiency in a single infusion. A transient decrease in serum phosphate concentrations is a frequent side effect of FCM. To characterize this adverse event and search for its predictors in a gastroenterology clinic patient cohort. Electronic medical records of patients attending the University Hospital of Innsbruck were searched for the keywords ferric carboxymaltose or iron isomaltoside. Eighty-one patients with documented administration of FCM or IIM with plasma phosphate concentrations before and after treatment were included. The prevalence of hypophosphatemia (<0.8 mmol/L) increased from 11% to 32.1% after treatment with i.v. iron. The hypophosphatemia risk was greater after FCM (45.5%) compared with IIM (4%). Severe hypophosphatemia (<0.6 mmol/L) occurred exclusively after FCM (32.7%). The odds for hypophosphatemia after i.v. iron treatment were independently determined by baseline phosphate and the choice of i.v. iron preparation (FCM vs. IIM-OR = 20.8; 95% CI, 2.6-166; p = 0.004). The median time with hypophosphatemia was 41 days, but prolonged hypophosphatemia of ≥ 2 months was documented in 13 of 17 patients in whom follow-up was available. A significant increase in the phosphaturic hormone intact FGF-23 in hypophosphatemic patients shows that this adverse event is caused by FCM-induced hormone dysregulation. Treatment with FCM is associated with a high risk of developing severe and prolonged hypophosphatemia and should therefore be monitored. Hypophosphatemia risk appears to be substantially lower with IIM.

Paving a Path to Understanding Metabolic Responses to Iron Bioavailability: Global Proteomic Analysis of Crocosphaera watsonii

NASA Astrophysics Data System (ADS)

Gauglitz, J.; McIlvin, M. R.; Moran, D. M.; Waterbury, J. B.; Saito, M. A.

2016-02-01

Marine diazotrophic cyanobacteria provide a key source of new nitrogen into the oceans and are important contributors to primary production. The geographic distribution of these cyanobacteria is impacted by available iron and phosphorus as well as environmental conditions such as temperature, however available iron concentrations are thought to be particularly critical due to the high demand for iron in cellular processes. Iron bioavailability and microorganismal adaptations to low iron environments may thus play a key role in dictating community structure, however the mechanisms by which cyanobacteria acquire iron and regulate its uptake are not well defined. In this study, the unicellular diazotroph, Crocosphaera watsonii WH8501, was acclimated to a range of bioavailable iron concentrations (from 0.001nM to 8.13nM Fe') using trace metal clean culturing techniques and the proteomes were analyzed by LC/MS-MS. Physiological and proteomic data indicate three distinct phenotypic ranges: iron-replete, iron-limited, and iron-starved. Trends in photosynthetic, carbon fixation and iron storage proteins across the iron gradient indicate that the C. watsonii proteome responds directly to iron availability. Further analysis of relative protein expression, which describes the physiological state of the cell, will lead to insights into how C. watsonii is able to adapt to iron-limited conditions and the resulting biogeochemical implications will be discussed.

Jasmonate signaling is activated in the very early stages of iron deficiency responses in rice roots.

PubMed

Kobayashi, Takanori; Itai, Reiko Nakanishi; Senoura, Takeshi; Oikawa, Takaya; Ishimaru, Yasuhiro; Ueda, Minoru; Nakanishi, Hiromi; Nishizawa, Naoko K

2016-07-01

Under low iron availability, plants induce the expression of various genes involved in iron uptake and translocation at the transcriptional level. This iron deficiency response is affected by various plant hormones, but the roles of jasmonates in this response are not well-known. We investigated the involvement of jasmonates in rice iron deficiency responses. High rates of jasmonate-inducible genes were induced during the very early stages of iron deficiency treatment in rice roots. Many jasmonate-inducible genes were also negatively regulated by the ubiquitin ligases OsHRZ1 and OsHRZ2 and positively regulated by the transcription factor IDEF1. Ten out of 35 genes involved in jasmonate biosynthesis and signaling were rapidly induced at 3 h of iron deficiency treatment, and this induction preceded that of known iron deficiency-inducible genes involved in iron uptake and translocation. Twelve genes involved in jasmonate biosynthesis and signaling were also upregulated in HRZ-knockdown roots. Endogenous concentrations of jasmonic acid and jasmonoyl isoleucine tended to be rapidly increased in roots in response to iron deficiency treatment, whereas these concentrations were higher in HRZ-knockdown roots under iron-sufficient conditions. Analysis of the jasmonate-deficient cpm2 mutant revealed that jasmonates repress the expression of many iron deficiency-inducible genes involved in iron uptake and translocation under iron sufficiency, but this repression is partly canceled under an early stage of iron deficiency. These results indicate that jasmonate signaling is activated during the very early stages of iron deficiency, which is partly regulated by IDEF1 and OsHRZs.

Effect of superconducting solenoid model cores on spanwise iron magnet roll control

NASA Technical Reports Server (NTRS)

Britcher, C. P.

1985-01-01

Compared with conventional ferromagnetic fuselage cores, superconducting solenoid cores appear to offer significant reductions in the projected cost of a large wind tunnel magnetic suspension and balance system. The provision of sufficient magnetic roll torque capability has been a long-standing problem with all magnetic suspension and balance systems; and the spanwise iron magnet scheme appears to be the most powerful system available. This scheme utilizes iron cores which are installed in the wings of the model. It was anticipated that the magnetization of these cores, and hence the roll torque generated, would be affected by the powerful external magnetic field of the superconducting solenoid. A preliminary study has been made of the effect of the superconducting solenoid fuselage model core concept on the spanwise iron magnet roll torque generation schemes. Computed data for one representative configuration indicate that reductions in available roll torque occur over a range of applied magnetic field levels. These results indicate that a 30-percent increase in roll electromagnet capacity over that previously determined will be required for a representative 8-foot wind tunnel magnetic suspension and balance system design.

Effect of Ammonium and Nitrate on Ferric Chelate Reductase and Nitrate Reductase in Vaccinium Species

PubMed Central

POONNACHIT, U.; DARNELL, R.

2004-01-01

• Background and Aims Most Vaccinium species have strict soil requirements for optimal growth, requiring low pH, high iron availability and nitrogen primarily in the ammonium form. These soils are limited and are often located near wetlands. Vaccinium arboreum is a wild species adapted to a wide range of soils, including high pH, low iron, and nitrate‐containing soils. This broader soil adaptation in V. arboreum may be related to increased efficiency of iron or nitrate uptake compared with the cultivated Vaccinium species. • Methods Nitrate, ammonium and iron uptake, and nitrate reductase (NR) and ferric chelate reductase (FCR) activities were compared in two Vaccinium species grown hydroponically in either nitrate or ammonia, with or without iron. The species studied were the wild V. arboreum and the cultivated V. corymbosum interspecific hybrid, which exhibits the strict soil requirements of most Vaccinium species. • Key Results Ammonium uptake was significantly greater than nitrate uptake in both species, while nitrate uptake was greater in the wild species, V. arboreum, compared with the cultivated species, V. corymbosum. The increased nitrate uptake in V. arboreum was correlated with increased root NR activity compared with V. corymbosum. The lower nitrate uptake in V. corymbosum was reflected in decreased plant dry weight in this species compared with V. arboreum. Root FCR activity increased significantly in V. corymbosum grown under iron‐deficient conditions, compared with the same species grown under iron‐sufficient conditions or with V. arboreum grown under either iron condition. • Conclusions. V. arboreum appears to be more efficient in acquiring nitrate compared with V. corymbosum, possibly due to increased NR activity and this may partially explain the wider soil adaptation of V. arboreum. PMID:14980973

Role of hepcidin-ferroportin axis in the pathophysiology, diagnosis, and treatment of anemia of chronic inflammation.

PubMed

Langer, Arielle L; Ginzburg, Yelena Z

2017-06-01

Anemia of chronic inflammation (ACI) is a frequently diagnosed anemia and portends an independently increased morbidity and poor outcome associated with multiple underlying diseases. The pathophysiology of ACI is multifactorial, resulting from the effects of inflammatory cytokines which both directly and indirectly suppress erythropoiesis. Recent advances in molecular understanding of iron metabolism provide strong evidence that immune mediators, such as IL-6, lead to hepcidin-induced hypoferremia, iron sequestration, and decreased iron availability for erythropoiesis. The role of hepcidin-ferroportin axis in the pathophysiology of ACI is stimulating the development of new diagnostics and targeted therapies. In this review, we present an overview of and rationale for inflammation-, iron-, and erythropoiesis-related strategies currently in development. © 2017 International Society for Hemodialysis.

Anemia and iron deficiency in gastrointestinal and liver conditions

PubMed Central

Stein, Jürgen; Connor, Susan; Virgin, Garth; Ong, David Eng Hui; Pereyra, Lisandro

2016-01-01

Iron deficiency anemia (IDA) is associated with a number of pathological gastrointestinal conditions other than inflammatory bowel disease, and also with liver disorders. Different factors such as chronic bleeding, malabsorption and inflammation may contribute to IDA. Although patients with symptoms of anemia are frequently referred to gastroenterologists, the approach to diagnosis and selection of treatment as well as follow-up measures is not standardized and suboptimal. Iron deficiency, even without anemia, can substantially impact physical and cognitive function and reduce quality of life. Therefore, regular iron status assessment and awareness of the clinical consequences of impaired iron status are critical. While the range of options for treatment of IDA is increasing due to the availability of effective and well-tolerated parenteral iron preparations, a comprehensive overview of IDA and its therapy in patients with gastrointestinal conditions is currently lacking. Furthermore, definitions and assessment of iron status lack harmonization and there is a paucity of expert guidelines on this topic. This review summarizes current thinking concerning IDA as a common co-morbidity in specific gastrointestinal and liver disorders, and thus encourages a more unified treatment approach to anemia and iron deficiency, while offering gastroenterologists guidance on treatment options for IDA in everyday clinical practice. PMID:27672287

Anemia and iron deficiency in gastrointestinal and liver conditions.

PubMed

Stein, Jürgen; Connor, Susan; Virgin, Garth; Ong, David Eng Hui; Pereyra, Lisandro

2016-09-21

Iron deficiency anemia (IDA) is associated with a number of pathological gastrointestinal conditions other than inflammatory bowel disease, and also with liver disorders. Different factors such as chronic bleeding, malabsorption and inflammation may contribute to IDA. Although patients with symptoms of anemia are frequently referred to gastroenterologists, the approach to diagnosis and selection of treatment as well as follow-up measures is not standardized and suboptimal. Iron deficiency, even without anemia, can substantially impact physical and cognitive function and reduce quality of life. Therefore, regular iron status assessment and awareness of the clinical consequences of impaired iron status are critical. While the range of options for treatment of IDA is increasing due to the availability of effective and well-tolerated parenteral iron preparations, a comprehensive overview of IDA and its therapy in patients with gastrointestinal conditions is currently lacking. Furthermore, definitions and assessment of iron status lack harmonization and there is a paucity of expert guidelines on this topic. This review summarizes current thinking concerning IDA as a common co-morbidity in specific gastrointestinal and liver disorders, and thus encourages a more unified treatment approach to anemia and iron deficiency, while offering gastroenterologists guidance on treatment options for IDA in everyday clinical practice.

Climatically sensitive transfer of iron to maritime Antarctic ecosystems by surface runoff

PubMed Central

Hodson, Andy; Nowak, Aga; Sabacka, Marie; Jungblut, Anne; Navarro, Francisco; Pearce, David; Ávila-Jiménez, María Luisa; Convey, Peter; Vieira, Gonçalo

2017-01-01

Iron supplied by glacial weathering results in pronounced hotspots of biological production in an otherwise iron-limited Southern Ocean Ecosystem. However, glacial iron inputs are thought to be dominated by icebergs. Here we show that surface runoff from three island groups of the maritime Antarctic exports more filterable (<0.45 μm) iron (6–81 kg km−2 a−1) than icebergs (0.0–1.2 kg km−2 a−1). Glacier-fed streams also export more acid-soluble iron (27.0–18,500 kg km−2 a−1) associated with suspended sediment than icebergs (0–241 kg km−2 a−1). Significant fluxes of filterable and sediment-derived iron (1–10 Gg a−1 and 100–1,000 Gg a−1, respectively) are therefore likely to be delivered by runoff from the Antarctic continent. Although estuarine removal processes will greatly reduce their availability to coastal ecosystems, our results clearly indicate that riverine iron fluxes need to be accounted for as the volume of Antarctic melt increases in response to 21st century climate change. PMID:28198359

Molecular pathogenesis and clinical consequences of iron overload in liver cirrhosis.

PubMed

Sikorska, Katarzyna; Bernat, Agnieszka; Wroblewska, Anna

2016-10-01

The liver, as the main iron storage compartment and the place of hepcidin synthesis, is the central organ involved in maintaining iron homeostasis in the body. Excessive accumulation of iron is an important risk factor in liver disease progression to cirrhosis and hepatocellular carcinoma. Here, we review the literature on the molecular pathogenesis of iron overload and its clinical consequences in chronic liver diseases. PubMed was searched for English-language articles on molecular genesis of primary and secondary iron overload, as well as on their association with liver disease progression. We have also included literature on adjuvant therapeutic interventions aiming to alleviate detrimental effects of excessive body iron load in liver cirrhosis. Excess of free, unbound iron induces oxidative stress, increases cell sensitivity to other detrimental factors, and can directly affect cellular signaling pathways, resulting in accelerated liver disease progression. Diagnosis of liver cirrhosis is, in turn, often associated with the identification of a pathological accumulation of iron, even in the absence of genetic background of hereditary hemochromatosis. Iron depletion and adjuvant therapy with antioxidants are shown to cause significant improvement of liver functions in patients with iron overload. Phlebotomy can have beneficial effects on liver histology in patients with excessive iron accumulation combined with compensated liver cirrhosis of different etiology. Excessive accumulation of body iron in liver cirrhosis is an important predictor of liver failure and available data suggest that it can be considered as target for adjuvant therapy in this condition.

Personalised iron supply for prophylaxis and treatment of pregnant women as a way to ensure normal iron levels in their breast milk

PubMed Central

Marin, GH; Mestorino, N; Errecalde, J; Huber, B; Uriarte, A; Orchuela, J

2012-01-01

Rationale: Because the characteristics of all body fluids depends on patient’s health status, is it possible that disadvantaged and socially vulnerable mothers may have lower amounts of iron in their breast milk, and that their babies receive lower content of the mineral for their normal growth and development. Assuring a preventive treatment of the mother might solve this problem. Objective: to demonstrate breast milk iron content from disadvantaged mothers and impact of personalized iron supplementation program. Materials and Methods: cross-sectional study. Breast milk samples were obtained for ferritin analysis. Health’s services usually provides free folic acid and iron treatment however, treatment compliance is low. Patients were random in two groups: “A: Controls” that had free iron tablets available from Health Centre; and “B: Intervention” group where patients accepted to be periodically contacted at home by health’s team for personalized iron dispensation. Results: 360 patients were included. Profilaxis and treatment compliance were 100% and 97,6% for B group while for “Control” one was 63% and 34%(p0.0001). Higher breast milk iron levels were detected in Intervention’s mothers compared with control’s patients (p0.007). Conclusion: Personalized iron prophylaxis and treatment increased breast milk iron levels. Public health policy must ensure iron dispensation for each underserved mother in order to reduce children problems associate to iron deficiency during the first year of their life. PMID:22574084

The severity of iron chlorosis in sensitive plants is related to soil phosphorus levels.

PubMed

Sánchez-Rodríguez, Antonio Rafael; del Campillo, María Carmen; Torrent, José

2014-10-01

Iron (Fe) deficiency chlorosis, a major nutritional problem in plants growing on calcareous soils, is related to the content and reactivity of soil iron oxides and carbonates. The effects of other soil components, however, need elucidation. In this paper we tested the hypothesis that application of high doses of phosphorus (P) to the soil can aggravate Fe chlorosis. Lupin and sorghum were grown on 24 calcareous soils. Leaf chlorophyll concentration (LCC) in lupin decreased with increasing available P/available Fe ratio in the native soil but LCC in sorghum was unaffected by that ratio. Application of P to the soil resulted in significant reduction of LCC and dry weight in lupin. In sorghum, LCC and dry weight were positively affected by P fertilisation for soils poor in available P whereas the opposite effect was generally observed for the P-rich soils. In another experiment where olive plants were pot-grown on two soils during the 2009–2011 period, P fertilisation affected LCC negatively only in 2009 and 2011 and in the soil that was poorer in iron oxides. Application of fertiliser P to Fe chlorosis-inducing soils is likely to aggravate this deficiency. However, this effect depends on the plant and the Fe and P statuses of the soil. © 2014 Society of Chemical Industry.

Grazing suppression of dimethylsulphoniopropionate (DMSP) accumulation in iron-fertilised, sub-Antarctic waters

NASA Astrophysics Data System (ADS)

Archer, S. D.; Safi, K.; Hall, A.; Cummings, D. G.; Harvey, M.

2011-03-01

The impact of in situ iron fertilisation on the production of particulate dimethylsulphoniopropionate (DMSPp) and its breakdown product dimethyl sulphide (DMS) was monitored during the SOLAS air-sea gas exchange experiment (SAGE). The experiment was conducted in the high nitrate, low chlorophyll (HNLC) waters of the sub-Antarctic Southern Ocean (46.7°S 172.5°E) to the south-east of New Zealand, during March-April, 2004. In addition to monitoring net changes in the standing stocks of DMSPp and DMS, a series of dilution experiments were used to determine the DMSPp production and consumption rates in relation to increased iron availability. In contrast to previous experiments in the Southern Ocean, DMS concentrations decreased over the course of the 15-d iron-fertilisation experiment, from an integrated volume-specific concentration in the mixed layer on day 0 of 0.78 nM (measured values 0.65-0.91 nM) to 0.46 nM (measured values 0.42-0.47 nM) by day 15, in parallel with the surrounding waters. DMSPp, chlorophyll a and the abundance of photosynthetic picoeukaryotes exhibited indiscernible or only moderate increases in response to the raised iron availability, despite an obvious physiological response by the phytoplankton. High specific growth rates of DMSPp, equivalent to 0.8-1.2 doublings d -1, occurred at the simulated 60% light level of the dilution experiments. Despite the high production rates, DMSPp accumulation was suppressed in part by microzooplankton grazers who consumed between 61% d -1 and 126% d -1 of the DMSPp production. Temporal trends in the rates of production and consumption illustrated a close coupling between the DMSP-producing phytoplankton and their microzooplankton grazers. Similar grazing and production rates were observed for the eukaryotic picophytoplankton that dominated the phytoplankton biomass, partial evidence that picoeukaryotes contributed a substantial proportion of the DMSP synthesis. These rates for DMSPp and picoeukaryotes were considerably higher than for chlorophyll a, indicating higher cycling rates of the DMSP-producing taxa than for the bulk phytoplankton community. When compared to the total phytoplankton community, there was no evidence of selection against the DMSP-containing phytoplankton by the microzooplankton grazers; the opposite appeared to be the case. SAGE demonstrated that increased iron availability in the HNLC waters of the Southern Ocean does not invariably lead to enhanced DMS sea-air flux. The potential suppression of DMSPp accumulation by grazers needs to be taken into account in future attempts to elevate DMS emission through in situ iron fertilisation and in understanding the hypothesised link between levels of Aeolian iron deposition in the Southern Ocean, DMS emission and global albedo.

Iron fertilization of the Subantarctic Ocean during the last ice age

NASA Astrophysics Data System (ADS)

Martinez-Garcia, A.

2015-12-01

Dust has the potential to modify global climate by influencing the radiative balance of the atmosphere and by supplying iron and other essential limiting micronutrients to the ocean. The scarcity of iron limits marine productivity and carbon uptake in one-quarter of the world ocean where the concentration of major nutrients (phosphorus and nitrogen) is perennially high. The Southern Ocean is the region where variations in iron availability can have the largest effect on Earth's carbon cycle through its fertilizing effect on marine ecosystems. Paleoceanographic records from the Subantarctic Atlantic have revealed a remarkable correlation between phytoplankton productivity and aeolian iron flux during glacial periods supporting the iron fertilization hypothesis. In addition, a recent study has shown that peak glacial times and millennial cold events were nearly universally associated not only with increases in dust flux and export production, but also with an increase in nutrient consumption (the last indicated by higher foraminifera-bound δ15N) (Martinez-Garcia et al. 2014). This combination of changes is uniquely consistent with ice age iron fertilization of the Subantarctic Atlantic. The strengthening of the biological pump associated with the observed increase in Subantarctic nutrient consumption during the high-dust intervals of the last two ice ages can explain up to ~40 ppm of the CO2 decrease that characterizes the transitions from mid-climate states to full ice age conditions. However, the impact of iron fertilization in other sectors of the Southern Ocean characterized by lower ice age dust fluxes than the Atlantic remains unclear. A series of recently published records from the Subantarctic Pacific indicate that dust deposition and marine export production were three times higher during glacial periods than during interglacials (Lamy et al. 2014). Here we present new measurements of foraminifera-bound nitrogen isotopes in a sediment core located in the Subantarctic Pacific (PS75/56-1), which allow us to evaluate the impact of iron fertilization on major nutrient consumption in the largest Southern Ocean sector.

Obesity alters adipose tissue macrophage iron content and tissue iron distribution.

PubMed

Orr, Jeb S; Kennedy, Arion; Anderson-Baucum, Emily K; Webb, Corey D; Fordahl, Steve C; Erikson, Keith M; Zhang, Yaofang; Etzerodt, Anders; Moestrup, Søren K; Hasty, Alyssa H

2014-02-01

Adipose tissue (AT) expansion is accompanied by the infiltration and accumulation of AT macrophages (ATMs), as well as a shift in ATM polarization. Several studies have implicated recruited M1 ATMs in the metabolic consequences of obesity; however, little is known regarding the role of alternatively activated resident M2 ATMs in AT homeostasis or how their function is altered in obesity. Herein, we report the discovery of a population of alternatively activated ATMs with elevated cellular iron content and an iron-recycling gene expression profile. These iron-rich ATMs are referred to as MFe(hi), and the remaining ATMs are referred to as MFe(lo). In lean mice, ~25% of the ATMs are MFe(hi); this percentage decreases in obesity owing to the recruitment of MFe(lo) macrophages. Similar to MFe(lo) cells, MFe(hi) ATMs undergo an inflammatory shift in obesity. In vivo, obesity reduces the iron content of MFe(hi) ATMs and the gene expression of iron importers as well as the iron exporter, ferroportin, suggesting an impaired ability to handle iron. In vitro, exposure of primary peritoneal macrophages to saturated fatty acids also alters iron metabolism gene expression. Finally, the impaired MFe(hi) iron handling coincides with adipocyte iron overload in obese mice. In conclusion, in obesity, iron distribution is altered both at the cellular and tissue levels, with AT playing a predominant role in this change. An increased availability of fatty acids during obesity may contribute to the observed changes in MFe(hi) ATM phenotype and their reduced capacity to handle iron.

Effect of iron deficiency on the expression of insulin-like growth factor-II and its receptor in neuronal and glial cells.

PubMed

Morales González, E; Contreras, I; Estrada, J A

2014-09-01

Many studies have demonstrated that iron deficiency modifies the normal function of the central nervous system and alters cognitive abilities. When cellular damage occurs in the central nervous system, neuroprotective mechanisms, such as the production of neurotrophic factors, are essential in order for nervous tissue to function correctly. Insulin-like growth factor II (IGF- II) is a neurotrophic factor that was recently shown to be involved in the normal functioning of cognitive processes in animal models. However, the impact of iron deficiency on the expression and function of this molecule has not yet been clarified. Mixed primary cell cultures from the central nervous system were collected to simulate iron deficiency using deferoxamine. The expression of IGF-I, IGF-II, IGF-IR, and IGF-IIR was determined with the western blot test. We observed increased expression of IGF-II, along with a corresponding decrease in the expression of IGF-IIR, in iron-deficient mixed primary cell cultures. We did not observe alterations in the expression of these proteins in isolated microglia or neuronal cultures under the same conditions. We did not detect differences in the expression of IGF-I and IGF-IR in iron-deficient cultures. In vitro iron deficiency increases the expression of IGF-II in mixed glial cell cultures, which may have a beneficial effect on brain tissue homeostasis in a situation in which iron availability is decreased. Copyright © 2013 Sociedad Española de Neurología. Published by Elsevier Espana. All rights reserved.

α-Lactalbumin and casein-glycomacropeptide do not affect iron absorption from formula in healthy term infants.

PubMed

Szymlek-Gay, Ewa A; Lönnerdal, Bo; Abrams, Steven A; Kvistgaard, Anne S; Domellöf, Magnus; Hernell, Olle

2012-07-01

Iron absorption from infant formula is relatively low. α-Lactalbumin and casein-glycomacropeptide have been suggested to enhance mineral absorption. We therefore assessed the effect of α-lactalbumin and casein-glycomacropeptide on iron absorption from infant formula in healthy term infants. Thirty-one infants were randomly assigned to receive 1 of 3 formulas (4 mg iron/L, 13.1 g protein/L) from 4-8 wk to 6 mo of age: commercially available whey-predominant standard infant formula (standard formula), α-lactalbumin-enriched infant formula (α-LAC), or α-lactalbumin-enriched/casein-glycomacropeptide-reduced infant formula (α-LAC/RGMP). Nine breast-fed infants served as a reference. At 5.5 mo of age, (58)Fe was administered to all infants in a meal. Blood samples were collected 14 d later for iron absorption and iron status indices. Iron deficiency was defined as depleted iron stores, iron-deficient erythropoiesis, or iron deficiency anemia. Iron absorption (mean ± SD) was 10.3 ± 7.0% from standard formula, 8.6 ± 3.8% from α-LAC, 9.2 ± 6.5% from α-LAC/RGMP, and 12.9 ± 6.5% from breast milk, with no difference between the formula groups (P = 0.79) or all groups (P = 0.44). In the formula-fed infants only, iron absorption was negatively correlated with serum ferritin (r = -0.49; P = 0.005) and was higher (P = 0.023) in iron-deficient infants (16.4 ± 12.4%) compared with those with adequate iron status (8.6 ± 4.4%). Our findings indicate that α-lactalbumin and casein-glycomacropeptide do not affect iron absorption from infant formula in infants. Low serum ferritin concentrations are correlated with increased iron absorption from infant formula.

Rapidly Escalating Hepcidin and Associated Serum Iron Starvation Are Features of the Acute Response to Typhoid Infection in Humans

PubMed Central

Darton, Thomas C.; Blohmke, Christoph J.; Giannoulatou, Eleni; Waddington, Claire S.; Jones, Claire; Sturges, Pamela; Webster, Craig; Drakesmith, Hal; Pollard, Andrew J.; Armitage, Andrew E.

2015-01-01

Background Iron is a key pathogenic determinant of many infectious diseases. Hepcidin, the hormone responsible for governing systemic iron homeostasis, is widely hypothesized to represent a key component of nutritional immunity through regulating the accessibility of iron to invading microorganisms during infection. However, the deployment of hepcidin in human bacterial infections remains poorly characterized. Typhoid fever is a globally significant, human-restricted bacterial infection, but understanding of its pathogenesis, especially during the critical early phases, likewise is poorly understood. Here, we investigate alterations in hepcidin and iron/inflammatory indices following experimental human typhoid challenge. Methodology/Principal Findings Fifty study participants were challenged with Salmonella enterica serovar Typhi and monitored for evidence of typhoid fever. Serum hepcidin, ferritin, serum iron parameters, C-reactive protein (CRP), and plasma IL-6 and TNF-alpha concentrations were measured during the 14 days following challenge. We found that hepcidin concentrations were markedly higher during acute typhoid infection than at baseline. Hepcidin elevations mirrored the kinetics of fever, and were accompanied by profound hypoferremia, increased CRP and ferritin, despite only modest elevations in IL-6 and TNF-alpha in some individuals. During inflammation, the extent of hepcidin upregulation associated with the degree of hypoferremia. Conclusions/Significance We demonstrate that strong hepcidin upregulation and hypoferremia, coincident with fever and systemic inflammation, are hallmarks of the early innate response to acute typhoid infection. We hypothesize that hepcidin-mediated iron redistribution into macrophages may contribute to S. Typhi pathogenesis by increasing iron availability for macrophage-tropic bacteria, and that targeting macrophage iron retention may represent a strategy for limiting infections with macrophage-tropic pathogens such as S. Typhi. PMID:26394303

Decreasing TfR1 expression reverses anemia and hepcidin suppression in β-thalassemic mice

PubMed Central

Li, Huihui; Choesang, Tenzin; Bao, Weili; Chen, Huiyong; Feola, Maria; Garcia-Santos, Daniel; Li, Jie; Sun, Shuming; Follenzi, Antonia; Pham, Petra; Liu, Jing; Zhang, Jinghua; Ponka, Prem; An, Xiuli; Mohandas, Narla; Fleming, Robert E.; Rivella, Stefano; Li, Guiyuan

2017-01-01

Iron availability for erythropoiesis and its dysregulation in β-thalassemia are incompletely understood. We previously demonstrated that exogenous apotransferrin leads to more effective erythropoiesis, decreasing erythroferrone (ERFE) and derepressing hepcidin in β-thalassemic mice. Transferrin-bound iron binding to transferrin receptor 1 (TfR1) is essential for cellular iron delivery during erythropoiesis. We hypothesize that apotransferrin’s effect is mediated via decreased TfR1 expression and evaluate TfR1 expression in β-thalassemic mice in vivo and in vitro with and without added apotransferrin. Our findings demonstrate that β-thalassemic erythroid precursors overexpress TfR1, an effect that can be reversed by the administration of exogenous apotransferrin. In vitro experiments demonstrate that apotransferrin inhibits TfR1 expression independent of erythropoietin- and iron-related signaling, decreases TfR1 partitioning to reticulocytes during enucleation, and enhances enucleation of defective β-thalassemic erythroid precursors. These findings strongly suggest that overexpressed TfR1 may play a regulatory role contributing to iron overload and anemia in β-thalassemic mice. To evaluate further, we crossed TfR1+/− mice, themselves exhibiting iron-restricted erythropoiesis with increased hepcidin, with β-thalassemic mice. Resultant double-heterozygote mice demonstrate long-term improvement in ineffective erythropoiesis, hepcidin derepression, and increased erythroid enucleation in relation to β-thalassemic mice. Our data demonstrate for the first time that TfR1+/− haploinsufficiency reverses iron overload specifically in β-thalassemic erythroid precursors. Taken together, decreasing TfR1 expression during β-thalassemic erythropoiesis, either directly via induced haploinsufficiency or via exogenous apotransferrin, decreases ineffective erythropoiesis and provides an endogenous mechanism to upregulate hepcidin, leading to sustained iron-restricted erythropoiesis and preventing systemic iron overload in β-thalassemic mice. PMID:28151426

Prolyl hydroxylase inhibition corrects functional iron deficiency and inflammation-induced anaemia in rats.

PubMed

Barrett, Terrance D; Palomino, Heather L; Brondstetter, Theresa I; Kanelakis, Kimon C; Wu, Xiaodong; Yan, Wen; Merton, Katherine P; Schoetens, Freddy; Ma, Jing Ying; Skaptason, Judy; Gao, Jingjin; Tran, Da-Thao; Venkatesan, Hariharan; Rosen, Mark D; Shankley, Nigel P; Rabinowitz, Michael H

2015-08-01

Small-molecule inhibitors of prolyl hydroxylase (PHD) enzymes are a novel target for the treatment of anaemia and functional iron deficiency (FID). Other than being orally bioavailable, the differentiation of PHD inhibitors from recombinant human erythropoietin (rhEPO) has not been demonstrated. JNJ-42905343 was identified and characterized as a novel inhibitor of PHD and its action was compared with rhEPO in healthy rats and in a rat model of inflammation-induced anaemia and FID [peptidoglycan-polysaccharide (PGPS) model]. Oral administration of JNJ-42905343 to healthy rats increased the gene expression of cytochrome b (DcytB) and divalent metal-ion transporter 1 (DMT1) in the duodenum, and increased plasma EPO. Repeated administration of JNJ-42905343 for 28 days increased blood haemoglobin, mean corpuscular haemoglobin (MCH) and mean corpuscular volume (MCV). The serum iron concentration was increased with low doses (0.3 mg·kg(-1) ) but reduced at high doses (6 mg·kg(-1) ). In PGPS-treated rats, administration of JNJ-42905343 for 28 days corrected FID and anaemia, as reflected by increased blood haemoglobin, MCH and MCV. Increased expression of DcytB and DMT1 genes in the duodenum resulting in increased iron availability was defined as the mechanism for these effects. rhEPO did not affect DcytB and DMT1 and was not effective in PGPS-treated rats. PHD inhibition has a beneficial effect on iron metabolism in addition to stimulating the release of EPO. Small-molecule inhibitors of PHD such as JNJ-42905343 represent a mechanism distinct from rhEPO to treat anaemia and FID. © 2015 The British Pharmacological Society.

Experimental determination of activities of FeO and Fe 2O 3 components in hydrous silicic melts under oxidizing conditions

NASA Astrophysics Data System (ADS)

Gaillard, Fabrice; Pichavant, Michel; Scaillet, Bruno

2003-11-01

The critical role of iron on crystal-silicate liquid relationships and melt differentiation is mainly controlled by the redox conditions prevailing in magmas, but the presently available database merely constrains the thermodynamic properties of iron-bearing components in strongly reduced and anhydrous molten silicate where iron is in the ferrous form. This paper provides new standard states for pure ferrous (FeOliq) and ferric (Fe2O3liq) molten iron oxides and extends the experimental database towards oxidizing and water-bearing domains. Iron-iridium, iron-platinum alloys, magnetite or hematite were equilibrated with synthetic silicic liquids at high temperature and high pressure under controlled oxygen fugacity (fO2) to determine activity-composition relationships for FeOliq and Fe2O3liq. Between 1000 and 1300°C, the fO2 ranges from that in air to 3-log units below that of the nickel-nickel oxide buffer (NNO). Experiments were performed on both anhydrous and hydrous melts containing up to 6-wt.% water. Incorporation of water under reducing conditions increases the activity coefficient of FeOliq but has an opposite effect on Fe2O3liq. As calcium is added to system, the effect of water becomes weaker and is inverted for Fe2O3liq. Under oxidizing conditions, water has a negligible effect on both activities of FeOliq and Fe2O3liq. In contrast, changes in redox conditions dominate the activity coefficients of both FeOliq and Fe2O3liq, which increase significantly with increasing fO2. The present results combined with the previous work provide a specific database on the energetics of iron in silicate melts that cover most of the condition prevailing in natural magmas.

A study of Reactive Red 198 adsorption on iron filings from aqueous solutions.

PubMed

Azhdarpoor, Abooalfazl; Nikmanesh, Roya; Khademi, Fahime

2014-01-01

In recent years, reactive dyes have been widely used in textile industries with particular efficiency. They dyes are often toxic, carcinogenic and mutagenic. Improper treatment and non-scientific disposal of dyed wastewater from these industries into water sources has created many environmental problems and concerns around the world. The purpose of the present study is to investigate the efficiency of iron filings in adsorption of Reactive Red 198 from aqueous solutions. This study was conducted using an experimental method at the laboratory scale. In this study, the effects of operating parameters such as pH (1-11), initial dye concentration (40-400 mg/L), contact time (5-120 min) and iron dose (0.1-1 g) with a mesh of<100 were studied. Dye concentration was determined using a spectrophotometer at a wavelength of 520 nm. The results indicated that maximum adsorption capacity of the dye in question was obtained at pH 3, contact time of 60 min and adsorbent dose of 1 g. At initial dye concentration of 100 and 200 mg/L, by increasing the dose of waste iron from 0.1 to 1 g, the removal percentage increased from approximately 76.89% to 97.28% and from 22.64% to 68.03%, respectively. At pH 3, contact time of 5 min and constant waste iron dose of 0.8 g, the dye removal efficiency was 85.34%. By increasing the contact time to 120 min, the removal efficiency increased to 99.2%. Welding iron waste as an inexpensive and available adsorbent has an optimum ability for adsorption of Reactive Red 198 from aqueous solutions.

Iron oxidation stimulates organic matter decomposition in humid tropical forest soils.

PubMed

Hall, Steven J; Silver, Whendee L

2013-09-01

Humid tropical forests have the fastest rates of organic matter decomposition globally, which often coincide with fluctuating oxygen (O2 ) availability in surface soils. Microbial iron (Fe) reduction generates reduced iron [Fe(II)] under anaerobic conditions, which oxidizes to Fe(III) under subsequent aerobic conditions. We demonstrate that Fe (II) oxidation stimulates organic matter decomposition via two mechanisms: (i) organic matter oxidation, likely driven by reactive oxygen species; and (ii) increased dissolved organic carbon (DOC) availability, likely driven by acidification. Phenol oxidative activity increased linearly with Fe(II) concentrations (P < 0.0001, pseudo R(2)  = 0.79) in soils sampled within and among five tropical forest sites. A similar pattern occurred in the absence of soil, suggesting an abiotic driver of this reaction. No phenol oxidative activity occurred in soils under anaerobic conditions, implying the importance of oxidants such as O2 or hydrogen peroxide (H2 O2 ) in addition to Fe(II). Reactions between Fe(II) and H2 O2 generate hydroxyl radical, a strong nonselective oxidant of organic compounds. We found increasing consumption of H2 O2 as soil Fe(II) concentrations increased, suggesting that reactive oxygen species produced by Fe(II) oxidation explained variation in phenol oxidative activity among samples. Amending soils with Fe(II) at field concentrations stimulated short-term C mineralization by up to 270%, likely via a second mechanism. Oxidation of Fe(II) drove a decrease in pH and a monotonic increase in DOC; a decline of two pH units doubled DOC, likely stimulating microbial respiration. We obtained similar results by manipulating soil acidity independently of Fe(II), implying that Fe(II) oxidation affected C substrate availability via pH fluctuations, in addition to producing reactive oxygen species. Iron oxidation coupled to organic matter decomposition contributes to rapid rates of C cycling across humid tropical forests in spite of periodic O2 limitation, and may help explain the rapid turnover of complex C molecules in these soils. © 2013 John Wiley & Sons Ltd.

Low-pH cola beverages do not affect women's iron absorption from a vegetarian meal.

PubMed

Collings, Rachel; Fairweather-Tait, Susan J; Dainty, Jack R; Roe, Mark A

2011-05-01

Preliminary data in the literature indicate that iron absorption from a meal may be increased when consumed with low-pH beverages such as cola, and it is also possible that sugar iron complexes may alter iron availability. A randomized, crossover trial was conducted to compare the bioavailability of nonheme iron from a vegetarian pizza meal when consumed with 3 different beverages (cola, diet cola, and mineral water). Sixteen women with serum ferritin concentrations of 11-54 µg/L were recruited and completed the study. The pizza meal contained native iron and added ferric chloride solution as a stable isotope extrinsic label; the total iron content of the meal was ~5.3 mg. Incorporation of iron from the meal into RBC was not affected by the type of drink (9.9% with cola, 9.4% with diet cola, and 9.6% with water). Serum ferritin and plasma hepcidin were correlated (r = 0.66; P<0.001) and both were significant predictors of iron bioavailability, but their combined effect explained only 30% of the inter-individual variation (P<0.001) and illustrates the current lack of understanding of mechanisms responsible for the fine-tuning of iron absorption. Although there was no effect of low-pH drinks on iron bioavailability in healthy women, their effect on absorption of fortification iron that requires solubilization in dilute acid, such as reduced iron, and in individuals with low gastric acid production, such as older people and individuals with Helicobacter pylori infection, warrants further investigation.

Assessing Phytoplankton Nutritional Status and Potential Impact of Wet Deposition in Seasonally Oligotrophic Waters of the Mid-Atlantic Bight

NASA Astrophysics Data System (ADS)

Sedwick, P. N.; Bernhardt, P. W.; Mulholland, M. R.; Najjar, R. G.; Blumen, L. M.; Sohst, B. M.; Sookhdeo, C.; Widner, B.

2018-04-01

To assess phytoplankton nutritional status in seasonally oligotrophic waters of the southern Mid-Atlantic Bight, and the potential for rain to stimulate primary production in this region during summer, shipboard bioassay experiments were performed using natural seawater and phytoplankton collected north and south of the Gulf Stream. Bioassay treatments comprised iron, nitrate, iron + nitrate, iron + nitrate + phosphate, and rainwater. Phytoplankton growth was inferred from changes in chlorophyll a, inorganic nitrogen, and carbon-13 uptake, relative to unamended control treatments. Results indicated the greatest growth stimulation by iron + nitrate + phosphate, intermediate growth stimulation by rainwater, modest growth stimulation by nitrate and iron + nitrate, and no growth stimulation by iron. Based on these data and analysis of seawater and atmospheric samples, nitrogen was the proximate limiting nutrient, with a secondary limitation imposed by phosphorus. Our results imply that summer rain events increase new production in these waters by contributing nitrogen and phosphorus, with the availability of the latter setting the upper limit on rain-stimulated new production.

Analysis of Nucleotide Variations in Genes of Iron Management in Patients of Parkinson's Disease and Other Movement Disorders

PubMed Central

Castiglioni, Emanuela; Finazzi, Dario; Goldwurm, Stefano; Pezzoli, Gianni; Forni, Gianluca; Girelli, Domenico; Maccarinelli, Federica; Poli, Maura; Ferrari, Maurizio; Cremonesi, Laura; Arosio, Paolo

2011-01-01

The capacity to act as an electron donor and acceptor makes iron an essential cofactor of many vital processes. Its balance in the body has to be tightly regulated since its excess can be harmful by favouring oxidative damage, while its deficiency can impair fundamental activities like erythropoiesis. In the brain, an accumulation of iron or an increase in its availability has been associated with the development and/or progression of different degenerative processes, including Parkinson's disease, while iron paucity seems to be associated with cognitive deficits, motor dysfunction, and restless legs syndrome. In the search of DNA sequence variations affecting the individual predisposition to develop movement disorders, we scanned by DHPLC the exons and intronic boundary regions of ceruloplasmin, iron regulatory protein 2, hemopexin, hepcidin and hemojuvelin genes in cohorts of subjects affected by Parkinson's disease and idiopathic neurodegeneration with brain iron accumulation (NBIA). Both novel and known sequence variations were identified in most of the genes, but none of them seemed to be significantly associated to the movement diseases of interest. PMID:20981230

IscR Regulates Synthesis of Colonization Factor Antigen I Fimbriae in Response to Iron Starvation in Enterotoxigenic Escherichia coli

PubMed Central

Arnaud-Barbe, Nadège; Poncet, David; Reverchon, Sylvie; Wawrzyniak, Julien; Nasser, William

2015-01-01

ABSTRACT Iron availability functions as an environmental cue for enteropathogenic bacteria, signaling arrival within the human host. As enterotoxigenic Escherichia coli (ETEC) is a major cause of human diarrhea, the effect of iron on ETEC virulence factors was evaluated here. ETEC pathogenicity is directly linked to production of fimbrial colonization factors and secretion of heat-labile enterotoxin (LT) and/or heat-stable enterotoxin (ST). Efficient colonization of the small intestine further requires at least the flagellin binding adhesin EtpA. Under iron starvation, production of the CFA/I fimbriae was increased in the ETEC H10407 prototype strain. In contrast, LT secretion was inhibited. Furthermore, under iron starvation, gene expression of the cfa (CFA/I) and etp (EtpBAC) operons was induced, whereas transcription of toxin genes was either unchanged or repressed. Transcriptional reporter fusion experiments focusing on the cfa operon further showed that iron starvation stimulated cfaA promoter activity in ETEC, indicating that the impact of iron on CFA/I production was mediated by transcriptional regulation. Evaluation of cfaA promoter activity in heterologous E. coli single mutant knockout strains identified IscR as the regulator responsible for inducing cfa fimbrial gene expression in response to iron starvation, and this was confirmed in an ETEC ΔiscR strain. The global iron response regulator, Fur, was not implicated. IscR binding sites were identified in silico within the cfaA promoter and fixation confirmed by DNase I footprinting, indicating that IscR directly binds the promoter region to induce CFA/I. IMPORTANCE Pathogenic enterobacteria modulate expression of virulence genes in response to iron availability. Although the Fur transcription factor represents the global regulator of iron homeostasis in Escherichia coli, we show that several ETEC virulence factors are modulated by iron, with expression of the major fimbriae under the control of the iron-sulfur cluster regulator, IscR. Furthermore, we demonstrate that the apo form of IscR, lacking an Fe-S cluster, is able to directly fix the corresponding promoter region. These results provide further evidence implicating IscR in bacterial virulence and suggest that IscR may represent a more general regulator mediating the iron response in enteropathogens. PMID:26124243

Changes in erythropoietin levels during space flight or space flight simulation

NASA Technical Reports Server (NTRS)

Dunn, C. D. R.; Hen, J. P.

1980-01-01

Two hundred and seventy samples from 24 subjects involved in 3 bedrest studies and from 3 subjects involved in Spacelab Mission Development Test 3 were assayed for erythropoietin (Ep), in an in vitro fetal mouse liver cell assay, and for ferritin using a commercially available immunoradiometric assay kit. No trends or significant changes in serum Ep were observed. Serum ferritin concentrations tended to increases slightly during the 'missions', reflecting a redirection of iron from the suppressed erythron into iron stores.

Results of the First American Prospective Study of Intravenous Iron in Oral Iron-Intolerant Iron-Deficient Gravidas.

PubMed

Auerbach, Michael; James, Stephanie E; Nicoletti, Melissa; Lenowitz, Steven; London, Nicola; Bahrain, Huzefa F; Derman, Richard; Smith, Samuel

2017-12-01

Anemia affects up to 42% of gravidas. Neonatal iron deficiency is associated with low birth weight, delayed growth and development, and increased cognitive and behavioral abnormalities. While oral iron is convenient, up to 70% report significant gastrointestinal toxicity. Intravenous iron formulations allowing replacement in one visit with favorable side-effect profiles decrease rates of anemia with improved hemoglobin responses and maternal fetal outcomes. Seventy-four oral iron-intolerant, second- and third-trimester iron-deficient gravidas were questioned for oral iron intolerance and treated with intravenous iron. All received 1000 mg of low-molecular-weight iron dextran in 250 mL normal saline. Fifteen minutes after a test dose, the remainder was infused over the balance of 1 hour. Subjects were called at 1, 2, and 7 days to assess delayed reactions. Four weeks postinfusion or postpartum, hemoglobin levels and iron parameters were measured. Paired t test was used for hemoglobin and iron; 58/73 women were questioned about interval growth and development of their babies. Seventy-three of 74 enrolled subjects completed treatment. Sixty had paired pre- and posttreatment data. The mean pre- and posthemoglobin concentrations were 9.7 and 10.8 g/dL (P < .00001), transferrin saturations 11.7% and 22.6% (P = .0003), and ferritins 14.5 and 126.3 ng/mL, respectively (P < .000001). Six experienced minor infusion reactions. All resolved. Data for 58 infants were available; one was low on its growth charts for 11 months. The remaining 57 were normal. None were diagnosed with iron deficiency anemia. Intravenous iron has less toxicity and is more effective, supporting moving it closer to frontline therapy. Copyright © 2017 Elsevier Inc. All rights reserved.

TNF, IFN, AND ENDOTOXIN INCREASE EXPRESSION OF DMT-1 IN BRONCHIAL EPITHELIAL CELLS

EPA Science Inventory

Regulation of the metal transport protein DMT1 may contribute to the uptake and detoxification of iron by cells resident in the respiratory tract. Inflammation has been associated with an increased availability of this metal resulting in an oxidative stress. Because pro-inflamm...

Modulation of transferrin receptor mRNA by transferrin-gallium in human myeloid HL60 and lymphoid CCRF-CEM leukaemic cells.

PubMed Central

Ul-Haq, R; Chitambar, C R

1993-01-01

Gallium binds to the iron transport protein transferrin (Tf), is incorporated into cells through transferrin receptors (TfR) and inhibits iron-dependent DNA synthesis. Since cellular TfR expression is tightly regulated by the availability of iron, we investigated the effects of transferrin-gallium (Tf-Ga) on TfR mRNA levels in myeloid HL60 and lymphoid CCRF-CEM cells. In HL60 cells, Tf-Ga increased TfR mRNA levels in a dose-dependent fashion. This increase in TfR mRNA was blocked by Tf-Fe and by cycloheximide. Analysis of the rate of mRNA decay in the presence of actinomycin D revealed that the half-life of TfR mRNA was increased in HL60 cells incubated with Tf-Ga. The rate of transcription of TfR mRNA was not increased by Tf-Ga. In contrast with HL60 cells, CCRF-CEM cells displayed a decrease in the level of TfR mRNA after incubation with Tf-Ga. Tf-Ga inhibited iron uptake in both HL60 and CCRF-CEM cells but increased the level of TfR mRNA only in HL60 cells, suggesting that the Tf-Ga induction of TfR mRNA was not solely due to inhibition of cellular iron uptake. At growth-inhibitory concentrations, Tf-Ga increased the TfR mRNA level in HL60 cells but decreased it in CCRF-CEM cells. Our studies suggest that in HL60 cells, gallium regulates TfR expression at the post-transcriptional level by mechanisms which require de novo protein synthesis and involve interaction with iron. The divergent effects of Tf-Ga on TfR mRNA in myeloid HL60 and lymphoid CCRF-CEM cells suggest that differences exist in the regulation of TfR expression between these two cell types. Images Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 PMID:8379943

Iron overload causes endolysosomal deficits modulated by NAADP-regulated 2-pore channels and RAB7A

PubMed Central

Fernández, Belén; Fdez, Elena; Gómez-Suaga, Patricia; Gil, Fernando; Molina-Villalba, Isabel; Ferrer, Isidro; Patel, Sandip; Churchill, Grant C.; Hilfiker, Sabine

2016-01-01

ABSTRACT Various neurodegenerative disorders are associated with increased brain iron content. Iron is known to cause oxidative stress, which concomitantly promotes cell death. Whereas endolysosomes are known to serve as intracellular iron storage organelles, the consequences of increased iron on endolysosomal functioning, and effects on cell viability upon modulation of endolysosomal iron release remain largely unknown. Here, we show that increasing intracellular iron causes endolysosomal alterations associated with impaired autophagic clearance of intracellular protein aggregates, increased cytosolic oxidative stress and increased cell death. These effects are subject to regulation by NAADP, a potent second messenger reported to target endolysosomal TPCNs (2-pore channels). Consistent with endolysosomal iron storage, cytosolic iron levels are modulated by NAADP, and increased cytosolic iron is detected when overexpressing active, but not inactive TPCNs, indicating that these channels can modulate endolysosomal iron release. Cell death triggered by altered intralysosomal iron handling is abrogated in the presence of an NAADP antagonist or when inhibiting RAB7A activity. Taken together, our results suggest that increased endolysosomal iron causes cell death associated with increased cytosolic oxidative stress as well as autophagic impairments, and these effects are subject to modulation by endolysosomal ion channel activity in a RAB7A-dependent manner. These data highlight alternative therapeutic strategies for neurodegenerative disorders associated with increased intracellular iron load. PMID:27383256

Dynamic characteristics of sulfur, iron and phosphorus in coastal polluted sediments, north China.

PubMed

Sun, Qiyao; Sheng, Yanqing; Yang, Jian; Di Bonito, Marcello; Mortimer, Robert J G

2016-12-01

The cycling of sulfur (S), iron (Fe) and phosphorus (P) in sediments and pore water can impact the water quality of overlying water. In a heavily polluted river estuary (Yantai, China), vertical profiles of fluxes of dissolved sulfide, Fe 2+ and dissolved reactive phosphorus (DRP) in sediment pore water were investigated by the Diffusive Gradients in Thin films technique (DGT). Vertical fluxes of S, Fe, P in intertidal sediment showed the availability of DRP increased while the sulfide decreased with depth in surface sediment, indicating that sulfide accumulation could enhance P release in anoxic sediment. In sites with contrasting salinity, the relative dominance of iron and sulfate reduction was different, with iron reduction dominant over sulfate reduction in the upper sediment at an intertidal site but the reverse true in a freshwater site, with the other process dominating at depth in each case. Phosphate release was largely controlled by iron reduction. Copyright © 2016 Elsevier Ltd. All rights reserved.

GNPAT p.D519G is independently associated with markedly increased iron stores in HFE p.C282Y homozygotes.

PubMed

Barton, James C; Chen, Wen-Pin; Emond, Mary J; Phatak, Pradyumna D; Subramaniam, V Nathan; Adams, Paul C; Gurrin, Lyle C; Anderson, Gregory J; Ramm, Grant A; Powell, Lawrie W; Allen, Katrina J; Phillips, John D; Parker, Charles J; McLaren, Gordon D; McLaren, Christine E

2017-03-01

GNPAT p.D519G positivity is significantly increased in HFE p.C282Y homozygotes with markedly increased iron stores. We sought to determine associations of p.D519G and iron-related variables with iron stores in p.C282Y homozygotes. We defined markedly increased iron stores as serum ferritin >2247pmol/L (>1000μg/L) and either hepatic iron >236μmol/g dry weight or iron >10g by induction phlebotomy (men and women). We defined normal or mildly elevated iron stores as serum ferritin <674.1pmol/L (<300μg/L) or either age≥40y with iron ≤2.5g iron by induction phlebotomy or age≥50y with ≤3.0g iron by induction phlebotomy (men only). We compared participant subgroups using univariate methods. Using multivariable logistic regression, we evaluated associations of markedly increased iron stores with these variables: age; iron supplement use (dichotomous); whole blood units donated; erythrocyte units received as transfusion; daily alcohol consumption, g; and p.D519G positivity (heterozygosity or homozygosity). The mean age of 56 participants (94.6% men) was 55±10 (SD) y; 41 had markedly increased iron stores. Prevalences of swollen/tender 2nd/3rd metacarpophalangeal joints and elevated aspartate or alanine aminotransferase were significantly greater in participants with markedly increased iron stores. Only participants with markedly increased iron stores had cirrhosis. In multivariable analyses, p.D519G positivity was the only exposure variable significantly associated with markedly increased iron stores (odds ratio 9.9, 95% CI [1.6, 60.3], p=0.0126). GNPAT p.D519G is strongly associated with markedly increased iron stores in p.C282Y homozygotes after correction for age, iron-related variables, and alcohol consumption. Copyright © 2016 Elsevier Inc. All rights reserved.

Effect of Dietary Iron Loading on Recognition Memory in Growing Rats

PubMed Central

Han, Murui; Kim, Jonghan

2015-01-01

While nutritional and neurobehavioral problems are associated with both iron deficiency during growth and overload in the elderly, the effect of iron loading in growing ages on neurobehavioral performance has not been fully explored. To characterize the role of dietary iron loading in memory function in the young, weanling rats were fed iron-loading diet (10,000 mg iron/kg diet) or iron-adequate control diet (50 mg/kg) for one month, during which a battery of behavioral tests were conducted. Iron-loaded rats displayed elevated non-heme iron levels in serum and liver, indicating a condition of systemic iron overload. In the brain, non-heme iron was elevated in the prefrontal cortex of iron-loaded rats compared with controls, whereas there was no difference in iron content in other brain regions between the two diet groups. While iron loading did not alter motor coordination or anxiety-like behavior, iron-loaded rats exhibited a better recognition memory, as represented by an increased novel object recognition index (22% increase from the reference value) than control rats (12% increase; P=0.047). Western blot analysis showed an up-regulation of dopamine receptor 1 in the prefrontal cortex from iron-loaded rats (142% increase; P=0.002). Furthermore, levels of glutamate receptors (both NMDA and AMPA) and nicotinic acetylcholine receptor (nAChR) were significantly elevated in the prefrontal cortex of iron-loaded rats (62% increase in NR1; 70% increase in Glu1A; 115% increase in nAChR). Dietary iron loading also increased the expression of NMDA receptors and nAChR in the hippocampus. These results support the idea that iron is essential for learning and memory and further reveal that iron supplementation during developmental and rapidly growing periods of life improves memory performance. Our investigation also demonstrates that both cholinergic and glutamatergic neurotransmission pathways are regulated by dietary iron and provides a molecular basis for the role of iron loading in improved memory. PMID:25746420

Asthma as a disruption in iron homeostasis | Science ...

EPA Pesticide Factsheets

Over several decades, asthma has evolved from being recognized as a single disease to include a diverse group of phenotypes with dissimilar natural histories, pathophysiologies, responses to treatment, and distinctive molecular pathways. With the application of Occam’s razor to asthma, it is proposed that there is one cause underlying the numerous phenotypes of this disease and that the responsible molecular pathway is a deficiency of iron in the lung tissues. This deficiency can be either absolute (e.g. asthma in the neonate and during both pregnancy and menstruation) or functional (e.g. asthma associated with infections, smoking, and obesity). Comparable associations between asthma co-morbidity (e.g. eczema, urticaria, restless leg syndrome, and pulmonary hypertension) with iron deficiency support such a shared mechanistic pathway. Therapies directed at asthma demonstrate a capacity to impact iron homeostasis, further strengthening the relationship. Finally, pathophysiologic events producing asthma, including inflammation, increases in Th2 cells, and muscle contraction, can correlate with iron availability. Recognition of a potential association between asthma and an absolute and/or functional iron deficiency suggests specific therapeutic interventions including inhaled iron. Asthma is a public health issue that has environmental triggers. Iron homeostasis is an essential mechanism whereby the body manages the impact of environmental agents on overall

Daily supplementation with iron increases lipid peroxidation in young women with low iron stores.

PubMed

King, Sarah M; Donangelo, Carmen M; Knutson, Mitchell D; Walter, Patrick B; Ames, Bruce N; Viteri, Fernando E; King, Janet C

2008-06-01

The aim of this study was to determine whether women with low iron stores (plasma ferritin

The Impact of Iron on Soil N2O Production Depends on Oxygen Availability

NASA Astrophysics Data System (ADS)

Zhu, X.; Doane, T. A.; Burger, M.; Horwath, W. R.

2014-12-01

The continuous increase of nitrous oxide (N2O) abundance in the atmosphere is a global concern. Soils are both an important source and sink of N2O, which is produced and consumed through biological processes including ammonia oxidation, heterotrophic denitrification, codenitrification, and through abiotic processes such as chemodenitrification. Iron is the most abundant element in the earth and is also the most prevalent redox-active metal in the biosphere. Its role in both chemical and biochemical reactions in N biogeochemistry cycling is well recognized. However, iron's significance to N2O production is poorly understood, especially under varying O2 concentration. We examined N2O production under different O2 concentrations following amorphous iron (III) oxyhydroxide and ammonical N fertilizer additions in four soil slurries and two static soils (soil moisture was 50% of water holding capacity). Under 21% O2, the addition of iron (III) significantly decreased N2O production in all the soil slurries and static soils, while the opposite phenomenon was observed once the O2 concentration became limited (≤3% in the soil slurry and ≤0.5% in the static soil). Our results show that the influence of iron on soil N2O production depends on O2 availability, which is the dominant controller of N2O production pathways. We hypothesize that under ambient O2 conditions, iron can react with nitrite produced during ammonia oxidation, thus reducing the probability of NO2- being used by nitrifiers as electron acceptor in nitrifier denitrification. In contrast, under anaerobic conditions (O2<0.5%), less nitrite was detected in the presence of the iron addition. Under these conditions, iron may have inhibited N2O reductase, or reduced iron (II) reacted with nitrite, both of which would lead to greater release of N2O.These findings imply that management practices which focus on mitigating N2O emission should avoid the application of iron-rich materials such as biosolids when anaerobic conditions might develop. In contrast, use of such materials could be a beneficial component of strategies to minimize N2O emission in well-aerated systems.

Fungal Iron Availability during Deep Seated Candidiasis Is Defined by a Complex Interplay Involving Systemic and Local Events

PubMed Central

Potrykus, Joanna; Stead, David; MacCallum, Donna M.; Urgast, Dagmar S.; Raab, Andrea; van Rooijen, Nico; Feldmann, Jörg; Brown, Alistair J. P.

2013-01-01

Nutritional immunity – the withholding of nutrients by the host – has long been recognised as an important factor that shapes bacterial-host interactions. However, the dynamics of nutrient availability within local host niches during fungal infection are poorly defined. We have combined laser ablation-inductively coupled plasma mass spectrometry (LA-ICP MS), MALDI imaging and immunohistochemistry with microtranscriptomics to examine iron homeostasis in the host and pathogen in the murine model of systemic candidiasis. Dramatic changes in the renal iron landscape occur during disease progression. The infection perturbs global iron homeostasis in the host leading to iron accumulation in the renal medulla. Paradoxically, this is accompanied by nutritional immunity in the renal cortex as iron exclusion zones emerge locally around fungal lesions. These exclusion zones correlate with immune infiltrates and haem oxygenase 1-expressing host cells. This local nutritional immunity decreases iron availability, leading to a switch in iron acquisition mechanisms within mature fungal lesions, as revealed by laser capture microdissection and qRT-PCR analyses. Therefore, a complex interplay of systemic and local events influences iron homeostasis and pathogen-host dynamics during disease progression. PMID:24146619

Trypanosoma cruzi: in vivo evaluation of iron in skin employing X-ray fluorescence (XRF) in mouse strains that differ in their susceptibility to infection.

PubMed

Estevam, Marcelo; Appoloni, Carlos Roberto; Malvezi, Aparecida Donizette; Tatakihara, Vera Lúcia Hideko; Panis, Carolina; Cecchini, Rubens; Rizzo, Luiz Vicente; Pinge-Filho, Phileno

2012-04-01

Trypanosoma cruzi, the causative agent of Chagas' disease (CD), is a substantial public health concern in Latin America. Laboratory mice inoculated with T. cruzi have served as important animal models of acute CD. Host hypoferremic responses occur during T. cruzi infection; therefore, it has been hypothesized that T. cruzi requires iron for optimal growth in host cells and, unlike extracellular pathogens, may benefit from host hypoferremic responses. Recent technological improvements of X-ray fluorescence are useful for diagnostics or monitoring in biomedical applications. The goal of our study was to determine whether the iron availabilities in Swiss and C57BL/6 mice differ during the acute phase of T. cruzi infection and whether the availability correlates with oxidative stress in the susceptible and resistant phenotypes identified in these mice. Our results showed that the decrease in iron levels in the skin of resistant infected mice correlated with the increase in oxidative stress associated with anemia and the reduction in parasite burden. © 2011 Federation of European Microbiological Societies. Published by Blackwell Publishing Ltd. All rights reserved.

MYB10 and MYB72 are required for growth under iron-limiting conditions.

PubMed

Palmer, Christine M; Hindt, Maria N; Schmidt, Holger; Clemens, Stephan; Guerinot, Mary Lou

2013-11-01

Iron is essential for photosynthesis and is often a limiting nutrient for plant productivity. Plants respond to conditions of iron deficiency by increasing transcript abundance of key genes involved in iron homeostasis, but only a few regulators of these genes have been identified. Using genome-wide expression analysis, we searched for transcription factors that are induced within 24 hours after transferring plants to iron-deficient growth conditions. Out of nearly 100 transcription factors shown to be up-regulated, we identified MYB10 and MYB72 as the most highly induced transcription factors. Here, we show that MYB10 and MYB72 are functionally redundant and are required for plant survival in alkaline soil where iron availability is greatly restricted. myb10myb72 double mutants fail to induce transcript accumulation of the nicotianamine synthase gene NAS4. Both myb10myb72 mutants and nas4-1 mutants have reduced iron concentrations, chlorophyll levels, and shoot mass under iron-limiting conditions, indicating that these genes are essential for proper plant growth. The double myb10myb72 mutant also showed nickel and zinc sensitivity, similar to the nas4 mutant. Ectopic expression of NAS4 rescues myb10myb72 plants, suggesting that loss of NAS4 is the primary defect in these plants and emphasizes the importance of nicotianamine, an iron chelator, in iron homeostasis. Overall, our results provide evidence that MYB10 and MYB72 act early in the iron-deficiency regulatory cascade to drive gene expression of NAS4 and are essential for plant survival under iron deficiency.

Heme controls ferroportin1 (FPN1) transcription involving Bach1, Nrf2 and a MARE/ARE sequence motif at position -7007 of the FPN1 promoter.

PubMed

Marro, Samuele; Chiabrando, Deborah; Messana, Erika; Stolte, Jens; Turco, Emilia; Tolosano, Emanuela; Muckenthaler, Martina U

2010-08-01

Macrophages of the reticuloendothelial system play a key role in recycling iron from hemoglobin of senescent or damaged erythrocytes. Heme oxygenase 1 degrades the heme moiety and releases inorganic iron that is stored in ferritin or exported to the plasma via the iron export protein ferroportin. In the plasma, iron binds to transferrin and is made available for de novo red cell synthesis. The aim of this study was to gain insight into the regulatory mechanisms that control the transcriptional response of iron export protein ferroportin to hemoglobin in macrophages. Iron export protein ferroportin mRNA expression was analyzed in RAW264.7 mouse macrophages in response to hemoglobin, heme, ferric ammonium citrate or protoporphyrin treatment or to siRNA mediated knockdown or overexpression of Btb And Cnc Homology 1 or nuclear accumulation of Nuclear Factor Erythroid 2-like. Iron export protein ferroportin promoter activity was analyzed using reporter constructs that contain specific truncations of the iron export protein ferroportin promoter or mutations in a newly identified MARE/ARE element. We show that iron export protein ferroportin is transcriptionally co-regulated with heme oxygenase 1 by heme, a degradation product of hemoglobin. The protoporphyrin ring of heme is sufficient to increase iron export protein ferroportin transcriptional activity while the iron released from the heme moiety controls iron export protein ferroportin translation involving the IRE in the 5'untranslated region. Transcription of iron export protein ferroportin is inhibited by Btb and Cnc Homology 1 and activated by Nuclear Factor Erythroid 2-like involving a MARE/ARE element located at position -7007/-7016 of the iron export protein ferroportin promoter. This finding suggests that heme controls a macrophage iron recycling regulon involving Btb and Cnc Homology 1 and Nuclear Factor Erythroid 2-like to assure the coordinated degradation of heme by heme oxygenase 1, iron storage and detoxification by ferritin, and iron export by iron export protein ferroportin.

Atmospheric iron supply and enhanced vertical carbon flux in the NE subarctic Pacific: Is there a connection?

NASA Astrophysics Data System (ADS)

Boyd, P. W.; Wong, C. S.; Merrill, J.; Whitney, F.; Snow, J.; Harrison, P. J.; Gower, J.

1998-09-01

Recent studies have confirmed the relationship between iron supply and phytoplankton growth rates in all three high-nitrate low-chlorophyll (HNLC) oceanic provinces. However, there is little evidence, so far, of the role of iron in altering the efficiency of the biological pump via increased downward export of particulate organic carbon (POC). The NE subarctic Pacific is unique among HNLC regions in that long time series pelagic observations and deep-moored sediment trap records exist which may provide the best opportunity thus far to test aspects of the iron hypothesis. Episodic elevated levels of chlorophyll a (> 2.0 μg L-1) were observed 6 times between 1964 and 1976 at the former site of Ocean Station Papa (OSP). In addition, between 1984 and 1990 on at least three occasions, concurrent pulses of POC and biogenic silica were recorded in deep-moored traps at OSP. Possible explanations for these events, such as lateral advection of more productive waters, iron-mediated blooms, or grazing by salp swarms are discussed and tested using an existing downward POC flux model. Owing to the episodic nature of such events, no available data are sufficiently comprehensive to unequivocally rule out any of these explanations. Nevertheless, from the data available, the occurrence of pelagic or deep water pulses, approximately once every 3 years, are most consistent with iron-mediated diatom blooms, and of the sinking of POC and biogenic silica (from such a bloom) to depth, respectively. A comparison of the timing of these iron-mediated pulses with that of the transport probabilities of atmospheric dust supply from Asia and Alaska provides an opportunity to assess the likelihood of a coupling between the atmosphere and the ocean.

Isolation and identification of ferric reducing bacteria and evaluation of their roles in iron availability in two calcareous soils

NASA Astrophysics Data System (ADS)

Ghorbanzadeh, N.; Lakzian, A.; Haghnia, G. H.; Karimi, A. R.

2014-12-01

Iron is an essential element for all organisms which plays a crucial role in important biochemical processes such as respiration and photosynthesis. Iron deficiency seems to be an important problem in many calcareous soils. Biological dissimilatory Fe(III) reduction increases iron availability through reduction of Fe(III) to Fe(II). The aim of this study was to isolate, identify and evaluate some bacterial isolates for their abilities to reduce Fe(III) in two calcareous soils. Three bacterial isolates were selected and identified from paddy soils by using 16S rRNA amplification and then inoculated to sterilized and non-sterilized calcareous soils in the presence and absence of glucose. The results showed that all isolates belonged to Bacillus genus and were capable of reducing Fe(III) to Fe(II) in vitro condition. The amount of Fe(III) reduction in sterilized calcareous soils was significantly higher when inoculated with PS23 isolate and Shewanella putrefaciens ( S. putrefaciens) (as positive control) compared to PS16 and PS11 isolates. No significant difference was observed between PS11 and PS16 isolates in the presence of indigenous microbial community. The results also revealed that glucose had a significant effect on Fe(III) reduction in the examined calcareous soil samples. The amount of Fe(III) reduction increased two-fold when soil samples were treated with glucose and inoculated by S. putrefaciens and PS23 in non-sterilized soils.

Preserving the national blood supply.

