Iron Chelation Therapy with Deferasirox Results in Improvement of Liver Enzyme Level in Patients with Iron Overload-Associated Liver Dysfunction

PubMed Central

Miura, Yasuo; Matsui, Yusuke; Kaneko, Hitomi; Watanabe, Mitsumasa; Tsudo, Mitsuru

2010-01-01

Iron chelation therapy (ICT) has been applied for the patients with iron overload-associated liver dysfunction since it is one of the causes of death in patients with intractable hematological diseases requiring multiple red blood cell transfusions. Recently, deferasirox (DSX), a novel, once-daily oral iron chelator, was demonstrated to have similar efficacy to the conventional continuous infusion of deferoxamine on a decrease in serum ferritin (SF) level in heavily transfused patients. We show three cases of transfusion-mediated iron-overloaded patients with an elevated serum alanine aminotransaminase (ALT). All three patients who received the ICT with DSX showed a decrease in ALT level in association with a decrease in SF level. It is suggested that DSX therapy could be considered to expect the improvement of liver damage for iron-overloaded patients with an abnormal ALT level. PMID:20592762

DIVALENT METAL TRANSPORTER-1 REGULATION BY IRON AND VANADIUM MODULATES HYDROGEN PEROXIDE-INDUCED DNA DAMAGE IN LUNG CELLS

EPA Science Inventory

The divalent metal transporter-1 (DMT1) participates in the detoxification of metals that can damage lung epithelium. Elevated iron levels increase the expression of DMT1 in bronchial epithelial cells stimulating its uptake and storage in ferritin, thus making iron unavailable t...

Iron-Chelating Therapy for Transfusional Iron Overload

PubMed Central

Brittenham, Gary M.

2011-01-01

A 16-year-old boy with sickle cell anemia undergoes routine screening with transcranial Doppler ultrasonography to assess the risk of stroke. This examination shows an abnormally elevated blood-flow velocity in the middle cerebral artery. The hemoglobin level is 7.2 g per deciliter, the reticulocyte count is 12.5%, and the fetal hemoglobin level is 8.0%. Long-term treatment with red-cell transfusion is initiated to prevent stroke. A hematologist recommends prophylactic iron-chelating therapy. PMID:21226580

Nuclear microscopy in Parkinson's disease

NASA Astrophysics Data System (ADS)

Watt, F.; Lee, T.; Thong, P. S. P.; Tang, S. M.

1995-09-01

Rats have been subjected to unilateral lesioning with the selective neurotoxin 6-OHDA in order to induce Parkinsonism. Analysis using the NUS Nuclear Microscope facility have shown that iron levels are raised by an average of 26% in the lesioned subtantia nigra region of the brain compared with the non-lesioned side. In addition the background tissue level of iron is also elevated by 31% in the lesioned side, indicating that there is a general increase in iron levels as a result of the lesioning. This result is consistent with the other observations that other diseases of the brain are frequently associated with altered iron levels (eg. progressive nuclear palsy, multiple system atrophy, Alzheimers disease, multiple sclerosis).

Oxidation-Induced Degradable Nanogels for Iron Chelation

NASA Astrophysics Data System (ADS)

Liu, Zhi; Wang, Yan; Purro, Max; Xiong, May P.

2016-02-01

Iron overload can increase cellular oxidative stress levels due to formation of reactive oxygen species (ROS); untreated, it can be extremely destructive to organs and fatal to patients. Since elevated oxidative stress levels are inherent to the condition in such patients, oxidation-induced degradable nanogels for iron chelation were rationally designed by simultaneously polymerizing oxidation-sensitive host-guest crosslinkers between β-cyclodextrin (β-CD) and ferrocene (Fc) and iron chelating moieties composed of deferoxamine (DFO) into the final gel scaffold in reverse emulsion reaction chambers. UV-Vis absorption and atomic absorption spectroscopy (AAS) was used to verify iron chelating capability of nanogels. These materials can degrade into smaller chelating fragments at rates proportional to the level of oxidative stress present. Conjugating DFO reduces the cytotoxicity of the chelator in the macrophage cells. Importantly, the nanogel can effectively reduce cellular ferritin expression in iron overloaded cells and regulate intracellular iron levels at the same time, which is important for maintaining a homeostatic level of this critical metal in cells.

Oxidation-Induced Degradable Nanogels for Iron Chelation

PubMed Central

Liu, Zhi; Wang, Yan; Purro, Max; Xiong, May P.

2016-01-01

Iron overload can increase cellular oxidative stress levels due to formation of reactive oxygen species (ROS); untreated, it can be extremely destructive to organs and fatal to patients. Since elevated oxidative stress levels are inherent to the condition in such patients, oxidation-induced degradable nanogels for iron chelation were rationally designed by simultaneously polymerizing oxidation-sensitive host-guest crosslinkers between β-cyclodextrin (β-CD) and ferrocene (Fc) and iron chelating moieties composed of deferoxamine (DFO) into the final gel scaffold in reverse emulsion reaction chambers. UV-Vis absorption and atomic absorption spectroscopy (AAS) was used to verify iron chelating capability of nanogels. These materials can degrade into smaller chelating fragments at rates proportional to the level of oxidative stress present. Conjugating DFO reduces the cytotoxicity of the chelator in the macrophage cells. Importantly, the nanogel can effectively reduce cellular ferritin expression in iron overloaded cells and regulate intracellular iron levels at the same time, which is important for maintaining a homeostatic level of this critical metal in cells. PMID:26868174

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.

Hfe Deficiency Impairs Pulmonary Neutrophil Recruitment in Response to Inflammation

PubMed Central

Benesova, Karolina; Vujić Spasić, Maja; Schaefer, Sebastian M.; Stolte, Jens; Baehr-Ivacevic, Tomi; Waldow, Katharina; Zhou, Zhe; Klingmueller, Ursula; Benes, Vladimir; Mall, Marcus A.; Muckenthaler, Martina U.

2012-01-01

Regulation of iron homeostasis and the inflammatory response are tightly linked to protect the host from infection. Here we investigate how imbalanced systemic iron homeostasis in a murine disease model of hereditary hemochromatosis (Hfe−/− mice) affects the inflammatory responses of the lung. We induced acute pulmonary inflammation in Hfe−/− and wild-type mice by intratracheal instillation of 20 µg of lipopolysaccharide (LPS) and analyzed local and systemic inflammatory responses and iron-related parameters. We show that in Hfe−/− mice neutrophil recruitment to the bronchoalveolar space is attenuated compared to wild-type mice although circulating neutrophil numbers in the bloodstream were elevated to similar levels in Hfe−/− and wild-type mice. The underlying molecular mechanisms are likely multifactorial and include elevated systemic iron levels, alveolar macrophage iron deficiency and/or hitherto unexplored functions of Hfe in resident pulmonary cell types. As a consequence, pulmonary cytokine expression is out of balance and neutrophils fail to be recruited efficiently to the bronchoalveolar compartment, a process required to protect the host from infections. In conclusion, our findings suggest a novel role for Hfe and/or imbalanced iron homeostasis in the regulation of the inflammatory response in the lung and hereditary hemochromatosis. PMID:22745741

Molecular Mediators Governing Iron-Copper Interactions

PubMed Central

Gulec, Sukru; Collins, James F.

2015-01-01

Given their similar physiochemical properties, it is a logical postulate that iron and copper metabolism are intertwined. Indeed, iron-copper interactions were first documented over a century ago, but the homeostatic effects of one on the other has not been elucidated at a molecular level to date. Recent experimental work has, however, begun to provide mechanistic insight into how copper influences iron metabolism. During iron deficiency, elevated copper levels are observed in the intestinal mucosa, liver, and blood. Copper accumulation and/or redistribution within enterocytes may influence iron transport, and high hepatic copper may enhance biosynthesis of a circulating ferroxidase, which potentiates iron release from stores. Moreover, emerging evidence has documented direct effects of copper on the expression and activity of the iron-regulatory hormone hepcidin. This review summarizes current experimental work in this field, with a focus on molecular aspects of iron-copper interplay and how these interactions relate to various disease states. PMID:24995690

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

Iron plaque formation and heavy metal uptake in Spartina alterniflora at different tidal levels and waterlogging conditions.

PubMed

Xu, Yan; Sun, Xiangli; Zhang, Qiqiong; Li, Xiuzhen; Yan, Zhongzheng

2018-05-30

Tidal flat elevation in the estuarine wetland determines the tidal flooding time and flooding frequency, which will inevitably affect the formation of iron plaque and accumulations of heavy metals (HMs) in wetland plants. The present study investigated the formation of iron plaque and HM's (copper, zinc, lead, and chromium) accumulation in S. alterniflora, a typical estuarine wetland species, at different tidal flat elevations (low, middle and high) in filed and at different time (3, 6, 9, 12 h per day) of waterlogging treatment in greenhouse conditions. Results showed that the accumulation of copper, zinc, lead, and chromium in S. alterniflora was proportional to the exchangeable fraction of these metals in the sediments, which generally increased with the increase of waterlogging time, whereas the formations of iron plaque in roots decreased with the increase of waterlogging time. Under field conditions, the uptake of copper and zinc in the different parts of the plants generally increased with the tidal levels despite the decrease in the metals' exchangeable fraction with increasing tidal levels. The formation of iron plaque was found to be highest in the middle tidal positions and significantly lower in low and high tidal positions. Longer waterlogging time increased the metals' accumulation but decreased the formation of iron plaque in S. alterniflora. The binding of metal ions on iron plaque helped impede the uptake and accumulation of copper and chromium in S. alterniflora. Copyright © 2018 Elsevier Inc. All rights reserved.

Effects of a 7-day military training exercise on inflammatory biomarkers, serum hepcidin, and iron status.

PubMed

McClung, James P; Martini, Svein; Murphy, Nancy E; Montain, Scott J; Margolis, Lee M; Thrane, Ingjerd; Spitz, Marissa G; Blatny, Janet-Martha; Young, Andrew J; Gundersen, Yngvar; Pasiakos, Stefan M

2013-11-04

Hepcidin, a peptide that is released into the blood in response to inflammation, prevents cellular iron export and results in declines in iron status. Elevated serum and urinary levels of hepcidin have been observed in athletes following exercise, and declines in iron status have been reported following prolonged periods of training. The objective of this observational study was to characterize the effects of an occupational task, military training, on iron status, inflammation, and serum hepcidin. Volunteers (n = 21 males) included Norwegian Soldiers participating in a 7-day winter training exercise that culminated in a 3-day, 54 km ski march. Fasted blood samples were collected at baseline, on day 4 (PRE, prior to the ski march), and again on day 7 (POST, following the ski march). Samples were analyzed for hemoglobin, serum ferritin, soluble transferrin receptor (sTfR), interleukin-6 (IL-6), and serum hepcidin. Military training affected inflammation and serum hepcidin levels, as IL-6 and hepcidin concentrations increased (P < 0.05) from the baseline to POST (mean ± SD, 9.1 ± 4.9 vs. 14.5 ± 8.4 pg/mL and 6.5 ± 3.5 vs. 10.2 ± 6.9 ng/mL, respectively). Iron status was not affected by the training exercise, as sTfR levels did not change over the course of the 7-day study. Military training resulted in significant elevations in IL-6 and serum hepcidin. Future studies should strive to identify the role of hepcidin in the adaptive response to exercise, as well as countermeasures for the prevention of chronic or repeated elevations in serum hepcidin due to exercise or sustained occupational tasks which may result in longer term decrements in iron status.

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

Gorodetsky, R.; Goldfarb, A.; Dagan, I.

Diagnostic x-ray spectrometry, a method based on x-ray fluorescence analysis, was used for noninvasive determination of iron and zinc in two distinct skin areas, representing predominantly dermal and epidermal tissues, in 56 patients with beta-thalassemia major and intermedia. The mean iron levels in the skin of patients with beta-thalassemia major and intermedia were elevated by greater than 200% and greater than 50%, respectively, compared with control values. The zinc levels of both skin areas examined were within the normal range. The data indicate that the rate and number of blood transfusions, which correlated well with serum ferritin levels (r .more » 0.8), are not the only factors that determine the amount of iron deposition in the skin (r less than 0.6). Other sources of iron intake contribute to the total iron load in the tissues, particularly in patients who are not given multiple transfusions. The noninvasive quantitation of skin levels may reflect the extent of iron deposition in major parenchymal organs. Repeated DXS examinations of the skin could monitor the clearance of iron from the tissues of patients with iron overload in the course of therapy with chelating agents.« less

Hepcidin: A Critical Regulator Of Iron Metabolism During Hypoxia

DTIC Science & Technology

2011-01-01

GDF15) has been demonstrated to suppress hepcidin expression and is elevated in patients with thalassemia [28]. Another erythrokine, twisted...Oneal et al., “High levels of GDF15 in thalassemia suppress expression of the iron regulatory protein hepcidin,” Nature Medicine, vol. 13, no. 9, pp

Lead poisoning in children.

PubMed

Warniment, Crista; Tsang, Katrina; Galazka, Sim S

2010-03-15

The prevalence and severity of childhood lead poisoning have been greatly reduced since the removal of lead from paint and gasoline in the 1970s. Despite these efforts, approximately 310,000 U.S. children younger than five years have elevated blood lead levels. Health care professionals should perform targeted screening for lead poisoning in children who are Medicaid-enrolled or -eligible, foreign born, or identified as high risk by the Centers for Disease Control and Prevention (CDC) location-specific recommendations or by a personal risk questionnaire. Venous sampling is the preferred method for measuring blood lead levels, but a carefully collected finger-stick sample is an acceptable alternative. Capillary samples of elevated levels should be confirmed by a venous sample. The CDC recommends that the threshold for follow-up and intervention of lead poisoning be a blood lead level of 10 microg per dL or higher. Recommendations for treatment of elevated blood levels include a thorough environmental investigation, laboratory testing when appropriate, iron supplementation for iron-deficient children, and chelation therapy for blood lead levels of 45 microg per dL or more. Prevention consists of education and avoidance of lead-contaminated products.

Iron dysregulation combined with aging prevents sepsis-induced apoptosis.

PubMed

Javadi, Pardis; Buchman, Timothy G; Stromberg, Paul E; Turnbull, Isaiah R; Vyas, Dinesh; Hotchkiss, Richard S; Karl, Irene E; Coopersmith, Craig M

2005-09-01

Sepsis, iron loading, and aging cause independent increases in gut epithelial and splenic apoptosis. It is unknown how their combination will affect apoptosis and systemic cytokine levels. Hfe-/- mice (a murine homologue of hemochromatosis) abnormally accumulate iron in their tissues. Aged (24-26 months) or mature (16-18 months) Hfe-/- mice and wild type (WT) littermates were subjected to cecal ligation and puncture (CLP) or sham laparotomy. Intestine, spleen, and blood were harvested 24 h later and assessed for apoptosis and cytokine levels. Gut epithelial and splenic apoptosis were low in both aged septic and sham Hfe-/- mice, regardless of the amount of iron in their diet. Mature septic WT mice had increased apoptosis compared to age-matched sham WT mice. Mature septic Hfe-/- mice had similar levels of intestinal cell death to age-matched septic WT mice but higher levels of splenic apoptosis. Apoptosis was significantly lower in septic aged Hfe-/- mice than septic mature Hfe-/- animals. Interleukin-6 was elevated in septic aged Hfe-/- mice compared to sham mice. Although sepsis, chronic iron dysregulation, and aging each increase gut and splenic apoptosis, their combination yields cell death levels similar to sham animals despite the fact that aged Hfe-/- mice are able to mount an inflammatory response following CLP and mature Hfe-/- mice have elevated sepsis-induced apoptosis. Combining sepsis with two risk factors that ordinarily increase cell death and increase mortality in CLP yields an apoptotic response that could not have been predicted based upon each element in isolation.

Hepcidin: an emerging biomarker for iron disorders, inflammatory diseases, and infections

NASA Astrophysics Data System (ADS)

Westerman, Mark E.; Olbina, Gordana; Ostland, Vaughn E.; Nemeth, Elizabeta; Ganz, Tomas

2010-04-01

The peptide hormone hepcidin, has emerged as the master regulator of iron homeostasis. Dysregulation of hepcidin is a principal or contributing factor in most genetic and acquired systemic iron disorders, including anemia of inflammation (anemia of chronic disease). Hepcidin maintains healthy blood iron levels by regulating dietary iron absorption and transport from body iron stores to plasma. High serum hepcidin levels observed in chronic and acute inflammatory conditions can cause anemia by limiting plasma iron available for erythropoiesis. Chronically low serum hepcidin levels cause iron-overload and ultimately, accumulation of iron in liver and heart. We recently validated the first immunoassay for serum hepcidin and established the normal ranges in adults. Hepcidin has excellent potential as a biomarker and has a known mechanism of action, good stability, and rapid response to iron stores, inflammatory stimuli, and bacterial infections. Hepcidin can be measured in blood, urine, and saliva, and is generally not measurable in iron deficient/anemic patients and highly elevated in inflammatory diseases and infections. Intrinsic LifeSciences (ILS) is developing second generation hepcidin immunoassays and lateral-flow POC devices for hepcidin, a well characterized multi-purpose biomarker with applications in global health security.

Synergistic Interaction of Light Alcohol Administration in the Presence of Mild Iron Overload in a Mouse Model of Liver Injury: Involvement of Triosephosphate Isomerase Nitration and Inactivation

PubMed Central

Gao, Wanxia; Zhao, Jie; Gao, Zhonghong

2017-01-01

It is well known that iron overload promotes alcoholic liver injury, but the doses of iron or alcohol used in studies are usually able to induce liver injury independently. Little attention has been paid to the coexistence of low alcohol consumption and mild iron overload when either of them is insufficient to cause obvious liver damage, although this situation is very common among some people. We studied the interactive effects and the underlining mechanism of mild doses of iron and alcohol on liver injury in a mouse model. Forty eight male Kunming mice were randomly divided into four groups: control, iron (300 mg/kg iron dextran, i.p.), alcohol (2 g/kg/day ethanol for four weeks i.g.), and iron plus alcohol group. After 4 weeks of treatment, mice were sacrificed and blood and livers were collected for biochemical analysis. Protein nitration level in liver tissue was determined by immunoprecipitation and Western blot analysis. Although neither iron overload nor alcohol consumption at our tested doses can cause severe liver injury, it was found that co-administration of the same doses of alcohol and iron resulted in liver injury and hepatic dysfunction, accompanied with elevated ratio of NADH/NAD+, reduced antioxidant ability, increased oxidative stress, and subsequent elevated protein nitration level. Further study revealed that triosephosphate isomerase, an important glycolytic enzyme, was one of the targets to be oxidized and nitrated, which was responsible for its inactivation. These data indicate that even under low alcohol intake, a certain amount of iron overload can cause significant liver oxidative damage, and the modification of triosephosphate isomerasemight be the important underlining mechanism of hepatic dysfunction. PMID:28103293

Improved preoperative iron status assessment by soluble transferrin receptor in elderly patients undergoing knee and hip replacement.

PubMed

Basora, M; Deulofeu, R; Salazar, F; Quinto, L; Gomar, C

2006-12-01

A poor preoperative haemoglobin (Hb) status is frequently encountered among adult patients scheduled for corrective surgery of the locomotive system, representing the main risk factor for blood transfusion. The soluble transferrin receptor (sTfR) has become a highly specific parameter for the detection of iron deficits as it can differentiate between iron deficiency anaemia and anaemia of chronic disease, because of the lack of effect by associated inflammation, unlike ferritin. The objectives of this study were to evaluate patients with the prevalence of risk for transfusion, the effect of inflammation on ferritin (F) values and functional iron deficiency in elderly patients with advanced degenerative arthropathy scheduled for hip or knee replacement. This observational, prospective study included patients over 50 years, operated for hip or knee replacements between April and June 2004. Of 218 patients studied, 87 (39%) presented with Hb levels between 10 and 13 g/dl. The prevalence of functional iron deficit was 27% (sTfR > 1.76 mg/l), while only 8.6% of patients displayed F levels below normal. As expected, C-reactive protein levels were elevated in 24.8% of patients and erythrocyte sedimentation rate was elevated in 50%. These inflammatory markers did not correlate with levels of either F or sTfR. Multiple factors can affect F levels, such as the inflammatory status of osteoarthritis in the elderly, obesity, nonsteroidal anti-inflammatory drugs therapy and low physical performance. As sTfR is not affected by inflammation, it has emerged as a primary parameter for the evaluation of iron status during preoperative assessment among patients scheduled for arthroplasty surgery. Our data strongly suggest that sTfR measurement contributes to improve patient management.

Iron toxicity and its possible association with treatment of Cancer: lessons from hemoglobinopathies and rare, transfusion-dependent anemias.

PubMed

Puliyel, Mammen; Mainous, Arch G; Berdoukas, Vasilios; Coates, Thomas D

2015-02-01

Exposure to elevated levels of iron causes tissue damage and organ failure, and increases the risk of cancer. The toxicity of iron is mediated through generation of oxidants. There is also solid evidence indicating that oxidant stress plays a significant role in a variety of human disease states, including malignant transformation. Iron toxicity is the main focus when managing thalassemia. However, the short- and long-term toxicities of iron have not been extensively considered in children and adults treated for malignancy, and only recently have begun to draw oncologists' attention. The treatment of malignancy can markedly increase exposure of patients to elevated toxic iron species without the need for excess iron input from transfusion. This under-recognized exposure likely enhances organ toxicity and may contribute to long-term development of secondary malignancy and organ failure. This review discusses the current understanding of iron metabolism, the mechanisms of production of toxic free iron species in humans, and the relation of the clinical marker, transferrin saturation (TS), to the presence of toxic free iron. We will present epidemiological data showing that high TS is associated with poor outcomes and development of cancer, and that lowering free iron may improve outcomes. Finally, we will discuss the possible relation between some late complications seen in survivors of cancer and those due to iron toxicity. Copyright © 2014 Elsevier Inc. All rights reserved.

Iron Supplementation during Three Consecutive Days of Endurance Training Augmented Hepcidin Levels.

PubMed

Ishibashi, Aya; Maeda, Naho; Kamei, Akiko; Goto, Kazushige

2017-07-30

Iron supplementation contributes an effort to improving iron status among athletes, but it does not always prevent iron deficiency. In the present study, we explored the effect of three consecutive days of endurance training (twice daily) on the hepcidin-25 (hepcidin) level. The effect of iron supplementation during this period was also determined. Fourteen male endurance athletes were enrolled and randomly assigned to either an iron-treated condition (Fe condition, n = 7) or a placebo condition (Control condition; CON, n = 7). They engaged in two 75-min sessions of treadmill running at 75% of maximal oxygen uptake on three consecutive days (days 1-3). The Fe condition took 12 mg of iron twice daily (24 mg/day), and the CON condition did not. On day 1, both conditions exhibited significant increases in serum hepcidin and plasma interleukin-6 levels after exercise ( p < 0.05). In the CON condition, the hepcidin level did not change significantly throughout the training period. However, in the Fe condition, the serum hepcidin level on day 4 was significantly higher than that of the CON condition ( p < 0.05). In conclusion, the hepcidin level was significantly elevated following three consecutive days of endurance training when moderate doses of iron were taken.

Iron Supplementation during Three Consecutive Days of Endurance Training Augmented Hepcidin Levels

PubMed Central

Ishibashi, Aya; Maeda, Naho; Kamei, Akiko; Goto, Kazushige

2017-01-01

Iron supplementation contributes an effort to improving iron status among athletes, but it does not always prevent iron deficiency. In the present study, we explored the effect of three consecutive days of endurance training (twice daily) on the hepcidin-25 (hepcidin) level. The effect of iron supplementation during this period was also determined. Fourteen male endurance athletes were enrolled and randomly assigned to either an iron-treated condition (Fe condition, n = 7) or a placebo condition (Control condition; CON, n = 7). They engaged in two 75-min sessions of treadmill running at 75% of maximal oxygen uptake on three consecutive days (days 1–3). The Fe condition took 12 mg of iron twice daily (24 mg/day), and the CON condition did not. On day 1, both conditions exhibited significant increases in serum hepcidin and plasma interleukin-6 levels after exercise (p < 0.05). In the CON condition, the hepcidin level did not change significantly throughout the training period. However, in the Fe condition, the serum hepcidin level on day 4 was significantly higher than that of the CON condition (p < 0.05). In conclusion, the hepcidin level was significantly elevated following three consecutive days of endurance training when moderate doses of iron were taken. PMID:28758951

Preliminary study of injury from heating systemically delivered, nontargeted dextran–superparamagnetic iron oxide nanoparticles in mice

PubMed Central

Kut, Carmen; Zhang, Yonggang; Hedayati, Mohammad; Zhou, Haoming; Cornejo, Christine; Bordelon, David; Mihalic, Jana; Wabler, Michele; Burghardt, Elizabeth; Gruettner, Cordula; Geyh, Alison; Brayton, Cory; Deweese, Theodore L; Ivkov, Robert

2013-01-01

Aim To assess the potential for injury to normal tissues in mice due to heating systemically delivered magnetic nanoparticles in an alternating magnetic field (AMF). Materials & methods Twenty three male nude mice received intravenous injections of dextran–superparamagnetic iron oxide nanoparticles on days 1–3. On day 6, they were exposed to AMF. On day 7, blood, liver and spleen were harvested and analyzed. Results Iron deposits were detected in the liver and spleen. Mice that had received a high-particle dose and a high AMF experienced increased mortality, elevated liver enzymes and significant liver and spleen necrosis. Mice treated with low-dose superparamagnetic iron oxide nanoparticles and a low AMF survived, but had elevated enzyme levels and local necrosis in the spleen. Conclusion Magnetic nanoparticles producing only modest heat output can cause damage, and even death, when sequestered in sufficient concentrations. Dextran–superparamagnetic iron oxide nanoparticles are deposited in the liver and spleen, making these the sites of potential toxicity. PMID:22830502

Iron overload promotes erythroid apoptosis through regulating HIF-1a/ROS signaling pathway in patients with myelodysplastic syndrome.

PubMed

Zheng, Qing-Qing; Zhao, You-Shan; Guo, Juan; Zhao, Si-da; Song, Lu-Xi; Fei, Cheng-Ming; Zhang, Zheng; Li, Xiao; Chang, Chun-Kang

2017-07-01

Erythroid apoptosis increases significantly in myelodysplastic syndrome (MDS) patients with iron overload, but the underlying mechanism is not fully clear. In this study, we aim to explore the effect of HIF-1a/ROS on erythroid apoptosis in MDS patients with iron overload. We found that iron overload injured cellular functions through up-regulating ROS levels in MDS/AML cells, including inhibited cell viability, increased cell apoptosis and blocked cell cycle at G0/G1 phase. Interestingly, overexpression of hypoxia inducible factor-1a (HIF-1a), which was under-expressed in iron overload models, reduced ROS levels and attenuated cell damage caused by iron overload in MDS/AML cells. And gene knockdown of HIF-1a got the similar results as iron overload in MDS/AML cells. Furthermore, iron overload caused high erythroid apoptosis was closely related with ROS in MDS patients. Importantly, the HIF-1a protein levels of erythrocytes elevated obviously after incubation with desferrioxamine (DFO) from MDS patients with iron overload, accompanied by ROS levels inhibited and erythroid apoptosis reduced. Taken together, our findings determine that the HIF-1a/ROS signaling pathway plays a key role in promoting erythroid apoptosis in MDS patients with iron overload. Copyright © 2017 Elsevier Ltd. All rights reserved.

Estrogen-dependent changes in serum iron levels as a translator of the adverse effects of estrogen during infection: a conceptual framework.

PubMed

Hamad, Mawieh; Awadallah, Samir

2013-12-01

Elevated levels of estrogen often associate with increased susceptibility to infection. This has been attributed to the ability of estrogen to concomitantly enhance the growth and virulence of pathogens and suppress host immunity. But the exact mechanism of how estrogen mediates such effects, especially in cases where the pathogen and/or the immune components in question do not express estrogen receptors, has yet to be elucidated. Here we propose that translating the adverse effects of estrogen during infection is dependent to a significant degree upon its ability to manipulate iron homeostasis. For elevated levels of estrogen alter the synthesis and/or activity of several factors involved in iron metabolism including hypoxia inducible factor 1α (HIF-1α) and hepcidin among others. This leads to the inhibition of hepcidin synthesis in hepatocytes and the maintenance of ferroportin (FPN) integrity on the surface of iron-releasing duodenal enterocytes, hepatocytes, and macrophages. Intact FPN permits the continuous efflux of dietary and stored iron into the circulation, which further enhances pathogen growth and virulence on the one hand and suppresses host immunity on the other. This new conceptual framework may help explain a multitude of disparate clinical and experimental observations pertinent to the relationship between estrogen and infection. Copyright © 2013 Elsevier Ltd. All rights reserved.

Anti-oxidative protection against iron overload-induced liver damage in mice by Cajanus cajan (L.) Millsp. leaf extract.

PubMed

Sarkar, Rhitajit; Hazra, Bibhabasu; Mandal, Nripendranath

2013-02-01

In view of the contribution of iron deposition in the oxidative pathologic process of liver disease, the potential of 70% methanolic extract of C. cajan leaf (CLME) towards antioxidative protection against iron-overload-induced liver damage in mice has been investigated. DPPH radical scavenging and protection of Fenton reaction induced DNA damage was conducted in vitro. Post oral administration of CLME to iron overloaded mice, the levels of antioxidant and serum enzymes, hepatic iron, serum ferritin, lipid peroxidation, and protein carbonyl and hydroxyproline contents were measured, in comparison to deferasirox treated mice. Oral treatment of the plant extract effectively lowered the elevated levels of liver iron, lipid peroxidation, protein carbonyl and hydroxyproline. There was notable increment in the dropped levels of hepatic antioxidants. The dosage of the plant extract not only made the levels of serum enzymes approach normal value, but also counteracted the overwhelmed serum ferritin level. The in vitro studies indicated potential antioxidant activity of CLME. The histopathological observations also substantiated the ameliorative function of the plant extract. Accordingly, it is suggested that Cajanus cajan leaf can be a useful herbal remedy to suppress oxidative damage caused by iron overload.

[Taste disturbance after general anesthesia with classic laryngeal mask airway (CLM)].

PubMed

Arimune, Mutsuaki

2007-07-01

A 27-year-old man underwent the right knee joint operation under general anesthesia with CLM. After the operation, he complained of taste disturbance of the left side of the tongue. We measured electrical taste threshold and the serum level of zinc, copper and iron. The taste threshold was elevated in the two nerve areas of the left side of the tongue (chorda tympani, N. glossopharyngeus) and the serum levels of zinc and iron were low. We concluded that he had been short of zinc and iron and the insertion of CLM had triggered taste disturbance.

Iron dysregulation combined with aging prevents sepsis-induced apoptosis

PubMed Central

Javadi, Pardis; Buchman, Timothy G.; Stromberg, Paul E.; Turnbull, Isaiah R.; Vyas, Dinesh; Hotchkiss, Richard S.; Karl, Irene E.; Coopersmith, Craig M.

2005-01-01

Background Sepsis, iron loading and aging cause independent increases in gut epithelial and splenic apoptosis. It is unknown how their combination will affect apoptosis and systemic cytokine levels. Methods Hfe−/− mice (a murine homolog of hemochromatosis) abnormally accumulate iron in their tissues. Aged (24–26 months) or mature (16–18 months) Hfe−/− mice and wild type (WT) littermates were subjected to cecal ligation and puncture (CLP) or sham laparotomy. Intestine, spleen, and blood were harvested 24 hours later and assessed for apoptosis and cytokine levels. Results Gut epithelial and splenic apoptosis were low in both aged septic and sham Hfe−/− mice, regardless of the amount of iron in their diet. Mature septic WT mice had increased apoptosis compared to age-matched sham WT mice. Mature septic Hfe−/− mice had similar levels of intestinal cell death to age-matched septic WT mice but higher levels of splenic apoptosis. Apoptosis was significantly lower in septic aged Hfe−/− mice than septic mature Hfe−/− animals. Interleukin-6 was elevated in septic aged Hfe−/− mice compared to sham mice. Conclusions Although sepsis, chronic iron dysregulation, and aging each increase gut and splenic apoptosis, their combination yields cell death levels similar to sham animals despite the fact that aged Hfe−/− mice are able to mount an inflammatory response following CLP and mature Hfe−/− mice have elevated sepsis-induced apoptosis. Combining sepsis with two risk factors that ordinarily increase cell death and increase mortality in CLP yields an apoptotic response that could not have been predicted based upon each element in isolation. PMID:15921699

The Impact of Iron Overload in Patients with Acute Leukemia and Myelodysplastic Syndrome on Hepatic and Endocrine functions.

PubMed

Yassin, Mohamed A; Soliman, Ashraf; De Sanctis, Vincenzo; Hmissi, Saloua M; Abdulla, Mohammad Aj; Ekeibed, Yeslem; Ismail, Omer; Nashwan, Abdulqadir; Soliman, Dina; Almusharaf, Mohammed; Hussein, Redwa

2018-04-03

Patients with hematologic malignancies undergoing chemotherapy and requiring blood transfusion usually have an elevated serum ferritin. These findings have led to the suggestion that iron overload is common and may have deleterious effects in these patients. However, the relationship between serum ferritin and parenchymal iron overload in such patients is unknown. Therefore, we measured the liver iron content (LIC) by the FerriScan® method and investigated the liver function and some endocrine tests in 27 patients with acute leukemia (AL) or myelodysplastic syndromes (MDS). Using FerriScan® method, the normal mean LIC levels are: 4.3 ± 2.9 mg Fe/g dry weight (d.w.). In our patients, the mean serum ferritin level was 1965 ± 2428 ng/mL. In our patients, the mean total iron in the blood received by them was 7177 ± 5009 mg. In 6 out of 27 patients LIC was > 7 mg Fe/g d.w. and in 11/27 serum ferritin was > 1000 ng/ml. Measuring fasting blood glucose revealed 3/27 with diabetes mellitus and 4/27 with impaired fasting glucose (IFG). All patients had normal serum concentrations of calcium, parathormone (PTH), free thyroxine (FT4) and thyrotropin (TSH). Four patients had elevated serum alanine transferase (ALT). LIC was correlated significantly with ferritin level (r = 0.5666; P < 0.001) and the cumulative amount of iron in the transfused blood (r = 0.523; P <0.001). LIC was correlated significantly with ALT (r = 0.277; P = 0.04) and fasting blood glucose (FBG) was correlated significantly with the amount of iron transfused (r = 0.52, p < 0.01) and ALT level (r = 0.44; P< 0.01). The age of patients did not correlate with LIC, FBG or ALT. In conclusions, these results contribute to our understanding of the prevalence of dysglycemia and hepatic dysfunction in relation to parenchymal iron overload in patients with hematologic malignancies undergoing chemotherapy and requiring blood transfusions.

The natural history of serum iron indices for HFE C282Y homozygosity associated with hereditary hemochromatosis.

PubMed

Gurrin, Lyle C; Osborne, Nicholas J; Constantine, Clare C; McLaren, Christine E; English, Dallas R; Gertig, Dorota M; Delatycki, Martin B; Southey, Melissa C; Hopper, John L; Giles, Graham G; Anderson, Gregory J; Olynyk, John K; Powell, Laurie W; Allen, Katrina J

2008-12-01

There are few longitudinal studies of serum ferritin (SF) and transferrin saturation (TS) levels in individuals homozygous for the C282Y mutation. We characterized the development of elevated iron measures in C282Y homozygotes followed for 12 years. From 31,192 people aged 40-69 years at baseline, we identified 203 C282Y homozygotes (95 males), of whom 116 had SF and fasting TS levels measured at baseline (mean age, 55 years) and 86 were untreated and had iron measures at follow-up (mean, 12 years later). The probabilities of SF at follow-up exceeding clinical thresholds were predicted from baseline SF and TS under a multivariate normal model. For C282Y homozygotes, at baseline, 84% of males and 65% of females had elevated SF and 37% of males and 3% of females had SF >1000 microg/L. For males with SF 300-1000 microg/L at baseline, the predicted probability of progressing to SF >1000 microg/L at follow-up was between 13% and 35% and, for females, between 16% and 22%. For C282Y homozygotes with normal baseline SF, <15% were predicted to develop SF >1000 microg/L if left untreated. The majority of C282Y homozygotes who are likely to develop SF levels sufficient to place them at risk of iron overload-related disease will have done so by mean age 55 years. TS >95% at mean age 55 years in males increases the likelihood that SF levels will be elevated at mean age 65 years, but this effect is absent in females, most likely because of physiologic blood loss associated with menstruation.

Measuring “Free” Iron Levels in Caenorhabditis Elegans Using Low-Temperature Fe(III) Electron Paramagnetic Resonance Spectroscopy

PubMed Central

Pate, Kira T.; Rangel, Natalie A.; Fraser, Brian; Clement, Matthew H. S.; Srinivasan, Chandra

2007-01-01

Oxidative stress, caused by free radicals within the body, has been associated with the process of aging and many human diseases. As free radicals, in particular superoxide, are difficult to measure, an alternative indirect method for measuring oxidative stress levels has been successfully used in E. coli and yeast. This method is based on a proposed connection between elevated superoxide levels and release of iron from solvent exposed [4Fe-4S] enzyme clusters, which eventually leads to an increase in hydroxyl radical production. In past studies using bacteria and yeast, a positive correlation was found between superoxide production or oxidative stress due to superoxide within the organism and EPR (electron paramagnetic resonance) detectable “free” iron levels. In the present study, we have developed a reliable and an efficient method for measuring “free” iron levels in C. elegans using low temperature Fe(III) EPR at g = 4.3. This method utilizes synchronized worm cultures grown on plates, which are homogenized and treated with desferrioxamine, an Fe(III) chelator, prior to packing the EPR tube. Homogenization was found not to alter “free” iron levels, while desferrioxamine treatment significantly raised these levels, indicating presence of both Fe(II) and Fe(III) in the “free” iron pool. The correlation between free radical levels and the observed “free” iron levels was examined by using heat stress and paraquat treatment. The intensity of the Fe(III) EPR signal and thus, the concentration of the “free” iron pool, varied with the treatments that altered radical levels without changing the total iron levels. This study provides the groundwork needed to uncover the correlation between oxidative stress, “free” iron levels, and longevity in C. elegans. PMID:17010298

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.

Practical implications of liver and heart iron load assessment by T2*-MRI in children and adults with transfusion-dependent anemias

PubMed Central

Chirnomas, Sarah Deborah; Geukes-Foppen, Marnix; Barry, Kristen; Braunstein, Jennifer; Kalish, Leslie A.; Neufeld, Ellis J.; Powell, Andrew J.

2017-01-01

This study examined the relationship between hepatic and myocardial iron concentration, assessed by T2*-MRI in 66 patients (3–82 years) with transfusion-dependent anemias and thalassemia intermedia, to determine whether hepatic iron levels alone suffice for chelation adjustments. We found a poor correlation between hepatic and myocardial iron (r = 0.10, P = 0.43) and identified a subgroup (14%) with increased myocardial iron without a matched degree of hepatic hemosiderosis. Left ventricular ejection fraction was insensitive for detecting elevated myocardial iron. These findings were present in both adult and pediatric patients. We recommend therapeutic monitoring of iron burden by evaluation of both liver and myocardial iron with T2*-MRI. PMID:18661491

Serum ferritin is an independent predictor of histologic severity and advanced fibrosis in patients with nonalcoholic fatty liver disease.