PubMed

Brittenham, G M; Klein, H G; Kushner, J P; Ajioka, R S

2001-01-01

This paper examines the current state of the blood supply in the US and focuses on the potential for augmenting blood availability by attention to the iron status of donors. Increasing demands are being made upon the national blood supply as rates of blood donation are declining, in part because of the loss of blood donors as a result of enhanced screening and testing procedures. Iron-related means of expanding the blood supply include the use of blood from individuals undergoing therapeutic phlebotomy for hereditary hemochromatosis and enhancing the retention and commitment of women of childbearing age as donors by using iron supplementation to prevent iron deficiency. In Section I, Dr. Klein discuss the circumstances responsible for a decline in the population of eligible donors, including public attitudes toward donation, factors influencing the retention of donors by blood centers, and the effects of increased screening and testing to maintain the safety of the blood supply. In Section II, Drs. Kushner and Ajioka focus on the consequences of the decision by the US Food and Drug Administration (FDA) to develop recommendations to permit blood centers to collect blood from patients with hereditary hemochromatosis and to distribute this blood obtained without disease labeling if all other screening and testing procedures are passed. After summarizing the pathophysiology of hereditary hemochromatosis, the use by blood centers of blood obtained from heterozygotes and homozygotes for hereditary hemochromatosis is considered. In Section III, Dr. Brittenham reviews the use of low dose, short-term carbonyl iron supplementation for women donors of childbearing age. Replacing the iron lost at donation can help prevent iron deficiency in women of childbearing age and, by decreasing deferral, enhance the retention and commitment of women who give blood regularly. He emphasizes the use by blood centers of iron-related means to enhance recruitment and retention of blood donors.

Co-regulation of Iron Metabolism and Virulence Associated Functions by Iron and XibR, a Novel Iron Binding Transcription Factor, in the Plant Pathogen Xanthomonas

PubMed Central

Pandey, Sheo Shankar; Patnana, Pradeep Kumar; Lomada, Santosh Kumar; Tomar, Archana; Chatterjee, Subhadeep

2016-01-01

Abilities of bacterial pathogens to adapt to the iron limitation present in hosts is critical to their virulence. Bacterial pathogens have evolved diverse strategies to coordinately regulate iron metabolism and virulence associated functions to maintain iron homeostasis in response to changing iron availability in the environment. In many bacteria the ferric uptake regulator (Fur) functions as transcription factor that utilize ferrous form of iron as cofactor to regulate transcription of iron metabolism and many cellular functions. However, mechanisms of fine-tuning and coordinated regulation of virulence associated function beyond iron and Fur-Fe2+ remain undefined. In this study, we show that a novel transcriptional regulator XibR (named X anthomonas iron binding regulator) of the NtrC family, is required for fine-tuning and co-coordinately regulating the expression of several iron regulated genes and virulence associated functions in phytopathogen Xanthomonas campestris pv. campestris (Xcc). Genome wide expression analysis of iron-starvation stimulon and XibR regulon, GUS assays, genetic and functional studies of xibR mutant revealed that XibR positively regulates functions involved in iron storage and uptake, chemotaxis, motility and negatively regulates siderophore production, in response to iron. Furthermore, chromatin immunoprecipitation followed by quantitative real-time PCR indicated that iron promoted binding of the XibR to the upstream regulatory sequence of operon’s involved in chemotaxis and motility. Circular dichroism spectroscopy showed that purified XibR bound ferric form of iron. Electrophoretic mobility shift assay revealed that iron positively affected the binding of XibR to the upstream regulatory sequences of the target virulence genes, an effect that was reversed by ferric iron chelator deferoxamine. Taken together, these data revealed that how XibR coordinately regulates virulence associated and iron metabolism functions in Xanthomonads in response to iron availability. Our results provide insight of the complex regulatory mechanism of fine-tuning of virulence associated functions with iron availability in this important group of phytopathogen. PMID:27902780

The effects of iron fortification and supplementation on the gut microbiome and diarrhea in infants and children: a review.

PubMed

Paganini, Daniela; Zimmermann, Michael B

2017-12-01

In infants and young children in Sub-Saharan Africa, iron-deficiency anemia (IDA) is common, and many complementary foods are low in bioavailable iron. In-home fortification of complementary foods using iron-containing micronutrient powders (MNPs) and oral iron supplementation are both effective strategies to increase iron intakes and reduce IDA at this age. However, these interventions produce large increases in colonic iron because the absorption of their high iron dose (≥12.5 mg) is typically <20%. We reviewed studies in infants and young children on the effects of iron supplements and iron fortification with MNPs on the gut microbiome and diarrhea. Iron-containing MNPs and iron supplements can modestly increase diarrhea risk, and in vitro and in vivo studies have suggested that this occurs because increases in colonic iron adversely affect the gut microbiome in that they decrease abundances of beneficial barrier commensal gut bacteria (e.g., bifidobacteria and lactobacilli) and increase the abundance of enterobacteria including entropathogenic Escherichia coli These changes are associated with increased gut inflammation. Therefore, safer formulations of iron-containing supplements and MNPs are needed. To improve MNP safety, the iron dose of these formulations should be reduced while maximizing absorption to retain efficacy. Also, the addition of prebiotics to MNPs is a promising approach to mitigate the adverse effects of iron on the infant gut. © 2017 American Society for Nutrition.

Acceptability and use of iron and iron-alloy cooking pots: implications for anaemia control programmes.

PubMed

Tripp, Katherine; Mackeith, Nancy; Woodruff, Bradley A; Talley, Leisel; Mselle, Laurent; Mirghani, Zahra; Abdalla, Fathia; Bhatia, Rita; Seal, Andrew J

2010-01-01

To evaluate the acceptability of iron and iron-alloy cooking pots prior to an intervention trial and to investigate factors affecting retention and use. Pre-trial research was conducted on five types of iron and iron-alloy pots using focus group discussions and a laboratory evaluation of Fe transfer during cooking was undertaken. Usage and retention during the subsequent intervention trial were investigated using focus group discussions and market monitoring. Three refugee camps in western Tanzania. Refugee health workers were selected for pre-trial research. Mothers of children aged 6-59 months participated in the investigation of retention and use. Pre-trial research indicated that the stainless steel pot would be the only acceptable type for use in this population due to excessive rusting and/or the high weight of other types. Cooking three typical refugee dishes in stainless steel pots led to an increase in Fe content of 3.2 to 17.1 mg/100 g food (P < 0.001). During the trial, the acceptability of the stainless steel pots was lower than expected owing to difficulties with using, cleaning and their utility for other purposes. Households also continued to use their pre-existing pots, and stainless steel pots were sold to increase household income. Pre-trial research led to the selection of a stainless steel pot that met basic acceptability criteria. The relatively low usage reported during the trial highlights the limitations of using high-value iron-alloy cooking pots as an intervention in populations where poverty and the availability of other pots may lead to selling.

Optimizing therapy for iron overload in the myelodysplastic syndromes: recent developments.

PubMed

Leitch, Heather A

2011-01-22

The myelodysplastic syndromes (MDS) are characterized by cytopenias and risk of progression to acute myeloid leukaemia (AML). Most MDS patients eventually require transfusion of red blood cells for anaemia, placing them at risk of transfusional iron overload. In β-thalassaemia major, transfusional iron overload leads to organ dysfunction and death; however, with iron chelation therapy, organ function is improved, and survival improved to near normal and correlated with the degree of compliance with chelation. In lower-risk MDS, several nonrandomized studies suggest an adverse effect of iron overload on survival and that lowering iron with chelation may minimize this impact. Emerging data indicate that chelation may improve organ function, particularly hepatic function, and a minority of patients may have improvement in cell counts and decreased transfusion requirements. While guidelines for MDS generally recommend chelation in selected lower-risk patients, data from nonrandomized trials suggest iron overload may impact adversely on the outcome of higher-risk MDS and stem cell transplantation (SCT). This effect may be due to increased transplant-related mortality, infection and AML progression, and preliminary data suggest that lowering iron may be beneficial in this patient group. Other areas of active and future investigation include optimizing the monitoring of iron overload using imaging such as T2* MRI and measures of labile iron and oxidative stress; correlating new methods of measuring iron to clinical outcomes; clarifying the contribution of different cellular and extracellular iron pools to iron toxicity; optimizing chelation by using agents that access the appropriate iron pools to minimize the relevant clinical consequences in individual patients; and incorporating measures of quality of life and co-morbidities into clinical trials of chelation in MDS. It should be noted that chelation is costly and potentially toxic, and in MDS should be initiated after weighing potential risks and benefits for each patient until more definitive data are available. In this review, data on the impact of iron overload in MDS and SCT are discussed; for example, several noncontrolled studies show inferior survival in patients with iron overload in these clinical settings, including an increase in transplant-related mortality and infection risk. Possible mechanisms of iron toxicity include oxidative stress, which can damage cellular components, and the documented impact of lowering iron on organ function with measures such as iron chelation therapy includes an improvement in elevated liver transaminases. Lowering iron also appears to improve survival in both lower-risk MDS and SCT in nonrandomized studies. Selected aspects of iron metabolism, transport, storage and distribution that may be amenable to future intervention and improved removal of iron from important cellular sites are discussed, as are attempts to quantify quality of life and the importance of co-morbidities in measures to treat MDS, including chelation therapy.

Introducing iron isomaltoside 1000 (Monofer®)-development rationale and clinical experience.

PubMed

Kalra, Philip A

2011-06-01

Patients with chronic kidney disease (CKD) often suffer from iron deficiency anaemia necessitating treatment with intravenous (IV) iron. Several studies demonstrate that oral iron is insufficient in these patients and that IV supplementation is a more effective treatment. Until now, use of available parenteral iron preparations has been limited by dosing schedules and the need, in some cases, for a test dose, and despite the availability of a range of different IV iron compounds, there is still a need for improved compounds. The new IV iron, iron isomaltoside 1000 Monofer®, is composed of iron and chemically modified isomalto-oligosaccharides which have a mean molecular weight of 1000 Da and consist predominantly of 3-5 glucose units. In contrast to dextrans, the carbohydrate isomaltoside 1000 is a linear and unbranched structure with theoretically a low immunological potential. Hence, a test dose is not necessary. Iron isomaltoside 1000 contains strongly bound iron within the iron-isomaltoside formulation, which enables a controlled slow release of bioavailable iron to the iron-binding proteins, with potentially a reduced risk of free iron toxicity. This allows flexible dosing including high and rapid dosing securing convenient iron therapy for a wide range of patients. The development of Monofer® has been enthusiastically acknowledged by clinicians, and in 2009, there has been fast approval by European authorities via a decentralized registration procedure. This new IV iron is currently being marketed in several European countries. This article describes the development rationale and summarizes the clinical data assessing the use of iron isomaltoside 1000 administered without a test dose by either repeated bolus injections or fast high single iron infusions [defined as total dose infusion (TDI)] to patients suffering from CKD. Since CKD is associated with a high prevalence of cardiovascular disease, data from a small trial applying high single doses of iron isomatoside 1000 in patients with chronic heart failure (CHF) are also reviewed. Collectively, the available data demonstrate adequate efficacy and a good safety profile of iron isomaltoside 1000 in CKD and CHF patients even when administered without a test dose and as single rapid high-dose infusions.

A European patient record study on diagnosis and treatment of chemotherapy-induced anaemia.

PubMed

Ludwig, Heinz; Aapro, M; Bokemeyer, C; Glaspy, J; Hedenus, M; Littlewood, T J; Österborg, A; Rzychon, B; Mitchell, D; Beguin, Y

2014-08-01

Patients with cancer frequently experience chemotherapy-induced anaemia (CIA) and iron deficiency. Erythropoiesis-stimulating agents (ESAs), iron supplementation and blood transfusions are available therapies. This study evaluated routine practice in CIA management. Medical oncologists and/or haematologists from nine European countries (n=375) were surveyed on their last five cancer patients treated for CIA (n=1,730). Information was collected on tests performed at diagnosis of anaemia, levels of haemoglobin (Hb), serum ferritin and transferrin saturation (TSAT), as well as applied anaemia therapies. Diagnostic tests and therapies for CIA varied across Europe. Anaemia and iron status were mainly assessed by Hb (94%) and ferritin (48%) measurements. TSAT was only tested in 14%. At anaemia diagnosis, 74% of patients had Hb ≤ 10 g/dL, including 15% with severe anaemia (Hb <8 g/dL). Low-iron levels (ferritin ≤ 100 ng/mL) were detected in 42% of evaluated patients. ESA was used in 63%of patients, blood transfusions in 52 % and iron supplementation in 31% (74% oral, 26% intravenous iron). Only 30% of ESA-treated patients received a combination of ESA and iron supplementation. Blood transfusions formed part of a regular anaemia treatment regimen in 76% of transfused patients. Management practices were similar in 2009 and 2011. Management of anaemia and iron status in patients treated for CIA varies substantially across Europe. Iron status is only assessed in half of the patients. In contrast to clinical evidence, iron treatment is under utilised and mainly based on oral iron supplementation. Implementation of guidelines needs to be increased to minimize the use of blood transfusions.

Impact on the Fe redox cycling of organic ligands released by Synechococcus PCC 7002, under different iron fertilization scenarios. Modeling approach

NASA Astrophysics Data System (ADS)

Samperio-Ramos, Guillermo; González-Dávila, Melchor; Santana-Casiano, J. Magdalena

2018-06-01

The kinetics of Fe redox transformations are of crucial importance in determining the bioavailability of iron, due to inorganic Fe(II) and Fe weakly organic complexes being the most easily assimilated species by phytoplankton. The role played by the natural organic ligands excreted by the cyanobacteria Synecococcus PCC 7002 on the iron redox chemistry was studied at different stages of growth, considering changes in the organic exudation of the cyanobacteria, associated with growth under two different scenarios of iron availability. The oxidation/reduction processes of iron were studied at nanomolar levels and under different physicochemical conditions of pH (7.2- 8.2), temperature (5- 35 °C) and salinity (10- 37). The presence of natural organic exudates of Synechococcus affected the redox behavior of iron. A pH-dependent and photo-induced Fe(III) reduction process was detected in the presence of exudates produced under Fe-Low conditions. Photolytic reactions also modified the reactivity of those exudates with respect to Fe(II), increasing its lifetime in seawater. Without light mediated processes, organic ligands excreted under iron deficient conditions intensified the Fe(II) oxidation at pH < 7.5. The organic exudates released under High-Fe conditions retarded the Fe(II) oxidation rate, as a function of DOC produced. The changes in the apparent oxidation rate were fitted to polynomial functions for both of the Fe-scenarios considered. A kinetic modeling approach to describe the speciation and the contribution of individual Fe(II) species to the overall oxidation rate was applied, considering the experimental data and delimiting the equilibrium and redox constants between iron and the major ligands present in solution. Two organic type ligands for the exudates of Synechococcus PCC 7002, with different iron-chelation properties were included in the model. The Fe(II) speciation was radically affected when organic ligands were considered. The individual contributions to the overall Fe(II) oxidation rate demonstrated that these organic ligands played a key role in the oxidation process, although their contributions were dependent on the prescribed iron conditions. The study, therefore, suggests that the variability in the composition and nature of organic exudates released, due to iron availability conditions, might determine the redox behaviour of iron in seawater.

Improvements in nanoscale zero-valent iron production by milling through the addition of alumina

NASA Astrophysics Data System (ADS)

Ribas, D.; Cernik, M.; Martí, V.; Benito, J. A.

2016-07-01

A new milling procedure for a cost-effective production of nanoscale zero-valent iron for environmental remediation is presented. Conventional ball milling of iron in an organic solvent as Mono Ethylene Glycol produces flattened iron particles that are unlikely to break even after very long milling times. With the aim of breaking down these iron flakes, in this new procedure, further milling is carried out by adding an amount of fine alumina powder to the previously milled solution. As the amount of added alumina increases from 9 to 54 g l-1, a progressive decrease of the presence of flakes is observed. In the latter case, the appearance of the particles formed by fragments of former flakes is rather homogeneous, with most of the final nanoparticles having an equivalent diameter well below 1 µm and with an average particle size in solution of around 400 nm. An additional increase of alumina content results in a highly viscous solution showing worse particle size distribution. Milled particles, in the case of alumina concentrations of 54 g l-1, have a fairly large specific surface area and high Fe(0) content. These new particles show a very good Cr(VI) removal efficiency compared with other commercial products available. This good reactivity is related to the absence of an oxide layer, the large amount of superficial irregularities generated by the repetitive fracture process during milling and the presence of a fine nanostructure within the iron nanoparticles.

Elevation of NO production increases Fe immobilization in the Fe-deficiency roots apoplast by decreasing pectin methylation of cell wall

PubMed Central

Ye, Yi Quan; Jin, Chong Wei; Fan, Shi Kai; Mao, Qian Qian; Sun, Cheng Liang; Yu, Yan; Lin, Xian Yong

2015-01-01

Cell wall is the major component of root apoplast which is the main reservoir for iron in roots, while nitric oxide (NO) is involved in regulating the synthesis of cell wall. However, whether such regulation could influence the reutilization of iron stored in root apoplast remains unclear. In this study, we observed that iron deficiency elevated NO level in tomato (Solanum lycopersicum) roots. However, application of S-nitrosoglutathione, a NO donor, significantly enhanced iron retention in root apoplast of iron-deficient plants, accompanied with a decrease of iron level in xylem sap. Consequently, S-nitrosoglutathione treatment increased iron concentration in roots, but decreased it in shoots. The opposite was true for the NO scavenging treatment with 2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide (cPTIO). Interestingly, S-nitrosoglutathione treatment increased pectin methylesterase activity and decreased degree of pectin methylation in root cell wall of both iron-deficient and iron-sufficient plants, which led to an increased iron retention in pectin fraction, thus increasing the binding capacity of iron to the extracted cell wall. Altogether, these results suggested that iron-deficiency-induced elevation of NO increases iron immobilization in root apoplast by decreasing pectin methylation in cell wall. PMID:26073914

Pumping Iron and Silica Bodybuilding

NASA Astrophysics Data System (ADS)

Mcnair, H.; Brzezinski, M. A.; Krause, J. W.; Parker, C.; Brown, M.; Coale, T.; Bruland, K. W.

2016-02-01

The availability of dissolved iron influences the stoichiometry of nutrient uptake by diatoms. Under nutrient replete conditions diatoms consume silicic acid and nitrate in a 1:1 ratio, this ratio increases under iron stress. Using the tracers 32Si and PDMPO, the total community and group-specific silica production rates were measured along a gradient of dissolved iron in an upwelling plume off the California coast. At each station, a control (ambient silicic acid) and +20 µM silicic acid treatment were conducted with each tracer to determine whether silicic acid limitation controlled the rate of silica production. Dissolved iron was 1.3 nmol kg-1 nearshore and decreased to 0.15 nmol kg-1 offshore. Silicic acid decreased more rapidly than nitrate, it was nearly 9 µM higher in the nearshore and 7 µM lower than nitrate in the middle of the transect where the iron concentration had decreased. The rate of diatom silica production decreased in tandem with silicic acid concentration, and silica production limitation by low silicic acid was most pronounced when iron concentrations were >0.4 nmol kg-1. The composition of the diatom assemblage shifted from Chaetoceros spp. dominated nearshore to a more sparse pennate-dominated assemblage offshore. Changes in taxa-specific silica production rates will be reported based on examination of PDMPO labeled cells using confocal microscopy.

Human L-ferritin deficiency is characterized by idiopathic generalized seizures and atypical restless leg syndrome

PubMed Central

Cozzi, Anna; Santambrogio, Paolo; Privitera, Daniela; Broccoli, Vania; Rotundo, Luisa Ida; Garavaglia, Barbara; Benz, Rudolf; Altamura, Sandro; Goede, Jeroen S.; Muckenthaler, Martina U.

2013-01-01

The ubiquitously expressed iron storage protein ferritin plays a central role in maintaining cellular iron homeostasis. Cytosolic ferritins are composed of heavy (H) and light (L) subunits that co-assemble into a hollow spherical shell with an internal cavity where iron is stored. The ferroxidase activity of the ferritin H chain is critical to store iron in its Fe3+ oxidation state, while the L chain shows iron nucleation properties. We describe a unique case of a 23-yr-old female patient affected by a homozygous loss of function mutation in the L-ferritin gene, idiopathic generalized seizures, and atypical restless leg syndrome (RLS). We show that L chain ferritin is undetectable in primary fibroblasts from the patient, and thus ferritin consists only of H chains. Increased iron incorporation into the FtH homopolymer leads to reduced cellular iron availability, diminished levels of cytosolic catalase, SOD1 protein levels, enhanced ROS production and higher levels of oxidized proteins. Importantly, key phenotypic features observed in fibroblasts are also mirrored in reprogrammed neurons from the patient’s fibroblasts. Our results demonstrate for the first time the pathophysiological consequences of L-ferritin deficiency in a human and help to define the concept for a new disease entity hallmarked by idiopathic generalized seizure and atypical RLS. PMID:23940258

Siderophore-producing bacteria from a sand dune ecosystem and the effect of sodium benzoate on siderophore production by a potential isolate.

PubMed

Gaonkar, Teja; Nayak, Pramoda Kumar; Garg, Sandeep; Bhosle, Saroj

2012-01-01

Bioremediation in natural ecosystems is dependent upon the availability of micronutrients and cofactors, of which iron is one of the essential elements. Under aerobic and alkaline conditions, iron oxidizes to Fe(+3) creating iron deficiency. To acquire this essential growth-limiting nutrient, bacteria produce low-molecular-weight, high-affinity iron chelators termed siderophores. In this study, siderophore-producing bacteria from rhizosphere and nonrhizosphere areas of coastal sand dunes were isolated using a culture-dependent approach and were assigned to 8 different genera with the predominance of Bacillus sp. Studies on the ability of these isolates to grow on sodium benzoate revealed that a pigmented bacterial culture TMR2.13 identified as Pseudomonas aeruginosa showed growth on mineral salts medium (MSM) with 2% of sodium benzoate and produced a yellowish fluorescent siderophore identified as pyoverdine. This was inhibited above 54 μM of added iron in MSM with glucose without affecting growth, while, in presence of sodium benzoate, siderophore was produced even up to the presence of 108 μM of added iron. Increase in the requirement of iron for metabolism of aromatic compounds in ecosystems where the nutrient deficiencies occur naturally would be one of the regulating factors for the bioremediation process.

Siderophore-Producing Bacteria from a Sand Dune Ecosystem and the Effect of Sodium Benzoate on Siderophore Production by a Potential Isolate

PubMed Central

Gaonkar, Teja; Nayak, Pramoda Kumar; Garg, Sandeep; Bhosle, Saroj

2012-01-01

Bioremediation in natural ecosystems is dependent upon the availability of micronutrients and cofactors, of which iron is one of the essential elements. Under aerobic and alkaline conditions, iron oxidizes to Fe+3 creating iron deficiency. To acquire this essential growth-limiting nutrient, bacteria produce low-molecular-weight, high-affinity iron chelators termed siderophores. In this study, siderophore-producing bacteria from rhizosphere and nonrhizosphere areas of coastal sand dunes were isolated using a culture-dependent approach and were assigned to 8 different genera with the predominance of Bacillus sp. Studies on the ability of these isolates to grow on sodium benzoate revealed that a pigmented bacterial culture TMR2.13 identified as Pseudomonas aeruginosa showed growth on mineral salts medium (MSM) with 2% of sodium benzoate and produced a yellowish fluorescent siderophore identified as pyoverdine. This was inhibited above 54 μM of added iron in MSM with glucose without affecting growth, while, in presence of sodium benzoate, siderophore was produced even up to the presence of 108 μM of added iron. Increase in the requirement of iron for metabolism of aromatic compounds in ecosystems where the nutrient deficiencies occur naturally would be one of the regulating factors for the bioremediation process. PMID:22629215

In Situ UV-Visible Assessment of Iron-Based High-Temperature Water-Gas Shift Catalysts Promoted with Lanthana: An Extent of Reduction Study

DOE PAGES

Hallac, Basseem B.; Brown, Jared C.; Stavitski, Eli; ...

2018-02-04

Here, the extent of reduction of unsupported iron-based high-temperature water-gas shift catalysts with small (<5 wt %) lanthana contents was studied using UV-visible spectroscopy. Temperature- programmed reduction measurements showed that lanthana content higher than 0.5 wt % increased the extent of reduction to metallic Fe, while 0.5 wt % of lanthana facilitated the reduction to Fe 3O 4. In situ measurements on the iron oxide catalysts using mass and UV-visible spectroscopies permitted the quantification of the extent of reduction under temperature-programmed reduction and high-temperature water-gas shift conditions. The oxidation states were successfully calibrated against normalized absorbance spectra of visible lightmore » using the Kubelka-Munk theory. The normalized absorbance relative to the fully oxidized Fe 2O 3 increased as the extent of reduction increased. XANES suggested that the average bulk iron oxidation state during the water-gas shift reaction was Fe +2.57 for the catalyst with no lanthana and Fe +2.54 for the catalysts with 1 wt % lanthana. However, the UV-vis spectra suggest that the surface oxidation state of iron would be Fe +2.31 for the catalyst with 1 wt % lanthana if the oxidation state of iron in the catalyst with 0 wt % lanthana were Fe +2.57. The findings of this paper emphasize the importance of surface sensitive UV-visible spectroscopy for determining the extent of catalyst reduction during operation. Furthermore, the paper highlights the potential to use bench-scale UV-visible spectroscopy to study the surface chemistry of catalysts instead of less-available synchrotron X-ray radiation facilities.« less

In Situ UV-Visible Assessment of Iron-Based High-Temperature Water-Gas Shift Catalysts Promoted with Lanthana: An Extent of Reduction Study

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hallac, Basseem B.; Brown, Jared C.; Stavitski, Eli

Here, the extent of reduction of unsupported iron-based high-temperature water-gas shift catalysts with small (<5 wt %) lanthana contents was studied using UV-visible spectroscopy. Temperature- programmed reduction measurements showed that lanthana content higher than 0.5 wt % increased the extent of reduction to metallic Fe, while 0.5 wt % of lanthana facilitated the reduction to Fe 3O 4. In situ measurements on the iron oxide catalysts using mass and UV-visible spectroscopies permitted the quantification of the extent of reduction under temperature-programmed reduction and high-temperature water-gas shift conditions. The oxidation states were successfully calibrated against normalized absorbance spectra of visible lightmore » using the Kubelka-Munk theory. The normalized absorbance relative to the fully oxidized Fe 2O 3 increased as the extent of reduction increased. XANES suggested that the average bulk iron oxidation state during the water-gas shift reaction was Fe +2.57 for the catalyst with no lanthana and Fe +2.54 for the catalysts with 1 wt % lanthana. However, the UV-vis spectra suggest that the surface oxidation state of iron would be Fe +2.31 for the catalyst with 1 wt % lanthana if the oxidation state of iron in the catalyst with 0 wt % lanthana were Fe +2.57. The findings of this paper emphasize the importance of surface sensitive UV-visible spectroscopy for determining the extent of catalyst reduction during operation. Furthermore, the paper highlights the potential to use bench-scale UV-visible spectroscopy to study the surface chemistry of catalysts instead of less-available synchrotron X-ray radiation facilities.« less

Deferasirox-induced iron depletion promotes BclxL downregulation and death of proximal tubular cells

PubMed Central

Martin-Sanchez, Diego; Gallegos-Villalobos, Angel; Fontecha-Barriuso, Miguel; Carrasco, Susana; Sanchez-Niño, Maria Dolores; Lopez-Hernandez, Francisco J; Ruiz-Ortega, Marta; Egido, Jesus; Ortiz, Alberto; Sanz, Ana Belén

2017-01-01

Iron deficiency has been associated with kidney injury. Deferasirox is an oral iron chelator used to treat blood transfusion-related iron overload. Nephrotoxicity is the most serious and common adverse effect of deferasirox and may present as an acute or chronic kidney disease. However, scarce data are available on the molecular mechanisms of nephrotoxicity. We explored the therapeutic modulation of deferasirox-induced proximal tubular cell death in culture. Deferasirox induced dose-dependent tubular cell death and AnexxinV/7AAD staining showed features of apoptosis and necrosis. However, despite inhibiting caspase-3 activation, the pan-caspase inhibitor zVAD-fmk failed to prevent deferasirox-induced cell death. Moreover, zVAD increased deferasirox-induced cell death, a feature sometimes found in necroptosis. Electron microscopy identified mitochondrial injury and features of necrosis. However, neither necrostatin-1 nor RIP3 knockdown prevented deferasirox-induced cell death. Deferasirox caused BclxL depletion and BclxL overexpression was protective. Preventing iron depletion protected from BclxL downregulation and deferasirox cytotoxicity. In conclusion, deferasirox promoted iron depletion-dependent cell death characterized by BclxL downregulation. BclxL overexpression was protective, suggesting a role for BclxL downregulation in iron depletion-induced cell death. This information may be used to develop novel nephroprotective strategies. Furthermore, it supports the concept that monitoring kidney tissue iron depletion may decrease the risk of deferasirox nephrotoxicity. PMID:28139717

Deferasirox-induced iron depletion promotes BclxL downregulation and death of proximal tubular cells.

PubMed

Martin-Sanchez, Diego; Gallegos-Villalobos, Angel; Fontecha-Barriuso, Miguel; Carrasco, Susana; Sanchez-Niño, Maria Dolores; Lopez-Hernandez, Francisco J; Ruiz-Ortega, Marta; Egido, Jesus; Ortiz, Alberto; Sanz, Ana Belén

2017-01-31

Iron deficiency has been associated with kidney injury. Deferasirox is an oral iron chelator used to treat blood transfusion-related iron overload. Nephrotoxicity is the most serious and common adverse effect of deferasirox and may present as an acute or chronic kidney disease. However, scarce data are available on the molecular mechanisms of nephrotoxicity. We explored the therapeutic modulation of deferasirox-induced proximal tubular cell death in culture. Deferasirox induced dose-dependent tubular cell death and AnexxinV/7AAD staining showed features of apoptosis and necrosis. However, despite inhibiting caspase-3 activation, the pan-caspase inhibitor zVAD-fmk failed to prevent deferasirox-induced cell death. Moreover, zVAD increased deferasirox-induced cell death, a feature sometimes found in necroptosis. Electron microscopy identified mitochondrial injury and features of necrosis. However, neither necrostatin-1 nor RIP3 knockdown prevented deferasirox-induced cell death. Deferasirox caused BclxL depletion and BclxL overexpression was protective. Preventing iron depletion protected from BclxL downregulation and deferasirox cytotoxicity. In conclusion, deferasirox promoted iron depletion-dependent cell death characterized by BclxL downregulation. BclxL overexpression was protective, suggesting a role for BclxL downregulation in iron depletion-induced cell death. This information may be used to develop novel nephroprotective strategies. Furthermore, it supports the concept that monitoring kidney tissue iron depletion may decrease the risk of deferasirox nephrotoxicity.

Evaluation and treatment of iron deficiency anemia: a gastroenterological perspective.

PubMed

Zhu, Amy; Kaneshiro, Marc; Kaunitz, Jonathan D

2010-03-01

A substantial volume of the consultations requested of gastroenterologists are directed towards the evaluation of anemia. Since iron deficiency anemia often arises from bleeding gastrointestinal lesions, many of which are malignant, establishment of a firm diagnosis usually obligates an endoscopic evaluation. Although the laboratory tests used to make the diagnosis have not changed in many decades, their interpretation has, and this is possibly due to the availability of extensive testing in key populations. We provide data supporting the use of the serum ferritin as the sole useful measure of iron stores, setting the lower limit at 100 microg/l for some populations in order to increase the sensitivity of the test. Trends of the commonly obtained red cell indices, mean corpuscular volume, and the red cell distribution width can provide valuable diagnostic information. Once the diagnosis is established, upper and lower gastrointestinal endoscopy is usually indicated. Nevertheless, in many cases a gastrointestinal source is not found after routine evaluation. Additional studies, including repeat upper and lower endoscopy and often investigation of the small intestine may thus be required. Although oral iron is inexpensive and usually effective, there are many gastrointestinal conditions that warrant treatment of iron deficiency with intravenous iron.

Sugars Increase Non-Heme Iron Bioavailability in Human Epithelial Intestinal and Liver Cells

PubMed Central

Christides, Tatiana; Sharp, Paul

2013-01-01

Previous studies have suggested that sugars enhance iron bioavailability, possibly through either chelation or altering the oxidation state of the metal, however, results have been inconclusive. Sugar intake in the last 20 years has increased dramatically, and iron status disorders are significant public health problems worldwide; therefore understanding the nutritional implications of iron-sugar interactions is particularly relevant. In this study we measured the effects of sugars on non-heme iron bioavailability in human intestinal Caco-2 cells and HepG2 hepatoma cells using ferritin formation as a surrogate marker for iron uptake. The effect of sugars on iron oxidation state was examined by measuring ferrous iron formation in different sugar-iron solutions with a ferrozine-based assay. Fructose significantly increased iron-induced ferritin formation in both Caco-2 and HepG2 cells. In addition, high-fructose corn syrup (HFCS-55) increased Caco-2 cell iron-induced ferritin; these effects were negated by the addition of either tannic acid or phytic acid. Fructose combined with FeCl3 increased ferrozine-chelatable ferrous iron levels by approximately 300%. In conclusion, fructose increases iron bioavailability in human intestinal Caco-2 and HepG2 cells. Given the large amount of simple and rapidly digestible sugars in the modern diet their effects on iron bioavailability may have important patho-physiological consequences. Further studies are warranted to characterize these interactions. PMID:24340076

Fractional solubility of aerosol iron: Synthesis of a global-scale data set

NASA Astrophysics Data System (ADS)

Sholkovitz, Edward R.; Sedwick, Peter N.; Church, Thomas M.; Baker, Alexander R.; Powell, Claire F.

2012-07-01

Aerosol deposition provides a major input of the essential micronutrient iron to the open ocean. A critical parameter with respect to biological availability is the proportion of aerosol iron that enters the oceanic dissolved iron pool - the so-called fractional solubility of aerosol iron (%FeS). Here we present a global-scale compilation of total aerosol iron loading (FeT) and estimated %FeS values for ∼1100 samples collected over the open ocean, the coastal ocean, and some continental sites, including a new data set from the Atlantic Ocean. Despite the wide variety of methods that have been used to define 'soluble' aerosol iron, our global-scale compilation reveals a remarkably consistent trend in the fractional solubility of aerosol iron as a function of total aerosol iron loading, with the great bulk of the data defining an hyperbolic trend. The hyperbolic trends that we observe for both global- and regional-scale data are adequately described by a simple two-component mixing model, whereby the fractional solubility of iron in the bulk aerosol reflects the conservative mixing of 'lithogenic' mineral dust (high FeT and low %FeS) and non-lithogenic 'combustion' aerosols (low FeT and high %FeS). An increasing body of empirical and model-based evidence points to anthropogenic fuel combustion as the major source of these non-lithogenic 'combustion' aerosols, implying that human emissions are a major determinant of the fractional solubility of iron in marine aerosols. The robust global-scale relationship between %FeS and FeT provides a simple heuristic method for estimating aerosol iron solubility at the regional to global scale.

[Iron absorption of the habitual diet in a population of low socioeconomic level].

PubMed

Morón, C; Kremenchuzky, S; Passamai, M I; D'Andrea de Rivero, S; Pérez de Galíndez, G; Gerschcovich, C

1985-06-01

Iron absorption using the extrinsic double-tag method was determined in the habitual diet consumed by a group of 32 volunteers of both sexes, pertaining to the low socioeconomic strata. The diet was made up of bread, spaghetti, vegetables and meat, totalling 2,022 kcal, 65.0 g protein, 17.57 mg iron, and 28.75 mg ascorbic acid. According to our findings, men were found to be neither anemic nor iron-deficient. Among the women, however, 4.8% had anemia and 57.1% suffered from iron deficiency. The non-heme iron absorption was very low: 1.35% at breakfast, 3.29% at lunch, and 3.82% at dinner. Among those subjects found to be normal, the absorption was half the above figures, whereas among those with iron deficiency it was threefold, the differences being highly significant. The absorption of heme-iron for lunch and dinner was 17.53%. The iron deficient group had an absorption value four times greater than the normal group, the differences also being highly significant. The daily availability of non-heme, heme and total iron was 0.44, 1.13 and 1.57 mg, respectively. In the subjects who formed the normal group, total iron available was 1.14 mg, barely covering a man's daily requirements, but not those of a woman. In the iron-deficient group, it was 4.31 mg, that is, four times greater than in the normal group; while this value improves the balance, it does not prevent deficiency in women, with great blood losses. Bearing these results in mind, it is suggested that measures tending to improve dietary iron content and bio-availability, be enforced.

Uncoupled iron homeostasis in type 2 diabetes mellitus.

PubMed

Altamura, Sandro; Kopf, Stefan; Schmidt, Julia; Müdder, Katja; da Silva, Ana Rita; Nawroth, Peter; Muckenthaler, Martina U

2017-12-01

Diabetes mellitus is frequently associated with iron overload conditions, such as primary and secondary hemochromatosis. Conversely, patients affected by type 2 diabetes mellitus (T2DM) show elevated ferritin levels, a biomarker for increased body iron stores. Despite these documented associations between dysregulated iron metabolism and T2DM, the underlying mechanisms are poorly understood. Here, we show that T2DM patients have reduced serum levels of hepcidin, the iron-regulated hormone that maintains systemic iron homeostasis. Consistent with this finding, we also observed an increase in circulating iron and ferritin levels. Our analysis of db/db mice demonstrates that this model recapitulates the systemic alterations observed in patients. Interestingly, db/db mice show an overall hepatic iron deficiency despite unaltered expression of ferritin and the iron importer TfR1. In addition, the liver correctly senses increased circulating iron levels by activating the BMP/SMAD signaling pathway even though hepcidin expression is decreased. We show that increased AKT phosphorylation may override active BMP/SMAD signaling and decrease hepcidin expression in 10-week old db/db mice. We conclude that the metabolic alterations occurring in T2DM impact on the regulation of iron homeostasis on multiple levels. As a result, metabolic perturbations induce an "iron resistance" phenotype, whereby signals that translate increased circulating iron levels into hepcidin production, are dysregulated. T2DM patients show increased circulating iron levels. T2DM is associated with inappropriately low hepcidin levels. Metabolic alterations in T2DM induce an "iron resistance" phenotype.

Regulation of yeast fatty acid desaturase in response to iron deficiency.

PubMed

Romero, Antonia María; Jordá, Tania; Rozès, Nicolas; Martínez-Pastor, María Teresa; Puig, Sergi

2018-06-01

Unsaturated fatty acids (UFA) are essential components of phospholipids that greatly contribute to the biophysical properties of cellular membranes. Biosynthesis of UFAs relies on a conserved family of iron-dependent fatty acid desaturases, whose representative in the model yeast Saccharomyces cerevisiae is Ole1. OLE1 expression is tightly regulated to adapt UFA biosynthesis and lipid bilayer properties to changes in temperature, and in UFA or oxygen availability. Despite iron deficiency being the most extended nutritional disorder worldwide, very little is known about the mechanisms and the biological relevance of fatty acid desaturases regulation in response to iron starvation. In this report, we show that endoplasmic reticulum-anchored transcription factor Mga2 activates OLE1 transcription in response to nutritional and genetic iron deficiencies. Cells lacking MGA2 display low UFA levels and do not grow under iron-limited conditions, unless UFAs are supplemented or OLE1 is overexpressed. The proteasome, E3 ubiquitin ligase Rsp5 and the Cdc48 Npl4/Ufd1 complex are required for OLE1 activation during iron depletion. Interestingly, Mga2 also activates the transcription of its own mRNA in response to iron deficiency, hypoxia, low temperature and low UFAs. MGA2 up-regulation contributes to increase OLE1 expression in these situations. These results reveal the mechanism of OLE1 regulation when iron is scarce and identify the MGA2 auto-regulation as a potential activation strategy in multiple stresses. Copyright © 2018 Elsevier B.V. All rights reserved.

Disruption of iron homeostasis and lung disease.

PubMed

Ghio, Andrew J

2009-07-01

As a result of a direct exchange with the external environment, the lungs are exposed to both iron and agents with a capacity to disrupt the homeostasis of this metal (e.g. particles). An increased availability of catalytically reactive iron can result from these exposures and, by generating an oxidative stress, this metal can contribute to tissue injury. By importing this Fe(3+) into cells for storage in a chemically less reactive form, the lower respiratory tract demonstrates an ability to mitigate both the oxidative stress presented by iron and its potential for tissue injury. This means that detoxification is accomplished by chemical reduction to Fe(2+) (e.g. by duodenal cytochrome b and other ferrireductases), iron import (e.g. by divalent metal transporter 1 and other transporters), and storage in ferritin. The metal can subsequently be exported from the cell (e.g. by ferroportin 1) in a less reactive state relative to that initially imported. Iron is then transported out of the lung via the mucociliary pathway or blood and lymphatic pathways to the reticuloendothelial system for long term storage. This coordinated handling of iron in the lung appears to be disrupted in several acute diseases on the lung including infections, acute respiratory distress syndrome, transfusion-related acute lung injury, and ischemia-reperfusion. Exposures to bleomycin, dusts and fibers, and paraquat similarly alter iron homeostasis in the lung to affect an oxidative stress. Finally, iron homeostasis is disrupted in numerous chronic lung diseases including pulmonary alveolar proteinosis, transplantation, cigarette smoking, and cystic fibrosis.

Rethinking iron regulation and assessment in iron deficiency, the anemia of chronic disease, and obesity: introducing Hepcidin

USDA-ARS?s Scientific Manuscript database

Adequate iron availability is essential to human development and overall health. Iron is a key component of oxygen-carrying proteins; a vital player in cellular metabolism, and essential to cell growth and differentiation. Tight regulation of iron at the systemic and cytosolic level is necessary bec...

The impact of fish and the commercial marine harvest on the ocean iron cycle.

PubMed

Moreno, Allison R; Haffa, Arlene L M

2014-01-01

Although iron is the fourth most abundant element in the Earth's crust, bioavailable iron limits marine primary production in about one third of the ocean. This lack of iron availability has implications in climate change because the removal of carbon dioxide from the atmosphere by phytoplankton requires iron. Using literature values for global fish biomass estimates, and elemental composition data we estimate that fish biota store between 0.7-7 × 10(11) g of iron. Additionally, the global fish population recycles through excretion between 0.4-1.5 × 10(12) g of iron per year, which is of a similar magnitude as major recognized sources of iron (e.g. dust, sediments, ice sheet melting). In terms of biological impact this iron could be superior to dust inputs due to the distributed deposition and to the greater solubility of fecal pellets compared to inorganic minerals. To estimate a loss term due to anthropogenic activity the total commercial catch for 1950 to 2010 was obtained from the Food and Agriculture Organization of the United Nations. Marine catch data were separated by taxa. High and low end values for elemental composition were obtained for each taxonomic category from the literature and used to calculate iron per mass of total harvest over time. The marine commercial catch is estimated to have removed 1-6 × 10(9) g of iron in 1950, the lowest values on record. There is an annual increase to 0.7-3 × 10(10) g in 1996, which declines to 0.6-2 × 10(10) g in 2010. While small compared to the total iron terms in the cycle, these could have compounding effects on distribution and concentration patterns globally over time. These storage, recycling, and export terms of biotic iron are not currently included in ocean iron mass balance calculations. These data suggest that fish and anthropogenic activity should be included in global oceanic iron cycles.

Thermodynamic and Kinetic Response of Microbial Reactions to High CO2.

PubMed

Jin, Qusheng; Kirk, Matthew F

2016-01-01

Geological carbon sequestration captures CO 2 from industrial sources and stores the CO 2 in subsurface reservoirs, a viable strategy for mitigating global climate change. In assessing the environmental impact of the strategy, a key question is how microbial reactions respond to the elevated CO 2 concentration. This study uses biogeochemical modeling to explore the influence of CO 2 on the thermodynamics and kinetics of common microbial reactions in subsurface environments, including syntrophic oxidation, iron reduction, sulfate reduction, and methanogenesis. The results show that increasing CO 2 levels decreases groundwater pH and modulates chemical speciation of weak acids in groundwater, which in turn affect microbial reactions in different ways and to different extents. Specifically, a thermodynamic analysis shows that increasing CO 2 partial pressure lowers the energy available from syntrophic oxidation and acetoclastic methanogenesis, but raises the available energy of microbial iron reduction, hydrogenotrophic sulfate reduction and methanogenesis. Kinetic modeling suggests that high CO 2 has the potential of inhibiting microbial sulfate reduction while promoting iron reduction. These results are consistent with the observations of previous laboratory and field studies, and highlight the complexity in microbiological responses to elevated CO 2 abundance, and the potential power of biogeochemical modeling in evaluating and quantifying these responses.

Thermodynamic and Kinetic Response of Microbial Reactions to High CO2

PubMed Central

Jin, Qusheng; Kirk, Matthew F.

2016-01-01

Geological carbon sequestration captures CO2 from industrial sources and stores the CO2 in subsurface reservoirs, a viable strategy for mitigating global climate change. In assessing the environmental impact of the strategy, a key question is how microbial reactions respond to the elevated CO2 concentration. This study uses biogeochemical modeling to explore the influence of CO2 on the thermodynamics and kinetics of common microbial reactions in subsurface environments, including syntrophic oxidation, iron reduction, sulfate reduction, and methanogenesis. The results show that increasing CO2 levels decreases groundwater pH and modulates chemical speciation of weak acids in groundwater, which in turn affect microbial reactions in different ways and to different extents. Specifically, a thermodynamic analysis shows that increasing CO2 partial pressure lowers the energy available from syntrophic oxidation and acetoclastic methanogenesis, but raises the available energy of microbial iron reduction, hydrogenotrophic sulfate reduction and methanogenesis. Kinetic modeling suggests that high CO2 has the potential of inhibiting microbial sulfate reduction while promoting iron reduction. These results are consistent with the observations of previous laboratory and field studies, and highlight the complexity in microbiological responses to elevated CO2 abundance, and the potential power of biogeochemical modeling in evaluating and quantifying these responses. PMID:27909425

Influence of atmospheric processes on the solubility and composition of iron in Saharan dust

DOE PAGES

Longo, Amelia F.; Feng, Yan; Lai, Barry; ...

2016-06-10

Aerosol iron was examined in Saharan dust plumes using a combination of iron near-edge X-ray absorption spectroscopy and wet-chemical techniques. Aerosol samples were collected at three sites located in the Mediterranean, the Atlantic, and Bermuda to characterize iron at different atmospheric transport lengths and time scales. Iron(III) oxides were a component of aerosols at all sampling sites and dominated the aerosol iron in Mediterranean samples. In Atlantic samples, iron(II and III) sulfate, iron(III) phosphate, and iron(II) silicates were also contributors to aerosol composition. With increased atmospheric transport time, iron(II) sulfates are found to become more abundant, aerosol iron oxidation statemore » became more reduced, and aerosol acidity increased. As a result, atmospheric processing including acidic reactions and photoreduction likely influence the form of iron minerals and oxidation state in Saharan dust aerosols and contribute to increases in aerosol-iron solubility.« less

Influence of Atmospheric Processes on the Solubility and Composition of Iron in Saharan Dust.

PubMed

Longo, Amelia F; Feng, Yan; Lai, Barry; Landing, William M; Shelley, Rachel U; Nenes, Athanasios; Mihalopoulos, Nikolaos; Violaki, Kalliopi; Ingall, Ellery D

2016-07-05

Aerosol iron was examined in Saharan dust plumes using a combination of iron near-edge X-ray absorption spectroscopy and wet-chemical techniques. Aerosol samples were collected at three sites located in the Mediterranean, the Atlantic, and Bermuda to characterize iron at different atmospheric transport lengths and time scales. Iron(III) oxides were a component of aerosols at all sampling sites and dominated the aerosol iron in Mediterranean samples. In Atlantic samples, iron(II and III) sulfate, iron(III) phosphate, and iron(II) silicates were also contributors to aerosol composition. With increased atmospheric transport time, iron(II) sulfates are found to become more abundant, aerosol iron oxidation state became more reduced, and aerosol acidity increased. Atmospheric processing including acidic reactions and photoreduction likely influence the form of iron minerals and oxidation state in Saharan dust aerosols and contribute to increases in aerosol-iron solubility.

Subsurface iron and arsenic removal for shallow tube well drinking water supply in rural Bangladesh.

PubMed

van Halem, D; Olivero, S; de Vet, W W J M; Verberk, J Q J C; Amy, G L; van Dijk, J C

2010-11-01

Subsurface iron and arsenic removal has the potential to be a cost-effective technology to provide safe drinking water in rural decentralized applications, using existing shallow tube wells. A community-scale test facility in Bangladesh was constructed for injection of aerated water (∼1 m(3)) into an anoxic aquifer with elevated iron (0.27 mmolL(-1)) and arsenic (0.27μmolL(-1)) concentrations. The injection (oxidation) and abstraction (adsorption) cycles were monitored at the test facility and simultaneously simulated in the laboratory with anoxic column experiments. Dimensionless retardation factors (R) were determined to represent the delayed arrival of iron or arsenic in the well compared to the original groundwater. At the test facility the iron removal efficacies increased after every injection-abstraction cycle, with retardation factors (R(Fe)) up to 17. These high removal efficacies could not be explained by the theory of adsorptive-catalytic oxidation, and therefore other ((a)biotic or transport) processes have contributed to the system's efficacy. This finding was confirmed in the anoxic column experiments, since the mechanism of adsorptive-catalytic oxidation dominated in the columns and iron removal efficacies did not increase with every cycle (stable at R(Fe)=∼8). R(As) did not increase after multiple cycles, it remained stable around 2, illustrating that the process which is responsible for the effective iron removal did not promote the co-removal of arsenic. The columns showed that subsurface arsenic removal was an adsorptive process and only the freshly oxidized adsorbed iron was available for the co-adsorption of arsenic. This indicates that arsenic adsorption during subsurface treatment is controlled by the amount of adsorbed iron that is oxidized, and not by the amount of removed iron. For operational purposes this is an important finding, since apparently the oxygen concentration of the injection water does not control the subsurface arsenic removal, but rather the injection volume. Additionally, no relation has been observed in this study between the amount of removed arsenic at different molar Fe:As ratios (28, 63, and 103) of the groundwater. It is proposed that the removal of arsenic was limited by the presence of other anions, such as phosphate, competing for the same adsorption sites. Copyright © 2010 Elsevier Ltd. All rights reserved.

Deferoxamine inhibition of malaria is independent of host iron status

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hershko, C.; Peto, T.E.

The mechanism whereby deferoxamine (DF) inhibits the growth of malaria parasites was studied in rats infected with Plasmodium berghei. Peak parasitemia was 32.6% (day 14) in untreated controls and 0.15% (day 7) in rats receiving 0.33 mg/g in 8 hourly DF injections, subcutaneously. DF inhibition of parasite growth was achieved without any reduction in transferrin saturation or hemoglobin synthesis and with only a partial (56%) depletion of hepatic iron stores. Dietary iron depletion resulted in anemia (hematocrit 25 vs. 46%), microcytosis (MCV 54 vs. 60 fl), and reduced transferrin saturation (17 vs. 96%) without any effect on infection (peak parasitemiamore » 30 vs. 36%). Similarly, parenteral iron loading with ferric citrate over 10 d (75 mg iron/kg) failed to aggravate infection. In a search for evidence of direct interaction between DF and parasitized erythrocytes, gel filtration and ultrafiltration was performed on hemolysates obtained from in vivo /sup 59/Fe-labeled parasitized erythrocytes. This showed that 1.1-1.9% of the intracellular radioiron was located in a chelatable, labile iron pool. Incubation of intact cells with 0-500 microM DF resulted in a proportional increase in intracellular iron chelation, and the chelation of all available labile intracellular iron was completed within 6 h. These observations indicate that the severity of P. berghei infection in rats and its in vivo suppression by DF are independent of host iron status and suggest that DF inhibition of malaria involves intracellular chelation of a labile iron pool in parasitized erythrocytes.« less

Zinc deficiency-induced iron accumulation, a consequence of alterations in iron regulatory protein-binding activity, iron transporters, and iron storage proteins.

PubMed

Niles, Brad J; Clegg, Michael S; Hanna, Lynn A; Chou, Susan S; Momma, Tony Y; Hong, Heeok; Keen, Carl L

2008-02-22

One consequence of zinc deficiency is an elevation in cell and tissue iron concentrations. To examine the mechanism(s) underlying this phenomenon, Swiss 3T3 cells were cultured in zinc-deficient (D, 0.5 microM zinc), zinc-supplemented (S, 50 microM zinc), or control (C, 4 microM zinc) media. After 24 h of culture, cells in the D group were characterized by a 50% decrease in intracellular zinc and a 35% increase in intracellular iron relative to cells in the S and C groups. The increase in cellular iron was associated with increased transferrin receptor 1 protein and mRNA levels and increased ferritin light chain expression. The divalent metal transporter 1(+)iron-responsive element isoform mRNA was decreased during zinc deficiency-induced iron accumulation. Examination of zinc-deficient cells revealed increased binding of iron regulatory protein 2 (IRP2) and decreased binding of IRP1 to a consensus iron-responsive element. The increased IRP2-binding activity in zinc-deficient cells coincided with an increased level of IRP2 protein. The accumulation of IRP2 protein was independent of zinc deficiency-induced intracellular nitric oxide production but was attenuated by the addition of the antioxidant N-acetylcysteine or ascorbate to the D medium. These data support the concept that zinc deficiency can result in alterations in iron transporter, storage, and regulatory proteins, which facilitate iron accumulation.

Iron deficiency alters megakaryopoiesis and platelet phenotype independent of thrombopoietin.

PubMed

Evstatiev, Rayko; Bukaty, Adam; Jimenez, Kristine; Kulnigg-Dabsch, Stefanie; Surman, Lidia; Schmid, Werner; Eferl, Robert; Lippert, Kathrin; Scheiber-Mojdehkar, Barbara; Kvasnicka, Hans Michael; Khare, Vineeta; Gasche, Christoph

2014-05-01

Iron deficiency is a common cause of reactive thrombocytosis, however, the exact pathways have not been revealed. Here we aimed to study the mechanisms behind iron deficiency-induced thrombocytosis. Within few weeks, iron-depleted diet caused iron deficiency in young Sprague-Dawley rats, as reflected by a drop in hemoglobin, mean corpuscular volume, hepatic iron content and hepcidin mRNA in the liver. Thrombocytosis established in parallel. Moreover, platelets produced in iron deficient animals displayed a higher mean platelet volume and increased aggregation. Bone marrow studies revealed subtle alterations that are suggestive of expansion of megakaryocyte progenitors, an increase in megakaryocyte ploidy and accelerated megakaryocyte differentiation. Iron deficiency did not alter the production of hematopoietic growth factors such as thrombopoietin, interleukin 6 or interleukin 11. Megakaryocytic cell lines grown in iron-depleted conditions exhibited reduced proliferation but increased ploidy and cell size. Our data suggest that iron deficiency increases megakaryopoietic differentiation and alters platelet phenotype without changes in megakaryocyte growth factors, specifically TPO. Iron deficiency-induced thrombocytosis may have evolved to maintain or increase the coagulation capacity in conditions with chronic bleeding. Copyright © 2014 Wiley Periodicals, Inc.

Variation in intravenous iron use internationally and over time: the Dialysis Outcomes and Practice Patterns Study (DOPPS).

PubMed

Bailie, George R; Larkina, Maria; Goodkin, David A; Li, Yun; Pisoni, Ronald L; Bieber, Brian; Mason, Nancy; Tong, Lin; Locatelli, Francesco; Marshall, Mark R; Inaba, Masaki; Robinson, Bruce M

2013-10-01

To examine patterns of intravenous (IV) iron use across 12 countries from 1999 to 2011. Trends in iron use are described among 32 192 hemodialysis (HD) patients in the Dialysis Outcomes and Practice Patterns Study. Adjusted associations of IV iron dose with serum ferritin and transferrin saturation (TSAT) values were also studied. IV iron was administered to 50% of patients over 4 months in 1999, increasing to 71% during 2009-11, with increasing use in most countries. Among patients receiving IV iron, the mean monthly dose increased from 232 ± 167 to 281 ± 211 mg. Most countries used 3 to 4 doses/month, but Canada used about 2 doses/month, Italy increased from 3 to almost 6 doses/month and Germany used 5 to 6 doses/month. The USA and most European countries predominantly used iron sucrose and sodium ferric gluconate. A significant use of iron dextran was limited to Canada and France; iron polymaltose was used in Australia and New Zealand; and Japan used ferric oxide saccharate, chondroitin polysulfate iron complex and cideferron. Ferritin values rose in most countries: 22% of patients had ≥ 800 ng/mL in the recent years of study. TSAT levels increased to a lesser degree over time. Japan had much lower IV iron dosing and ferritin levels, but similar TSAT levels. In adjusted analyses, serum ferritin and TSAT levels increased signifcantly by 14 ng/mL and 0.16%, respectively, for every 100 mg/month higher mean monthly iron dose. IV iron prescription patterns varied between countries and changed over time from 1999 to 2011. IV iron use and dose increased in most countries, with notable increases in ferritin but not TSAT levels. With rising cumulative IV iron doses, studies of the effects of changing IV iron dosing and other anemia management practices on clinical outcomes should be a high priority.

Role of alcohol in the regulation of iron metabolism

PubMed Central

Harrison-Findik, Duygu Dee

2007-01-01

Patients with alcoholic liver disease frequently exhibit increased body iron stores, as reflected by elevated serum iron indices (transferrin saturation, ferritin) and hepatic iron concentration. Even mild to moderate alcohol consumption has been shown to increase the prevalence of iron overload. Moreover, increased hepatic iron content is associated with greater mortality from alcoholic cirrhosis, suggesting a pathogenic role for iron in alcoholic liver disease. Alcohol increases the severity of disease in patients with genetic hemochromatosis, an iron overload disorder common in the Caucasian population. Both iron and alcohol individually cause oxidative stress and lipid peroxidation, which culminates in liver injury. Despite these observations, the underlying mechanisms of iron accumulation and the source of the excess iron observed in alcoholic liver disease remain unclear. Over the last decade, several novel iron-regulatory proteins have been identified and these have greatly enhanced our understanding of iron metabolism. For example, hepcidin, a circulatory antimicrobial peptide synthesized by the hepatocytes of the liver is now known to play a central role in the regulation of iron homeostasis. This review attempts to describe the interaction of alcohol and iron-regulatory molecules. Understanding these molecular mechanisms is of considerable clinical importance because both alcoholic liver disease and genetic hemochromatosis are common diseases, in which alcohol and iron appear to act synergistically to cause liver injury. PMID:17854133

Associations between iron concentration and productivity in montane streams of the Black Hills, South Dakota

USGS Publications Warehouse

Hayer, Cari Ann; Holcomb, Benjamin M.; Chipps, Steven R.

2013-01-01

Iron is an important micronutrient found in aquatic systems that can influence nutrient availability (e.g., phosphorus) and primary productivity. In streams, high iron concentrations often are associated with low pH as a result of acid mine drainage, which is known to affect fish and invertebrate communities. Streams in the Black Hills of South Dakota are generally circumneutral in pH, yet select streams exhibit high iron concentrations associated with natural iron deposits. In this study, we examined relationships among iron concentration, priphyton biomass, macroinvertebrate abundance, and fish assemblages in four Black Hills streams. The stream with the highest iron concentration (~5 mg Fe/L) had reduced periphyton biomass, invertebrate abundance, and fish biomass compared to the three streams with lower iron levels (0.1 to 0.6 mg Fe/L). Reduced stream productivity was attributed to indirect effects of ferric iron Fe+++), owing to iron-hydroxide precipitation that influenced habitat quality (i.e., substrate and turbidity) and food availability (periphyton and invertebrates) for higher trophic levels (e.g., fish). Additionally, reduced primary and secondary production was associated with reduced standing stocks of salmonid fishes. Our findings suggested that naturally occurring iron deposits may constrain macroinvertebrate and fish production.

Long-term aerobic exercise increases redox-active iron through nitric oxide in rat hippocampus.

PubMed

Chen, Qian; Xiao, De-Sheng

2014-01-30

Adult hippocampus is highly vulnerable to iron-induced oxidative stress. Aerobic exercise has been proposed to reduce oxidative stress but the findings in the hippocampus are conflicting. This study aimed to observe the changes of redox-active iron and concomitant regulation of cellular iron homeostasis in the hippocampus by aerobic exercise, and possible regulatory effect of nitric oxide (NO). A randomized controlled study was designed in the rats with swimming exercise treatment (for 3 months) and/or an unselective inhibitor of NO synthase (NOS) (L-NAME) treatment. The results from the bleomycin-detectable iron assay showed additional redox-active iron in the hippocampus by exercise treatment. The results from nonheme iron content assay, combined with the redox-active iron content, showed increased storage iron content by exercise treatment. NOx (nitrate plus nitrite) assay showed increased NOx content by exercise treatment. The results from the Western blot assay showed decreased ferroportin expression, no changes of TfR1 and DMT1 expressions, increased IRP1 and IRP2 expression, increased expressions of eNOS and nNOS rather than iNOS. In these effects of exercise treatment, the increased redox-active iron content, storage iron content, IRP1 and IRP2 expressions were completely reversed by L-NAME treatment, and decreased ferroportin expression was in part reversed by L-NAME. L-NAME treatment completely inhibited increased NOx and both eNOS and nNOS expression in the hippocampus. Our findings suggest that aerobic exercise could increase the redox-active iron in the hippocampus, indicating an increase in the capacity to generate hydroxyl radicals through the Fenton reactions, and aerobic exercise-induced iron accumulation in the hippocampus might mainly result from the role of the endogenous NO. Copyright © 2013 Elsevier Inc. All rights reserved.

In vivo iron metabolism by IRMS

USDA-ARS?s Scientific Manuscript database

Iron isotopes are used in both biological and geological investigations. Three low-abundance stable isotopes are available for human studies. They have been widely used to study iron metabolism. They have provided valuable insights into iron deficiency, one of the most common micronutrient deficienc...

Enhanced Biogas Production from Nanoscale Zero Valent Iron-Amended Anaerobic Bioreactors

PubMed Central

Carpenter, Alexis Wells; Laughton, Stephanie N.; Wiesner, Mark R.

2015-01-01

Abstract Addition of nanoscale zero valent iron (NZVI) to anaerobic batch reactors to enhance methanogenic activity is described. Two NZVI systems were tested: a commercially available NZVI (cNZVI) slurry and a freshly synthesized NZVI (sNZVI) suspension that was prepared immediately before addition to the reactors. In both systems, the addition of NZVI increased pH and decreased oxidation/reduction potential compared with unamended control reactors. Biodegradation of a model brewery wastewater was enhanced as indicated by an increase in chemical oxygen demand removal with both sNZVI and cNZVI amendments at all concentrations tested (1.25–5.0 g Fe/L). Methane production increased for all NZVI-amended bioreactors, with a maximum increase of 28% achieved on the addition of 2.5 and 5.0 g/L cNZVI. Addition of bulk zero-valent iron resulted in only a 5% increase in methane, indicating the advantage of using the nanoscale particles. NZVI amendments further improved produced biogas by decreasing the amount of CO2 released from the bioreactor by approximately 58%. Overall, addition of cNZVI proved more beneficial than the sNZVI at equal iron concentrations, due to decreased colloidal stability and larger effective particle size of sNZVI. Although some have reported cytotoxicity of NZVI to anaerobic microorganisms, work presented here suggests that NZVI of a certain particle size and reactivity can serve as an amendment to anaerobic digesters to enhance degradation and increase the value of the produced biogas, yielding a more energy-efficient anaerobic method for wastewater treatment. PMID:26339183

Current status of the measurement of blood hepcidin levels in chronic kidney disease.

PubMed

Macdougall, Iain C; Malyszko, Jolanta; Hider, Robert C; Bansal, Sukhvinder S

2010-09-01

Hepcidin is a small defensin-like peptide produced in the liver in response to anemia, hypoxia, or inflammation. In addition to its anti-microbial properties, it has also been found to be a key regulator of iron utilization, providing increased understanding of why chronic kidney disease patients absorb iron poorly from the gut and also why many hemodialysis patients develop functional iron deficiency in the presence of inflammation. Hepcidin synthesis is upregulated in uremia, as in other inflammatory states. The ability to measure hepcidin in biologic fluids has stimulated interest in the potential applicability of this measurement as a more informative marker of iron status than the traditional iron indices such as serum ferritin and transferrin saturation. Until recently, however, the assays for measuring hepcidin have lacked precision, accuracy, and internal validation. Over the last few years, however, several assays have become available that address these limitations. Broadly speaking, these can be divided into radioimmunoassays, ELISAs, and mass spectrometry methods. The purpose of this review is to outline the various assays available at the present time, to critique their advantages and limitations, and to report comparative data in patients with chronic kidney disease. A concern with the immunoassays is that they detect more than biologically active hepcidin-25. Mass spectrometric assays are specific for hepcidin-25 but are labor intensive and require more costly and sophisticated instrumentation. Thus, although mass spectrometry is more accurate, it is less practical for routine clinical use at the present time.

Evaluation of ferrolysis in arsenate adsorption on the paddy soil derived from an Oxisol.

PubMed

Jiang, Jun; Dai, Zhaoxia; Sun, Rui; Zhao, Zhenjie; Dong, Ying; Hong, Zhineng; Xu, Renkou

2017-07-01

Iron oxides are dominant effective adsorbents for arsenate in iron oxide-rich variable charge soils. Oxisol-derived paddy soils undergo intensive ferrolysis, which results in high leaching and transformation of iron oxides. However, little information is available concerning the effect of ferrolysis on arsenate adsorption by paddy soil and parent Oxisol. In the present study, we examined the arsenate affinity of soils using arsenate adsorption/desorption isotherms, zeta potential, adsorption kinetics, pH effect and phosphate competition experiments. Results showed that ferrolysis in an alternating flooding-drying Oxisol-derived paddy soil resulted in a significant decrease of free iron oxides and increase of amorphous iron oxides in the surface and subsurface layers. There were more reactive sites exposed on amorphous than on crystalline iron oxides. Therefore, disproportionate ratios of arsenate adsorption capacities and contents of free iron oxides were observed in the studied Oxisols compared with paddy soils. The Gibbs free energy values corroborated that both electrostatic and non-electrostatic adsorption mechanisms contributed to the arsenate adsorption by bulk soils, and the kinetic adsorption data further suggested that the rate-limiting step was chemisorption. The zeta potential of soil colloids decreased after arsenate was adsorbed on the surfaces, forming inner-sphere complexes and thus transferring their negative charges to the soil particle surfaces. The adsorption/desorption isotherms showed that non-electrostatic adsorption was the main mechanism responsible for arsenate binding to the Oxisol and derived paddy soils, representing 91.42-94.65% of the adsorption capacities. Further studies revealed that arsenate adsorption was greatly inhibited by increasing suspension pH and incorporation of phosphate. Copyright © 2017 Elsevier Ltd. All rights reserved.

Consequences and costs of noncompliance with iron chelation therapy in patients with transfusion-dependent thalassemia: a literature review.

PubMed

Delea, Thomas E; Edelsberg, John; Sofrygin, Oleg; Thomas, Simu K; Baladi, Jean-Francois; Phatak, Pradyumna D; Coates, Thomas D

2007-10-01

Patients with thalassemia major require iron chelation therapy (ICT) to prevent complications from transfusional iron overload. Deferoxamine is effective, but requires administration as a slow continuous subcutaneous or intravenous infusion five to seven times per week. Deferiprone is a three-times-daily oral iron chelator, but has limited availability in the United States. Deferasirox is a once-daily oral iron chelator that was approved in the United States in 2005 for patients older than 2 years of age with transfusional iron overload. Published evidence on rates of compliance with ICT and the association between compliance, and the incidence and costs of complications of iron overload, in patients with thalassemia major was reviewed. A total of 18 studies were identified reporting data on compliance with ICT, including 7 that examined deferoxamine only, 6 that examined deferiprone only, and 5 that compared deferoxamine and deferiprone; no studies reporting compliance with deferasirox were identified. In studies of deferoxamine only, estimated mean compliance ranged from 59 to 78 percent. Studies of deferiprone generally reported better compliance, ranging from 79 to 98 percent. Results of comparative studies of deferoxamine and deferiprone suggest that compliance may be better with oral therapy. Numerous studies demonstrate that that poor compliance with ICT results in increased risk of cardiac disease and endocrinopathies, as well as lower survival. Although data on the costs of noncompliance are limited, a recent model-based study estimated the lifetime costs of inadequate compliance with deferoxamine to be $33,142. Inadequate compliance with ICT in thalassemia major is common and results in substantial morbidity and mortality, as well as increased costs.

Influence of indigenous and added iron on copper extraction from soil.

PubMed

Di Palma, Luca

2009-10-15

Experimental tests of copper leaching from a low permeability soil are presented and discussed. The objective of the experiments was to investigate the influence of indigenous and added iron in the soil towards copper mobilization. Metals' leaching was performed by flushing (column tests) or washing (batch tests) the soil with an aqueous solution of ethylenediaminetetraacetic acid, EDTA. An excess of EDTA was used in flushing tests (up to a EDTA:Cu molar ratio of about 26.2:1), while, in washing tests, the investigated EDTA vs. copper molar ratios were in the range between 1 (equimolar tests) and 8. Copper extraction yield in flushing tests (up to about 85%) was found to depend upon contact time between the soil and the leaching solution and the characteristics of the conditioning solution. The saturation of the soil with a NaNO(3) solution before the treatment, favoured the flushing process reducing the time of percolation, but resulted in a lower metal extraction during the following percolation of EDTA. The indigenous iron was competitive with copper to form EDTA complexes only when it was present in the organic and oxides-hydroxides fractions. Artificial iron addition to the soil resulted in an increase of both the exchangeable iron and the iron bonded to the organic fraction of the soil, thus increasing the overall amount of iron available to extraction. In both batch and continuous tests, the mechanism of copper extraction was found to involve the former dissolution of metal salts, that lead to an initial high concentration of both copper and selected competitive cations (essentially Ca(2+)), and the following EDTA exchange reaction between calcium and copper complexes. The initial metal salts dissolution was found to be pH-dependant.

Iron, zinc and copper in the Alzheimer’s disease brain: a quantitative meta-analysis. Some insight on the influence of citation bias on scientific opinion

PubMed Central

Schrag, Matthew; Mueller, Claudius; Oyoyo, Udochukwu; Kirsch, Wolff M.

2011-01-01

Dysfunctional homeostasis of transition metals is believed to play a role in the pathogenesis of Alzheimer’s disease (AD). Although questioned by some, brain copper, zinc, and particularly iron overload are widely accepted features of AD which have led to the hypothesis that oxidative stress generated from aberrant homeostasis of these transition metals might be a pathogenic mechanism behind AD. This meta-analysis compiled and critically assessed available quantitative data on brain iron, zinc and copper levels in AD patients compared to aged controls. The results were very heterogeneous. A series of heavily cited articles from one laboratory reported a large increase in iron in AD neocortex compared to age-matched controls (p<0.0001) while seven laboratories failed to reproduce these findings reporting no significant difference between the groups (p=0.76). A more than three-fold citation bias was found to favor outlier studies reporting increases in iron and this bias was particularly prominent among narrative review articles. Additionally, while zinc was not significantly changed in the neocortex (p=0.29), copper was significantly depleted in AD (p=0.0003). In light of these findings, it will be important to re-evaluate the hypothesis that transition metal overload accounts for oxidative injury noted in AD. PMID:21600264

Sequential induction of Fur-regulated genes in response to iron limitation in Bacillus subtilis.

PubMed

Pi, Hualiang; Helmann, John D

2017-11-28

Bacterial cells modulate transcription in response to changes in iron availability. The ferric uptake regulator (Fur) senses intracellular iron availability and plays a central role in maintaining iron homeostasis in Bacillus subtilis Here we utilized FrvA, a high-affinity Fe 2+ efflux transporter from Listeria monocytogenes , as an inducible genetic tool to deplete intracellular iron. We then characterized the responses of the Fur, FsrA, and PerR regulons as cells transition from iron sufficiency to deficiency. Our results indicate that the Fur regulon is derepressed in three distinct waves. First, uptake systems for elemental iron ( efeUOB ), ferric citrate ( fecCDEF ), and petrobactin ( fpbNOPQ ) are induced to prevent iron deficiency. Second, B. subtilis synthesizes its own siderophore bacillibactin ( dhbACEBF ) and turns on bacillibactin ( feuABC ) and hydroxamate siderophore ( fhuBCGD ) uptake systems to scavenge iron from the environment and flavodoxins ( ykuNOP ) to replace ferredoxins. Third, as iron levels decline further, an "iron-sparing" response ( fsrA , fbpAB , and fbpC ) is induced to block the translation of abundant iron-utilizing proteins and thereby permit the most essential iron-dependent enzymes access to the limited iron pools. ChIP experiments demonstrate that in vivo occupancy of Fur correlates with derepression of each operon, and the graded response observed here results, at least in part, from higher-affinity binding of Fur to the "late"-induced genes.

Influence of Iron and Aeration on Staphylococcus aureus Growth, Metabolism, and Transcription

PubMed Central

Ledala, Nagender; Zhang, Bo; Seravalli, Javier; Powers, Robert

2014-01-01

Staphylococcus aureus is a prominent nosocomial pathogen and a major cause of biomaterial-associated infections. The success of S. aureus as a pathogen is due in part to its ability to adapt to stressful environments. As an example, the transition from residing in the nares to residing in the blood or deeper tissues is accompanied by changes in the availability of nutrients and elements such as oxygen and iron. As such, nutrients, oxygen, and iron are important determinants of virulence factor synthesis in S. aureus. In addition to influencing virulence factor synthesis, oxygen and iron are critical cofactors in enzymatic and electron transfer reactions; thus, a change in iron or oxygen availability alters the bacterial metabolome. Changes in metabolism create intracellular signals that alter the activity of metabolite-responsive regulators such as CodY, RpiRc, and CcpA. To assess the extent of metabolomic changes associated with oxygen and iron limitation, S. aureus cells were cultivated in iron-limited medium and/or with decreasing aeration, and the metabolomes were examined by nuclear magnetic resonance (NMR) spectroscopy. As expected, oxygen and iron limitation dramatically decreased tricarboxylic acid (TCA) cycle activity, creating a metabolic block and significantly altering the metabolome. These changes were most prominent during post-exponential-phase growth, when TCA cycle activity was maximal. Importantly, many of the effects of iron limitation were obscured by aeration limitation. Aeration limitation not only obscured the metabolic effects of iron limitation but also overrode the transcription of iron-regulated genes. Finally, in contrast to previous speculation, we confirmed that acidification of the culture medium occurs independent of the availability of iron. PMID:24706736

Lack of Plasma Protein Hemopexin Results in Increased Duodenal Iron Uptake.

PubMed

Fiorito, Veronica; Geninatti Crich, Simonetta; Silengo, Lorenzo; Aime, Silvio; Altruda, Fiorella; Tolosano, Emanuela

2013-01-01

The body concentration of iron is regulated by a fine equilibrium between absorption and losses of iron. Iron can be absorbed from diet as inorganic iron or as heme. Hemopexin is an acute phase protein that limits iron access to microorganisms. Moreover, it is the plasma protein with the highest binding affinity for heme and thus it mediates heme-iron recycling. Considering its involvement in iron homeostasis, it was postulated that hemopexin may play a role in the physiological absorption of inorganic iron. Hemopexin-null mice showed elevated iron deposits in enterocytes, associated with higher duodenal H-Ferritin levels and a significant increase in duodenal expression and activity of heme oxygenase. The expression of heme-iron and inorganic iron transporters was normal. The rate of iron absorption was assessed by measuring the amount of (57)Fe retained in tissues from hemopexin-null and wild-type animals after administration of an oral dose of (57)FeSO4 or of (57)Fe-labelled heme. Higher iron retention in the duodenum of hemopexin-null mice was observed as compared with normal mice. Conversely, iron transfer from enterocytes to liver and bone marrow was unaffected in hemopexin-null mice. The increased iron level in hemopexin-null duodenum can be accounted for by an increased iron uptake by enterocytes and storage in ferritins. These data indicate that the lack of hemopexin under physiological conditions leads to an enhanced duodenal iron uptake thus providing new insights to our understanding of body iron homeostasis.

Iron homeostasis in the liver

PubMed Central

Anderson, Erik R; Shah, Yatrik M

2014-01-01

Iron is an essential nutrient that is tightly regulated. A principal function of the liver is the regulation of iron homeostasis. The liver senses changes in systemic iron requirements and can regulate iron concentrations in a robust and rapid manner. The last 10 years have led to the discovery of several regulatory mechanisms in the liver which control the production of iron regulatory genes, storage capacity, and iron mobilization. Dysregulation of these functions leads to an imbalance of iron, which is the primary causes of iron-related disorders. Anemia and iron overload are two of the most prevalent disorders worldwide and affect over a billion people. Several mutations in liver-derived genes have been identified, demonstrating the central role of the liver in iron homeostasis. During conditions of excess iron, the liver increases iron storage and protects other tissues, namely the heart and pancreas from iron-induced cellular damage. However, a chronic increase in liver iron stores results in excess reactive oxygen species production and liver injury. Excess liver iron is one of the major mechanisms leading to increased steatohepatitis, fibrosis, cirrhosis, and hepatocellular carcinoma. PMID:23720289

DOE Office of Scientific and Technical Information (OSTI.GOV)

Longo, Amelia F.; Feng, Yan; Lai, Barry

Aerosol iron was examined in Saharan dust plumes using a combination of iron near-edge X-ray absorption spectroscopy and wet-chemical techniques. Aerosol samples were collected at three sites located in the Mediterranean, the Atlantic, and Bermuda to characterize iron at different atmospheric transport lengths and time scales. Iron(III) oxides were a component of aerosols at all sampling sites and dominated the aerosol iron in Mediterranean samples. In Atlantic samples, iron(II and III) sulfate, iron(III) phosphate, and iron(II) silicates were also contributors to aerosol composition. With increased atmospheric transport time, iron(II) sulfates are found to become more abundant, aerosol iron oxidation statemore » became more reduced, and aerosol acidity increased. As a result, atmospheric processing including acidic reactions and photoreduction likely influence the form of iron minerals and oxidation state in Saharan dust aerosols and contribute to increases in aerosol-iron solubility.« less

Higher concentrations of nanoscale zero-valent iron (nZVI) in soil induced rice chlorosis due to inhibited active iron transportation.

PubMed

Wang, Jie; Fang, Zhanqiang; Cheng, Wen; Yan, Xiaomin; Tsang, Pokeung Eric; Zhao, Dongye

2016-03-01

In this study, the effects of concentrations 0, 100, 250, 500, 750 and 1000 mg kg(-1) of nanoscale zero-valent iron (nZVI) on germination, seedlings growth, physiology and toxicity mechanisms were investigated. The results showed that nZVI had no effect on germination, but inhibited the rice seedlings growth in higher concentrations (>500 mg kg(-1) nZVI). The highest suppression rate of the length of roots and shoots reached 46.9% and 57.5%, respectively. The 1000mg kg(-1) nZVI caused the highest suppression rates for chlorophyll and carotenoids, at 91.6% and 85.2%, respectively. In addition, the activity of antioxidant enzymes was altered by the translocation of nanoparticles and changes in active iron content. Visible symptoms of iron deficiency were observed at higher concentrations, at which the active iron content decreased 61.02% in the shoots, but the active iron content not decreased in roots. Interestingly, the total and available amounts of iron in the soil were not less than those in the control. Therefore, the plants iron deficiency was not caused by (i) deficiency of available iron in the soil and (ii) restraint of the absorption that plant takes in the available iron, while induced by (ⅲ) the transport of active iron from the root to the shoot was blocked. The cortex tissues were seriously damaged by nZVI which was transported from soil to the root, these were proved by scanning electron microscopy (SEM), transmission electron microscopy (TEM) and energy dispersive spectroscopy (EDS). This current study shows that the mechanism of iron deficiency in rice seedling was due to transport of active iron from the root to the shoot blocked, which was caused by the uptake of nZVI. Copyright © 2016 Elsevier Ltd. All rights reserved.

Nifedipine Increases Iron Content in WKPT-0293 Cl.2 Cells via Up-Regulating Iron Influx Proteins

PubMed Central

Yu, Shuang-Shuang; Jiang, Li-Rong; Ling, Yan; Qian, Zhong-Ming; Zhou, Yu-Fu; Li, Juan; Ke, Ya

2017-01-01

Nifedipine was reported to enhance urinary iron excretion in iron overloaded mice. However, it remains unknown how nifedipine stimulates urinary iron excretion in the kidney. We speculated that nifedipine might inhibit the TfR1/ DMT1 (transferrin receptor 1/divalent metal transporter1)-mediated iron uptake by proximal tubule cells in addition to blocking L-type Ca2+ channels, leading to an increase in iron in lumen-fluid and then urinary iron excretion. To test this hypothesis, we investigated the effects of nifedipine on iron content and expression of TfR1, DMT1 and ferroportin1 (Fpn1) in WKPT-0293 Cl.2 cells of the S1 segment of the proximal tubule in rats, using a graphite furnace atomic absorption spectrophotometer and Western blot analysis, respectively. We demonstrated for the first time that nifedipine significantly enhanced iron content as well as TfR1 and DMT1 expression and had no effect on Fpn1 levels in the cells. We also found that ferric ammonium citrate decreased TfR1 levels, increased Fpn1 expression and had no effect on DMT1 content, while co-treatment with nifedipine and FAC increase TfR1 and DMT1 expression and also had no effect on Fpn1 levels. These findings suggest that the nifedipine-induced increase in cell iron may mainly be due to the corresponding increase in TfR1 and DMT1 expression and also imply that the effects of nifedipine on iron transport in proximal tubule cells can not explain the increase in urinary iron excretion. PMID:28243203

Angiotensin II alters the expression of duodenal iron transporters, hepatic hepcidin, and body iron distribution in mice.

PubMed

Tajima, Soichiro; Ikeda, Yasumasa; Enomoto, Hideaki; Imao, Mizuki; Horinouchi, Yuya; Izawa-Ishizawa, Yuki; Kihira, Yoshitaka; Miyamoto, Licht; Ishizawa, Keisuke; Tsuchiya, Koichiro; Tamaki, Toshiaki

2015-08-01

Angiotensin II (ANG II) has been shown to affect iron metabolism through alteration of iron transporters, leading to increased cellular and tissue iron contents. Serum ferritin, a marker of body iron storage, is elevated in various cardiovascular diseases, including hypertension. However, the associated changes in iron absorption and the mechanism underlying increased iron content in a hypertensive state remain unclear. The C57BL6/J mice were treated with ANG II to generate a model of hypertension. Mice were divided into three groups: (1) control, (2) ANG II-treated, and (3) ANG II-treated and ANG II receptor blocker (ARB)-administered (ANG II-ARB) groups. Mice treated with ANG II showed increased serum ferritin levels compared to vehicle-treated control mice. In ANG II-treated mice, duodenal divalent metal transporter-1 and ferroportin (FPN) expression levels were increased and hepatic hepcidin mRNA expression and serum hepcidin concentration were reduced. The mRNA expression of bone morphogenetic protein 6 and CCAAT/enhancer-binding protein alpha, which are regulators of hepcidin, was also down-regulated in the livers of ANG II-treated mice. In terms of tissue iron content, macrophage iron content and renal iron content were increased by ANG II treatment, and these increases were associated with reduced expression of transferrin receptor 1 and FPN and increased expression of ferritin. These changes induced by ANG II treatment were ameliorated by the administration of an ARB. Angiotensin II (ANG II) altered the expression of duodenal iron transporters and reduced hepcidin levels, contributing to the alteration of body iron distribution.

The Evolution of Sulfide in Shallow Aquatic Ecosystem Sediments: An Analysis of the Roles of Sulfate, Organic Carbon, and Iron and Feedback Constraints Using Structural Equation Modeling

NASA Astrophysics Data System (ADS)

Pollman, C. D.; Swain, E. B.; Bael, D.; Myrbo, A.; Monson, P.; Shore, M. D.

2017-11-01

The generation of elevated concentrations of sulfide in sediment pore waters that are toxic to rooted macrophytes is problematic in both marine and freshwaters. In marine waters, biogeochemical conditions that lead to toxic levels of sulfide generally relate to factors that affect oxygen dynamics or the sediment iron concentration. In freshwaters, increases in surface water sulfate have been implicated in decline of Zizania palustris (wild rice), which is important in wetlands across the Great Lakes region of North America. We developed a structural equation (SE) model to elucidate key variables that govern the evolution of sulfide in pore waters in shallow aquatic habitats that are potentially capable of supporting wild rice. The conceptual basis for the model is the hypothesis that dissimilatory sulfate reduction is limited by the availability of both sulfate and total organic carbon (TOC) in the sediment. The conceptual model also assumes that pore water sulfide concentrations are constrained by the availability of pore water iron and that sediment iron supports the supply of dissolved iron to the pore water. A key result from the SE model is that variations in three external variables (sulfate, sediment TOC, and sediment iron) contribute nearly equally to the observed variations in pore water sulfide. As a result, management efforts to mitigate against the toxic effects of pore water sulfide on macrophytes such as wild rice should approach defining a protective sulfate threshold as an exercise tailored to the geochemistry of each site that quantitatively considers the effects of ambient concentrations of sediment Fe and TOC.

Phosphoric acid addition effect on the microstructure and magnetic properties of iron-based soft magnetic composites

NASA Astrophysics Data System (ADS)

Hsiang, Hsing-I.; Fan, Liang-Fang; Hung, Jia-Jing

2018-02-01

The phosphoric acid addition effect on phosphate insulation coating microstructure was investigated in this study. The relationships between the phosphate insulation coating microstructure and temperature resistance, corrosion resistance and magnetic properties of iron-based soft magnetic composites (SMCs) were studied by using SEM, TEM/EDS and FTIR. It was observed that an iron phosphate/carbonyl iron core/shell structure is formed with carbonyl iron powder after phosphatizing treatment. The iron phosphate phase was identified as amorphous and its thickness increased from 30 nm to 60 nm as the phosphoric acid concentration was increased from 1 wt% to 2 wt%. When the phosphoric acid concentration was further increased to 5 wt%, the excess iron phosphate precipitates between the soft magnetic composite particles. The temperature and corrosion resistance and resistivity of the iron-based SMCs can be effectively improved using carbonyl iron powders after phosphatizing. The initial permeability of the iron-based SMCs decreased with increasing phosphoric acid concentration due to thicker insulation layer formation. However, the imaginary permeability below the domain wall displacement resonance frequency decreased with increasing phosphoric acid concentration. The DC-bias superposition characteristic can also be improved by increasing the phosphoric acid concentration. Iron-based SMCs with superior temperature and corrosion resistance, initial permeability, magnetic loss and DC-bias superposition characteristics can be obtained by controlling the phosphoric acid concentration during phosphatizing to adjust the iron phosphate precipitate thickness on the iron powder surface.

Facilitated citrate-dependent iron translocation increases rice endosperm iron and zinc concentrations.

PubMed

Wu, Ting-Ying; Gruissem, Wilhelm; Bhullar, Navreet K

2018-05-01

Iron deficiency affects one third of the world population. Most iron biofortification strategies have focused on genes involved in iron uptake and storage but facilitating internal long-distance iron translocation has been understudied for increasing grain iron concentrations. Citrate is a primary iron chelator, and the transporter FERRIC REDUCTASE DEFECTIVE 3 (FRD3) loads citrate into the xylem. We have expressed AtFRD3 in combination with AtNAS1 (NICOTIANAMINE SYNTHASE 1) and PvFER (FERRITIN) or with PvFER alone to facilitate long-distance iron transport together with efficient iron uptake and storage in the rice endosperm. The citrate and iron concentrations in the xylem sap of transgenic plants increased two-fold compared to control plants. Iron and zinc levels increased significantly in polished and unpolished rice grains to more than 70% of the recommended estimated average requirement (EAR) for iron and 140% of the recommended EAR for zinc in polished rice grains. Furthermore, the transformed lines showed normal phenotypic growth, were tolerant to iron deficiency and aluminum toxicity, and had grain cadmium levels similar to control plants. Together, our results demonstrate that deploying FRD for iron biofortification has no obvious anti-nutritive effects and should be considered as an effective strategy for reducing human iron deficiency anemia. Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.

77 FR 18827 - Draft Guidance for Industry on Bioequivalence Recommendations for Iron Sucrose Injection...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-03-28

...] Draft Guidance for Industry on Bioequivalence Recommendations for Iron Sucrose Injection; Availability... Recommendations for Iron Sucrose.'' The recommendations provide specific guidance on the design of bioequivalence (BE) studies to support abbreviated new drug applications (ANDAs) for iron sucrose injection. DATES...

Organic synthesis via magnetic attraction: benign and sustainable protocols using magnetic nanoferrites

EPA Science Inventory

Magnetic nano-catalysts have been prepared using simple modification of iron ferrites wherein their quasi-homogeneous state, because of nm size range, facilitates the catalysis process as increased surface is available for reaction; the easy separation of the catalysts by externa...

Carbonate counter pump stimulated by natural iron fertilization in the Polar Frontal Zone

NASA Astrophysics Data System (ADS)

Salter, Ian; Schiebel, Ralf; Ziveri, Patrizia; Movellan, Aurore; Lampitt, Richard; Wolff, George A.

2014-12-01

The production of organic carbon in the ocean's surface and its subsequent downward export transfers carbon dioxide to the deep ocean. This CO2 drawdown is countered by the biological precipitation of carbonate, followed by sinking of particulate inorganic carbon, which is a source of carbon dioxide to the surface ocean, and hence the atmosphere over 100-1,000 year timescales. The net transfer of CO2 to the deep ocean is therefore dependent on the relative amount of organic and inorganic carbon in sinking particles. In the Southern Ocean, iron fertilization has been shown to increase the export of organic carbon, but it is unclear to what degree this effect is compensated by the export of inorganic carbon. Here we assess the composition of sinking particles collected from sediment traps located in the Polar Frontal Zone of the Southern Ocean. We find that in high-nutrient, low-chlorophyll regions that are characterized by naturally high iron concentrations, fluxes of both organic and inorganic carbon are higher than in regions with no iron fertilization. However, the excess flux of inorganic carbon is greater than that of organic carbon. We estimate that the production and flux of carbonate in naturally iron-fertilized waters reduces the overall amount of CO2 transferred to the deep ocean by 6-32%, compared to 1-4% at the non-fertilized site. We suggest that an increased export of organic carbon, stimulated by iron availability in the glacial sub-Antarctic oceans, may have been accompanied by a strengthened carbonate counter pump.

Altered Erythropoiesis in Mouse Models of Type 3 Hemochromatosis

PubMed Central

Pellegrino, R. M.; Ferbo, L.; Boero, M.; Palmieri, A.; Osella, L.; Pollicino, P.; Miniscalco, B.

2017-01-01

Type 3 haemochromatosis (HFE3) is a rare genetic iron overload disease which ultimately lead to compromised organs functioning. HFE3 is caused by mutations in transferrin receptor 2 (TFR2) gene that codes for two main isoforms (Tfr2α and Tfr2β). Tfr2α is one of the hepatic regulators of iron inhibitor hepcidin. Tfr2β is an intracellular isoform of the protein involved in the regulation of iron levels in reticuloendothelial cells. It has been recently demonstrated that Tfr2 is also involved in erythropoiesis. This study aims to further investigate Tfr2 erythropoietic role by evaluating the erythropoiesis of two Tfr2 murine models wherein either one or both of Tfr2 isoforms have been selectively silenced (Tfr2 KI and Tfr2 KO). The evaluations were performed in bone marrow and spleen, in 14 days' and 10 weeks' old mice, to assess erythropoiesis in young versus adult animals. The lack of Tfr2α leads to macrocytosis with low reticulocyte number and increased hemoglobin values, together with an anticipation of adult BM erythropoiesis and an increased splenic erythropoiesis. On the other hand, lack of Tfr2β (Tfr2 KI mice) causes an increased and immature splenic erythropoiesis. Taken together, these data confirm the role of Tfr2α in modulation of erythropoiesis and of Tfr2β in favoring iron availability for erythropoiesis. PMID:28540293

75 FR 3201 - Floor-Standing, Metal-Top Ironing Tables and Certain Parts Thereof From the People's Republic of...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-01-20

... available with various features, including iron rests, linen racks, and others. The subject ironing tables... linen rack. The term ``complete'' ironing table means product sold as a ready-to-use ensemble consisting... linen rack. The term ``incomplete'' ironing table means product shipped or sold as a ``bare board''--i.e...

Dissociation between iron accumulation and ferritin upregulation in the aged substantia nigra: attenuation by dietary restriction

PubMed Central

Walker, Thomas; Michaelides, Christos; Ekonomou, Antigoni; Geraki, Kalotina; Parkes, Harold G; Suessmilch, Maria; Herlihy, Amy H; Crum, William R; So, Po-Wah

2016-01-01

Despite regulation, brain iron increases with aging and may enhance aging processes including neuroinflammation. Increases in magnetic resonance imaging transverse relaxation rates, R2 and R2*, in the brain have been observed during aging. We show R2 and R2* correlate well with iron content via direct correlation to semi-quantitative synchrotron-based X-ray fluorescence iron mapping, with age-associated R2 and R2* increases reflecting iron accumulation. Iron accumulation was concomitant with increased ferritin immunoreactivity in basal ganglia regions except in the substantia nigra (SN). The unexpected dissociation of iron accumulation from ferritin-upregulation in the SN suggests iron dyshomeostasis in the SN. Occurring alongside microgliosis and astrogliosis, iron dyshomeotasis may contribute to the particular vulnerability of the SN. Dietary restriction (DR) has long been touted to ameliorate brain aging and we show DR attenuated agerelated in vivo R2 increases in the SN over ages 7 – 19 months, concomitant with normal iron-induction of ferritin expression and decreased microgliosis. Iron is known to induce microgliosis and conversely, microgliosis can induce iron accumulation, which of these may be the initial pathological aging event warrants further investigation. We suggest iron chelation therapies and anti-inflammatory treatments may be putative ‘antibrain aging’ therapies and combining these strategies may be synergistic. PMID:27743512

Ferritin Levels and Their Association With Regional Brain Volumes in Tourette's Syndrome

PubMed Central

Gorman, Daniel A.; Zhu, Hongtu; Anderson, George M.; Davies, Mark; Peterson, Bradley S.

2008-01-01

Objective A previous small study showed lower serum ferritin levels in subjects with Tourette's syndrome than in healthy subjects. The authors measured peripheral iron indices in a large group of Tourette's syndrome and comparison subjects and explored associations of ferritin levels with regional brain volumes. Method Ferritin was measured in 107 children and adults (63 Tourette's syndrome, 44 comparison); serum iron was measured in 73 (41 Tourette's syndrome, 32 comparison). Magnetic resonance imaging scans were used to measure volumes of the basal ganglia and cortical gray matter. Results Ferritin and serum iron were significantly lower in the Tourette's syndrome subjects, although still within the normal range. No association was found between tic severity and either iron index. In the Tourette's syndrome subjects, ferritin did not correlate significantly with caudate volume but did correlate positively with putamen volume. In the comparison subjects, ferritin correlated inversely with caudate volume but did not correlate significantly with putamen volume. Irrespective of diagnosis, ferritin correlated positively with volumes of the sensorimotor, midtemporal, and subgenual cortices. Conclusions The lower peripheral ferritin and iron levels in persons with Tourette's syndrome are consistent with findings in other movement disorders and suggest that lower iron availability may have a causal role in the pathophysiology of tic disorders. Lower iron stores may contribute to hypoplasia of the caudate and putamen, increasing vulnerability to developing tics or to having more severe tics. Lower iron stores may also contribute to smaller cortical volumes and consequently to reduced inhibitory control of tics. PMID:16816233

Geochemical patterns and microbial contribution to iron plaque formation in the rice plant rhizosphere

NASA Astrophysics Data System (ADS)

Maisch, Markus; Murata, Chihiro; Unger, Julia; Kappler, Andreas; Schmidt, Caroline

2015-04-01

Rice is the major food source for more than half of the world population and 80 percent of the worldwide rice cultivation is performed on water logged paddy soils. The establishment of reducing conditions in the soil and across the soil-water interface not only stimulates the microbial production and release of the greenhouse gas methane. These settings also create optimal conditions for microbial iron(III) reduction and therefore saturate the system with reduced ferrous iron. Through the reduction and dissolution of ferric minerals that are characterized by their high surface activity, sorbed nutrients and contaminants (e.g. arsenic) will be mobilized and are thus available for uptake by plants. Rice plants have evolved a strategy to release oxygen from their roots in order to prevent iron toxification in highly ferrous environments. The release of oxygen to the reduced paddy soil causes ferric iron plaque formation on the rice roots and finally increases the sorption capacity for toxic metals. To this date the geochemical and microbiological processes that control the formation of iron plaque are not deciphered. It has been hypothesized that iron(II)-oxidizing bacteria play a potential role in the iron(III) mineral formation along the roots. However, not much is known about the actual processes, mineral products, and geochemical gradients that establish within the rhizosphere. In the present study we have developed a growth set-up that allows the co-cultivation of rice plants and iron(II)-oxidizing bacteria, as well as the visual observation and in situ measurement of geochemical parameters. Oxygen and dissolved iron(II) gradients have been measured using microelectrodes and show geochemical hot spots that offer optimal growth conditions for microaerophilic iron(II) oxidizers. First mineral identification attempts of iron plaque have been performed using Mössbauer spectroscopy and microscopy. The obtained results on mineraology and crystallinity have been compared to mineralogical data from purely biotic (microaerophilic) and abiotic iron mineral formation processes.

Mercury mobilization and speciation linked to bacterial iron oxide and sulfate reduction: A column study to mimic reactive transfer in an anoxic aquifer.

PubMed

Hellal, Jennifer; Guédron, Stéphane; Huguet, Lucie; Schäfer, Jörg; Laperche, Valérie; Joulian, Catherine; Lanceleur, Laurent; Burnol, André; Ghestem, Jean-Philippe; Garrido, Francis; Battaglia-Brunet, Fabienne

2015-09-01

Mercury (Hg) mobility and speciation in subsurface aquifers is directly linked to its surrounding geochemical and microbial environment. The role of bacteria on Hg speciation (i.e., methylation, demethylation and reduction) is well documented, however little data is available on their impact on Hg mobility. The aim of this study was to test if (i) Hg mobility is due to either direct iron oxide reduction by iron reducing bacteria (IRB) or indirect iron reduction by sulfide produced by sulfate reducing bacteria (SRB), and (ii) to investigate its subsequent fate and speciation. Experiments were carried out in an original column setup combining geochemical and microbiological approaches that mimic an aquifer including an interface of iron-rich and iron depleted zones. Two identical glass columns containing iron oxides spiked with Hg(II) were submitted to (i) direct iron reduction by IRB and (ii) to indirect iron reduction by sulfides produced by SRB. Results show that in both columns Hg was leached and methylated during the height of bacterial activity. In the column where IRB are dominant, Hg methylation and leaching from the column was directly correlated to bacterial iron reduction (i.e., Fe(II) release). In opposition, when SRB are dominant, produced sulfide induced indirect iron oxide reduction and rapid adsorption of leached Hg (or produced methylmercury) on neoformed iron sulfides (e.g., Mackinawite) or its precipitation as HgS. At the end of the SRB column experiment, when iron-oxide reduction was complete, filtered Hg and Fe concentrations increased at the outlet suggesting a leaching of Hg bound to FeS colloids that may be a dominant mechanism of Hg transport in aquifer environments. These experimental results highlight different biogeochemical mechanisms that can occur in stratified sub-surface aquifers where bacterial activities play a major role on Hg mobility and changes in speciation. Copyright © 2015 Elsevier B.V. All rights reserved.

Serum ferritin as an indicator of iron status: what do we need to know?

PubMed

Daru, Jahnavi; Colman, Katherine; Stanworth, Simon J; De La Salle, Barbara; Wood, Erica M; Pasricha, Sant-Rayn

2017-12-01

Determination of iron status in pregnancy and in young children is essential for both clinical and public health practice. Clinical diagnosis of iron deficiency (ID) through sampling of bone marrow to identify the absence of body iron stores is impractical in most cases. Serum ferritin (SF) concentrations are the most commonly deployed indicator for determining ID, and low SF concentrations reflect a state of iron depletion. However, there is considerable variation in SF cutoffs recommended by different expert groups to diagnose ID. Moreover, the cutoffs used in different clinical laboratories are heterogeneous. There are few studies of diagnostic test accuracy to establish the sensitivity and specificity of SF compared with key gold standards (such as absent bone marrow iron stores, increased intestinal iron absorption, and hemoglobin response to SF) among noninflamed, outpatient populations. The limited data available suggest the commonly recommended SF cutoff of <15 μg/L is a specific but not sensitive cutoff, although evidence is limited. Data from women during pregnancy or from young children are especially uncommon. Most data are from studies conducted >30 y ago, do not reflect ethnic or geographic diversity, and were performed in an era for which laboratory methods no longer reflect present practice. Future studies to define the appropriate SF cutoffs are urgently needed and would also provide an opportunity to compare this indicator with other established and emerging iron indexes. In addition, future work would benefit from a focus on elucidating cutoffs and indexes relevant to iron adequacy. © 2017 American Society for Nutrition.

Impacts of amount of impregnated iron in granular activated carbon on arsenate adsorption capacities and kinetics.

PubMed

Chang, Qigang; Lin, Wei; Ying, Wei-Chi

2012-06-01

Iron-impregnated granular activated carbons (Fe-GAC) can remove arsenic effectively from water. In this study, Fe-GACs with iron content of 1.64 to 28.90% were synthesized using a new multi-step procedure for the investigation of effects of iron amount on arsenic adsorption capacities and kinetics. Langmuir model satisfactorily fit arsenic adsorption on Fe-GACs. The maximum arsenic adsorption capacity (q(m)) increased significantly with iron impregnation and reached 1,867 to 1,912 microg/g with iron content of 9.96 to 13.59%. Further increase of iron content (> 13.59%) caused gradual decrease of q(m). It was found that the amount of impregnated iron showed little impact on the affinity for arsenate. Kinetic study showed that the amount of impregnated iron affected the arsenic intraparticle diffusion rate greatly. The pseudo-second-order kinetic model fit arsenic adsorption kinetics on Fe-GACs better than the pseudo-first-order model. The arsenic adsorption rate increased with increasing of iron content from 1.64% to 13.59%, and then decreased with more impregnated iron (13.59 to 28.90%).

Transcriptional response of Leptospira interrogans to iron limitation and characterization of a PerR homolog

USDA-ARS?s Scientific Manuscript database

Leptospira interrogans is the causative agent of leptospirosis, a zoonosis of global significance. Iron is essential for growth of most bacterial species. Since availability of iron is low in the host, pathogens have evolved complex iron acquisition mechanisms to survive and establish infection. In ...

Testing the iron hypothesis in a mouse model of atherosclerosis

PubMed Central

Kautz, Léon; Gabayan, Victoria; Wang, Xuping; Wu, Judy; Onwuzurike, James; Jung, Grace; Qiao, Bo; Lusis, Aldons J.; Ganz, Tomas; Nemeth, Elizabeta

2013-01-01

SUMMARY Hepcidin, the iron-regulatory hormone and acute phase reactant, is proposed to contribute to the pathogenesis of atherosclerosis by promoting iron accumulation in plaque macrophages, leading to increased oxidative stress and inflammation in the plaque (the “iron hypothesis”). Hepcidin and iron may thus represent modifiable risk factors in atherosclerosis. We measured hepcidin expression in Apoe−/− mice with varying diets and ages. To assess the role of macrophage iron in atherosclerosis, we generated Apoe−/− mice with macrophage-specific iron accumulation by introducing the ferroportin ffe mutation. Macrophage iron loading was also enhanced by intravenous iron injection. Contrary to the iron hypothesis, we found that hepatic hepcidin expression was not increased at any stage of the atherosclerosis progression in Apoe−/− or Apoe/ffe mice and the atherosclerotic plaque size was not increased in mice with elevated macrophage iron. Our results strongly argue against any significant role of macrophage iron in atherosclerosis progression in mice. PMID:24316081

Iron, zinc and iodide status in Mexican children under 12 years and women 12-49 years of age. A probabilistic national survey.

PubMed

Villalpando, Salvador; García-Guerra, Armando; Ramírez-Silva, Claudia Ivonne; Mejía-Rodríguez, Fabiola; Matute, Guadalupe; Shamah-Levy, Teresa; Rivera, Juan A

2003-01-01

To describe the epidemiology of iron, zinc and iodide deficiencies in a probabilistic sample of Mexican women and children and explore its association with some dietary and socio-demographic variables. We carried out in 1999 an epidemiological description of iron (percent transferrin saturation, PTS, < 16%), serum zinc (< 65 ug/dl) and iodide (< 50 ug/l urine) deficiencies in a probabilistic sample of 1,363 Mexican children under 12 years and of 731 women of child-bearing age. Serum iron, Total Iron Binding Capacity (TIBC) and zinc were measured by atomic absorption spectrometry, and urinary iodide by a colorimetric method. Logistic regression models explored determinants for such micromineral deficiencies. Iron deficiency was higher (67%) in infants < 2 years of age. Prevalence declined (34-39%) at school age. The prevalence for iron deficiency in women was 40%. Zinc deficiency was higher in infants < 2 years of age (34%) than in school-age children (19-24%). Prevalence in women was 30%, with no rural/urban difference. In women the likelihood of iron deficiency decreased as SEL improved (p = 0.04) and increased with the intake of cereals (p = 0.01). The likelihood of low serum zinc levels was greater in women and children of low socioeconomic level (SEL) (p < 0.02 and p = 0.001) iodide deficiency was negligible in both children and women. The data shows high prevalence of iron deficiency-specially in infants 12 to 24 months of age. It is suggested that in older children and women 12 to 49 years of age that iron bioavailability is low. The prevalence of zinc deficiency was also very high. The English version of this paper is available too at: http://www.insp.mx/salud/index.html.

Reduced risk for placental malaria in iron deficient women

PubMed Central

2011-01-01

Background Nutritional iron deficiency may limit iron availability to the malaria parasite reducing infection risk, and/or impair host immunity thereby increasing this risk. In pregnant women, there is evidence of an adverse effect with iron supplementation, but the few reported studies are strongly confounded. Methods A case control study in pregnant Malawian women was undertaken in Chikhwawa southern Malawi in order to describe iron status in relation to placental malaria controlling for several confounding factors. Pregnancy characteristics were obtained and a blood sample at delivery. A full blood count was performed and serum ferritin and transferrin receptor quantified by enzyme-linked immunoassay. DNA analysis was used to identify genetic polymorphisms for ABO phenotype, hemoglobin HbS, and glucose -6 phosphate dehydrogenase deficiency. Placental tissue was obtained and malaria histology classified as active, past or no malaria infection. Results 112 cases with placental malaria were identified and 110 women with no evidence of placental infection. Iron deficiency was less frequent in women with placental Plasmodium falciparum infection. In those with acute, chronic or past placental infections the odds ratio for iron deficiency was 0.4, 95% CI 0.2-0.8, p = 0.01; for acute and chronic infections 0.4, 0.2-0.8, p = 0.006; for acute infection 0.3, 0.1-0.7, p = 0.001. The association was greater in multigravidae. Conclusion Women with either acute, or acute and chronic placental malaria were less likely to have iron deficiency than women without placental malaria infection There is a priority to establish if reversing iron deficiency through iron supplementation programs either prior to or during pregnancy enhances malaria risk. PMID:21345193

Impact of Iron Deficiency on Response to and Remodeling After Cardiac Resynchronization Therapy.

PubMed

Martens, Pieter; Verbrugge, Frederik; Nijst, Petra; Dupont, Matthias; Tang, W H Wilson; Mullens, Wilfried

2017-01-01

Iron deficiency is prevalent in heart failure with reduced ejection fraction and relates to symptomatic status, readmission, and all-cause mortality. The relation between iron status and response to cardiac resynchronization therapy (CRT) remains insufficiently elucidated. This study assesses the impact of iron deficiency on clinical response and reverse cardiac remodeling and outcome after CRT. Baseline characteristics, change in New York Heart Association functional class, reverse cardiac remodeling on echocardiography, and clinical outcome (i.e., all-cause mortality and heart failure readmissions) were retrospectively evaluated in consecutive CRT patients who had full iron status and complete blood count available at implantation, implanted at a single tertiary care center with identical dedicated multidisciplinary CRT follow-up from October 2008 to August 2015. A total of 541 patients were included with mean follow-up of 38 ± 22 months. Prevalence of iron deficiency was 56% at implantation. Patients with iron deficiency exhibited less symptomatic improvement 6 months after implantation (p value <0.001). In addition, both the decrease in left ventricular end-diastolic diameter (-3.1 vs -6.2 mm; p value = 0.011) and improvement in ejection fraction (+11% vs +15%, p value = 0.001) were significantly lower in patients with iron deficiency. Iron deficiency was significantly associated with an increased risk for heart failure admission or all-cause mortality (adjusted hazard ratio 1.718, 95% confidence interval 1.178 to 2.506), irrespectively of the presence of anemia (Hemoglobin <12 g/dl in women and <13 g/dl in men). In conclusion, iron deficiency is prevalent and affects both clinical response and reverse cardiac remodeling after CRT implantation. Moreover, it is a powerful predictor of adverse clinical outcomes in CRT. Copyright © 2016 Elsevier Inc. All rights reserved.

Determinants of the use of alternatives to arsenic-contaminated shallow groundwater: an exploratory study in rural West Bengal, India.

PubMed

Delaire, Caroline; Das, Abhijit; Amrose, Susan; Gadgil, Ashok; Roy, Joyashree; Ray, Isha

2017-10-01

Shallow groundwater containing toxic concentrations of arsenic is the primary source of drinking water for millions of households in rural West Bengal, India. Often, this water also contains unpleasant levels of iron and non-negligible fecal contamination. Alternatives to shallow groundwater are increasingly available, including government-built deep tubewells, water purchased from independent providers, municipal piped water, and household filters. We conducted a survey of 501 households in Murshidabad district in 2014 to explore what influenced the use of available alternatives. Socioeconomic status and the perceived likelihood of gastrointestinal (GI) illness (which was associated with dissatisfaction with iron in groundwater) were the primary determinants of the use of alternatives. Arsenic knowledge was limited. The choice amongst alternatives was influenced by economic, social, and aesthetic factors, but not by health risk perceptions. The use of purchased water was rarely exclusive and was strongly associated with socioeconomic status, suggesting that this form of market-based water provision does not ensure universal access. Demand for purchased water appeared to decrease significantly shortly after free piped water became available at public taps. Our results suggest that arsenic mitigation interventions that also address co-occurring water problems (iron, GI illness) could be more effective than a focus on arsenic alone.

IRON AND FREE RADICAL OXIDATIONS IN CELL MEMBRANES

PubMed Central

Schafer, Freya Q.; Yue Qian, Steven; Buettner, Garry R.

2013-01-01

Brain tissue being rich in polyunsaturated fatty acids, is very susceptible to lipid peroxidation. Iron is well known to be an important initiator of free radical oxidations. We propose that the principal route to iron-mediated lipid peroxidations is via iron-oxygen complexes rather than the reaction of iron with hydrogen peroxide, the Fenton reaction. To test this hypothesis, we enriched leukemia cells (K-562 and L1210 cells) with docosahexaenoic acid (DHA) as a model for brain tissue, increasing the amount of DHA from approximately 3 mole % to 32 mole %. These cells were then subjected to ferrous iron and dioxygen to initiate lipid peroxidation in the presence or absence of hydrogen peroxide. Lipid-derived radicals were detected using EPR spin trapping with α-(4-pyridyl-1-oxide)-N-t-butylnitrone (POBN). As expected, lipid-derived radical formation increases with increasing cellular lipid unsaturation. Experiments with Desferal demonstrate that iron is required for the formation of lipid radicals from these cells. Addition of iron to DHA-enriched L1210 cells resulted in significant amounts of radical formation; radical formation increased with increasing amount of iron. However, the exposure of cells to hydrogen peroxide before the addition of ferrous iron did not increase cellular radical formation, but actually decreased spin adduct formation. These data suggest that iron-oxygen complexes are the primary route to the initiation of biological free radical oxidations. This model proposes a mechanism to explain how catalytic iron in brain tissue can be so destructive. PMID:10872752

Secoisolariciresinol Diglucoside Abrogates Oxidative Stress-Induced Damage in Cardiac Iron Overload Condition

PubMed Central

Puukila, Stephanie; Bryan, Sean; Laakso, Anna; Abdel-Malak, Jessica; Gurney, Carli; Agostino, Adrian; Belló-Klein, Adriane; Prasad, Kailash; Khaper, Neelam

2015-01-01

Cardiac iron overload is directly associated with cardiac dysfunction and can ultimately lead to heart failure. This study examined the effect of secoisolariciresinol diglucoside (SDG), a component of flaxseed, on iron overload induced cardiac damage by evaluating oxidative stress, inflammation and apoptosis in H9c2 cardiomyocytes. Cells were incubated with 50 μ5M iron for 24 hours and/or a 24 hour pre-treatment of 500 μ M SDG. Cardiac iron overload resulted in increased oxidative stress and gene expression of the inflammatory mediators tumor necrosis factor-α, interleukin-10 and interferon γ, as well as matrix metalloproteinases-2 and -9. Increased apoptosis was evident by increased active caspase 3/7 activity and increased protein expression of Forkhead box O3a, caspase 3 and Bax. Cardiac iron overload also resulted in increased protein expression of p70S6 Kinase 1 and decreased expression of AMP-activated protein kinase. Pre-treatment with SDG abrogated the iron-induced increases in oxidative stress, inflammation and apoptosis, as well as the increased p70S6 Kinase 1 and decreased AMP-activated protein kinase expression. The decrease in superoxide dismutase activity by iron treatment was prevented by pre-treatment with SDG in the presence of iron. Based on these findings we conclude that SDG was cytoprotective in an in vitro model of iron overload induced redox-inflammatory damage, suggesting a novel potential role for SDG in cardiac iron overload. PMID:25822525

Secoisolariciresinol diglucoside abrogates oxidative stress-induced damage in cardiac iron overload condition.

PubMed

Puukila, Stephanie; Bryan, Sean; Laakso, Anna; Abdel-Malak, Jessica; Gurney, Carli; Agostino, Adrian; Belló-Klein, Adriane; Prasad, Kailash; Khaper, Neelam

2015-01-01

Cardiac iron overload is directly associated with cardiac dysfunction and can ultimately lead to heart failure. This study examined the effect of secoisolariciresinol diglucoside (SDG), a component of flaxseed, on iron overload induced cardiac damage by evaluating oxidative stress, inflammation and apoptosis in H9c2 cardiomyocytes. Cells were incubated with 50 μ5M iron for 24 hours and/or a 24 hour pre-treatment of 500 μ M SDG. Cardiac iron overload resulted in increased oxidative stress and gene expression of the inflammatory mediators tumor necrosis factor-α, interleukin-10 and interferon γ, as well as matrix metalloproteinases-2 and -9. Increased apoptosis was evident by increased active caspase 3/7 activity and increased protein expression of Forkhead box O3a, caspase 3 and Bax. Cardiac iron overload also resulted in increased protein expression of p70S6 Kinase 1 and decreased expression of AMP-activated protein kinase. Pre-treatment with SDG abrogated the iron-induced increases in oxidative stress, inflammation and apoptosis, as well as the increased p70S6 Kinase 1 and decreased AMP-activated protein kinase expression. The decrease in superoxide dismutase activity by iron treatment was prevented by pre-treatment with SDG in the presence of iron. Based on these findings we conclude that SDG was cytoprotective in an in vitro model of iron overload induced redox-inflammatory damage, suggesting a novel potential role for SDG in cardiac iron overload.

Improving iron absorption from a Peruvian school breakfast meal by adding ascorbic acid or Na2EDTA.

PubMed

Davidsson, L; Walczyk, T; Zavaleta, N; Hurrell, R

2001-02-01

Iron-fortified school breakfasts have been introduced in Peru to combat childhood iron deficiency. We evaluated whether iron absorption from a school breakfast meal was improved by increasing the ascorbic acid content or by adding an alternative enhancer of iron absorption, Na2EDTA. In a crossover design, iron absorption from test meals was evaluated by erythrocyte incorporation of 58Fe and 57Fe. The test meals (wheat bread and a drink containing cereal, milk, and soy) contained 14 mg added Fe (as ferrous sulfate) including 2.0-2.6 mg 58Fe or 4.0-7.0 mg 57Fe. Geometric mean iron absorption increased significantly from 5.1% to 8.2% after the molar ratio of ascorbic acid to fortification iron was increased from 0.6:1 to 1.6:1 (P < 0.01; n = 9). Geometric mean iron absorption increased significantly from 2.9% to 3.8%, from 2.2% to 3.5%, and from 2.4% to 3.7% after addition of Na2EDTA at molar ratios relative to fortification iron of 0.3:1, 0.7:1, and 1:1, respectively, compared with test meals containing no added enhancers (P < 0.01; n = 10 for all). Iron absorption after addition of ascorbic acid (molar ratio 0.6:1) was not significantly different from that after addition of Na2EDTA (molar ratio 0.7:1). Ascorbic acid and Na2EDTA did not differ significantly in their enhancing effects on iron absorption at molar ratios of 0.6:1 to 0.7:1 relative to fortification iron. Additional ascorbic acid (molar ratio 1.6:1) increased iron absorption significantly. Increasing the molar ratio of Na2EDTA to fortification iron from 0.3:1 to 1:1 had no effect on iron absorption.

Iron storage disease (hemochromatosis) and hepcidin response to iron load in two species of pteropodid fruit bats relative to the common vampire bat.

PubMed

Stasiak, Iga M; Smith, Dale A; Ganz, Tomas; Crawshaw, Graham J; Hammermueller, Jutta D; Bienzle, Dorothee; Lillie, Brandon N

2018-07-01

Hepcidin is the key regulator of iron homeostasis in the body. Iron storage disease (hemochromatosis) is a frequent cause of liver disease and mortality in captive Egyptian fruit bats (Rousettus aegyptiacus), but reasons underlying this condition are unknown. Hereditary hemochromatosis in humans is due to deficiency of hepcidin or resistance to the action of hepcidin. Here, we investigated the role of hepcidin in iron metabolism in one species of pteropodid bat that is prone to iron storage disease [Egyptian fruit bat (with and without hemochromatosis)], one species of pteropodid bat where iron storage disease is rare [straw-colored fruit bat (Eidolon helvum)], and one species of bat with a natural diet very high in iron, in which iron storage disease is not reported [common vampire bat (Desmodus rotundus)]. Iron challenge via intramuscular injection of iron dextran resulted in significantly increased liver iron content and histologic iron scores in all three species, and increased plasma iron in Egyptian fruit bats and straw-colored fruit bats. Hepcidin mRNA expression increased in response to iron administration in healthy Egyptian fruit bats and common vampire bats, but not in straw-colored fruit bats or Egyptian fruit bats with hemochromatosis. Hepcidin gene expression significantly correlated with liver iron content in Egyptian fruit bats and common vampire bats, and with transferrin saturation and plasma ferritin concentration in Egyptian fruit bats. Induction of hepcidin gene expression in response to iron challenge is absent in straw-colored fruit bats and in Egyptian fruit bats with hemochromatosis and, relative to common vampire bats and healthy humans, is low in Egyptain fruit bats without hemochromatosis. Limited hepcidin response to iron challenge may contribute to the increased susceptibility of Egyptian fruit bats to iron storage disease.

Effects of oral iron(III) hydroxide polymaltose complex supplementation on hemoglobin increase, cognitive function, affective behavior and scholastic performance of adolescents with varying iron status: a single centre prospective placebo controlled study.

PubMed

Devaki, Pallaki Baby; Chandra, Ranjit K; Geisser, Peter

2009-01-01

To assess the effects of iron supplementation on iron status, cognitive function, affective behavior and scholastic performance in adolescents with varying iron status. Adolescents of both sexes with varying iron status were allocated to four treatment groups by using inclusion criteria. Three of the four groups (iron deficient anemic, iron deficient and control supplement) received iron(III) hydroxide polymaltose complex (IPC, Maltofer) containing 100 mg of elemental iron 6 days a week for 8 months, while the fourth group (control placebo) was given a placebo. Hematological parameters, cognitive function, affective behavior and scholastic performance were assessed at baseline, 4 months and 8 months of supplementation. Cognitive and scholastic performance test scores for the three supplemented groups increased from baseline to 4 months and from 4 months to 8 months (with concomitant increases in hematological parameters), whereas no increase was observed in the placebo group. No increase was seen in affective behavior scores for any of the groups during or after supplementation. IPC supplementation for eight months yielded significant improvements in cognitive function and scholastic performance in Indian adolescents with and without iron deficiency and anemia.

Serum ceruloplasmin protein expression and activity increases in iron-deficient rats and is further enhanced by higher dietary copper intake

PubMed Central

Ranganathan, Perungavur N.; Lu, Yan; Jiang, Lingli; Kim, Changae

2011-01-01

Increases in serum and liver copper content are noted during iron deficiency in mammals, suggesting that copper-dependent processes participate during iron deprivation. One point of intersection between the 2 metals is the liver-derived, multicopper ferroxidase ceruloplasmin (Cp) that is important for iron release from certain tissues. The current study sought to explore Cp expression and activity during physiologic states in which hepatic copper loading occurs (eg, iron deficiency). Weanling rats were fed control or low iron diets containing low, normal, or high copper for ∼ 5 weeks, and parameters of iron homeostasis were measured. Liver copper increased in control and iron-deficient rats fed extra copper. Hepatic Cp mRNA levels did not change; however, serum Cp protein was higher during iron deprivation and with higher copper consumption. In-gel and spectrophotometric ferroxidase and amine oxidase assays demonstrated that Cp activity was enhanced when hepatic copper loading occurred. Interestingly, liver copper levels strongly correlated with Cp protein expression and activity. These observations support the possibility that liver copper loading increases metallation of the Cp protein, leading to increased production of the holo enzyme. Moreover, this phenomenon may play an important role in the compensatory response to maintain iron homeostasis during iron deficiency. PMID:21768302

Importance of pre-pregnancy and pregnancy iron status: can long-term weekly preventive iron and folic acid supplementation achieve desirable and safe status?

PubMed

Viteri, Fernando E; Berger, Jacques

2005-12-01

Most women worldwide enter pregnancy without adequate iron reserves or are already iron deficient. Estimates of iron needs during pregnancy are markedly reduced when iron reserves are available. The needs of absorbed iron to correct mild to moderate anemia in the last two trimesters are estimated. Pre-pregnancy and prenatal weekly supplementation can improve iron reserves effectively and safely, preventing excess iron and favoring better pregnancy outcomes. We explain how the weekly supplementation idea was developed, why current hemoglobin norms may be inadequately high (especially in pregnancy), and why excess iron as recommended by many agencies for developing populations can be undesirable.

Transitioning Patients With Iron Overload From Exjade to Jadenu.

PubMed

Tinsley, Sara M; Hoehner-Cooper, Christine M

Iron overload is a concern for patients who require chronic transfusions as a result of inherited or acquired anemias, including sickle cell disease, thalassemia, and myelodysplastic syndromes. Iron chelation therapy (ICT) is the primary treatment for iron overload in these patients. The ICT deferasirox, which has been available as an oral dispersible tablet for liquid suspension, is now also available as a once-daily, film-coated tablet (FCT). Deferasirox FCT allows greater convenience and may be associated with fewer gastrointestinal side effects versus the original formulation. Dose adjustment increments, determined by titration monitoring, are lower for the FCT because of greater bioavailability.

Enhanced labile plasma iron and outcome in acute myeloid leukaemia and myelodysplastic syndrome after allogeneic haemopoietic cell transplantation (ALLIVE): a prospective, multicentre, observational trial.

PubMed

Wermke, Martin; Eckoldt, Julia; Götze, Katharina S; Klein, Stefan A; Bug, Gesine; de Wreede, Liesbeth C; Kramer, Michael; Stölzel, Friedrich; von Bonin, Malte; Schetelig, Johannes; Laniado, Michael; Plodeck, Verena; Hofmann, Wolf-Karsten; Ehninger, Gerhard; Bornhäuser, Martin; Wolf, Dominik; Theurl, Igor; Platzbecker, Uwe

2018-05-01

The effect of systemic iron overload on outcomes after allogeneic haemopoietic cell transplantation (HCT) has been a matter of substantial debate. We aimed to investigate the predictive value of both stored (MRI-derived liver iron content) and biologically active iron (enhanced labile plasma iron; eLPI) on post-transplantation outcomes in patients with acute myeloid leukaemia or myelodysplastic syndrome undergoing allogenic HCT. The prospective, multicentre, observational, ALLogeneic Iron inVEstigators (ALLIVE) trial recruited patients at five centres in Germany. We enrolled patients with acute myeloid leukaemia or myelodysplastic syndrome undergoing allogeneic HCT. Patients underwent cytotoxic conditioning for a median of 6 days (IQR 6-7) before undergoing allogeneic HCT and were followed up for up to 1 year (±3 months) post-transplantation. eLPI was measured in serum samples with the FeROS eLPI kit (Aferrix, Tel-Aviv, Israel) and values greater than 0·4 μmol/L were considered to represent raised eLPI. Liver iron content was measured by MRI. The primary endpoints were the quantitative delineation of eLPI dynamics during allogeneic HCT and the correlation coefficient between liver iron content before HCT and dynamic eLPI (eLPI dyn ; maximum eLPI minus baseline eLPI). All patients with available data were included in all analyses. This is the final analysis of this completed trial, which is registered with ClinicalTrials.gov, number NCT01746147. Between Dec 13, 2012, and Dec 23, 2014, 112 patients underwent allogeneic HCT. Liver iron content before allogeneic HCT was not significantly correlated with eLPI dyn (ρ=0·116, p=0·22). Serum eLPI concentrations rapidly increased during conditioning, and most (79 [73%] of 108) patients had raised eLPI by the day of transplantation. Patients with a pretransplant liver iron content greater than or equal to 125 μmol/g had an increased incidence of non-relapse mortality (20%, 95% CI 14-26) compared with those with lower concentrations (7%, 2-12; p=0·039) at day 100. Patients who had raised eLPI at baseline also had a significantly increased incidence of non-relapse mortality at day 100 (33%, 15-52) compared with those who had normal eLPI at baseline (7%, 2-13; p=0·00034). eLPI is a possible biological mediator of iron-related toxicity. Peritransplantation eLPI-scavenging strategies could be explored in prospective interventional clinical trials for patients with systemic iron overload. The Technical University of Dresden and Novartis. Copyright © 2018 Elsevier Ltd. All rights reserved.

Increased Renal Iron Accumulation in Hypertensive Nephropathy of Salt-Loaded Hypertensive Rats

PubMed Central

Naito, Yoshiro; Sawada, Hisashi; Oboshi, Makiko; Fujii, Aya; Hirotani, Shinichi; Iwasaku, Toshihiro; Okuhara, Yoshitaka; Eguchi, Akiyo; Morisawa, Daisuke; Ohyanagi, Mitsumasa; Tsujino, Takeshi; Masuyama, Tohru

2013-01-01

Although iron is reported to be associated with the pathogenesis of chronic kidney disease, it is unknown whether iron participates in the pathophysiology of nephrosclerosis. Here, we investigate whether iron is involved in the development of hypertensive nephropathy and the effects of iron restriction on nephrosclerosis in salt- loaded stroke-prone spontaneously hypertensive rats (SHRSP). SHRSP were given either a normal or high-salt diet for 8 weeks. Another subset of SHRSP were fed a high-salt with iron-restricted diet. SHRSP given a high-salt diet developed severe hypertension and nephrosclerosis. As a result, survival rate was decreased after 8 weeks diet. Importantly, massive iron accumulation and increased iron content were observed in the kidneys of salt-loaded SHRSP, along with increased superoxide production, urinary 8-Hydroxy-2′-deoxyguanosine excretion, and urinary iron excretion; however, these changes were markedly attenuated by iron restriction. Of interest, expression of cellular iron transport proteins, transferrin receptor 1 and divalent metal transporter 1, was increased in the tubules of salt-loaded SHRSP. Notably, iron restriction attenuated the development of severe hypertension and nephrosclerosis, thereby improving survival rate in salt-loaded SHRSP. Taken together, these results suggest a novel mechanism by which iron plays a role in the development of hypertensive nephropathy and establish the effects of iron restriction on salt-induced nephrosclerosis. PMID:24116080

China's emergence as the world's leading iron-ore-consuming country

USGS Publications Warehouse

Kirk, W.S.

2004-01-01

China has become the leading iron ore consuming nation, and, based on recent steel production capacity increases and plans for more, its consumption will almost certainly to continue to grow. China's iron ore industry, however, faces a number of problems. China's iron ore is low-grade, expensive to process, and its mines are being depleted. For many Chinese steelmakers, particularly in the coastal regions, the delivered cost of domestic iron ore, is more than the delivered cost of foreign ore. Thus China's iron ore imports are expected to increase. As China's growth continues, it will almost certainly surpass Japan to become the leading iron ore importing country as well. Without China's increasing appetite for iron ore, the world iron ore market would be flat or declining. China's recent imports largely offset the slump in demand in North America and Europe. China is regarded by the iron ore industry as the growth sector for the next decade. Although Chinese imports are expected to continue their rapid increase and imports in other Asian countries are expected to continue growing, there appears to be enough greenfield and expansion projects to meet future demand for iron ore worldwide. Present suppliers of iron ore, Australia, Brazil, India, and South Africa, will probably be the chief beneficiaries of China's increasing consumption of iron ore. How long China can continue its extraordinary growth is the primary issue for the future of the iron ore industry. Based on the number and size of planned blast furnaces it appears that China's growth could continue for several more years. ?? 2004 Taylor and Francis.

H+ -pyrophosphatase IbVP1 promotes efficient iron use in sweet potato [Ipomoea batatas (L.) Lam.].

PubMed

Fan, Weijuan; Wang, Hongxia; Wu, Yinliang; Yang, Nan; Yang, Jun; Zhang, Peng

2017-06-01

Iron (Fe) deficiency is one of the most common micronutrient deficiencies limiting crop production globally, especially in arid regions because of decreased availability of iron in alkaline soils. Sweet potato [Ipomoea batatas (L.) Lam.] grows well in arid regions and is tolerant to Fe deficiency. Here, we report that the transcription of type I H + -pyrophosphatase (H + -PPase) gene IbVP1 in sweet potato plants was strongly induced by Fe deficiency and auxin in hydroponics, improving Fe acquisition via increased rhizosphere acidification and auxin regulation. When overexpressed, transgenic plants show higher pyrophosphate hydrolysis and plasma membrane H + -ATPase activity compared with the wild type, leading to increased rhizosphere acidification. The IbVP1-overexpressing plants showed better growth, including enlarged root systems, under Fe-sufficient or Fe-deficient conditions. Increased ferric precipitation and ferric chelate reductase activity in the roots of transgenic lines indicate improved iron uptake, which is also confirmed by increased Fe content and up-regulation of Fe uptake genes, e.g. FRO2, IRT1 and FIT. Carbohydrate metabolism is significantly affected in the transgenic lines, showing increased sugar and starch content associated with the increased expression of AGPase and SUT1 genes and the decrease in β-amylase gene expression. Improved antioxidant capacities were also detected in the transgenic plants, which showed reduced H 2 O 2 accumulation associated with up-regulated ROS-scavenging activity. Therefore, H + -PPase plays a key role in the response to Fe deficiency by sweet potato and effectively improves the Fe acquisition by overexpressing IbVP1 in crops cultivated in micronutrient-deficient soils. © 2016 The Authors. Plant Biotechnology Journal published by Society for Experimental Biology and The Association of Applied Biologists and John Wiley & Sons Ltd.

Determination of Iron in Water. Training Module 5.210.2.77.

ERIC Educational Resources Information Center

Bonte, John L.; Davidson, Arnold C.

This document is an instructional module package prepared in objective form for use by an instructor familiar with the spectrophotometric analysis of total iron, filtrable iron and ferrous iron in a water supply. Included are objectives, an instructor guide, student handouts, and transparency masters. A video tape is also available from the…

Iron Deficiency in Autism and Asperger Syndrome.

ERIC Educational Resources Information Center

Latif, A.; Heinz, P.; Cook, R.

2002-01-01

Retrospective analysis of the full blood count and, when available, serum ferritin measurements of 96 children (52 with autism and 44 with Asperger syndrome) found six autistic children had iron deficiency and 12 of the 23 autistic children with serum ferritin measures were iron deficient. Far fewer Asperger children were iron deficient. Results…

Factors influencing lead and iron release from some Egyptian drinking water pipes.

PubMed

Lasheen, M R; Sharaby, C M; El-Kholy, N G; Elsherif, I Y; El-Wakeel, S T

2008-12-30

The major objective of this study is to assess the effect of stagnation time, pipe age, pipes material and water quality parameters such as pH, alkalinity and chloride to sulfate mass ratio on lead and iron release from different types of water pipes used in Egypt namely polyvinyl chloride (PVC), polypropylene (PP) and galvanized iron (GI), by using fill and dump method. Low pH increased lead and iron release from pipes. Lead and iron release decreased as pH and alkalinity increased. Lead and iron release increased with increasing chloride to sulfate mass ratio in all pipes. EDTA was used as an example of natural organic matter which may be influence metals release. It is found that lead and iron release increased then this release decreased with time. In general, GI pipes showed to be the most effected by water quality parameters tested and the highest iron release. PVC pipes are the most lead releasing pipes while PP pipes are the least releasing.

Review: The Potential of the Common Bean (Phaseolus vulgaris) as a Vehicle for Iron Biofortification

PubMed Central

Petry, Nicolai; Boy, Erick; Wirth, James P.; Hurrell, Richard F.

2015-01-01

Common beans are a staple food and the major source of iron for populations in Eastern Africa and Latin America. Bean iron concentration is high and can be further increased by biofortification. A major constraint to bean iron biofortification is low iron absorption, attributed to inhibitory compounds such as phytic acid (PA) and polyphenol(s) (PP). We have evaluated the usefulness of the common bean as a vehicle for iron biofortification. High iron concentrations and wide genetic variability have enabled plant breeders to develop high iron bean varieties (up to 10 mg/100 g). PA concentrations in beans are high and tend to increase with iron biofortification. Short-term human isotope studies indicate that iron absorption from beans is low, PA is the major inhibitor, and bean PP play a minor role. Multiple composite meal studies indicate that decreasing the PA level in the biofortified varieties substantially increases iron absorption. Fractional iron absorption from composite meals was 4%–7% in iron deficient women; thus the consumption of 100 g biofortified beans/day would provide about 30%–50% of their daily iron requirement. Beans are a good vehicle for iron biofortification, and regular high consumption would be expected to help combat iron deficiency (ID). PMID:25679229

Characteristics of the Freshwater Cyanobacterium Microcystis aeruginosa Grown in Iron-Limited Continuous Culture

PubMed Central

Dang, T. C.; Fujii, M.; Rose, A. L.; Bligh, M.

2012-01-01

A continuous culturing system (chemostat) made of metal-free materials was successfully developed and used to maintain Fe-limited cultures of Microcystis aeruginosa PCC7806 at nanomolar iron (Fe) concentrations (20 to 50 nM total Fe). EDTA was used to maintain Fe in solution, with bioavailable Fe controlled by absorption of light by the ferric EDTA complex and resultant reduction of Fe(III) to Fe(II). A kinetic model describing Fe transformations and biological uptake was applied to determine the biologically available form of Fe (i.e., unchelated ferrous iron) that is produced by photoreductive dissociation of the ferric EDTA complex. Prediction by chemostat theory modified to account for the light-mediated formation of bioavailable Fe rather than total Fe was in good agreement with growth characteristics of M. aeruginosa under Fe limitation. The cellular Fe quota increased with increasing dilution rates in a manner consistent with the Droop theory. Short-term Fe uptake assays using cells maintained at steady state indicated that M. aeruginosa cells vary their maximum Fe uptake rate (ρmax) depending on the degree of Fe stress. The rate of Fe uptake was lower for cells grown under conditions of lower Fe availability (i.e., lower dilution rate), suggesting that cells in the continuous cultures adjusted to Fe limitation by decreasing ρmax while maintaining a constant affinity for Fe. PMID:22210212

Oxygen- and NssR-dependent Globin Expression and Enhanced Iron Acquisition in the Response of Campylobacter to Nitrosative Stress*S⃞

PubMed Central

Monk, Claire E.; Pearson, Bruce M.; Mulholland, Francis; Smith, Holly K.; Poole, Robert K.

2008-01-01

Pathogenic bacteria experience nitrosative stress from NO generated in the host and from nitrosating species such as S-nitrosoglutathione. The food-borne pathogen Campylobacter jejuni responds by activating gene expression from a small regulon under the control of the NO-sensitive regulator, NssR. Here, we describe the full extent of the S-nitrosoglutathione response using transcriptomic and proteomic analysis of batch- and chemostat-cultured C. jejuni. In addition to the NssR regulon, which includes two hemoglobins (Cgb and Ctb), we identify more than 90 other up-regulated genes, notably those encoding heat shock proteins and proteins involved in oxidative stress tolerance and iron metabolism/transport. Up-regulation of a subset of these genes, including cgb, is also elicited by NO-releasing compounds. Mutation of the iron-responsive regulator Fur results in insensitivity of growth to NO, suggesting that derepression of iron-regulated genes and augmentation of iron acquisition is a physiological response to nitrosative damage. We describe the effect of oxygen availability on nitrosative stress tolerance; cells cultured at higher rates of oxygen diffusion have elevated levels of hemoglobins, are more resistant to inhibition by NO of both growth and respiration, and consume NO more rapidly. The oxygen response is mediated by NssR. Thus, in addition to NO detoxification catalyzed by the hemoglobins Cgb and possibly Ctb, C. jejuni mounts an extensive stress response. We suggest that inhibition of respiration by NO may increase availability of oxygen for Cgb synthesis and function. PMID:18682395

Organic iron (III) complexing ligands during an iron enrichment experiment in the western subarctic North Pacific

NASA Astrophysics Data System (ADS)

Kondo, Yoshiko; Takeda, Shigenobu; Nishioka, Jun; Obata, Hajime; Furuya, Ken; Johnson, William Keith; Wong, C. S.

2008-06-01

Complexation of iron (III) with natural organic ligands was investigated during a mesoscale iron enrichment experiment in the western subarctic North Pacific (SEEDS II). After the iron infusions, ligand concentrations increased rapidly with subsequent decreases. While the increases of ligands might have been partly influenced by amorphous iron colloids formation (12-29%), most in-situ increases were attributable to the <200 kDa fraction. Dilution of the fertilized patch may have contributed to the rapid decreases of the ligands. During the bloom decline, ligand concentration increased again, and the high concentrations persisted for 10 days. The conditional stability constant was not different between inside and outside of the fertilized patch. These results suggest that the chemical speciation of the released iron was strongly affected by formation of the ligands; the production of ligands observed during the bloom decline will strongly impact the iron cycle and bioavailability in the surface water.

Heterogeneity in horse ferritins. A comparative study of surface charge, iron content and kinetics of iron uptake.

PubMed Central

Russell, S M; Harrison, P M

1978-01-01

Horse ferritins from different organs show heterogeneity on electrofocusing in Ampholine gradients. Both ferritin and apoferritin from liver and spleen could be fractionated with respect to surface charge by serial precipitation with (NH4)2SO4. In the ferritin fractions, increasing iron content parallels increasing isoelectric point. After removal of their iron, those fractions which originally contained most iron accumulated added iron at the fastest rates. When unfractionated ferritins from different organs were compared the average isoelectric point increased in order spleen less than liver less than kidney less than heart. The order of initial rates of iron uptake by the apoferritins was spleen greater than kidney greater than heart and initial average iron contents also followed this order. The relatively low rates of iron accumulation by iron-poor molecules may have been due to structural alteration, to degradation, to activation of the iron-rich molecules or to other factors. Images Fig. 1. Fig. 2. PMID:736908

Cosmic meteor dust: potentially the dominant source of bio-available iron in the Southern Ocean

NASA Astrophysics Data System (ADS)

Dyrud, L. P.; Marsh, D. R.; Del Castillo, C. E.; Fentzke, J.; Lopez-Rosado, R.; Behrenfeld, M.