PubMed

Kowdley, Kris V; Belt, Patricia; Wilson, Laura A; Yeh, Matthew M; Neuschwander-Tetri, Brent A; Chalasani, Naga; Sanyal, Arun J; Nelson, James E

2012-01-01

Serum ferritin (SF) levels are commonly elevated in patients with nonalcoholic fatty liver disease (NAFLD) because of systemic inflammation, increased iron stores, or both. The aim of this study was to examine the relationship between elevated SF and NAFLD severity. Demographic, clinical, histologic, laboratory, and anthropometric data were analyzed in 628 adult patients with NAFLD (age, ≥ 18 years) with biopsy-proven NAFLD and an SF measurement within 6 months of their liver biopsy. A threshold SF >1.5 × upper limit of normal (ULN) (i.e., >300 ng/mL in women and >450 ng/mL in men) was significantly associated with male sex, elevated serum alanine aminotransferase, aspartate aminotransferase, iron, transferrin-iron saturation, iron stain grade, and decreased platelets (P < 0.01). Histologic features of NAFLD were more severe among patients with SF >1.5 × ULN, including steatosis, fibrosis, hepatocellular ballooning, and diagnosis of NASH (P < 0.026). On multiple regression analysis, SF >1.5 × ULN was independently associated with advanced hepatic fibrosis (odds ratio [OR], 1.66; 95% confidence interval [CI], 1.05-2.62; P = 0.028) and increased NAFLD Activity Score (NAS) (OR, 1.99; 95% CI, 1.06-3.75; P = 0.033). A SF >1.5 × ULN is associated with hepatic iron deposition, a diagnosis of NASH, and worsened histologic activity and is an independent predictor of advanced hepatic fibrosis among patients with NAFLD. Furthermore, elevated SF is independently associated with higher NAS, even among patients without hepatic iron deposition. We conclude that SF is useful to identify NAFLD patients at risk for NASH and advanced fibrosis. Copyright © 2011 American Association for the Study of Liver Diseases.

Chromium ion release from stainless steel pediatric scoliosis instrumentation.

PubMed

Cundy, Thomas P; Delaney, Christopher L; Rackham, Matthew D; Antoniou, Georgia; Oakley, Andrew P; Freeman, Brian J C; Sutherland, Leanne M; Cundy, Peter J

2010-04-20

Case-control study. To determine whether serum metal ion levels and erythrocyte chromium levels in adolescents with stainless steel spinal instrumentation are elevated when compared with 2 control groups. Instrumented spinal arthrodesis is a common procedure to correct scoliosis. The long-term consequences of retained implants are unclear. Possible toxic effects related to raised metal ion levels have been reported in the literature. Thirty patients who underwent posterior spinal arthrodesis with stainless steel instrumentation for scoliosis (group 1) were included. Minimum postoperative duration was 3 years. Serum chromium, molybdenum, iron, and ferritin levels were measured. Participants with elevated above normal serum chromium levels (n = 11) also underwent erythrocyte chromium analysis. Comparisons were made with 2 control groups; 10 individuals with scoliosis with no spinal surgery (group 2) and 10 volunteers without scoliosis (group 3). All control group participants underwent serum and erythrocyte analysis. Elevated above normal serum chromium levels were demonstrated in 11 of 30 (37%) group 1 participants. Elevated serum chromium levels were demonstrated in 0 of 10 participants (0%) in group 2 and 1 of 10 (10%) in group 3. There was a statistically significant elevation in serum chromium levels between group 1 and group 2 participants (P = 0.001). There was no significant association between groups 1, 2, and 3 for serum molybdenum, iron, and ferritin levels. Erythrocyte chromium measurements were considered within the normal range for all participants tested (n = 31). Raised serum chromium levels were detected in 37% of patients following instrumented spinal arthrodesis for correction of scoliosis. This new finding has relatively unknown health implications but potential mutagenic, teratogenic and carcinogenic sequelae. This is especially concerning with most scoliosis patients being adolescent females with their reproductive years ahead.

Impact of iron overload on interleukin-10 levels, biochemical parameters and oxidative stress in patients with sickle cell anemia

PubMed Central

Barbosa, Maritza Cavalcante; dos Santos, Talyta Ellen Jesus; de Souza, Geane Félix; de Assis, Lívia Coêlho; Freitas, Max Victor Carioca; Gonçalves, Romélia Pinheiro

2013-01-01

Objective The aim of this study was to evaluate the impact of iron overload on the profile of interleukin-10 levels, biochemical parameters and oxidative stress in sickle cell anemia patients. Methods A cross-sectional study was performed of 30 patients with molecular diagnosis of sickle cell anemia. Patients were stratified into two groups, according to the presence of iron overload: Iron overload (n = 15) and Non-iron overload (n = 15). Biochemical analyses were performed utilizing the Wiener CM 200 automatic analyzer. The interleukin-10 level was measured by capture ELISA using the BD OptEIAT commercial kit. Oxidative stress parameters were determined by spectrophotometry. Statistical analysis was performed using GraphPad Prism software (version 5.0) and statistical significance was established for p-values < 0.05 in all analyses. Results Biochemical analysis revealed significant elevations in the levels of uric acid, triglycerides, very low-density lipoprotein (VLDL), alanine aminotransferase (ALT), lactate dehydrogenase (LDH), urea and creatinine in the Iron overload Group compared to the Non-iron overload Group and significant decreases in the high-density lipoprotein (HDL) and low-density lipoprotein (LDL). Ferritin levels correlated positively with uric acid concentrations (p-value < 0.05). The Iron overload Group showed lower interleukin-10 levels and catalase activity and higher nitrite and malondialdehyde levels compared with the Non-iron overload Group. Conclusion The results of this study are important to develop further consistent studies that evaluate the effect of iron overload on the inflammatory profile and oxidative stress of patients with sickle cell anemia. PMID:23580881

Plasma Levels of Aminothiols, Nitrite, Nitrate, and Malondialdehyde in Myelodysplastic Syndromes in the Context of Clinical Outcomes and as a Consequence of Iron Overload

PubMed Central

Pimková, Kristýna; Chrastinová, Leona; Suttnar, Jiří; Štikarová, Jana; Kotlín, Roman; Čermák, Jaroslav; Dyr, Jan Evangelista

2014-01-01

The role of oxidative stress in the initiation and progression of myelodysplastic syndromes (MDS) as a consequence of iron overload remains unclear. In this study we have simultaneously quantified plasma low-molecular-weight aminothiols, malondialdehyde, nitrite, and nitrate and have studied their correlation with serum iron/ferritin levels, patient treatment (chelation therapy), and clinical outcomes. We found significantly elevated plasma levels of total, oxidized, and reduced forms of cysteine (P < 0.001) , homocysteine (P < 0.001), and cysteinylglycine (P < 0.006) and significantly depressed levels of total and oxidized forms of glutathione (P < 0.03) and nitrite (P < 0.001) in MDS patients compared to healthy donors. Moreover, total (P < 0.032) and oxidized cysteinylglycine (P = 0.029) and nitrite (P = 0.021) differed significantly between the analyzed MDS subgroups with different clinical classifications. Malondialdehyde levels in plasma correlated moderately with both serum ferritin levels (r = 0.78, P = 0.001) and serum free iron levels (r = 0.60, P = 0.001) and were significantly higher in patients with iron overload. The other analyzed compounds lacked correlation with iron overload (represented by serum iron/ferritin levels). For the first time our results have revealed significant differences in the concentrations of plasma aminothiols in MDS patients, when compared to healthy donors. We found no correlation of these parameters with iron overload and suggest the role of oxidative stress in the development of MDS disease. PMID:24669287

Plasma levels of aminothiols, nitrite, nitrate, and malondialdehyde in myelodysplastic syndromes in the context of clinical outcomes and as a consequence of iron overload.

PubMed

Pimková, Kristýna; Chrastinová, Leona; Suttnar, Jiří; Štikarová, Jana; Kotlín, Roman; Čermák, Jaroslav; Dyr, Jan Evangelista

2014-01-01

The role of oxidative stress in the initiation and progression of myelodysplastic syndromes (MDS) as a consequence of iron overload remains unclear. In this study we have simultaneously quantified plasma low-molecular-weight aminothiols, malondialdehyde, nitrite, and nitrate and have studied their correlation with serum iron/ferritin levels, patient treatment (chelation therapy), and clinical outcomes. We found significantly elevated plasma levels of total, oxidized, and reduced forms of cysteine (P < 0.001), homocysteine (P < 0.001), and cysteinylglycine (P < 0.006) and significantly depressed levels of total and oxidized forms of glutathione (P < 0.03) and nitrite (P < 0.001) in MDS patients compared to healthy donors. Moreover, total (P < 0.032) and oxidized cysteinylglycine (P = 0.029) and nitrite (P = 0.021) differed significantly between the analyzed MDS subgroups with different clinical classifications. Malondialdehyde levels in plasma correlated moderately with both serum ferritin levels (r = 0.78, P = 0.001) and serum free iron levels (r = 0.60, P = 0.001) and were significantly higher in patients with iron overload. The other analyzed compounds lacked correlation with iron overload (represented by serum iron/ferritin levels). For the first time our results have revealed significant differences in the concentrations of plasma aminothiols in MDS patients, when compared to healthy donors. We found no correlation of these parameters with iron overload and suggest the role of oxidative stress in the development of MDS disease.

Coupling fibroblast growth factor 23 production and cleavage: iron deficiency, rickets, and kidney disease.

PubMed

Wolf, Myles; White, Kenneth E

2014-07-01

High levels of fibroblast growth factor 23 (FGF23) cause the rare disorders of hypophosphatemic rickets and are a risk factor for cardiovascular disease and death in patients with chronic kidney disease (CKD). Despite major advances in understanding FGF23 biology, fundamental aspects of FGF23 regulation in health and in CKD remain mostly unknown. Autosomal dominant hypophosphatemic rickets (ADHR) is caused by gain-of-function mutations in FGF23 that prevent its proteolytic cleavage, but affected individuals experience a waxing and waning course of phosphate wasting. This led to the discovery that iron deficiency is an environmental trigger that stimulates FGF23 expression and hypophosphatemia in ADHR. Unlike osteocytes in ADHR, normal osteocytes couple increased FGF23 production with commensurately increased FGF23 cleavage to ensure that normal phosphate homeostasis is maintained in the event of iron deficiency. Simultaneous measurement of FGF23 by intact and C-terminal assays supported these breakthroughs by providing minimally invasive insight into FGF23 production and cleavage in bone. These findings also suggest a novel mechanism of FGF23 elevation in patients with CKD, who are often iron deficient and demonstrate increased FGF23 production and decreased FGF23 cleavage, consistent with an acquired state that mimics the molecular pathophysiology of ADHR. Iron deficiency stimulates FGF23 production, but normal osteocytes couple increased FGF23 production with increased cleavage to maintain normal circulating levels of biologically active hormone. These findings uncover a second level of FGF23 regulation within osteocytes, failure of which culminates in elevated levels of biologically active FGF23 in ADHR and perhaps CKD.

Results of a preimpoundment water-quality study of Swatara Creek, Pennsylvania

USGS Publications Warehouse

Fishel, David K.; Richardson, J.E.

1986-01-01

The impoundment will act as a sediment trap and thus reduce the concentrations of total phosphorus, iron, aluminum, lead, copper, and zinc immediately downstream from the impoundment. Large storm discharges and releases from the hypolimnion of the reservoir to attain the winter-pool level may contain low oxygen concentrations and elevated concentrations of iron, aluminum, lead, copper, and zinc. Unless conservation releases from the multi-level release gates are carefully controlled, low dissolved-oxygen levels and high metal concentrations may degrade the downstream water quality and be detrimental to the aquatic community.

Metal Dyshomeostasis and Inflammation in Alzheimer's and Parkinson's Diseases: Possible Impact of Environmental Exposures

PubMed Central

Myhre, Oddvar; Utkilen, Hans; Duale, Nur; Brunborg, Gunnar; Hofer, Tim

2013-01-01

A dysregulated metal homeostasis is associated with both Alzheimer's (AD) and Parkinson's (PD) diseases; AD patients have decreased cortex and elevated serum copper levels along with extracellular amyloid-beta plaques containing copper, iron, and zinc. For AD, a putative hepcidin-mediated lowering of cortex copper mechanism is suggested. An age-related mild chronic inflammation and/or elevated intracellular iron can trigger hepcidin production followed by its binding to ferroportin which is the only neuronal iron exporter, thereby subjecting it to lysosomal degradation. Subsequently raised neuronal iron levels can induce translation of the ferroportin assisting and copper binding amyloid precursor protein (APP); constitutive APP transmembrane passage lowers the copper pool which is important for many enzymes. Using in silico gene expression analyses, we here show significantly decreased expression of copper-dependent enzymes in AD brain and metallothioneins were upregulated in both diseases. Although few AD exposure risk factors are known, AD-related tauopathies can result from cyanobacterial microcystin and β-methylamino-L-alanine (BMAA) intake. Several environmental exposures may represent risk factors for PD; for this disease neurodegeneration is likely to involve mitochondrial dysfunction, microglial activation, and neuroinflammation. Administration of metal chelators and anti-inflammatory agents could affect disease outcomes. PMID:23710288

Iron Enhances Hepatic Fibrogenesis and Activates Transforming Growth Factor-β Signaling in Murine Hepatic Stellate Cells.

PubMed

Mehta, Kosha J; Coombes, Jason D; Briones-Orta, Marco; Manka, Paul P; Williams, Roger; Patel, Vinood B; Syn, Wing-Kin

2018-02-01

Although excess iron induces oxidative stress in the liver, it is unclear whether it directly activates the hepatic stellate cells (HSC). We evaluated the effects of excess iron on fibrogenesis and transforming growth factor beta (TGF-β) signaling in murine HSC. Cells were treated with holotransferrin (0.005-5g/L) for 24 hours, with or without the iron chelator deferoxamine (10µM). Gene expressions (α-SMA, Col1-α1, Serpine-1, TGF-β, Hif1-α, Tfrc and Slc40a1) were analyzed by quantitative real time-polymerase chain reaction, whereas TfR1, ferroportin, ferritin, vimentin, collagen, TGF-β RII and phospho-Smad2 proteins were evaluated by immunofluorescence, Western blot and enzyme-linked immunosorbent assay. HSC expressed the iron-uptake protein transferrin receptor 1 (TfR1) and the iron-export protein ferroportin. Holotransferrin upregulated TfR1 expression by 1.8-fold (P < 0.03) and ferritin accumulation (iron storage) by 2-fold (P < 0.01), and activated HSC with 2-fold elevations (P < 0.03) in α-SMA messenger RNA and collagen secretion, and a 1.6-fold increase (P < 0.01) in vimentin protein. Moreover, holotransferrin activated the TGF-β pathway with TGF-β messenger RNA elevated 1.6-fold (P = 0.05), and protein levels of TGF-β RII and phospho-Smad2 increased by 1.8-fold (P < 0.01) and 1.6-fold (P < 0.01), respectively. In contrast, iron chelation decreased ferritin levels by 30% (P < 0.03), inhibited collagen secretion by 60% (P < 0.01), repressed fibrogenic genes α-SMA (0.2-fold; P < 0.05) and TGF-β (0.4-fold; P < 0.01) and reduced levels of TGF-β RII and phospho-Smad2 proteins. HSC express iron-transport proteins. Holotransferrin (iron) activates HSC fibrogenesis and the TGF-β pathway, whereas iron depletion by chelation reverses this, suggesting that this could be a useful adjunct therapy for patients with fibrosis. Further studies in primary human HSC and animal models are necessary to confirm this. Published by Elsevier Inc.

Influence of diurnal variation and fasting on serum iron concentrations in a community-based population.

PubMed

Nguyen, Leonard T; Buse, Joshua D; Baskin, Leland; Sadrzadeh, S M Hossein; Naugler, Christopher

2017-12-01

Serum iron is an important clinical test to help identify cases of iron deficiency or overload. Fluctuations caused by diurnal variation and diet are thought to influence test results, which may affect clinical patient management. We examined the impact of these preanalytical factors on iron concentrations in a large community-based cohort. Serum iron concentration, blood collection time, fasting duration, patient age and sex were obtained for community-based clinical testing from the Laboratory Information Service at Calgary Laboratory Services for the period of January 2011 to December 2015. A total of 276,307 individual test results were obtained. Iron levels were relatively high over a long period from 8:00 to 15:00. Mean concentrations were highest at blood collection times of 11:00 for adult men and 12:00 for adult women and children, however iron levels peaked as late as 15:00 in teenagers. With regard to fasting, iron levels required approximately 5h post-prandial time to return to a baseline, except for children and teenage females where no significant variation was seen until after 11h fasting. After 10h fasting, iron concentrations in all patient groups gradually increased to higher levels compared to earlier fasting times. Serum iron concentrations remain reasonably stable during most daytime hours for testing purposes. In adults, blood collection after 5 to 9h fasting provides a representative estimate of a patient's iron levels. For patients who have fasted overnight, i.e. ≥12h fasting, clinicians should be aware that iron concentrations may be elevated beyond otherwise usual levels. Copyright © 2017. Published by Elsevier Inc.

[2,3-diphosphoglycerate level during the active and maintenance treatment of iron-deficiency anemia patients].

PubMed

Iordanova, E; Dosheva, I; Lulcheva, F; Tsvetkova, N; Dobrev, K

1985-01-01

The objective of the present study was to obtain information about the duration of tissue hypoxia in patients with iron deficiency anemia. That fact is of importance for the determination of the duration of maintenance iron therapy. The level of 2,3-diphosphoglycerate was studied during the treatment, after the correction of anemic syndrome and after 60-day out-patient department treatment. The data obtained revealed that the level of 2,3-diphosphoglycerate was considerably elevated, as compared with the norm, before the treatment. After the active treatment and correction of anemic syndrome it was decreased, but remaining above the norm. By the 60th day of the out-patient department treatment the decrease continued and the level of 2,3-diphosphoglycerate approached the norm.

Effect of increased temperature, CO2, and iron on nitrate uptake and primary productivity in the coastal Ross Sea

NASA Astrophysics Data System (ADS)

Bronk, D. A.; Spackeen, J.; Sipler, R. E.; Bertrand, E. M.; Roberts, Q. N.; Xu, K.; Baer, S. E.; McQuaid, J.; Zhu, Z.; Walworth, N. G.; Hutchins, D. A.; Allen, A. E.

2016-02-01

Western Antarctic Seas are rapidly changing as a result of elevated concentrations of CO2 and rising sea surface temperatures. It is critical to determine how the structure and function of microbial communities will be impacted by these changes in the future because the Southern Ocean has seasonally high rates of primary production, is an important sink for anthropogenic CO2, and supports a diverse assemblage of higher trophic level organisms. During the Austral summer of 2013 and 2015, a collaborative research group conducted a series of experiments to understand how the individual and combined effects of temperature, CO2, and iron impact Ross Sea microorganisms. Our project used a variety of approaches, including batch experiments, semi-continuous experiments, and continuous-culturing over extended time intervals, to determine how future changes may shift Ross Sea microbial communities and how nutrient cycling and carbon biogeochemistry may subsequently be altered. Chemical and biological parameters were measured throughout the experiments to assess changes in community composition and nutrient cycling, including uptake rate measurements of nitrate and bicarbonate by different size fractions of microorganisms. Relative to the control, nitrate uptake rates significantly increased when temperature and iron were elevated indicating that temperature and iron are important physical drivers that influence nutrient cycling. Elevations in temperature and iron independently and synergistically produced higher rates than elevated CO2. Our nutrient uptake results also suggest that the physiology of large microorganisms will be more impacted by climate change variables than small microorganisms.

Current Review of Iron Overload and Related Complications in Hematopoietic Stem Cell Transplantation

PubMed Central

Atilla, Erden; Toprak, Selami K.; Demirer, Taner

2017-01-01

Iron overload is an adverse prognostic factor for patients undergoing hematopoietic stem cell transplantation (HSCT). In the HSCT setting, pretransplant and early posttransplant ferritin and transferrin saturation were found to be highly elevated due to high transfusion requirements. In addition to that, post-HSCT iron overload was shown to be related to infections, hepatic sinusoidal obstruction syndrome, mucositis, liver dysfunction, and acute graft-versus-host disease. Hyperferritinemia causes decreased survival rates in both pre- and posttransplant settings. Serum ferritin levels, magnetic resonance imaging, and liver biopsy are diagnostic tools for iron overload. Organ dysfunction due to iron overload may cause high mortality rates and therefore sufficient iron chelation therapy is recommended in this setting. In this review the management of iron overload in adult HSCT is discussed. PMID:27956374

Nitric oxide ameliorates the damaging effects of oxidative stress induced by iron deficiency in cyanobacterium Anabaena 7120.