2012-12-01

Johnson, 2001 [Johnson, Kenneth. S. (2001), Iron supply and demand in the upper ocean: Is extraterrestrial dust a significant source of bioavailable iron?, Global Biogeochem. Cycles, 15(1), 61-63, doi:10.1029/2000GB001295], first suggested that meteoric particulate flux could be a significant source of bio-available iron, particularly in regions with little or no eolean sources, such as the Southern Ocean. While these calculations raised intriguing questions, there were many large unknowns in the input calculations between meteor flux and bio-available ocean molecular densities. There has been significant research in the intervening decade on related topics, such as the magnitude (~200 ktons per year) and composition of the meteoric flux, its atmospheric evaporation, transport, mesospheric formation of potentially soluble meteoric smoke, and extraterrestrial iron isotope identification. Paramount of these findings are recent NCAR WACCM atmosphere model results demonstrating that the majority of meteoric constituents are transported towards the winter poles and the polar vortex. This may lead to a focusing of meteoritic iron deposition towards the Southern Ocean. We present a proposed research plan involving Southern Ocean sample collection and analysis and atmospheric and biological modeling to determine both the current relevance of meteoric iron, and examine the past and future consequences of cosmic dust under a changing climate.

Simultaneous addition of zero-valent iron and activated carbon on enhanced mesophilic anaerobic digestion of waste-activated sludge.

PubMed

Wang, Tongyu; Qin, Yujie; Cao, Yan; Han, Bin; Ren, Junyi

2017-10-01

The performance of biogas generation and sludge degradation was studied under different zero-valent iron/activated carbon (ZVI/AC) ratios in detail in mesophilic anaerobic digestion of sludge. A good enhancement of methane production was obtained at the 10:1 ZVI/AC ratio, and the cumulative methane production was 132.1 mL/g VS, 37.6% higher than the blank. The methane content at the 10:1 ZVI/AC ratio reached 68.8%, which was higher than the blank (55.2%) and the sludge-added AC alone (59.6%). For sludge degradation, the removal efficiencies of total chemical oxygen demand (TCOD), proteins, and polysaccharides were all the highest at the 10:1 ZVI/AC ratio. The concentration of available phosphorus (AP) decreased after anaerobic digestion process. On the other hand, the concentrations of available nitrogen (AN) and available potassium (AK) increased after the anaerobic digestion process and showed a gradually decreasing trend with increasing ZVI/AC ratio. The concentrations of AN and AK were 2303.1-4200.3 and 274.7-388.3 mg/kg, showing a potential for land utilization.

Influence of iron precipitated condition and light intensity on microalgae activated sludge based wastewater remediation.

PubMed

Anbalagan, Anbarasan; Schwede, Sebastian; Lindberg, Carl-Fredrik; Nehrenheim, Emma

2017-02-01

The indigenous microalgae-activated sludge (MAAS) process during remediation of municipal wastewater was investigated by studying the influence of iron flocculation step and light intensity. In addition, availability of total phosphorous (P) and photosynthetic activity was examined in fed-batch and batch mode under northern climatic conditions and limited lighting. This was followed by a semi-continuous operation with 4 d of hydraulic retention time and mean cell residence time of 6.75 d in a photo-bioreactor (PBR) with varying P availability. The fed-batch condition showed that P concentrations of 3-4 mg L -1 were effective for photosynthetic chl. a development in iron flocculated conditions. In the PBR, the oxygen evolution rate increased with increase in the concentration of MAAS (from 258 to 573 mg TSS L -1 ) at higher surface photosynthetic active radiation (250 and 500 μmol m -2 s -1 ). Additionally, the rate approached a saturation phase at low MAAS (110 mg L -1 ) with higher light intensities. Semi-continuous operation with luxury P uptake and effective P condition showed stable average total nitrogen removal of 88 and 92% respectively, with residual concentrations of 3.77 and 2.21 mg L -1 . The corresponding average P removal was 68 and 59% with residual concentrations of 2.32 and 1.75 mg L -1 . The semi-continuous operation produced a rapidly settleable MAAS under iron flocculated condition with a settling velocity of 92-106 m h -1 and sludge volume index of 31-43 ml g -1 in the studied cases. Copyright © 2016 Elsevier Ltd. All rights reserved.

Diagnosis and management of transfusion iron overload: The role of imaging

PubMed Central

Wood, John C.

2010-01-01

The characterization of iron stores is important to prevent and treat iron overload. Serum markers such as ferritin, serum iron, iron binding capacity, transferrin saturation, and nontransferrin-bound iron can be used to follow trends in iron status; however, variability in these markers limits predictive power for any given individual. Liver iron represents the best single marker of total iron balance. Measures of liver iron include biopsy, superconducting quantum interference device, computer tomography, and magnetic resonance imaging (MRI). MRI is the most accurate and widely available noninvasive tool to assess liver iron. The main advantages of MRI include a low-rate of variability between measurements and the ability to assess iron loading in endocrine tissues, the heart and the liver. This manuscript describes the principles, validation, and clinical utility of MRI for tissue iron estimation. PMID:17963249

A comparative gene expression analysis of iron-limited cultures of Chaetoceros socialis and Pseudo-nitzschia arenysensis using newly developed iron assays

NASA Astrophysics Data System (ADS)

Abdala, Z. M.; Powell, K.; Cronin, D.; Chappell, D.

2016-02-01

A comparative gene expression analysis of iron-limited cultures of Chaetoceros socialis and Pseudo-nitzschia arenysensisusing newly developed iron assays Zuzanna M. Abdala, Kimberly Powell, Dylan P. Cronin, P. Dreux Chappell Diatoms, accounting for about 40% of the primary production in marine ecosystems, play a vital role in the dynamics of marine systems. Iron availability is understood to be a driving factor controlling productivity of many marine phytoplankton, including diatoms, as it functions as a cofactor for many proteins including several involved with photosynthetic processes. Previous work examining transcriptomes of diatoms of the Thalassiosira genus grown in controlled laboratory settings has identified genes whose expression can be used as sensitive markers of iron status. Data mining publically available diatom transcriptome data for these genes enables development of additional iron status assays for environmentally-relevant diatoms. For the present study, gene expression analysis of iron-limited laboratory cultures of Chaetoceros socialis and Pseudo-nitzschia arenysensis grown in continuous light was done using quantitative reverse transcriptase polymerase chain reaction (qRT-PCR). C. socialis and P. arenysensis serve as comparative models for analyzing gene expression in iron limitation in different ecological community assemblages. These data may ultimately assist to illuminate the function of iron in photosynthetic activity in diatoms.

The essential role of coumarin secretion for Fe acquisition from alkaline soil

PubMed Central

Clemens, Stephan; Weber, Michael

2016-01-01

ABSTRACT Plant productivity is limited by the scarcity of the essential micronutrient iron particularly in alkaline soils. The root secretion of phenolics has long been recognized as a component of the acidification-reduction strategy to acquire iron (strategy I). However, very little molecular insight into this process was available until recently several research groups independently discovered the important role of coumarins for the growth of Arabidopsis thaliana under Fe-limited conditions. Genome-wide analyses of iron deficiency responses, mutant screening and metabolomics experiments all converged on the finding that the synthesis and root exudation of scopoletin, esculetin and other coumarins is essential for iron uptake from substrates with low iron availability. Here we describe the evidence supporting this conclusion and discuss important questions that now have to be addressed in order to better understand the mechanistic basis of coumarin-dependent iron uptake and its significance within the plant kingdom. PMID:26618918

TIMP3 deficiency exacerbates iron overload-mediated cardiomyopathy and liver disease.

PubMed

Zhabyeyev, Pavel; Das, Subhash K; Basu, Ratnadeep; Shen, Mengcheng; Patel, Vaibhav B; Kassiri, Zamaneh; Oudit, Gavin Y

2018-05-01

Chronic iron overload results in heart and liver diseases and is a common cause of morbidity and mortality in patients with genetic hemochromatosis and secondary iron overload. We investigated the role of tissue inhibitor of metalloproteinase 3 (TIMP3) in iron overload-mediated tissue injury by subjecting male mice lacking Timp3 ( Timp3 -/- ) and wild-type (WT) mice to 12 wk of chronic iron overload. Whereas WT mice with iron overload developed diastolic dysfunction, iron-overloaded Timp3 -/- mice showed worsened cardiac dysfunction coupled with systolic dysfunction. In the heart, loss of Timp3 was associated with increased myocardial fibrosis, greater Timp1, matrix metalloproteinase ( Mmp) 2, and Mmp9 expression, increased active MMP-2 levels, and gelatinase activity. Iron overload in Timp3 -/- mice showed twofold higher iron accumulation in the liver compared with WT mice because of constituently lower levels of ferroportin. Loss of Timp3 enhanced the hepatic inflammatory response to iron overload, leading to greater neutrophil and macrophage infiltration and increased hepatic fibrosis. Expression of inflammation-related MMPs (MMP-12 and MMP-13) and inflammatory cytokines (IL-1β and monocyte chemoattractant protein-1) was elevated to a greater extent in iron-overloaded Timp3 -/- livers. Gelatin zymography demonstrated equivalent increases in MMP-2 and MMP-9 levels in WT and Timp3 -/- iron-overloaded livers. Loss of Timp3 enhanced the susceptibility to iron overload-mediated heart and liver injury, suggesting that Timp3 is a key protective molecule against iron-mediated pathology. NEW & NOTEWORTHY In mice, loss of tissue inhibitor of metalloproteinase 3 ( Timp3) was associated with systolic and diastolic dysfunctions, twofold higher hepatic iron accumulation (attributable to constituently lower levels of ferroportin), and increased hepatic inflammation. Loss of Timp3 enhanced the susceptibility to iron overload-mediated injury, suggesting that Timp3 plays a key protective role against iron-mediated pathology.

Infant iron status affects iron absorption in Peruvian breastfed infants at 2 and 5 mo of age.

PubMed

Finkelstein, Julia L; O'Brien, Kimberly O; Abrams, Steven A; Zavaleta, Nelly

2013-12-01

Effects of prenatal iron supplementation on maternal postpartum iron status and early infant iron homeostasis remain largely unknown. We examined iron absorption and growth in exclusively breastfed infants in relation to fetal iron exposure and iron status during early infancy. Longitudinal, paired iron-absorption (⁵⁸Fe) studies were conducted in 59 exclusively breastfed Peruvian infants at 2-3 mo of age (2M) and 5-6 mo of age (5M). Infants were born to women who received ≥ 5100 or ≤ 1320 mg supplemental prenatal Fe. Iron status was assessed in mothers and infants at 2M and 5M. Infant iron absorption from breast milk averaged 7.1% and 13.9% at 2M and 5M. Maternal iron status (at 2M) predicted infant iron deficiency (ID) at 5M. Although no infants were iron deficient at 2M, 28.6% of infants had depleted iron stores (ferritin concentration <12 μg/L) by 5M. Infant serum ferritin decreased (P < 0.0001), serum transferrin receptor (sTfR) increased (P < 0.0001), and serum iron decreased from 2M to 5M (P < 0.01). Higher infant sTfR (P < 0.01) and breast-milk copper (P < 0.01) predicted increased iron absorption at 5M. Prenatal iron supplementation had no effects on infant iron status or breast-milk nutrient concentrations at 2M or 5M. However, fetal iron exposure predicted increased infant length at 2M (P < 0.01) and 5M (P < 0.05). Fetal iron exposure affected early infant growth but did not significantly improve iron status or absorption. Young, exclusively breastfed infants upregulated iron absorption when iron stores were depleted at both 2M and 5M.

Influence of physicochemical treatments on iron-based spent catalyst for catalytic oxidation of toluene.

PubMed

Kim, Sang Chai; Shim, Wang Geun

2008-06-15

The catalytic oxidation of toluene was studied over an iron-based spent and regenerated catalysts. Air, hydrogen, or four different acid solutions (oxalic acid (C2H2O4), citric acid (C6H8O7), acetic acid (CH3COOH), and nitric acid (HNO3)) were employed to regenerate the spent catalyst. The properties of pretreated spent catalyst were characterized by the Brunauer Emmett Teller (BET), inductively coupled plasma (ICP), temperature programmed reduction (TPR), and X-ray diffraction (XRD) analyses. The air pretreatment significantly enhanced the catalytic activity of the spent catalyst in the pretreatment temperature range of 200-400 degrees C, but its catalytic activity diminished at the pretreatment temperature of 600 degrees C. The catalytic activity sequence with respect to the air pretreatment temperatures was 400 degrees C>200 degrees C>parent>600 degrees C. The TPR results indicated that the catalytic activity was correlated with both the oxygen mobility and the amount of available oxygen on the catalyst. In contrast, the hydrogen pretreatment had a negative effect on the catalytic activity, and toluene conversion decreased with increasing pretreatment temperatures (200-600 degrees C). The XRD and TPR results confirmed the formation of metallic iron which had a negative effect on the catalytic activity with increasing pretreatment temperature. The acid pretreatment improved the catalytic activity of the spent catalyst. The catalytic activity sequence with respect to different acids pretreatment was found to be oxalic acid>citric acid>acetic acid>or=nitric acid>parent. The TPR results of acid pretreated samples showed an increased amount of available oxygen which gave a positive effect on the catalytic activity. Accordingly, air or acid pretreatments were more promising methods of regenerating the iron-based spent catalyst. In particular, the oxalic acid pretreatment was found to be most effective in the formation of FeC2O4 species which contributed highly to the catalytic combustion of toluene.

Yap5 Protein-regulated Transcription of the TYW1 Gene Protects Yeast from High Iron Toxicity*

PubMed Central

Li, Liangtao; Jia, Xuan; Ward, Diane M.; Kaplan, Jerry

2011-01-01

The budding yeast Saccharomyces cerevisiae responds to high cytosolic iron by inducing Yap5-mediated transcription. We identified genes regulated by Yap5 in response to iron and show that one of the genes induced is TYW1, which encodes an iron-sulfur cluster enzyme that participates in the synthesis of wybutosine-modified tRNA. Strains deleted for TYW1 do not show a phenotype in standard yeast medium. In contrast, overexpression of TYW1 results in decreased cell growth and induction of the iron regulon, leading to increased expression of the high affinity iron transporters. We identified a minimal domain of S. cerevisiae Tyw1 that is sufficient to induce the iron regulon. CCC1, a vacuolar iron importer, is a Yap5-regulated gene, and deletion of either CCC1 or YAP5 resulted in high iron sensitivity. Deletion of TYW1 in a Δccc1 strain led to increased iron sensitivity. The increased iron sensitivity of Δccc1Δtyw1 could be suppressed by overexpression of iron-sulfur cluster enzymes. We conclude that the Yap5-mediated induction of TYW1 provides protection from high iron toxicity by the consumption of free cytosolic iron through the formation of protein-bound iron-sulfur clusters. PMID:21917924

Association of Pro-Inflammatory Cytokines and Iron Regulatory Protein 2 (IRP2) with Leishmania Burden in Canine Visceral Leishmaniasis

PubMed Central

do Nascimento, Paulo Ricardo Porfírio; Martins, Daniella Regina Arantes; Monteiro, Glória Regina Góis; Queiroz, Paula Vivianne; Freire-Neto, Francisco Paulo; Queiroz, José Wilton; Morais Lima, Ádila Lorena; Jeronimo, Selma Maria Bezerra

2013-01-01

Leishmania infantum infection in humans and dogs can evolve with a wide range of clinical presentations, varying from asymptomatic infections to visceral leishmaniasis. We hypothesized that the immune response elicited by L. infantum infection could modulate whether the host will remain asymptomatic or progress to disease. A total of 44 dogs naturally infected with L. infantum were studied. Leishmania burden was estimated in the blood and spleen by qPCR. The expression of IFN-γ, TNF-α, IL-10 and Iron Regulatory Protein 2 (IRP2) were determined in the spleen by quantitative PCR. Sera cytokines were evaluated by ELISA. Dogs were grouped in quartiles according parasite burden. Increased expression of IFN-γ and TNF-α was associated with reduced Leishmania burden, whereas increased IL-10 and IRP2 expressions were associated with higher Leishmania load. Increased plasma albumin and IFN-γ expression explained 22.8% of the decrease in parasite burden in the spleen. These data confirm that lower IFN-γ response and higher IL-10 correlated with increased parasite load and severity of the visceral leishmaniasis in dogs. The balance between the branches of immune response and the intracellular iron availability could determine, in part, the course of Leishmania infection. PMID:24146743

NOD promoter-controlled AtIRT1 expression functions synergistically with NAS and FERRITIN genes to increase iron in rice grains.

PubMed

Boonyaves, Kulaporn; Gruissem, Wilhelm; Bhullar, Navreet K

2016-02-01

Rice is a staple food for over half of the world's population, but it contains only low amounts of bioavailable micronutrients for human nutrition. Consequently, micronutrient deficiency is a widespread health problem among people who depend primarily on rice as their staple food. Iron deficiency anemia is one of the most serious forms of malnutrition. Biofortification of rice grains for increased iron content is an effective strategy to reduce iron deficiency. Unlike other grass species, rice takes up iron as Fe(II) via the IRON REGULATED TRANSPORTER (IRT) in addition to Fe(III)-phytosiderophore chelates. We expressed Arabidopsis IRT1 (AtIRT1) under control of the Medicago sativa EARLY NODULIN 12B promoter in our previously developed high-iron NFP rice lines expressing NICOTIANAMINE SYNTHASE (AtNAS1) and FERRITIN. Transgenic rice lines expressing AtIRT1 alone had significant increases in iron and combined with NAS and FERRITIN increased iron to 9.6 µg/g DW in the polished grains that is 2.2-fold higher as compared to NFP lines. The grains of AtIRT1 lines also accumulated more copper and zinc but not manganese. Our results demonstrate that the concerted expression of AtIRT1, AtNAS1 and PvFERRITIN synergistically increases iron in both polished and unpolished rice grains. AtIRT1 is therefore a valuable transporter for iron biofortification programs when used in combination with other genes encoding iron transporters and/or storage proteins.

Effects of iron content in Ni-Cr-xFe alloys and immersion time on the oxide films formed in a simulated PWR water environment

NASA Astrophysics Data System (ADS)

Ru, Xiangkun; Lu, Zhanpeng; Chen, Junjie; Han, Guangdong; Zhang, Jinlong; Hu, Pengfei; Liang, Xue

2017-12-01

The iron content in Ni-Cr-xFe (x = 0-9 at.%) alloys strongly affected the properties of oxide films after 978 h of immersion in the simulated PWR primary water environment at 310 °C. Increasing the iron content in the alloys increased the amount of iron-bearing polyhedral spinel oxide particles in the outer oxide layer and increased the local oxidation penetrations into the alloy matrix from the chromium-rich inner oxide layer. The effects of iron content in the alloys on the oxide film properties after 500 h of immersion were less significant than those after 978 h. Iron content increased, and chromium content decreased, in the outer oxide layer with increasing iron content in the alloys. Increasing the immersion time facilitated the formation of the local oxidation penetrations along the matrix/film interface and the nickel-bearing spinel oxides in the outer oxide layer.

Iron metabolism and the polycystic ovary syndrome.

PubMed

Escobar-Morreale, Héctor F

2012-10-01

The polycystic ovary syndrome (PCOS) is associated with insulin resistance and abnormal glucose tolerance. Iron overload may lead also to insulin resistance and diabetes. Serum ferritin levels are increased in PCOS, especially when glucose tolerance is abnormal, suggesting mild iron overload. Factors contributing to potential iron overload in PCOS include the iron sparing effect of chronic menstrual dysfunction, insulin resistance, and a decrease in hepcidin leading to increased iron absorption. Enhancement of erythropoiesis by androgen excess is unlikely, because soluble transferrin receptor levels are not increased in PCOS. Future venues of research should address the long-term effects of PCOS treatment on iron overload and, conversely, the possible effects of iron lowering strategies on the glucose tolerance of patients with PCOS. Copyright © 2012 Elsevier Ltd. All rights reserved.

Cell wall targeted in planta iron accumulation enhances biomass conversion and seed iron concentration in Arabidopsis and rice

DOE PAGES

Yang, Haibing; Wei, Hui; Ma, Guojie; ...

2016-04-07

Conversion of nongrain biomass into liquid fuel is a sustainable approach to energy demands as global population increases. Previously, we showed that iron can act as a catalyst to enhance the degradation of lignocellulosic biomass for biofuel production. However, direct addition of iron catalysts to biomass pretreatment is diffusion-limited, would increase the cost and complexity of biorefinery unit operations and may have deleterious environmental impacts. Here, we show a new strategy for in planta accumulation of iron throughout the volume of the cell wall where iron acts as a catalyst in the deconstruction of lignocellulosic biomass. We engineered CBM-IBP fusionmore » polypeptides composed of a carbohydrate-binding module family 11 (CBM11) and an iron-binding peptide (IBP) for secretion into Arabidopsis and rice cell walls. CBM-IBP transformed Arabidopsis and rice plants show significant increases in iron accumulation and biomass conversion compared to respective controls. Further, CBM-IBP rice shows a 35% increase in seed iron concentration and a 40% increase in seed yield in greenhouse experiments. In conclusion, CBM-IBP rice potentially could be used to address iron deficiency, the most common and widespread nutritional disorder according to the World Health Organization.« less

Cell wall targeted in planta iron accumulation enhances biomass conversion and seed iron concentration in Arabidopsis and rice

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yang, Haibing; Wei, Hui; Ma, Guojie

Conversion of nongrain biomass into liquid fuel is a sustainable approach to energy demands as global population increases. Previously, we showed that iron can act as a catalyst to enhance the degradation of lignocellulosic biomass for biofuel production. However, direct addition of iron catalysts to biomass pretreatment is diffusion-limited, would increase the cost and complexity of biorefinery unit operations and may have deleterious environmental impacts. Here, we show a new strategy for in planta accumulation of iron throughout the volume of the cell wall where iron acts as a catalyst in the deconstruction of lignocellulosic biomass. We engineered CBM-IBP fusionmore » polypeptides composed of a carbohydrate-binding module family 11 (CBM11) and an iron-binding peptide (IBP) for secretion into Arabidopsis and rice cell walls. CBM-IBP transformed Arabidopsis and rice plants show significant increases in iron accumulation and biomass conversion compared to respective controls. Further, CBM-IBP rice shows a 35% increase in seed iron concentration and a 40% increase in seed yield in greenhouse experiments. CBM-IBP rice potentially could be used to address iron deficiency, the most common and widespread nutritional disorder according to the World Health Organization.« less

Cell wall targeted in planta iron accumulation enhances biomass conversion and seed iron concentration in Arabidopsis and rice

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yang, Haibing; Wei, Hui; Ma, Guojie

Conversion of nongrain biomass into liquid fuel is a sustainable approach to energy demands as global population increases. Previously, we showed that iron can act as a catalyst to enhance the degradation of lignocellulosic biomass for biofuel production. However, direct addition of iron catalysts to biomass pretreatment is diffusion-limited, would increase the cost and complexity of biorefinery unit operations and may have deleterious environmental impacts. Here, we show a new strategy for in planta accumulation of iron throughout the volume of the cell wall where iron acts as a catalyst in the deconstruction of lignocellulosic biomass. We engineered CBM-IBP fusionmore » polypeptides composed of a carbohydrate-binding module family 11 (CBM11) and an iron-binding peptide (IBP) for secretion into Arabidopsis and rice cell walls. CBM-IBP transformed Arabidopsis and rice plants show significant increases in iron accumulation and biomass conversion compared to respective controls. Further, CBM-IBP rice shows a 35% increase in seed iron concentration and a 40% increase in seed yield in greenhouse experiments. In conclusion, CBM-IBP rice potentially could be used to address iron deficiency, the most common and widespread nutritional disorder according to the World Health Organization.« less

Potential of common bean to enhance dietary iron availability in humans: Germplasm diversity and QTL analysis

USDA-ARS?s Scientific Manuscript database

We are interested in the improvement of iron nutritional status of humans living in developing world countries where iron deficiency anemia is quite severe. We also wish to promote the use of plant-based food sources to improve human iron status, and thus are focusing on staple food crops like comm...

The usefulness of iron bioavailability as a target for breeding maize (Zea mays L.) with enhanced nutritional value

USDA-ARS?s Scientific Manuscript database

Iron deficiency is the most widespread nutritional problem, affecting as many as half of the world’s population. Only a small fraction (2-15%) of iron from plant sources is typically bioavailable, that is, available for absorption and nutritionally useful for humans. This study evaluated iron conc...

Silica-Induced Protein (Sip) in Thermophilic Bacterium Thermus thermophilus Responds to Low Iron Availability

PubMed Central

Fujino, Yasuhiro; Nagayoshi, Yuko; Iwase, Makoto; Yokoyama, Takushi; Ohshima, Toshihisa

2016-01-01

ABSTRACT Thermus thermophilus HB8 expresses silica-induced protein (Sip) when cultured in medium containing supersaturated silicic acids. Using genomic information, Sip was identified as a Fe3+-binding ABC transporter. Detection of a 1-kb hybridized band in Northern analysis revealed that sip transcription is monocistronic and that sip has its own terminator and promoter. The sequence of the sip promoter showed homology with that of the σA-dependent promoter, which is known as a housekeeping promoter in HB8. Considering that sip is transcribed when supersaturated silicic acids are added, the existence of a repressor is presumed. DNA microarray analysis suggested that supersaturated silicic acids and iron deficiency affect Thermus cells similarly, and enhanced sip transcription was detected under both conditions. This suggested that sip transcription was initiated by iron deficiency and that the ferric uptake regulator (Fur) controlled the transcription. Three Fur gene homologues (TTHA0255, TTHA0344, and TTHA1292) have been annotated in the HB8 genome, and electrophoretic mobility shift assays revealed that the TTHA0344 product interacts with the sip promoter region. In medium containing supersaturated silicic acids, free Fe3+ levels were decreased due to Fe3+ immobilization on colloidal silica. This suggests that, because Fe3+ ions are captured by colloidal silica in geothermal water, Thermus cells are continuously exposed to the risk of iron deficiency. Considering that Sip is involved in iron acquisition, Sip production may be a strategy to survive under conditions of low iron availability in geothermal water. IMPORTANCE The thermophilic bacterium Thermus thermophilus HB8 produces silica-induced protein (Sip) in the presence of supersaturated silicic acids. Sip has homology with iron-binding ABC transporter; however, the mechanism by which Sip expression is induced by silicic acids remains unexplained. We demonstrate that Sip captures iron and its transcription is regulated by the repressor ferric uptake regulator (Fur). This implies that Sip is expressed with iron deficiency. In addition, it is suggested that negatively charged colloidal silica in supersaturated solution absorbs Fe3+ ions and decreases iron availability. Considering that geothermal water contains ample silicic acids, it is suggested that thermophilic bacteria are always facing iron starvation. Sip production may be a strategy for surviving under conditions of low iron availability in geothermal water. PMID:26994077

Mobilization of soil-borne arsenic by three common organic acids: Dosage and time effects.

PubMed

Onireti, Olaronke O; Lin, Chuxia

2016-03-01

A batch experiment was conducted to investigate the mobilization of soil-borne arsenic by three common low-molecular-weight organic acids with a focus on dosage and time effects. The results show that oxalic acid behaved differently from citric acid and malic acid in terms of mobilizing As that was bound to iron compounds. At an equivalent molar concentration, reactions between oxalic acid and soil-borne Fe were kinetically more favourable, as compared to those between either citric acid or malic acid and the soil-borne Fe. It was found that reductive dissolution of soil-borne Fe played a more important role in liberating As, as compared to non-reductive reactions. Prior to the 7th day of the experiment, As mobility increased with increasing dose of oxalic acid while there was no significant difference (P > 0.05) in mobilized As among the treatments with different doses of citric acid or malic acid. The dosage effect on soil-borne As mobilization in the citric acid and malic acid treatments became clear only after the 7th day of the experiment. Soluble Ca present in the soils could cause re-immobilization of As by competing with solution-borne Fe for available organic ligands to form practically insoluble organic compounds of calcium (i.e. calcium oxalate). This resulted in transformation of highly soluble organic complexes of iron (i.e. iron oxalate complexes) into slightly soluble organic compounds of iron (i.e. iron oxalate) or free ferric ion, which then reacted with the solution-borne arsenate ions to form practically insoluble iron arsenates in the latter part of the experiment. Copyright © 2015 Elsevier Ltd. All rights reserved.

Arsenic adsorption and plant availability in an agricultural soil irrigated with As-rich water: Effects of Fe-rich amendments and organic and inorganic fertilisers.

PubMed

Arco-Lázaro, Elena; Pardo, Tania; Clemente, Rafael; Bernal, Ma Pilar

2018-03-01

The use of As-rich water for irrigation in agricultural soils may result in As accumulation in soil and crops, with the consequent risk of its entry into the food chain. The effectiveness of three different Fe-based materials (a commercial iron oxide (Bayoxide ® ), lamination slag (a by-product of the hot rolling of steel) and a commercial red mud derivative (ViroBind™)) used as soil amendments to minimise the impact of irrigation with As-rich water in an agricultural soil-plant system was evaluated in a pot experiment. Simultaneously, the influence of organic and inorganic fertilisation (olive oil mill waste compost versus NPK fertiliser) on the effectiveness of iron oxide in As adsorption processes was also assessed. The As adsorption capacity of the amendments was determined in a preliminary batch experiment using sorption isotherms. Then, a pot experiment was carried out in a growth chamber using an agricultural soil (arenosol) from Segovia province (central Spain), amended with the different materials, in which Lactuca sativa (lettuce) was grown for two months. The As adsorption capacity was higher in the commercial iron oxide and in the red mud derivative, which fitted the Freundlich model (no saturation), than in the lamination slag, which fitted the Langmuir model (limited adsorption). All the materials decreased the pore water As concentration compared to the control (by 29-80%), but only iron oxide reduced As availability in the soil, and none of the amendments decreased the As concentration in plant leaves. The combination of iron oxide and compost did not significantly improve plant growth, but increased nutrients (N, K, Ca, Na and Mg) concentrations and availability in the soil and their concentration in the plants, relative to the other treatments and the control. Therefore, this seems to be a viable option to prevent As leaching and improve the plant nutritional status. Copyright © 2017 Elsevier Ltd. All rights reserved.

Micromilling enhances iron bioaccessibility from wholegrain wheat.

PubMed

Latunde-Dada, G O; Li, X; Parodi, A; Edwards, C H; Ellis, P R; Sharp, P A

2014-11-19

Cereals constitute important sources of iron in human diet; however, much of the iron in wheat is lost during processing for the production of white flour. This study employed novel food processing techniques to increase the bioaccessibility of naturally occurring iron in wheat. Iron was localized in wheat by Perl's Prussian blue staining. Soluble iron from digested wheat flour was measured by a ferrozine spectrophotometric assay. Iron bioaccessibility was determined using an in vitro simulated peptic-pancreatic digestion, followed by measurement of ferritin (a surrogate marker for iron absorption) in Caco-2 cells. Light microscopy revealed that iron in wheat was encapsulated in cells of the aleurone layer and remained intact after in vivo digestion and passage through the gastrointestinal tract. The solubility of iron in wholegrain wheat and in purified wheat aleurone increased significantly after enzymatic digestion with Driselase, and following mechanical disruption using micromilling. Furthermore, following in vitro simulated peptic-pancreatic digestion, iron bioaccessibility, measured as ferritin formation in Caco-2 cells, from micromilled aleurone flour was significantly higher (52%) than from whole aleurone flour. Taken together our data show that disruption of aleurone cell walls could increase iron bioaccessibility. Micromilled aleurone could provide an alternative strategy for iron fortification of cereal products.

Treatment of Anemia in Heart Failure: Potential Risks and Benefits of Intravenous Iron Therapy in Cardiovascular Disease

PubMed Central

Jelani, Qurat-ul-ain; Katz, Stuart D.

2010-01-01

Iron-deficiency anemia is common is patients with heart failure (HF), but the optimum diagnostic tests to detect iron deficiency and the treatment options to replete iron have not been fully characterized. Recent studies in patients with HF indicate that intravenous iron can rapidly replenish iron stores in patients having iron-deficiency anemia, with resultant increased hemoglobin levels and improved functional capacity. Preliminary data from a sub-group analysis also suggests that supplemental intravenous iron therapy can improve functional capacity even in those subjects without anemia. The mechanisms responsible for this observation are not fully characterized, but may be related to beneficial effects of iron supplementation on mitochondrial respiration in skeletal muscle. The long-term safety of using intravenous iron supplementation in HF populations is not known. Iron is a known pro-oxidant factor that can inhibit nitric oxide signaling and irreversibly injury cells. Increased iron stores are associated with vascular endothelial dysfunction and increased risk of coronary heart disease events. Additional clinical trials are needed to more fully characterize the therapeutic potential and safety of intravenous iron in HF patients. PMID:20699672

Iron therapy for pre-operative anaemia.

PubMed

Ng, Oliver; Keeler, Barrie D; Mishra, Amitabh; Simpson, Alastair; Neal, Keith; Brookes, Matthew J; Acheson, Austin G

2015-12-22

Pre-operative anaemia is common and occurs in up to 76% of patients. It is associated with increased peri-operative allogeneic blood transfusions, longer hospital lengths of stay and increased morbidity and mortality. Iron deficiency is one of the most common causes of this anaemia. Oral iron therapy has traditionally been used to treat anaemia but newer, safer parenteral iron preparations have been shown to be more effective in other conditions such as inflammatory bowel disease, chronic heart failure and post-partum haemorrhage. A limited number of studies look at iron therapy for the treatment of pre-operative anaemia. The aim of this Cochrane review is to summarise the evidence for use of iron supplementation, both enteral and parenteral, for the management of pre-operative anaemia. The objective of this review is to evaluate the effects of pre-operative iron therapy (enteral or parenteral) in reducing the need for allogeneic blood transfusions in anaemic patients undergoing surgery. We ran the search on 25 March 2015. We searched the Cochrane Injuries Group's Specialised Register, Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library), Ovid MEDLINE(R), Ovid MEDLINE(R) In-Process & Other Non-Indexed Citations, Ovid MEDLINE(R) Daily and Ovid OLDMEDLINE(R), EMBASE Classic and EMBASE (Ovid), CINAHL Plus (EBSCO), PubMed, clinical trials registries, conference abstracts, and we screened reference lists. We included all randomised controlled trials (RCTs) which compared pre-operative iron monotherapy to placebo, no treatment, standard of care or another form of iron therapy for anaemic adults undergoing surgery. Anaemia was defined by haemoglobin values less than 13 g/dL for males and 12 g/dL for non-pregnant females. Data were collected by two authors on the proportion of patients who receive a blood transfusion, amount of blood transfused per patient (units) and haemoglobin measured as continuous variables at pre-determined time-points: pre-treatment, pre-operatively but post-treatment, and post-operatively. Statistical analysis was performed using the Cochrane statistical software, Review Manager 2014. Outcome data were summarised in tables and a forest plot. Three prospective randomised controlled studies evaluated pre-operative iron therapy to correct anaemia (two in colorectal and one in gynaecological surgery) and included 114 patients in total. One compared oral iron versus standard care (Lidder 2007); one intravenous iron versus control (Edwards 2009); and one study compared oral versus intravenous iron (Kim 2009). Both colorectal trials reported the primary outcome (proportion of patients who received allogeneic blood transfusions) and meta-analysis showed a reduction in blood transfusions with the administration of iron therapy, but the reduction was not statistically significant (risk ratio (RR) 0.56, 95% confidence interval (CI) 0.27 to 1.18). All studies reported haemoglobin change but data for the anaemic patients were only available for two studies (Edwards 2009 and Kim 2009). Edwards 2009 showed no difference in haemoglobin at the end of treatment pre-operatively. The intravenous versus oral iron study showed an increase in haemoglobin with intravenous iron at the end of treatment pre-operatively (MD 1.90 g/dL, 95% CI 1.16 to 2.64; participants = 56), but the results are at high risk of bias because participants with less than 80% compliance with therapy were excluded from the analysis and compliance was lower in the oral iron group due to the side-effects of treatment (Kim 2009).None of the studies reported quality of life, short- or long-term mortality or post-operative morbidity. The use of iron therapy for pre-operative anaemia does not show a statistically significant reduction in the proportion of patients who received an allogeneic blood transfusion compared to no iron therapy. However, the 38 patients in our analysis falls far short of the 819 patients our information size calculation recommended to detect a 30% reduction in blood transfusions. Intravenous iron may be more effective than oral iron at increasing haemoglobin. However, all these conclusions are drawn from only three small randomised controlled studies. Further well designed, adequately powered randomised controlled studies are required to determine the true effectiveness of iron therapy for pre-operative anaemia.

Iron Accumulates in Huntington’s Disease Neurons: Protection by Deferoxamine

PubMed Central

Chen, Jianfang; Lai, Barry; Zhang, Zhaojie; Duce, James A.; Lam, Linh Q.; Volitakis, Irene; Bush, Ashley I.; Hersch, Steven

2013-01-01

Huntington’s disease (HD) is a progressive neurodegenerative disorder caused by a polyglutamine-encoding CAG expansion in the huntingtin gene. Iron accumulates in the brains of HD patients and mouse disease models. However, the cellular and subcellular sites of iron accumulation, as well as significance to disease progression are not well understood. We used independent approaches to investigate the location of brain iron accumulation. In R6/2 HD mouse brain, synchotron x-ray fluorescence analysis revealed iron accumulation as discrete puncta in the perinuclear cytoplasm of striatal neurons. Further, perfusion Turnbull’s staining for ferrous iron (II) combined with transmission electron microscope ultra-structural analysis revealed increased staining in membrane bound peri-nuclear vesicles in R6/2 HD striatal neurons. Analysis of iron homeostatic proteins in R6/2 HD mice revealed decreased levels of the iron response proteins (IRPs 1 and 2) and accordingly decreased expression of iron uptake transferrin receptor (TfR) and increased levels of neuronal iron export protein ferroportin (FPN). Finally, we show that intra-ventricular delivery of the iron chelator deferoxamine results in an improvement of the motor phenotype in R6/2 HD mice. Our data supports accumulation of redox-active ferrous iron in the endocytic / lysosomal compartment in mouse HD neurons. Expression changes of IRPs, TfR and FPN are consistent with a compensatory response to an increased intra-neuronal labile iron pool leading to increased susceptibility to iron-associated oxidative stress. These findings, together with protection by deferoxamine, support a potentiating role of neuronal iron accumulation in HD. PMID:24146952

Heme compounds as iron sources for nonpathogenic Rhizobium bacteria.

PubMed Central

Noya, F; Arias, A; Fabiano, E

1997-01-01

Many animal-pathogenic bacteria can use heme compounds as iron sources. Like these microorganisms, rhizobium strains interact with host organisms where heme compounds are available. Results presented in this paper indicate that the use of hemoglobin as an iron source is not restricted to animal-pathogenic microorganisms. We also demonstrate that heme, hemoglobin, and leghemoglobin can act as iron sources under iron-depleted conditions for Rhizobium meliloti 242. Analysis of iron acquisition mutant strains indicates that siderophore-, heme-, hemoglobin-, and leghemoglobin-mediated iron transport systems expressed by R. meliloti 242 share at least one component. PMID:9139934

Heme compounds as iron sources for nonpathogenic Rhizobium bacteria.

PubMed

Noya, F; Arias, A; Fabiano, E

1997-05-01

Many animal-pathogenic bacteria can use heme compounds as iron sources. Like these microorganisms, rhizobium strains interact with host organisms where heme compounds are available. Results presented in this paper indicate that the use of hemoglobin as an iron source is not restricted to animal-pathogenic microorganisms. We also demonstrate that heme, hemoglobin, and leghemoglobin can act as iron sources under iron-depleted conditions for Rhizobium meliloti 242. Analysis of iron acquisition mutant strains indicates that siderophore-, heme-, hemoglobin-, and leghemoglobin-mediated iron transport systems expressed by R. meliloti 242 share at least one component.

Importance of Boreal Rivers in Providing Iron to Marine Waters

PubMed Central

Kritzberg, Emma S.; Bedmar Villanueva, Ana; Jung, Marco; Reader, Heather E.

2014-01-01

This study reports increasing iron concentrations in rivers draining into the Baltic Sea. Given the decisive role of iron to the structure and biogeochemical function of aquatic ecosystems, this trend is likely one with far reaching consequences to the receiving system. What those consequences may be depends on the fate of the iron in estuarine mixing. We here assess the stability of riverine iron by mixing water from seven boreal rivers with artificial sea salts. The results show a gradual loss of iron from suspension with increasing salinity. However, the capacity of the different river waters to maintain iron in suspension varied greatly, i.e. between 1 and 54% of iron was in suspension at a salinity of 30. The variability was best explained by iron:organic carbon ratios in the riverine waters – the lower the ratio the more iron remained in suspension. Water with an initially low iron:organic carbon ratio could keep even higher than ambient concentrations of Fe in suspension across the salinity gradient, as shown in experiments with iron amendments. Moreover, there was a positive relationship between the molecular size of the riverine organic matter and the amount of iron in suspension. In all, the results point towards a remarkably high transport capacity of iron from boreal rivers, suggesting that increasing concentrations of iron in river mouths may result in higher concentrations of potentially bioavailable iron in the marine system. PMID:25233197

Lead induced changes in growth and micronutrient uptake of Jatropha curcas L.

PubMed

Shu, Xiao; Zhang, QuanFa; Wang, WeiBo

2014-11-01

Effects of lead treatment on growth and micronutrient uptake in Jatropha curcas L. seedlings were assessed by means of microcosm experiments. Results suggested that superoxide dismutase (SOD) activity increased with increasing lead concentration. There was significant positive correlation between lead treatment concentration and SOD and peroxidase activity. Catalase activity was initiated under lower lead stress but, was inhibited under higher lead exposure. Lead had a stimulating effect on seedlings height and leaf area at lower lead concentrations. The J. curcas can accumulate higher amounts of available lead from soil but can translocate only low amounts to the shoots. Results indicating SOD and peroxidase activity in J. curcas seedlings played an important role in resisting the oxidative stress induced by lead. The addition of lead significantly increased the content of zinc in plant tissue and enhanced the transport of iron from roots to shoots but contributed to a decrease in measured copper, iron, and manganese content.

Soybean Ferritin Expression in Saccharomyces cerevisiae Modulates Iron Accumulation and Resistance to Elevated Iron Concentrations

PubMed Central

de Llanos, Rosa; Martínez-Garay, Carlos Andrés; Fita-Torró, Josep; Romero, Antonia María; Martínez-Pastor, María Teresa

2016-01-01

ABSTRACT Fungi, including the yeast Saccharomyces cerevisiae, lack ferritin and use vacuoles as iron storage organelles. This work explored how plant ferritin expression influenced baker's yeast iron metabolism. Soybean seed ferritin H1 (SFerH1) and SFerH2 genes were cloned and expressed in yeast cells. Both soybean ferritins assembled as multimeric complexes, which bound yeast intracellular iron in vivo and, consequently, induced the activation of the genes expressed during iron scarcity. Soybean ferritin protected yeast cells that lacked the Ccc1 vacuolar iron detoxification transporter from toxic iron levels by reducing cellular oxidation, thus allowing growth at high iron concentrations. Interestingly, when simultaneously expressed in ccc1Δ cells, SFerH1 and SFerH2 assembled as heteropolymers, which further increased iron resistance and reduced the oxidative stress produced by excess iron compared to ferritin homopolymer complexes. Finally, soybean ferritin expression led to increased iron accumulation in both wild-type and ccc1Δ yeast cells at certain environmental iron concentrations. IMPORTANCE Iron deficiency is a worldwide nutritional disorder to which women and children are especially vulnerable. A common strategy to combat iron deficiency consists of dietary supplementation with inorganic iron salts, whose bioavailability is very low. Iron-enriched yeasts and cereals are alternative strategies to diminish iron deficiency. Animals and plants possess large ferritin complexes that accumulate, detoxify, or buffer excess cellular iron. However, the yeast Saccharomyces cerevisiae lacks ferritin and uses vacuoles as iron storage organelles. Here, we explored how soybean ferritin expression influenced yeast iron metabolism, confirming that yeasts that express soybean seed ferritin could be explored as a novel strategy to increase dietary iron absorption. PMID:26969708

Cp/Heph mutant mice have iron-induced neurodegeneration diminished by deferiprone

PubMed Central

Zhao, Liangliang; Hadziahmetovic, Majda; Wang, Chenguang; Xu, Xueying; Song, Ying; Jinnah, H.A.; Wodzinska, Jolanta; Iacovelli, Jared; Wolkow, Natalie; Krajacic, Predrag; Weissberger, Alyssa Cwanger; Connelly, John; Spino, Michael; Lee, Michael K.; Connor, James; Giasson, Benoit; Harris, Z. Leah; Dunaief, Joshua L.

2016-01-01

Brain iron accumulates in several neurodegenerative diseases and can cause oxidative damage, but mechanisms of brain iron homeostasis are incompletely understood. Patients with mutations in the cellular iron-exporting ferroxidase ceruloplasmin (Cp) have brain iron accumulation causing neurodegeneration. Here, we assessed the brains of mice with combined mutation of Cp and its homolog hephaestin. Compared to single mutants, brain iron accumulation was accelerated in double mutants in the cerebellum, substantia nigra, and hippocampus. Iron accumulated within glia, while neurons were iron deficient. There was loss of both neurons and glia. Mice developed ataxia and tremor, and most died by 9 months. Treatment with the oral iron chelator deferiprone diminished brain iron levels, protected against neuron loss, and extended lifespan. Ferroxidases play important, partially overlapping roles in brain iron homeostasis by facilitating iron export from glia, making iron available to neurons. PMID:26303407

History of bioavailable lead and iron in the Greater North Sea and Iceland during the last millennium - a bivalve sclerochronological reconstruction.

PubMed

Holland, Hilmar A; Schöne, Bernd R; Marali, Soraya; Jochum, Klaus P

2014-10-15

We present the first annually resolved record of biologically available Pb and Fe in the Greater North Sea and Iceland during 1040-2004 AD based on shells of the long-lived marine bivalve Arctica islandica. The iron content in pre-industrial shells from the North Sea largely remained below the detection limit. Only since 1830, shell Fe levels rose gradually reflecting the combined effect of increased terrestrial runoff of iron-bearing sediments and eutrophication. Although the lead gasoline peak of the 20th century was well recorded by the shells, bivalves that lived during the medieval heyday of metallurgy showed four-fold higher shell Pb levels than modern specimens. Presumably, pre-industrial bivalves were offered larger proportions of resuspended (Pb-enriched) organics, whereas modern specimens receive fresh increased amounts of (Pb-depleted) phytoplankton. As expected, metal loads in the shells from Iceland were much lower. Our study confirms that bivalve shells provide a powerful tool for retrospective environmental biomonitoring. Copyright © 2014 Elsevier Ltd. All rights reserved.

Methods and options in vitro dialyzability; benefits and limitations.

PubMed

Sandberg, Ann-Sofie

2005-11-01

In vitro dialyzability methods involve a two-step digestion process simulating the gastric and intestinal phase, and dialysis through a semi-permeable membrane with a selected molecular weight cut-off. Dialyzable iron/zinc is used as an estimation of available mineral. Final pH adjustment and use of a strict time schedule were found to be critical factors for standardization. In addition the selected cut-off of the dialysis membrane and the method used for iron and zinc determination influence the results. For screening purposes, simple solubility or dialyzability methods seem preferable to the more sophisticated computer-controlled gastrointestinal model. This is likely more valuable in studies of different transit times and sites of dialyzability. In vitro solubility/dialyzability methods correlate in most cases with human absorption studies in ranking iron and zinc availability from different meals. Exceptions may be that effects of milk, certain proteins, tea, and organic acids cannot be predicted. The dialyzability methods exclude iron bound to large molecules, which in some cases is available and include iron bound to small molecules, which is not always available. In vitro experiments based on solubility/dialyzability are tools to understand factors that may affect subsequent mineral absorption.

Effect of dissolved oxygen concentration on iron efficiency: Removal of three chloroacetic acids.

PubMed

Tang, Shun; Wang, Xiao-mao; Mao, Yu-qin; Zhao, Yu; Yang, Hong-wei; Xie, Yuefeng F

2015-04-15

The monochloroacetic, dichloroacetic and trichloroacetic acid (MCAA, DCAA and TCAA) removed by metallic iron under controlled dissolved oxygen conditions (0, 0.75, 1.52, 2.59, 3.47 or 7.09 mg/L DO) was investigated in well-mixed batch systems. The removal of CAAs increased first and then decreased with increasing DO concentration. Compared with anoxic condition, the reduction of MCAA and DCAA was substantially enhanced in the presence of O2, while TCAA reduction was significantly inhibited above 2.59 mg/L. The 1.52 mg/L DO was optimum for the formation of final product, acetic acid. Chlorine mass balances were 69-102%, and carbon mass balances were 92-105%. With sufficient mass transfer from bulk to the particle surface, the degradation of CAAs was limited by their reduction or migration rate within iron particles, which were dependent on the change of reducing agents and corrosion coatings. Under anoxic conditions, the reduction of CAAs was mainly inhibited by the available reducing agents in the conductive layer. Under low oxic conditions, the increasing reducing agents and thin lepidocrocite layer were favorable for CAA dechlorination. Under high oxic conditions, the redundant oxygen competing for reducing agents and significant lepidocrocite growth became the major restricting factors. Various CAA removal mechanisms could be potentially applied to explaining the effect of DO concentration on iron efficiency for contaminant reduction in water and wastewater treatment. Copyright © 2015 Elsevier Ltd. All rights reserved.

Chelator free gallium-68 radiolabelling of silica coated iron oxide nanorods via surface interactions

NASA Astrophysics Data System (ADS)

Burke, Benjamin P.; Baghdadi, Neazar; Kownacka, Alicja E.; Nigam, Shubhanchi; Clemente, Gonçalo S.; Al-Yassiry, Mustafa M.; Domarkas, Juozas; Lorch, Mark; Pickles, Martin; Gibbs, Peter; Tripier, Raphaël; Cawthorne, Christopher; Archibald, Stephen J.

2015-09-01

The commercial availability of combined magnetic resonance imaging (MRI)/positron emission tomography (PET) scanners for clinical use has increased demand for easily prepared agents which offer signal or contrast in both modalities. Herein we describe a new class of silica coated iron-oxide nanorods (NRs) coated with polyethylene glycol (PEG) and/or a tetraazamacrocyclic chelator (DO3A). Studies of the coated NRs validate their composition and confirm their properties as in vivo T2 MRI contrast agents. Radiolabelling studies with the positron emitting radioisotope gallium-68 (t1/2 = 68 min) demonstrate that, in the presence of the silica coating, the macrocyclic chelator was not required for preparation of highly stable radiometal-NR constructs. In vivo PET-CT and MR imaging studies show the expected high liver uptake of gallium-68 radiolabelled nanorods with no significant release of gallium-68 metal ions, validating our innovation to provide a novel simple method for labelling of iron oxide NRs with a radiometal in the absence of a chelating unit that can be used for high sensitivity liver imaging.The commercial availability of combined magnetic resonance imaging (MRI)/positron emission tomography (PET) scanners for clinical use has increased demand for easily prepared agents which offer signal or contrast in both modalities. Herein we describe a new class of silica coated iron-oxide nanorods (NRs) coated with polyethylene glycol (PEG) and/or a tetraazamacrocyclic chelator (DO3A). Studies of the coated NRs validate their composition and confirm their properties as in vivo T2 MRI contrast agents. Radiolabelling studies with the positron emitting radioisotope gallium-68 (t1/2 = 68 min) demonstrate that, in the presence of the silica coating, the macrocyclic chelator was not required for preparation of highly stable radiometal-NR constructs. In vivo PET-CT and MR imaging studies show the expected high liver uptake of gallium-68 radiolabelled nanorods with no significant release of gallium-68 metal ions, validating our innovation to provide a novel simple method for labelling of iron oxide NRs with a radiometal in the absence of a chelating unit that can be used for high sensitivity liver imaging. Electronic supplementary information (ESI) available. See DOI: 10.1039/c5nr02753e

Effect of different home-cooking methods on the bioaccessibility of zinc and iron in conventionally bred cowpea (Vigna unguiculata L. Walp) consumed in Brazil.

PubMed

Pereira, Elenilda J; Carvalho, Lucia M J; Dellamora-Ortiz, Gisela M; Cardoso, Flávio S N; Carvalho, José L V

2016-01-01

The cowpea (Vigna unguiculata L. Wap.) is an excellent source of iron and zinc. However, iron from plant sources is poorly absorbed compared with iron from animal sources. The objective of this study was to evaluate iron and zinc bioaccessibility in cowpea cultivars after processing. Zinc and iron bioaccessibilities in cowpea samples were determined based on an in vitro method involving simulated gastrointestinal digestion with suitable modifications. When water-soaked beans were cooked in a regular pan, the highest percentage of bioaccessible iron obtained was 8.92%, whereas when they were cooked in a pressure cooker without previous soaking, the highest percentage was 44.33%. Also, the percentage of bioaccessible zinc was 52.78% when they were cooked in a regular pan without prior soaking. Higher percentages of bioaccessible iron were found when cooking was done in a pressure cooker compared with regular pan cooking. In all cultivars, cooking of cowpea beans in both pressure cooker and in a regular pan yielded higher percentages of bioaccessible zinc compared with availability of bioaccessible iron. Iron bioaccessibility values suggest that cooking in a regular pan did not have a good effect on iron availability, since the percentage of bioaccessible iron was lower than that of zinc. The determination of iron and zinc bioaccessibility makes it possible to find out the actual percentage of absorption of such minerals and allows the development of efficient strategies for low-income groups to access foods with high levels of these micronutrients.

Iron is a signal for Stenotrophomonas maltophilia biofilm formation, oxidative stress response, OMPs expression, and virulence

PubMed Central

García, Carlos A.; Alcaraz, Eliana S.; Franco, Mirta A.; Passerini de Rossi, Beatriz N.

2015-01-01

Stenotrophomonas maltophilia is an emerging nosocomial pathogen. In many bacteria iron availability regulates, through the Fur system, not only iron homeostasis but also virulence. The aim of this work was to assess the role of iron on S. maltophilia biofilm formation, EPS production, oxidative stress response, OMPs regulation, quorum sensing (QS), and virulence. Studies were done on K279a and its isogenic fur mutant F60 cultured in the presence or absence of dipyridyl. This is the first report of spontaneous fur mutants obtained in S. maltophilia. F60 produced higher amounts of biofilms than K279a and CLSM analysis demonstrated improved adherence and biofilm organization. Under iron restricted conditions, K279a produced biofilms with more biomass and enhanced thickness. In addition, F60 produced higher amounts of EPS than K279a but with a similar composition, as revealed by ATR-FTIR spectroscopy. With respect to the oxidative stress response, MnSOD was the only SOD isoenzyme detected in K279a. F60 presented higher SOD activity than the wt strain in planktonic and biofilm cultures, and iron deprivation increased K279a SOD activity. Under iron starvation, SDS-PAGE profile from K279a presented two iron-repressed proteins. Mass spectrometry analysis revealed homology with FepA and another putative TonB-dependent siderophore receptor of K279a. In silico analysis allowed the detection of potential Fur boxes in the respective coding genes. K279a encodes the QS diffusible signal factor (DSF). Under iron restriction K279a produced higher amounts of DSF than under iron rich condition. Finally, F60 was more virulent than K279a in the Galleria mellonella killing assay. These results put in evidence that iron levels regulate, likely through the Fur system, S. maltophilia biofilm formation, oxidative stress response, OMPs expression, DSF production and virulence. PMID:26388863

IRON REGULATES XANTHINE OXIDASE ACTIVITY IN THE LUNG

EPA Science Inventory

The iron chelator deferoxamine has been reported to inhibit both xanthine oxidase (XO) and xanthine dehydrogenase activity, but the relationship of this effect to the availability of iron in the cellular and tissue environment remains unexplored. XO and total xanthine oxidoreduct...

Effects of calcium on hepatocyte iron uptake from transferrin, iron-pyrophosphate and iron-ascorbate.

PubMed

Nilsen, T

1991-10-16

Calcium stimulates hepatocyte iron uptake from transferrin, ferric-iron-pyrophosphate and ferrous-iron-ascorbate. Maximal stimulation of iron uptake is observed at 1-1.5 mM of extra-cellular calcium and the effect is reversible and immediate. Neither the receptor affinity for transferrin, nor the total amounts of transferrin associated with the cells or the rate of transferrin endocytosis are significantly affected by calcium. In the presence of calcium the rate of iron uptake of non-transferrin bound iron increases abruptly at approximate 17 degrees C and 27 degrees C and as assessed by Arrhenius plots, the activation energy is reduced in a calcium dependent manner at approx. 27 degrees C. At a similar temperature, i.e., between 25 degrees C and 28 degrees C, calcium increases the rates of cellular iron uptake from transferrin in a way that is not reflected in the rate of transferrin endocytosis. By the results of this study it is concluded that calcium increases iron transport across the plasma membrane by a mechanism dependent on membrane fluidity.

Comparison of food habits, iron intake and iron status in adolescents before and after the withdrawal of the general iron fortification in Sweden.

PubMed

Sjöberg, A; Hulthén, L

2015-04-01

Sifted flour was fortified with carbonyl iron for 50 years in Sweden. This study evaluates changes in food habits, intake of iron, factors affecting iron absorption and iron status after the discontinuation of the general iron fortification in adolescents with the highest requirements. A total of 2285 15- to 16-year-old students in 1994 (634 girls and 611 boys) and in 2000 (534 girls and 486 boys) in 13 schools in Gothenburg, Sweden, were included in two cross-sectional surveys assessing food habits with diet history interviews and iron deficiency defined with serum ferritin stores ⩽ 15 μg/l and no preceding infection. In girls, iron deficiency increased from 37 to 45%, while in boys, it was stable at 23%. Total iron intake decreased from 15.7 to 9.5 mg/day and 22.5 to 13.9 mg/day in girls and boys, respectively. Cereals were the main iron source. Among girls, the increase of fish and decrease of calcium intake may not counteract the effect of decreased intake of fortification iron. Among boys, more meat, less calcium and more vitamin C may have favoured the bioavailability of iron. The discontinuation of the general iron fortification resulted in a 39% decrease in total iron intake and iron deficiency increased substantially in girls. However, in boys no change in iron deficiency was observed. Whether this was a result of changed bioavailability of dietary iron or simultaneous changes of non-dietary factors remains to be explored.

Ethylene response factor AtERF72 negatively regulates Arabidopsis thaliana response to iron deficiency.

PubMed

Liu, Wei; Li, Qiwei; Wang, Yi; Wu, Ting; Yang, Yafei; Zhang, Xinzhong; Han, Zhenhai; Xu, Xuefeng

2017-09-23

Ethylene regulates the plant's response to stress caused by iron (Fe) deficiency. However, specific roles of ERF proteins in response to Fe deficiency remain poorly understood. Here, we investigated the role of ERF72 in response to iron deficiency in Arabidopsis thaliana. In this study, the levels of the ethylene response factor AtERF72 increased in leaves and roots induced under the iron deficient conditions. erf72 mutant plants showed increased growth compared to wild type (WT) when grown in iron deficient medium for 5 d. erf72 mutants had increased root H + velocity and the ferric reductase activity, and increase in the expression of the iron deficiency response genes iron-regulated transporter 1 (IRT1) and H + -ATPase (HA2) levels in iron deficient conditions. Compared to WT plants, erf72 mutants retained healthy chloroplast structure with significantly higher Fe and Mg content, and decreased chlorophyll degradation gene pheophorbide a oxygenase (PAO) and chlorophyllase (CLH1) expression when grown in iron deficient media. Yeast one-hybrid analysis showed that ERF72 could directly bind to the promoter regions of iron deficiency responses genes IRT1, HA2 and CLH1. Based on our results, we suggest that ethylene released from plants under iron deficiency stress can activate the expression of ERF72, which responds to iron deficiency in the negative regulation. Copyright © 2017 Elsevier Inc. All rights reserved.

Longitudinal trends in serum ferritin levels and associated factors in a national incident hemodialysis cohort.

PubMed

Kim, Taehee; Rhee, Connie M; Streja, Elani; Obi, Yoshitsugu; Brunelli, Steven M; Kovesdy, Csaba P; Kalantar-Zadeh, Kamyar

2017-02-01

The rise in serum ferritin levels among US maintenance hemodialysis patients has been attributed to higher intravenous iron administration and other changes in practice. We examined ferritin trends over time in hemodialysis patients and whether iron utilization patterns and other factors [erythropoietin-stimulating agent (ESA) prescribing patterns, inflammatory markers] were associated with ferritin trajectory. In a 5-year (January 2007–December 2011) cohort of 81 864 incident US hemodialysis patients, we examined changes in ferritin averaged over 3-month intervals using linear mixed effects models adjusted for intravenous iron dose, malnutrition and inflammatory markers. We then examined ferritin trends across strata of baseline ferritin level, dialysis initiation year, cumulative iron and ESA use in the first dialysis year and baseline hemoglobin level. In models adjusted for iron dose, malnutrition and inflammation, mean ferritin levels increased over time in the overall cohort and across the three lower baseline ferritin strata. Among patients initiating dialysis in 2007, mean ferritin levels increased sharply in the first versus second year of dialysis and again abruptly increased in the fifth year independent of iron dose, malnutrition and inflammatory markers; similar trends were observed among patients who initiated dialysis in 2008 and 2009. In analyses stratified by cumulative iron use, mean ferritin increased among groups receiving iron, but decreased in the no iron group. In analyses stratified by cumulative ESA dose and baseline hemoglobin, mean ferritin increased over time. While ferritin trends correlated with patterns of iron use, increases in ferritin over time persisted independent of intravenous iron and ESA exposure, malnutrition and inflammation.

Increasing dissolved-oxygen disrupts iron homeostasis in production cultures of Escherichia coli.

PubMed

Baez, Antonino; Shiloach, Joseph

2017-01-01

The damaging effect of high oxygen concentration on growth of Escherichia coli is well established. Over-oxygenation increases the intracellular concentration of reactive oxygen species (ROS), causing the destruction of the [4Fe-4S] cluster of dehydratases and limiting the biosynthesis of both branched-chain amino acids and nicotinamide adenine dinucleotide. A key enzyme that reduces the damaging effect of superoxide is superoxide dismutase (SOD). Its transcriptional regulation is controlled by global transcription regulators that respond to changes in oxygen and iron concentrations and pH. Production of biological compounds from E. coli is currently achieved using cultures grown to high cell densities which require oxygen-enriched air supply. It is, therefore, important to study the effect of over-oxygenation on E. coli metabolism and the bacterial protecting mechanism. The effect of over-oxygenation on the superoxide dismutase regulation system was evaluated in cultures grown in a bioreactor by increasing the oxygen concentration from 30 to 300 % air saturation. Following the change in the dissolved oxygen (DO), the expression of sodC, the periplasmic CuZn-containing SOD, and sodA, the cytosolic Mn-containing SOD, was higher in all the tested strains, while the expression of the sodB, the cytosolic Fe-containing SOD, was lower. The down-regulation of the sodB was found to be related to the activation of the small RNA RyhB. It was revealed that iron homeostasis, in particular ferric iron, was involved in the RyhB activation and in sodB regulation but not in sodA. Supplementation of amino acids to the culture medium reduced the intracellular ROS accumulation and reduced the activation of both SodA and SodC following the increase in the oxygen concentration. The study provides evidence that at conditions of over-oxygenation, sodA and sodC are strongly regulated by the amount of ROS, in particular superoxide; and sodB is regulated by iron availability through the small RNA RyhB. In addition, information on the impact of NADH, presence of amino acids and type of iron on SOD regulation, and consequently, on the ROS concentration is provided.

Females Are Protected From Iron-Overload Cardiomyopathy Independent of Iron Metabolism: Key Role of Oxidative Stress.

PubMed

Das, Subhash K; Patel, Vaibhav B; Basu, Ratnadeep; Wang, Wang; DesAulniers, Jessica; Kassiri, Zamaneh; Oudit, Gavin Y

2017-01-23

Sex-related differences in cardiac function and iron metabolism exist in humans and experimental animals. Male patients and preclinical animal models are more susceptible to cardiomyopathies and heart failure. However, whether similar differences are seen in iron-overload cardiomyopathy is poorly understood. Male and female wild-type and hemojuvelin-null mice were injected and fed with a high-iron diet, respectively, to develop secondary iron overload and genetic hemochromatosis. Female mice were completely protected from iron-overload cardiomyopathy, whereas iron overload resulted in marked diastolic dysfunction in male iron-overloaded mice based on echocardiographic and invasive pressure-volume analyses. Female mice demonstrated a marked suppression of iron-mediated oxidative stress and a lack of myocardial fibrosis despite an equivalent degree of myocardial iron deposition. Ovariectomized female mice with iron overload exhibited essential pathophysiological features of iron-overload cardiomyopathy showing distinct diastolic and systolic dysfunction, severe myocardial fibrosis, increased myocardial oxidative stress, and increased expression of cardiac disease markers. Ovariectomy prevented iron-induced upregulation of ferritin, decreased myocardial SERCA2a levels, and increased NCX1 levels. 17β-Estradiol therapy rescued the iron-overload cardiomyopathy in male wild-type mice. The responses in wild-type and hemojuvelin-null female mice were remarkably similar, highlighting a conserved mechanism of sex-dependent protection from iron-overload-mediated cardiac injury. Male and female mice respond differently to iron-overload-mediated effects on heart structure and function, and females are markedly protected from iron-overload cardiomyopathy. Ovariectomy in female mice exacerbated iron-induced myocardial injury and precipitated severe cardiac dysfunction during iron-overload conditions, whereas 17β-estradiol therapy was protective in male iron-overloaded mice. © 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.

Rapid establishment of the CO2 sink associated with Kerguelen's bloom observed during the KEOPS2/OISO20 cruise

NASA Astrophysics Data System (ADS)

Lo Monaco, C.; Metzl, N.; D'Ovidio, F.; Llort, J.; Ridame, C.

2014-12-01

Iron and light are the main factors limiting the biological pump of CO2 in the Southern Ocean. Iron fertilization experiments have demonstrated the potential for increased uptake of atmospheric CO2, but little is known about the evolution of fertilized environnements. This paper presents observations collected in one of the largest phytoplankton bloom of the Southern Ocean sustained by iron originating from the Kerguelen Plateau. We first complement previous studies by investigating the mechanisms that control air-sea CO2 fluxes over and downstream of the Kerguelen Plateau at the onset of the bloom based on measurements obtained in October-November 2011. These new observations show the rapid establishment of a strong CO2 sink in waters fertilized with iron as soon as vertical mixing is reduced. The magnitude of the CO2 sink was closely related to chlorophyll a and iron concentrations. Because iron concentration strongly depends on the distance from the iron source and the mode of delivery, we identified lateral advection as the main mechanism controlling air-sea CO2 fluxes downtream the Kerguelen Plateau during the growing season. In the southern part of the bloom, situated over the Plateau (iron source), the CO2 sink was stronger and spatially more homogeneous than in the plume offshore. However, we also witnessed a substantial reduction in the uptake of atmospheric CO2 over the Plateau following a strong winds event. Next, we used all the data available in this region in order to draw the seasonal evolution of air-sea CO2 fluxes. The CO2 sink is rapidly reduced during the course of the growing season, which we attribute to iron and silicic acid depletion. South of the Polar Front, where nutrients depletion is delayed, we suggest that the amplitude and duration of the CO2 sink is mainly controlled by vertical mixing. The impact of iron fertilization on air-sea CO2 fluxes is revealed by comparing the uptake of CO2 integrated over the productive season in the bloom, between 1 and 1.5 mol C m-2 yr-1, and in the iron-poor HNLC waters, where we found a typical value of 0.4 mol C m-2 yr-1. Extrapolating our results to the ice-free Southern Ocean (~50-60° S) suggests that iron fertilization of the whole area would increase the contemporay oceanic uptake of CO2 by less than 0.1 Pg C yr-1, i.e., less than 1% of the current anthropogenic CO2 emissions.

Iron-induced nitric oxide leads to an increase in the expression of ferritin during the senescence of Lotus japonicus nodules.

PubMed

Chungopast, Sirinapa; Duangkhet, Mallika; Tajima, Shigeyuki; Ma, Jian Feng; Nomura, Mika

2017-01-01

Iron is an essential nutrient for legume-rhizobium symbiosis and accumulates abundantly in the nodules. However, the concentration of free iron in the cells is strictly controlled to avoid toxicity. It is known that ferritin accumulates in the cells as an iron storage protein. During nodule senescence, the expression of the ferritin gene, Ljfer1, was induced in Lotus japonicus. We investigated a signal transduction pathway leading to the increase of Ljfer1 in the nodule. The Ljfer1 promoter of L. japonicus contains a conserved Iron-Dependent Regulatory Sequence (IDRS). The expression of Ljfer1 was induced by the application of iron or sodium nitroprusside, which is a nitric oxide (NO) donor. The application of iron to the nodule increased the level of NO. These data strongly suggest that iron-induced NO leads to increased expression of Ljfer1 during the senescence of L. japonicus nodules. Copyright © 2016 Elsevier GmbH. All rights reserved.

Iron homeostasis during transfusional iron overload in beta-thalassemia and sickle cell disease: changes in iron regulatory protein, hepcidin, and ferritin expression.

PubMed

Jenkins, Zandra A; Hagar, Ward; Bowlus, Christopher L; Johansson, Hans E; Harmatz, Paul; Vichinsky, Elliott P; Theil, Elizabeth C

2007-06-01

Hypertransfusional (>8 transfusions/year) iron in liver biopsies collected immediately after transfusions in beta-thalassemia and sickle cell disease correlated with increased expression (RNA) for iron regulatory proteins 1 and 2 (3-, 9- to 11-fold) and hepcidin RNA: (5- to 8-fold) (each p <.01), while ferritin H and L RNA remained constant. A different H:L ferritin ratio in RNA (0.03) and protein (0.2-0.6) indicated disease-specific trends and suggests novel post-transcriptional effects. Increased iron regulatory proteins could stabilize the transferrin receptor mRNA and, thereby, iron uptake. Increased hepcidin, after correction of anemia by transfusion, likely reflects excess liver iron. Finally, the absence of a detectable change in ferritin mRNA indicates insufficient oxidative stress to significantly activate MARE/ARE promoters.

Iron chelation therapy for transfusional iron overload: a swift evolution.

PubMed

Musallam, Khaled M; Taher, Ali T

2011-01-01

Chronic transfusional iron overload leads to significant morbidity and mortality. While deferoxamine (DFO) is an effective iron chelator with over four decades of experience, it requires tedious subcutaneous infusions that reflect negatively on patient compliance. The novel oral iron chelators deferiprone (L1) and deferasirox (DFRA) opened new horizons for the management of transfusional siderosis. A large body of evidence is now available regarding their efficacy and safety in various populations and settings. Nevertheless, experience with both drugs witnessed some drawbacks, and the search for an ideal and cost-effective iron chelator continues.

Sequestration and Scavenging of Iron in Infection

PubMed Central

Parrow, Nermi L.; Fleming, Robert E.

2013-01-01

The proliferative capability of many invasive pathogens is limited by the bioavailability of iron. Pathogens have thus developed strategies to obtain iron from their host organisms. In turn, host defense strategies have evolved to sequester iron from invasive pathogens. This review explores the mechanisms employed by bacterial pathogens to gain access to host iron sources, the role of iron in bacterial virulence, and iron-related genes required for the establishment or maintenance of infection. Host defenses to limit iron availability for bacterial growth during the acute-phase response and the consequences of iron overload conditions on susceptibility to bacterial infection are also examined. The evidence summarized herein demonstrates the importance of iron bioavailability in influencing the risk of infection and the ability of the host to clear the pathogen. PMID:23836822

Effects of Iron and Nitrogen Limitation on Sulfur Isotope Fractionation during Microbial Sulfate Reduction

PubMed Central

Ono, Shuhei; Bosak, Tanja

2012-01-01

Sulfate-reducing microbes utilize sulfate as an electron acceptor and produce sulfide that is depleted in heavy isotopes of sulfur relative to sulfate. Thus, the distribution of sulfur isotopes in sediments can trace microbial sulfate reduction (MSR), and it also has the potential to reflect the physiology of sulfate-reducing microbes. This study investigates the relationship between the availability of iron and reduced nitrogen and the magnitude of S-isotope fractionation during MSR by a marine sulfate-reducing bacterium, DMSS-1, a Desulfovibrio species, isolated from salt marsh in Cape Cod, MA. Submicromolar levels of iron increase sulfur isotope fractionation by about 50% relative to iron-replete cultures of DMSS-1. Iron-limited cultures also exhibit decreased cytochrome c-to-total protein ratios and cell-specific sulfate reduction rates (csSRR), implying changes in the electron transport chain that couples carbon and sulfur metabolisms. When DMSS-1 fixes nitrogen in ammonium-deficient medium, it also produces larger fractionation, but it occurs at faster csSRRs than in the ammonium-replete control cultures. The energy and reducing power required for nitrogen fixation may be responsible for the reverse trend between S-isotope fractionation and csSRR in this case. Iron deficiency and nitrogen fixation by sulfate-reducing microbes may lead to the large observed S-isotope effects in some euxinic basins and various anoxic sediments. PMID:23001667

The anatomy of an anomaly. [data on LANDSAT multispectral band scanning in Wyoming

NASA Technical Reports Server (NTRS)

Short, N. M.; Marrs, R. W.

1975-01-01

An anomalous tonal pattern, apparently associated with the Beaver Creek oil field in central Wyoming, was identified using an MSS Band 5 to 4 ratio image made from digital LANDSAT data. This pattern was attributed to an increase in iron with rocks and/or soils which might have resulted from escaping hydrocarbons. The nature of this anomaly was investigated by producing several different combinations of band ratios and by conducting appropriate field studies. The results indicated (1) the existence of a well-defined oval feature related to exposure of iron-cemented red sandstones in a badlands topography, (2) a broader iron-influenced anomaly surrounding this feature, and (3) a spectral response of the rocks, soils, and alluvium making up this iron-colored surface that is readily distinguishable from that of iron-rich reddish Chugwater siltstones exposed in nearby anticlines. The general pattern of the broad anomaly extending beyond the Beaver Creek field is controlled by several factors including variations in vegetation (mainly sage and tall grasses), soil composition and moisture, and topography in addition to variations in iron content of the rock materials. From the available evidence, there is no provable correlation between the oval or the broad anomalies and the distribution of petroleum-producing structures or possible surface alteration effects related to uranium deposits known to occur within this region.

Deferasirox for managing transfusional iron overload in people with sickle cell disease.

PubMed

Meerpohl, Joerg J; Antes, Gerd; Rücker, Gerta; Fleeman, Nigel; Niemeyer, Charlotte; Bassler, Dirk

2010-08-04

Sickle cell disease (SCD) is a group of genetic haemoglobin disorders. Increasingly, some people with SCD develop secondary iron overload due to occasional red blood cell transfusions or are on long-term transfusion programmes for e.g. secondary stroke prevention. Iron chelation therapy can prevent long-term complications.Deferoxamine and deferiprone have been found to be efficacious. However, questions exist about the effectiveness and safety of the new oral chelator deferasirox. To assess the effectiveness and safety of oral deferasirox in people with SCD and secondary iron overload. We searched the Cystic Fibrosis & Genetic Disorders Group's Haemoglobinopathies Trials Register (06 April 2010).We searched MEDLINE, EMBASE, EBMR, Biosis Previews, Web of Science, Derwent Drug File, XTOXLINE and three trial registries: www.controlled-trials.com; www.clinicaltrials.gov; www.who.int./ictrp/en/. Most recent searches: 22 June 2009. Randomised controlled trials comparing deferasirox with no therapy or placebo or with another iron chelating treatment schedule. Two authors independently assessed study quality and extracted data. We contacted the study author for additional information. One study (203 people) was included comparing the efficacy and safety of deferasirox and deferoxamine after 12 months. Data were not available on mortality or end-organ damage. Using a pre-specified dosing algorithm serum ferritin reduction was similar in both groups, mean difference (MD) 375.00 microg/l in favour of deferoxamine; (95% confidence interval (CI) -106.08 to 856.08). Liver iron concentration measured by superconduction quantum interference device showed no difference for the overall group of patients adjusted for transfusion category, MD -0.20 mg Fe/g dry weight (95% CI -3.15 to 2.75).Mild stable increases in creatine were observed more often in people treated with deferasirox, risk ratio 1.64 (95% CI 0.98 to 2.74). Abdominal pain and diarrhoea occurred significantly more often in people treated with deferasirox. Rare adverse events (less than 5% increase) were not reported; long-term adverse events could not be measured in the included study (follow-up 52 weeks). Patient satisfaction with, and convenience of treatment were significantly better with deferasirox. Deferasirox appears to be as effective as deferoxamine. However, only limited evidence is available assessing the efficacy regarding patient-important outcomes. The short-term safety of deferasirox seems to be acceptable, however, follow-up was too short to exclude long-term side effects and thus treatment with deferasirox cannot be judged completely safe. Future studies should assess long-term outcomes for safety and efficacy, and also evaluate rarer adverse effects.

Retention of iron by infants.

PubMed

Fomon, S J; Nelson, S E; Ziegler, E E

2000-01-01

Throughout the world, the most common nutritional deficiency disorder of infants is iron deficiency. Developing effective strategies for preventing iron deficiency requires detailed knowledge of iron retention under ordinary living conditions. For the adult population, such knowledge is at an advanced stage, but relatively little is known about infants. Many reports of iron retention by infants have been based on the assumption that, as in normal and iron-deficient adults, 80%-100% of newly absorbed iron is promptly incorporated into circulating erythrocytes, but this assumption is not supported by available data. This communication presents a review of iron retention by term and preterm infants, as determined by metabolic balance studies or (59)Fe whole-body counting studies, and it explores the relationship between iron retention and postnatal age, iron nutritional status, iron intake (or dose), and type of feeding.

[Current understanding of iron overload hazard in patients with myelodysplastic syndrome].

PubMed

Song, Lu-Xi; Su, Ji-Ying; Zhang, Zhen; Chang, Chun-Kang

2013-04-01

Patients with myelodysplastic syndromes (MDS) become dependent on blood transfusions and develop into transfusional iron overload, which is exacerbated by increased absorption of dietary iron in response to ineffective erythropoiesis. However, it is uncertain whether there is an association among iron accumulation, clinical complications, and decreased likelihood of survival in MDS patients. Thereby our current understanding of the effects of transfusion dependency and iron overload in MDS are discussed. Particular emphasis should be placed on further characterizing the role of redox-active forms of labile iron and oxidative stress in iron overload, decreased life expectancy and increased risk of leukemic transformation in MDS patients with iron overload.

Physiological and Proteomic Analysis of Escherichia coli Iron-Limited Chemostat Growth

PubMed Central

Folsom, James Patrick; Parker, Albert E.

2014-01-01

Iron bioavailability is a major limiter of bacterial growth in mammalian host tissue and thus represents an important area of study. Escherichia coli K-12 metabolism was studied at four levels of iron limitation in chemostats using physiological and proteomic analyses. The data documented an E. coli acclimation gradient where progressively more severe iron scarcity resulted in a larger percentage of substrate carbon being directed into an overflow metabolism accompanied by a decrease in biomass yield on glucose. Acetate was the primary secreted organic by-product for moderate levels of iron limitation, but as stress increased, the metabolism shifted to secrete primarily lactate (∼70% of catabolized glucose carbon). Proteomic analysis reinforced the physiological data and quantified relative increases in glycolysis enzyme abundance and decreases in tricarboxylic acid (TCA) cycle enzyme abundance with increasing iron limitation stress. The combined data indicated that E. coli responds to limiting iron by investing the scarce resource in essential enzymes, at the cost of catabolic efficiency (i.e., downregulating high-ATP-yielding pathways containing enzymes with large iron requirements, like the TCA cycle). Acclimation to iron-limited growth was contrasted experimentally with acclimation to glucose-limited growth to identify both general and nutrient-specific acclimation strategies. While the iron-limited cultures maximized biomass yields on iron and increased expression of iron acquisition strategies, the glucose-limited cultures maximized biomass yields on glucose and increased expression of carbon acquisition strategies. This study quantified ecologically competitive acclimations to nutrient limitations, yielding knowledge essential for understanding medically relevant bacterial responses to host and to developing intervention strategies. PMID:24837288

Phototrophs in high-iron-concentration microbial mats: physiological ecology of phototrophs in an iron-depositing hot spring

NASA Technical Reports Server (NTRS)

Pierson, B. K.; Parenteau, M. N.; Griffin, B. M.

1999-01-01

At Chocolate Pots Hot Springs in Yellowstone National Park the source waters have a pH near neutral, contain high concentrations of reduced iron, and lack sulfide. An iron formation that is associated with cyanobacterial mats is actively deposited. The uptake of [(14)C]bicarbonate was used to assess the impact of ferrous iron on photosynthesis in this environment. Photoautotrophy in some of the mats was stimulated by ferrous iron (1.0 mM). Microelectrodes were used to determine the impact of photosynthetic activity on the oxygen content and the pH in the mat and sediment microenvironments. Photosynthesis increased the oxygen concentration to 200% of air saturation levels in the top millimeter of the mats. The oxygen concentration decreased with depth and in the dark. Light-dependent increases in pH were observed. The penetration of light in the mats and in the sediments was determined. Visible radiation was rapidly attenuated in the top 2 mm of the iron-rich mats. Near-infrared radiation penetrated deeper. Iron was totally oxidized in the top few millimeters, but reduced iron was detected at greater depths. By increasing the pH and the oxygen concentration in the surface sediments, the cyanobacteria could potentially increase the rate of iron oxidation in situ. This high-iron-content hot spring provides a suitable model for studying the interactions of microbial photosynthesis and iron deposition and the role of photosynthesis in microbial iron cycling. This model may help clarify the potential role of photosynthesis in the deposition of Precambrian banded iron formations.

METABOLISM OF IRON STORES

PubMed Central

SAITO, HIROSHI

2014-01-01

ABSTRACT Remarkable progress was recently achieved in the studies on molecular regulators of iron metabolism. Among the main regulators, storage iron, iron absorption, erythropoiesis and hepcidin interact in keeping iron homeostasis. Diseases with gene-mutations resulting in iron overload, iron deficiency, and local iron deposition have been introduced in relation to the regulators of storage iron metabolism. On the other hand, the research on storage iron metabolism has not advanced since the pioneering research by Shoden in 1953. However, we recently developed a new method for determining ferritin iron and hemosiderin iron by computer-assisted serum ferritin kinetics. Serum ferritin increase or decrease curves were measured in patients with normal storage iron levels (chronic hepatitis C and iron deficiency anemia treated by intravenous iron injection), and iron overload (hereditary hemochromatosis and transfusion dependent anemia). We thereby confirmed the existence of two iron pathways where iron flows followed the numbered order (1) labile iron, (2) ferritin and (3) hemosiderin in iron deposition and mobilization among many previously proposed but mostly unproven routes. We also demonstrated the increasing and decreasing phases of ferritin iron and hemosiderin iron in iron deposition and mobilization. The author first demonstrated here the change in proportion between pre-existing ferritin iron and new ferritin iron synthesized by removing iron from hemosiderin in the course of iron removal. In addition, the author disclosed the cause of underestimation of storage iron turnover rate which had been reported by previous investigators in estimating storage iron turnover rate of normal subjects. PMID:25741033

Efficacy and safety of iron-chelation therapy with deferoxamine, deferiprone, and deferasirox for the treatment of iron-loaded patients with non-transfusion-dependent thalassemia syndromes

PubMed Central

Kontoghiorghe, Christina N; Kontoghiorghes, George J

2016-01-01

The prevalence rate of thalassemia, which is endemic in Southeast Asia, the Middle East, and the Mediterranean, exceeds 100,000 live births per year. There are many genetic variants in thalassemia with different pathological severity, ranging from a mild and asymptomatic anemia to life-threatening clinical effects, requiring lifelong treatment, such as regular transfusions in thalassemia major (TM). Some of the thalassemias are non-transfusion-dependent, including many thalassemia intermedia (TI) variants, where iron overload is caused by chronic increase in iron absorption due to ineffective erythropoiesis. Many TI patients receive occasional transfusions. The rate of iron overloading in TI is much slower in comparison to TM patients. Iron toxicity in TI is usually manifested by the age of 30–40 years, and in TM by the age of 10 years. Subcutaneous deferoxamine (DFO), oral deferiprone (L1), and DFO–L1 combinations have been effectively used for more than 20 years for the treatment of iron overload in TM and TI patients, causing a significant reduction in morbidity and mortality. Selected protocols using DFO, L1, and their combination can be designed for personalized chelation therapy in TI, which can effectively and safely remove all the excess toxic iron and prevent cardiac, liver, and other organ damage. Both L1 and DF could also prevent iron absorption. The new oral chelator deferasirox (DFX) increases iron excretion and decreases liver iron in TM and TI. There are drawbacks in the use of DFX in TI, such as limitations related to dose, toxicity, and cost, iron load of the patients, and ineffective removal of excess iron from the heart. Furthermore, DFX appears to increase iron and other toxic metal absorption. Future treatments of TI and related iron-loading conditions could involve the use of the iron-chelating drugs and other drug combinations not only for increasing iron excretion but also for preventing iron absorption. PMID:26893541

Efficacy and safety of iron-chelation therapy with deferoxamine, deferiprone, and deferasirox for the treatment of iron-loaded patients with non-transfusion-dependent thalassemia syndromes.

PubMed

Kontoghiorghe, Christina N; Kontoghiorghes, George J

2016-01-01

The prevalence rate of thalassemia, which is endemic in Southeast Asia, the Middle East, and the Mediterranean, exceeds 100,000 live births per year. There are many genetic variants in thalassemia with different pathological severity, ranging from a mild and asymptomatic anemia to life-threatening clinical effects, requiring lifelong treatment, such as regular transfusions in thalassemia major (TM). Some of the thalassemias are non-transfusion-dependent, including many thalassemia intermedia (TI) variants, where iron overload is caused by chronic increase in iron absorption due to ineffective erythropoiesis. Many TI patients receive occasional transfusions. The rate of iron overloading in TI is much slower in comparison to TM patients. Iron toxicity in TI is usually manifested by the age of 30-40 years, and in TM by the age of 10 years. Subcutaneous deferoxamine (DFO), oral deferiprone (L1), and DFO-L1 combinations have been effectively used for more than 20 years for the treatment of iron overload in TM and TI patients, causing a significant reduction in morbidity and mortality. Selected protocols using DFO, L1, and their combination can be designed for personalized chelation therapy in TI, which can effectively and safely remove all the excess toxic iron and prevent cardiac, liver, and other organ damage. Both L1 and DF could also prevent iron absorption. The new oral chelator deferasirox (DFX) increases iron excretion and decreases liver iron in TM and TI. There are drawbacks in the use of DFX in TI, such as limitations related to dose, toxicity, and cost, iron load of the patients, and ineffective removal of excess iron from the heart. Furthermore, DFX appears to increase iron and other toxic metal absorption. Future treatments of TI and related iron-loading conditions could involve the use of the iron-chelating drugs and other drug combinations not only for increasing iron excretion but also for preventing iron absorption.

Parenteral irons versus transfused red blood cells for treatment of anemia during canine experimental bacterial pneumonia.

PubMed

Suffredini, Dante A; Xu, Wanying; Sun, Junfeng; Barea-Mendoza, Jesús; Solomon, Steven B; Brashears, Samuel L; Perlegas, Andreas; Kim-Shapiro, Daniel B; Klein, Harvey G; Natanson, Charles; Cortés-Puch, Irene

2017-10-01

No studies have been performed comparing intravenous (IV) iron with transfused red blood cells (RBCs) for treating anemia during infection. In a previous report, transfused older RBCs increased free iron release and mortality in infected animals when compared to fresher cells. We hypothesized that treating anemia during infection with transfused fresh RBCs, with minimal free iron release, would prove superior to IV iron therapy. Purpose-bred beagles (n = 42) with experimental Staphylococcus aureus pneumonia rendered anemic were randomized to be transfused RBCs stored for 7 days or one of two IV iron preparations (7 mg/kg), iron sucrose, a widely used preparation, or ferumoxytol, a newer formulation that blunts circulating iron levels. Both irons increased the alveolar-arterial oxygen gradient at 24 to 48 hours (p = 0.02-0.001), worsened shock at 16 hours (p = 0.02-0.003, respectively), and reduced survival (transfusion 56%; iron sucrose 8%, p = 0.01; ferumoxytol 9%, p = 0.04). Compared to fresh RBC transfusion, plasma iron measured by non-transferrin-bound iron levels increased with iron sucrose at 7, 10, 13, 16, 24, and 48 hours (p = 0.04 to p < 0.0001) and ferumoxytol at 7, 24, and 48 hours (p = 0.04 to p = 0.004). No significant differences in cardiac filling pressures or performance, hemoglobin (Hb), or cell-free Hb were observed. During canine experimental bacterial pneumonia, treatment of mild anemia with IV iron significantly increased free iron levels, shock, lung injury, and mortality compared to transfusion of fresh RBCs. This was true for iron preparations that do or do not blunt circulating free iron level elevations. These findings suggest that treatment of anemia with IV iron during infection should be undertaken with caution. © 2017 AABB.

Hemolytic anemia repressed hepcidin level without hepatocyte iron overload: lesson from Günther disease model

PubMed Central

Millot, Sarah; Delaby, Constance; Moulouel, Boualem; Lefebvre, Thibaud; Pilard, Nathalie; Ducrot, Nicolas; Ged, Cécile; Lettéron, Philippe; de Franceschi, Lucia; Deybach, Jean Charles; Beaumont, Carole; Gouya, Laurent; De Verneuil, Hubert; Lyoumi, Saïd; Puy, Hervé; Karim, Zoubida

2017-01-01

Hemolysis occurring in hematologic diseases is often associated with an iron loading anemia. This iron overload is the result of a massive outflow of hemoglobin into the bloodstream, but the mechanism of hemoglobin handling has not been fully elucidated. Here, in a congenital erythropoietic porphyria mouse model, we evaluate the impact of hemolysis and regenerative anemia on hepcidin synthesis and iron metabolism. Hemolysis was confirmed by a complete drop in haptoglobin, hemopexin and increased plasma lactate dehydrogenase, an increased red blood cell distribution width and osmotic fragility, a reduced half-life of red blood cells, and increased expression of heme oxygenase 1. The erythropoiesis-induced Fam132b was increased, hepcidin mRNA repressed, and transepithelial iron transport in isolated duodenal loops increased. Iron was mostly accumulated in liver and spleen macrophages but transferrin saturation remained within the normal range. The expression levels of hemoglobin-haptoglobin receptor CD163 and hemopexin receptor CD91 were drastically reduced in both liver and spleen, resulting in heme- and hemoglobin-derived iron elimination in urine. In the kidney, the megalin/cubilin endocytic complex, heme oxygenase 1 and the iron exporter ferroportin were induced, which is reminiscent of significant renal handling of hemoglobin-derived iron. Our results highlight ironbound hemoglobin urinary clearance mechanism and strongly suggest that, in addition to the sequestration of iron in macrophages, kidney may play a major role in protecting hepatocytes from iron overload in chronic hemolysis. PMID:28143953

Hemolytic anemia repressed hepcidin level without hepatocyte iron overload: lesson from Günther disease model.

PubMed

Millot, Sarah; Delaby, Constance; Moulouel, Boualem; Lefebvre, Thibaud; Pilard, Nathalie; Ducrot, Nicolas; Ged, Cécile; Lettéron, Philippe; de Franceschi, Lucia; Deybach, Jean Charles; Beaumont, Carole; Gouya, Laurent; De Verneuil, Hubert; Lyoumi, Saïd; Puy, Hervé; Karim, Zoubida

2017-02-01

Hemolysis occurring in hematologic diseases is often associated with an iron loading anemia. This iron overload is the result of a massive outflow of hemoglobin into the bloodstream, but the mechanism of hemoglobin handling has not been fully elucidated. Here, in a congenital erythropoietic porphyria mouse model, we evaluate the impact of hemolysis and regenerative anemia on hepcidin synthesis and iron metabolism. Hemolysis was confirmed by a complete drop in haptoglobin, hemopexin and increased plasma lactate dehydrogenase, an increased red blood cell distribution width and osmotic fragility, a reduced half-life of red blood cells, and increased expression of heme oxygenase 1. The erythropoiesis-induced Fam132b was increased, hepcidin mRNA repressed, and transepithelial iron transport in isolated duodenal loops increased. Iron was mostly accumulated in liver and spleen macrophages but transferrin saturation remained within the normal range. The expression levels of hemoglobin-haptoglobin receptor CD163 and hemopexin receptor CD91 were drastically reduced in both liver and spleen, resulting in heme- and hemoglobin-derived iron elimination in urine. In the kidney, the megalin/cubilin endocytic complex, heme oxygenase 1 and the iron exporter ferroportin were induced, which is reminiscent of significant renal handling of hemoglobin-derived iron. Our results highlight ironbound hemoglobin urinary clearance mechanism and strongly suggest that, in addition to the sequestration of iron in macrophages, kidney may play a major role in protecting hepatocytes from iron overload in chronic hemolysis. Copyright© Ferrata Storti Foundation.

Iron acquisition in the cystic fibrosis lung and potential for novel therapeutic strategies

PubMed Central

Tyrrell, Jean

2016-01-01

Iron acquisition is vital to microbial survival and is implicated in the virulence of many of the pathogens that reside in the cystic fibrosis (CF) lung. The multifaceted nature of iron acquisition by both bacterial and fungal pathogens encompasses a range of conserved and species-specific mechanisms, including secretion of iron-binding siderophores, utilization of siderophores from other species, release of iron from host iron-binding proteins and haemoproteins, and ferrous iron uptake. Pathogens adapt and deploy specific systems depending on iron availability, bioavailability of the iron pool, stage of infection and presence of competing pathogens. Understanding the dynamics of pathogen iron acquisition has the potential to unveil new avenues for therapeutic intervention to treat both acute and chronic CF infections. Here, we examine the range of strategies utilized by the primary CF pathogens to acquire iron and discuss the different approaches to targeting iron acquisition systems as an antimicrobial strategy. PMID:26643057

Submerged Glow-Discharge Plasma: An Economical Approach to Convert Construction Scrap Metal into Nanomaterials

NASA Astrophysics Data System (ADS)

Yek, Peter Nai Yuh; Rafiq Mirza Julaihi, Muhammad; Shahril Osman, Mohammad; Tiong, Tung Chuan; Lee, Wak Ha; Leing Lee, Chern

2018-03-01

Submerged glow-discharge plasma (SGDP) is relatively new among the various methods available for nanomaterials synthesis (NMs) techniques. This method allows great control over the production cost of nanomaterials synthesis. A lab-scale batch type SDGP technology has been constructed to produce nanomaterials and investigate the inter-relationship between plasma excitation voltages, electrodes submerged areas and electrolyte concentration. Metal oxide nanospheres has been synthesised from different electrolyte concentrations (1M-0.001M) and characterized by Scanning Electron Microscopy (SEM) and Energy Dispersive Spectroscopy (EDS). As the major results showed that the nanospheres are uniformly spherical with diameter size distribution are between 100 nm - 2μm. EDS analysis shown the nano-Iron Oxide have been formed. Scrap metal initially showed around 6.45% and 93.55% of Carbon and Iron composition respectively. After SGDP process to the scrap metal, Carbon content has increased to 34-35% and Iron content has reduced to around 15-40%. EDS results also shown the higher percentage of Iron amount has remained with lower electrolyte concentration and Current is proportionally related to submersion area of cathode.

Targeting iron metabolism in drug discovery and delivery

PubMed Central

Crielaard, Bart J.; Lammers, Twan; Rivella, Stefano

2017-01-01

Iron fulfils a central role in many essential biochemical processes in human physiology, which makes proper processing of iron crucial. Although iron metabolism is subject to relatively strict physiological control, in recent years numerous disorders, such as cancer and neurodegenerative diseases, have been linked to deregulated iron homeostasis. Because of its involvement in the pathogenesis of these diseases, iron metabolism constitutes a promising and largely unexploited therapeutic target for the development of new pharmacological treatments. Several iron metabolism-targeted therapies are already under clinical evaluation for haematological disorders, and these and newly developed therapeutic agents will likely have substantial benefit in the clinical management of iron metabolism-associated diseases, for which few efficacious treatments are often available. PMID:28154410

Role of iron in the pathogenesis of cysteamine-induced duodenal ulceration in rats

PubMed Central

Khomenko, Tetyana; Szabo, Sandor; Deng, Xiaoming; Ishikawa, Hideki; Anderson, Gregory J.; McLaren, Gordon D.

2009-01-01

Cysteamine induces perforating duodenal ulcers in rats within 24–48 h. This reducing aminothiol generates hydrogen peroxide in the presence of transition metals (e.g., ferric iron), producing oxidative stress, which may contribute to organ-specific tissue damage. Since most intestinal iron absorption takes place in the proximal duodenum, we hypothesized that cysteamine may disrupt regulation of mucosal iron transport, and iron may facilitate cysteamine-induced duodenal ulceration. We show here that cysteamine-induced ulceration was aggravated by pretreatment of rats with Fe3+ or Fe2+ compounds, which elevated iron concentration in the duodenal mucosa. In contrast, feeding rats an iron-deficient diet was associated with a 4.6-fold decrease in ulcer formation, accompanied by a 34% decrease (P < 0.05) in the duodenal mucosal iron concentration. Administration of deferoxamine inhibited ulceration by 65%. We also observed that the antiulcer effect of H2 receptor antagonist cimetidine included a 35% decrease in iron concentration in the duodenal mucosa. Cysteamine-induced duodenal ulcers were also decreased in iron-deficient Belgrade rats (P < 0.05). In normal rats, cysteamine administration increased the iron concentration in the proximal duodenal mucosa by 33% in the preulcerogenic stage but at the same time decreased serum iron (P < 0.05). Cysteamine also enhanced activation of mucosal iron regulatory protein 1 and increased the expression of divalent metal transporter 1 mRNA and protein. Transferrin receptor 1 protein expression was also increased, although mucosal ferroportin and ferritin remained almost unchanged. These results indicate an expansion of the intracellular labile iron pool in the duodenal mucosa, increasing its susceptibility to oxidative stress, and suggest a role for iron in the pathogenesis of organ-specific tissue injury such as duodenal ulcers. PMID:19342511

Effects of iron overload in a rat nutritional model of non-alcoholic fatty liver disease.

PubMed

Kirsch, Richard; Sijtsema, Helene P; Tlali, Mpho; Marais, Adrian D; Hall, Pauline de la M

2006-12-01

This study sought to determine whether excess hepatic iron potentiates liver injury in the methionine choline-deficient (MCD) model of non-alcoholic fatty liver disease (NAFLD). Iron-loaded rats were fed either MCD or control diets [MCD diet plus choline bitartrate (2 g/kg) and DL-methionine (3 g/kg)] for 4 and 12 weeks, after which liver pathology, hepatic iron, triglyceride, lipid peroxidation products and hydroxyproline (HYP) levels and serum alanine aminotransferase (ALT) levels were evaluated. Iron supplementation in MCD animals resulted in histologic evidence of hepatic iron overload at 4 and 12 weeks and a 14-fold increase in hepatic iron concentration at 12 weeks (P < 0.001). Iron supplementation in these animals was associated with increased lobular necroinflammation at 4 weeks (P < 0.02) and decreased hepatic steatosis (P < 0.01), hepatic triglyceride levels (P < 0.01), hepatic-conjugated dienes (CD; P < 0.02) and serum ALT levels (P < 0.002) at 12 weeks. Reduced hepatic steatosis (P < 0.005) and CD (P < 0.01) were apparent by 4 weeks. Iron supplementation was associated with a trend towards increased perivenular fibrosis not hepatic HYP content. Hepatic iron overload in the MCD model of NAFLD is associated with decreased hepatic lipid, decreased early lipid peroxidation products, increased necroinflammation and a trend towards increased perivenular fibrosis.

Cell wall targeted in planta iron accumulation enhances biomass conversion and seed iron concentration in Arabidopsis and rice.

PubMed

Yang, Haibing; Wei, Hui; Ma, Guojie; Antunes, Mauricio S; Vogt, Stefan; Cox, Joseph; Zhang, Xiao; Liu, Xiping; Bu, Lintao; Gleber, S Charlotte; Carpita, Nicholas C; Makowski, Lee; Himmel, Michael E; Tucker, Melvin P; McCann, Maureen C; Murphy, Angus S; Peer, Wendy A

2016-10-01

Conversion of nongrain biomass into liquid fuel is a sustainable approach to energy demands as global population increases. Previously, we showed that iron can act as a catalyst to enhance the degradation of lignocellulosic biomass for biofuel production. However, direct addition of iron catalysts to biomass pretreatment is diffusion-limited, would increase the cost and complexity of biorefinery unit operations and may have deleterious environmental impacts. Here, we show a new strategy for in planta accumulation of iron throughout the volume of the cell wall where iron acts as a catalyst in the deconstruction of lignocellulosic biomass. We engineered CBM-IBP fusion polypeptides composed of a carbohydrate-binding module family 11 (CBM11) and an iron-binding peptide (IBP) for secretion into Arabidopsis and rice cell walls. CBM-IBP transformed Arabidopsis and rice plants show significant increases in iron accumulation and biomass conversion compared to respective controls. Further, CBM-IBP rice shows a 35% increase in seed iron concentration and a 40% increase in seed yield in greenhouse experiments. CBM-IBP rice potentially could be used to address iron deficiency, the most common and widespread nutritional disorder according to the World Health Organization. © 2016 The Authors. Plant Biotechnology Journal published by Society for Experimental Biology and The Association of Applied Biologists and John Wiley & Sons Ltd.

Overexpression of native ferritin gene MusaFer1 enhances iron content and oxidative stress tolerance in transgenic banana plants

PubMed Central

Yadav, Karuna; Patel, Prashanti; Srivastava, Ashish Kumar

2017-01-01

Iron is an indispensable element for plant growth and defense and hence it is essential to improve the plant’s ability to accumulate iron. Besides, it is also an important aspect for human health. In view of this, we attempted to increase the iron content in banana cultivar Rasthali using MusaFer1 as a candidate gene. Initially, the expression of all five genes of the MusaFer family (MusaFer1-5) was quantified under iron-excess and -deficient conditions. The supplementation of 250 and 350 μM iron enhanced expression of all MusaFer genes; however, MusaFer1 was increased maximally by 2- and 4- fold in leaves and roots respectively. Under iron deficient condition, all five MusaFer genes were downregulated, indicating their iron dependent regulation. In MusaFer1 overexpressing lines, iron content was increased by 2- and 3-fold in leaves and roots respectively, as compared with that of untransformed lines. The increased iron was mainly localized in the epidermal regions of petiole. The analysis of MusaFer1 promoter indicated that it might control the expression of iron metabolism related genes and also other genes of MusaFer family. MusaFer1 overexpression led to downregulated expression of MusaFer3, MusaFer4 and MusaFer5 in transgenic leaves which might be associated with the plant’s compensatory mechanism in response to iron flux. Other iron metabolism genes like Ferric reductase (FRO), transporters (IRT, VIT and YSL) and chelators (NAS, DMAS and NAAT) were also differentially expressed in transgenic leaf and root, suggesting the multifaceted impact of MusaFer1 towards iron uptake and organ distribution. Additionally, MusaFer1 overexpression increased plant tolerance against methyl viologen and excess iron which was quantified in terms of photosynthetic efficiency and malondialdehyde content. Thus, the study not only broadens our understanding about iron metabolism but also highlights MusaFer1 as a suitable candidate gene for iron fortification in banana. PMID:29190821

Additional oxidative stress reroutes the global response of Aspergillus fumigatus to iron depletion.

PubMed

Kurucz, Vivien; Krüger, Thomas; Antal, Károly; Dietl, Anna-Maria; Haas, Hubertus; Pócsi, István; Kniemeyer, Olaf; Emri, Tamás

2018-05-10

Aspergillus fumigatus has to cope with a combination of several stress types while colonizing the human body. A functional interplay between these different stress responses can increase the chances of survival for this opportunistic human pathogen during the invasion of its host. In this study, we shed light on how the H 2 O 2 -induced oxidative stress response depends on the iron available to this filamentous fungus, using transcriptomic analysis, proteomic profiles, and growth assays. The applied H 2 O 2 treatment, which induced only a negligible stress response in iron-replete cultures, deleteriously affected the fungus under iron deprivation. The majority of stress-induced changes in gene and protein expression was not predictable from data coming from individual stress exposure and was only characteristic for the combination of oxidative stress plus iron deprivation. Our experimental data suggest that the physiological effects of combined stresses and the survival of the fungus highly depend on fragile balances between economization of iron and production of essential iron-containing proteins. One observed strategy was the overproduction of iron-independent antioxidant proteins to combat oxidative stress during iron deprivation, e.g. the upregulation of superoxide dismutase Sod1, the thioredoxin reductase Trr1, and the thioredoxin orthologue Afu5g11320. On the other hand, oxidative stress induction overruled iron deprivation-mediated repression of several genes. In agreement with the gene expression data, growth studies underlined that in A. fumigatus iron deprivation aggravates oxidative stress susceptibility. Our data demonstrate that studying stress responses under separate single stress conditions is not sufficient to understand how A. fumigatus adapts in a complex and hostile habitat like the human body. The combinatorial stress of iron depletion and hydrogen peroxide caused clear non-additive effects upon the stress response of A. fumigatus. Our data further supported the view that the ability of A. fumigatus to cause diseases in humans strongly depends on its fitness attributes and less on specific virulence factors. In summary, A. fumigatus is able to mount and coordinate complex and efficient responses to combined stresses like iron deprivation plus H 2 O 2 -induced oxidative stress, which are exploited by immune cells to kill fungal pathogens.

Silencing the Menkes Copper-Transporting ATPase (Atp7a) Gene in Rat Intestinal Epithelial (IEC-6) Cells Increases Iron Flux via Transcriptional Induction of Ferroportin 1 (Fpn1)123

PubMed Central

Gulec, Sukru; Collins, James F.

2014-01-01

The Menkes copper-transporting ATPase (Atp7a) gene is induced in rat duodenum during iron deficiency, consistent with copper accumulation in the intestinal mucosa and liver. To test the hypothesis that ATP7A influences intestinal iron metabolism, the Atp7a gene was silenced in rat intestinal epithelial (IEC-6) cells using short hairpin RNA (shRNA) technology. Perturbations in intracellular copper homeostasis were noted in knockdown cells, consistent with the dual roles of ATP7A in pumping copper into the trans-Golgi (for cuproenzyme synthesis) and exporting copper from cells. Intracellular iron concentrations were unaffected by Atp7a knockdown. Unexpectedly, however, vectorial iron (59Fe) transport increased (∼33%) in knockdown cells grown in bicameral inserts and increased further (∼70%) by iron deprivation (compared with negative control shRNA-transfected cells). Additional experiments were designed to elucidate the molecular mechanism of increased transepithelial iron flux. Enhanced iron uptake by knockdown cells was associated with increased expression of a ferrireductase (duodenal cytochrome b) and activity of a cell-surface ferrireductase. Increased iron efflux from knockdown cells was likely mediated via transcriptional activation of the ferroportin 1 gene (by an unknown mechanism). Moreover, Atp7a knockdown significantly attenuated expression of an iron oxidase [hephaestin (HEPH); by ∼80%] and membrane ferroxidase activity (by ∼50%). Cytosolic ferroxidase activity, however, was retained in knockdown cells (75% of control cells), perhaps compensating for diminished HEPH activity. This investigation has thus documented alterations in iron homeostasis associated with Atp7a knockdown in enterocyte-like cells. Alterations in copper transport, trafficking, or distribution may underlie the increase in transepithelial iron flux noted when ATP7A activity is diminished. PMID:24174620

Effects of iron on optical properties of dissolved organic matter.

PubMed

Poulin, Brett A; Ryan, Joseph N; Aiken, George R

2014-09-02

Iron is a source of interference in the spectroscopic analysis of dissolved organic matter (DOM); however, its effects on commonly employed ultraviolet and visible (UV-vis) light adsorption and fluorescence measurements are poorly defined. Here, we describe the effects of iron(II) and iron(III) on the UV-vis absorption and fluorescence of solutions containing two DOM fractions and two surface water samples. In each case, regardless of DOM composition, UV-vis absorption increased linearly with increasing iron(III). Correction factors were derived using iron(III) absorption coefficients determined at wavelengths commonly used to characterize DOM. Iron(III) addition increased specific UV absorbances (SUVA) and decreased the absorption ratios (E2:E3) and spectral slope ratios (SR) of DOM samples. Both iron(II) and iron(III) quenched DOM fluorescence at pH 6.7. The degree and region of fluorescence quenching varied with the iron:DOC concentration ratio, DOM composition, and pH. Regions of the fluorescence spectra associated with greater DOM conjugation were more susceptible to iron quenching, and DOM fluorescence indices were sensitive to the presence of both forms of iron. Analyses of the excitation-emission matrices using a 7- and 13-component parallel factor analysis (PARAFAC) model showed low PARAFAC sensitivity to iron addition.

Effects of iron on optical properties of dissolved organic matter

USGS Publications Warehouse

Poulin, Brett; Ryan, Joseph N.; Aiken, George R.

2014-01-01

Iron is a source of interference in the spectroscopic analysis of dissolved organic matter (DOM); however, its effects on commonly employed ultraviolet and visible (UV–vis) light adsorption and fluorescence measurements are poorly defined. Here, we describe the effects of iron(II) and iron(III) on the UV–vis absorption and fluorescence of solutions containing two DOM fractions and two surface water samples. In each case, regardless of DOM composition, UV–vis absorption increased linearly with increasing iron(III). Correction factors were derived using iron(III) absorption coefficients determined at wavelengths commonly used to characterize DOM. Iron(III) addition increased specific UV absorbances (SUVA) and decreased the absorption ratios (E2:E3) and spectral slope ratios (SR) of DOM samples. Both iron(II) and iron(III) quenched DOM fluorescence at pH 6.7. The degree and region of fluorescence quenching varied with the iron:DOC concentration ratio, DOM composition, and pH. Regions of the fluorescence spectra associated with greater DOM conjugation were more susceptible to iron quenching, and DOM fluorescence indices were sensitive to the presence of both forms of iron. Analyses of the excitation–emission matrices using a 7- and 13-component parallel factor analysis (PARAFAC) model showed low PARAFAC sensitivity to iron addition.

Sphagnum-dominated bog systems are highly effective yet variable sources of bio-available iron to marine waters.

PubMed

Krachler, Regina; Krachler, Rudolf F; Wallner, Gabriele; Steier, Peter; El Abiead, Yasin; Wiesinger, Hubert; Jirsa, Franz; Keppler, Bernhard K

2016-06-15

Iron is a micronutrient of particular interest as low levels of iron limit primary production of phytoplankton and carbon fluxes in extended regions of the world's oceans. Sphagnum-peatland runoff is extraordinarily rich in dissolved humic-bound iron. Given that several of the world's largest wetlands are Sphagnum-dominated peatlands, this ecosystem type may serve as one of the major sources of iron to the ocean. Here, we studied five near-coastal creeks in North Scotland using freshwater/seawater mixing experiments of natural creek water and synthetic seawater based on a (59)Fe radiotracer technique combined with isotopic characterization of dissolved organic carbon by Accelerator Mass Spectrometry. Three of the creeks meander through healthy Sphagnum-dominated peat bogs and the two others through modified peatlands which have been subject to artificial drainage for centuries. The results revealed that, at the time of sampling (August 16-24, 2014), the creeks that run through modified peatlands delivered 11-15μg iron per liter creek water to seawater, whereas the creeks that run through intact peatlands delivered 350-470μg iron per liter creek water to seawater. To find out whether this humic-bound iron is bio-available to marine algae, we performed algal growth tests using the unicellular flagellated marine prymnesiophyte Diacronema lutheri and the unicellular marine green alga Chlorella salina, respectively. In both cases, the riverine humic material provided a highly bio-available source of iron to the marine algae. These results add a new item to the list of ecosystem services of Sphagnum-peatlands. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

Water resources of the Marquette Iron Range area, Michigan

USGS Publications Warehouse

Wiitala, Sulo Werner; Newport, Thomas Gwyn; Skinner, Earl L.

1967-01-01

Large quantities of water are needed in the beneficiation and pelletizing processes by which the ore mined from low-grade iron-formations is upgraded into an excellent raw material for the iron and steel industry. Extensive reserves of low-grade iron-formation available for development herald an intensification of the demands upon the area's water supplies. This study was designed to provide water facts for public and private agencies in planning orderly development and in guiding the management of the water resources to meet existing and new requirements. Inland lakes and streams are the best potential sources of water for immediate development. The natural flow available for 90 percent of the time in the Middle and East Branches of the Escanaba River, the Carp River, and the Michigamme River is about 190 cubic feet per second. Potential storage sites are identified, and their complete development could increase the available supply from the above streams to about 450 cubic feet per second. Outwash deposits are the best potential sources of ground water. Large supplies could be developed from extensive outwash deposits in the eastern part of the area adjacent to Goose Lake Outlet and the East Branch Escanaba River. Other areas of outwash occur in the vicinity of Humboldt, West Branch Creek, and along the stream valleys. Streamflow data were used to make rough approximations of the ground-water potential in some areas. In general, however, the available data were not sufficient to permit quantitative evaluation of the potential ground-water supplies. Chemical quality of the surface and ground waters of the area is generally acceptable for most uses. Suspended sediment in the form of mineral tailings in effluents from ore-processing plants is a potential problem. Existing plants use settling basins to effectively remove most of the suspended material. Available records indicate that suspended-sediment concentrations and loads in the receiving waters have not been significantly increased by these operations. Present water use is about 60 cubic feet per second in the area. Thus, available water supplies are believed to be adequate for existing and foreseeable new uses. Water management, rather than water availability, is of prime consideration in this area. Time distribution of available water supplies, distribution of water to points of use, effect of surface-water development upon ground water and vice versa, and possible conflicts with competing uses are some of the management problems that are discussed. The presence of many inland lakes, favorable storage sites on streams, and several promising acquifers provide flexibility in possible water-management operations. A discussion of the interrelationships between surface and ground water and a ground-water budget are presented to render a better understanding of the hydrologic system with which water management will be concerned.

Iron-binding haemerythrin RING ubiquitin ligases regulate plant iron responses and accumulation

PubMed Central

Kobayashi, Takanori; Nagasaka, Seiji; Senoura, Takeshi; Itai, Reiko Nakanishi; Nakanishi, Hiromi; Nishizawa, Naoko K.

2013-01-01

Iron is essential for most living organisms. Plants transcriptionally induce genes involved in iron acquisition under conditions of low iron availability, but the nature of the deficiency signal and its sensors are unknown. Here we report the identification of new iron regulators in rice, designated Oryza sativa Haemerythrin motif-containing Really Interesting New Gene (RING)- and Zinc-finger protein 1 (OsHRZ1) and OsHRZ2. OsHRZ1, OsHRZ2 and their Arabidopsis homologue BRUTUS bind iron and zinc, and possess ubiquitination activity. OsHRZ1 and OsHRZ2 are susceptible to degradation in roots irrespective of iron conditions. OsHRZ-knockdown plants exhibit substantial tolerance to iron deficiency, and accumulate more iron in their shoots and grains irrespective of soil iron conditions. The expression of iron deficiency-inducible genes involved in iron utilization is enhanced in OsHRZ-knockdown plants, mostly under iron-sufficient conditions. These results suggest that OsHRZ1 and OsHRZ2 are iron-binding sensors that negatively regulate iron acquisition under conditions of iron sufficiency. PMID:24253678

Whole cow's milk in infancy.

PubMed

Leung, Alexander Kc; Sauve, Reginald S

2003-09-01

Early introduction of whole cow's milk may lead to iron deficiency anemia. From a nutritional point of view, it is best to delay the introduction of whole cow's milk until the infant is one year old. While there is no evidence to suggest adverse clinical sequelae associated with the increased renal solute load in healthy infants, feeding with whole cow's milk would narrow the margin of safety in situations that may lead to dehydration. Early exposure to cow's milk proteins increases the risk of developing allergy to milk proteins. Because of the possible association between early exposure to cow's milk proteins and risk for type 1 diabetes mellitus, breast-feeding and avoidance of commercially available cow's milk and products containing intact cow's milk protein during the first year of life are strongly encouraged in families with a strong history of insulin dependent diabetes mellitus. The authors suggest that the optimal food in infancy is human breast milk. If human milk is not available, it is preferred that iron-fortified formulas rather than whole cow's milk be used during the first year of life.

Tubular iron deposition and iron handling proteins in human healthy kidney and chronic kidney disease.

PubMed

Raaij, Sanne van; Swelm, Rachel van; Bouman, Karlijn; Cliteur, Maaike; Heuvel, Marius van den; Pertijs, Jeanne; Patel, Dominic; Bass, Paul; Goor, Harry van; Unwin, Robert; Srai, Surjit Kaila; Swinkels, Dorine

2018-06-19

Iron is suggested to play a detrimental role in the progression of chronic kidney disease (CKD). The kidney recycles iron back into the circulation. However, the localization of proteins relevant for physiological tubular iron handling and their potential role in CKD remain unclear. We examined associations between iron deposition, expression of iron handling proteins and tubular injury in kidney biopsies from CKD patients and healthy controls using immunohistochemistry. Iron was deposited in proximal (PT) and distal tubules (DT) in 33% of CKD biopsies, predominantly in pathologies with glomerular dysfunction, but absent in controls. In healthy kidney, PT contained proteins required for iron recycling including putative iron importers ZIP8, ZIP14, DMT1, iron storage proteins L- and H-ferritin and iron exporter ferroportin, while DT only contained ZIP8, ZIP14, and DMT1. In CKD, iron deposition associated with increased intensity of iron importers (ZIP14, ZIP8), storage proteins (L-, H-ferritin), and/or decreased ferroportin abundance. This demonstrates that tubular iron accumulation may result from increased iron uptake and/or inadequate iron export. Iron deposition associated with oxidative injury as indicated by heme oxygenase-1 abundance. In conclusion, iron deposition is relatively common in CKD, and may result from altered molecular iron handling and may contribute to renal injury.

Response of Phytoplankton Iron Contents to Gradients in Iron Availability in the California Current System

NASA Astrophysics Data System (ADS)

Twining, B. S.; Jacquot, J. E.; Rauschenberg, S.; Enright, J.; Marchetti, A.; Cohen, N.; Brown, M.; Parker, C.; Bruland, K. W.

2016-02-01

Iron is a critical micronutrient that controls primary production in large swaths of the global ocean. Experiments with laboratory cultures indicate that phytoplankton differ in their ability to compete for and store Fe in response to varying ambient Fe concentrations. However there are very few measurements of the physiological responses of natural phytoplankton populations to gradients in Fe availability. Incubation experiments were conducted off the coast of California and Oregon at two sites characterized by a 10-fold difference in dissolved Fe (0.3 and 3 nM). In each experiment, incubation water was amended with either dissolved Fe (5-10 nM), the model siderophore desferrioxamine B (DFB; 200 nM), or left unamended. Iron contents of three abundant diatom groups (Chaetoceros sp. and large and small pennate diatoms) were monitored by synchrotron X-ray fluorescence, along with dissolved and bulk particulate trace metals and macronutrients over the course of 3 days. Transcriptomic samples were also collected at daily timepoints to assess molecular responses. Added dissolved Fe was drawn down in both experiments, while DFB appeared to solubilize a fraction of ambient particulate Fe in the high-Fe experiment. Iron quotas of unamended diatoms were nearly 10-fold higher under high-Fe conditions. Quotas increased in response to added Fe in both experiments, but the magnitude of changes varied between diatom taxa. DFB additions resulted in reduced Fe quotas in the low-Fe incubation, since cells were presumably forced to use internal Fe stores to support growth. These data demonstrate significant plasticity in the abilities of phytoplankton to take advantage of changing micronutrient inputs. Quota data will be compared to transcript abundance data to ascertain mechanisms of Fe quota maintenance.

A Comparative Study of Iron Uptake Mechanisms in Marine Microalgae: Iron Binding at the Cell Surface Is a Critical Step1[W][OA

PubMed Central

Sutak, Robert; Botebol, Hugo; Blaiseau, Pierre-Louis; Léger, Thibaut; Bouget, François-Yves; Camadro, Jean-Michel; Lesuisse, Emmanuel

2012-01-01

We investigated iron uptake mechanisms in five marine microalgae from different ecologically important phyla: the diatoms Phaeodactylum tricornutum and Thalassiosira pseudonana, the prasinophyceae Ostreococcus tauri and Micromonas pusilla, and the coccolithophore Emiliania huxleyi. Among these species, only the two diatoms were clearly able to reduce iron, via an inducible (P. tricornutum) or constitutive (T. pseudonana) ferrireductase system displaying characteristics similar to the yeast (Saccharomyces cerevisiae) flavohemoproteins proteins. Iron uptake mechanisms probably involve very different components according to the species, but the species we studied shared common features. Regardless of the presence and/or induction of a ferrireductase system, all the species were able to take up both ferric and ferrous iron, and iron reduction was not a prerequisite for uptake. Iron uptake decreased with increasing the affinity constants of iron-ligand complexes and with increasing ligand-iron ratios. Therefore, at least one step of the iron uptake mechanism involves a thermodynamically controlled process. Another step escapes to simple thermodynamic rules and involves specific and strong binding of ferric as well as ferrous iron at the cell surface before uptake of iron. Binding was paradoxically increased in iron-rich conditions, whereas uptake per se was induced in all species only after prolonged iron deprivation. We sought cell proteins loaded with iron following iron uptake. One such protein in O. tauri may be ferritin, and in P. tricornutum, Isip1 may be involved. We conclude that the species we studied have uptake systems for both ferric and ferrous iron, both involving specific iron binding at the cell surface. PMID:23033141

High dietary iron increases oxidative stress and radiosensitivity in the rat retina and vasculature after exposure to fractionated gamma radiation

PubMed Central

Theriot, Corey A; Westby, Christian M; Morgan, Jennifer L L; Zwart, Sara R; Zanello, Susana B

2016-01-01

Radiation exposure in combination with other space environmental factors including microgravity, nutritional status, and deconditioning is a concern for long-duration space exploration missions. Astronauts experience altered iron homeostasis due to adaptations to microgravity and an iron-rich food system. Iron intake reaches three to six times the recommended daily allowance due to the use of fortified foods on the International Space Station. Iron is associated with certain optic neuropathies and can potentiate oxidative stress. This study examined the response of eye and vascular tissue to gamma radiation exposure (3 Gy fractionated at 37.5 cGy per day every other day for 8 fractions) in rats fed an adequate-iron diet or a high-iron diet. Twelve-week-old Sprague-Dawley rats were assigned to one of four experimental groups: adequate-iron diet/no radiation (CON), high-iron diet/no radiation (IRON), adequate-iron diet/radiation (RAD), and high-iron diet/radiation (IRON+RAD). Animals were maintained on the corresponding iron diet for 2 weeks before radiation exposure. As previously published, the high-iron diet resulted in elevated blood and liver iron levels. Dietary iron overload altered the radiation response observed in serum analytes, as evidenced by a significant increase in catalase levels and smaller decrease in glutathione peroxidase and total antioxidant capacity levels. 8-OHdG immunostaining, showed increased intensity in the retina after radiation exposure. Gene expression profiles of retinal and aortic vascular samples suggested an interaction between the response to radiation and high dietary iron. This study suggests that the combination of gamma radiation and high dietary iron has deleterious effects on retinal and vascular health and physiology. PMID:28725729

Influence of Atmospheric Processes on the Solubility and Composition of Iron in Saharan Dust

NASA Astrophysics Data System (ADS)

Ingall, E. D.; Longo, A.; Feng, Y.; Lai, B.; Landing, W. M.; Shelley, R.; Nenes, A.; Mihalopoulos, N.; Violaki, K.

2016-12-01

Iron is a key micronutrient that is vital for all organisms. The supply of bioavailable, soluble iron controls primary productivity in approximately 30% of the world's oceans. The significant contribution of atmospheric aerosols to the bioavailable iron budget in vast ocean regions, underscores the need to understand the controls and transformations of aerosol iron solubility during atmospheric transport. The Sahara Desert contains the largest and most active sources of aerosol dust globally and can be a key source of nutrients to the Mediterranean Sea, much of the North Atlantic Ocean, and even as far as the Gulf of Mexico. Aerosol iron was examined in Saharan dust plumes using a combination of iron near-edge X-ray absorption spectroscopy and wet chemical techniques. Aerosol samples were collected at three sites located in the Mediterranean, the Atlantic, and Bermuda to characterize iron at different atmospheric transport lengths and time scales. Iron(III) oxides were a component of aerosols at all sampling sites and dominated aerosol iron in Mediterranean samples. In Atlantic samples, iron(II & III) sulfate, iron(III) phosphate, and iron(II) silicates were also contributors to aerosol composition. With increased atmospheric transport time, iron(II) sulfates are found to become more abundant, aerosol iron oxidation state became more reduced, and aerosol acidity increased. Atmospheric processing, including acidic reactions and photo-reduction, likely influence the form of iron minerals and the oxidation state in Saharan dust aerosols and contribute to increases in aerosol iron solubility. Overall, these findings suggest that a combination of factors affects aerosol iron solubility during long-distance atmospheric transport and emphasize the need to consider reductive mechanisms as well as proton-induced solubilization of aerosol iron in modeling studies.

Iron Deficiency in Long-Term Parenteral Nutrition Therapy.

PubMed

Hwa, Yi L; Rashtak, Shahrooz; Kelly, Darlene G; Murray, Joseph A

2016-08-01

Iron is not routinely added to parenteral nutrition (PN) formulations in the United States because of the risk of anaphylaxis and concerns about incompatibilities. Studies have shown that iron dextran in non-lipid-containing PN solutions is safe. Data are limited on iron status, prevalence of iron deficiency anemia (IDA), and efficacy of intravenous iron infusion in long-term home PN (HPN). We aimed to determine the incidence of IDA and to examine the effectiveness of parenteral iron replacement in patients receiving HPN. Medical records of patients receiving HPN at the Mayo Clinic from 1977 to 2010 were reviewed. Diagnoses, time to IDA development, and hemoglobin, ferritin, and mean corpuscular volume (MCV) values were extracted. Response of iron indices to intravenous iron replacement was investigated. Of 185 patients (122 women), 60 (32.4%) were iron deficient. Five patients were iron deficient, and 18 had unknown iron status before HPN. Of 93 patients who had sufficient iron storage, 37 had IDA development after a mean of 27.2 months (range, 2-149 months) of therapy. Iron was replaced by adding maintenance iron dextran to PN or by therapeutic iron infusion. Patients with both replacement methods had significant improvement in iron status. With intravenous iron replacement, mean ferritin increased from 10.9 to 107.6 mcg/L (P < .0001); mean hemoglobin increased from 11.0 to 12.5 g/dL (P = .0001); and mean MCV increased from 84.5 to 89.0 fL (P = .007). Patients receiving HPN are susceptible to IDA. Iron supplementation should be addressed for patients who rely on PN. © 2015 American Society for Parenteral and Enteral Nutrition.

Iron and malaria: a dangerous liaison?

PubMed

Moya-Alvarez, Violeta; Bodeau-Livinec, Florence; Cot, Michel

2016-10-01

Malaria increases the burden of anemia in low-income countries, where, according to 2012 data from the World Health Organization, 40% of children are anemic. Moreover, iron is a cofactor for Plasmodium falciparum development, raising fears that iron supplementation might be harmful in patients with P. falciparum infection. The primary objective of this narrative review is to describe current knowledge on the iron-malaria association, including recent findings and substantive qualitative results. Between 2012 and 2016 the MEDLINE database was searched for literature published about malaria and iron levels. Observational studies reported some protection of iron supplementation against malaria among iron-deficient children, while older clinical trials reported increased susceptibility to malaria among iron-supplemented children. However, iron supplements were not significantly associated with increased malaria risk in recent clinical trials or in a 2016 Cochrane review. Evidence of an iron-malaria association is limited by the following factors: the protective effect of control interventions, the limited follow-up of children, and the lack of homogenous iron indicators. The effects of previous health status and possible thresholds in iron levels should be investigated using a gold-standard combination of iron markers. Moreover, the benefits of iron supplementation require further evaluation. © The Author(s) 2016. Published by Oxford University Press on behalf of the International Life Sciences Institute. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Antioxidant-Mediated Effects in a Gerbil Model of Iron Overload

PubMed Central

Otto-Duessel, Maya; Aguilar, Michelle; Moats, Rex; Wood, John C.

2010-01-01

Introduction Iron cardiomyopathy is a lethal complication of transfusion therapy in thalassemia major. Nutritional supplements decreasing cardiac iron uptake or toxicity would have clinical significance. Murine studies suggest taurine may prevent oxidative damage and inhibit Ca2+-channel-mediated iron transport. We hypothesized that taurine supplementation would decrease cardiac iron-overloaded toxicity by decreasing cardiac iron. Vitamin E and selenium served as antioxidant control. Methods Animals were divided into control, iron, taurine, and vitamin E/selenium groups. Following sacrifice, iron and selenium measurements, histology, and biochemical analyses were performed. Results No significant differences were found in heart and liver iron content between treatment groups, except for higher hepatic dry-weight iron concentrations in taurine-treated animals (p < 0.03). Serum iron increased with iron loading (751 ± 66 vs. 251 ± 54 μg/dl, p < 0.001) and with taurine (903 ± 136 μg/dl, p = 0.03). Conclusion Consistent with oxidative stress, iron overload increased cardiac malondialdehyde levels, decreased heart glutathione peroxidase (GPx) activity, and increased serum aspartate aminotransferase. Taurine ameliorated these changes, but only significantly for liver GPx activity. Selenium and vitamin E supplementation did not improve oxidative markers and worsened cardiac GPx activity. These results suggest that taurine acts primarily as an antioxidant rather than inhibiting iron uptake. Future studies should illuminate the complexity of these results. PMID:17940334

Heme oxygenase activity correlates with serum indices of iron homeostasis in healthy nonsmokers

EPA Science Inventory

Heme oxygenase (HO) catalyzes the breakdown of heme to carbon monoxide, iron, and biliverdin. While the use of genetically altered animal models in investigation has established distinct associations between HO activity and systemic iron availability, studies have not yet confirm...

Poly iron sulfate flocculant as an effective additive for improving the performance of microbial fuel cells.

PubMed

Miyahara, Morio; Sakamoto, Akihiro; Kouzuma, Atsushi; Watanabe, Kazuya

2016-12-01

Laboratory microbial fuel cells were supplied with artificial wastewater and used to examine how supplementation with poly iron sulfate, an inorganic polymer flocculant widely used in wastewater-treatment plants, affects electricity generation and anode microbiomes. It is shown that poly iron sulfate substantially increases electric outputs from microbial fuel cells. Microbiological analyses show that iron and sulfate separately affect anode microbiomes, and the increase in power output is associated with the increases in bacteria affiliated with the families Geobacteraceae and/or Desulfuromonadaceae. We suggest that poly iron sulfate is an effective additive for increasing the electric output from microbial fuel cells. Other utilities of poly iron sulfate in microbial fuel cells are also discussed. Copyright © 2016 Elsevier Ltd. All rights reserved.

CD1 Mouse Retina Is Shielded From Iron Overload Caused by a High Iron Diet

PubMed Central

Bhoiwala, Devang L.; Song, Ying; Cwanger, Alyssa; Clark, Esther; Zhao, Liang-liang; Wang, Chenguang; Li, Yafeng; Song, Delu; Dunaief, Joshua L.

2015-01-01

Purpose High RPE iron levels have been associated with age-related macular degeneration. Mutation of the ferroxidase ceruloplasmin leads to RPE iron accumulation and degeneration in patients with aceruloplasminemia; mice lacking ceruloplasmin and its homolog hephaestin have a similar RPE degeneration. To determine whether a high iron diet (HID) could cause RPE iron accumulation, possibly contributing to RPE oxidative stress in AMD, we tested the effect of dietary iron on mouse RPE iron. Methods Male CD1 strain mice were fed either a standard iron diet (SID) or the same diet with extra iron added (HID) for either 3 months or 10 months. Mice were analyzed with immunofluorescence and Perls' histochemical iron stain to assess iron levels. Levels of ferritin, transferrin receptor, and oxidative stress gene mRNAs were measured by quantitative PCR (qPCR) in neural retina (NR) and isolated RPE. Morphology was assessed in plastic sections. Results Ferritin immunoreactivity demonstrated a modest increase in the RPE in 10-month HID mice. Analysis by qPCR showed changes in mRNA levels of iron-responsive genes, indicating moderately increased iron in the RPE of 10-month HID mice. However, even by age 18 months, there was no Perls' signal in the retina or RPE and no retinal degeneration. Conclusions These findings indicate that iron absorbed from the diet can modestly increase the level of iron deposition in the wild-type mouse RPE without causing RPE or retinal degeneration. This suggests regulation of retinal iron uptake at the blood-retinal barriers. PMID:26275132

Effects of sulfur in flooded paddy soils: Implications for iron chemistry and arsenic mobilization

NASA Astrophysics Data System (ADS)

Avancha, S.; Boye, K.

2013-12-01

In the Mekong delta in Cambodia, naturally occurring arsenic (amplified by erosion in the Himalaya Mountains) in paddy soils is mobilized during the seasonal flooding. As a consequence, rice grown on the flooded soils may take up arsenic and expose people eating the rice to this carcinogenic substance. Iron and sulfur both interact strongly with arsenic in paddy soils: iron oxides are strong adsorbents for arsenic in oxic conditions, and sulfur (in the form of sulfide) is a strong adsorbent under anoxic conditions. In the process of reductive dissolution of iron oxides, arsenic, which had been adsorbed to the iron oxides, is released. Therefore, higher levels of reduced iron (ferrous iron) will likely correlate with higher levels of mobilized arsenic. However, the mobilized arsenic may then co-precipitate with or adsorb to iron sulfides, which form under sulfate-reducing conditions and with the aid of certain microbes already present in the soil. In a batch experiment, we investigated how these processes correlate and which has the greatest influence on arsenic mobilization and potential plant availability. The experiment was designed to measure the effects of various sources of sulfur (dried rice straw, charred rice straw, and gypsum) on the iron and arsenic release in an arsenic-contaminated paddy soil from Cambodia under flooded conditions. The two types of rice straw were designed to introduce the same amount of organic sulfur (7.7 μg/g of soil), but different levels of available carbon, since carbon stimulates microbial activity in the soil. In comparison, two different levels of gypsum (calcium sulfate) were used, 7.7 and 34.65 μg/g of soil, to test the effect of directly available inorganic sulfate without carbon addition. The soil was flooded with a buffer solution at pH 7.07 in airtight serum vials and kept as a slurry on a shaker at 25 °C. We measured pH, alkalinity, ferrous iron, ferric iron, sulfide, sulfate, total iron, sulfur, and arsenic in the aqueous phase on days 1, 3, 8, 15, 22, 29 and 38 from the start of the experiment.

Changes of the corrosion potential of iron in stagnation and flow conditions and their relationship with metal release.

PubMed

Fabbricino, Massimiliano; Korshin, Gregory V

2014-10-01

This study examined the behavior of corrosion potential (Ecorr) of iron exposed to drinking water during episodes of stagnation and flow. These measurements showed that during stagnation episodes, Ecorr values decrease prominently and consistently. This decrease is initially rapid but it becomes slower as the stagnation time increases. During flow episodes, the Ecorr values increase and reach a quasi-steady state. Experiments with varying concentrations of dissolved oxygen showed that the decrease of Ecorr values characteristic for stagnation is likely to be associated with the consumption of dissolved oxygen by the exposed metal. The corrosion potential of iron and its changes during stagnation were sensitive to the concentrations of sulfate and chloride ions. Measurements of iron release showed that both the absolute values of Ecorr measured prior to or after stagnation episodes were well correlated with the logarithms of concentrations of total iron. The slope of this dependence showed that the observed correlations between Ecorr values and Fe concentrations corresponded to the coupling between the oxidant consumption and changes of Fe redox status. These results demonstrate that in situ Ecorr measurements can be a sensitive method with which to ascertain effects of hydrodynamic conditions and short-term variations of water chemistry on metal release and corrosion in drinking water. This approach is valuable practically because Ecorr measurements are precise, can be carried out in situ with any desired time resolution, do not affect the state of exposed surface in any extent and can be carried out with readily available equipment. Copyright © 2014 Elsevier Ltd. All rights reserved.

Iron availability limits the ocean nitrogen inventory stabilizing feedbacks between marine denitrification and nitrogen fixation

NASA Astrophysics Data System (ADS)

Moore, J. Keith; Doney, Scott C.

2007-06-01

Recent upward revisions in key sink/source terms for fixed nitrogen (N) in the oceans imply a short residence time and strong negative feedbacks involving denitrification and N fixation to prevent large swings in the ocean N inventory over timescales of a few centuries. We tested the strength of these feedbacks in a global biogeochemical elemental cycling (BEC) ocean model that includes water column denitrification and an explicit N fixing phytoplankton group. In the northern Indian Ocean and over longer timescales in the tropical Atlantic, we find strong stabilizing feedbacks that minimize changes in marine N inventory over timescales of ˜30-200 years. In these regions high atmospheric dust/iron inputs lead to phosphorus limitation of diazotrophs, and thus a tight link between N fixation and surface water N/P ratios. Maintenance of the oxygen minimum zones in these basins depends on N fixation driven export. The stabilizing feedbacks in other regions are significant but weaker owing to iron limitation of the diazotrophs. Thus Fe limitation appears to restrict the ability of N fixation to compensate for changes in denitrification in the current climate, perhaps leading the oceans to lose fixed N. We suggest that iron is the ultimate limiting nutrient leading to nitrogen being the proximate limiting nutrient over wide regions today. Iron stress was at least partially alleviated during more dusty, glacial times, leading to a higher marine N inventory, increased export production, and perhaps widespread phosphorus limitation of the phytoplankton community. The increased efficiency of the biological pump would have contributed to the glacial drawdown in atmospheric CO2.

The association between malaria and iron status or supplementation in pregnancy: a systematic review and meta-analysis.