PubMed

Kaushik, Manish Singh; Srivastava, Meenakshi; Srivastava, Alka; Singh, Anumeha; Mishra, Arun Kumar

2016-11-01

In cyanobacterium Anabaena 7120, iron deficiency leads to oxidative stress with unavoidable consequences. Nitric oxide reduces pigment damage and supported the growth of Anabaena 7120 in iron-deficient conditions. Elevation in nitric oxide accumulation and reduced superoxide radical production justified the role of nitric oxide in alleviating oxidative stress in iron deficiency. Increased activities of antioxidative enzymes and higher levels of ROS scavengers (ascorbate, glutathione and thiol) in iron deficiency were also observed in the presence of nitric oxide. Nitric oxide also supported the membrane integrity of Anabaena cells and reduces protein and DNA damage caused by oxidative stress induced by iron deficiency. Results suggested that nitric oxide alleviates the damaging effects of oxidative stress induced by iron deficiency in cyanobacterium Anabaena 7120.

Elevated temperature inhibits recruitment of transferrin-positive vesicles and induces iron-deficiency genes expression in Aiptasia pulchella host-harbored Symbiodinium.

PubMed

Song, Po-Ching; Wu, Tsung-Meng; Hong, Ming-Chang; Chen, Ming-Chyuan

2015-10-01

Coral bleaching is the consequence of disruption of the mutualistic Cnidaria-dinoflagellate association. Elevated seawater temperatures have been proposed as the most likely cause of coral bleaching whose severity is enhanced by a limitation in the bioavailability of iron. Iron is required by numerous organisms including the zooxanthellae residing inside the symbiosome of cnidarian cells. However, the knowledge of how symbiotic zooxanthellae obtain iron from the host cells and how elevated water temperature affects the association is very limited. Since cellular iron acquisition is known to be mediated through transferrin receptor-mediated endocytosis, a vesicular trafficking pathway specifically regulated by Rab4 and Rab5, we set out to examine the roles of these key proteins in the iron acquisition by the symbiotic Symbiodinium. Thus, we hypothesized that the iron recruitments into symbiotic zooxanthellae-housed symbiosomes may be dependent on rab4/rab5-mediated fusion with vesicles containing iron-bound transferrins and will be retarded under elevated temperature. In this study, we cloned a novel monolobal transferrin (ApTF) gene from the tropical sea anemone Aiptasia pulchella and confirmed that the association of ApTF with A. pulchella Rab4 (ApRab4) or A. pulchella Rab5 (ApRab5) vesicles is inhibited by elevated temperature through immunofluorescence analysis. We confirmed the iron-deficient phenomenon by demonstrating the induced overexpression of iron-deficiency-responsive genes, flavodoxin and high-affinity iron permease 1, and reduced intracellular iron concentration in zooxanthellae under desferrioxamine B (iron chelator) and high temperature treatment. In conclusion, our data are consistent with algal iron deficiency being a contributing factor for the thermal stress-induced bleaching of symbiotic cnidarians. Copyright © 2015 Elsevier Inc. All rights reserved.

Persistence and Decontamination of Bacillus atrophaeus subsp. globigii Spores on Corroded Iron in a Model Drinking Water System▿

PubMed Central

Szabo, Jeffrey G.; Rice, Eugene W.; Bishop, Paul L.

2007-01-01

Persistence of Bacillus atrophaeus subsp. globigii spores on corroded iron coupons in drinking water was studied using a biofilm annular reactor. Spores were inoculated at 106 CFU/ml in the dechlorinated reactor bulk water. The dechlorination allowed for observation of the effects of hydraulic shear and biofilm sloughing on persistence. Approximately 50% of the spores initially adhered to the corroded iron surface were not detected after 1 month. Addition of a stable 10 mg/liter free chlorine residual after 1 month led to a 2-log10 reduction of adhered B. atrophaeus subsp. globigii, but levels on the coupons quickly stabilized thereafter. Increasing the free chlorine concentration to 25 or 70 mg/liter had no additional effect on inactivation. B. atrophaeus subsp. globigii spores injected in the presence of a typical distribution system chlorine residual (∼0.75 mg/liter) resulted in a steady reduction of adhered B. atrophaeus subsp. globigii over 1 month, but levels on the coupons eventually stabilized. Adding elevated chlorine levels (10, 25, and 70 mg/liter) after 1 month had no effect on the rate of inactivation. Decontamination with elevated free chlorine levels immediately after spore injection resulted in a 3-log10 reduction within 2 weeks, but the rate of inactivation leveled off afterward. This indicates that free chlorine did not reach portions of the corroded iron surface where B. atrophaeus subsp. globigii spores had adhered. B. atrophaeus subsp. globigii spores are capable of persisting for an extended time in the presence of high levels of free chlorine. PMID:17308186

Hemochromatosis detection in a health screening program at an Alabama forest products mill.

PubMed

Barton, James C; Cheatwood, Susan M; Key, Timothy J; Acton, Ronald T

2002-08-01

We analyzed hemochromatosis detection in a 11.5-year multiphasic health screening program at a forest products mill. There were 2199 participants: 2032 Whites (1506 men, 526 women) and 167 African Americans (124 men, 43 women); 85.0% of employees were screened. Iron and transferrin saturation were measured in a serum biochemistry profile on specimens obtained after overnight fasting; ferritin was measured in participants with elevated iron concentrations or transferrin saturation > 48%. Participants with elevated ferritin levels underwent further evaluation. Eight White men were diagnosed to have hemochromatosis (frequency 0.0039 in Whites, 0.0053 in White men). The estimated cost per case detected was $8826. Family members of two participants with hemochromatosis were also diagnosed to have hemochromatosis or iron overload. We conclude that detecting hemochromatosis in a workplace multiphasic health screening program is efficacious and economical.

Non-transferrin bound iron: a key role in iron overload and iron toxicity.

PubMed

Brissot, Pierre; Ropert, Martine; Le Lan, Caroline; Loréal, Olivier

2012-03-01

Besides transferrin iron, which represents the normal form of circulating iron, non-transferrin bound iron (NTBI) has been identified in the plasma of patients with various pathological conditions in which transferrin saturation is significantly elevated. To show that: i) NTBI is present not only during chronic iron overload disorders (hemochromatosis, transfusional iron overload) but also in miscellaneous diseases which are not primarily iron overloaded conditions; ii) this iron species represents a potentially toxic iron form due to its high propensity to induce reactive oxygen species and is responsible for cellular damage not only at the plasma membrane level but also towards different intracellular organelles; iii) the NTBI concept may be expanded to include intracytosolic iron forms which are not linked to ferritin, the major storage protein which exerts, at the cellular level, the same type of protective effect towards the intracellular environment as transferrin in the plasma. Plasma NTBI and especially labile plasma iron determinations represent a new important biological tool since elimination of this toxic iron species is a major therapeutic goal. The NTBI approach represents an important mechanistic concept for explaining cellular iron excess and toxicity and provides new important biochemical diagnostic tools. This article is part of a Special Issue entitled Transferrins: Molecular mechanisms of iron transport and disorders. Copyright © 2011 Elsevier B.V. All rights reserved.

PfeT, a P1B4 -type ATPase, effluxes ferrous iron and protects Bacillus subtilis against iron intoxication.

PubMed

Guan, Guohua; Pinochet-Barros, Azul; Gaballa, Ahmed; Patel, Sarju J; Argüello, José M; Helmann, John D

2015-11-01

Iron is an essential element for nearly all cells and limited iron availability often restricts growth. However, excess iron can also be deleterious, particularly when cells expressing high affinity iron uptake systems transition to iron rich environments. Bacillus subtilis expresses numerous iron importers, but iron efflux has not been reported. Here, we describe the B. subtilis PfeT protein (formerly YkvW/ZosA) as a P1B4 -type ATPase in the PerR regulon that serves as an Fe(II) efflux pump and protects cells against iron intoxication. Iron and manganese homeostasis in B. subtilis are closely intertwined: a pfeT mutant is iron sensitive, and this sensitivity can be suppressed by low levels of Mn(II). Conversely, a pfeT mutant is more resistant to Mn(II) overload. In vitro, the PfeT ATPase is activated by both Fe(II) and Co(II), although only Fe(II) efflux is physiologically relevant in wild-type cells, and null mutants accumulate elevated levels of intracellular iron. Genetic studies indicate that PfeT together with the ferric uptake repressor (Fur) cooperate to prevent iron intoxication, with iron sequestration by the MrgA mini-ferritin playing a secondary role. Protection against iron toxicity may also be a key role for related P1B4 -type ATPases previously implicated in bacterial pathogenesis. © 2015 John Wiley & Sons Ltd.

Large G protein α-subunit XLαs limits clathrin-mediated endocytosis and regulates tissue iron levels in vivo.

PubMed

He, Qing; Bouley, Richard; Liu, Zun; Wein, Marc N; Zhu, Yan; Spatz, Jordan M; Wang, Chia-Yu; Divieti Pajevic, Paola; Plagge, Antonius; Babitt, Jodie L; Bastepe, Murat

2017-11-07

Alterations in the activity/levels of the extralarge G protein α-subunit (XLαs) are implicated in various human disorders, such as perinatal growth retardation. Encoded by GNAS , XLαs is partly identical to the α-subunit of the stimulatory G protein (Gsα), but the cellular actions of XLαs remain poorly defined. Following an initial proteomic screen, we identified sorting nexin-9 (SNX9) and dynamins, key components of clathrin-mediated endocytosis, as binding partners of XLαs. Overexpression of XLαs in HEK293 cells inhibited internalization of transferrin, a process that depends on clathrin-mediated endocytosis, while its ablation by CRISPR/Cas9 in an osteocyte-like cell line (Ocy454) enhanced it. Similarly, primary cardiomyocytes derived from XLαs knockout (XLKO) pups showed enhanced transferrin internalization. Early postnatal XLKO mice showed a significantly higher degree of cardiac iron uptake than wild-type littermates following iron dextran injection. In XLKO neonates, iron and ferritin levels were elevated in heart and skeletal muscle, where XLαs is normally expressed abundantly. XLKO heart and skeletal muscle, as well as XLKO Ocy454 cells, showed elevated SNX9 protein levels, and siRNA-mediated knockdown of SNX9 in XLKO Ocy454 cells prevented enhanced transferrin internalization. In transfected cells, XLαs also inhibited internalization of the parathyroid hormone and type 2 vasopressin receptors. Internalization of transferrin and these G protein-coupled receptors was also inhibited in cells expressing an XLαs mutant missing the Gα portion, but not Gsα or an N-terminally truncated XLαs mutant unable to interact with SNX9 or dynamin. Thus, XLαs restricts clathrin-mediated endocytosis and plays a critical role in iron/transferrin uptake in vivo. Published under the PNAS license.

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

The interplay between siderophore secretion and coupled iron and copper transport in the heterocyst-forming cyanobacterium Anabaena sp. PCC 7120.

PubMed

Nicolaisen, Kerstin; Hahn, Alexander; Valdebenito, Marianne; Moslavac, Suncana; Samborski, Anastazia; Maldener, Iris; Wilken, Corinna; Valladares, Ana; Flores, Enrique; Hantke, Klaus; Schleiff, Enrico

2010-11-01

Iron uptake is essential for Gram-negative bacteria including cyanobacteria. In cyanobacteria, however, the iron demand is higher than in proteobacteria due to the function of iron as a cofactor in photosynthesis and nitrogen fixation, but our understanding of iron uptake by cyanobacteria stands behind the knowledge in proteobacteria. Here, two genes involved in this process in the heterocyst-forming cyanobacterium Anabaena sp. PCC 7120 were identified. ORF all4025 encodes SchE, a putative cytoplasmic membrane-localized transporter involved in TolC-dependent siderophore secretion. Inactivation of schE resulted in an enhanced sensitivity to high metal concentrations and decreased secretion of hydroxamate-type siderophores. ORF all4026 encodes a predicted outer membrane-localized TonB-dependent iron transporter, IacT. Inactivation of iacT resulted in decreased sensitivity to elevated iron and copper levels. Expression of iacT from the artificial trc promoter (P(trc)) resulted in sensitization against tested metals. Further analysis showed that iron and copper effects are synergistic because a decreased supply of iron induced a significant decrease of copper levels in the iacT insertion mutant but an increase of those levels in the strain carrying P(trc)-iacT. Our results unravel a link between iron and copper homeostasis in Anabaena sp. PCC 7120. Copyright © 2010 Elsevier B.V. All rights reserved.

Relationships between iron dose, hospitalizations and mortality in incident haemodialysis patients: a propensity-score matched approach.

PubMed

Varas, Javier; Ramos, Rosa; Aljama, Pedro; Pérez-García, Rafael; Moreso, Francesc; Pinedo, Miguel; Ignacio Merello, José; Stuard, Stefano; Canaud, Bernard; Martín-Malo, Alejandro

2018-01-01

Intravenous iron management is common in the haemodialysis population. However, the safest dosing strategy remains uncertain, in terms of the risk of hospitalization and mortality. We aimed to determine the effects of cumulative monthly iron doses on mortality and hospitalization. This multicentre observational retrospective propensity-matched score study included 1679 incident haemodialysis patients. We measured baseline demographic variables, haemodialysis clinical parameters and laboratory analytical values. We compared outcomes among quartiles of cumulative iron dose (mg/kg/month). We implemented propensity-score matching (PSM) to reduce confounding due to indication. In the PSM cohort (330 patients), we compared outcomes between groups that received cumulative iron doses above and below 5.66 mg/kg/month. Kaplan-Meier analyses showed that the high iron dose group had significantly worse survival than the low iron dose group. A univariate analysis indicated that the monthly iron dose could significantly predict mortality. However, a multivariate regression did not confirm that finding. The multivariate regression analysis revealed that iron doses  >5.58 mg/kg/month were not associated with elevated mortality risk, but they were associated with elevated risks of all-cause and cardiovascular-related hospitalizations. These results were ratified in the PSM population. Intravenous iron administration is advisable for maintaining haemoglobin levels in patients that receive haemodialysis. Our data suggested that large monthly iron doses, adjusted for body weight, were associated with more hospitalizations, but not with mortality or infection-related hospitalizations. © The Author 2017. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.

Obesity as an emerging risk factor for iron deficiency.

PubMed

Aigner, Elmar; Feldman, Alexandra; Datz, Christian

2014-09-11

Iron homeostasis is affected by obesity and obesity-related insulin resistance in a many-facetted fashion. On one hand, iron deficiency and anemia are frequent findings in subjects with progressed stages of obesity. This phenomenon has been well studied in obese adolescents, women and subjects undergoing bariatric surgery. On the other hand, hyperferritinemia with normal or mildly elevated transferrin saturation is observed in approximately one-third of patients with metabolic syndrome (MetS) or nonalcoholic fatty liver disease (NAFLD). This constellation has been named the "dysmetabolic iron overload syndrome (DIOS)". Both elevated body iron stores and iron deficiency are detrimental to health and to the course of obesity-related conditions. Iron deficiency and anemia may impair mitochondrial and cellular energy homeostasis and further increase inactivity and fatigue of obese subjects. Obesity-associated inflammation is tightly linked to iron deficiency and involves impaired duodenal iron absorption associated with low expression of duodenal ferroportin (FPN) along with elevated hepcidin concentrations. This review summarizes the current understanding of the dysregulation of iron homeostasis in obesity.

Deferasirox improves hematologic and hepatic function with effective reduction of serum ferritin and liver iron concentration in transfusional iron overload patients with myelodysplastic syndrome or aplastic anemia.

PubMed

Cheong, June-Won; Kim, Hyeoung-Joon; Lee, Kyoo-Hyung; Yoon, Sung-Soo; Lee, Jae Hoon; Park, Hee-Sook; Kim, Ho Young; Shim, Hyeok; Seong, Chu-Myung; Kim, Chul Soo; Chung, Jooseop; Hyun, Myung Soo; Jo, Deog-Yeon; Jung, Chul Won; Sohn, Sang Kyun; Yoon, Hwi-Joong; Kim, Byung Soo; Joo, Young-Don; Park, Chi-Young; Min, Yoo Hong

2014-06-01

Transfusional iron overload and its consequences are challenges in chronically transfused patients with myelodysplastic syndromes (MDSs) or aplastic anemia (AA). This was a prospective, multicenter, open-label study to investigate the efficacy of deferasirox (DFX) by serial measurement of serum ferritin (S-ferritin) level, liver iron concentration (LIC) level using relaxation rates magnetic resonance imaging, and other laboratory variables in patients with MDS or AA. A total of 96 patients showing S-ferritin level of at least 1000 ng/mL received daily DFX for up to 1 year. At the end of the study, S-ferritin level was significantly decreased in MDS (p=0.02366) and AA (p=0.0009). LIC level was also significantly reduced by more than 6.7 mg Fe/g dry weight from baseline. Hemoglobin level and platelet counts were significantly increased from baseline (p=0.002 and p=0.025, respectively) for patients showing significant anemia or thrombocytopenia. Elevated alanine aminotransferase was also significantly decreased from baseline. This study shows that DFX is effective in reducing S-ferritin and LIC level in transfusional iron overload patients with MDS or AA and is well tolerated. In addition, positive effects in hematologic and hepatic function can be expected with DFX. Iron chelation treatment should be considered in transfused patients with MDS and AA when transfusion-related iron overload is documented. © 2013 AABB.

Dysregulation of iron and copper homeostasis in nonalcoholic fatty liver

PubMed Central

Aigner, Elmar; Weiss, Günter; Datz, Christian

2015-01-01

Elevated iron stores as indicated by hyperferritinemia with normal or mildly elevated transferrin saturation and mostly mild hepatic iron deposition are a characteristic finding in subjects with non-alcoholic fatty liver disease (NAFLD). Excess iron is observed in approximately one third of NAFLD patients and is commonly referred to as the “dysmetabolic iron overload syndrome”. Clinical evidence suggests that elevated body iron stores aggravate the clinical course of NAFLD with regard to liver-related and extrahepatic disease complications which relates to the fact that excess iron catalyses the formation of toxic hydroxyl-radicals subsequently resulting in cellular damage. Iron removal improves insulin sensitivity, delays the onset of type 2 diabetes mellitus, improves pathologic liver function tests and likewise ameliorates NAFLD histology. Several mechanisms contribute to pathologic iron accumulation in NAFLD. These include impaired iron export from hepatocytes and mesenchymal Kupffer cells as a consequence of imbalances in the concentrations of iron regulatory factors, such as hepcidin, cytokines, copper or other dietary factors. This review summarizes the knowledge about iron homeostasis in NAFLD and the rationale for its therapeutic implications. PMID:25729473

Management of Anemia in Patients with Inflammatory Bowel Disease (IBD).