PubMed

Sangaré, Laura; van Eijk, Anna Maria; Ter Kuile, Feiko O; Walson, Judd; Stergachis, Andy

2014-01-01

Malaria prevention and iron supplementation are associated with improved maternal and infant outcomes. However, evidence from studies in children suggests iron may adversely modify the risk of malaria. We reviewed the evidence in pregnancy of the association between malaria and markers of iron status, iron supplementation or parenteral treatment. We searched MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials, the Global Health Library, and the Malaria in Pregnancy library to identify studies that investigated the association between iron status, iron treatment or supplementation during pregnancy and malaria. Thirty one studies contributed to the analysis; 3 experimental and 28 observational studies. Iron supplementation was not associated with an increased risk of P. falciparum malaria during pregnancy or delivery in Africa (summary Relative Risk = 0.89, 95% Confidence Interval (CI) 0.66-1.20, I(2) = 78.8%, 5 studies). One study in Asia reported an increased risk of P. vivax within 30 days of iron supplementation (e.g. adjusted Hazard Ratio = 1.75, 95% CI 1.14-2.70 for 1-15 days), but not after 60 days. Iron deficiency (based on ferritin and C-reactive protein) was associated with lower odds for malaria infection (summary Odds Ratio = 0.35, 0.24-0.51, I(2) = 59.2%, 5 studies). With the exception of the acute phase protein ferritin, biomarkers of iron deficiency were generally not associated with malaria infection. Iron supplementation was associated with a temporal increase in P vivax, but not with an increased risk of P. falciparum; however, data are insufficient to rule out the potential for an increased risk of P. falciparum. Iron deficiency was associated with a decreased malaria risk in pregnancy only when measured with ferritin. Until there is more evidence, it is prudent to provide iron in combination with malaria prevention during pregnancy.

The Association between Malaria and Iron Status or Supplementation in Pregnancy: A Systematic Review and Meta-Analysis

PubMed Central

Sangaré, Laura; van Eijk, Anna Maria; ter Kuile, Feiko O.; Walson, Judd; Stergachis, Andy

2014-01-01

Introduction Malaria prevention and iron supplementation are associated with improved maternal and infant outcomes. However, evidence from studies in children suggests iron may adversely modify the risk of malaria. We reviewed the evidence in pregnancy of the association between malaria and markers of iron status, iron supplementation or parenteral treatment. Methods and Findings We searched MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials, the Global Health Library, and the Malaria in Pregnancy library to identify studies that investigated the association between iron status, iron treatment or supplementation during pregnancy and malaria. Thirty one studies contributed to the analysis; 3 experimental and 28 observational studies. Iron supplementation was not associated with an increased risk of P. falciparum malaria during pregnancy or delivery in Africa (summary Relative Risk = 0.89, 95% Confidence Interval (CI) 0.66–1.20, I2 = 78.8%, 5 studies). One study in Asia reported an increased risk of P. vivax within 30 days of iron supplementation (e.g. adjusted Hazard Ratio = 1.75, 95% CI 1.14–2.70 for 1–15 days), but not after 60 days. Iron deficiency (based on ferritin and C-reactive protein) was associated with lower odds for malaria infection (summary Odds Ratio = 0.35, 0.24–0.51, I2 = 59.2%, 5 studies). With the exception of the acute phase protein ferritin, biomarkers of iron deficiency were generally not associated with malaria infection. Conclusions Iron supplementation was associated with a temporal increase in P vivax, but not with an increased risk of P. falciparum; however, data are insufficient to rule out the potential for an increased risk of P. falciparum. Iron deficiency was associated with a decreased malaria risk in pregnancy only when measured with ferritin. Until there is more evidence, it is prudent to provide iron in combination with malaria prevention during pregnancy. PMID:24551064

Iron addiction: a novel therapeutic target in ovarian cancer

DOE PAGES

Basuli, D.; Tesfay, L.; Deng, Z.; ...

2017-03-20

Ovarian cancer is a lethal malignancy that has not seen a major therapeutic advance in over 30 years. We demonstrate that ovarian cancer exhibits a targetable alteration in iron metabolism. Ferroportin (FPN), the iron efflux pump, is decreased, and transferrin receptor (TFR1), the iron importer, is increased in tumor tissue from patients with high grade but not low grade serous ovarian cancer. A similar profile of decreased FPN and increased TFR1 is observed in a genetic model of ovarian cancer tumor-initiating cells (TICs). The net result of these changes is an accumulation of excess intracellular iron and an augmented dependencemore » on iron for proliferation. A forced reduction in intracellular iron reduces the proliferation of ovarian cancer TICs in vitro, and inhibits both tumor growth and intraperitoneal dissemination of tumor cells in vivo. Some mechanistic studies demonstrate that iron increases metastatic spread by facilitating invasion through expression of matrix metalloproteases and synthesis of interleukin 6 (IL-6). Here, we show that the iron dependence of ovarian cancer TICs renders them exquisitely sensitive in vivo to agents that induce iron-dependent cell death (ferroptosis) as well as iron chelators, and thus creates a metabolic vulnerability that can be exploited therapeutically.« less

Iron addiction: a novel therapeutic target in ovarian cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Basuli, D.; Tesfay, L.; Deng, Z.

Ovarian cancer is a lethal malignancy that has not seen a major therapeutic advance in over 30 years. We demonstrate that ovarian cancer exhibits a targetable alteration in iron metabolism. Ferroportin (FPN), the iron efflux pump, is decreased, and transferrin receptor (TFR1), the iron importer, is increased in tumor tissue from patients with high grade but not low grade serous ovarian cancer. A similar profile of decreased FPN and increased TFR1 is observed in a genetic model of ovarian cancer tumor-initiating cells (TICs). The net result of these changes is an accumulation of excess intracellular iron and an augmented dependencemore » on iron for proliferation. A forced reduction in intracellular iron reduces the proliferation of ovarian cancer TICs in vitro, and inhibits both tumor growth and intraperitoneal dissemination of tumor cells in vivo. Some mechanistic studies demonstrate that iron increases metastatic spread by facilitating invasion through expression of matrix metalloproteases and synthesis of interleukin 6 (IL-6). Here, we show that the iron dependence of ovarian cancer TICs renders them exquisitely sensitive in vivo to agents that induce iron-dependent cell death (ferroptosis) as well as iron chelators, and thus creates a metabolic vulnerability that can be exploited therapeutically.« less

Iron Overload Accelerates the Progression of Diabetic Retinopathy in Association with Increased Retinal Renin Expression.

PubMed

Chaudhary, Kapil; Promsote, Wanwisa; Ananth, Sudha; Veeranan-Karmegam, Rajalakshmi; Tawfik, Amany; Arjunan, Pachiappan; Martin, Pamela; Smith, Sylvia B; Thangaraju, Muthusamy; Kisselev, Oleg; Ganapathy, Vadivel; Gnana-Prakasam, Jaya P

2018-02-14

Diabetic retinopathy (DR) is a leading cause of blindness among working-age adults. Increased iron accumulation is associated with several degenerative diseases. However, there are no reports on the status of retinal iron or its implications in the pathogenesis of DR. In the present study, we found that retinas of type-1 and type-2 mouse models of diabetes have increased iron accumulation compared to non-diabetic retinas. We found similar iron accumulation in postmortem retinal samples from human diabetic patients. Further, we induced diabetes in HFE knockout (KO) mice model of genetic iron overload to understand the role of iron in the pathogenesis of DR. We found increased neuronal cell death, vascular alterations and loss of retinal barrier integrity in diabetic HFE KO mice compared to diabetic wildtype mice. Diabetic HFE KO mouse retinas also exhibited increased expression of inflammation and oxidative stress markers. Severity in the pathogenesis of DR in HFE KO mice was accompanied by increase in retinal renin expression mediated by G-protein-coupled succinate receptor GPR91. In light of previous reports implicating retinal renin-angiotensin system in DR pathogenesis, our results reveal a novel relationship between diabetes, iron and renin-angiotensin system, thereby unraveling new therapeutic targets for the treatment of DR.

Serum Iron Protects from Renal Postischemic Injury.

PubMed

Vaugier, Céline; Amano, Mariane T; Chemouny, Jonathan M; Dussiot, Michael; Berrou, Claire; Matignon, Marie; Ben Mkaddem, Sanae; Wang, Pamella H M; Fricot, Aurélie; Maciel, Thiago T; Grapton, Damien; Mathieu, Jacques R R; Beaumont, Carole; Peraldi, Marie-Noëlle; Peyssonnaux, Carole; Mesnard, Laurent; Daugas, Eric; Vrtovsnik, François; Monteiro, Renato C; Hermine, Olivier; Ginzburg, Yelena Z; Benhamou, Marc; Camara, Niels O S; Flamant, Martin; Moura, Ivan C

2017-12-01

Renal transplants remain a medical challenge, because the parameters governing allograft outcome are incompletely identified. Here, we investigated the role of serum iron in the sterile inflammation that follows kidney ischemia-reperfusion injury. In a retrospective cohort study of renal allograft recipients ( n =169), increased baseline levels of serum ferritin reliably predicted a positive outcome for allografts, particularly in elderly patients. In mice, systemic iron overload protected against renal ischemia-reperfusion injury-associated sterile inflammation. Furthermore, chronic iron injection in mice prevented macrophage recruitment after inflammatory stimuli. Macrophages cultured in high-iron conditions had reduced responses to Toll-like receptor-2, -3, and -4 agonists, which associated with decreased reactive oxygen species production, increased nuclear localization of the NRF2 transcription factor, increased expression of the NRF2-related antioxidant response genes, and limited NF- κ B and proinflammatory signaling. In macrophage-depleted animals, the infusion of macrophages cultured in high-iron conditions did not reconstitute AKI after ischemia-reperfusion, whereas macrophages cultured in physiologic iron conditions did. These findings identify serum iron as a critical protective factor in renal allograft outcome. Increasing serum iron levels in patients may thus improve prognosis of renal transplants. Copyright © 2017 by the American Society of Nephrology.

Neonatal Iron Supplementation Induces Striatal Atrophy in Female YAC128 Huntington's Disease Mice.

PubMed

Berggren, Kiersten L; Lu, Zhen; Fox, Julia A; Dudenhoeffer, Megan; Agrawal, Sonal; Fox, Jonathan H

2016-01-01

Dysregulation of iron homeostasis is implicated in the pathogenesis of Huntington's disease. We have previously shown that increased iron intake in R6/2 HD neonatal mice, but not adult R6/2 HD mice potentiates disease outcomes at 12-weeks of age corresponding to advanced HD [Redox Biol. 2015;4 : 363-74]. However, whether these findings extend to other HD models is unknown. In particular, it is unclear if increased neonatal iron intake can promote neurodegeneration in mouse HD models where disease onset is delayed to mid-adult life. To determine if increased dietary iron intake in neonatal and adult life-stages potentiates HD in the slowly progressive YAC128 HD mouse model. Female neonatal mice were supplemented daily from days 10-17 with 120μg/g body weight of carbonyl iron. Adult mice were provided diets containing low (50 ppm), medium (150 ppm) and high (500 ppm) iron concentrations from 2-months of age. HD progression was determined using behavioral, brain morphometric and biochemical approaches. Neonatal-iron supplemented YAC128 HD mice had significantly lower striatal volumes and striatal neuronal cell body volumes as compared to control HD mice at 1-year of age. Neonatal-iron supplementation of HD mice had no effect on rota-rod motor endurance and brain iron or glutathione status. Adult iron intake level had no effect on HD progression. YAC128 HD mice had altered peripheral responses to iron intake compared to iron-matched wild-type controls. Female YAC128 HD mice supplemented with nutritionally-relevant levels of iron as neonates demonstrate increased striatal degeneration 1-year later.

Neonatal Iron Supplementation Induces Striatal Atrophy in Female YAC128 Huntington’s Disease Mice

PubMed Central

Berggren, Kiersten L.; Lu, Zhen; Fox, Julia A.; Dudenhoeffer, Megan; Agrawal, Sonal; Fox, Jonathan H.

2016-01-01

Background: Dysregulation of iron homeostasis is implicated in the pathogenesis of Huntington’s disease. We have previously shown that increased iron intake in R6/2 HD neonatal mice, but not adult R6/2 HD mice potentiates disease outcomes at 12-weeks of age corresponding to advanced HD [Redox Biol. 2015;4 : 363–74]. However, whether these findings extend to other HD models is unknown. In particular, it is unclear if increased neonatal iron intake can promote neurodegeneration in mouse HD models where disease onset is delayed to mid-adult life. Objective: To determine if increased dietary iron intake in neonatal and adult life-stages potentiates HD in the slowly progressive YAC128 HD mouse model. Methods: Female neonatal mice were supplemented daily from days 10–17 with 120μg/g body weight of carbonyl iron. Adult mice were provided diets containing low (50 ppm), medium (150 ppm) and high (500 ppm) iron concentrations from 2-months of age. HD progression was determined using behavioral, brain morphometric and biochemical approaches. Results: Neonatal-iron supplemented YAC128 HD mice had significantly lower striatal volumes and striatal neuronal cell body volumes as compared to control HD mice at 1-year of age. Neonatal-iron supplementation of HD mice had no effect on rota-rod motor endurance and brain iron or glutathione status. Adult iron intake level had no effect on HD progression. YAC128 HD mice had altered peripheral responses to iron intake compared to iron-matched wild-type controls. Conclusions: Female YAC128 HD mice supplemented with nutritionally-relevant levels of iron as neonates demonstrate increased striatal degeneration 1-year later. PMID:27079948

Evaluation of Brain Iron Content Based on Magnetic Resonance Imaging (MRI): Comparison among Phase Value, R2* and Magnitude Signal Intensity

PubMed Central

Yan, Shen-Qiang; Sun, Jian-Zhong; Yan, Yu-Qing; Wang, He; Lou, Min

2012-01-01

Background and Purpose Several magnetic resonance imaging (MRI) techniques are being exploited to measure brain iron levels increasingly as iron deposition has been implicated in some neurodegenerative diseases. However, there remains no unified evaluation of these methods as postmortem measurement isn't commonly available as the reference standard. The purpose of this study was to make a comparison among these methods and try to find a new index of brain iron. Methods We measured both phase values and R2* in twenty-four adults, and performed correlation analysis among the two methods and the previously published iron concentrations. We also proposed a new method using magnitude signal intensity and compared it with R2* and brain iron. Results We found phase value correlated with R2* in substantia nigra (r = −0.723, p<0.001) and putamen (r = −0.514, p = 0.010), while no correlations in red nucleus (r = −0.236, p = 0.268) and globus pallidus (r = −0.111, p = 0.605). And the new magnitude method had significant correlations in red nucleus (r = −0.593, p = 0.002), substantia nigra (r = −0.521, p = 0.009), globus pallidus (r = −0.750, p<0.001) and putamen (r = −0.547, p = 0.006) with R2*. A strong inverse correlation was also found between the new magnitude method and previously published iron concentrations in seven brain regions (r = −0.982, P<0.001). Conclusions Our study indicates that phase value may not be used for assessing the iron content in some brain regions especially globus pallidus. The new magnitude method is highly consistent with R2* especially in globus pallidus, and we assume that this approach may be acceptable as an index of iron content in iron-rich brain regions. PMID:22363719

Fetal and neonatal iron deficiency but not copper deficiency increases vascular complexity in the developing rat brain

PubMed Central

Bastian, Thomas W.; Santarriaga, Stephanie; Nguyen, Thu An; Prohaska, Joseph R.; Georgieff, Michael K.; Anderson, Grant W.

2015-01-01

Objectives Anemia caused by nutritional deficiencies, such as iron and copper deficiencies, is a global health problem. Iron and copper deficiencies have their most profound effect on the developing fetus/infant, leading to brain development deficits and poor cognitive outcomes. Tissue iron depletion or chronic anemia can induce cellular hypoxic signaling. In mice, chronic hypoxia induces a compensatory increase in brain blood vessel outgrowth. We hypothesized that developmental anemia, due to iron or copper deficiencies, induces angiogenesis/vasculogenesis in the neonatal brain. Methods To test our hypothesis, three independent experiments were performed where pregnant rats were fed iron- or copper-deficient diets from gestational day 2 through mid-lactation. Effects on the neonatal brain vasculature were determined using qPCR to assess mRNA levels of angiogenesis/vasculogenesis-associated genes and GLUT1 immunohistochemistry (IHC) to assess brain blood vessel density and complexity. Results Iron deficiency, but not copper deficiency, increased mRNA expression of brain endothelial cell- and angiogenesis/vasculogenesis-associated genes (i.e. Glut1, Vwf, Vegfa, Ang2, Cxcl12, and Flk1) in the neonatal brain, suggesting increased cerebrovascular density. Iron deficiency also increased hippocampal and cerebral cortical blood vessel branching by 62% and 78%, respectively. Discussion This study demonstrates increased blood vessel complexity in the neonatal iron-deficient brain, which is likely due to elevated angiogenic/vasculogenic signaling. At least initially, this is probably an adaptive response to maintain metabolic substrate homeostasis in the developing iron-deficient brain. However, this may also contribute to long-term neurodevelopmental deficits. PMID:26177275

Algal and aquatic plant carbon concentrating mechanisms in relation to environmental change.

PubMed

Raven, John A; Giordano, Mario; Beardall, John; Maberly, Stephen C

2011-09-01

Carbon dioxide concentrating mechanisms (also known as inorganic carbon concentrating mechanisms; both abbreviated as CCMs) presumably evolved under conditions of low CO(2) availability. However, the timing of their origin is unclear since there are no sound estimates from molecular clocks, and even if there were, there are no proxies for the functioning of CCMs. Accordingly, we cannot use previous episodes of high CO(2) (e.g. the Palaeocene-Eocene Thermal Maximum) to indicate how organisms with CCMs responded. Present and predicted environmental change in terms of increased CO(2) and temperature are leading to increased CO(2) and HCO(3)(-) and decreased CO(3)(2-) and pH in surface seawater, as well as decreasing the depth of the upper mixed layer and increasing the degree of isolation of this layer with respect to nutrient flux from deeper waters. The outcome of these forcing factors is to increase the availability of inorganic carbon, photosynthetic active radiation (PAR) and ultraviolet B radiation (UVB) to aquatic photolithotrophs and to decrease the supply of the nutrients (combined) nitrogen and phosphorus and of any non-aeolian iron. The influence of these variations on CCM expression has been examined to varying degrees as acclimation by extant organisms. Increased PAR increases CCM expression in terms of CO(2) affinity, whilst increased UVB has a range of effects in the organisms examined; little relevant information is available on increased temperature. Decreased combined nitrogen supply generally increases CO(2) affinity, decreased iron availability increases CO(2) affinity, and decreased phosphorus supply has varying effects on the organisms examined. There are few data sets showing interactions amongst the observed changes, and even less information on genetic (adaptation) changes in response to the forcing factors. In freshwaters, changes in phytoplankton species composition may alter with environmental change with consequences for frequency of species with or without CCMs. The information available permits less predictive power as to the effect of the forcing factors on CCM expression than for their overall effects on growth. CCMs are currently not part of models as to how global environmental change has altered, and is likely to further alter, algal and aquatic plant primary productivity.

Anemia management in cancer patients with chronic kidney disease.

PubMed

Deak, Andras T; Troppan, Katharina; Rosenkranz, Alexander R

2016-12-01

Anemia is a common complication of cancer and chronic kidney disease (CKD) associated with decreased physical performance as well as poor prognosis for life expectancy. Renal and cancer-induced anemia share common features regarding pathogenesis and therapeutic strategies. It is typically treated with iron substitution, erythropoiesis-stimulating agents (ESA) and in refractory cases with red blood cell transfusions. However, studies of the past few years unveiled numerous setbacks in the use of ESAs. These included a higher risk of cerebrovascular events and increased mortality without the improvement of cardiovascular outcomes in patients with CKD. Moreover, particularly negative results were observed in patients with previous cancer history under ESA therapy. These unfavorable findings have forced the clinicians to reevaluate the management of renal anemia. This led to decrease of ESA usage, while iron substitution and alternative therapeutic options gained more significance. Iron supplementation is also accompanied with certain risks ranging from gastrointestinal complications to severe allergic reactions and increased rate of infections. Furthermore, the evaluation of the long-term safety of excessive iron therapy is still lacking, especially in CKD patients with cancer. In the absence of these clinical studies, this review aims to summarize the currently available therapeutic strategies in anemia management of CKD patients with concomitant cancer. Copyright © 2016 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved.

Relative Bioavailability of Iron in Bangladeshi Traditional Meals Prepared with Iron-Fortified Lentil Dal

PubMed Central

Podder, Rajib; M. DellaValle, Diane; T. Tyler, Robert; P. Glahn, Raymond; Tako, Elad; Vandenberg, Albert

2018-01-01

Due to low Fe bioavailability and low consumption per meal, lentil must be fortified to contribute significant bioavailable Fe in the Bangladeshi diet. Moreover, since red lentil is dehulled prior to consumption, an opportunity exists at this point to fortify lentil with Fe. Thus, in the present study, lentil was Fe-fortified (using a fortificant Fe concentration of 2800 µg g−1) and used in 30 traditional Bangladeshi meals with broad differences in concentrations of iron, phytic acid (PA), and relative Fe bioavailability (RFeB%). Fortification with NaFeEDTA increased the iron concentration in lentil from 60 to 439 µg g−1 and resulted in a 79% increase in the amount of available Fe as estimated by Caco-2 cell ferritin formation. Phytic acid levels were reduced from 6.2 to 4.6 mg g−1 when fortified lentil was added, thereby reducing the PA:Fe molar ratio from 8.8 to 0.9. This effect was presumably due to dephytinization of fortified lentil during the fortification process. A significant (p ≤ 0.01) Pearson correlation was observed between Fe concentration and RFeB% and between RFeB% and PA:Fe molar ratio in meals with fortified lentil, but not for the meal with unfortified lentil. In conclusion, fortified lentil can contribute significant bioavailable Fe to populations at risk of Fe deficiency. PMID:29543712

Relative Bioavailability of Iron in Bangladeshi Traditional Meals Prepared with Iron-Fortified Lentil Dal.

PubMed

Podder, Rajib; M DellaValle, Diane; T Tyler, Robert; P Glahn, Raymond; Tako, Elad; Vandenberg, Albert

2018-03-15

Due to low Fe bioavailability and low consumption per meal, lentil must be fortified to contribute significant bioavailable Fe in the Bangladeshi diet. Moreover, since red lentil is dehulled prior to consumption, an opportunity exists at this point to fortify lentil with Fe. Thus, in the present study, lentil was Fe-fortified (using a fortificant Fe concentration of 2800 µg g -1 ) and used in 30 traditional Bangladeshi meals with broad differences in concentrations of iron, phytic acid (PA), and relative Fe bioavailability (RFeB%). Fortification with NaFeEDTA increased the iron concentration in lentil from 60 to 439 µg g -1 and resulted in a 79% increase in the amount of available Fe as estimated by Caco-2 cell ferritin formation. Phytic acid levels were reduced from 6.2 to 4.6 mg g -1 when fortified lentil was added, thereby reducing the PA:Fe molar ratio from 8.8 to 0.9. This effect was presumably due to dephytinization of fortified lentil during the fortification process. A significant ( p ≤ 0.01) Pearson correlation was observed between Fe concentration and RFeB% and between RFeB% and PA:Fe molar ratio in meals with fortified lentil, but not for the meal with unfortified lentil. In conclusion, fortified lentil can contribute significant bioavailable Fe to populations at risk of Fe deficiency.

78 FR 66743 - Draft Guidance for Industry on Bioequivalence Recommendations for Iron Sucrose; Availability

Federal Register 2010, 2011, 2012, 2013, 2014

2013-11-06

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2007-D-0369] Draft Guidance for Industry on Bioequivalence Recommendations for Iron Sucrose; Availability AGENCY... guidance, FDA recommended an in vivo fasting BE study with pharmacokinetic endpoints and in vitro studies...

DOE Office of Scientific and Technical Information (OSTI.GOV)

Brown, Kyle E.; Division of Gastroenterology-Hepatology, University of Iowa Roy J. and Lucille A. Carver College of Medicine; Program in Free Radical and Radiation Biology, University of Iowa Roy J. and Lucille A. Carver College of Medicine, Iowa City, IA

Introduction:: Oxidative stress can trigger a cellular stress response characterized by induction of antioxidants, acute phase reactants (APRs) and heat shock proteins (HSPs), which are presumed to play a role in limiting tissue damage. In rodents, hepatic iron overload causes oxidative stress that results in upregulation of antioxidant defenses with minimal progressive liver injury. The aim of this study was to determine whether iron overload modulates expression of other stress-responsive proteins such as APRs and HSPs that may confer protection against iron-induced damage in rodent liver. Methods:: Male rats received repeated injections of iron dextran or dextran alone over amore » 6-month period. Hepatic transcript levels for a panel of APRs and HSPs were quantitated by real-time PCR and protein expression was evaluated by Western blot and immunohistochemistry. Results:: Hepatic iron concentrations were increased > 50-fold in the iron-loaded rats compared to controls. Iron loading resulted in striking increases in mRNAs for Hsp32 (heme oxygenase-1; 12-fold increase vs. controls) and metallothionein-1 and -2 (both increased {approx} 6-fold). Transcripts for {alpha}1-acid glycoprotein, the major rat APR, were increased {approx} 3-fold, while expression of other classical APRs was unaltered. Surprisingly, although mRNA levels for the HSPs were not altered by iron, the abundance of Hsp25, Hsp70 and Hsp90 proteins was uniformly reduced in the iron-loaded livers, as were levels of NAD(P)H:quinone oxidoreductase 1, an Hsp70 client protein. Conclusions:: Chronic iron administration elicits a unique pattern of stress protein expression. These alterations may modulate hepatic responses to iron overload, as well as other injury processes.« less

Association between renal iron accumulation and renal interstitial fibrosis in a rat model of chronic kidney disease.

PubMed

Naito, Yoshiro; Fujii, Aya; Sawada, Hisashi; Oboshi, Makiko; Iwasaku, Toshihiro; Okuhara, Yoshitaka; Morisawa, Daisuke; Eguchi, Akiyo; Hirotani, Shinichi; Masuyama, Tohru

2015-07-01

Iron accumulation is associated with the pathophysiology of chronic kidney disease (CKD). Renal fibrosis is a final common feature that contributes to the progression of CKD; however, little is known about the association between renal iron accumulation and renal interstitial fibrosis in CKD. Here we investigate the effects of iron chelation on renal interstitial fibrosis in a rat model of CKD. CKD was induced by 5/6 nephrectomy in Sprague-Dawley rats. At 8 weeks after operation, 5/6 nephrectomized rats were administered an oral iron chelator, deferasirox (DFX), in chow for 8 weeks. Other CKD rats were given a normal diet. Sham-operative rats given a normal diet served as a control. CKD rats exhibited hypertension, glomerulosclerosis and renal interstitial fibrosis. Iron chelation with DFX did not change hypertension and glomerulosclerosis; however, renal interstitial fibrosis was attenuated in CKD rats. Consistent with these findings, renal gene expression of collagen type III and transforming growth factor-β was increased in CKD rats compared with the controls, while iron chelation suppressed these increments. In addition, a decrease in vimentin along an increase in E-cadherin in renal gene expression was observed in CKD rats with iron chelation. CKD rats also showed increased CD68-positive cells in the kidney, whereas its increase was attenuated by iron deprivation. Similarly, increased renal gene expression of CD68, tumor necrosis factor-α and monocyte chemoattractant protein-1 was suppressed in CKD rats with iron chelation. Renal iron accumulation seems to be associated with renal interstitial fibrosis in a rat model of CKD.

Iatrogenic Iron Overload in Dialysis Patients at the Beginning of the 21st Century.

PubMed

Rostoker, Guy; Vaziri, Nosratola D; Fishbane, Steven

2016-05-01

Iron overload used to be considered rare in hemodialysis patients but its clinical frequency is now increasingly realized. The liver is the main site of iron storage and the liver iron concentration (LIC) is closely correlated with total iron stores in patients with secondary hemosideroses and genetic hemochromatosis. Magnetic resonance imaging is now the gold standard method for LIC estimation and monitoring in non-renal patients. Studies of LIC in hemodialysis patients by quantitative magnetic resonance imaging and magnetic susceptometry have demonstrated a strong relation between the risk of iron overload and the use of intravenous (IV) iron products prescribed at doses determined by the iron biomarker cutoffs contained in current anemia management guidelines. These findings have challenged the validity of both iron biomarker cutoffs and current clinical guidelines, especially with respect to recommended IV iron doses. Three long-term observational studies have recently suggested that excessive IV iron doses may be associated with an increased risk of cardiovascular events and death in hemodialysis patients. We postulate that iatrogenic iron overload in the era of erythropoiesis-stimulating agents may silently increase complications in dialysis patients without creating frank clinical signs and symptoms. High hepcidin-25 levels were recently linked to fatal and nonfatal cardiovascular events in dialysis patients. It is therefore tempting to postulate that the main pathophysiological pathway leading to these events may involve the pleiotropic master hormone hepcidin (synergized by fibroblast growth factor 23), which regulates iron metabolism. Oxidative stress as a result of IV iron infusions and iron overload, by releasing labile non-transferrin-bound iron, might represent a 'second hit' on the vascular bed. Finally, iron deposition in the myocardium of patients with severe iron overload might also play a role in the pathogenesis of sudden death in some patients.

Iron, growth, and the global epidemic of obesity.

EPA Science Inventory

Abstract: Iron is an essential nutrient utilized in almost every aspect of cell function and its availability has previously limited life. Those same properties which allow iron to function as a catalyst in the reactions of life also present a threat via generation of oxygen-ba...

Iron-impregnated granular activated carbon for arsenic removal from drinking water

NASA Astrophysics Data System (ADS)

Chang, Qigang

A new multi-step iron impregnation method was developed in this study to impregnate GAC with a high amount of iron that possesses desired characteristics: stable, even distribution, and high arsenic adsorption capacity. Research was carried out to investigate the impact of the amount of impregnated iron on arsenic adsorption properties: capacity, affinity, and kinetics. Fe-GACs were characterized in terms of the amount, stability, distribution, morphology, and species of impregnated iron. It was found that a high amount of iron was stably impregnated in GAC. Scanning electron microscopy (SEM) and energy dispersive X-ray spectroscopy (EDS) analysis demonstrated that the impregnated iron was evenly distributed on the internal surface of GAC. Impregnated iron formed nano-size particles and existed in both crystalline (akaganeite) and amorphous iron. Arsenic adsorption tests were conducted using Fe-GACs with iron content of 1.64--28.90% in a low arsenic concentration that is typical for drinking water treatment. The amount of impregnated iron affects arsenic maximum adsorption capacity (qm) but has little impact on the Langmuir constant h (the affinity of adsorbent for adsorbate). The qm for both As(V) and As(III) adsorptions increased significantly with increase of the amount of impregnated iron up to 13.59%. Further increase of iron amounts caused a gradual decrease of qm for As(V). BET analysis indicated impregnated iron possesses the highest surface area at iron content of 13.59%. A new second-order kinetic model was developed to investigate the impact of the amounts of impregnated iron on arsenic adsorption kinetics. With iron content increased from 1.64% to 28.90%, the intrinsic adsorption rate constants reduced from 4.6x10-2 1/hr to 1.18x10 -3 1/hr, which indicates that impregnated iron slows arsenic intraparticle diffusion rate in Fe-GAC. The decreased arsenic intraparticle diffusion rate was most likely caused by reduced pore size of Fe-GACs. Column tests were conducted to investigate the performance of Fe-GACs in real implementations using groundwater taken from a former superfund site in North Dakota. Fe-GACs can remove arsenic below 10 microg/L and the performance of Fe-GACs was significantly enhanced with increasing empty bed contact time.

Transcuprein is a Macroglobulin Regulated by Copper and Iron Availability

PubMed Central

Liu, Nanmei; Lo, Louis Shi-li; Askary, S. Hassan; Jones, LaTrice; Kidane, Theodros Z.; Nguyen, Trisha Trang Minh; Goforth, Jeremy; Chu, Yu-Hsiang; Vivas, Esther; Tsai, Monta; Westbrook, Terence; Linder, Maria C.

2009-01-01

SUMMARY Transcuprein is a high affinity copper carrier in the plasma involved in the initial distribution of copper entering the blood from the digestive tract. To identify and obtain cDNA for this protein, it was purified from rat plasma by size exclusion and copper chelate affinity chromatography, and amino acid sequences were obtained. These revealed a 190 kDa glycosylated protein identified as the macroglobulin, α1inhibitorIII, the main macroglobulin of rodent blood plasma. Albumin (65 kDa) co-purified in variable amounts and was concluded to be a contaminant (although it transiently can bind the macroglobulin). The main macroglobulin in human blood plasma (α2-macroglobulin), homologous to α1inhibitorIII, also bound copper tightly. Expression of α1I3 (transcuprein) mRNA by the liver was examined in rats with and without copper deficiency, using quantitative PCR and Northern analysis. Protein expression was examined by Western blotting. Deficient rats with 40% less ceruloplasmin oxidase activity and liver copper concentrations expressed about twice as much α1I3 mRNA, but circulating levels of transcuprein did not differ. Iron deficiency, which increased liver copper concentrations 3-fold, reduced transcuprein mRNA expression and 7circulating levels of transcuprein relative to what occurred in rats with normal or excess iron. We conclude that transcupreins are specific macroglobulins that not only carry zinc but also transport copper in the blood; and that their expression can be modulated by copper and iron availability. PMID:17363239

Limitation of Bacterial Growth by Dissolved Organic Matter and Iron in the Southern Ocean†

PubMed Central

Church, Matthew J.; Hutchins, David A.; Ducklow, Hugh W.

2000-01-01

The importance of resource limitation in controlling bacterial growth in the high-nutrient, low-chlorophyll (HNLC) region of the Southern Ocean was experimentally determined during February and March 1998. Organic- and inorganic-nutrient enrichment experiments were performed between 42°S and 55°S along 141°E. Bacterial abundance, mean cell volume, and [3H]thymidine and [3H]leucine incorporation were measured during 4- to 5-day incubations. Bacterial biomass, production, and rates of growth all responded to organic enrichments in three of the four experiments. These results indicate that bacterial growth was constrained primarily by the availability of dissolved organic matter. Bacterial growth in the subtropical front, subantarctic zone, and subantarctic front responded most favorably to additions of dissolved free amino acids or glucose plus ammonium. Bacterial growth in these regions may be limited by input of both organic matter and reduced nitrogen. Unlike similar experimental results in other HNLC regions (subarctic and equatorial Pacific), growth stimulation of bacteria in the Southern Ocean resulted in significant biomass accumulation, apparently by stimulating bacterial growth in excess of removal processes. Bacterial growth was relatively unchanged by additions of iron alone; however, additions of glucose plus iron resulted in substantial increases in rates of bacterial growth and biomass accumulation. These results imply that bacterial growth efficiency and nitrogen utilization may be partly constrained by iron availability in the HNLC Southern Ocean. PMID:10653704

Effects of Iron Depletion on CALM-AF10 Leukemias

PubMed Central

Heath, Jessica L.; Weiss, Joshua M.

2014-01-01

Iron, an essential nutrient for cellular growth and proliferation, enters cells via clathrin-mediated endocytosis (CME). The clathrin assembly lymphoid myeloid (CALM) protein plays an essential role in the cellular import of iron by CME. CALM-AF10 leukemias harbor a single copy of the normal CALM gene, and may therefore be more sensitive to the growth inhibitory effect of iron restriction compared with normal hematopoietic cells. We found that Calm heterozygous (CalmHET) murine fibroblasts exhibit signs of iron deficiency, with increased surface transferrin receptor (sTfR) levels and reduced growth rates. CalmHET hematopoietic cells are more sensitive in vitro to iron chelators than their wild type counterparts. Iron chelation also displayed toxicity towards cultured CalmHET CALM-AF10 leukemia cells and this effect was additive to that of chemotherapy. In mice transplanted with CalmHET CALM-AF10 leukemia, we found that dietary iron restriction reduces tumor burden in the spleen. However, dietary iron restriction, used alone or in conjunction with chemotherapy, did not increase survival of mice with CalmHET CALM-AF10 leukemia. In summary, while Calm heterozygosity results in iron deficiency and increased sensitivity to iron chelation in vitro, our data in mice do not suggest that iron depletion strategies would be beneficial for the therapy of CALM-AF10 leukemia patients. PMID:25193880

Iron prophylaxis in pregnancy--general or individual and in which dose?

PubMed

Milman, Nils

2006-12-01

Iron is mandatory for normal fetal development, including the brain. Iron deficiency may have deleterious effects for intelligence and behavioral development. It is important to prevent iron deficiency in the fetus by preventing iron deficiency in the pregnant woman. Iron deficiency anemia during pregnancy is a risk factor for preterm delivery and low birth weight. In the Western countries there is no consensus on iron prophylaxis to pregnant women. An adequate iron balance during pregnancy implies body iron reserves of >or=500 mg at conception. The physiologic iron requirements in the second half of gestation cannot be fulfilled solely through dietary iron. Iron supplements during gestation consistently increase serum ferritin and hemoglobin and reduce the prevalence of iron deficiency anemia. Iron has a negative influence on absorption of other divalent metals and increases oxidative stress in pregnancy, for which reason minimum effective iron dose should be advised. From a physiologic point of view, individual iron prophylaxis according to serum ferritin concentration should be preferred to general prophylaxis. Suggested guidelines are (1) ferritin>70 microg/l: no iron supplements; (2) ferritin 30-70 microg/l: 40 mg ferrous iron daily; and (3) ferritin<30 microg/l: 80-100 mg ferrous iron daily. In controlled studies, there are no documented side effects of iron supplements below 100 mg/day. Iron supplements should be taken at bedtime or between meals to ensure optimum absorption.

Iron Absorption in Drosophila melanogaster

PubMed Central

Mandilaras, Konstantinos; Pathmanathan, Tharse; Missirlis, Fanis

2013-01-01

The way in which Drosophila melanogaster acquires iron from the diet remains poorly understood despite iron absorption being of vital significance for larval growth. To describe the process of organismal iron absorption, consideration needs to be given to cellular iron import, storage, export and how intestinal epithelial cells sense and respond to iron availability. Here we review studies on the Divalent Metal Transporter-1 homolog Malvolio (iron import), the recent discovery that Multicopper Oxidase-1 has ferroxidase activity (iron export) and the role of ferritin in the process of iron acquisition (iron storage). We also describe what is known about iron regulation in insect cells. We then draw upon knowledge from mammalian iron homeostasis to identify candidate genes in flies. Questions arise from the lack of conservation in Drosophila for key mammalian players, such as ferroportin, hepcidin and all the components of the hemochromatosis-related pathway. Drosophila and other insects also lack erythropoiesis. Thus, systemic iron regulation is likely to be conveyed by different signaling pathways and tissue requirements. The significance of regulating intestinal iron uptake is inferred from reports linking Drosophila developmental, immune, heat-shock and behavioral responses to iron sequestration. PMID:23686013

Incorporating Geochemical And Microbial Kinetics In Reactive Transport Models For Generation Of Acid Rock Drainage

NASA Astrophysics Data System (ADS)

Andre, B. J.; Rajaram, H.; Silverstein, J.

2010-12-01

Acid mine drainage, AMD, results from the oxidation of metal sulfide minerals (e.g. pyrite), producing ferrous iron and sulfuric acid. Acidophilic autotrophic bacteria such as Acidithiobacillus ferrooxidans and Leptospirillum ferrooxidans obtain energy by oxidizing ferrous iron back to ferric iron, using oxygen as the electron acceptor. Most existing models of AMD do not account for microbial kinetics or iron geochemistry rigorously. Instead they assume that oxygen limitation controls pyrite oxidation and thus focus on oxygen transport. These models have been successfully used for simulating conditions where oxygen availability is a limiting factor (e.g. source prevention by capping), but have not been shown to effectively model acid generation and effluent chemistry under a wider range of conditions. The key reactions, oxidation of pyrite and oxidation of ferrous iron, are both slow kinetic processes. Despite being extensively studied for the last thirty years, there is still not a consensus in the literature about the basic mechanisms, limiting factors or rate expressions for microbially enhanced oxidation of metal sulfides. An indirect leaching mechanism (chemical oxidation of pyrite by ferric iron to produce ferrous iron, with regeneration of ferric iron by microbial oxidation of ferrous iron) is used as the foundation of a conceptual model for microbially enhanced oxidation of pyrite. Using literature data, a rate expression for microbial consumption of ferrous iron is developed that accounts for oxygen, ferrous iron and pH limitation. Reaction rate expressions for oxidation of pyrite and chemical oxidation of ferrous iron are selected from the literature. A completely mixed stirred tank reactor (CSTR) model is implemented coupling the kinetic rate expressions, speciation calculations and flow. The model simulates generation of AMD and effluent chemistry that qualitatively agrees with column reactor and single rock experiments. A one dimensional reaction diffusion model at the scale of a single rock is developed incorporating the proposed kinetic rate expressions. Simulations of initiation, washout and AMD flows are discussed to gain a better understanding of the role of porosity, effective diffusivity and reactive surface area in generating AMD. Simulations indicate that flow boundary conditions control generation of acid rock drainage as porosity increases.

Adipocyte iron regulates leptin and food intake

PubMed Central

Gao, Yan; Li, Zhonggang; Gabrielsen, J. Scott; Simcox, Judith A.; Lee, Soh-hyun; Jones, Deborah; Cooksey, Bob; Stoddard, Gregory; Cefalu, William T.; McClain, Donald A.

2015-01-01

Dietary iron supplementation is associated with increased appetite. Here, we investigated the effect of iron on the hormone leptin, which regulates food intake and energy homeostasis. Serum ferritin was negatively associated with serum leptin in a cohort of patients with metabolic syndrome. Moreover, the same inverse correlation was observed in mice fed a high-iron diet. Adipocyte-specific loss of the iron exporter ferroportin resulted in iron loading and decreased leptin, while decreased levels of hepcidin in a murine hereditary hemochromatosis (HH) model increased adipocyte ferroportin expression, decreased adipocyte iron, and increased leptin. Treatment of 3T3-L1 adipocytes with iron decreased leptin mRNA in a dose-dependent manner. We found that iron negatively regulates leptin transcription via cAMP-responsive element binding protein activation (CREB activation) and identified 2 potential CREB-binding sites in the mouse leptin promoter region. Mutation of both sites completely blocked the effect of iron on promoter activity. ChIP analysis revealed that binding of phosphorylated CREB is enriched at these two sites in iron-treated 3T3-L1 adipocytes compared with untreated cells. Consistent with the changes in leptin, dietary iron content was also directly related to food intake, independently of weight. These findings indicate that levels of dietary iron play an important role in regulation of appetite and metabolism through CREB-dependent modulation of leptin expression. PMID:26301810

Integration to Implementation and the Micronutrient Forum: A Coordinated Approach for Global Nutrition. Case Study Application: Safety and Effectiveness of Iron Interventions123

PubMed Central

Raiten, Daniel J; Neufeld, Lynnette M; De-Regil, Luz-Maria; Pasricha, Sant-Rayn; Darnton-Hill, Ian; Hurrell, Richard; Murray-Kolb, Laura E; Nair, K Madhavan; Wefwafwa, Terry; Kupka, Roland; Phall, Modou Cheyassin; Sakr Ashour, Fayrouz A

2016-01-01

Paramount among the challenges to our ability to address the role of food and nutrition in health promotion and disease prevention is how to design and implement context-specific interventions and guidance. The Integration to Effective Implementation (I-to-I) concept is intended to address the complexities of the global health context through engagement of the continuum of stakeholders involved in the food and nutrition enterprise. The 2014 Micronutrient Forum (MNF) Global Conference held in Addis Ababa, Ethiopia, in June 2014 offered the opportunity to apply the I-to-I approach with the use of current concerns about the safety and effectiveness of interventions to prevent and treat iron deficiency (ID) as a case study. ID is associated with a range of adverse outcomes, especially in pregnant and nonpregnant women, infants, and primary school-age children. Strategies to combat ID include iron supplementation, multiple micronutrient powders, and food-based interventions to enhance dietary iron intake. Recent reports indicate potential increased adverse risks when iron is provided in areas with high infection burdens (e.g., malaria). This paradox has weakened iron intervention programs. Furthermore, the selection and interpretation of available biomarkers for assessing iron nutrition have been found to be compromised by the inflammatory process. These issues highlight the need for a comprehensive approach that considers basic biology, assessment, interventions, and how these can be translated into appropriate programs and policies. The application of the I-to-I with the use of the MNF offered an opportunity to explore how that might be achieved. PMID:26773021

Responses of Saccharomyces cerevisiae Strains from Different Origins to Elevated Iron Concentrations

PubMed Central

Martínez-Garay, Carlos Andrés; de Llanos, Rosa; Romero, Antonia María; Martínez-Pastor, María Teresa

2016-01-01

Iron is an essential micronutrient for all eukaryotic organisms. However, the low solubility of ferric iron has tremendously increased the prevalence of iron deficiency anemia, especially in women and children, with dramatic consequences. Baker's yeast Saccharomyces cerevisiae is used as a model eukaryotic organism, a fermentative microorganism, and a feed supplement. In this report, we explore the genetic diversity of 123 wild and domestic strains of S. cerevisiae isolated from different geographical origins and sources to characterize how yeast cells respond to elevated iron concentrations in the environment. By using two different forms of iron, we selected and characterized both iron-sensitive and iron-resistant yeast strains. We observed that when the iron concentration in the medium increases, iron-sensitive strains accumulate iron more rapidly than iron-resistant isolates. We observed that, consistent with excess iron leading to oxidative stress, the redox state of iron-sensitive strains was more oxidized than that of iron-resistant strains. Growth assays in the presence of different oxidative reagents ruled out that this phenotype was due to alterations in the general oxidative stress protection machinery. It was noteworthy that iron-resistant strains were more sensitive to iron deficiency conditions than iron-sensitive strains, which suggests that adaptation to either high or low iron is detrimental for the opposite condition. An initial gene expression analysis suggested that alterations in iron homeostasis genes could contribute to the different responses of distant iron-sensitive and iron-resistant yeast strains to elevated environmental iron levels. PMID:26773083

The effect of iron plaque on lead translocation in soil-Carex cinerascens kukenth. system.

PubMed

Liu, Chunying; Gong, Xiaofeng; Chen, Chunli; Yang, Juyun; Xu, Sheng

2016-01-01

A pot experiment was conducted to investigate the effect of iron plaque on Pb uptake by and translocation in Carex cinerascens Kukenth. grown under open-air conditions. Using Scanning Electron Microscopy and Energy Dispersive X-Ray Spectrometry, iron plaque was present as an amorphous coating on root surfaces with uneven distribution. The amount of iron plaque increased significantly with increasing Fe additions regardless of Pb additions. The presence of iron plaque on the root surface of Carex cinerascens Kukenth. increased the concentrations of Pb adsorbed by iron plaque. The Pb percentage in whole roots increased by 14.52% at 500 mg kg(-1) Fe treatment than at 0 mg kg(-1) Fe, and the distribution coefficient (DC) of Pb and translocation factor (TF) root increased with Fe additions, but translocation factor (TF) shoot decreased with Fe additions. The results suggested that iron plaque could promote the translocation of Pb from soil to roots to some extent, and it played a role to reduce heavy metals pollution of Poyang Lake wetland.

Gallium Potentiates the Antibacterial Effect of Gentamicin against Francisella tularensis

PubMed Central

Lindgren, Helena

2015-01-01

The reasons why aminoglycosides are bactericidal have not been not fully elucidated, and evidence indicates that the cidal effects are at least partly dependent on iron. We demonstrate that availability of iron markedly affects the susceptibility of the facultative intracellular bacterium Francisella tularensis strain SCHU S4 to the aminoglycoside gentamicin. Specifically, the intracellular depots of iron were inversely correlated to gentamicin susceptibility, whereas the extracellular iron concentrations were directly correlated to the susceptibility. Further proof of the intimate link between iron availability and antibiotic susceptibility were the findings that a ΔfslA mutant, which is defective for siderophore-dependent uptake of ferric iron, showed enhanced gentamicin susceptibility and that a ΔfeoB mutant, which is defective for uptake of ferrous iron, displayed complete growth arrest in the presence of gentamicin. Based on the aforementioned findings, it was hypothesized that gallium could potentiate the effect of gentamicin, since gallium is sequestered by iron uptake systems. The ferrozine assay demonstrated that the presence of gallium inhibited >70% of the iron uptake. Addition of gentamicin and/or gallium to infected bone marrow-derived macrophages showed that both 100 μM gallium and 10 μg/ml of gentamicin inhibited intracellular growth of SCHU S4 and that the combined treatment acted synergistically. Moreover, treatment of F. tularensis-infected mice with gentamicin and gallium showed an additive effect. Collectively, the data demonstrate that SCHU S4 is dependent on iron to minimize the effects of gentamicin and that gallium, by inhibiting the iron uptake, potentiates the bactericidal effect of gentamicin in vitro and in vivo. PMID:26503658

DEPLETION OF IRON AND ASCORBATE IN RODENTS DIMINISHES LUNG INJURY AFTER SILICA

EPA Science Inventory

Exposures of the lung to iron chelates can be associated with an injury. The catalysis of oxygen-based free radicals is postulated to participate in this injury. Such oxidant generation by mineral oxide particles can be dependent on availability of both iron and a reductant. We t...

Rising atmospheric CO2 lowers food zinc, iron, and protein concentrations

USDA-ARS?s Scientific Manuscript database

Dietary deficiencies of zinc and iron are a major global public health problem. Most people who experience these deficiencies depend on agricultural crops for zinc and iron. In this context, the influence of rising concentrations of atmospheric CO2 on the availability of these nutrients from crops i...

A longitudinal study of serum ferritin in 319 adolescent Danish boys and girls examined in 1986 and 1992.

PubMed

Milman, N; Byg, K E; Backer, V; Ulrik, C; Graudal, N

1999-10-01

This study examined trends in iron status in adolescents. Serum ferritin was measured in 1986 and 1992 in 319 Danes (161 males) stratified into 5 groups: I. median age 9 yr in 1986 vs. 15 yr in 1992; II. 11 vs. 17 yr; III. 13 vs. 19 yr; IV. 15 vs. 21 yr; V. 17 vs. 23 yr. Males in group I demonstrated no change in ferritin or estimated iron stores in mg/kg; groups II-V displayed an increase in iron status parameters. All groups showed an increase in estimated total iron stores. Changes in iron status parameters were inversely correlated with height velocity in group III, and positively correlated with height velocity in group V. Females in age groups I and II demonstrated a fall in ferritin and estimated iron stores in mg/kg in association with menarche; values were unchanged in groups III and IV, and increased in group V. All groups showed an increase in estimated total iron stores. Changes in iron status parameters were inversely correlated with height velocity in groups I and II. In conclusion, ferritin levels in adolescents display great variation during growth spurt and at menarche. Changes in ferritin showed no consistent association with growth velocity. In both genders, estimated total iron stores increased with age.

Chorioamnionitis-induced changes of fetal extramedullar hematopoiesis in the second trimester of gestation. Is diagnosis from fetal autopsy possible?

PubMed

Pfisterer, Cora; Faber, Renaldo; Horn, Lars-Christian

2005-02-01

Chorioamnionitis, as the most frequent cause of second trimester abortions, is commonly diagnosed by histomorphological examination of placental tissue. We determined whether chorioamnionitis induces a fetal extramedullary hematopoietic response and estimated whether chorioamnionitis can be diagnosed from fetal liver alone. Clinical data and morphological and histological findings of 39 second trimester abortions, caused by chorioamnionitis, were compared with 32 age-matched control cases. Using hematoxylin and eosin staining, naphtol-ASD-chloracetate esterase and "Berliner Blau" reaction, total hematopoiesis, erythropoiesis, myelopoiesis and intracytoplasmatic iron of fetal liver were examined. In the study group, total hematopoiesis was increased compared with the controls (94.9% versus 84.4%). The same was seen in erythropoiesis (69.2% versus 56.2%, P>0.05). Chorioamnionitis resulted in a significant increase of fetal myelopoiesis with clustering of leukocytes in 56.4% (P=0.001). Neutrophiles were located predominantly intrasinusoidal and periportal (74.4%), while an isolated periportal location was often observed in controls (50.0%). Isolated perivenous iron storing was more often seen with chorioamnionitis (28.3% versus 3.1%) and correlated with the increasing severity of chorioamnionitis. It can be stated that infectious diseases, such as chorioamnionitis, increase fetal intrahepatic myelopoiesis as one defense mechanism. The morphology of fetal intrahepatic hematopoiesis and iron storing might also be helpful in the diagnosis of chorioamnionitis, especially when the placenta is not available for examination.

Resolving the paradigm crisis in intravenous iron and erythropoietin management.

PubMed

Besarab, A

2006-05-01

Despite the proven benefits of intravenous (i.v.) iron therapy in anemia management, it remains underutilized in the hemodialysis population. Although overall i.v. iron usage continues to increase slowly, monthly usage statistics compiled by the US Renal Data System suggest that clinicians are not implementing continued dosing regimens following repletion of iron stores. Continued therapy with i.v. iron represents a key opportunity to improve patient outcomes and increase the efficiency of anemia treatment. Regular administration of low doses of i.v. iron prevents the recurrence of iron deficiency, enhances response to recombinant human erythropoietin therapy, minimizes fluctuation of hemoglobin levels, hematocrit levels, and iron stores, and may reduce overall costs of care. This article reviews the importance of i.v. iron dosing on a regular basis in the hemodialysis patient with iron-deficiency anemia and explores reasons why some clinicians may still be reluctant to employ these protocols in the hemodialysis setting.

Iron homeostasis: a new job for macrophages in adipose tissue?

PubMed Central

Hubler, Merla J.; Peterson, Kristin R.; Hasty, Alyssa H.

2015-01-01

Elevated serum ferritin and increased cellular iron concentrations are risk factors for diabetes; however, the etiology of this association is unclear. Metabolic tissues such as pancreas, liver, and adipose tissue (AT), as well as the immune cells resident in these tissues, may be involved. Recent studies demonstrate that the polarization status of macrophages has important relevance to their iron handling capabilities. Furthermore, a subset of macrophages in AT have elevated iron concentrations and a gene expression profile indicative of iron handling, a capacity diminished in obesity. Because iron overload in adipocytes increases systemic insulin resistance, iron handling by AT macrophages may have relevance not only to adipocyte iron stores but also to local and systemic insulin sensitivity. PMID:25600948

Differential bioaccumulation and translocation patterns in three mangrove plants experimentally exposed to iron. Consequences for environmental sensing.

PubMed

Arrivabene, Hiulana Pereira; Campos, Caroline Quenupe; Souza, Iara da Costa; Wunderlin, Daniel Alberto; Milanez, Camilla Rozindo Dias; Machado, Silvia Rodrigues

2016-08-01

Avicennia schaueriana, Laguncularia racemosa and Rhizophora mangle were experimentally exposed to increasing levels of iron (0, 10, 20 and 100 mg L(-1) added Fe(II) in Hoagland's nutritive medium). The uptake and translocation of iron from roots to stems and leaves, Fe-secretion through salt glands (Avicennia schaueriana and Laguncularia racemosa) as well as anatomical and histochemical changes in plant tissues were evaluated. The main goal of this work was to assess the diverse capacity of these plants to detect mangroves at risk in an area affected by iron pollution (Vitoria, Espírito Santo, Brazil). Results show that plants have differential patterns with respect to bioaccumulation, translocation and secretion of iron through salt glands. L. racemosa showed the best environmental sensing capacity since the bioaccumulation of iron in both Fe-plaque and roots was higher and increased as the amount of added-iron rose. Fewer changes in translocation factors throughout increasing added-iron were observed in this species. Furthermore, the amount of iron secreted through salt glands of L. racemosa was strongly inhibited when exposed to added-iron. Among three studied species, A. schaueriana showed the highest levels of iron in stems and leaves. On the other hand, Rhizophora mangle presented low values of iron in these compartments. Even so, there was a significant drop in the translocation factor between aerial parts with respect to roots, since the bioaccumulation in plaque and roots of R. mangle increased as iron concentration rose. Moreover, rhizophores of R. mangle did not show changes in bioaccumulation throughout the studied concentrations. So far, we propose L. racemosa as the best species for monitoring iron pollution in affected mangroves areas. To our knowledge, this is the first detailed report on the response of these plants to increasing iron concentration under controlled conditions, complementing existing data on the behavior of the same plants under field exposure. Copyright © 2016 Elsevier Ltd. All rights reserved.

Iron and cell death in Parkinson's disease: a nuclear microscopic study into iron-rich granules in the parkinsonian substantia nigra of primate models

NASA Astrophysics Data System (ADS)

Thong, P. S. P.; Watt, F.; Ponraj, D.; Leong, S. K.; He, Y.; Lee, T. K. Y.

1999-10-01

Parkinson's disease is a degenerative brain disease characterised by a loss of cells in the substantia nigra (SN) region of the brain and accompanying biochemical changes such as inhibition of mitochondrial function, increased iron concentrations and decreased glutathione levels in the parkinsonian SN. Though the aetiology of the disease is still unknown, the observed biochemical changes point to the involvement of oxidative stress. In particular, iron is suspected to play a role by promoting free radical production, leading to oxidative stress and cell death. The increase in iron in the parkinsonian SN has been confirmed by several research groups, both in human post-mortem brains and in brain tissue from parkinsonian animal models. However, the question remains as to whether the observed increase in iron is a cause or a consequence of the SN cell death process. Our previous study using unilaterally 1-methyl-4-phenyl-1,2,3,6-tetrahydro-pyridine (MPTP)-lesioned monkeys in a time sequence experiment has shown that the increase in bulk iron concentrations follow rather than precede dopaminergic cell death. However, changes in the localised iron concentrations, which may play a more direct role in SN cell death, may not be reflected at the bulk level. Indeed, we have observed iron-rich granules in parkinsonian SNs. From this time sequence study into the iron content of iron-rich granules in the SNs of an untreated control and unilaterally MPTP-lesioned parkinsonian models, we present the following observations: (1) Iron-rich granules are found in both control and parkinsonian SNs and are variable in size and iron content in any one model. (2) These iron-rich granules may be associated with neuromelanin granules found in the SN and are known to accumulate transition metal ions such as iron. (3) The early onset of bulk SN cell loss (35%) was accompanied by a significant elevation of iron in granules found in the MPTP-injected SN compared to the contra-lateral SN. This shows that localised iron increase may be an early event contributing to cell death. (4) The iron content in granules found in both the MPTP-injected and contra-lateral SNs is correlated with the degree of bulk SN cell loss (assessed by TH-immunohistochemistry) in individual models. This indicates a correlation between localised iron increase and cell loss, at least at the whole SN level. Our results are consistent with the observation that in Parkinson's disease (PD), neuronal cell death seems to be related to their neuromelanin content and support the proposal that iron-melanin interaction may play a role in oxidative neuronal cell death. Indeed, iron-saturated neuromelanin granules may act as centres of free radical production, contributing to localised cell death.

Characterization of a Novel Iron Acquisition Activity That Coordinates the Iron Response with Population Density under Iron-Replete Conditions in Bacillus subtilis.

PubMed

Roy, Emily M; Griffith, Kevin L

2017-01-01

Iron is an essential micronutrient required for the viability of many organisms. Under oxidizing conditions, ferric iron is highly insoluble (∼10 -9 to 10 -18 M), yet bacteria typically require ∼10 -6 M for survival. To overcome this disparity, many bacteria have adopted the use of extracellular iron-chelating siderophores coupled with specific iron-siderophore uptake systems. In the case of Bacillus subtilis, undomesticated strains produce the siderophore bacillibactin. However, many laboratory strains, e.g., JH642, have lost the ability to produce bacillibactin during the process of domestication. In this work, we identified a novel iron acquisition activity from strain JH642 that accumulates in the growth medium and coordinates the iron response with population density. The molecule(s) responsible for this activity was named elemental Fe(II/III) (Efe) acquisition factor because efeUOB (ywbLMN) is required for its activity. Unlike most iron uptake molecules, including siderophores and iron reductases, Efe acquisition factor is present under iron-replete conditions and is regulated independently of Fur repressor. Restoring bacillibactin production in strain JH642 inhibits the activity of Efe acquisition factor, presumably by sequestering available iron. A similar iron acquisition activity is produced from a mutant of Escherichia coli unable to synthesize the siderophore enterobactin. Given the conservation of efeUOB and its regulation by catecholic siderophores in B. subtilis and E. coli, we speculate that Efe acquisition factor is utilized by many bacteria, serves as an alternative to Fur-mediated iron acquisition systems, and provides cells with biologically available iron that would normally be inaccessible during aerobic growth under iron-replete conditions. Iron is an essential micronutrient required for a variety of biological processes, yet ferric iron is highly insoluble during aerobic growth. In this work, we identified a novel iron acquisition activity that coordinates the iron response with population density in laboratory strains of Bacillus subtilis We named the molecule(s) responsible for this activity elemental Fe(II/III) (Efe) acquisition factor after the efeUOB (ywbLMN) operon required for its uptake into cells. Unlike most iron uptake systems, Efe acquisition factor is present under iron-replete conditions and is regulated independently of Fur, the master regulator of the iron response. We speculate that Efe acquisition factor is highly conserved among bacteria and serves as a backup to Fur-mediated iron acquisition systems. Copyright © 2016 American Society for Microbiology.

Shigella Iron Acquisition Systems and their Regulation.

PubMed

Wei, Yahan; Murphy, Erin R

2016-01-01

Survival of Shigella within the host is strictly dependent on the ability of the pathogen to acquire essential nutrients, such as iron. As an innate immune defense against invading pathogens, the level of bio-available iron within the human host is maintained at exceeding low levels, by sequestration of the element within heme and other host iron-binding compounds. In response to sequestration mediated iron limitation, Shigella produce multiple iron-uptake systems that each function to facilitate the utilization of a specific host-associated source of nutrient iron. As a mechanism to balance the essential need for iron and the toxicity of the element when in excess, the production of bacterial iron acquisition systems is tightly regulated by a variety of molecular mechanisms. This review summarizes the current state of knowledge on the iron-uptake systems produced by Shigella species, their distribution within the genus, and the molecular mechanisms that regulate their production.

Iron inhibits hydroxyapatite crystal growth in vitro.

PubMed

Guggenbuhl, Pascal; Filmon, Robert; Mabilleau, Guillaume; Baslé, Michel F; Chappard, Daniel

2008-07-01

Hemochromatosis is a known cause of osteoporosis in which the pathophysiology of bone loss is largely unknown and the role of iron remains questionable. We have investigated the effects of iron on the growth of hydroxyapatite crystals in vitro on carboxymethylated poly(2-hydroxyethyl methacrylate) pellets. This noncellular and enzyme-independent model mimics the calcification of woven bone (composed of calcospherites made of hydroxyapatite crystals). Polymer pellets were incubated with body fluid containing iron at increasing concentrations (20, 40, 60 micromol/L). Hydroxyapatite growth was studied by chemical analysis, scanning electron microscopy, and Raman microscopy. When incubated in body fluid containing iron, significant differences were observed with control pellets. Iron was detected at a concentration of 5.41- to 7.16-fold that of controls. In pellets incubated with iron, there was a approximately 3- to 4-fold decrease of Ca and P and a approximately 1.3- to 1.4-fold increase in the Ca/P ratio. There was no significant difference among the iron groups of pellets, but a trend to a decrease of Ca with the increase of iron concentration was noted. Calcospherite diameters were significantly lower on pellets incubated with iron. Raman microspectroscopy showed a decrease in crystallinity (measured by the full width of the half height of the 960 Deltacm(-1) band) with a significant increase in carbonate substitution (measured by the intensity ratio of 1071 to 960 Deltacm(-1) band). Energy dispersive x-ray analysis identified iron in the calcospherites. In vitro, iron is capable to inhibit bone crystal growth with significant changes in crystallinity and carbonate substitution.

A randomized trial of iron isomaltoside 1000 versus oral iron in non-dialysis-dependent chronic kidney disease patients with anaemia.

PubMed

Kalra, Philip A; Bhandari, Sunil; Saxena, Sanjiv; Agarwal, Dhananjai; Wirtz, Georg; Kletzmayr, Josef; Thomsen, Lars L; Coyne, Daniel W

2016-04-01

Iron deficiency anaemia is common in patients with non-dialysis-dependent chronic kidney disease (NDD-CKD) and is often treated with oral or intravenous (IV) iron therapy. This trial compared the efficacy and safety of IV iron isomaltoside 1000 (Monofer®) and oral iron in NDD-CKD patients with renal-related anaemia. The trial was a Phase III open-label, comparative, multicentre, non-inferiority trial conducted in 351 iron-deficient NDD-CKD patients, randomized 2:1 to either iron isomaltoside 1000 (Group A) or iron sulphate administered as 100 mg elemental oral iron twice daily (200 mg daily) for 8 weeks (Group B). The patients in Group A were randomized into A1 (infusion of max. 1000 mg single doses over 15 min) and A2 (bolus injections of 500 mg over 2 min). A modified Ganzoni formula was used to calculate IV iron need. The primary end point was change in haemoglobin concentrations from baseline to Week 4. Iron isomaltoside 1000 was both non-inferior to oral iron at Week 4 (P < 0.001) and sustained a superior increase in haemoglobin from Week 3 until the end of the study at Week 8 (P = 0.009 at Week 3). The haemoglobin response was more pronounced with iron isomaltoside 1000 doses ≥1000 mg (P < 0.05). Serum-ferritin and transferrin saturation concentrations were also significantly increased with IV iron. Adverse drug reactions were observed in 10.5% in the iron isomaltoside 1000 group and 10.3% in the oral iron group. More patients treated with oral iron sulphate withdrew from the study due to adverse events (4.3 versus 0.9%, P = 0.2). Iron isomaltoside 1000 was more efficacious than oral iron for increase in haemoglobin and proved to be well tolerated at the tested dose levels in NDD-CKD patients. © The Author 2015. Published by Oxford University Press on behalf of ERA-EDTA.

The dose-dependent effects of chronic iron overload on the production of oxygen free radicals and vitamin E concentrations in the liver of a murine model.

PubMed

McCullough, Karey D; Bartfay, Wally J

2007-04-01

Genetic disorders of iron metabolism such as primary and secondary hemochromatosis affect thousands of individuals worldwide and are major causes of liver dysfunction, morbidity, and mortality. Although the exact mechanism of hepatic injury associated with these genetic disorders is not fully understood, the propagation of excess concentrations of iron-catalyzed oxygen free radicals (OFRs) may play a role. The authors hypothesized that chronic iron burden would result in dose-dependent (a) increases in hepatic iron stores, (b) increases in hepatic OFR-mediated hepatic cellular injury as quantified by the cytotoxic aldehydes malondialdehyde (MDA) and hexanal, and (c) decreases in protective antioxidant reserve status as quantified by plasma vitamin E (alpha-tocopherol) levels in a murine model. Twenty B(6)D(2)F1 male mice were randomized to the (a) saline control (0.05 mL intraperiotoneal [i.p.]/mouse/day, n = 5), (b) 100 mg total iron burden (n = 5), (c) 200 mg total iron burden (n = 5), or (d) 400 mg total iron burden (n = 5) group. Iron burden was achieved by daily injections of iron dextran (Imferon, 0.05 mL i.p./mouse/day). In comparison to control mice and in support of the hypothesis, the authors observed significant dose-dependent increases in total hepatic iron burden (p < .001) with corresponding increases in MDA and hexanal concentrations (p < .001) and decreases in the protective plasma antioxidant vitamin E (p < .001). These findings suggest that iron-catalyzed OFR-mediated damage may play a role in damaging the liver in chronic states of iron burden.

Overexpression of Arabidopsis VIT1 increases accumulation of iron in cassava roots and stems

USDA-ARS?s Scientific Manuscript database

Iron is extremely abundant in the soil, but its uptake in plants is limited due to low solubility in neutral or alkaline soils. Plants can rely on rhizosphere acidification to increase iron solubility. AtVIT1 was previously found to be involved in mediating vacuolar sequestration of iron, which indi...

Crop acquisition of phosphorus, iron and zinc from soil in cereal/legume intercropping systems: a critical review

PubMed Central

Xue, Yanfang; Xia, Haiyong; Christie, Peter; Zhang, Zheng; Li, Long; Tang, Caixian

2016-01-01

Background Phosphorus (P), iron (Fe) and zinc (Zn) are essential elements for plant growth and development, but their availability in soil is often limited. Intercropping contributes to increased P, Fe and Zn uptake and thereby increases yield and improves grain nutritional quality and ultimately human health. A better understanding of how intercropping leads to increased plant P, Fe and Zn availability will help to improve P-fertilizer-use efficiency and agronomic Fe and Zn biofortification. Scope This review synthesizes the literature on how intercropping of legumes with cereals increases acquisition of P, Fe and Zn from soil and recapitulates what is known about root-to-shoot nutrient translocation, plant-internal nutrient remobilization and allocation to grains. Conclusions Direct interspecific facilitation in intercropping involves below-ground processes in which cereals increase Fe and Zn bioavailability while companion legumes benefit. This has been demonstrated and verified using isotopic nutrient tracing and molecular analysis. The same methodological approaches and field studies should be used to explore direct interspecific P facilitation. Both niche complementarity and interspecific facilitation contribute to increased P acquisition in intercropping. Niche complementarity may also contribute to increased Fe and Zn acquisition, an aspect poorly understood. Interspecific mobilization and uptake facilitation of sparingly soluble P, Fe and Zn from soil, however, are not the only determinants of the concentrations of P, Fe and Zn in grains. Grain yield and nutrient translocation from roots to shoots further influence the concentrations of these nutrients in grains. PMID:26749590

[Effect on iron release in drinking water distribution systems].

PubMed

Niu, Zhang-bin; Wang, Yang; Zhang, Xiao-jian; Chen, Chao; Wang, Sheng-hui

2007-10-01

Batch-scale experiments were done to quantitatively study the effect of inorganic chemical parameters on iron release in drinking water distribution systems. The parameters include acid-base condition, oxidation-reduction condition, and neutral ion condition. It was found that the iron release rate decreased with pH, alkalinity, the concentration of dissolved oxygen increasing, and the iron release rate increased with the concentration of chloride increasing. The theoretical critical formula of iron release rate was elucidated. According to the formula, the necessary condition for controlling iron release is that pH is above 7.6, the concentration of alkalinity and dissolved oxygen is more than 150 mg/L and 2 mg/L, and the concentration of chloride is less than 150 mg/L of distributed water.

Iron clad wetlands: Soil iron-sulfur buffering determines coastal wetland response to salt water incursion

NASA Astrophysics Data System (ADS)

Schoepfer, Valerie A.; Bernhardt, Emily S.; Burgin, Amy J.

2014-12-01

Coastal freshwater wetland chemistry is rapidly changing due to increased frequency of salt water incursion, a consequence of global change. Seasonal salt water incursion introduces sulfate, which microbially reduces to sulfide. Sulfide binds with reduced iron, producing iron sulfide (FeS), recognizable in wetland soils by its characteristic black color. The objective of this study is to document iron and sulfate reduction rates, as well as product formation (acid volatile sulfide (AVS) and chromium reducible sulfide (CRS)) in a coastal freshwater wetland undergoing seasonal salt water incursion. Understanding iron and sulfur cycling, as well as their reduction products, allows us to calculate the degree of sulfidization (DOS), from which we can estimate how long soil iron will buffer against chemical effects of sea level rise. We show that soil chloride, a direct indicator of the degree of incursion, best predicted iron and sulfate reduction rates. Correlations between soil chloride and iron or sulfur reduction rates were strongest in the surface layer (0-3 cm), indicative of surface water incursion, rather than groundwater intrusion at our site. The interaction between soil moisture and extractable chloride was significantly related to increased AVS, whereas increased soil chloride was a stronger predictor of CRS. The current DOS in this coastal plains wetland is very low, resulting from high soil iron content and relatively small degree of salt water incursion. However, with time and continuous salt water exposure, iron will bind with incoming sulfur, creating FeS complexes, and DOS will increase.

Marine sediments microbes capable of electrode oxidation as a surrogate for lithotrophic insoluble substrate metabolism.

PubMed

Rowe, Annette R; Chellamuthu, Prithiviraj; Lam, Bonita; Okamoto, Akihiro; Nealson, Kenneth H

2014-01-01

Little is known about the importance and/or mechanisms of biological mineral oxidation in sediments, partially due to the difficulties associated with culturing mineral-oxidizing microbes. We demonstrate that electrochemical enrichment is a feasible approach for isolation of microbes capable of gaining electrons from insoluble minerals. To this end we constructed sediment microcosms and incubated electrodes at various controlled redox potentials. Negative current production was observed in incubations and increased as redox potential decreased (tested -50 to -400 mV vs. Ag/AgCl). Electrode-associated biomass responded to the addition of nitrate and ferric iron as terminal electron acceptors in secondary sediment-free enrichments. Elemental sulfur, elemental iron and amorphous iron sulfide enrichments derived from electrode biomass demonstrated products indicative of sulfur or iron oxidation. The microbes isolated from these enrichments belong to the genera Halomonas, Idiomarina, Marinobacter, and Pseudomonas of the Gammaproteobacteria, and Thalassospira and Thioclava from the Alphaproteobacteria. Chronoamperometry data demonstrates sustained electrode oxidation from these isolates in the absence of alternate electron sources. Cyclic voltammetry demonstrated the variability in dominant electron transfer modes or interactions with electrodes (i.e., biofilm, planktonic or mediator facilitated) and the wide range of midpoint potentials observed for each microbe (from 8 to -295 mV vs. Ag/AgCl). The diversity of extracellular electron transfer mechanisms observed in one sediment and one redox condition, illustrates the potential importance and abundance of these interactions. This approach has promise for increasing our understanding the extent and diversity of microbe mineral interactions, as well as increasing the repository of microbes available for electrochemical applications.

Maternal iron – infection interactions and neonatal mortality, with an emphasis on developing countries

PubMed Central

Brabin, Loretta; Brabin, Bernard J.; Gies, Sabine

2013-01-01

Infection is a major cause of neonatal death in developing countries. We address the question whether host iron status affects maternal and/or neonatal infection risk, potentially contributing to neonatal death. We summarize the iron acquisition mechanisms described for pathogens causing stillbirth, preterm birth, and congenital infection. There is in vitro evidence that iron availability influences severity and chronicity of infections that cause these outcomes. The risk in vivo is unknown as relevant studies of maternal iron supplementation have not assessed infection risk. Reducing iron deficiency anemia among women is beneficial and should improve the iron stores of babies, but there is evidence that iron status in young children predicts malaria risk and possibly invasive bacterial diseases. Caution with maternal iron supplementation is indicated in iron-replete women who have high infection exposure, although distinguishing iron-replete and iron-deficient women is currently difficult. Further research is indicated to investigate infection risk in relation to iron status in mothers and babies in order to avoid iron intervention strategies that result in detrimental birth outcomes for some groups of women. PMID:23865798

The Janus transcription factor HapX controls fungal adaptation to both iron starvation and iron excess

PubMed Central

Gsaller, Fabio; Hortschansky, Peter; Beattie, Sarah R; Klammer, Veronika; Tuppatsch, Katja; Lechner, Beatrix E; Rietzschel, Nicole; Werner, Ernst R; Vogan, Aaron A; Chung, Dawoon; Mühlenhoff, Ulrich; Kato, Masashi; Cramer, Robert A; Brakhage, Axel A; Haas, Hubertus

2014-01-01

Balance of physiological levels of iron is essential for every organism. In Aspergillus fumigatus and other fungal pathogens, the transcription factor HapX mediates adaptation to iron limitation and consequently virulence by repressing iron consumption and activating iron uptake. Here, we demonstrate that HapX is also essential for iron resistance via activating vacuolar iron storage. We identified HapX protein domains that are essential for HapX functions during either iron starvation or high-iron conditions. The evolutionary conservation of these domains indicates their wide-spread role in iron sensing. We further demonstrate that a HapX homodimer and the CCAAT-binding complex (CBC) cooperatively bind an evolutionary conserved DNA motif in a target promoter. The latter reveals the mode of discrimination between general CBC and specific HapX/CBC target genes. Collectively, our study uncovers a novel regulatory mechanism mediating both iron resistance and adaptation to iron starvation by the same transcription factor complex with activating and repressing functions depending on ambient iron availability. PMID:25092765

Iron-catalyzed synthesis of secondary amines: on the way to green reductive aminations.

PubMed

Stemmler, Tobias; Surkus, Annette-Enrika; Pohl, Marga-Martina; Junge, Kathrin; Beller, Matthias

2014-11-01

Amines represent important intermediates in chemical and biological processes. Herein, we describe the use of a nanostructured iron-based catalyst for the tandem reductive amination between nitroarenes and aldehydes using hydrogen as reductant. The nanostructured iron-catalyst is prepared by immobilization of an iron-phenanthroline complex onto a commercially available carbon support. In the reaction sequence a primary amine is formed in situ from the corresponding nitro compound. Reversible condensation with aldehydes forms the respective imines, which are finally reduced to the desired secondary amine. This synthesis of secondary amines is atom-economical and environmentally attractive using cheap and readily available organic compounds as starting materials. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Dysfunction of Iron Metabolism and Iron-Regulatory Proteins in the Rat Hippocampus After Heat Stroke.

PubMed

Liu, Jing; Wan, Shengming; Zhang, Yun; Zhang, Shu; Zhang, Hongying; Wu, Shiwen

2018-05-11

Heat stroke, the most serious type of heat illness, refers to the presence of hyperthermia (core temperature >40°C), accompanied by central nervous system dysfunction. The hippocampus is a particularly vulnerable region in the early stage of heat stroke. Increasing evidence suggests that dysregulation of brain iron metabolism is involved in many neurodegenerative diseases. However, whether heat stroke causes dysfunction of iron metabolism, as well as iron-regulatory proteins, in the hippocampus remains unknown. The present study was conducted to explore the effects on spatial learning and memory, as well as iron content, ferroportin 1 (Fpn1), and hepcidin expression in the hippocampus after heat stroke in rats. Compared with the Sham group, learning ability and memory declined in rats after heat stroke. Iron concentration was significantly increased in the hippocampus. Expression of Fpn1 protein significantly decreased in the hippocampus, while expression of hepcidin increased. Interestingly, Fpn1 mRNA expression in the hippocampus increased. Our data thereby indicate that heat stroke can decrease learning ability and memory in rats. The mechanism may be related to changes of iron levels, as well as Fpn1 and hepcidin expression, in the hippocampus. Furthermore, hepcidin may rapidly decrease cellular Fpn1 protein levels, even under conditions of iron loading, indicating that hepcidin is a more dominant regulator of Fpn1 than is iron.

Protective effects of Mangifera indica L extract (Vimang), and its major component mangiferin, on iron-induced oxidative damage to rat serum and liver.

PubMed

Pardo-Andreu, Gilberto L; Barrios, Mariela Forrellat; Curti, Carlos; Hernández, Ivones; Merino, Nelson; Lemus, Yeny; Martínez, Ioanna; Riaño, Annia; Delgado, René

2008-01-01

In vivo preventive effects of a Mangifera indica L extract (Vimang) or its major component mangiferin on iron overload injury have been studied in rats given respectively, 50, 100, 250 mg kg(-1) body weight of Vimang, or 40 mg kg(-1) body weight of mangiferin, for 7 days prior to, and for 7 days following the administration of toxic amounts of iron-dextran. Both Vimang or mangiferin treatment prevented iron overload in serum as well as liver oxidative stress, decreased serum and liver lipid peroxidation, serum GPx activity, and increased serum and liver GSH, serum SOD and the animals overall antioxidant condition. Serum iron concentration was decreased although at higher doses, Vimang tended to increase it; percent tranferrin saturation, liver weight/body mass ratios, liver iron content was decreased. Treatment increased serum iron-binding capacity and decreased serum levels of aspartate-amine transferase (ASAT) and alanine-amine transferase (ALAT), as well as the number of abnormal Kupffer cells in iron-loaded livers. It is suggested that besides acting as antioxidants, Vimang extract or its mangiferin component decrease liver iron by increasing its excretion. Complementing earlier in vitro results from our group, it appears possible to support the hypothesis that Vimang and mangiferin present therapeutically useful effects in iron overload related diseases.

In vivo assessment of iron content of the cerebral cortex in healthy aging using 7-Tesla T2*-weighted phase imaging.

PubMed

Buijs, Mathijs; Doan, Nhat Trung; van Rooden, Sanneke; Versluis, Maarten J; van Lew, Baldur; Milles, Julien; van der Grond, Jeroen; van Buchem, Mark A

2017-05-01

Accumulation of brain iron has been suggested as a biomarker of neurodegeneration. Increased iron has been seen in the cerebral cortex in postmortem studies of neurodegenerative diseases and healthy aging. Until recently, the diminutive thickness of the cortex and its relatively low iron content have hampered in vivo study of cortical iron accumulation. Using phase images of a T2*-weighted sequence at ultrahigh field strength (7 Tesla), we examined the iron content of 22 cortical regions in 70 healthy subjects aged 22-80 years. The cortex was automatically segmented and parcellated, and phase shift was analyzed using an in-house developed method. We found a significant increase in phase shift with age in 20 of 22 cortical regions, concurrent with current understanding of cortical iron accumulation. Our findings suggest that increased cortical iron content can be assessed in healthy aging in vivo. The high spatial resolution and sensitivity to iron of our method make it a potentially useful tool for studying cortical iron accumulation in healthy aging and neurodegenerative diseases. Copyright © 2016 Elsevier Inc. All rights reserved.

Ferric reductase activity of low molecular weight human milk fraction is associated with enhanced iron solubility and uptake in Caco-2 cells.

PubMed

Pullakhandam, Raghu; Nair, Madhavan Krishnapillai; Kasula, Sunanda; Kilari, Sreenivasulu; Thippande, Tippeswamy Gowda

2008-09-19

It is known that the fractional absorption of extrinsic iron from human milk is higher in infants and adults. A low molecular weight milk fraction has been proposed to increase the bioavailability of iron from human milk. Nevertheless, the mechanisms remained elusive. Here in we demonstrate ferric reductase activity (Km7.73x10(-6)M) in low molecular weight human milk fraction (10kF, filtrate derived from ultra filtration of milk whey through 10kDa cutoff membrane), which increased ferric iron solubility and iron uptake in Caco-2 cells. The 10kF fraction was as effective as ascorbic acid (1:20 iron to ascorbic acid) in increasing the ferric iron solubility and uptake in Caco-2 cells. Further, gel filtration chromatography on peptide column led to co-elution of ferric reductase and iron solubilization activities at an apparent molecular mass of <1500Da. Interestingly, only these fractions containing ferric reductase activity also stimulated the uptake of iron in Caco-2 cells. Thus, it is concluded that human milk possesses ferric reductase activity and is associated with ferric iron solubilization and enhanced absorption.

Removal of arsenic from aqueous solutions using waste iron columns inoculated with iron bacteria.

PubMed

Azhdarpoor, Abooalfazl; Nikmanesh, Roya; Samaei, Mohammad Reza

2015-01-01

Arsenic contamination of water resources is one of the serious risks threatening natural ecosystems and human health. This study investigates arsenic removal using a waste iron column with and without iron bacteria in continuous and batch phases. In batch experiments, the effects of pH, contact time, initial concentration of arsenic and adsorbent dose were investigated. Results indicated that the highest arsenate removal efficiency occurred at pH 7 (96.76%). On increasing the amount of waste iron from 0.25 to 1 g, the removal rate changed from about 42.37%-96.70%. The results of continuous experiments on the column containing waste iron showed that as the empty bed contact time increased from 5 to 60 min, the secondary arsenate concentration changed from 23 to 6 µg/l. In experiments involving a waste iron column with iron bacteria, an increase in residence time from 5 to 60 min decreased the secondary arsenate concentration from 14.97 to 4.86 µg/l. The results of this study showed that waste iron containing iron bacteria is a good adsorbent for removal of arsenic from contaminated water.

Iron, zinc, folate, and vitamin B12 status increased among women and children in Yaounde and Douala, Cameroon, one year after introducing fortified wheat flour

USDA-ARS?s Scientific Manuscript database

Background: Few data, to our knowledge, are available on the effectiveness of large-scale food fortification programs. Objective: We assessed the impact of mandatory wheat flour fortification on micronutrient status in Yaounde and Douala, Cameroon. Methods: We conducted representative surveys 2 y ...

Prooxidant Mechanisms in Iron Overload Cardiomyopathy

PubMed Central

Cheng, Ching-Feng; Lian, Wei-Shiung

2013-01-01

Iron overload cardiomyopathy (IOC), defined as the presence of systolic or diastolic cardiac dysfunction secondary to increased deposition of iron, is emerging as an important cause of heart failure due to the increased incidence of this disorder seen in thalassemic patients and in patients of primary hemochromatosis. At present, although palliative treatment by regular iron chelation was recommended; whereas IOC is still the major cause for mortality in patient with chronic heart failure induced by iron-overloading. Because iron is a prooxidant and the associated mechanism seen in iron-overload heart is still unclear; therefore, we intend to delineate the multiple signaling pathways involved in IOC. These pathways may include organelles such as calcium channels, mitochondria; paracrine effects from both macrophages and fibroblast, and novel mediators such as thromboxane A2 and adiponectin; with increased oxidative stress and inflammation found commonly in these signaling pathways. With further understanding on these complex and inter-related molecular mechanisms, we can propose potential therapeutic strategies to ameliorate the cardiac toxicity induced by iron-overloading. PMID:24350287

Iron repletion relocalizes hephaestin to a proximal basolateral compartment in polarized MDCK and Caco2 cells

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lee, Seung-Min; Department of Nutritional Science and Toxicology, University of California, Berkeley, CA; Attieh, Zouhair K.

2012-05-11

Highlights: Black-Right-Pointing-Pointer Hephaestin localizes in the perinuclear space in non-polarized cells. Black-Right-Pointing-Pointer Hephaestin localizes in the perinuclear space in iron deficient and polarized cells. Black-Right-Pointing-Pointer Hephaestin with apical iron moves near to basolateral membrane of polarized cells. Black-Right-Pointing-Pointer Peri-basolateral location of hephaestin is accessible to the extracellular space. Black-Right-Pointing-Pointer Hephaestin is involved in iron mobilization from the intestine to circulation. -- Abstract: While intestinal cellular iron entry in vertebrates employs multiple routes including heme and non-heme routes, iron egress from these cells is exclusively channeled through the only known transporter, ferroportin. Reduced intestinal iron export in sex-linked anemia mice implicatesmore » hephaestin, a ferroxidase, in this process. Polarized cells are exposed to two distinct environments. Enterocytes contact the gut lumen via the apical surface of the cell, and through the basolateral surface, to the body. Previous studies indicate both local and systemic control of iron uptake. We hypothesized that differences in iron availability at the apical and/or basolateral surface may modulate iron uptake via cellular localization of hephaestin. We therefore characterized the localization of hephaestin in two models of polarized epithelial cell lines, MDCK and Caco2, with varying iron availability at the apical and basolateral surfaces. Our results indicate that hephaestin is expressed in a supra-nuclear compartment in non-polarized cells regardless of the iron status of the cells and in iron deficient and polarized cells. In polarized cells, we found that both apical (as FeSO{sub 4}) and basolateral iron (as the ratio of apo-transferrin to holo-transferrin) affect mobilization of hephaestin from the supra-nuclear compartment. We find that the presence of apical iron is essential for relocalization of hephaestin to a cellular compartment in close proximity but not overlapping with the basolateral surface. Surface biotinylation studies indicate that hephaestin in the peri-basolateral location is accessible to the extra-cellular environment. These results support the hypothesis that hephaestin is involved in iron mobilization of iron from the intestine to circulation.« less

New insights into transfusion-related iron toxicity: Implications for the oncologist.

PubMed

Porter, John B; de Witte, Theo; Cappellini, M Domenica; Gattermann, Norbert

2016-03-01

Iron overload is a potentially life-threatening consequence of multiple red-blood-cell transfusions. Here, we review factors affecting excess iron distribution and its damage to specific tissues, as well as mechanisms of oncogenesis by iron. Although consequences of transfusional iron overload are best described in thalassemia major and related inherited anemias, they are increasingly recognized in acquired conditions, such as myelodysplastic syndromes (MDS). Iron overload in MDS not only impacts on certain tissues, but may affect the clonal evolution of MDS through generation of reactive oxygen species. Iron overload may also influence hematopoietic-stem-cell-transplantation outcomes. Novel MRI methods for assessing body iron have impacted significantly on outcome in inherited anemias by allowing monitoring of iron burden and iron chelation therapy. This approach is increasingly being used in MDS and stem-cell-transplant procedures. Knowledge gained from managing transfusional iron overload in inherited anemias may be translated to general oncology, with potential for improved patient outcomes. Copyright © 2016. Published by Elsevier Ireland Ltd.

Brain mitochondrial iron accumulates in Huntington's disease, mediates mitochondrial dysfunction, and can be removed pharmacologically.

PubMed

Agrawal, Sonal; Fox, Julia; Thyagarajan, Baskaran; Fox, Jonathan H

2018-05-20

Mitochondrial bioenergetic dysfunction is involved in neurodegeneration in Huntington's disease (HD). Iron is critical for normal mitochondrial bioenergetics but can also contribute to pathogenic oxidation. The accumulation of iron in the brain occurs in mouse models and in human HD. Yet the role of mitochondria-related iron dysregulation as a contributor to bioenergetic pathophysiology in HD is unclear. We demonstrate here that human HD and mouse model HD (12-week R6/2 and 12-month YAC128) brains accumulated mitochondrial iron and showed increased expression of iron uptake protein mitoferrin 2 and decreased iron-sulfur cluster synthesis protein frataxin. Mitochondria-enriched fractions from mouse HD brains had deficits in membrane potential and oxygen uptake and increased lipid peroxidation. In addition, the membrane-permeable iron-selective chelator deferiprone (1 μM) rescued these effects ex-vivo, whereas hydrophilic iron and copper chelators did not. A 10-day oral deferiprone treatment in 9-week R6/2 HD mice indicated that deferiprone removed mitochondrial iron, restored mitochondrial potentials, decreased lipid peroxidation, and improved motor endurance. Neonatal iron supplementation potentiates neurodegeneration in mouse models of HD by unknown mechanisms. We found that neonatal iron supplementation increased brain mitochondrial iron accumulation and potentiated markers of mitochondrial dysfunction in HD mice. Therefore, bi-directional manipulation of mitochondrial iron can potentiate and protect against markers of mouse HD. Our findings thus demonstrate the significance of iron as a mediator of mitochondrial dysfunction and injury in mouse models of human HD and suggest that targeting the iron-mitochondrial pathway may be protective. Copyright © 2018 Elsevier Inc. All rights reserved.

A long-term high-fat diet changes iron distribution in the body, increasing iron accumulation specifically in the mouse spleen.

PubMed

Yamano, Noriko; Ikeda, Yasumasa; Sakama, Minoru; Izawa-Ishizawa, Yuki; Kihira, Yoshitaka; Ishizawa, Keisuke; Miyamoto, Licht; Tomita, Shuhei; Tsuchiya, Koichiro; Tamaki, Toshiaki

2015-01-01

Although iron is an essential trace metal, its presence in excess causes oxidative stress in the human body. Recent studies have indicated that iron storage is a risk factor for type 2 diabetes mellitus. Dietary iron restriction or iron chelation ameliorates symptoms of type 2 diabetes in mouse models. However, whether iron content in the body changes with the development of diabetes is unknown. Here, we investigated the dynamics of iron accumulation and changes in iron absorption-related genes in mice that developed obesity and diabetes by consuming a high-fat diet (HFD-fed mice). HFD-fed mice (18-20 wk) were compared with control mice for hematologic features, serum ferritin levels, and iron contents in the gastrocnemius muscle, heart, epididymal fat, testis, liver, duodenum, and spleen. In addition, the spleen was examined histologically. Iron absorption-related gene expression in the liver and duodenum was also examined. Hemoglobin and serum ferritin levels were increased in HFD-fed mice. The HFD-fed mice showed iron accumulation in the spleen, but not in the heart or liver. Increased percentages of the splenic red pulp and macrophages were observed in HFD-fed mice and iron accumulation in the spleen was found mainly in the splenic red pulp. The HFD-fed mice also showed decreased iron content in the duodenum. The mRNA expression of divalent metal transporter-1 (DMT-1), an iron absorption-related gene, was elevated in the duodenum of HFD-fed mice. These results indicate that iron accumulation (specifically accumulation in the spleen) is enhanced by the development of type 2 diabetes induced by HFD.

Hepcidin expression does not rescue the iron-poor phenotype of Kupffer cells in Hfe-null mice after liver transplantation.

PubMed

Garuti, Cinzia; Tian, Yinghua; Montosi, Giuliana; Sabelli, Manuela; Corradini, Elena; Graf, Rolf; Ventura, Paolo; Vegetti, Alberto; Clavien, Pierre-Alain; Pietrangelo, Antonello

2010-07-01

Hemochromatosis is a common hereditary disease caused by mutations in HFE and characterized by increased absorption of iron in the intestine. However, the intestine does not appear to be the site of mutant HFE activity in the disease; we investigated the role of the liver-the source of the iron regulatory hormone hepcidin-in pathogenesis in mice. We exchanged livers between Hfe wild-type (+/+) and Hfe null (-/-) mice by orthotopic liver transplantation (OLT) and assessed histopathology, serum and tissue iron parameters, and hepatic hepcidin messenger RNA expression. At 6-8 months after OLT, Hfe(-/-) mice that received Hfe(-/-) livers maintained the hemochromatosis phenotype: iron accumulation in hepatocytes but not Kupffer cells (KC), increased transferrin levels, and low levels of iron in the spleen. Hfe(+/+) mice that received Hfe(-/-) livers had increased levels of iron in serum and liver and low levels of iron in spleen. However, they did not develop the iron-poor KCs that characterize hemochromatosis: KCs appeared iron rich, although hepatic hepcidin expression was low. Transplantation of Hfe(+/+) livers into Hfe(-/-) mice prevented hepatic iron accumulation but did not return spleen and plasma levels of iron to normal; KCs still appeared to be iron poor, despite normal hepcidin expression. In Hfe(-/-) mice, transplantation of livers from Hfe(+/+) mice reversed the iron-loading phenotype associated with hemochromatosis (regardless of Hfe expression in intestine). However, KCs still had low levels of iron that were not affected by hepatic hepcidin expression. These findings indicate an independent, iron-modifying effect of HFE in KCs. Copyright 2010 AGA Institute. Published by Elsevier Inc. All rights reserved.

The interaction of phytosiderophores with soil as a function of time

NASA Astrophysics Data System (ADS)

Schenkeveld, W. D. C.; Oburger, E.; Schindlegger, Y.; Regelsberger, A.; Hann, S.; Puschenreiter, M.; Kraemer, S. M.

2012-04-01

Graminaceous plant species (grasses) exude natural chelating agents, called phytosiderophores (PS) for the purpose of iron acquisition, in particular under conditions of iron deficiency stress. The biogeochemistry of phytosiderophores in the rhizosphere is still poorly understood. Processes like mobilization of iron or other metals by PS, and the degradation of the chelating agent were previously studied under conditions quite remote from those observed in the rhizosphere, e.g. in hydroponics systems or in soil suspensions with low soils to solution ratios. Such experimental conditions may lead to artifacts like for instance the depletion of available metal fractions. The aim of the present study is to contribute to a more accurate quantification of the source and sink terms determining PS concentrations in the rhizosphere. The mobilization of iron and other metals from two clay soils and two sandy soils by the PS deoxymugineic acid (DMA) was studied as a function of time in a batch experiment with a soil-solution ratio of 1. Both soils causing iron deficiency stress in plants and a reference soil not doing so were included. To examine the effect of ligand biodegradation on metal mobilization, treatments with and without sterilant (azide) were included. The fraction of added DMA mobilizing Fe ranged from 10 to 60% and correlates positively with Fe availability (DTPA-extractable Fe) and negatively with the clay content of the soils. In particular in soils of low Fe availability, Fe mobilization by DMA was severely compromised by mobilization of other metals including Cu, Zn, Ni and Co. The relative importance of Zn as competing cation decreases over time, while the importance of Cu increases. In the treatment without sterilant addition, metal-DMA complexes were removed from solution after 4 days in all soils; in the clay soils, Fe-DMA complexes were already removed before. The highest concentration of mobilized Fe did not depend on whether sterilant was added or not, except in one soil; this concentration was reached after 0.25 up to 8 hours. Also in treatments with sterilant addition, the FeDMA concentration eventually declined, but removal from solution was not complete when the experiment ended after one week. This indicates that besides biodegradation there are other processes significantly compromising the FeDMA concentration in the soil. In summary, these results emphasize the importance of the kinetics and thermodynamics of coupled rhizosphere processes for plant iron acquisition.

Identification of iron-regulated genes of Bifidobacterium breve UCC2003 as a basis for controlled gene expression

PubMed Central

Cronin, Michelle; Zomer, Aldert; Fitzgerald, Gerald; van Sinderen, Douwe

2012-01-01

Iron is an essential growth factor for virtually all organisms. However, iron is not readily available in most environments and microorganisms have evolved specialized mechanisms, such as the use of siderophores and high-affinity transport systems, to acquire iron when confronted with iron-limiting conditions. In general these systems are tightly regulated to prevent iron-induced toxicity and because they are quite costly to the microbe. Because of this tight regulation we chose to explore the response of Bifidobacterium breve UCC2003 to iron limitation. Through microarray and complementation analyses we identified and characterized a presumed ferrous iron uptake system, encoded by bfeUOB, from B. breve UCC2003 and exploited its regulated transcription to develop an inducible expression system for use in bifidobacteria. PMID:22179149

Pathways of iron acquisition and utilization in Leishmania

PubMed Central

Flannery, Andrew R.; Renberg, Rebecca L.; Andrews, Norma W.

2013-01-01

Iron is essential for many metabolic pathways, but is toxic in excess. Recent identification of the ferric iron reductase LFR1, the ferrous iron transporter LIT1, and the heme transporter LHR1 greatly advanced our understanding of how Leishmania parasites acquire iron and regulate its uptake. LFR1 and LIT1 have close orthologs in plants, and are required for Leishmania virulence. Consistent with the lack of heme biosynthesis in trypanosomatids, LHR1 and LABCG5, a protein involved in heme salvage from hemoglobin, seem essential for Leishmania survival. LFR1, LIT1 and LHR1 are upregulated under low iron availability, in agreement with the need to prevent excessive iron uptake. Future studies should clarify how Leishmania interacts with the iron homeostasis machinery of its host cell, the macrophage. PMID:23962817

Iron Deficiency in Patients with Nonalcoholic Fatty Liver Disease is Associated with Obesity, Female Sex, and Low Serum Hepcidin

PubMed Central

Siddique, Asma; Nelson, James E.; Aouizerat, Bradley; Yeh, Matthew M.; Kowdley, Kris V.

2014-01-01

Background & Aims Iron deficiency is often observed in obese individuals. The iron regulatory hormone hepcidin is regulated by iron and cytokines IL6 and IL1β. We examine the relationship between obesity, circulating levels of hepcidin and IL6 and IL1β, and other risk factors in patients with non-alcoholic fatty liver disease (NAFLD) with iron deficiency. Methods We collected data on 675 adult subjects (>18 y old) enrolled in the Nonalcoholic Steatohepatitis Clinical Research Network. Subjects with transferrin saturation <20% were categorized as iron deficient, whereas those with transferrin saturation ≥20% were classified as iron normal. We assessed clinical, demographic, anthropometric, laboratory, dietary, and histologic data from patients, as well as serum levels of hepcidin and cytokines IL6 and IL1β. Univariate and multivariate analysis were used to identify risk factors for iron deficiency. Results One third of patients (231/675; 34%) were iron deficient. Obesity, diabetes, and metabolic syndrome were more common in subjects with iron deficiency (P<.01), compared with those that were iron normal. Serum levels of hepcidin were significantly lower in subjects with iron deficiency (61±45 vs 81±51 ng/mL; P<.0001). Iron deficiency was significantly associated with female sex, obesity, increased body mass index and waist circumference, presence of diabetes, lower alcohol consumption, Black or American Indian/Alaska Native race (P≤.018), and increased levels of IL6 and IL1β (6.6 vs 4.8 for iron normal; P≤.0001 and 0.45 vs 0.32 for iron normal; P≤.005). Conclusion Iron deficiency is prevalent in patients with NAFLD and associated with female sex, increased body mass index, and non-white race. Serum levels of hepcidin were lower in iron-deficient subjects, reflecting an appropriate physiological response to decreased circulating levels of iron, rather than a primary cause of iron deficiency in the setting of obesity and NAFLD. PMID:24269922

[Causes of iron deficiency in children].

PubMed

Olives, J-P

2017-05-01

Iron deficiency and iron deficiency anemia are common conditions worldwide affecting especially children. In developing countries, iron deficiency is caused by poor iron intake and parasitic infection. Poor iron intake linked to inadequate diets, low iron intestinal absorption, chronic blood losses and increased requirements are common causes in high-income countries. © 2017 Elsevier Masson SAS. Tous droits réservés.

DETERMINATION OF FERRITIN AND HEMOSIDERIN IRON IN PATIENTS WITH NORMAL IRON STORES AND IRON OVERLOAD BY SERUM FERRITIN KINETICS

PubMed Central

SAITO, HIROSHI; TOMITA, AKIHIRO; OHASHI, HARUHIKO; MAEDA, HIDEAKI; HAYASHI, HISAO; NAOE, TOMOKI

2012-01-01

ABSTRACT We attempted to clarify the storage iron metabolism from the change in the serum ferritin level. We assumed that the nonlinear decrease in serum ferritin was caused by serum ferritin increase in iron mobilization. Under this assumption, we determined both ferritin and hemosiderin iron levels by computer-assisted simulation of the row of decreasing assay-dots of serum ferritin in 11 patients with normal iron stores free of both iron deficiency and iron overload; chronic hepatitis C (CHC) and iron deficiency anemia after treatment, and 11 patients with iron overload; hereditary hemochromatosis (HH) and transfusion-dependent anemias (TD). We determined the iron removal rates of 20 and 17 mg/day by administering mean doses of deferasirox at 631 and 616 mg/day in 2 TD during the period of balance of iron addition and removal as indicated by the serum ferritin returned to the previous level. The ferritin-per-hemosiderin ratio was almost the same in both HH and CHC. This matched the localized hepatic hemosiderin deposition in CHC with normal iron stores. We detected the ferritin increased by utilizing the hemosiderin iron in iron removal and the ferritin reduced by transforming ferritin into hemosiderin in iron additions. The iron storing capacity of hemosiderin was limitless, while that of ferritin was suppressed when ferritin iron exceeded around 5 grams. We confirmed the pathway of iron from hemosiderin to ferritin in iron mobilization, and that from ferritin to hemosiderin in iron deposition. Thus, serum ferritin kinetics enabled us to be the first to clinically clarify storage iron metabolism. PMID:22515110

A Role for Iron-Sulfur Clusters in the Regulation of Transcription Factor Yap5-dependent High Iron Transcriptional Responses in Yeast*

PubMed Central

Li, Liangtao; Miao, Ren; Bertram, Sophie; Jia, Xuan; Ward, Diane M.; Kaplan, Jerry

2012-01-01

Yeast respond to increased cytosolic iron by activating the transcription factor Yap5 increasing transcription of CCC1, which encodes a vacuolar iron importer. Using a genetic screen to identify genes involved in Yap5 iron sensing, we discovered that a mutation in SSQ1, which encodes a mitochondrial chaperone involved in iron-sulfur cluster synthesis, prevented expression of Yap5 target genes. We demonstrated that mutation or reduced expression of other genes involved in mitochondrial iron-sulfur cluster synthesis (YFH1, ISU1) prevented induction of the Yap5 response. We took advantage of the iron-dependent catalytic activity of Pseudaminobacter salicylatoxidans gentisate 1,2-dioxygenase expressed in yeast to measure changes in cytosolic iron. We determined that reductions in iron-sulfur cluster synthesis did not affect the activity of cytosolic gentisate 1,2-dioxygenase. We show that loss of activity of the cytosolic iron-sulfur cluster assembly complex proteins or deletion of cytosolic glutaredoxins did not reduce expression of Yap5 target genes. These results suggest that the high iron transcriptional response, as well as the low iron transcriptional response, senses iron-sulfur clusters. PMID:22915593

Use of Magnetic Resonance Imaging to Monitor Iron Overload

PubMed Central

Wood, John C.

2014-01-01

SYNOPSIS Treatment of iron overload requires robust estimates of total body iron burden and its response to iron chelation therapy. Compliance with chelation therapy varies considerably among patients and individual reporting is notoriously unreliable. Even with perfect compliance, intersubject variability in chelator effectiveness is extremely high, necessitating reliable iron estimates to guide dose titration. In addition, each chelator has a unique profile with respect to clearing iron stores from different organs. This chapter will present the tools available to clinicians monitoring their patients, focusing on non-invasive magnetic resonance imaging methods because they have become the de-facto standard of care. PMID:25064711

Effect of temperature on biogeochemistry of marine organic-enriched systems: implications in a global warming scenario.

PubMed

Sanz-Lázaro, Carlos; Valdemarsen, Thomas; Marín, Arnaldo; Holmer, Marianne

2011-10-01

Coastal biogeochemical cycles are expected to be affected by global warming. By means of a mesocosm experiment, the effect of increased water temperature on the biogeochemical cycles of coastal sediments affected by organic-matter enrichment was tested, focusing on the carbon, sulfur, and iron cycles. Nereis diversicolor was used as a model species to simulate macrofaunal bioirrigation activity in natural sediments. Although bioirrigation rates of N. diversicolor were not temperature dependent, temperature did have a major effect on the sediment metabolism. Under organic-enrichment conditions, the increase in sediment metabolism was greater than expected and occurred through the enhancement of anaerobic metabolic pathway rates, mainly sulfate reduction. There was a twofold increase in sediment metabolism and the accumulation of reduced sulfur. The increase in the benthic metabolism was maintained by the supply of electron acceptors through bioirrigation and as a result of the availability of iron in the sediment. As long as the sediment buffering capacity toward sulfides is not surpassed, an increase in temperature might promote the recovery of organic-enriched sediments by decreasing the time for mineralization of excess organic matter.

Overexpression of Arabidopsis VIT1 increases accumulation of iron in cassava roots and stems.

PubMed

Narayanan, Narayanan; Beyene, Getu; Chauhan, Raj Deepika; Gaitán-Solis, Eliana; Grusak, Michael A; Taylor, Nigel; Anderson, Paul

2015-11-01

Iron is extremely abundant in the soil, but its uptake in plants is limited due to low solubility in neutral or alkaline soils. Plants can rely on rhizosphere acidification to increase iron solubility. AtVIT1 was previously found to be involved in mediating vacuolar sequestration of iron, which indicates a potential application for iron biofortification in crop plants. Here, we have overexpressed AtVIT1 in the starchy root crop cassava using a patatin promoter. Under greenhouse conditions, iron levels in mature cassava storage roots showed 3-4 times higher values when compared with wild-type plants. Significantly, the expression of AtVIT1 showed a positive correlation with the increase in iron concentration of storage roots. Conversely, young leaves of AtVIT1 transgenic plants exhibit characteristics of iron deficiency such as interveinal chlorosis of leaves (yellowing) and lower iron concentration when compared with the wild type plants. Interestingly, the AtVIT1 transgenic plants showed 4 and 16 times higher values of iron concentration in the young stem and stem base tissues, respectively. AtVIT1 transgenic plants also showed 2-4 times higher values of iron content when compared with wild-type plants, with altered partitioning of iron between source and sink tissues. These results demonstrate vacuolar iron sequestration as a viable transgenic strategy to biofortify crops and to help eliminate micronutrient malnutrition in at-risk human populations. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Effect of excess iron on oxidative stress and gluconeogenesis through hepcidin during mitochondrial dysfunction.

PubMed

Lee, Hyo Jung; Choi, Joo Sun; Lee, Hye Ja; Kim, Won-Ho; Park, Sang Ick; Song, Jihyun

2015-12-01

Excessive tissue iron levels are a risk factor for insulin resistance and type 2 diabetes, which are associated with alterations in iron metabolism. However, the mechanisms underlying this association are not well understood. This study used human liver SK-HEP-1 cells to examine how excess iron induces mitochondrial dysfunction and how hepcidin controls gluconeogenesis. Excess levels of reactive oxygen species (ROS) and accumulated iron due to iron overload induced mitochondrial dysfunction, leading to a decrease in cellular adenosine triphosphate content and cytochrome c oxidase III expression, with an associated increase in gluconeogenesis. Disturbances in mitochondrial function caused excess iron deposition and unbalanced expression of iron metabolism-related proteins such as hepcidin, ferritin H and ferroportin during the activation of p38 mitogen-activated protein kinase (MAPK) and CCAAT/enhancer-binding protein alpha (C/EBPα), which are responsible for increased phosphoenolpyruvate carboxykinase expression. Desferoxamine and n-acetylcysteine ameliorated these deteriorations by inhibiting p38 MAPK and C/EBPα activity through iron chelation and ROS scavenging activity. Based on experiments using hepcidin shRNA and hepcidin overexpression, the activation of hepcidin affects ROS generation and iron deposition, which disturbs mitochondrial function and causes an imbalance in iron metabolism and increased gluconeogenesis. Repression of hepcidin activity can reverse these changes. Our results demonstrate that iron overload is associated with mitochondrial dysfunction and that together they can cause abnormal hepatic gluconeogenesis. Hepcidin expression may modulate this disorder by regulating ROS generation and iron deposition. Copyright © 2015 Elsevier Inc. All rights reserved.

[Growth characteristics and control of iron bacteria on cast iron in drinking water distribution systems].

PubMed

Wang, Yang; Zhang, Xiao-Jian; Chen, Yu-Qiao; Lu, Pin-Pin; Chen, Chao

2009-11-01

This study investigated the growth characteristics of iron bacteria on cast iron and relationship between suspended and attached iron bacteria. The steady-state growth of iron bacteria would need 12 d and iron bacteria level in effluents increased 1 lg. Hydraulics influence on iron bacteria level and detachment rate of steady-state attached iron bacteria was not significant. But it could affect the time of attached iron bacteria on cast-iron coupons reaching to steady state. When the chlorine residual was 0.3 mg/L, the iron bacteria growth could be controlled effectively and suspended and attached iron bacteria levels both decreased 1 lg. When the chlorine residual was more than 1.0 mg/L, it could not inactivate the iron bacteria of internal corrosion scale yet. There was little effect on inhibiting the iron bacteria growth that the chlorine residual was 0.05 mg/L in drinking water quality standard of China. The iron bacteria on coupons reached to steady state without disinfectant and then increased the chlorine residual to 1.25 mg/L, the attached iron bacteria level could decrease 2 lg to 3 lg. Under steady-state, the suspended iron bacteria levels were linearly dependent on the attached iron bacteria. The control of iron bacteria in drinking water distribution systems was advanced: maintaining the chlorine residual (0.3 mg/L), flushing the pipeline with high dosage disinfectant, adopting corrosion-resistant pipe materials and renovating the old pipe loop.

Management of transfusional iron overload – differential properties and efficacy of iron chelating agents

PubMed Central

Kwiatkowski, Janet L

2011-01-01

Regular red cell transfusion therapy ameliorates disease-related morbidity and can be lifesaving in patients with various hematological disorders. Transfusion therapy, however, causes progressive iron loading, which, if untreated, results in endocrinopathies, cardiac arrhythmias and congestive heart failure, hepatic fibrosis, and premature death. Iron chelation therapy is used to prevent iron loading, remove excess accumulated iron, detoxify iron, and reverse some of the iron-related complications. Three chelators have undergone extensive testing to date: deferoxamine, deferasirox, and deferiprone (although the latter drug is not currently licensed for use in North America where it is available only through compassionate use programs and research protocols). These chelators differ in their modes of administration, pharmacokinetics, efficacy with regard to organ-specific iron removal, and adverse-effect profiles. These differential properties influence acceptability, tolerability and adherence to therapy, and, ultimately, the effectiveness of treatment. Chelation therapy, therefore, must be individualized, taking into account patient preferences, toxicities, ongoing transfusional iron intake, and the degree of cardiac and hepatic iron loading. PMID:22287873

Management of transfusional iron overload - differential properties and efficacy of iron chelating agents.

PubMed

Kwiatkowski, Janet L

2011-01-01

Regular red cell transfusion therapy ameliorates disease-related morbidity and can be lifesaving in patients with various hematological disorders. Transfusion therapy, however, causes progressive iron loading, which, if untreated, results in endocrinopathies, cardiac arrhythmias and congestive heart failure, hepatic fibrosis, and premature death. Iron chelation therapy is used to prevent iron loading, remove excess accumulated iron, detoxify iron, and reverse some of the iron-related complications. Three chelators have undergone extensive testing to date: deferoxamine, deferasirox, and deferiprone (although the latter drug is not currently licensed for use in North America where it is available only through compassionate use programs and research protocols). These chelators differ in their modes of administration, pharmacokinetics, efficacy with regard to organ-specific iron removal, and adverse-effect profiles. These differential properties influence acceptability, tolerability and adherence to therapy, and, ultimately, the effectiveness of treatment. Chelation therapy, therefore, must be individualized, taking into account patient preferences, toxicities, ongoing transfusional iron intake, and the degree of cardiac and hepatic iron loading.

Study of effective utilization of iron ore sinter through arc plasma

NASA Astrophysics Data System (ADS)

Swain, Biswajit; Samal, S. K.; Mohanty, M. K.; Behera, A.; Mishra, S. C.

2018-03-01

Generation of fines is common in mining, sizing, and beneficiation and also in high-temperature metallurgical processes as the disintegration of agglomerate/compact occurs. Extraction of metallic iron from ore fines is one of the challenging aspects of iron making industries as the liberation of fines blocks, the charge burden porosity and hence hinders the reduction rate. Along with size factor, mineral composition plays a vital role in the extraction process; particularly silica. As silica has the very high tendency towards iron oxide, at comparatively low temperature, the activity of silica should be suppressed to prevent silicate phases. Adjustment of such conditions is controlled by addition of lime, but sometimes excessive slag generation increases the cost of production. In the present work, carbothermic reduction of partially reduced iron bearing pellets has been melted through 20 KW DC arc plasma furnace, and a comparative study has been made for considering different slag chemistry approaches. Pellets as aforementioned are made available from Patnaik Steel and Alloys Ltd, Odisha, having high silica content ore fines (of about 8.6%) as obtained from the chemical analysis. X-Ray analysis and optical image analyzer result of sinter thus obtained reveal that fayalite phase has major fractional value. Smelting works were done for sinter with/without adjustment of slag chemistry, where argon and nitrogen were used as plasma forming gases. A range of recovery rates (between 87-94%) is achieved by charge composition, ionizing gases, and smelting duration. It is observed that use of nitrogen as plasma forming gas increases the recovery rate than that of using only argon plasma; due to high energy flux of nitrogen which increases the enthalpy due to its diatomicity. A maximum recovery rate of about 94% is achieved for process duration of 13minutes utilizing nitrogen plasma. Smelting of charge with the addition of hydrated lime targeting melilite as final slag resulted in the formation of metallic iron as confirmed from XRD and XRF analyses. In the other hand, ferrosilicon is liberated in the metallic parts where smelting of charge was done without adjustment of slag chemistry. Both metal and slag thus obtained are characterized by XRD, XRF, microhardness and wet chemical analysis suitably.

Can an increase in leaf iron reductase activity enhance seed iron accumulation in soybean?

USDA-ARS?s Scientific Manuscript database

Iron is an important micronutrient for human nutrition, with plant foods providing a significant amount of dietary iron in certain population groups, and in some cases, providing the sole source of dietary iron. Because iron deficiency is unfortunately common in many human populations, we have been...

Oxidative stress and damage in liver, but not in brain, of Fischer 344 rats subjected to dietary iron supplementation with lipid-soluble [(3,5,5-trimethylhexanoyl)ferrocene].

PubMed

Lykkesfeldt, Jens; Morgan, Evan; Christen, Stephan; Skovgaard, Lene Theil; Moos, Torben

2007-01-01

Accumulation of iron probably predisposes the aging brain to progressive neuronal loss. We examined various markers of oxidative stress and damage in the brain and liver of 3- and 24-month-old rats following supplementation with the lipophilic iron derivative [(3,5,5-trimethylhexanoyl)ferrocene] (TMHF), which is capable of crossing the blood-brain barrier. At both ages, iron concentration increased markedly in the liver but failed to increase in the brain. In the liver of TMHF-treated young rats, levels of alpha- and gamma-tocopherols and glutathione (GSH) were also higher. In contrast, the brain displayed unaltered levels of the tocopherols and GSH. Malondialdehyde (MDA) level was also higher in the cerebrospinal fluid (CSF) and the liver but not in the brain. In old rats, the absence of an increase in iron concentration in the brain was reflected by unaltered concentrations of GSH, tocopherols, and MDA as compared to that in untreated rats. In the aging liver, concentrations of GSH and MDA increased with TMHF treatment. Morphological studies revealed unaltered levels of iron, ferritin, heme oxygenase-1 (HO-1), nitrotyrosine (NT), or MDA in the brains of both young and old rats treated with TMHF. In contrast, TMHF treatment increased the level of HO-1 in Kupffer cells, NT in hepatic endothelial cells, and MDA and ferritin in hepatocytes. Although these results demonstrated an increase in the biochemical markers of oxidative stress and damage in response to increasing concentrations of iron in the liver, they also demonstrated that the brain is well protected against dietary iron overload by using iron in a lipid-soluble formulation.

The iron chelator deferasirox protects mice from mucormycosis through iron starvation

PubMed Central

Ibrahim, Ashraf S.; Gebermariam, Teclegiorgis; Fu, Yue; Lin,, Lin; Husseiny, Mohamed I.; French, Samuel W.; Schwartz, Julie; Skory, Christopher D.; Edwards, John E.; Spellberg, Brad J.

2007-01-01

Mucormycosis causes mortality in at least 50% of cases despite current first-line therapies. Clinical and animal data indicate that the presence of elevated available serum iron predisposes the host to mucormycosis. Here we demonstrate that deferasirox, an iron chelator recently approved for use in humans by the US FDA, is a highly effective treatment for mucormycosis. Deferasirox effectively chelated iron from Rhizopus oryzae and demonstrated cidal activity in vitro against 28 of 29 clinical isolates of Mucorales at concentrations well below clinically achievable serum levels. When administered to diabetic ketoacidotic or neutropenic mice with mucormycosis, deferasirox significantly improved survival and decreased tissue fungal burden, with an efficacy similar to that of liposomal amphotericin B. Deferasirox treatment also enhanced the host inflammatory response to mucormycosis. Most importantly, deferasirox synergistically improved survival and reduced tissue fungal burden when combined with liposomal amphotericin B. These data support clinical investigation of adjunctive deferasirox therapy to improve the poor outcomes of mucormycosis with current therapy. As iron availability is integral to the pathogenesis of other infections (e.g., tuberculosis, malaria), broader investigation of deferasirox as an antiinfective treatment is warranted. PMID:17786247

Iron overload in thalassemia and related conditions: therapeutic goals and assessment of response to chelation therapies.

PubMed

Porter, John B; Shah, Farrukh T

2010-12-01

Transfusional iron loading inevitably results in hepatic iron accumulation, with variable extrahepatic distribution that is typically less pronounced in sickle cell disease than in thalassemia disorders. Iron chelation therapy has the goal of preventing iron-mediated tissue damage through controlling tissue iron levels, without incurring chelator-mediated toxicity. Historically, target levels for tissue iron control have been limited by the increased frequency of deferoxamine-mediated toxicity and low levels of iron loading. With newer chelation regimes, these limitations are less evident. The reporting of responses to chelation therapies has typically focused on average changes in serum ferritin in patient populations. This approach has three limitations. First, changes in serum ferritin may not reflect trends in iron balance equally in all patients or for all chelation regimens. Second, this provides no information about the proportion of patients likely respond. Third, this gives insufficient information about iron trends in tissues such as the heart. Monitoring of iron overload has advanced with the increasing use of MRI techniques to estimate iron balance (changes in liver iron concentration) and extrahepatic iron distribution (myocardial T2*). The term nonresponder has been increasingly used to describe individuals who fail to show a downward trend in one or more of these variables. Lack of a response of an individual may result from inadequate dosing, high transfusion requirement, poor treatment adherence, or unfavorable pharmacology of the chelation regime. This article scrutinizes evidence for response rates to deferoxamine, deferiprone (and combinations), and deferasirox. Copyright © 2010 Elsevier Inc. All rights reserved.

Effect of Infant Formula on Streptococcus Mutans Biofilm Formation.

PubMed

Hinds, Laura M; Moser, Elizabeth A S; Eckert, George; Gregory, Richard L

This study investigated the effect that infant formula had on biofilm growth of Streptococcus mutans. Specifically, it compared biofilm growth in media containing lactose-based and sucrose-based formulas. It also analyzed biofilm formation with formulas of varying iron content. Biofilm growth was tested with the specific infant formula components sucrose, lactose, and ferric chloride. The study was designed to determine if these types of infant formulas and components affected S. mutans biofilm formation differently. A 24-hour culture of S. mutans was treated with various concentrations of infant formula diluted in bacteriological media. To test for biofilm formation, S. mutans was cultured with and without the infant formula and formula components. The biofilms were washed, fixed, and stained with crystal violet. The absorbance was measured to evaluate biofilm growth and total absorbance. Sucrose-based formulas provided significant increases in biofilm growth when compared to lactose-based formulas at two dilutions (1:5, 1:20). Similac Sensitive RS (sucrose-based) at most dilutions provided the most significant increase in biofilm growth when compared to the control. Sucrose tested as an individual component provided more of a significant increase on biofilm growth than lactose or iron when compared to the control. A low iron formula provided a significant increase in biofilm growth at one dilution (1:5) when compared to formula containing a normal iron content. There was no significant difference in biofilm growth when comparing high iron formula to normal iron formula or low iron formula. There was no significant difference when comparing Similac PM 60/40 (low iron formula) to Similac PM 60/40 with additional ferric chloride. The results of this study demonstrated that sucrose-based formula provided more of a significant increase in biofilm growth compared to lactose-based formula. Sucrose alone provided a significant increase of biofilm growth at more dilutions when compared to the control than lactose and iron. The amount of iron in formula had a significant effect on biofilm formation only when comparing low iron formula to normal iron formula at the highest concentration (1:5). There was no significant difference in biofilm growth when iron was added to the low iron formula. The information obtained expands current knowledge regarding the influence of infant formula on the primary dentition and reinforces the importance of oral hygiene habits once the first tooth erupts.

Accumulation of iron by primary rat hepatocytes in long-term culture: changes in nuclear shape mediated by non-transferrin-bound forms of iron.

PubMed Central

Cable, E. E.; Connor, J. R.; Isom, H. C.

1998-01-01

We have previously shown that hepatocytes in long-term dimethylsulfoxide (DMSO) culture, fed a chemically defined medium, are highly differentiated and an excellent in vitro model of adult liver. Hepatocytes in long-term DMSO culture can be iron loaded by exposure to non-transferrin-bound iron (NTBI) in the form of ferrous sulfate (FeSO4), ferric nitrilotriacetate, or trimethylhexanoyl (TMH)-ferrocene. Holotransferrin, at equivalent times and concentrations, was unable to load hepatocytes. Of the iron compounds tested, TMH-ferrocene most accurately simulated the morphological features of iron-loaded hepatocytes in vivo. When exposed to 25 micromol/L TMH-ferrocene, hepatocytes loaded increasing amounts of iron for 2 months before the cells died. When exposed to lower concentrations of TMH-ferrocene (as low as 2.5 micromol/L), hepatocytes continuously loaded iron and remained viable for more than 2 months. The cellular deposition of iron was different in hepatocytes exposed to TMH-ferrocene compared with those exposed to FeSO4; exposure to TMH-ferrocene resulted in the presence of more ferritin cores within lysosomes than were seen with FeSO4. When the concentration of TMH-ferrocene was increased, a greater number of ferritin cores were observed within the lysosome, and total cellular ferritin, as assessed by Western blot, increased. The formation of hemosiderin was also observed. Furthermore, nuclear shape was distorted in iron-loaded hepatocytes. The extent of deviation from circularity in the nucleus correlated with increasing concentrations of TMH-ferrocene and was greater in hepatocytes exposed to FeSO4 than an equivalent concentration of TMH-ferrocene. The deviation from circularity was smallest in hepatocytes that contained well formed ferritin cores and increased in hepatocytes that contained greater amounts of hemosiderin. Furthermore, in hepatocytes treated with FeSO4, a large amount of cell-associated iron was detected but without a significant increase in the total amount of ferritin. The deviation from circularity was the largest in FeSO4-treated hepatocytes, indicating that iron not properly incorporated into ferritin caused more cellular damage. We conclude that iron-loaded hepatocytes in long-term DMSO culture represent a flexible system for studying the effects of chronic iron loading on hepatocytes. Images Figure 1 Figure 2 Figure 5 Figure 7 PMID:9502420

Pathophysiology of Hereditary Hemochromatosis

PubMed Central

Fleming, Robert E.; Britton, Robert S.; Waheed, Abdul; Sly, William S.; Bacon, Bruce R.

2008-01-01

Hereditary hemochromatosis (HH) encompasses several inherited disorders of iron homeostasis characterized by increased gastrointestinal iron absorption and tissue iron deposition. The most common form of this disorder is HFE-related HH, nearly always caused by homozygosity for the C282Y mutation. A substantial proportion of C282Y homozygotes do not develop clinically significant iron overload, suggesting roles for environmental factors and modifier genes in determining the phenotype. Recent studies have demonstrated that the pathogenesis of nearly all forms of HH involves inappropriately decreased expression of the iron-regulatory hormone hepcidin. Hepcidin serves to decrease the export of iron from reticuloendothelial cells and absorptive enterocytes. Thus, HH patients demonstrate increased iron release from these cell types, elevated circulating iron, and iron deposition in vulnerable tissues. The mechanism by which HFE influences hepcidin expression is an area of current investigation and may offer insights into the phenotypic variability observed in persons with mutations in HFE. PMID:16315135

Effect of iron supplementation during lactation on maternal iron status and oxidative stress: A randomized controlled trial.

PubMed

Jorgensen, Josh M; Yang, Zhenyu; Lönnerdal, Bo; Chantry, Caroline J; Dewey, Kathryn G

2017-10-01

We examined the effect of iron-containing prenatal vitamin-mineral supplements taken postpartum on biomarkers of iron status and oxidative stress. Lactating women (n = 114) were randomly assigned to consume daily one iron-free prenatal vitamin-mineral supplement plus either 27 mg of iron or placebo for approximately 3.5 months. The placebo group took the tablets between meals, while those given iron took the tablets either with (Fe-W) or between meals (Fe-B). Blood and urine samples were collected before and after the supplementation period to analyze hemoglobin (Hb), ferritin, hepcidin, transferrin saturation (TfSat), total plasma iron, and biomarkers of oxidative stress (isoprostane and 8-hydroxy-2-deoxyguanosine (8-OHdG)) and inflammation (C-reactive protein (CRP) and alpha-1-acid glycoprotein (AGP)). There was a trend toward a greater change in Hb among women in the Fe-B group compared to placebo (+2.5 vs. -3.7 g/L, respectively, p = 0.063). When the iron groups were combined, there was a greater change in Hb (+1.4 g/L) compared to placebo (p = 0.010). There were trends toward greater changes in TfSat (p = 0.087) and total plasma iron (p = 0.065) in the iron groups compared to placebo, yet no significant differences between the three groups in change in hepcidin (p = 0.291), isoprostane (p = 0.319), or 8-OHdG (p = 0.659), nor in change in ferritin among those with elevated CRP at baseline (60% of women; p = 0.946); among those without elevated CRP (40% of women), ferritin increased more in the iron groups compared to placebo (p = 0.001). Iron consumption during lactation moderately increased iron status, particularly among women without elevated CRP, and increased Hb, but did not significantly increase oxidative stress. © 2016 John Wiley & Sons Ltd.

Absorption of Iron from Ferritin Is Independent of Heme Iron and Ferrous Salts in Women and Rat Intestinal Segments123

PubMed Central

Chen, Huijun; Miranda, Constanza; Janser, Heinz; Elsenhans, Bernd; Núñez, Marco T.; Pizarro, Fernando; Schümann, Klaus

2012-01-01

Ferritin iron from food is readily bioavailable to humans and has the potential for treating iron deficiency. Whether ferritin iron absorption is mechanistically different from iron absorption from small iron complexes/salts remains controversial. Here, we studied iron absorption (RBC 59Fe) from radiolabeled ferritin iron (0.5 mg) in healthy women with or without non-ferritin iron competitors, ferrous sulfate, or hemoglobin. A 9-fold excess of non-ferritin iron competitor had no significant effect on ferritin iron absorption. Larger amounts of iron (50 mg and a 99-fold excess of either competitor) inhibited iron absorption. To measure transport rates of iron that was absorbed inside ferritin, rat intestinal segments ex vivo were perfused with radiolabeled ferritin and compared to perfusion with ferric nitrilotriacetic (Fe-NTA), a well-studied form of chelated iron. Intestinal transport of iron absorbed inside exogenous ferritin was 14.8% of the rate measured for iron absorbed from chelated iron. In the steady state, endogenous enterocyte ferritin contained >90% of the iron absorbed from Fe-NTA or ferritin. We found that ferritin is a slow release source of iron, readily available to humans or animals, based on RBC iron incorporation. Ferritin iron is absorbed by a different mechanism than iron salts/chelates or heme iron. Recognition of a second, nonheme iron absorption process, ferritin endocytosis, emphasizes the need for more mechanistic studies on ferritin iron absorption and highlights the potential of ferritin present in foods such as legumes to contribute to solutions for global iron deficiency. PMID:22259191

Iron-mediated changes in phytoplankton photosynthetic competence during SOIREE

NASA Astrophysics Data System (ADS)

Boyd, P. W.; Abraham, E. R.

Active fluorescence (fast repetition rate fluorometry, FRRF) was used to follow the photosynthetic response of the phytoplankton community during the 13-day Southern Ocean Iron RElease Experiment (SOIREE). This in situ iron enrichment was conducted in the polar waters of the Australasian-Pacific sector of the Southern Ocean in February 1999. Iron fertilisation of these high nitrate low chlorophyll (HNLC) waters resulted in an increase in the photosynthetic competence ( Fv/ Fm) of the resident cells from around 0.20 to greater than 0.60 (i.e. close to the theoretical maximum) by 10/11 days after the first enrichment. Although a significant iron-mediated response in Fv/ Fm was detected as early as 24 h after the initial fertilisation, the increase in Fv/ Fm to double ambient levels took 6 days. This response was five-fold slower than observed in iron enrichments (in situ and in vitro) in the HNLC waters of the subarctic and equatorial Pacific. Although little is known about the relationship between water temperature and Fv/ Fm, it is likely that low water temperatures — and possibly the deep mixed layer — were responsible for this slow response time. During SOIREE, the photosynthetic competence of the resident phytoplankton in iron-enriched waters increased at dissolved iron levels above 0.2 nM, suggesting that iron limitation was alleviated at this concentration. Increases in Fv/ Fm of cells within four algal size classes suggested that all taxa displayed a photosynthetic response to iron enrichment. Other physiological proxies of algal iron stress (such as flavodoxin levels in diatoms) exhibited different temporal trends to iron-enrichment than Fv/ Fm during the time-course of SOIREE. The relationship between Fv/ Fm, algal growth rate and such proxies in Southern Ocean waters is discussed.

A High Serum Iron Level Causes Mouse Retinal Iron Accumulation Despite an Intact Blood-Retinal Barrier

PubMed Central

Zhao, Liangliang; Li, Yafeng; Song, Delu; Song, Ying; Theurl, Milan; Wang, Chenguang; Cwanger, Alyssa; Su, Guanfang; Dunaief, Joshua L.

2015-01-01

The retina can be shielded by the blood-retinal barrier. Because photoreceptors are damaged by excess iron, it is important to understand whether the blood-retinal barrier protects against high serum iron levels. Bone morphogenic protein 6 (Bmp6) knockout mice have serum iron overload. Herein, we tested whether the previously documented retinal iron accumulation in Bmp6 knockout mice might result from the high serum iron levels or, alternatively, low levels of retinal hepcidin, an iron regulatory hormone whose transcription can be up-regulated by Bmp6. Furthermore, to determine whether increases in serum iron can elevate retinal iron levels, we i.v. injected iron into wild-type mice. Retinas were analyzed by real-time quantitative PCR and immunofluorescence to assess the levels of iron-regulated genes/proteins and oxidative stress. Retinal hepcidin mRNA levels in Bmp6 knockout retinas were the same as, or greater than, those in age-matched wild-type retinas, indicating that Bmp6 knockout does not cause retinal hepcidin deficiency. Changes in mRNA levels of L ferritin and transferrin receptor indicated increased retinal iron levels in i.v. iron-injected wild-type mice. Oxidative stress markers were elevated in photoreceptors of mice receiving i.v. iron. These findings suggest that elevated serum iron levels can overwhelm local retinal iron regulatory mechanisms. PMID:25174877

Retinal iron homeostasis in health and disease

PubMed Central

Song, Delu; Dunaief, Joshua L.

2013-01-01

Iron is essential for life, but excess iron can be toxic. As a potent free radical creator, iron generates hydroxyl radicals leading to significant oxidative stress. Since iron is not excreted from the body, it accumulates with age in tissues, including the retina, predisposing to age-related oxidative insult. Both hereditary and acquired retinal diseases are associated with increased iron levels. For example, retinal degenerations have been found in hereditary iron overload disorders, like aceruloplasminemia, Friedreich's ataxia, and pantothenate kinase-associated neurodegeneration. Similarly, mice with targeted mutation of the iron exporter ceruloplasmin and its homolog hephaestin showed age-related retinal iron accumulation and retinal degeneration with features resembling human age-related macular degeneration (AMD). Post mortem AMD eyes have increased levels of iron in retina compared to age-matched healthy donors. Iron accumulation in AMD is likely to result, in part, from inflammation, hypoxia, and oxidative stress, all of which can cause iron dysregulation. Fortunately, it has been demonstrated by in vitro and in vivo studies that iron in the retinal pigment epithelium (RPE) and retina is chelatable. Iron chelation protects photoreceptors and retinal pigment epithelial cells (RPE) in a variety of mouse models. This has therapeutic potential for diminishing iron-induced oxidative damage to prevent or treat AMD. PMID:23825457

Iron homeostasis and its disruption in mouse lung in iron deficiency and overload.

PubMed

Giorgi, Gisela; D'Anna, María Cecilia; Roque, Marta Elena

2015-10-01

What is the central question of this study? The aim was to explore the role and hitherto unclear mechanisms of action of iron proteins in protecting the lung against the harmful effects of iron accumulation and the ability of pulmonary cells to mobilize iron in iron deficiency. What is the main finding and its importance? We show that pulmonary hepcidin appears not to modify cellular iron mobilization in the lung. We propose pathways for supplying iron to the lung in iron deficiency and for protecting the lung against iron excess in iron overload, mediated by the co-ordinated action of iron proteins, such as divalent metal transporter 1, ZRT-IRE-like-protein 14, transferrin receptor, ferritin, haemochromatosis-associated protein and ferroportin. Iron dyshomeostasis is associated with several forms of chronic lung disease, but its mechanisms of action remain to be elucidated. The aim of the present study was to determine the role of the lung in whole-animal models with iron deficiency and iron overload, studying the divalent metal transporter 1 (DMT1), ZRT-IRE-like protein 14 (ZIP14), transferrin receptor (TfR), haemochromatosis-associated protein (HFE), hepcidin, ferritin and ferroportin (FPN) expression. In each model, adult CF1 mice were divided into the following groups (six mice per group): (i) iron-overload model, iron saccharate i.p. and control group (iron adequate), 0.9% NaCl i.p.; and (ii) iron-deficiency model, induced by repeated bleeding, and control group (sham operated). Proteins were assessed by immunohistochemistry and Western blot. In control mice, DMT1 was localized in the cytoplasm of airway cells, and in iron deficiency and overload it was in the apical membrane. Divalent metal transporter 1 and TfR increased in iron deficiency, without changes in iron overload. ZRT-IRE-like protein 14 decreased in airway cells in iron deficiency and increased in iron overload. In iron deficiency, HFE and FPN were immunolocalized close to the apical membrane. Ferroportin increased in iron overload. Prohepcidin was present in control groups, with no changes in iron deficiency and iron overload. In iron overload, ferritin showed intracytoplasmic localization close to the apical membrane of airway cells and intense immunostaining in macrophage-like cells. The results show that pulmonary hepcidin does not appear to modify cellular iron mobilization in the lung. We propose the following two novel pathways in the lung: (i) for supplying iron in iron deficiency, mediated principally by DMT1 and TfR and regulated by the action of FPN and HFE; and (ii) for iron detoxification in order to protect the lung against iron overload, facilitated by the action of DMT1, ZIP14, FPN and ferritin. © 2015 The Authors. Experimental Physiology © 2015 The Physiological Society.

Iron deficiency and iron excess damage mitochondria and mitochondrial DNA in rats

PubMed Central

Walter, Patrick B.; Knutson, Mitchell D.; Paler-Martinez, Andres; Lee, Sonia; Xu, Yu; Viteri, Fernando E.; Ames, Bruce N.

2002-01-01

Approximately two billion people, mainly women and children, are iron deficient. Two studies examined the effects of iron deficiency and supplementation on rats. In study 1, mitochondrial functional parameters and mitochondrial DNA (mtDNA) damage were assayed in iron-deficient (≤5 μg/day) and iron-normal (800 μg/day) rats and in both groups after daily high-iron supplementation (8,000 μg/day) for 34 days. This dose is equivalent to the daily dose commonly given to iron-deficient humans. Iron-deficient rats had lower liver mitochondrial respiratory control ratios and increased levels of oxidants in polymorphonuclear-leukocytes, as assayed by dichlorofluorescein (P < 0.05). Rhodamine 123 fluorescence of polymorphonuclear-leukocytes also increased (P < 0.05). Lowered respiratory control ratios were found in daily high-iron-supplemented rats regardless of the previous iron status (P < 0.05). mtDNA damage was observed in both iron-deficient rats and rats receiving daily high-iron supplementation, compared with iron-normal rats (P < 0.05). Study 2 compared iron-deficient rats given high doses of iron (8,000 μg) either daily or every third day and found that rats given iron supplements every third day had less mtDNA damage on the second and third day after the last dose compared to daily high iron doses. Both inadequate and excessive iron (10 × nutritional need) cause significant mitochondrial malfunction. Although excess iron has been known to cause oxidative damage, the observation of oxidant-induced damage to mitochondria from iron deficiency has been unrecognized previously. Untreated iron deficiency, as well as excessive-iron supplementation, are deleterious and emphasize the importance of maintaining optimal iron intake. PMID:11854522

Siderophore-mediated iron acquisition mechanisms in Vibrio vulnificus biotype 2.

PubMed Central

Biosca, E G; Fouz, B; Alcaide, E; Amaro, C

1996-01-01

Vibrio vulnificus biotype 2 is a primary pathogen for eels and, as has recently been suggested, an opportunistic pathogen for humans. In this study we have investigated the ability of V. vulnificus biotype 2 to obtain iron by siderophore-mediated mechanisms and evaluated the importance of free iron in vibriosis. The virulence degree for eels was dependent on iron availability from host fluids, as was revealed by a reduction in the 50% lethal dose for iron-overloaded eels. This biotype produced both phenolate- and hydroxamate-type siderophores of an unknown nature and two new outer membrane proteins of around 84 and 72 kDa in response to iron starvation. No alterations in lipopolysaccharide patterns were detected in response to iron stress. Finally, our data suggest that V. vulnificus biotype 2 uses the hydroxamate-type siderophore for removal of iron from transferrin rather than relying on a receptor for this iron-binding protein. PMID:8975620

Randomized clinical trial on acute effects of i.v. iron sucrose during haemodialysis.