PubMed

Patel, Dhruvan; Trivedi, Chinmay; Khan, Nabeel

2018-03-01

Anemia is the most common complication as well as an extra intestinal manifestation of inflammatory bowel disease (IBD). It is associated with a significant impact on patient's quality of life (QoL); as well it represents a common cause of frequent hospitalization, delay of hospital inpatient discharge and overall increased healthcare burden. In spite of all these, anemia is still often underdiagnosed and undertreated. Our aim in this review is to provide a pathway for physicians to help them achieve early diagnosis as well as timely and appropriate treatment of anemia which in turn would hopefully reduce the prevalence and subsequent complications of this condition among IBD patients. The etiology of anemia among IBD patients is most commonly due to iron deficiency anemia (IDA) followed by anemia of chronic disease. Despite this, more than a third of anemic ulcerative colitis (UC) patients are not tested for IDA and among those tested and diagnosed with IDA, a quarter are not treated with iron replacement therapy. A new algorithm has been validated to predict who will develop moderate to severe anemia at the time of UC diagnosis. While oral iron is effective for the treatment of mild iron deficiency-related anemia, the absorption of iron is influenced by chronic inflammatory states as a consequence of the presence of elevated levels of hepcidin. Also, it is important to recognize that ferritin is elevated in chronic inflammatory states and among patients with active IBD, ferritin levels less than 100 are considered to be diagnostic of iron deficiency. Newer formulations of intra-venous (IV) iron have a good safety profile and can be used for replenishment of iron stores and prevention of iron deficiency in the future. Routine screening for anemia is important among patients with IBD. The cornerstone for the accurate management of anemia in IBD patients lies in accurately diagnosing the type of anemia. All IBD patients with IDA should be considered appropriate for therapy with iron supplementation whereas IV administration of iron is recommended in patients with clinically active IBD, or for patients who are previously intolerant to oral iron, with hemoglobin levels below 10 g/dL, and in patients who need erythropoiesis-stimulating agents (ESAs). As the recurrence of anemia is common after resolution, the monitoring for recurrent anemia is equally important during the course of therapy.

Overload of iron in the skin of patients with varicose ulcers. Possible contributing role of iron accumulation in progression of the disease

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

Ackerman, Z.; Seidenbaum, M.; Loewenthal, E.

1988-09-01

The brown pigmentation of the skin associated with venous ulceration is caused by increased local iron deposition. Diagnostic x-ray spectrometry, a method based on x-ray fluorescence analysis, was used for the noninvasive determination of iron levels in the skin of patients with venous ulceration. The mean (+/- SEM) iron concentration in the skin around the venous ulcer was elevated, compared with control values of nonulcerated skin (250 +/- 54 vs 128 +/- 39 micrograms) and compared with normal skin from the forearm (250 +/- 54 vs 14 +/- 2.5 micrograms). These data suggest that dermal iron deposition may not bemore » an incidental by-product of increased venous pressure, but may actively perpetuate tissue damage in venous ulcerations.« less

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 deficiency associated with higher blood lead in children living in contaminated environments.

PubMed Central

Bradman, A; Eskenazi, B; Sutton, P; Athanasoulis, M; Goldman, L R

2001-01-01

The evidence that iron deficiency increases lead child exposure is based primarily on animal data and limited human studies, and some of this evidence is contradictory. No studies of iron status and blood lead levels in children have accounted for environmental lead contamination and, therefore, the source of their exposure. Thus, no studies have directly determined whether iron deficiency modifies the relationship of environmental lead and blood lead. In this study, we compared blood lead levels of iron-deficient and iron-replete children living in low, medium, or highly contaminated environments. Measurements of lead in paint, soil, dust, and blood, age of housing, and iron status were collected from 319 children ages 1-5. We developed two lead exposure factors to summarize the correlated exposure variables: Factor 1 summarized all environmental measures, and Factor 2 was weighted for lead loading of house dust. The geometric mean blood lead level was 4.9 microg/dL; 14% exceeded 10 microg/dL. Many of the children were iron deficient (24% with ferritin < 12 ng/dL). Seventeen percent of soil leads exceeded 500 microg/g, and 23% and 63% of interior and exterior paint samples exceeded 5,000 microg/g. The unadjusted geometric mean blood lead level for iron-deficient children was higher by 1 microg/dL; this difference was greater (1.8 microg/dL) after excluding Asians. Blood lead levels were higher for iron-deficient children for each tertile of exposure as estimated by Factors 1 and 2 for non-Asian children. Elevated blood lead among iron-deficient children persisted after adjusting for potential confounders by multivariate regression; the largest difference in blood lead levels between iron-deficient and -replete children, approximately 3 microg/dL, was among those living in the most contaminated environments. Asian children had a paradoxical association of sufficient iron status and higher blood lead level, which warrants further investigation. Improving iron status, along with reducing exposures, may help reduce blood lead levels among most children, especially those living in the most contaminated environments. PMID:11675273

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.

Hormone Replacement Therapy, Iron, and Breast Cancer

DTIC Science & Technology

2004-11-01

accumulates due to the mutation of the HFE gene (hemochromatosis EeJ, iron elevated in the mouse body mimics the post-menopausal condition. In the present...model. Since iron slowly accumulates due to the mutation of the HFE gene (hemochromatosis Fe), iron elevated in the mouse body mimics the post...menopausal condition. Development of iron overloaded transgenic mice: The murine HFE gene is structurally similar to the human gene . Four different HFE gene

Iron, Oxidative Stress, and Δ9 Stearoyl-CoenzymeA Desaturase Index (C16:1/C16:0): An Analysis Applying the National Health and Nutrition Examination Survey 2003–04

PubMed Central

Wu, Yue; Baylin, Ana; Colacino, Justin A

2018-01-01

Abstract Background Stearoyl-coenzyme A desaturase (SCD) is a key enzyme in fatty acid metabolism, and elevated SCD activity is associated with multiple adverse health outcomes. Diet, hormone levels, and environmental exposures are potential factors affecting SCD activity. Less is known about the relationship between micronutrients, including iron, and SCD activity. Objective The aim of this study was to investigate the association between serum ferritin level, a biomarker of circulating iron levels, and the Δ9 desaturase index (C16:1/C16:0), a biomarker of estimated SCD activity, among women in the United States. Methods The association between serum ferritin and the Δ9 desaturase index was assessed in a cross-sectional study of 447 female participants, aged 20–49 y, from NHANES 2003–2004. The multivariate analyses were performed utilizing generalized linear modeling, adjusting for potential confounders. Mediation of the relationship between serum ferritin and Δ9 desaturase index by γ-glutamyltranspeptidase (GGT), a biomarker of oxidative stress, was also assessed. Results Increased ferritin was significantly associated with a higher Δ9 desaturase index. Adjusting for waist circumference, age, race, and cotinine levels, an interquartile range increase in serum ferritin corresponded to 3.92% (95% CI: 0.88%, 7.05%) higher Δ9 desaturase index. GGT, the biomarker used to measure oxidative stress level, did not appear to mediate the association between ferritin and Δ9 desaturase index. After stratifying by pregnancy status, these associations were limited to nonpregnant individuals. Conclusions Elevated SCD activity may be associated with increased iron storage inside the human body; the association did not appear to be mediated via oxidative stress, as estimated by GGT levels.

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.

39. PORTAL ELEVATION. Photocopy of engraving from illustrated pamphlet titled ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

39. PORTAL ELEVATION. Photocopy of engraving from illustrated pamphlet titled 'Wrought Iron Bridges Built by Wrought Iron Bridge Company,' Wrought Iron Bridge Company, Canton, Ohio, 1885 (artist unknown). - Emlenton Bridge, Spanning Allegheny River, Travel Route 38 (Legislative Route 75), Emlenton, Venango County, PA

Ascorbic acid deficiency, iron overload and alcohol abuse underlie the severe osteoporosis in black African patients with hip fractures--a bone histomorphometric study.

PubMed

Schnitzler, C M; Schnaid, E; MacPhail, A P; Mesquita, J M; Robson, H J

2005-02-01

Osteoporosis and femoral neck fractures (FNF) are uncommon in black Africans although osteoporosis accompanying iron overload (from traditional beer brewed in iron containers) associated with ascorbic acid deficiency (oxidative catabolism by iron) has been described from sub-Saharan Africa. This study describes histomorphometric findings of iliac crest bone biopsies and serum biochemical markers of iron overload and of alcohol abuse and ascorbic acid levels in 50 black patients with FNFs (29 M, 21 F), age 62 years (40-95) years (median [min-max]), and in age- and gender-matched black controls. We found evidence of iron overload in 88% of patients and elevated markers of alcohol abuse in 72%. Significant correlations between markers of iron overload and of alcohol abuse reflect a close association between the two toxins. Patients had higher levels of iron markers, i.e., siderin deposits in bone marrow (P < 0.0001), chemical non-heme bone iron (P = 0.012), and serum ferritin (P = 0.017) than controls did. Leukocyte ascorbic acid levels were lower (P = 0.0008) than in controls. The alcohol marker mean red blood cell volume was elevated (P = 0.002) but not liver enzymes or uric acid. Bone volume, trabecular thickness, and trabecular number were lower, and trabecular separation was greater in patients than in controls, all at P < 0.0005; volume, surface, and thickness of osteoid were lower and eroded surface was greater, all at P < 0.0001. There was no osteomalacia. Ascorbic acid deficiency accounted significantly for decrease in bone volume and trabecular number, and increase in trabecular separation, osteoid surface, and eroded surface; iron overload accounted for a reduction in mineral apposition rate. Alcohol markers correlated negatively with osteoblast surface and positively with eroded surface. Relative to reported data in white FNF patients, the osteoporosis was more severe, showed lower osteoid variables and greater eroded surface; FNFs occurred 12 years earlier and were more common among men. We conclude that the osteoporosis underlying FNFs in black Africans is severe, with marked uncoupling of resorption and formation in favor of resorption. All three factors--ascorbic acid deficiency, iron overload, and alcohol abuse--contributed to the osteoporosis, in that order.

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.

The Effects of Dietary Iron and Capsaicin on Hemoglobin, Blood Glucose, Insulin Tolerance, Cholesterol, and Triglycerides, in Healthy and Diabetic Wistar Rats.

PubMed

Márquez-Ibarra, Adriana; Huerta, Miguel; Villalpando-Hernández, Salvador; Ríos-Silva, Mónica; Díaz-Reval, María I; Cruzblanca, Humberto; Mancilla, Evelyn; Trujillo, Xóchitl

2016-01-01

Our aim was to assess the effects of dietary iron, and the compound capsaicin, on hemoglobin as well as metabolic indicators including blood glucose, cholesterol, triglycerides, insulin, and glucose tolerance. Our animal model was the Wistar rat, fed a chow diet, with or without experimentally induced diabetes. Diabetic males were fed control, low, or high-iron diets, the latter, with or without capsaicin. Healthy rats were fed identical diets, but without the capsaicin supplement. We then measured the parameters listed above, using the Student t-test and ANOVA, to compare groups. Healthy rats fed a low-iron diet exhibited significantly reduced total cholesterol and triglyceride levels, compared with rats fed a control diet. Significantly reduced blood lipid was also provoked by low dietary iron in diabetic rats, compared with those fed a control diet. Insulin, and glucose tolerance was only improved in healthy rats fed the low-iron diet. Significant increases in total cholesterol were found in diabetic rats fed a high-iron diet, compared with healthy rats fed the same diet, although no statistical differences were found for triglycerides. Hemoglobin levels, which were not statistically different in diabetic versus healthy rats fed the high-iron diet, fell when capsaicin was added. Capsaicin also provoked a fall in the level of cholesterol and triglycerides in diabetic animals, versus diabetics fed with the high iron diet alone. In conclusion, low levels of dietary iron reduced levels of serum triglycerides, hemoglobin, and cholesterol, and significantly improved insulin, and glucose tolerance in healthy rats. In contrast, a high-iron diet increased cholesterol significantly, with no significant changes to triglyceride concentrations. The addition of capsaicin to the high-iron diet (for diabetic rats) further reduced levels of hemoglobin, cholesterol, and triglycerides. These results suggest that capsaicin, may be suitable for the treatment of elevated hemoglobin, in patients.

Obesity as an Emerging Risk Factor for Iron Deficiency

PubMed Central

Aigner, Elmar; Feldman, Alexandra; Datz, Christian

2014-01-01

Iron homeostasis is affected by obesity and obesity-related insulin resistance in a many-facetted fashion. On one hand, iron deficiency and anemia are frequent findings in subjects with progressed stages of obesity. This phenomenon has been well studied in obese adolescents, women and subjects undergoing bariatric surgery. On the other hand, hyperferritinemia with normal or mildly elevated transferrin saturation is observed in approximately one-third of patients with metabolic syndrome (MetS) or nonalcoholic fatty liver disease (NAFLD). This constellation has been named the “dysmetabolic iron overload syndrome (DIOS)”. Both elevated body iron stores and iron deficiency are detrimental to health and to the course of obesity-related conditions. Iron deficiency and anemia may impair mitochondrial and cellular energy homeostasis and further increase inactivity and fatigue of obese subjects. Obesity-associated inflammation is tightly linked to iron deficiency and involves impaired duodenal iron absorption associated with low expression of duodenal ferroportin (FPN) along with elevated hepcidin concentrations. This review summarizes the current understanding of the dysregulation of iron homeostasis in obesity. PMID:25215659

Proceedings: 2002 Workshop on Pressurized Water Reactor Elevated Feedwater Iron Transport

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

None

2002-11-01

Some pressurized water reactor (PWR) stations have experienced difficulty with maintaining feedwater (FW) iron concentrations below recommended concentration on a regular basis. A workshop held on September 17-18 in Dana Point, California, addressed the challenge of elevated feedwater iron transport in PWRs.

Serum Iron Level Is Associated with Time to Antibiotics in Cystic Fibrosis.

PubMed

Gifford, Alex H; Dorman, Dana B; Moulton, Lisa A; Helm, Jennifer E; Griffin, Mary M; MacKenzie, Todd A

2015-12-01

Serum levels of hepcidin-25, a peptide hormone that reduces blood iron content, are elevated when patients with cystic fibrosis (CF) develop pulmonary exacerbation (PEx). Because hepcidin-25 is unavailable as a clinical laboratory test, we questioned whether a one-time serum iron level was associated with the subsequent number of days until PEx, as defined by the need to receive systemic antibiotics (ABX) for health deterioration. Clinical, biochemical, and microbiological parameters were simultaneously checked in 54 adults with CF. Charts were reviewed to determine when they first experienced a PEx after these parameters were assessed. Time to ABX was compared in subgroups with and without specific attributes. Multivariate linear regression was used to identify parameters that significantly explained variation in time to ABX. In univariate analyses, time to ABX was significantly shorter in subjects with Aspergillus-positive sputum cultures and CF-related diabetes. Multivariate linear regression models demonstrated that shorter time to ABX was associated with younger age, lower serum iron level, and Aspergillus sputum culture positivity. Serum iron, age, and Aspergillus sputum culture positivity are factors associated with shorter time to subsequent PEx in CF adults. © 2015 Wiley Periodicals, Inc.

Iron Status and the Acute Post-Exercise Hepcidin Response in Athletes

PubMed Central

Peeling, Peter; Sim, Marc; Badenhorst, Claire E.; Dawson, Brian; Govus, Andrew D.; Abbiss, Chris R.; Swinkels, Dorine W.; Trinder, Debbie

2014-01-01

This study explored the relationship between serum ferritin and hepcidin in athletes. Baseline serum ferritin levels of 54 athletes from the control trial of five investigations conducted in our laboratory were considered; athletes were grouped according to values <30 μg/L (SF<30), 30–50 μg/L (SF30–50), 50–100 μg/L (SF50–100), or >100 μg/L (SF>100). Data pooling resulted in each athlete completing one of five running sessions: (1) 8×3 min at 85% vVO2peak; (2) 5×4 min at 90% vVO2peak; (3) 90 min continuous at 75% vVO2peak; (4) 40 min continuous at 75% vVO2peak; (5) 40 min continuous at 65% vVO2peak. Athletes from each running session were represented amongst all four groups; hence, the mean exercise duration and intensity were not different (p>0.05). Venous blood samples were collected pre-, post- and 3 h post-exercise, and were analysed for serum ferritin, iron, interleukin-6 (IL-6) and hepcidin-25. Baseline and post-exercise serum ferritin levels were different between groups (p<0.05). There were no group differences for pre- or post-exercise serum iron or IL-6 (p>0.05). Post-exercise IL-6 was significantly elevated compared to baseline within each group (p<0.05). Pre- and 3 h post-exercise hepcidin-25 was sequentially greater as the groups baseline serum ferritin levels increased (p<0.05). However, post-exercise hepcidin levels were only significantly elevated in three groups (SF30–50, SF50–100, and SF>100; p<0.05). An athlete's iron stores may dictate the baseline hepcidin levels and the magnitude of post-exercise hepcidin response. Low iron stores suppressed post-exercise hepcidin, seemingly overriding any inflammatory-driven increases. PMID:24667393

Excess adiposity, inflammation, and iron-deficiency in female adolescents.

PubMed

Tussing-Humphreys, Lisa M; Liang, Huifang; Nemeth, Elizabeta; Freels, Sally; Braunschweig, Carol A

2009-02-01

Iron deficiency is more prevalent in overweight children and adolescents but the mechanisms that underlie this condition remain unclear. The purpose of this cross-sectional study was to assess the relationship between iron status and excess adiposity, inflammation, menarche, diet, physical activity, and poverty status in female adolescents included in the National Health and Nutrition Examination Survey 2003-2004 dataset. Descriptive and simple comparative statistics (t test, chi(2)) were used to assess differences between normal-weight (5th < or = body mass index [BMI] percentile <85th) and heavier-weight girls (< or = 85th percentile for BMI) for demographic, biochemical, dietary, and physical activity variables. In addition, logistic regression analyses predicting iron deficiency and linear regression predicting serum iron levels were performed. Heavier-weight girls had an increased prevalence of iron deficiency compared to those with normal weight. Dietary iron, age of and time since first menarche, poverty status, and physical activity were similar between the two groups and were not independent predictors of iron deficiency or log serum iron levels. Logistic modeling predicting iron deficiency revealed having a BMI > or = 85th percentile and for each 1 mg/dL increase in C-reactive protein the odds ratio for iron deficiency more than doubled. The best-fit linear model to predict serum iron levels included both serum transferrin receptor and C-reactive protein following log-transformation for normalization of these variables. Findings indicate that heavier-weight female adolescents are at greater risk for iron deficiency and that inflammation stemming from excess adipose tissue contributes to this phenomenon. Food and nutrition professionals should consider elevated BMI as an additional risk factor for iron deficiency in female adolescents.

Predicting redox-sensitive contaminant concentrations in groundwater using random forest classification

NASA Astrophysics Data System (ADS)

Tesoriero, Anthony J.; Gronberg, Jo Ann; Juckem, Paul F.; Miller, Matthew P.; Austin, Brian P.

2017-08-01

Machine learning techniques were applied to a large (n > 10,000) compliance monitoring database to predict the occurrence of several redox-active constituents in groundwater across a large watershed. Specifically, random forest classification was used to determine the probabilities of detecting elevated concentrations of nitrate, iron, and arsenic in the Fox, Wolf, Peshtigo, and surrounding watersheds in northeastern Wisconsin. Random forest classification is well suited to describe the nonlinear relationships observed among several explanatory variables and the predicted probabilities of elevated concentrations of nitrate, iron, and arsenic. Maps of the probability of elevated nitrate, iron, and arsenic can be used to assess groundwater vulnerability and the vulnerability of streams to contaminants derived from groundwater. Processes responsible for elevated concentrations are elucidated using partial dependence plots. For example, an increase in the probability of elevated iron and arsenic occurred when well depths coincided with the glacial/bedrock interface, suggesting a bedrock source for these constituents. Furthermore, groundwater in contact with Ordovician bedrock has a higher likelihood of elevated iron concentrations, which supports the hypothesis that groundwater liberates iron from a sulfide-bearing secondary cement horizon of Ordovician age. Application of machine learning techniques to existing compliance monitoring data offers an opportunity to broadly assess aquifer and stream vulnerability at regional and national scales and to better understand geochemical processes responsible for observed conditions.

Predicting redox-sensitive contaminant concentrations in groundwater using random forest classification

USGS Publications Warehouse

Tesoriero, Anthony J.; Gronberg, Jo Ann M.; Juckem, Paul F.; Miller, Matthew P.; Austin, Brian P.