PubMed

Garcia-Fernandez, Nuria; Echeverria, Aitziber; Sanchez-Ibarrola, Alfonso; Páramo, José Antonio; Coma-Canella, Isabel

2010-03-01

Haemodialysis induces endothelial dysfunction by oxidation and inflammation. Intravenous iron administration during haemodialysis could worsen endothelial dysfunction. The aim of this study was to ascertain if iron produces endothelial dysfunction and the possible neutralizing effect of N-acetylcysteine when infused before iron. The oxidative and inflammatory effects of iron during haemodialysis were also assessed. Forty patients undergoing haemodialysis were studied in a randomized and cross-over design with and without N-acetylcysteine infused before iron sucrose (50 or 100 mg). Plasma Von Willebrand factor (vWF), soluble intercellular adhesion molecule-1 (sICAM-1) levels, malondialdehyde, total antioxidant capacity, CD11b/CD18 expression in monocytes, interleukin (IL)-8 in monocytes and plasma IL-8 were studied at baseline and during haemodialysis. Haemodialysis produced significant (P < 0.001) increase in plasma vWF, sICAM-1, malondialdehyde, IL-8 and CD11b/CD18 expression in monocytes, as well as decrease in total antioxidant capacity. Iron induced significant increase in plasma malondialdehyde and IL-8 in monocytes, but had no effect on total antioxidant capacity, CD11b/CD18 expression, plasma IL-8, vWF and sICAM-1. The addition of N-acetylcysteine to 50 mg of iron produced a significant (P = 0.040) decrease in malondialdehyde. Standard (100 mg) and low (50 mg) doses of iron during haemodialysis had no effects on endothelium. Iron only had minor effects on inflammation and produced an increase in oxidative stress, which was neutralized by N-acetylcysteine at low iron dose. Haemodialysis caused a significant increase in oxidative stress, inflammation and endothelial dysfunction markers.

Gallium Potentiates the Antibacterial Effect of Gentamicin against Francisella tularensis.

PubMed

Lindgren, Helena; Sjöstedt, Anders

2016-01-01

The reasons why aminoglycosides are bactericidal have not been not fully elucidated, and evidence indicates that the cidal effects are at least partly dependent on iron. We demonstrate that availability of iron markedly affects the susceptibility of the facultative intracellular bacterium Francisella tularensis strain SCHU S4 to the aminoglycoside gentamicin. Specifically, the intracellular depots of iron were inversely correlated to gentamicin susceptibility, whereas the extracellular iron concentrations were directly correlated to the susceptibility. Further proof of the intimate link between iron availability and antibiotic susceptibility were the findings that a ΔfslA mutant, which is defective for siderophore-dependent uptake of ferric iron, showed enhanced gentamicin susceptibility and that a ΔfeoB mutant, which is defective for uptake of ferrous iron, displayed complete growth arrest in the presence of gentamicin. Based on the aforementioned findings, it was hypothesized that gallium could potentiate the effect of gentamicin, since gallium is sequestered by iron uptake systems. The ferrozine assay demonstrated that the presence of gallium inhibited >70% of the iron uptake. Addition of gentamicin and/or gallium to infected bone marrow-derived macrophages showed that both 100 μM gallium and 10 μg/ml of gentamicin inhibited intracellular growth of SCHU S4 and that the combined treatment acted synergistically. Moreover, treatment of F. tularensis-infected mice with gentamicin and gallium showed an additive effect. Collectively, the data demonstrate that SCHU S4 is dependent on iron to minimize the effects of gentamicin and that gallium, by inhibiting the iron uptake, potentiates the bactericidal effect of gentamicin in vitro and in vivo. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

Excessive sulfur supply reduces cadmium accumulation in brown rice (Oryza sativa L.).

PubMed

Fan, Jian-Ling; Hu, Zheng-Yi; Ziadi, Noura; Xia, Xu; Wu, Cong-Yang-Hui

2010-02-01

Human activities have resulted in cadmium (Cd) and sulfur (S) accumulation in paddy soils in parts of southern China. A combined soil-sand pot experiment was conducted to investigate the influence of excessive S supply on iron plaque formation and Cd accumulation in rice plants, using two Cd levels (0, 1.5 mg kg(-1)) combined with three S concentrations (0, 60, 120 mg kg(-1)). The results showed that excessive S supply significantly decreased Cd accumulation in brown rice due to the decrease of Cd availability and the increase of glutathione in rice leaves. But excessive S supply obviously increased Cd accumulation in roots due to the decrease of iron plaque formation on the root surface of rice. Therefore, excessive S supply may result in loss of rice yield, but it could effectively reduce Cd accumulation in brown rice exposed to Cd contaminated soils. Copyright (c) 2009 Elsevier Ltd. All rights reserved.

Making bread with sourdough improves mineral bioavailability from reconstituted whole wheat flour in rats.

PubMed

Lopez, Hubert W; Duclos, Virgile; Coudray, Charles; Krespine, Virginie; Feillet-Coudray, Christine; Messager, Arnaud; Demigné, Christian; Rémésy, Christian

2003-06-01

We compared the effects of different kinds of bread fermentation on mineral bioavailability. Wistar rats were fed one of the following experimental diets for 21 d: control, reconstituted whole wheat flour (white flour plus bran), yeast bread, and sourdough bread. The apparent mineral absorption and intestinal fermentation were measured in each animal. Phytate contents in yeast and sourdough bread were lower than in reconstituted whole wheat flour (-52% and -71%, respectively). Total cecal pool of short-chain fatty acids, in particular the butyrate pool, was significantly increased by the ingestion of unrefined products. Calcium homeostasis was not modified by these nutritional conditions, whereas magnesium absorption was significantly greater in rats fed the control and sourdough diets than in those consuming whole wheat flour and yeast bread. Magnesium kidney excretion was slightly stimulated by sourdough bread. Compared with the control diet, iron balance was significantly reduced by reconstituted whole wheat flour diet. Yeast bread making counteracted the deleterious effects of whole wheat on iron absorption, whereas sourdough bread making enhanced iron absorption. Further, liver and plasma iron and transferrin saturation levels were lower in rats adapted to the flour diet than in other groups. Zinc absorption was strongly depressed in the presence of unprocessed reconstituted whole wheat flour in the diet, but yeast fermentation afforded a zinc assimilation comparable to the control diet, whereas the sourdough bread led to maximal zinc absorption. Copper absorption increased significantly when rats were fed the sourdough bread, whereas unprocessed whole flour depressed copper absorption (-41% versus control diet). Mineral bioavailability from reconstituted whole wheat flour can be improved by bread making. Although yeast fermentation minimizes the unfavorable effects of phytic acid, sourdough bread is a better source of available minerals, especially magnesium, iron, and zinc.

A role for sex and a common HFE gene variant in brain iron uptake.

PubMed

Duck, Kari A; Neely, Elizabeth B; Simpson, Ian A; Connor, James R

2018-03-01

HFE (high iron) is an essential protein for regulating iron transport into cells. Mutations of the HFE gene result in loss of this regulation causing accumulation of iron within the cell. The mutated protein has been found increasingly in numerous neurodegenerative disorders in which increased levels of iron in the brain are reported. Additionally, evidence that these mutations are associated with elevated brain iron challenges the paradigm that the brain is protected by the blood-brain barrier. While much has been studied regarding the role of HFE in cellular iron uptake, it has remained unclear what role the protein plays in the transport of iron into the brain. We investigated regulation of iron transport into the brain using a mouse model with a mutation in the HFE gene. We demonstrated that the rate of radiolabeled iron ( 59 Fe) uptake was similar between the two genotypes despite higher brain iron concentrations in the mutant. However, there were significant differences in iron uptake between males and females regardless of genotype. These data indicate that brain iron status is consistently maintained and tightly regulated at the level of the blood-brain barrier.

Hydroxyurea could be a good clinically relevant iron chelator.

PubMed

Italia, Khushnooma; Colah, Roshan; Ghosh, Kanjaksha

2013-01-01

Our previous study showed a reduction in serum ferritin of β-thalassemia patients on hydroxyurea therapy. Here we aimed to evaluate the efficacy of hydroxyurea alone and in combination with most widely used iron chelators like deferiprone and deferasirox for reducing iron from experimentally iron overloaded mice. 70 BALB/c mice received intraperitonial injections of iron-sucrose. The mice were then divided into 8 groups and were orally given hydroxyurea, deferiprone or deferasirox alone and their combinations for 4 months. CBC, serum-ferritin, TBARS, sTfr and hepcidin were evaluated before and after iron overload and subsequently after 4 months of drug therapy. All animals were then killed. Iron staining of the heart and liver tissue was done using Perl's Prussian Blue stain. Dry weight of iron in the heart and liver was determined by atomic absorption spectrometry. Increased serum-ferritin, TBARS, hepcidin and dry weight of iron in the liver and heart showed a significant reduction in groups treated with iron chelators with maximum reduction in the group treated with a combination of deferiprone, deferasirox and hydroxyurea. Thus hydroxyurea proves its role in reducing iron from iron overloaded mice. The iron chelating effect of these drugs can also be increased if given in combination.

Remedying acidification and deterioration of aerobic post-treatment of digested effluent by using zero-valent iron.

PubMed

Wang, Shen; Zheng, Dan; Wang, Shuang; Wang, Lan; Lei, Yunhui; Xu, Ze; Deng, Liangwei

2018-01-01

This study presents a novel strategy for remedying acidification and improving the removal efficiency of pollutants from digested effluent by using Zero-Valent Iron (iron scraps) in a sequencing batch reactor. Through this strategy, the pH increased from 5.7 (mixed liquid in the reactor without added ZVI) to 7.8 (reactors with added ZVI) because of Fe 0 oxidation and NO 3 - reduction. The removal efficiencies of COD increased from 11.5% to 77.5% because of oxidation of ferric ion and OH produced in chemical reactions of ZVI with oxygen and because of flocculation of iron ions. The removal efficiencies of total nitrogen rose from 1.83% to 93.3% probably because of autotrophic denitrification using electron donors produced by the corrosion of iron, as well as the favorable conditions for anammox due to iron ions. Total phosphorus increased from -25.8% to 77.1% because of the increase in pH and the precipitation with iron ions. Copyright © 2017 Elsevier Ltd. All rights reserved.

Reductive dechlorination of trichloroethylene by iron bimetallics

DOE Office of Scientific and Technical Information (OSTI.GOV)

Orth, R.G.; Dauda, T.; McKenzie, D.E.

1998-07-01

Reductive dechlorination using a zero valence metal such as iron has seen an increase in interest with the extension of iron dechlorination to in-situ treatment of ground water. Studies to increase the rate of dechlorination and the long term stability have lead many to examine the use of bimetallic iron systems. Results are shown for bimetallic iron systems of Cu, Sn, Ni, Ag, Au, and Pd. All of these bimetallic couples form a galvanic couple which increase corrosion rates and the production of hydrogen. Increased rates of reaction normalized to surface area were observed for all the couples. The reactionmore » rates were found to depended on surface area and surface coverage of the iron. The results of studies in deuterium oxide indicate that the pathways changed as the bimetallic is changed and that the pathway in all cases could be a combination of dehydrohalgenation and sequential dechlorination. Degradation of DNAPL TCE by iron was found to be zero order and the type of product observed was different from that observed for TCE dissolved in water.« less

Trends in the treatment of chronic kidney disease-associated anaemia in a cohort of haemodialysis patients: the Irish experience.

PubMed

Gardiner, Roisin; Roshan, Davood; Brennan, Ann; Connolly, Denise; Murray, Susan; Reddan, Donal

2018-04-27

Anaemia among haemodialysis patients is treated with iron and erythropoietin-stimulating agents (ESAs). ESAs reduce requirements for blood transfusions but are also expensive and overzealous use may be associated with adverse outcomes. Recent international trends have been characterised by reduced ESA doses and a greater reliance on intravenous (IV) iron. We determined trends in prescribing patterns of ESAs and IV iron for the treatment of anaemia in two representative Irish dialysis centres and correlated with current guidelines and international trends. Patient data was accessed from the Kidney Disease Clinical Patient Management System (KDCPMS) for the period 2012 to 2014. We generated reports on ESA and iron doses, lab data (haemoglobin (Hb), transferrin saturation (TSAT) and ferritin) and patient population characteristics. We mapped the trends in ESA, iron dosing and lab parameters achieved. A linear mixed model determined the significance of these trends over time. ESA dosing became lower in the second, third and fourth quarters of 2014. Dosing of iron increased throughout but a large increase was seen in the third and fourth quarters of 2014. Ferritin levels decreased and TSAT and haemoglobin levels increased. Changes in iron dosing were significant with p value of < 0.05. Our findings are consistent with recent global trends toward increasing iron use. Such trends may have economic implications given the high cost of ESAs and the relative affordability of iron. In addition, the potential harm of excessive iron dosing may need to be considered.

Impact of iron and vitamin C-containing supplements on preterm human milk: in vitro.

PubMed

Friel, James K; Diehl-Jones, William L; Suh, Miyoung; Tsopmo, Apollinaire; Shirwadkar, Vaibhav P

2007-05-15

Stress due to reactive oxygen species (ROS) may lead to neonatal diseases, such as necrotizing enterocolitis and respiratory distress. Enteral supplements for premature infants (PREM) added to human milk (HM) to increase nutrient content may induce lipid oxidation due to free radical formation via Fenton chemistry. We hypothesized that ferrous iron and vitamin C-containing supplements added to HM in vitro cause oxidation of milk fats, affect intracellular redox balance, and induce DNA damage. Lipid peroxidation in HM was measured by FOX-2 and TBARS assays; fatty acid composition of supplemented HM was measured by gas chromatography. Two cell culture bioassays were used for assessing either intracellular oxidative stress or DNA damage: the former involved Caco-2BBe cells, a secondary differentiated cell line, and the latter utilized FHS-74 Int cells, a primary fetal small intestinal culture. Lipid oxidation products of HM increased after the addition of iron alone, iron and vitamin C, or iron and a vitamin C-containing supplement (Trivisol, TVS). A reduced content of mono and polyunsaturated fatty acids in HM was also observed. Iron, not iron+vitamin C, but iron+TVS induced significant intracellular oxidative stress in FHS-74 Int cells. In contrast, iron, either alone or in combination with TVS or vitamin C, increased DNA damage in Caco-2BBE cells. Iron supplementation may increase oxidative stress in PREM infants and should be given separately from vitamin C-containing supplements.

Iron status and its relations with oxidative damage and bone loss during long-duration space flight on the International Space Station.

PubMed

Zwart, Sara R; Morgan, Jennifer L L; Smith, Scott M

2013-07-01

Increases in stored iron and dietary intake of iron during space flight have raised concern about the risk of excess iron and oxidative damage, particularly in bone. The objectives of this study were to perform a comprehensive assessment of iron status in men and women before, during, and after long-duration space flight and to quantify the association of iron status with oxidative damage and bone loss. Fasting blood and 24-h urine samples were collected from 23 crew members before, during, and after missions lasting 50 to 247 d to the International Space Station. Serum ferritin and body iron increased early in flight, and transferrin and transferrin receptors decreased later, which indicated that early increases in body iron stores occurred through the mobilization of iron to storage tissues. Acute phase proteins indicated no evidence of an inflammatory response during flight. Serum ferritin was positively correlated with the oxidative damage markers 8-hydroxy-2'-deoxyguanosine (r = 0.53, P < 0.001) and prostaglandin F2α (r = 0.26, P < 0.001), and the greater the area under the curve for ferritin during flight, the greater the decrease in bone mineral density in the total hip (P = 0.031), trochanter (P = 0.006), hip neck (P = 0.044), and pelvis (P = 0.049) after flight. Increased iron stores may be a risk factor for oxidative damage and bone resorption.

Mössbauer study of the effect of pH on Fe valence in iron-polygalacturonate as a medicine for human anaemia

NASA Astrophysics Data System (ADS)

Kuzmann, E.; Garg, V. K.; de Oliveira, A. C.; Klencsár, Z.; Szentmihályi, K.; Fodor, J.; May, Z.; Homonnay, Z.

2015-02-01

Iron-polygalacturonate complexes have been synthesized from polygalacturonic acid by applying a novel preparation method in order to develop medicine suitable for the effective iron supplementation of the human body in the case of anemia. Since the iron uptake depends on the oxidation state of iron, 57Fe Mössbauer spectroscopy was used to study the occurrence of different valence states in the iron-polygalacturonate complexes prepared under different circumstances. The Mössbauer-spectra indicated the presence of iron both in FeII and FeIII states in the investigated iron-polygalacturonate compounds, the occurrence of which varied with the preparation parameters. A correlation of the relative occurrence of iron valence states with the pH has been found. The relative occurrence of FeIII was found to increase with increasing pH. The knowledge of this correlation can help find optimum preparation conditions of iron-polygalacturonates to cure human anemia.

An overview of methods for assessment of iron bioavailability from foods nutritionally enhanced through biotechnology.

PubMed

Cockell, Kevin A

2007-01-01

Iron deficiency and iron deficiency anemia continue to be significant public health problems worldwide. While supplementation and fortification have been viable means to improve iron nutriture of the population in developed countries, they may be less successful in developing regions for a number of reasons, including complexities in distribution and consumer compliance. Biofortification of staple crops, through conventional plant breeding strategies or modern methods of biotechnology, provides an alternative approach that may be more sustainable once initial investments have been made. Three types of biofortification strategies are being essayed, singly or in combination: increasing the total iron content of edible portions of the plant, decreasing the levels of inhibitors of iron absorption, and increasing the levels of factors that enhance iron absorption. Bioavailability is a key concept in iron nutrition, particularly for nonheme iron such as is found in these biofortified foods. An overview is presented of methods for evaluation of iron bioavailability from foods nutritionally enhanced through biotechnology.

Oxygenic photosynthesis as a protection mechanism for cyanobacteria against iron-encrustation in environments with high Fe2+ concentrations

PubMed Central

Ionescu, Danny; Buchmann, Bettina; Heim, Christine; Häusler, Stefan; de Beer, Dirk; Polerecky, Lubos

2014-01-01

If O2 is available at circumneutral pH, Fe2+ is rapidly oxidized to Fe3+, which precipitates as FeO(OH). Neutrophilic iron oxidizing bacteria have evolved mechanisms to prevent self-encrustation in iron. Hitherto, no mechanism has been proposed for cyanobacteria from Fe2+-rich environments; these produce O2 but are seldom found encrusted in iron. We used two sets of illuminated reactors connected to two groundwater aquifers with different Fe2+ concentrations (0.9 μM vs. 26 μM) in the Äspö Hard Rock Laboratory (HRL), Sweden. Cyanobacterial biofilms developed in all reactors and were phylogenetically different between the reactors. Unexpectedly, cyanobacteria growing in the Fe2+-poor reactors were encrusted in iron, whereas those in the Fe2+-rich reactors were not. In-situ microsensor measurements showed that O2 concentrations and pH near the surface of the cyanobacterial biofilms from the Fe2+-rich reactors were much higher than in the overlying water. This was not the case for the biofilms growing at low Fe2+ concentrations. Measurements with enrichment cultures showed that cyanobacteria from the Fe2+-rich environment increased their photosynthesis with increasing Fe2+ concentrations, whereas those from the low Fe2+ environment were inhibited at Fe2+ > 5 μM. Modeling based on in-situ O2 and pH profiles showed that cyanobacteria from the Fe2+-rich reactor were not exposed to significant Fe2+ concentrations. We propose that, due to limited mass transfer, high photosynthetic activity in Fe2+-rich environments forms a protective zone where Fe2+ precipitates abiotically at a non-lethal distance from the cyanobacteria. This mechanism sheds new light on the possible role of cyanobacteria in precipitation of banded iron formations. PMID:25228899

Role of Siderophores in Dissimilatory Iron Reduction in Arctic Soils : Effect of Direct Amendment of Siderophores to Arctic Soil

NASA Astrophysics Data System (ADS)

Srinivas, A. J.; Dinsdale, E. A.; Lipson, D.

2014-12-01

Dissimilatory iron reduction (DIR), where ferric iron (Fe3+) is reduced to ferrous iron (Fe2+) anaerobically, is an important respiratory pathway used by soil bacteria. DIR contributes to carbon dioxide (CO2) efflux from the wet sedge tundra biome in the Arctic Coastal Plain (ACP) in Alaska, and could competitively inhibit the production of methane, a stronger greenhouse gas than CO2, from arctic soils. The occurrence of DIR as a dominant anaerobic process depends on the availability of substantial levels of Fe3+ in soils. Siderophores are metabolites made by microbes to dissolve Fe3+ from soil minerals in iron deficient systems, making Fe3+ soluble for micronutrient uptake. However, as the ACP is not iron deficient, siderophores in arctic soils may play a vital role in anaerobic respiration by dissolving Fe3+ for DIR. We studied the effects of direct siderophore addition to arctic soils through a field study conducted in Barrow, Alaska, and a laboratory incubation study conducted at San Diego State University. In the field experiment, 50μM deferroxamine mesylate (a siderophore), 50μM trisodium nitrilotriacetate (an organic chelator) or an equal volume of water was added to isolated experimental plots, replicated in clusters across the landscape. Fe2+ concentrations were measured in soil pore water samples collected periodically to measure DIR over time in each. In the laboratory experiment, frozen soil samples obtained from drained thaw lake basins in the ACP, were cut into cores and treated with the above-mentioned compounds to the same final concentrations. Along with measuring Fe2+ concentrations, CO2 output was also measured to monitor DIR over time in each core. Experimental addition of siderophores to soils in both the field and laboratory resulted in increased concentrations of soluble Fe3+ and a sustained increase in Fe2+concentrations over time, along with increased respiration rates in siderophore-amended cores. These results show increased DIR in siderophore treated cores compared to the other treatments. From the results of these experiments, we conclude that arctic soil microbes can use siderophores to maintain a pool of dissolved Fe3+ for DIR. This study provides insight into the mechanisms of DIR in this ecosystem, and has relevance for understanding anaerobic soil respiration in the Arctic.

Diversity and Evolutionary History of Iron Metabolism Genes in Diatoms

PubMed Central

Groussman, Ryan D.; Parker, Micaela S.; Armbrust, E. Virginia

2015-01-01

Ferroproteins arose early in Earth’s history, prior to the emergence of oxygenic photosynthesis and the subsequent reduction of bioavailable iron. Today, iron availability limits primary productivity in about 30% of the world’s oceans. Diatoms, responsible for nearly half of oceanic primary production, have evolved molecular strategies for coping with variable iron concentrations. Our understanding of the evolutionary breadth of these strategies has been restricted by the limited number of species for which molecular sequence data is available. To uncover the diversity of strategies marine diatoms employ to meet cellular iron demands, we analyzed 367 newly released marine microbial eukaryotic transcriptomes, which include 47 diatom species. We focused on genes encoding proteins previously identified as having a role in iron management: iron uptake (high-affinity ferric reductase, multi-copper oxidase, and Fe(III) permease); iron storage (ferritin); iron-induced protein substitutions (flavodoxin/ferredoxin, and plastocyanin/cytochrome c6) and defense against reactive oxygen species (superoxide dismutases). Homologs encoding the high-affinity iron uptake system components were detected across the four diatom Classes suggesting an ancient origin for this pathway. Ferritin transcripts were also detected in all Classes, revealing a more widespread utilization of ferritin throughout diatoms than previously recognized. Flavodoxin and plastocyanin transcripts indicate possible alternative redox metal strategies. Predicted localization signals for ferredoxin identify multiple examples of gene transfer from the plastid to the nuclear genome. Transcripts encoding four superoxide dismutase metalloforms were detected, including a putative nickel-coordinating isozyme. Taken together, our results suggest that the majority of iron metabolism genes in diatoms appear to be vertically inherited with functional diversity achieved via possible neofunctionalization of paralogs. This refined view of iron use strategies in diatoms elucidates the history of these adaptations, and provides potential molecular markers for determining the iron nutritional status of different diatom species in environmental samples. PMID:26052941

Recovering from iron deficiency chlorosis in near-isogenic soybeans: a microarray study.

PubMed

O'Rourke, Jamie A; Graham, Michelle A; Vodkin, Lila; Gonzalez, Delkin Orlando; Cianzio, Silvia R; Shoemaker, Randy C

2007-05-01

Iron deficiency chlorosis (IDC) in soybeans has proven to be a perennial problem in the calcareous soils of the U.S. upper Midwest. A historically difficult trait to study in fields, the use of hydroponics in a controlled greenhouse environment has provided a mechanism to study genetic variation while limiting environmental complications. IDC susceptible plants growing in calcareous soils and in iron-controlled hydroponic experiments often exhibit a characteristic chlorotic phenotype early in the growing season but are able to re-green later in the season. To examine the changes in gene expression of these plants, near-isogenic lines, iron efficient PI548553 (Clark) and iron inefficient PI547430 (IsoClark), developed for their response to iron deficiency stress [USDA, ARS, National Genetic Resources Program, Germplasm Resources Information Network - GRIN. (Online Database) National Germplasm Resources Laboratory, Beltsville, MD, 2004. Available: http://www.ars.grin.gov/cgi-bin/npgs/html/acc_search.pl?accid=PI+547430. [22] were grown in iron-deficient hydroponic conditions for one week, then transferred to iron sufficient conditions for another week. This induced a phenotypic response mimicking the growth of the plants in the field; initial chlorosis followed by re-greening. RNA was isolated from root tissue and transcript profiles were examined between the two near-isogenic lines using publicly available cDNA microarrays. By alleviating the iron deficiency stress our expectation was that plants would return to baseline expression levels. However, the microarray comparison identified four cDNAs that were under-expressed by a two-fold or greater difference in the iron inefficient plant compared to the iron efficient plant. This differential expression was re-examined and confirmed by real time PCR experimentation. Control experiments showed that these genes are not differentially expressed in plants grown continually under iron rich hydroponic conditions. The expression differences suggest potential residual effects of iron deficiency on plant health.

Electronic structure and reactivity of three-coordinate iron complexes.

PubMed

Holland, Patrick L

2008-08-01

[Reaction: see text]. The identity and oxidation state of the metal in a coordination compound are typically thought to be the most important determinants of its reactivity. However, the coordination number (the number of bonds to the metal) can be equally influential. This Account describes iron complexes with a coordination number of only three, which differ greatly from iron complexes with octahedral (six-coordinate) geometries with respect to their magnetism, electronic structure, preference for ligands, and reactivity. Three-coordinate complexes with a trigonal-planar geometry are accessible using bulky, anionic, bidentate ligands (beta-diketiminates) that steer a monodentate ligand into the plane of their two nitrogen donors. This strategy has led to a variety of three-coordinate iron complexes in which iron is in the +1, +2, and +3 oxidation states. Systematic studies on the electronic structures of these complexes have been useful in interpreting their properties. The iron ions are generally high spin, with singly occupied orbitals available for pi interactions with ligands. Trends in sigma-bonding show that iron(II) complexes favor electronegative ligands (O, N donors) over electropositive ligands (hydride). The combination of electrostatic sigma-bonding and the availability of pi-interactions stabilizes iron(II) fluoride and oxo complexes. The same factors destabilize iron(II) hydride complexes, which are reactive enough to add the hydrogen atom to unsaturated organic molecules and to take part in radical reactions. Iron(I) complexes use strong pi-backbonding to transfer charge from iron into coordinated alkynes and N 2, whereas iron(III) accepts charge from a pi-donating imido ligand. Though the imidoiron(III) complex is stabilized by pi-bonding in the trigonal-planar geometry, addition of pyridine as a fourth donor weakens the pi-bonding, which enables abstraction of H atoms from hydrocarbons. The unusual bonding and reactivity patterns of three-coordinate iron compounds may lead to new catalysts for oxidation and reduction reactions and may be used by nature in transient intermediates of nitrogenase enzymes.

A mutation in the HFE gene is associated with altered brain iron profiles and increased oxidative stress in mice.

PubMed

Nandar, Wint; Neely, Elizabeth B; Unger, Erica; Connor, James R

2013-06-01

Because of the increasing evidence that H63D HFE polymorphism appears in higher frequency in neurodegenerative diseases, we evaluated the neurological consequences of H63D HFE in vivo using mice that carry H67D HFE (homologous to human H63D). Although total brain iron concentration did not change significantly in the H67D mice, brain iron management proteins expressions were altered significantly. The 6-month-old H67D mice had increased HFE and H-ferritin expression. At 12 months, H67D mice had increased H- and L-ferritin but decreased transferrin expression suggesting increased iron storage and decreased iron mobilization. Increased L-ferritin positive microglia in H67D mice suggests that microglia increase iron storage to maintain brain iron homeostasis. The 6-month-old H67D mice had increased levels of GFAP, increased oxidatively modified protein levels, and increased cystine/glutamate antiporter (xCT) and hemeoxygenase-1 (HO-1) expression indicating increased metabolic and oxidative stress. By 12 months, there was no longer increased astrogliosis or oxidative stress. The decrease in oxidative stress at 12 months could be related to an adaptive response by nuclear factor E2-related factor 2 (Nrf2) that regulates antioxidant enzymes expression and is increased in the H67D mice. These findings demonstrate that the H63D HFE impacts brain iron homeostasis, and promotes an environment of oxidative stress and induction of adaptive mechanisms. These data, along with literature reports on humans with HFE mutations provide the evidence to overturn the traditional paradigm that the brain is protected from HFE mutations. The H67D knock-in mouse can be used as a model to evaluate how the H63D HFE mutation contributes to neurodegenerative diseases. Copyright © 2013 Elsevier B.V. All rights reserved.

Assessing the Roles of Iron, Macronutrients and Wet deposition in Controlling Phytoplankton Growth in Seasonally Oligotrophic Waters of the Mid-Atlantic Bight

NASA Astrophysics Data System (ADS)

Sedwick, P.; Mulholland, M. R.; Najjar, R.; Bernhardt, P. W.; Price, L. M.; Sohst, B. M.; Sookhdeo, C.; Widner, B.

2016-02-01

The role of iron supply in regulating phytoplankton production in high-nutrient, low-chlorophyll ocean regions has been well established. Less clear, however, is the importance of iron for phytoplankton processes in other oceanic settings, such as coastal and oligotrophic waters, where differential changes in the supply and removal of dissolved iron (dFe) can result in limitation or co-limitation of growth due to iron deficiency. One such region of interest is the Mid-Atlantic Bight (MAB), where previous field experiments have provided some evidence of co-limitation of algal growth by nitrogen and iron. In summer 2014 we conducted field sampling and shipboard experiments to assess the role of iron and macronutrient availability in controlling primary production in seasonally oligotrophic waters over the MAB continental slope, with a focus on the the impacts of wet deposition. Our results indicate that nitrogen was the proximate limiting nutrient, with a secondary limitation imposed by availability of phosphorus; we found no evidence for a deficiency in dFe, which was present at concentrations in the range 0.3-0.9 nM. Phytoplankton growth was clearly stimulated by the addition of natural rainwater, suggesting that summer rain events stimulate primary production in the MAB by contributing new nitrogen (primarily as ammonium) and phosphorus, whilst maintaining iron-replete conditions.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Marchenko, A. V.; Terukov, E. I.; Egorova, A. Yu.

Impurity iron atoms in vitreous arsenic-selenide As{sub 2}Se{sub 3} films modified by iron form one-electron donor centers with an ionization energy of 0.24 (3) eV (the energy is counted from the conduction-band bottom). The Fermi level is shifted with an increase in the iron concentration from the mid-gap to the donorlevel position of iron due to the filling of one-electron states of the acceptor type lying below the Fermi level. At an iron concentration of ≥3 at %, the electron-exchange process is observed between neutral and ionized iron centers resulting in a change both in the electron density and inmore » the tensor of the electric-field gradient at iron-atom nuclei with increasing temperature above 350 K.« less

Hereditary hemochromatosis, iron, hepcidin, and coronary heart disease.

PubMed

Mascitelli, Luca; Goldstein, Mark R

2014-03-01

Mounting evidence suggests that a state of sustained iron depletion may exert a primary protective action against coronary heart disease. A persistent criticism of the iron hypothesis has been that atherosclerosis may not be a prominent feature of hereditary hemochromatosis. The essence of this criticism is that iron cannot be a significant factor in atherogenesis in those unaffected by inherited iron overload unless an increase in atherosclerosis is observed in hereditary hemochromatosis. However, the emerging details of the physiology of hepcidin, the key hormone in iron recycling, suggest a resolution of the apparent paradox of an important role for iron in atherogenesis in the possible absence of increased plaque burden in most types of hereditary hemochromatosis. Copyright © 2013 Elsevier Ltd. All rights reserved.

Biocorrosion properties and blood and cell compatibility of pure iron as a biodegradable biomaterial.

PubMed

Zhang, Erlin; Chen, Haiyan; Shen, Feng

2010-07-01

Biocorrosion properties and blood- and cell compatibility of pure iron were studied in comparison with 316L stainless steel and Mg-Mn-Zn magnesium alloy to reveal the possibility of pure iron as a biodegradable biomaterial. Both electrochemical and weight loss tests showed that pure iron showed a relatively high corrosion rate at the first several days and then decreased to a low level during the following immersion due to the formation of phosphates on the surface. However, the corrosion of pure iron did not cause significant increase in pH value to the solution. In comparison with 316L and Mg-Mn-Zn alloy, the pure iron exhibited biodegradable property in a moderate corrosion rate. Pure iron possessed similar dynamic blood clotting time, prothrombin time and plasma recalcification time to 316L and Mg-Mn-Zn alloy, but a lower hemolysis ratio and a significant lower number density of adhered platelets. MTT results revealed that the extract except the one with 25% 24 h extract actually displayed toxicity to cells and the toxicity increased with the increasing of the iron ion concentration and the incubation time. It was thought there should be an iron ion concentration threshold in the effect of iron ion on the cell toxicity.

Antioxidant capacity of parsley cells (Petroselinum crispum L.) in relation to iron-induced ferritin levels and static magnetic field.

PubMed

Rajabbeigi, Elham; Ghanati, Faezeh; Abdolmaleki, Parviz; Payez, Atefeh

2013-12-01

This study was aimed to evaluate antioxidant response of parsley cells to 21 ppm iron and static magnetic field (SMF; 30 mT). The activity of catalase (CAT) and ascorbate peroxidase (APX) and the contents of malonyldialdehyde, iron and ferritin were measured at 6 and 12 h after treatments. Exposure to SMF increased the activity of CAT in treated cells, while combination of iron and SMF treatments as well as iron supply alone decreased CAT activity, compared to that of control cells. Combination of SMF with iron treatment reduced iron content of the cells and ameliorated mal effect of iron on CAT activity. All treatments reduced APX activity; however, the content of total ascorbate increased in response to iron and SMF+iron. The results showed that among the components of antioxidant system of parsley cells, enhanced activity of CAT in SMF-treated cells and increase of ascorbate in SMF+Fe-treated ones were responsible for the maintenance of membranes integrity. Ferritin contents of SMF- and SMF+Fe-treated cells also decreased significantly 12 h after treatments, compared to those of the control cells. These results cast doubt on the proposed functions of ferritin as a putative reactive oxygen species detoxifying molecule.

Bioavailability of iron from a traditional Tunisian meal with chickpeas fed to healthy rats.

PubMed

Hamdaoui, M; Doghri, T; Tritar, B

1992-01-01

The influence of a diet of couscous with chickpeas, a traditional Tunisian meal, or one providing iron as ferrous sulfate, on the utilization of 59Fe was evaluated in studies with rats. The iron content of the couscous and chickpea preparation was 30 mg/kg dry weight. There was no difference in the relative absorption of iron from ferrous sulfate or couscous with chickpeas, suggesting that iron from this preparation may be a good dietary source of nonheme iron for rats. Couscous and chickpeas consumption in Tunisia are estimated at 13.3 and 3.2 kg per capita/year, respectively. Our results in rats indicate that these foods could contribute a large proportion of an individual's iron requirement. We conclude that the plant foods, especially the chickpeas, can be excellent sources of dietary-available iron.

A comparison of iron extraction methods for the determination of degree of pyritisation and the recognition of iron-limited pyrite formation

NASA Technical Reports Server (NTRS)

Raiswell, R.; Canfield, D. E.; Berner, R. A.

1994-01-01

Measurements of degree of pyritisation require an estimate of sediment iron which is capable of reaction with dissolved sulphide to form pyrite, either directly or indirectly via iron monosulphide precursors. Three dissolution techniques (buffered dithionite, cold 1 M HCl, boiling 12 M HCl) were examined for their capacity to extract iron from a variety of iron minerals, and iron-bearing sediments, as a function of different extraction times and different grain sizes. All the iron oxides studied are quantitatively extracted by dithionite and boiling HCl (but not by cold HCl). Both HCl techniques extract more iron from silicates than does dithionite but probably about the same amounts as are potentially capable of sulphidation. Modern sediment studies indicate that most sedimentary pyrite is formed rapidly from iron oxides, with smaller amounts formed more slowly from iron silicates (if sufficient geologic time is available). It is therefore recommended that the degree of pyritisation be defined with respect to the dithionite-extractable (mainly iron oxide) pool and/or the boiling HCl-extractable pool (which includes some silicate iron) for the recognition of iron-limited pyritisation.

Iron is associated with the development of hypoxia-induced pulmonary vascular remodeling in mice.

PubMed

Naito, Yoshiro; Hosokawa, Manami; Sawada, Hisashi; Oboshi, Makiko; Iwasaku, Toshihiro; Okuhara, Yoshitaka; Eguchi, Akiyo; Nishimura, Koichi; Soyama, Yuko; Hirotani, Shinichi; Mano, Toshiaki; Ishihara, Masaharu; Masuyama, Tohru

2016-12-01

Several recent observations provide the association of iron deficiency with pulmonary hypertension (PH) in human and animal studies. However, it remains completely unknown whether PH leads to iron deficiency or iron deficiency enhances the development of PH. In addition, it is obscure whether iron is associated with the development of pulmonary vascular remodeling in PH. In this study, we investigate the impacts of dietary iron restriction on the development of hypoxia-induced pulmonary vascular remodeling in mice. Eight- to ten-week-old male C57BL/6J mice were exposed to chronic hypoxia for 4 weeks. Mice exposed to hypoxia were randomly divided into two groups and were given a normal diet or an iron-restricted diet. Mice maintained in room air served as normoxic controls. Chronic hypoxia induced pulmonary vascular remodeling, while iron restriction led a modest attenuation of this change. In addition, chronic hypoxia exhibited increased RV systolic pressure, which was attenuated by iron restriction. Moreover, the increase in RV cardiomyocyte cross-sectional area and RV interstitial fibrosis was observed in mice exposed to chronic hypoxia. In contrast, iron restriction suppressed these changes. Consistent with these changes, RV weight to left ventricular + interventricular septum weight ratio was increased in mice exposed to chronic hypoxia, while this increment was inhibited by iron restriction. Taken together, these results suggest that iron is associated with the development of hypoxia-induced pulmonary vascular remodeling in mice.

Iron Indices in Bottlenose Dolphins (Tursiops truncatus)

PubMed Central

Mazzaro, Lisa M; Johnson, Shawn P; Fair, Patricia A; Bossart, Greg; Carlin, Kevin P; Jensen, Eric D; Smith, Cynthia R; Andrews, Gordon A; Chavey, Patricia S; Venn-Watson, Stephanie

2012-01-01

Bottlenose dolphins can have iron overload (that is, hemochromatosis), and managed populations of dolphins may be more susceptible to this disease than are wild dolphins. Serum iron, total iron-binding capacity (TIBC), transferrin saturation, and ferritin were measured in 181 samples from 141 dolphins in 2 managed collections and 2 free-ranging populations. Although no iron indices increased with age among free-ranging dolphins, ferritin increased with age in managed collections. Dolphins from managed collections had higher iron, ferritin, and transferrin saturation values than did free-ranging dolphins. Dolphins with high serum iron (exceeding 300 μg/dL) were more likely to have elevated ferritin but not ceruloplasmin or haptoglobin, demonstrating that high serum levels of iron are due to a true increase in total body iron. A time-series study of 4 dolphins with hemochromatosis that were treated with phlebotomy demonstrated significant decreases in serum ferritin, iron, and TIBC between pre- and posttreatment samples; transferrin saturation initially fell but returned to prephlebotomy levels by 6 mo after treatment. Compared with those in managed collections, wild dolphins were 15 times more likely to have low serum iron (100 μg/dL or less), and this measure was associated with lower haptoglobin. In conclusion, bottlenose dolphins in managed collections are more likely to have greater iron stores than are free-ranging dolphins. Determining why this situation occurs among some dolphin populations and not others may improve the treatment of hemochromatosis in dolphins and provide clues to causes of nonhereditary hemochromatosis in humans. PMID:23561885

Relationship between Hepatitis C Virus Infection and Iron Overload.

PubMed

Zou, Dong-Mei; Sun, Wan-Ling

2017-04-05

The aim of this study was to summarize the interactions between hepatitis C virus (HCV) infection and iron overload, and to understand the mechanisms of iron overload in chronic hepatitis C (CHC) and the role iron plays in HCV life cycle. This review was based on data in articles published in the PubMed databases up to January 28, 2017, with the keywords "hepatitis C virus", "iron overload", "iron metabolism", "hepcidin", "translation", and "replication". Articles related to iron metabolism, iron overload in patients with CHC, or the effects of iron on HCV life cycle were selected for the review. Iron overload is common in patients with CHC. The mechanisms involve decreased hepcidin levels caused by HCV through signal transducer and activator of transcription 3, mitogen-activated protein kinase, or bone morphogenetic protein/SMAD signaling pathways, and the altered expression of other iron-metabolism-related genes. Some studies found that iron increases HCV replication, while other studies found the opposite result. Most of the studies suggest the positive role of iron on HCV translation, the mechanisms of which involve increased expression levels of factors associated with HCV internal ribosome entry site-dependent translation, such as eukaryotic initiation factor 3 and La protein. The growing literature demonstrates that CHC leads to iron overload, and iron affects the HCV life cycle in turn. Further research should be conducted to clarify the mechanism involved in the complicated interaction between iron and HCV.

Iron deficiency and new insights into therapy.

PubMed

Low, Michael Sy; Grigoriadis, George

2017-07-17

Iron deficiency and iron deficiency anaemia remain prevalent in Australia. The groups at highest risk are pre-menopausal women, socially disadvantaged people and those of Indigenous background. Diagnosing iron deficiency using a full blood examination and iron studies can be difficult and can be further complicated by concomitant inflammation. Results of iron studies should always be interpreted as an overall picture rather than focusing on individual parameters. In difficult clinical scenarios, soluble transferrin receptor assays can be useful. Management of iron deficiency involves identification and treatment of the cause of iron deficiency, as well as effective iron replacement. Clinicians should always take a detailed history and perform a comprehensive physical examination of a patient with iron deficiency. Patients should be monitored even if a likely cause of iron deficiency is identified. Patients who fail to respond to iron replacement or maintain iron status should be referred for further investigation, including endoscopy to exclude internal bleeding. Both enteral and parenteral iron are effective at replacing iron. For most adult patients, we recommend trialling daily oral iron (30-100 mg of elemental iron) as the first-line therapy. Safety and efficacy of intravenous iron infusions have improved with the availability of a newer formulation, ferric carboxymaltose. Patients who fail to respond to oral iron replacement can be safely managed with intravenous iron. Blood transfusion for iron deficiency anaemia should be reserved for life-threatening situations and should always be followed by appropriate iron replacement.

Tissue distribution of manganese in iron-sufficient or iron-deficient rats after stainless steel welding-fume exposure.

PubMed

Park, Jung-Duck; Kim, Ki-Young; Kim, Dong-Won; Choi, Seong-Jin; Choi, Byung-Sun; Chung, Yong Hyun; Han, Jeong Hee; Sung, Jae Hyuck; Kwon, Il Hoon; Mun, Je-Hyeok; Yu, Il Je

2007-05-01

Welders can be exposed to high levels of manganese through welding fumes. Although it has already been suggested that excessive manganese exposure causes neurotoxicity, called manganism, the pathway of manganese transport to the brain with welding-fume exposure remains unclear. Iron is an essential metal that maintains a homeostasis in the body. The divalent metal transporter 1 (DMT1) transports iron and other divalent metals, such as manganese, and the depletion of iron is known to upregulate DMT1 expression. Accordingly, this study investigated the tissue distribution of manganese in iron-sufficient and iron-deficient rats after welding-fume exposure. The feeding of an iron-deficient diet for 4 wk produced a depletion of body iron, such as decreased iron levels in the serum and tissues, and upregulated the DMT1 expression in the rat duodenum. The iron-sufficient and iron-deficient rats were then exposed to welding fumes generated from manual metal arc stainless steel at a concentration of 63.5 +/- 2.3 mg/m3 for 2 h per day over a 30-day period. Animals were sacrificed on days 1, 15, and 30. The level of body iron in the iron-deficient rats was restored to the control level after the welding-fume exposure. However, the tissue distributions of manganese after the welding-fume exposure showed similar patterns in both the iron-sufficient and iron-deficient groups. The concentration of manganese increased in the lungs and liver on days 15 and 30, and increased in the olfactory bulb on day 30. Slight and heterogeneous increases of manganese were observed in different brain regions. Consequently, these findings suggest that the presence of Fe in the inhaled welding fumes may not have a significant effect on the uptake of Mn into the brain. Thus, the condition of iron deficiency did not seem to have any apparent effect on the transport of Mn into the brain after the inhalation of welding fumes.

Iron and ferritin accumulate in separate cellular locations in Phaseolus seeds

PubMed Central

2010-01-01

Background Iron is an important micronutrient for all living organisms. Almost 25% of the world population is affected by iron deficiency, a leading cause of anemia. In plants, iron deficiency leads to chlorosis and reduced yield. Both animals and plants may suffer from iron deficiency when their diet or environment lacks bioavailable iron. A sustainable way to reduce iron malnutrition in humans is to develop staple crops with increased content of bioavailable iron. Knowledge of where and how iron accumulates in seeds of crop plants will increase the understanding of plant iron metabolism and will assist in the production of staples with increased bioavailable iron. Results Here we reveal the distribution of iron in seeds of three Phaseolus species including thirteen genotypes of P. vulgaris, P. coccineus, and P. lunatus. We showed that high concentrations of iron accumulate in cells surrounding the provascular tissue of P. vulgaris and P. coccineus seeds. Using the Perls' Prussian blue method, we were able to detect iron in the cytoplasm of epidermal cells, cells near the epidermis, and cells surrounding the provascular tissue. In contrast, the protein ferritin that has been suggested as the major iron storage protein in legumes was only detected in the amyloplasts of the seed embryo. Using the non-destructive micro-PIXE (Particle Induced X-ray Emission) technique we show that the tissue in the proximity of the provascular bundles holds up to 500 μg g-1 of iron, depending on the genotype. In contrast to P. vulgaris and P. coccineus, we did not observe iron accumulation in the cells surrounding the provascular tissues of P. lunatus cotyledons. A novel iron-rich genotype, NUA35, with a high concentration of iron both in the seed coat and cotyledons was bred from a cross between an Andean and a Mesoamerican genotype. Conclusions The presented results emphasize the importance of complementing research in model organisms with analysis in crop plants and they suggest that iron distribution criteria should be integrated into selection strategies for bean biofortification. PMID:20149228

Iron in the aquifer system of Suffolk County, New York, 1990–98

USGS Publications Warehouse

Brown, Craig J.; Walter, Donald A.; Colabufo, Steven

1999-01-01

High concentrations of dissolved iron in ground water contribute to the biofouling of public-supply wells, and the treatment and remediation of biofouling are costly. Water companies on Long Island, N.Y., spend several million dollars annually to recondition, redevelop, and replace supply wells and distribution lines; treat dissolved iron with sequestering agents or by filtration; and respond to iron-related complaints by customers. This report summarizes the results of studies done by the U.S. Geological Survey, in cooperation with the Suffolk County Water Authority, to characterize the geochemistry and microbiology of iron in the aquifer system of Suffolk County. This information should be helpful for the siting and operation of supply wells.Concentrations of dissolved iron in Long Island's ground water, and the frequency of iron biofouling of wells, are highest in ground-water-discharge zones, particularly near the south shore. Ground water along a deep north-south flowpath of the Magothy aquifer in southwestern Suffolk County becomes anaerobic (oxygen deficient) and Fe(III) reducing at a distance of 8 to 10 kilometers south of the ground-water divide, and this change coincides with the downgradient increase in dissolved iron concentrations. The distribution of organic carbon, and the distribution and local variations in reactivity of Fe(III), in Magothy aquifer sediments have resulted in localized differences in redox microenvironments. For example, Fe(III)-reducing zones are associated with anaerobic conditions, where relatively large amounts of Fe(III) oxyhydroxide grain coatings are present, whereas sulfate-reducing zones are associated with lignite-rich lenses of silt and clay and appear to have developed in response to the depletion of available Fe(III) oxyhydroxides. The sulfate-reducing zones are characterized by relatively low concentrations of dissolved iron (resulting from iron-disulfide precipitation) and may be large enough to warrant water-supply development.Specific-capacity and water-quality data from wells screened in the Magothy aquifer indicate that water from biofouled wells contains higher median concentrations of total and dissolved iron and manganese, total phosphate, and dissolved sulfate, and lower median concentrations of dissolved oxygen and alkalinity, and lower pH, than does water from unaffected wells. Corresponding data from wells screened in the upper glacial aquifer indicate that water from biofouled wells contains higher median concentrations of total and dissolved manganese and dissolved sulfate, and lower pH, than does water from unaffected wells.Filamentous bacteria were detected in 31 (or 72 percent) of the 43 biofilm samples obtained from biofouled wells during reconditioning. The predominant filamentous organism was Gallionella ferruginea, a major biofouling agent in the upper glacial and Magothy aquifers throughout Suffolk County. Mineral-saturation indices indicate that most of the well-encrusting material is deposited when the wells are shut down. Furthermore, the use of treated water (which has a high pH and sometimes high concentrations of dissolved iron) for pump prelubrication when wells are shut down could greatly increase the rate of iron oxidation.

Trace Element Removal in Distributed Drinking Water Treatment Systems by Cathodic H2O2 Production and UV Photolysis

PubMed Central

2017-01-01

As water scarcity intensifies, point-of-use and point-of-entry treatment may provide a means of exploiting locally available water resources that are currently considered to be unsafe for human consumption. Among the different classes of drinking water contaminants, toxic trace elements (e.g., arsenic and lead) pose substantial operational challenges for distributed drinking water treatment systems. Removal of toxic trace elements via adsorption onto iron oxides is an inexpensive and robust treatment method; however, the presence of metal-complexing ligands associated with natural organic matter (NOM) often prevents the formation of iron precipitates at the relatively low concentrations of dissolved iron typically present in natural water sources, thereby requiring the addition of iron which complicates the treatment process and results in a need to dispose of relatively large amounts of accumulated solids. A point-of-use treatment device consisting of a cathodic cell that produced hydrogen peroxide (H2O2) followed by an ultraviolet (UV) irradiation chamber was used to decrease colloid stabilization and metal-complexing capacity of NOM present in groundwater. Exposure to UV light altered NOM, converting ∼6 μM of iron oxides into settable forms that removed between 0.5 and 1 μM of arsenic (As), lead (Pb), and copper (Cu) from solution via adsorption. After treatment, changes in NOM consistent with the loss of iron-complexing carboxylate ligands were observed, including decreases in UV absorbance and shifts in the molecular composition of NOM to higher H/C and lower O/C ratios. Chronoamperometric experiments conducted in synthetic groundwater revealed that the presence of Ca2+ and Mg2+ inhibited intramolecular charge-transfer within photoexcited NOM, leading to substantially increased removal of iron and trace elements. PMID:29240414

Integration to Implementation and the Micronutrient Forum: A Coordinated Approach for Global Nutrition. Case Study Application: Safety and Effectiveness of Iron Interventions.

PubMed

Raiten, Daniel J; Neufeld, Lynnette M; De-Regil, Luz-Maria; Pasricha, Sant-Rayn; Darnton-Hill, Ian; Hurrell, Richard; Murray-Kolb, Laura E; Nair, K Madhavan; Wefwafwa, Terry; Kupka, Roland; Phall, Modou Cheyassin; Sakr Ashour, Fayrouz A

2016-01-01

Paramount among the challenges to our ability to address the role of food and nutrition in health promotion and disease prevention is how to design and implement context-specific interventions and guidance. The Integration to Effective Implementation (I-to-I) concept is intended to address the complexities of the global health context through engagement of the continuum of stakeholders involved in the food and nutrition enterprise. The 2014 Micronutrient Forum (MNF) Global Conference held in Addis Ababa, Ethiopia, in June 2014 offered the opportunity to apply the I-to-I approach with the use of current concerns about the safety and effectiveness of interventions to prevent and treat iron deficiency (ID) as a case study. ID is associated with a range of adverse outcomes, especially in pregnant and nonpregnant women, infants, and primary school-age children. Strategies to combat ID include iron supplementation, multiple micronutrient powders, and food-based interventions to enhance dietary iron intake. Recent reports indicate potential increased adverse risks when iron is provided in areas with high infection burdens (e.g., malaria). This paradox has weakened iron intervention programs. Furthermore, the selection and interpretation of available biomarkers for assessing iron nutrition have been found to be compromised by the inflammatory process. These issues highlight the need for a comprehensive approach that considers basic biology, assessment, interventions, and how these can be translated into appropriate programs and policies. The application of the I-to-I with the use of the MNF offered an opportunity to explore how that might be achieved. © 2016 American Society for Nutrition.

Trace Element Removal in Distributed Drinking Water Treatment Systems by Cathodic H2O2 Production and UV Photolysis.

PubMed

Barazesh, James M; Prasse, Carsten; Wenk, Jannis; Berg, Stephanie; Remucal, Christina K; Sedlak, David L

2018-01-02

As water scarcity intensifies, point-of-use and point-of-entry treatment may provide a means of exploiting locally available water resources that are currently considered to be unsafe for human consumption. Among the different classes of drinking water contaminants, toxic trace elements (e.g., arsenic and lead) pose substantial operational challenges for distributed drinking water treatment systems. Removal of toxic trace elements via adsorption onto iron oxides is an inexpensive and robust treatment method; however, the presence of metal-complexing ligands associated with natural organic matter (NOM) often prevents the formation of iron precipitates at the relatively low concentrations of dissolved iron typically present in natural water sources, thereby requiring the addition of iron which complicates the treatment process and results in a need to dispose of relatively large amounts of accumulated solids. A point-of-use treatment device consisting of a cathodic cell that produced hydrogen peroxide (H 2 O 2 ) followed by an ultraviolet (UV) irradiation chamber was used to decrease colloid stabilization and metal-complexing capacity of NOM present in groundwater. Exposure to UV light altered NOM, converting ∼6 μM of iron oxides into settable forms that removed between 0.5 and 1 μM of arsenic (As), lead (Pb), and copper (Cu) from solution via adsorption. After treatment, changes in NOM consistent with the loss of iron-complexing carboxylate ligands were observed, including decreases in UV absorbance and shifts in the molecular composition of NOM to higher H/C and lower O/C ratios. Chronoamperometric experiments conducted in synthetic groundwater revealed that the presence of Ca 2+ and Mg 2+ inhibited intramolecular charge-transfer within photoexcited NOM, leading to substantially increased removal of iron and trace elements.

Effect of bicarbonate on iron-mediated oxidation of low-density lipoprotein

NASA Astrophysics Data System (ADS)

Arai, Hirofumi; Berlett, Barbara S.; Chock, P. Boon; Stadtman, Earl R.

2005-07-01

Oxidation of low-density lipoprotein (LDL) may play an important role in atherosclerosis. We studied the effects of bicarbonate/CO2 and phosphate buffer systems on metal ion-catalyzed oxidation of LDL to malondialdehyde (MDA) and to protein carbonyl and MetO derivatives. Our results revealed that LDL oxidation in mixtures containing free iron or heme derivatives was much greater in bicarbonate/CO2 compared with phosphate buffer. However, when copper was substituted for iron in these mixtures, the rate of LDL oxidation in both buffers was similar. Iron-catalyzed oxidation of LDL was highly sensitive to inhibition by phosphate. Presence of 0.3-0.5 mM phosphate, characteristic of human serum, led to 30-40% inhibition of LDL oxidation in bicarbonate/CO2 buffer. Iron-catalyzed oxidation of LDL to MDA in phosphate buffer was inhibited by increasing concentrations of albumin (10-200 μM), whereas MDA formation in bicarbonate/CO2 buffer was stimulated by 10-50 μM albumin but inhibited by higher concentrations. However, albumin stimulated the oxidation of LDL proteins to carbonyl derivatives at all concentrations examined in both buffers. Conversion of LDL to MDA in bicarbonate/CO2 buffer was greatly stimulated by ADP, ATP, and EDTA but only when EDTA was added at a concentration equal to that of iron. At higher than stoichiometric concentrations, EDTA prevented oxidation of LDL. Results of these studies suggest that interactions between bicarbonate and iron or heme derivatives leads to complexes with redox potentials that favor the generation of reactive oxygen species and/or to the generation of highly reactive CO2 anion or bicarbonate radical that facilitates LDL oxidation. Freely available online through the PNAS open access option.Abbreviations: LDL, low-density lipoprotein; MDA, malondialdehyde; MetO, methionine sulfoxide.

The complex interplay of iron, biofilm formation, and mucoidy affecting antimicrobial resistance of Pseudomonas aeruginosa

PubMed Central

Oglesby-Sherrouse, Amanda G.; Djapgne, Louise; Nguyen, Angela T.; Vasil, Adriana I.; Vasil, Michael L.

2014-01-01

Pseudomonas aeruginosa is a Gram-negative opportunistic bacterial pathogen that is refractory to a variety of current antimicrobial therapeutic regimens. Complicating treatment of such infections is the ability of P. aeruginosa to form biofilms, as well as several innate and acquired resistance mechanisms. Previous studies suggest iron plays a role in resistance to antimicrobial therapy, including the efficacy of an FDA-approved iron chelator, deferasirox (DSX), or Gallium, an iron analog, in potentiating antibiotic-dependent killing of P. aeruginosa biofilms. Here we show that iron-replete conditions enhance resistance of P. aeruginosa nonbiofilm growth against tobramycin and tigecycline. Interestingly, the mechanism of iron-enhanced resistance to each of these antibiotics is distinct. Whereas pyoverdine-mediated iron uptake is important for optimal resistance to tigecycline, it does not enhance tobramycin resistance. In contrast, heme supplementation results in increased tobramycin resistance, while having no significant effect on tigecycline resistance. Thus, non-siderophore bound iron plays an important role in resistance to tobramycin, while pyoverdine increases the ability of P. aeruginosa to resist tigecycline treatment. Lastly, we show that iron increases the minimal concentration of tobramycin, but not tigecycline, required to eradicate P. aeruginosa biofilms. Moreover, iron depletion blocks the previous observed induction of biofilm formation by sub-inhibitory concentrations of tobramycin, suggesting iron and tobramycin signal through overlapping regulatory pathways to affect biofilm formation. These data further support the role of iron in P. aeruginosa antibiotic resistance, providing yet another compelling case for targeting iron acquisition for future antimicrobial drug development. PMID:24436170

Effect of angiotensin II on iron-transporting protein expression and subsequent intracellular labile iron concentration in human glomerular endothelial cells.

PubMed

Tajima, Soichiro; Tsuchiya, Koichiro; Horinouchi, Yuya; Ishizawa, Keisuke; Ikeda, Yasumasa; Kihira, Yoshitaka; Shono, Masayuki; Kawazoe, Kazuyoshi; Tomita, Shuhei; Tamaki, Toshiaki

2010-07-01

Angiotensin II (Ang II)-induced endothelial injury, which is associated with atherosclerosis, is believed to be mediated by intracellular reactive oxygen species (ROS) through stimulation of nicotinamide adenine dinucleotide phosphate oxidase (NOX). Iron is essential for the amplification of oxidative stress. In this study, we investigated whether Ang II altered iron metabolism and whether the Ang II-induced endothelial injury is attributable to changes in iron metabolism of human glomerular endothelial cells (HGECs). When 90% iron-saturated human transferrin (90% Tf) was applied to HGECs without Ang II, the labile ferrous iron level was same as the effect of control in spite of a significant increase in the total cellular iron concentration. Treatment with Ang II and 30% Tf or 90% Tf significantly (P<0.01) increased the intracellular iron concentration, as well as labile ferrous iron and protein oxidation levels, compared with the effect of separate administration of each compound. Ang II treatment facilitated the protein expression of the Tf receptor, divalent metal transporter 1, and ferroportin 1 in a dose- and time-dependent manner. It was also found that simultaneous exposure of HGECs to Ang II and 90% Tf accelerated hydroxyl radical production, as shown by using an electron paramagnetic resonance spectrometer. These results suggest that Ang II not only induces production of ROS by NOX activation but also iron incorporation followed by an increase in labile iron in HGECs. Both of these events may participate in the progression of oxidative stress because of endothelial cell dysfunction through ferrous iron-mediated ROS generation.

Deletion of Iron Regulatory Protein 1 Causes Polycythemia and Pulmonary Hypertension in Mice through Translational De-repression of HIF2α

PubMed Central

Ghosh, Manik C.; Zhang, De-Liang; Jeong, Suh Young; Kovtunovych, Gennadiy; Ollivierre-Wilson, Hayden; Noguchi, Audrey; Tu, Tiffany; Senecal, Thomas; Robinson, Gabrielle; Crooks, Daniel R.; Tong, Wing-Hang; Ramaswamy, Kavitha; Singh, Anamika; Graham, Brian B.; Tuder, Rubin M.; Yu, Zu-Xi; Eckhaus, Michael; Lee, Jaekwon; Springer, Danielle A.; Rouault, Tracey A.

2013-01-01

SUMMARY Iron regulatory proteins 1 and 2 (Irps) post-transcriptionally control the expression of transcripts that contain iron responsive element (IRE) sequences, including ferritin, ferroportin, transferrin receptor and hypoxia inducible factor 2α (HIF2α). We report here that mice with targeted deletion of Irp1 developed pulmonary hypertension and polycythemia that was exacerbated by a low iron diet. Hematocrits increased to 65% in iron-starved mice, and many polycythemic mice died of abdominal hemorrhages. Irp1 deletion enhanced HIF2α protein expression in kidneys of Irp1−/− mice, which led to increased erythropoietin (EPO) expression, polycythemia and concomitant tissue iron deficiency. Increased HIF2α expression in pulmonary endothelial cells induced high expression of endothelin-1, likely contributing to the pulmonary hypertension of Irp1−/− mice. Our results reveal why anemia is an early physiological consequence of iron deficiency, highlight the physiological significance of Irp1 in regulating erythropoiesis and iron distribution, and provide important insights into the molecular pathogenesis of pulmonary hypertension. PMID:23395173

Cognitive Performance and Iron Status are Negatively Associated with Hookworm Infection in Cambodian Schoolchildren.

PubMed

Kuong, Khov; Fiorentino, Marion; Perignon, Marlene; Chamnan, Chhoun; Berger, Jacques; Sinuon, Muth; Molyden, Vann; Burja, Kurt; Parker, Megan; Ly, Sou Chheng; Friis, Henrik; Roos, Nanna; Wieringa, Frank T

2016-10-05

Soil-transmitted helminth (STH) infection has been associated with lower cognitive performance of schoolchildren. To identify pathways through which STH infection might affect school performance, baseline data from a large rice-fortification trial in Cambodian schoolchildren were used to investigate associations between STH infection, micronutrient status, anemia, and cognitive performance. Complete data on anthropometry, cognitive performance, and micronutrient status were available for 1,760 schoolchildren, 6-16 years of age. STH infection was identified using Kato-Katz, whereas cognitive performance was assessed using Raven's Colored Progressive Matrices (RCPM), block design, and picture completion. STH infection was found in 18% of the children; almost exclusively hookwork infection. After adjusting for age and gender, raw cognitive test scores were significantly lower in hookworm-infected children (-0.65; -0.78; -2.03 points for picture completion, RCPM, and block design, respectively; P < 0.05 for all). Hookworm infection was associated with iron status (total body iron), but not with vitamin A and zinc status, nor with inflammation or anthropometry. Body iron was negatively associated with increased intensity of hookworm infection (R = 0.22, P < 0.001). Hookworm infection in Cambodian schoolchildren was associated with lower cognitive performance, an effect most likely mediated through lower body iron. Interventions that are more effective against hookworm infection are needed to contribute to better health and improvement of cognitive performance. © The American Society of Tropical Medicine and Hygiene.

Genome Wide Identification of Orthologous ZIP Genes Associated with Zinc and Iron Translocation in Setaria italica.

PubMed

Alagarasan, Ganesh; Dubey, Mahima; Aswathy, Kumar S; Chandel, Girish

2017-01-01

Genes in the ZIP family encode transcripts to store and transport bivalent metal micronutrient, particularly iron (Fe) and or zinc (Zn). These transcripts are important for a variety of functions involved in the developmental and physiological processes in many plant species, including most, if not all, Poaceae plant species and the model species Arabidopsis. Here, we present the report of a genome wide investigation of orthologous ZIP genes in Setaria italica and the identification of 7 single copy genes. RT-PCR shows 4 of them could be used to increase the bio-availability of zinc and iron content in grains. Of 36 ZIP members, 25 genes have traces of signal peptide based sub-cellular localization, as compared to those of plant species studied previously, yet translocation of ions remains unclear. In silico analysis of gene structure and protein nature suggests that these two were preeminent in shaping the functional diversity of the ZIP gene family in S. italica . NAC, bZIP and bHLH are the predominant Fe and Zn responsive transcription factors present in SiZIP genes. Together, our results provide new insights into the signal peptide based/independent iron and zinc translocation in the plant system and allowed identification of ZIP genes that may be involved in the zinc and iron absorption from the soil, and thus transporting it to the cereal grain underlying high micronutrient accumulation.

Effect of tannic acid on iron absorption in straw-colored fruit bats(Eidolon helvum)

USDA-ARS?s Scientific Manuscript database

Excessive absorption and subsequent storage of dietary iron has been found in a variety of captively held birds and mammals, including fruit bats. It is thought that feeding a diet that is low in iron can prevent the onset of this disease; however, manufacturing a diet with commonly available foodst...

Biogeochemical controls on interactions of microbial iron and sulfate reduction

NASA Astrophysics Data System (ADS)

Kirk, M. F.; Paper, J. M.; Haller, B. R.; Shodunke, G. O.; Marquart, K. A.; Jin, Q.

2016-12-01

Although iron and sulfate reduction are two of the most common microbial electron accepting processes in anoxic settings, the relative influences of environmental factors that guide interactions between each are poorly known. Identifying these factors is a key to predicting how those interactions will respond to future environmental changes. In this study, we used semi-continuous bioreactors to examine the influence of pH, electron donor flux, and sulfate availability. The reactors contained 100 mL of aqueous media and 1 g of marsh sediment amended with goethite (1 mmol). One set of reactors received acidic media (pH 6) while the other set received alkaline media (pH 7.5). Media for both sets of reactors included acetate (0.25 and 1 mM), which served as an electron donor, and sulfate (2.5 mM). We also included sets of sulfate-deficient and acetate-deficient control reactors. We maintained a fluid residence time of 35 days in the reactors by sampling and feeding them every seven days during the 91-day incubation. Our results show that, under the conditions tested, pH had a larger influence on the balance between each reaction than acetate concentration. In acidic reactors, the molar amount of iron reduced exceeded the amount of sulfate reduced by a factor of 3 in reactors receiving media with 0 and 0.25 mM acetate and a factor of 2 in reactors receiving 1 mM acetate. Under alkaline conditions, iron and sulfate were reduced in nearly equal proportions, regardless of influent acetate concentration. Results from sulfate-deficient control reactors show that the presence of sulfate reduction increased the extent of iron reduction in all reactors, but particularly those with alkaline pH. Under acidic conditions, the amount of iron reduced was greater by a factor of 1.2 if sulfate reduction occurred simultaneously than if it did not. Under alkaline conditions, that factor increased to 8.2. Hence, pH influenced the extent to which sulfate reduction promoted iron reduction.

Desferrithiocin: A Search for Clinically Effective Iron Chelators

PubMed Central

2015-01-01

The successful search for orally active iron chelators to treat transfusional iron-overload diseases, e.g., thalassemia, is overviewed. The critical role of iron in nature as a redox engine is first described, as well as how primitive life forms and humans manage the metal. The problems that derive when iron homeostasis in humans is disrupted and the mechanism of the ensuing damage, uncontrolled Fenton chemistry, are discussed. The solution to the problem, chelator-mediated iron removal, is clear. Design options for the assembly of ligands that sequester and decorporate iron are reviewed, along with the shortcomings of the currently available therapeutics. The rationale for choosing desferrithiocin, a natural product iron chelator (a siderophore), as a platform for structure–activity relationship studies in the search for an orally active iron chelator is thoroughly developed. The study provides an excellent example of how to systematically reengineer a pharmacophore in order to overcome toxicological problems while maintaining iron clearing efficacy and has led to three ligands being evaluated in human clinical trials. PMID:25207964

The role of heterotrophic bacteria in iron-limited ocean ecosystems

NASA Astrophysics Data System (ADS)

Tortell, Philippe D.; Maldonado, Maria T.; Price, Nell M.

1996-09-01

IRON availability limits phytoplankton growth in large areas of the world's oceans1-3 and may influence the strength of the biological carbon pump4,5. Very little is known of the iron requirements of oceanic heterotrophic bacteria, which constitute up to 50% of the total particulate organic carbon in open ocean waters6,7 and are important in carbon cycling as remineralizers of dissolved organic matter and hence producers of CO2 (ref. 8). Here we report that oceanic bacteria contain more iron per biomass than phytoplankton. In the subarctic Pacific, they constitute a large fraction of biogenic iron and account for 20-45% of biological iron uptake. Bacterial iron quotas in the field are similar to those of iron-deficient laboratory cultures, which exhibit reduced elec-tron transport, slow growth, and low carbon growth efficiency. Heterotrophic bacteria therefore play a major role in the biogeo-chemical cycling of iron. In situ iron limitation of heterotrophic metabolism may have profound effects on carbon flux in the ocean.