2017-01-01

Machine learning techniques were applied to a large (n > 10,000) compliance monitoring database to predict the occurrence of several redox-active constituents in groundwater across a large watershed. Specifically, random forest classification was used to determine the probabilities of detecting elevated concentrations of nitrate, iron, and arsenic in the Fox, Wolf, Peshtigo, and surrounding watersheds in northeastern Wisconsin. Random forest classification is well suited to describe the nonlinear relationships observed among several explanatory variables and the predicted probabilities of elevated concentrations of nitrate, iron, and arsenic. Maps of the probability of elevated nitrate, iron, and arsenic can be used to assess groundwater vulnerability and the vulnerability of streams to contaminants derived from groundwater. Processes responsible for elevated concentrations are elucidated using partial dependence plots. For example, an increase in the probability of elevated iron and arsenic occurred when well depths coincided with the glacial/bedrock interface, suggesting a bedrock source for these constituents. Furthermore, groundwater in contact with Ordovician bedrock has a higher likelihood of elevated iron concentrations, which supports the hypothesis that groundwater liberates iron from a sulfide-bearing secondary cement horizon of Ordovician age. Application of machine learning techniques to existing compliance monitoring data offers an opportunity to broadly assess aquifer and stream vulnerability at regional and national scales and to better understand geochemical processes responsible for observed conditions.

Proteomics of Pseudomonas aeruginosa Australian epidemic strain 1 (AES-1) cultured under conditions mimicking the cystic fibrosis lung reveals increased iron acquisition via the siderophore pyochelin.

PubMed

Hare, Nathan J; Soe, Cho Zin; Rose, Barbara; Harbour, Colin; Codd, Rachel; Manos, Jim; Cordwell, Stuart J

2012-02-03

Pseudomonas aeruginosa is an opportunistic pathogen that is the major cause of morbidity and mortality in patients with cystic fibrosis (CF). While most CF patients are thought to acquire P. aeruginosa from the environment, person-to-person transmissible strains have been identified in CF clinics worldwide, and the molecular basis for transmissibility remains poorly understood. We undertook a complementary proteomics approach to characterize protein profiles from a transmissible, acute isolate of the Australian epidemic strain 1 (AES-1R), the virulent burns/wound isolate PA14, and the poorly virulent, laboratory-associated strain PAO1 when grown in an artificial medium that mimics the CF lung environment compared to growth in standard laboratory medium. Proteins elevated in abundance in AES-1R included those involved in methionine and S-adenosylmethionine biosynthesis and in the synthesis of phenazines. Proteomic data were validated by measuring culture supernatant levels of the virulence factor pyocyanin, which is the final product of the phenazine pathway. AES-1R and PAO1 released higher extracellular levels of pyocyanin compared to PA14 when grown in conditions that mimic the CF lung. Proteins associated with biosynthesis of the iron-scavenging siderophore pyochelin (PchDEFGH and FptA) were also present at elevated abundance in AES-1R and at much higher levels than in PAO1, whereas they were reduced in PA14. These protein changes resulted phenotypically in increased extracellular iron acquisition potential and, specifically, elevated pyochelin levels in AES-1R culture supernatants as detected by chrome azurol-S assay and fluorometry, respectively. Transcript analysis of pyochelin genes (pchDFG and fptA) showed they were highly expressed during the early stage of growth in artificial sputum medium (18 h) but returned to basal levels following the establishment of microcolony growth (72 h) consistent with that observed in the CF lung. This provides further evidence that iron acquisition by pyochelin may play a role in the early stages of transmissible CF infection associated with AES-1R.

Hemochromatosis Enhances Tumor Progression via Upregulation of Intracellular Iron in Head and Neck Cancer

PubMed Central

Lenarduzzi, Michelle; Hui, Angela B. Y.; Yue, Shijun; Ito, Emma; Shi, Wei; Williams, Justin; Bruce, Jeff; Sakemura-Nakatsugawa, Noriko; Xu, Wei; Schimmer, Aaron; Liu, Fei-Fei

2013-01-01

Introduction Despite improvements in treatment strategies for head and neck squamous cell carcinoma (HNSCC), outcomes have not significantly improved; highlighting the importance of identifying novel therapeutic approaches to target this disease. To address this challenge, we proceeded to evaluate the role of iron in HNSCC. Experimental Design Expression levels of iron-related genes were evaluated in HNSCC cell lines using quantitative RT-PCR. Cellular phenotypic effects were assessed using viability (MTS), clonogenic survival, BrdU, and tumor formation assays. The prognostic significance of iron-related proteins was determined using immunohistochemistry. Results In a panel of HNSCC cell lines, hemochromatosis (HFE) was one of the most overexpressed genes involved in iron regulation. In vitro knockdown of HFE in HNSCC cell lines significantly decreased hepcidin (HAMP) expression and intracellular iron level. This in turn, resulted in a significant decrease in HNSCC cell viability, clonogenicity, DNA synthesis, and Wnt signalling. These cellular changes were reversed by re-introducing iron back into HNSCC cells after HFE knockdown, indicating that iron was mediating this phenotype. Concordantly, treating HNSCC cells with an iron chelator, ciclopirox olamine (CPX), significantly reduced viability and clonogenic survival. Finally, patients with high HFE expression experienced a reduced survival compared to patients with low HFE expression. Conclusions Our data identify HFE as potentially novel prognostic marker in HNSCC that promotes tumour progression via HAMP and elevated intracellular iron levels, leading to increased cellular proliferation and tumour formation. Hence, these findings suggest that iron chelators might have a therapeutic role in HNSCC management. PMID:23991213

Iron stores and obesity are negatively associated with ovarian volume and anti-Müllerian hormone levels in women with polycystic ovary syndrome.

PubMed

Yang, Jehn-Hsiahn; Chou, Chia-Hung; Yang, Wei-Shiung; Ho, Hong-Nerng; Yang, Yu-Shih; Chen, Mei-Jou

2015-12-01

Obesity and insulin resistance are associated with increased iron stores, but have conflicting effects on ovarian reserve in women with polycystic ovary syndrome (PCOS). Iron-catalyzed oxidative stress might be detrimental to ovarian tissue and granulosa cell function. In this study we determined the association between body iron stores, obesity, and ovarian reserve in women with PCOS. One hundred and fifty-six women diagnosed with PCOS according to Rotterdam criteria and 30 normoweight healthy control women were enrolled in this cross-sectional study. Ovarian volume, total antral follicle count, and the anti-Müllerian hormone (AMH) level were measured as an indicator of ovarian reserve. Ferritin and transferrin-bound iron levels were significantly higher in women with PCOS than normoweight controls. Obese women with PCOS had higher ferritin levels (p = 0.006), but lower AMH levels (p < 0.0001) than nonobese women with PCOS. Using univariate analysis, the AMH level and mean ovarian volume were inversely related to the ferritin level, homeostasis model assessment of insulin resistance, and body mass index in women with PCOS. Body mass index and ferritin level remained significantly correlated with a lower AMH level and reduced ovarian volume, respectively, after considering other confounding variables. An elevated ferritin level and obesity were negatively associated with ovarian volume and the AMH level, respectively, in women with PCOS. Copyright © 2015. Published by Elsevier B.V.

Lentiviral Nef suppresses iron uptake in a strain specific manner through inhibition of Transferrin endocytosis

PubMed Central

2014-01-01

Background Increased cellular iron levels are associated with high mortality in HIV-1 infection. Moreover iron is an important cofactor for viral replication, raising the question whether highly divergent lentiviruses actively modulate iron homeostasis. Here, we evaluated the effect on cellular iron uptake upon expression of the accessory protein Nef from different lentiviral strains. Results Surface Transferrin receptor (TfR) levels are unaffected by Nef proteins of HIV-1 and its simian precursors but elevated in cells expressing Nefs from most other primate lentiviruses due to reduced TfR internalization. The SIV Nef-mediated reduction of TfR endocytosis is dependent on an N-terminal AP2 binding motif that is not required for downmodulation of CD4, CD28, CD3 or MHCI. Importantly, SIV Nef-induced inhibition of TfR endocytosis leads to the reduction of Transferrin uptake and intracellular iron concentration and is accompanied by attenuated lentiviral replication in macrophages. Conclusion Inhibition of Transferrin and thereby iron uptake by SIV Nef might limit viral replication in myeloid cells. Furthermore, this new SIV Nef function could represent a virus-host adaptation that evolved in natural SIV-infected monkeys. PMID:24383984

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.

HFE Genotyping in Patients with Elevated Serum Iron Indices and Liver Diseases

PubMed Central

Evangelista, Andreia Silva; de Araújo, Thiago Ferreira; Abrantes-Lemos, Clarice Pires; Deguti, Marta Mitiko; Cançado, Eduardo Luiz Rachid

2015-01-01

Iron abnormalities in chronic liver disease may be the result of genetic diseases or secondary factors. The present study aimed to identify subjects with HFE-HH in order to describe the frequency of clinical manifestations, identify risk factors for iron elevation, and compare the iron profile of HFE-HH to other genotypes in liver disease patients. A total of 108 individuals with hepatic disease, transferrin saturation (TS) > 45%, and serum ferritin (SF) > 350 ng/mL were tested for HFE mutations. Two groups were characterized: C282Y/C282Y or C282Y/H63D genotypes (n = 16) were the HFE hereditary hemochromatosis (HFE-HH) group; and C282Y and H63D single heterozygotes, the H63D/H63D genotype, and wild-type were considered group 2 (n = 92). Nonalcoholic liver disease, alcoholism, and chronic hepatitis C were detected more frequently in group 2, whereas arthropathy, hepatocarcinoma, diabetes, and osteoporosis rates were significantly higher in the HFE-HH group. TS > 82%, SF > 2685 ng/mL, and serum iron > 178 μg/dL were the cutoffs for diagnosis of HFE-HH in patients with liver disease. Thus, in non-Caucasian populations with chronic liver disease, HFE-HH diagnosis is more predictable in those with iron levels higher than those proposed in current guidelines for the general population. PMID:25654085

Elevated catalase expression in a fungal pathogen is a double-edged sword of iron

PubMed Central

Belmonte, Rodrigo; Budge, Susan; Lopez Garcia, Angela; Lee, Keunsook K.; Bebes, Attila; Quinn, Janet

2017-01-01

Most fungal pathogens of humans display robust protective oxidative stress responses that contribute to their pathogenicity. The induction of enzymes that detoxify reactive oxygen species (ROS) is an essential component of these responses. We showed previously that ectopic expression of the heme-containing catalase enzyme in Candida albicans enhances resistance to oxidative stress, combinatorial oxidative plus cationic stress, and phagocytic killing. Clearly ectopic catalase expression confers fitness advantages in the presence of stress, and therefore in this study we tested whether it enhances fitness in the absence of stress. We addressed this using a set of congenic barcoded C. albicans strains that include doxycycline-conditional tetON-CAT1 expressors. We show that high basal catalase levels, rather than CAT1 induction following stress imposition, reduce ROS accumulation and cell death, thereby promoting resistance to acute peroxide or combinatorial stress. This conclusion is reinforced by our analyses of phenotypically diverse clinical isolates and the impact of stochastic variation in catalase expression upon stress resistance in genetically homogeneous C. albicans populations. Accordingly, cat1Δ cells are more sensitive to neutrophil killing. However, we find that catalase inactivation does not attenuate C. albicans virulence in mouse or invertebrate models of systemic candidiasis. Furthermore, our direct comparisons of fitness in vitro using isogenic barcoded CAT1, cat1Δ and tetON-CAT1 strains show that, while ectopic catalase expression confers a fitness advantage during peroxide stress, it confers a fitness defect in the absence of stress. This fitness defect is suppressed by iron supplementation. Also high basal catalase levels induce key iron assimilatory functions (CFL5, FET3, FRP1, FTR1). We conclude that while high basal catalase levels enhance peroxide stress resistance, they place pressure on iron homeostasis through an elevated cellular demand for iron, thereby reducing the fitness of C. albicans in iron-limiting tissues within the host. PMID:28542620

Elevated catalase expression in a fungal pathogen is a double-edged sword of iron.

PubMed

Pradhan, Arnab; Herrero-de-Dios, Carmen; Belmonte, Rodrigo; Budge, Susan; Lopez Garcia, Angela; Kolmogorova, Aljona; Lee, Keunsook K; Martin, Brennan D; Ribeiro, Antonio; Bebes, Attila; Yuecel, Raif; Gow, Neil A R; Munro, Carol A; MacCallum, Donna M; Quinn, Janet; Brown, Alistair J P

2017-05-01

Most fungal pathogens of humans display robust protective oxidative stress responses that contribute to their pathogenicity. The induction of enzymes that detoxify reactive oxygen species (ROS) is an essential component of these responses. We showed previously that ectopic expression of the heme-containing catalase enzyme in Candida albicans enhances resistance to oxidative stress, combinatorial oxidative plus cationic stress, and phagocytic killing. Clearly ectopic catalase expression confers fitness advantages in the presence of stress, and therefore in this study we tested whether it enhances fitness in the absence of stress. We addressed this using a set of congenic barcoded C. albicans strains that include doxycycline-conditional tetON-CAT1 expressors. We show that high basal catalase levels, rather than CAT1 induction following stress imposition, reduce ROS accumulation and cell death, thereby promoting resistance to acute peroxide or combinatorial stress. This conclusion is reinforced by our analyses of phenotypically diverse clinical isolates and the impact of stochastic variation in catalase expression upon stress resistance in genetically homogeneous C. albicans populations. Accordingly, cat1Δ cells are more sensitive to neutrophil killing. However, we find that catalase inactivation does not attenuate C. albicans virulence in mouse or invertebrate models of systemic candidiasis. Furthermore, our direct comparisons of fitness in vitro using isogenic barcoded CAT1, cat1Δ and tetON-CAT1 strains show that, while ectopic catalase expression confers a fitness advantage during peroxide stress, it confers a fitness defect in the absence of stress. This fitness defect is suppressed by iron supplementation. Also high basal catalase levels induce key iron assimilatory functions (CFL5, FET3, FRP1, FTR1). We conclude that while high basal catalase levels enhance peroxide stress resistance, they place pressure on iron homeostasis through an elevated cellular demand for iron, thereby reducing the fitness of C. albicans in iron-limiting tissues within the host.

Model of reticuloendothelial iron metabolism in humans: Abnormal behavior in idiopathic hemochromatosis and in inflammation

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

Fillet, G.; Beguin, Y.; Baldelli, L.

1989-08-01

Iron transport in the reticuloendothelial (RE) system plays a central role in iron metabolism, but its regulation has not been characterized physiologically in vivo in humans. In particular, why serum iron is elevated and RE cells are much less iron-loaded than parenchymal cells in idiopathic hemochromatosis is not known. The processing of erythrocyte iron by the RE system was studied after intravenous (IV) injection of 59Fe heat-damaged RBCs (HDRBCs) and 55Fe transferrin in normal subjects and in patients with iron deficiency, idiopathic hemochromatosis, inflammation, marrow aplasia, or hyperplastic erythropoiesis. Early release of 59Fe by the RE system was calculated frommore » the plasma iron turnover and the 59Fe plasma reappearance curve. Late release was calculated from the ratio of 59Fe/55Fe RBC utilization in 2 weeks. The partitioning of iron between the early (release from heme catabolism) and late (release from RE stores) phases depended on the size of RE iron stores, as illustrated by the inverse relationship observed between early release and plasma ferritin (P less than .001). There was a strong correlation between early release and the rate of change of serum iron levels during the first three hours in normal subjects (r = .85, P less than .001). Inflammation produced a blockade of the early release phase, whereas in idiopathic hemochromatosis early release was considerably increased as compared with subjects with similar iron stores. Based on these results, we describe a model of RE iron metabolism in humans. We conclude that the RE system appears to determine the diurnal fluctuations in serum iron levels through variations in the immediate output of heme iron. In idiopathic hemochromatosis, a defect of the RE cell in withholding iron freed from hemoglobin could be responsible for the high serum iron levels and low RE iron stores.« less

Iron supplementation at high altitudes induces inflammation and oxidative injury to lung tissues in rats

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

Salama, Samir A., E-mail: salama.3@buckeyemail.osu.edu; Department of Biochemistry, Faculty of Pharmacy, Al-Azhar University, Cairo 11751; Department of Pharmacology and GTMR Unit, College of Clinical Pharmacy, Taif University, Al-Haweiah, Taif 21974

2014-01-01

Exposure to high altitudes is associated with hypoxia and increased vulnerability to oxidative stress. Polycythemia (increased number of circulating erythrocytes) develops to compensate the high altitude associated hypoxia. Iron supplementation is, thus, recommended to meet the demand for the physiological polycythemia. Iron is a major player in redox reactions and may exacerbate the high altitudes-associated oxidative stress. The aim of this study was to explore the potential iron-induced oxidative lung tissue injury in rats at high altitudes (6000 ft above the sea level). Iron supplementation (2 mg elemental iron/kg, once daily for 15 days) induced histopathological changes to lung tissuesmore » that include severe congestion, dilatation of the blood vessels, emphysema in the air alveoli, and peribronchial inflammatory cell infiltration. The levels of pro-inflammatory cytokines (IL-1β, IL-6, and TNF-α), lipid peroxidation product and protein carbonyl content in lung tissues were significantly elevated. Moreover, the levels of reduced glutathione and total antioxidant capacity were significantly reduced. Co-administration of trolox, a water soluble vitamin E analog (25 mg/kg, once daily for the last 7 days of iron supplementation), alleviated the lung histological impairments, significantly decreased the pro-inflammatory cytokines, and restored the oxidative stress markers. Together, our findings indicate that iron supplementation at high altitudes induces lung tissue injury in rats. This injury could be mediated through excessive production of reactive oxygen species and induction of inflammatory responses. The study highlights the tissue injury induced by iron supplementation at high altitudes and suggests the co-administration of antioxidants such as trolox as protective measures. - Highlights: • Iron supplementation at high altitudes induced lung histological changes in rats. • Iron induced oxidative stress in lung tissues of rats at high altitudes. • Iron increased the levels of IL-1β, IL-6 and TNF-α in lung tissues at high altitudes. • Trolox alleviated the iron-induced histological and biochemical changes to the lungs.« less

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

Fibroblast growth factor 23, iron and inflammation - are they related in early stages of chronic kidney disease?

PubMed

Lukaszyk, Ewelina; Lukaszyk, Mateusz; Koc-Zorawska, Ewa; Bodzenta-Lukaszyk, Anna; Malyszko, Jolanta

2017-06-01

Fibroblast growth factor 23 (FGF-23) levels are elevated in impaired renal function. Inflammation and iron are potential regulators of FGF-23. The aim of the study was to evaluate the association between FGF-23 concentration, novel iron status biomarkers and inflammatory parameters among patients with early stages of chronic kidney disease (CKD). The study population included 84 patients with CKD in the early stage. Serum hemoglobin, fibrinogen, creatinine, iron, transferrin saturation and ferritin levels were measured using standard laboratory methods. Commercially available kits were used to measure: intact FGF-23, hepcidin, soluble transferrin receptor (sTfR), interleukin 6 (IL-6) and high-sensitivity C-reactive protein (hsCRP). In patients with CKD no differences in FGF-23 concentration according to iron status were observed. Lower iron concentration was associated with higher concentrations of hsCRP, IL-6 and fibrinogen. In univariate and multivariate analysis FGF-23 correlated with fibrinogen ( r = -0.23, p < 0.05) and eGFR ( r = -0.36, p < 0.05). FGF-23 is affected by kidney function and fibrinogen but not iron status parameters in the early stages of CKD. Our data are paving the way for further studies on the role of FGF-23 in iron metabolism, especially in early stages of CKD.

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

Washing older blood units before transfusion reduces plasma iron and improves outcomes in experimental canine pneumonia.

PubMed

Cortés-Puch, Irene; Wang, Dong; Sun, Junfeng; Solomon, Steven B; Remy, Kenneth E; Fernandez, Melinda; Feng, Jing; Kanias, Tamir; Bellavia, Landon; Sinchar, Derek; Perlegas, Andreas; Solomon, Michael A; Kelley, Walter E; Popovsky, Mark A; Gladwin, Mark T; Kim-Shapiro, Daniel B; Klein, Harvey G; Natanson, Charles

2014-02-27

In a randomized controlled blinded trial, 2-year-old purpose-bred beagles (n = 24), with Staphylococcus aureus pneumonia, were exchanged-transfused with either 7- or 42-day-old washed or unwashed canine universal donor blood (80 mL/kg in 4 divided doses). Washing red cells (RBC) before transfusion had a significantly different effect on canine survival, multiple organ injury, plasma iron, and cell-free hemoglobin (CFH) levels depending on the age of stored blood (all, P < .05 for interactions). Washing older units of blood improved survival rates, shock score, lung injury, cardiac performance and liver function, and reduced levels of non-transferrin bound iron and plasma labile iron. In contrast, washing fresh blood worsened all these same clinical parameters and increased CFH levels. Our data indicate that transfusion of fresh blood, which results in less hemolysis, CFH, and iron release, is less toxic than transfusion of older blood in critically ill infected subjects. However, washing older blood prevented elevations in plasma circulating iron and improved survival and multiple organ injury in animals with an established pulmonary infection. Our data suggest that fresh blood should not be washed routinely because, in a setting of established infection, washed RBC are prone to release CFH and result in worsened clinical outcomes.

Washing older blood units before transfusion reduces plasma iron and improves outcomes in experimental canine pneumonia

PubMed Central

Wang, Dong; Sun, Junfeng; Solomon, Steven B.; Remy, Kenneth E.; Fernandez, Melinda; Feng, Jing; Kanias, Tamir; Bellavia, Landon; Sinchar, Derek; Perlegas, Andreas; Solomon, Michael A.; Kelley, Walter E.; Popovsky, Mark A.; Gladwin, Mark T.; Kim-Shapiro, Daniel B.; Klein, Harvey G.; Natanson, Charles

2014-01-01

In a randomized controlled blinded trial, 2-year-old purpose-bred beagles (n = 24), with Staphylococcus aureus pneumonia, were exchanged-transfused with either 7- or 42-day-old washed or unwashed canine universal donor blood (80 mL/kg in 4 divided doses). Washing red cells (RBC) before transfusion had a significantly different effect on canine survival, multiple organ injury, plasma iron, and cell-free hemoglobin (CFH) levels depending on the age of stored blood (all, P < .05 for interactions). Washing older units of blood improved survival rates, shock score, lung injury, cardiac performance and liver function, and reduced levels of non-transferrin bound iron and plasma labile iron. In contrast, washing fresh blood worsened all these same clinical parameters and increased CFH levels. Our data indicate that transfusion of fresh blood, which results in less hemolysis, CFH, and iron release, is less toxic than transfusion of older blood in critically ill infected subjects. However, washing older blood prevented elevations in plasma circulating iron and improved survival and multiple organ injury in animals with an established pulmonary infection. Our data suggest that fresh blood should not be washed routinely because, in a setting of established infection, washed RBC are prone to release CFH and result in worsened clinical outcomes. PMID:24366359

Clinical features and dysfunctions of iron metabolism in Parkinson disease patients with hyper echogenicity in substantia nigra: a cross-sectional study.

PubMed

Yu, Shu-Yang; Cao, Chen-Jie; Zuo, Li-Jun; Chen, Ze-Jie; Lian, Teng-Hong; Wang, Fang; Hu, Yang; Piao, Ying-Shan; Li, Li-Xia; Guo, Peng; Liu, Li; Yu, Qiu-Jin; Wang, Rui-Dan; Chan, Piu; Chen, Sheng-di; Wang, Xiao-Min; Zhang, Wei

2018-01-17

Transcranial ultrasound is a useful tool for providing the evidences for the early diagnosis and differential diagnosis of Parkinson disease (PD). However, the relationship between hyper echogenicity in substantia nigra (SN) and clinical symptoms of PD patients remains unknown, and the role of dysfunction of iron metabolism on the pathogenesis of SN hyper echogenicity is unclear. PD patients was detected by transcranial sonography and divided into with no hyper echogenicity (PDSN-) group and with hyper echogenicity (PDSN+) group. Motor symptoms (MS) and non-motor symptoms (NMS) were evaluated, and the levels of iron and related proteins in serum and cerebrospinal fluid (CSF) were detected for PD patients. Data comparison between the two groups and correlation analyses were performed. PDSN+ group was significantly older, and had significantly older age of onset, more advanced Hohen-Yahr stage, higher SCOPA-AUT score and lower MoCA score than PDSN- group (P < 0.05). Compared with PDSN- group, the levels of transferrin and light-ferritin in serum and iron level in CSF were significantly elevated (P < 0.05), but ferroportin level in CSF was significantly decreased in PDSN+ group (P < 0.05). PD patients with hyper echogenicity in SN are older, at more advanced disease stage, have severer motor symptoms, and non-motor symptoms of cognitive impairment and autonomic dysfunction. Hyper echogenicity of SN in PD patients is related to dysfunction of iron metabolism, involving increased iron transport from peripheral system to central nervous system, reduction of intracellular iron release and excessive iron deposition in brain.

Calcium channel blockers ameliorate iron overload-associated hepatic fibrosis by altering iron transport and stellate cell apoptosis

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

Zhang, Ying

Liver fibrosis is the principal cause of morbidity and mortality in patients with iron overload. Calcium channel blockers (CCBs) can antagonize divalent cation entry into renal and myocardial cells and inhibit fibrogenic gene expression. We investigated the potential of CCBs to resolve iron overload-associated hepatic fibrosis. Kunming mice were assigned to nine groups (n = 8 per group): control, iron overload, deferoxamine, high and low dose verapamil, high and low dose nimodipine, and high and low dose diltiazem. Iron deposition and hepatic fibrosis were measured in mouse livers. Expression levels of molecules associated with transmembrane iron transport were determined bymore » molecular biology approaches. In vitro HSC-T6 cells were randomized into nine groups (the same groups as the mice). Changes in proliferation, apoptosis, and metalloproteinase expression in cells were detected to assess the anti-fibrotic effects of CCBs during iron overload conditions. We found that CCBs reduced hepatic iron content, intracellular iron deposition, the number of hepatic fibrotic areas, collagen expression levels, and hydroxyproline content. CCBs rescued abnormal expression of α1C protein in L-type voltage-dependent calcium channel (LVDCC) and down-regulated divalent metal transporter-1 (DMT-1) expression in mouse livers. In iron-overloaded HSC-T6 cells, CCBs reduced iron deposition, inhibited proliferation, induced apoptosis, and elevated expression of matrix metalloproteinase-13 (MMP-13) and tissue inhibitor of metalloproteinase-1 (TIMP-1). CCBs are potential therapeutic agents that can be used to address hepatic fibrosis during iron overload. They resolve hepatic fibrosis probably correlated with regulating transmembrane iron transport and inhibiting HSC growth. - Highlights: • Calcium channel blockers (CCBs) reduced hepatic iron content. • CCBs decreased hepatic fibrotic areas and collagen expression levels. • CCBs resolve fibrosis by regulating iron transport and inhibiting HSC growth.« less

Multiple Osmotic Stress Responses in Acidihalobacter prosperus Result in Tolerance to Chloride Ions.

PubMed

Dopson, Mark; Holmes, David S; Lazcano, Marcelo; McCredden, Timothy J; Bryan, Christopher G; Mulroney, Kieran T; Steuart, Robert; Jackaman, Connie; Watkin, Elizabeth L J

2016-01-01

Extremely acidophilic microorganisms (pH optima for growth of ≤3) are utilized for the extraction of metals from sulfide minerals in the industrial biotechnology of "biomining." A long term goal for biomining has been development of microbial consortia able to withstand increased chloride concentrations for use in regions where freshwater is scarce. However, when challenged by elevated salt, acidophiles experience both osmotic stress and an acidification of the cytoplasm due to a collapse of the inside positive membrane potential, leading to an influx of protons. In this study, we tested the ability of the halotolerant acidophile Acidihalobacter prosperus to grow and catalyze sulfide mineral dissolution in elevated concentrations of salt and identified chloride tolerance mechanisms in Ac. prosperus as well as the chloride susceptible species, Acidithiobacillus ferrooxidans . Ac. prosperus had optimum iron oxidation at 20 g L -1 NaCl while At. ferrooxidans iron oxidation was inhibited in the presence of 6 g L -1 NaCl. The tolerance to chloride in Ac. prosperus was consistent with electron microscopy, determination of cell viability, and bioleaching capability. The Ac. prosperus proteomic response to elevated chloride concentrations included the production of osmotic stress regulators that potentially induced production of the compatible solute, ectoine uptake protein, and increased iron oxidation resulting in heightened electron flow to drive proton export by the F 0 F 1 ATPase. In contrast, At. ferrooxidans responded to low levels of Cl - with a generalized stress response, decreased iron oxidation, and an increase in central carbon metabolism. One potential adaptation to high chloride in the Ac. prosperus Rus protein involved in ferrous iron oxidation was an increase in the negativity of the surface potential of Rus Form I (and Form II) that could help explain how it can be active under elevated chloride concentrations. These data have been used to create a model of chloride tolerance in the salt tolerant and susceptible species Ac. prosperus and At. ferrooxidans , respectively.

Multiple Osmotic Stress Responses in Acidihalobacter prosperus Result in Tolerance to Chloride Ions

PubMed Central

Dopson, Mark; Holmes, David S.; Lazcano, Marcelo; McCredden, Timothy J.; Bryan, Christopher G.; Mulroney, Kieran T.; Steuart, Robert; Jackaman, Connie; Watkin, Elizabeth L. J.

2017-01-01

Extremely acidophilic microorganisms (pH optima for growth of ≤3) are utilized for the extraction of metals from sulfide minerals in the industrial biotechnology of “biomining.” A long term goal for biomining has been development of microbial consortia able to withstand increased chloride concentrations for use in regions where freshwater is scarce. However, when challenged by elevated salt, acidophiles experience both osmotic stress and an acidification of the cytoplasm due to a collapse of the inside positive membrane potential, leading to an influx of protons. In this study, we tested the ability of the halotolerant acidophile Acidihalobacter prosperus to grow and catalyze sulfide mineral dissolution in elevated concentrations of salt and identified chloride tolerance mechanisms in Ac. prosperus as well as the chloride susceptible species, Acidithiobacillus ferrooxidans. Ac. prosperus had optimum iron oxidation at 20 g L−1 NaCl while At. ferrooxidans iron oxidation was inhibited in the presence of 6 g L−1 NaCl. The tolerance to chloride in Ac. prosperus was consistent with electron microscopy, determination of cell viability, and bioleaching capability. The Ac. prosperus proteomic response to elevated chloride concentrations included the production of osmotic stress regulators that potentially induced production of the compatible solute, ectoine uptake protein, and increased iron oxidation resulting in heightened electron flow to drive proton export by the F0F1 ATPase. In contrast, At. ferrooxidans responded to low levels of Cl− with a generalized stress response, decreased iron oxidation, and an increase in central carbon metabolism. One potential adaptation to high chloride in the Ac. prosperus Rus protein involved in ferrous iron oxidation was an increase in the negativity of the surface potential of Rus Form I (and Form II) that could help explain how it can be active under elevated chloride concentrations. These data have been used to create a model of chloride tolerance in the salt tolerant and susceptible species Ac. prosperus and At. ferrooxidans, respectively. PMID:28111571

Iron Supplementation During Pregnancy- A Necessary or Toxic Supplement?

PubMed Central

Wilmet, Stephanie; Legssyer, Rachida; Crichton, Robert R.

2003-01-01

The effects of a single intramuscular iron dose, 10mg, to pregnant rats on Day of pregnancy, on the outcome of pregnancy, with respect to foetal weight and mother’s immune function has been investigated. Despite significantly elevated hepatic iron stores after iron supplementation in pregnant rats this had no significant effect upon blood haemoglobin or transferrin saturation levels. However the mean weight of the foetuses at Day 20-21 was significantly lower than that of the non-supplemented pregnant rats. Iron supplements significantly increased the activity of NADPH oxidase in the maternal alveolar macrophages, the primary event in the formation of the phagolysosome to combat invading organisms. However inducible nitric oxide synthase activity was significantly reduced in these macrophages as shown by decreases in LPSinduced and LPS+IFNγ-induced NOS activation. Iron supplementation to rats of normal iron status at the commencement of pregnancy did not show any beneficial effects to either the foetus or the mother. PMID:18365051

A Mammalian Siderophore Synthesized by an Enzyme with a Bacterial Homologue Involved in Enterobactin Production

PubMed Central

Devireddy, Laxminarayana R.; Hart, Daniel O.; Goetz, David; Green, Michael R.

2010-01-01

SUMMARY Intracellular iron homeostasis is critical for survival and proliferation. Lipocalin 24p3 is an iron trafficking protein that binds iron through association with a bacterial siderophore, such as enterobactin, or a postulated mammalian siderophore. Here we show that the iron-binding moiety of the 24p3-associated mammalian siderophore is 2,5-dihydroxybenzoic acid (2,5-DHBA), which is similar to 2,3-DHBA, the iron-binding component of enterobactin. We find that the murine enzyme responsible for 2,5-DHBA synthesis is the homologue of bacterial EntA, which catalyzes 2,3-DHBA production during enterobactin biosynthesis. RNA interference-mediated knockdown of the murine homologue of EntA results in siderophore depletion. Mammalian cells lacking the siderophore accumulate abnormally high amounts of cytoplasmic iron, resulting in elevated levels of reactive oxygen species, whereas the mitochondria are iron deficient. Siderophore-depleted mammalian cells and zebrafish embryos fail to synthesize heme, an iron-dependent mitochondrial process. Our results reveal features of intracellular iron homeostasis that are conserved from bacteria through humans. PMID:20550936

Increased endogenous DNA oxidation correlates to increased iron levels in melanocytes relative to keratinocytes.

PubMed

Pelle, Edward; Huang, Xi; Zhang, Qi; Pernodet, Nadine; Yarosh, Daniel B; Frenkel, Krystyna

2014-01-01

The endogenous oxidative state of normal human epidermal melanocytes was investigated and compared to normal human epidermal keratinocytes (NHEKs) in order to gain new insight into melanocyte biology. Previously, we showed that NHEKs contain higher levels of hydrogen peroxide (H2O2) than melanocytes and that it can migrate from NHEKs to melanocytes by passive permeation. Nevertheless, despite lower concentrations of H2O2, we now report higher levels of oxidative DNA in melanocytes as indicated by increased levels of 8-oxo-2'-deoxyguanosine (8-oxo-dG): 4.49 (±0.55 SEM) 8-oxo-dG/10(6) dG compared to 1.49 (±0.11 SEM) 8-oxo-dG/10(6) dG for NHEKs. An antioxidant biomarker, glutathione (GSH), was also lower in melanocytes (3.14 nmoles (±0.15 SEM)/cell) in comparison to NHEKs (5.98 nmoles (±0.33 SEM)/cell). Intriguingly, cellular bioavailable iron as measured in ferritin was found to be nearly fourfold higher in melanocytes than in NHEKs. Further, ferritin levels in melanocytes were also higher than in hepatocarcinoma cells, an iron-rich cell, and it indicates that higher relative iron levels may be characteristic of melanocytes. To account for the increased oxidative DNA and lower GSH and H2O2 levels that we observe, we propose that iron may contribute to higher levels of oxidation by reacting with H2O2 through a Fenton reaction leading to the generation of DNA-reactive hydroxyl radicals. In conclusion, our data support the concept of elevated oxidation and high iron levels as normal parameters of melanocytic activity. We present new evidence that may contribute to our understanding of the melanogenic process and lead to the development of new skin care products.

WEST ELEVATION, LOOKING EAST. AveryBartholomew Patent Railroad Iron Bridge, ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

WEST ELEVATION, LOOKING EAST. - Avery-Bartholomew Patent Railroad Iron Bridge, Town park south of Route 222, west of Owasco Inlet (moved from Elm Street Extension spanning Fall Creek, Nubia, NY), Groton, Tompkins County, NY

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.

The novel compound PBT434 prevents iron mediated neurodegeneration and alpha-synuclein toxicity in multiple models of Parkinson's disease.

PubMed

Finkelstein, David I; Billings, Jessica L; Adlard, Paul A; Ayton, Scott; Sedjahtera, Amelia; Masters, Colin L; Wilkins, Simon; Shackleford, David M; Charman, Susan A; Bal, Wojciech; Zawisza, Izabela A; Kurowska, Ewa; Gundlach, Andrew L; Ma, Sheri; Bush, Ashley I; Hare, Dominic J; Doble, Philip A; Crawford, Simon; Gautier, Elisabeth Cl; Parsons, Jack; Huggins, Penny; Barnham, Kevin J; Cherny, Robert A

2017-06-28

Elevated iron in the SNpc may play a key role in Parkinson's disease (PD) neurodegeneration since drug candidates with high iron affinity rescue PD animal models, and one candidate, deferirpone, has shown efficacy recently in a phase two clinical trial. However, strong iron chelators may perturb essential iron metabolism, and it is not yet known whether the damage associated with iron is mediated by a tightly bound (eg ferritin) or lower-affinity, labile, iron pool. Here we report the preclinical characterization of PBT434, a novel quinazolinone compound bearing a moderate affinity metal-binding motif, which is in development for Parkinsonian conditions. In vitro, PBT434 was far less potent than deferiprone or deferoxamine at lowering cellular iron levels, yet was found to inhibit iron-mediated redox activity and iron-mediated aggregation of α-synuclein, a protein that aggregates in the neuropathology. In vivo, PBT434 did not deplete tissue iron stores in normal rodents, yet prevented loss of substantia nigra pars compacta neurons (SNpc), lowered nigral α-synuclein accumulation, and rescued motor performance in mice exposed to the Parkinsonian toxins 6-OHDA and MPTP, and in a transgenic animal model (hA53T α-synuclein) of PD. These improvements were associated with reduced markers of oxidative damage, and increased levels of ferroportin (an iron exporter) and DJ-1. We conclude that compounds designed to target a pool of pathological iron that is not held in high-affinity complexes in the tissue can maintain the survival of SNpc neurons and could be disease-modifying in PD.

In vivo bioluminescence imaging of labile iron accumulation in a murine model of Acinetobacter baumannii infection.

PubMed

Aron, Allegra T; Heffern, Marie C; Lonergan, Zachery R; Vander Wal, Mark N; Blank, Brian R; Spangler, Benjamin; Zhang, Yaofang; Park, Hyo Min; Stahl, Andreas; Renslo, Adam R; Skaar, Eric P; Chang, Christopher J

2017-11-28

Iron is an essential metal for all organisms, yet disruption of its homeostasis, particularly in labile forms that can contribute to oxidative stress, is connected to diseases ranging from infection to cancer to neurodegeneration. Iron deficiency is also among the most common nutritional deficiencies worldwide. To advance studies of iron in healthy and disease states, we now report the synthesis and characterization of iron-caged luciferin-1 (ICL-1), a bioluminescent probe that enables longitudinal monitoring of labile iron pools (LIPs) in living animals. ICL-1 utilizes a bioinspired endoperoxide trigger to release d-aminoluciferin for selective reactivity-based detection of Fe 2+ with metal and oxidation state specificity. The probe can detect physiological changes in labile Fe 2+ levels in live cells and mice experiencing iron deficiency or overload. Application of ICL-1 in a model of systemic bacterial infection reveals increased iron accumulation in infected tissues that accompany transcriptional changes consistent with elevations in both iron acquisition and retention. The ability to assess iron status in living animals provides a powerful technology for studying the contributions of iron metabolism to physiology and pathology.

Minerals, haem and non-haem iron contents of rhea meat.

PubMed

Ramos, A; Cabrera, M C; Del Puerto, M; Saadoun, A

2009-01-01

Mineral contents, haem and non-haem iron of rhea (Rhea americana) muscles Obturatorius medialis (OM), Iliotibialis lateralis (IL) and Iliofibularis (I) were determined. No differences between the three muscles were observed for calcium, phosphorus, magnesium and sodium. There is more potassium, zinc and copper in IL muscle than in OM and I muscles. For Manganese, OM and IL muscles show a higher content in comparison with I muscle. For selenium, IL and I muscles show the highest content compared to OM muscle. For total, haem and non-haem iron, the IL muscle shows the highest content respect to the other muscles. When compared to other meats, the minerals content of rhea meat show an elevated level in phosphorus, selenium and total and haem iron. The human health concern due to the deficient diet in selenium and iron, and their high contents in rhea meat will be of great importance in the promotion of this meat.

Organ iron accumulation in chronically transfused children with sickle cell anaemia: baseline results from the TWiTCH trial.

PubMed

Wood, John C; Cohen, Alan R; Pressel, Sara L; Aygun, Banu; Imran, Hamayun; Luchtman-Jones, Lori; Thompson, Alexis A; Fuh, Beng; Schultz, William H; Davis, Barry R; Ware, Russell E

2016-01-01

Transcranial Doppler (TCD) With Transfusions Changing to Hydroxyurea (TWiTCH) trial is a randomized, open-label comparison of hydroxycarbamide (also termed hydroxyurea) versus continued chronic transfusion therapy for primary stroke prevention in patients with sickle cell anaemia (SCA) and abnormal TCD. Severity and location of iron overload is an important secondary outcome measure. We report the baseline findings of abdominal organ iron burden in 121 participants. At enrollment, patients were young (9·8 ± 2·9 years), predominantly female (60:40), and previously treated with transfusions (4·1 ± 2·4 years) and iron chelation (3·1 ± 2·1 years). Liver iron concentration (LIC; 9·0 ± 6·6 mg/g dry weight) and serum ferritin were moderately elevated (2696 ± 1678 μg/l), but transferrin was incompletely saturated (47·2 ± 23·6%). Spleen R2* was 509 ± 399 Hz (splenic iron ~13·9 mg/g) and correlated with LIC (r(2)  = 0·14, P = 0·0008). Pancreas R2* was increased in 38·3% of patients but not to levels associated with endocrine toxicity. Kidney R2* was increased in 80·7% of patients; renal iron correlated with markers of intravascular haemolysis and was elevated in patients with increased urine albumin-creatinine ratios. Extra-hepatic iron deposition is common among children with SCA who receive chronic transfusions, and could potentiate oxidative stress caused by reperfusion injury and decellularized haemoglobin. © 2015 John Wiley & Sons Ltd.

ROS-mediated iron overload injures the hematopoiesis of bone marrow by damaging hematopoietic stem/progenitor cells in mice

PubMed Central

Chai, Xiao; Li, Deguan; Cao, Xiaoli; Zhang, Yuchen; Mu, Juan; Lu, Wenyi; Xiao, Xia; Li, Chengcheng; Meng, Juanxia; Chen, Jie; Li, Qing; Wang, Jishi; Meng, Aimin; Zhao, Mingfeng

2015-01-01

Iron overload, caused by hereditary hemochromatosis or repeated blood transfusions in some diseases, such as beta thalassemia, bone marrow failure and myelodysplastic syndrome, can significantly induce injured bone marrow (BM) function as well as parenchyma organ dysfunctions. However, the effect of iron overload and its mechanism remain elusive. In this study, we investigated the effects of iron overload on the hematopoietic stem and progenitor cells (HSPCs) from a mouse model. Our results showed that iron overload markedly decreased the ratio and clonogenic function of murine HSPCs by the elevation of reactive oxygen species (ROS). This finding is supported by the results of NAC or DFX treatment, which reduced ROS level by inhibiting NOX4 and p38MAPK and improved the long-term and multi-lineage engrafment of iron overload HSCs after transplantation. Therefore, all of these data demonstrate that iron overload injures the hematopoiesis of BM by enhancing ROS through NOX4 and p38MAPK. This will be helpful for the treatment of iron overload in patients with hematopoietic dysfunction. PMID:25970748

Fluoride-induced iron overload contributes to hepatic oxidative damage in mouse and the protective role of Grape seed proanthocyanidin extract.

PubMed

Niu, Qiang; He, Ping; Xu, Shangzhi; Ma, Ruling; Ding, Yusong; Mu, Lati; Li, Shugang

2018-01-01

Emerging evidence has demonstrated that iron overload plays an important role in oxidative stress in the liver. This study aimed to explore whether fluoride-induced hepatic oxidative stress is associated with iron overload and whether grape seed proanthocyanidin extract (GSPE) alleviates oxidative stress by reducing iron overload. Forty Kunming male mice were randomly divided into 4 groups and treated for 5 weeks with distilled water (control), sodium fluoride (NaF) (100 mg/L), GSPE (400 mg/kg bw), or NaF (100 mg/L) + GSPE (400 mg/kg bw). Mice exposed to NaF showed typical poisoning changes of morphology, increased aspartate aminotransferase and alanine aminotransferase activities in the liver. NaF treatment also increased MDA accumulation, decreased GSH-Px, SOD and T-AOC levels in liver, indicative of oxidative stress. Intriguingly, all these detrimental effects were alleviated by GSPE. Further study revealed that NaF induced disorders of iron metabolism, as manifested by elevated iron level with increased hepcidin but decreased ferroportin expression, which contributed to hepatic oxidative stress. Importantly, the iron dysregulation induced by NaF could be normalized by GSPE. Collectively, these data provide a novel insight into mechanisms underlying fluorosis and highlight the potential of GSPE as a naturally occurring prophylactic treatment for fluoride-induced hepatotoxicity associated with iron overload.

Epoetin beta pegol alleviates oxidative stress and exacerbation of renal damage from iron deposition, thereby delaying CKD progression in progressive glomerulonephritis rats.

PubMed

Hirata, Michinori; Tashiro, Yoshihito; Aizawa, Ken; Kawasaki, Ryohei; Shimonaka, Yasushi; Endo, Koichi

2015-12-01

The increased deposition of iron in the kidneys that occurs with glomerulopathy hinders the functional and structural recovery of the tubules and promotes progression of chronic kidney disease (CKD). Here, we evaluated whether epoetin beta pegol (continuous erythropoietin receptor activator: CERA), which has a long half-life in blood and strongly suppresses hepcidin-25, exerts renoprotection in a rat model of chronic progressive glomerulonephritis (cGN). cGN rats showed elevated urinary total protein excretion (uTP) and plasma urea nitrogen (UN) from day 14 after the induction of kidney disease (day 0) and finally declined into end-stage kidney disease (ESKD), showing reduced creatinine clearance with glomerulosclerosis, tubular dilation, and tubulointerstitial fibrosis. A single dose of CERA given on day 1, but not on day 16, alleviated increasing uTP and UN, thereby delaying ESKD. In the initial disease phase, CERA significantly suppressed urinary 8-OHdG and liver-type fatty acid-binding protein (L-FABP), a tubular damage marker. CERA also inhibited elevated plasma hepcidin-25 levels and alleviated subsequent iron accumulation in kidneys in association with elevated urinary iron excretion and resulted in alleviation of growth of Ki67-positive tubular and glomerular cells. In addition, at day 28 when the exacerbation of uTP occurs, a significant correlation was observed between iron deposition in the kidney and urinary L-FABP. In our study, CERA mitigated increasing kidney damage, thereby delaying CKD progression in this glomerulonephritis rat model. Alleviation by CERA of the exacerbation of kidney damage could be attributable to mitigation of tubular damage that might occur with lowered iron deposition in tubules. © 2015 Chugai Pharmaceutical Co., Ltd. Physiological Reports published by Wiley Periodicals, Inc. on behalf of the American Physiological Society and The Physiological Society.

Iron Modifies Plasma FGF23 Differently in Autosomal Dominant Hypophosphatemic Rickets and Healthy Humans

PubMed Central

Peacock, Munro; Gray, Amie K.; Padgett, Leah R.; Hui, Siu L.; Econs, Michael J.

2011-01-01

Context: In autosomal dominant hypophosphatemic rickets (ADHR), fibroblast growth factor 23 (FGF23) resists cleavage, causing increased plasma FGF23 levels. The clinical phenotype includes variable onset during childhood or adulthood and waxing/waning of hypophosphatemia. Delayed onset after puberty in females suggests iron status may be important. Objective: Studies were performed to test the hypothesis that plasma C-terminal and intact FGF23 concentrations are related to serum iron concentrations in ADHR. Design and Setting: Cross-sectional and longitudinal studies of ADHR and a cross-sectional study in healthy subjects were conducted at an academic medical center. Participants: Participants included 37 subjects with ADHR mutations from four kindreds and 158 healthy adult controls. Main Outcome Measure: The relationships of serum iron concentrations with plasma C-terminal and intact FGF23 concentrations were evaluated. Results: Serum phosphate and 1,25-dihydroxyvitamin D correlated negatively with C-terminal FGF23 and intact FGF23 in ADHR but not in controls. Serum iron was negatively correlated to both C-terminal FGF23 (r = −0.386; P < 0.05) and intact FGF23 (r = −0.602; P < 0.0001) in ADHR. However, control subjects also demonstrated a negative relationship of serum iron with C-terminal FGF23 (r = −0.276; P < 0.001) but no relationship with intact FGF23. Longitudinally in ADHR subjects, C-terminal FGF23 and intact FGF23 concentrations changed negatively with iron concentrations (P < 0.001 and P = 0.055, respectively), serum phosphate changed negatively with C-terminal FGF23 and intact FGF23 (P < 0.001), and there was a positive relationship between serum iron and phosphate (P < 0.001). Conclusions: Low serum iron is associated with elevated FGF23 in ADHR. However, in controls, low serum iron was also associated with elevated C-terminal FGF23, but not intact FGF23, suggesting cleavage maintains homeostasis despite increased FGF23 expression. PMID:21880793

Iron modifies plasma FGF23 differently in autosomal dominant hypophosphatemic rickets and healthy humans.

PubMed

Imel, Erik A; Peacock, Munro; Gray, Amie K; Padgett, Leah R; Hui, Siu L; Econs, Michael J

2011-11-01

In autosomal dominant hypophosphatemic rickets (ADHR), fibroblast growth factor 23 (FGF23) resists cleavage, causing increased plasma FGF23 levels. The clinical phenotype includes variable onset during childhood or adulthood and waxing/waning of hypophosphatemia. Delayed onset after puberty in females suggests iron status may be important. Studies were performed to test the hypothesis that plasma C-terminal and intact FGF23 concentrations are related to serum iron concentrations in ADHR. Cross-sectional and longitudinal studies of ADHR and a cross-sectional study in healthy subjects were conducted at an academic medical center. Participants included 37 subjects with ADHR mutations from four kindreds and 158 healthy adult controls. The relationships of serum iron concentrations with plasma C-terminal and intact FGF23 concentrations were evaluated. Serum phosphate and 1,25-dihydroxyvitamin D correlated negatively with C-terminal FGF23 and intact FGF23 in ADHR but not in controls. Serum iron was negatively correlated to both C-terminal FGF23 (r = -0.386; P < 0.05) and intact FGF23 (r = -0.602; P < 0.0001) in ADHR. However, control subjects also demonstrated a negative relationship of serum iron with C-terminal FGF23 (r = -0.276; P < 0.001) but no relationship with intact FGF23. Longitudinally in ADHR subjects, C-terminal FGF23 and intact FGF23 concentrations changed negatively with iron concentrations (P < 0.001 and P = 0.055, respectively), serum phosphate changed negatively with C-terminal FGF23 and intact FGF23 (P < 0.001), and there was a positive relationship between serum iron and phosphate (P < 0.001). Low serum iron is associated with elevated FGF23 in ADHR. However, in controls, low serum iron was also associated with elevated C-terminal FGF23, but not intact FGF23, suggesting cleavage maintains homeostasis despite increased FGF23 expression.

Iron overload across the spectrum of non-transfusion-dependent thalassaemias: role of erythropoiesis, splenectomy and transfusions.

PubMed

Porter, John B; Cappellini, Maria Domenica; Kattamis, Antonis; Viprakasit, Vip; Musallam, Khaled M; Zhu, Zewen; Taher, Ali T

2017-01-01

Non-transfusion-dependent thalassaemias (NTDT) encompass a spectrum of anaemias rarely requiring blood transfusions. Increased iron absorption, driven by hepcidin suppression secondary to erythron expansion, initially causes intrahepatic iron overload. We examined iron metabolism biomarkers in 166 NTDT patients with β thalassaemia intermedia (n = 95), haemoglobin (Hb) E/β thalassaemia (n = 49) and Hb H syndromes (n = 22). Liver iron concentration (LIC), serum ferritin (SF), transferrin saturation (TfSat) and non-transferrin-bound iron (NTBI) were elevated and correlated across diagnostic subgroups. NTBI correlated with soluble transferrin receptor (sTfR), labile plasma iron (LPI) and nucleated red blood cells (NRBCs), with elevations generally confined to previously transfused patients. Splenectomised patients had higher NTBI, TfSat, NRBCs and SF relative to LIC, than non-splenectomised patients. LPI elevations were confined to patients with saturated transferrin. Erythron expansion biomarkers (sTfR, growth differentiation factor-15, NRBCs) correlated with each other and with iron overload biomarkers, particularly in Hb H patients. Plasma hepcidin was similar across subgroups, increased with >20 prior transfusions, and correlated inversely with TfSat, NTBI, LPI and NRBCs. Hepcidin/SF ratios were low, consistent with hepcidin suppression relative to iron overload. Increased NTBI and, by implication, risk of extra-hepatic iron distribution are more likely in previously transfused, splenectomised and iron-overloaded NTDT patients with TfSat >70%. © 2016 The Authors. British Journal of Haematology published by John Wiley & Sons Ltd.

Brain iron concentrations in regions of interest and relation with serum iron levels in Parkinson disease.

PubMed

Costa-Mallen, Paola; Gatenby, Christopher; Friend, Sally; Maravilla, Kenneth R; Hu, Shu-Ching; Cain, Kevin C; Agarwal, Pinky; Anzai, Yoshimi

2017-07-15

Brain iron has been previously found elevated in the substantia nigra pars compacta (SNpc), but not in other brain regions, of Parkinson's disease (PD) patients. However, iron in circulation has been recently observed to be lower than normal in PD patients. The regional selectivity of iron deposition in brain as well as the relationship between SNpc brain iron and serum iron within PD patients has not been completely elucidated. In this pilot study we measured brain iron in six regions of interest (ROIs) as well as serum iron and serum ferritin, in 24 PD patients and 27 age- gender-matched controls. Brain iron was measured on magnetic resonance imaging (MRI) with a T2 prime (T2') method. Difference in brain iron deposition between PD cases and controls for the six ROIs were calculated. SNpc/white matter brain iron ratios and SNpc/serum iron ratios were calculated for each study participant, and differences between PD patients and controls were tested. PD patients overall had higher brain iron than controls in the SNpc. PD patients had significantly higher SNpc/white matter brain iron ratios than controls, and significantly higher brain SNpc iron/serum iron ratios than controls. These results indicate that PD patients' iron metabolism is disrupted toward a higher partitioning of iron to the brain SNpc at the expenses of iron in the circulation. Copyright © 2017 Elsevier B.V. All rights reserved.

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

Wiengmoon, A., E-mail: ampornw@nu.ac.th

The effects of Si on microstructure and phase transformation at elevated temperature of ferritic 31wt.%Cr-1.1wt.%C white cast irons with up to 3wt.%Si have been studied. Applications of these irons include parts requiring heat resistance at elevated temperature. The irons were produced by sand casting. The microstructure in as-cast condition and after being subjected to high temperature (700 to 1000 °C) was investigated by light microscopy, X-ray diffraction, and electron microscopy. The results revealed that the as-cast microstructure consisted mainly of primary ferrite dendrites and eutectic (ferrite + M{sub 7}C{sub 3}). Si promotes M{sub 7}C{sub 3}-to-M{sub 23}C{sub 6} transformation in themore » irons subjected to transformation at elevated temperature, but no sigma phase was found. The extent of M{sub 7}C{sub 3}-to-M{sub 23}C{sub 6} transformation increases proportional to the increasing transformation temperature, holding time and Si content in the irons. For the iron with 1.0wt.%Si content after holding at elevated temperatures, martensite was also found, which could be attributed to carbon accretion effects in eutectic ferrite. Si was incorporated in M{sub 23}C{sub 6} such that M{sub 23}C{sub 6} containing Si can show darker contrast under SEM-BEI as compared to M{sub 7}C{sub 3}; this is the opposite to what has been observed for the cases of typical M{sub 23}C{sub 6} and M{sub 23}C{sub 6} containing Mo or W. The results obtained are important to understand the change in properties of ferritic, high chromium irons containing Si subjected to elevated temperature.« less

Impact of p53 status on heavy-ion radiation-induced micronuclei in circulating erythrocytes

NASA Technical Reports Server (NTRS)

Chang, P. Y.; Torous, D.; Lutze-Mann, L.; Winegar, R.

2000-01-01

Transgenic mice that differed in their p53 genetic status were exposed to an acute dose of highly charged and energetic (HZE) iron particle radiation. Micronuclei (MN) in two distinct populations of circulating peripheral blood erythrocytes, the immature reticulocytes (RETs) and the mature normochromatic erythrocytes (NCEs), were measured using a simple and efficient flow cytometric procedure. Our results show significant elevation in the frequency of micronucleated RETs (%MN-RETs) at 2 and 3 days post-radiation. At 3 days post-irradiation, the magnitude of the radiation-induced MN-RET was 2.3-fold higher in the irradiated p53 wild-type animals compared to the unirradiated controls, 2.5-fold higher in the p53 hemizygotes and 4.3-fold higher in the p53 nullizygotes. The persistence of this radiation-induced elevation of MN-RETs is dependent on the p53 genetic background of the animal. In the p53 wild-type and p53 hemizygotes, %MN-RETs returned to control levels by 9 days post-radiation. However, elevated levels of %MN-RETs in p53 nullizygous mice persisted beyond 56 days post-radiation. We also observed elevated MN-NCEs in the peripheral circulation after radiation, but the changes in radiation-induced levels of MN-NCEs appear dampened compared to those of the MN-RETs for all three strains of animals. These results suggest that the lack of p53 gene function may play a role in the iron particle radiation-induced genomic instability in stem cell populations in the hematopoietic system.

Hepcidin-Induced Iron Deficiency Is Related to Transient Anemia and Hypoferremia in Kawasaki Disease Patients

PubMed Central

Huang, Ying-Hsien; Kuo, Ho-Chang; Huang, Fu-Chen; Yu, Hong-Ren; Hsieh, Kai-Sheng; Yang, Ya-Ling; Sheen, Jiunn-Ming; Li, Sung-Chou; Kuo, Hsing-Chun

2016-01-01

Kawasaki disease (KD) is a type of systemic vasculitis that primarily affects children under the age of five years old. For sufferers of KD, intravenous immunoglobulin (IVIG) has been found to successfully diminish the occurrence of coronary artery lesions. Anemia is commonly found in KD patients, and we have shown that in appropriately elevated hepcidin levels are related to decreased hemoglobin levels in these patients. In this study, we investigated the time period of anemia and iron metabolism during different stages of KD. A total of 100 patients with KD and 20 control subjects were enrolled in this study for red blood cell and hemoglobin analysis. Furthermore, plasma, urine hepcidin, and plasma IL-6 levels were evaluated using enzyme-linked immunosorbent assay in 20 KD patients and controls. Changes in hemoglobin, plasma iron levels, and total iron binding capacity (TIBC) were also measured in patients with KD. Hemoglobin, iron levels, and TIBC were lower (p < 0.001, p = 0.009, and p < 0.001, respectively) while plasma IL-6 and hepcidin levels (both p < 0.001) were higher in patients with KD than in the controls prior to IVIG administration. Moreover, plasma hepcidin levels were positively and significantly correlated with urine hepcidin levels (p < 0.001) prior to IVIG administration. After IVIG treatment, plasma hepcidin and hemoglobin levels significantly decreased (both p < 0.001). Of particular note was a subsequent gradual increase in hemoglobin levels during the three weeks after IVIG treatment; nevertheless, the hemoglobin levels stayed lower in KD patients than in the controls (p = 0.045). These findings provide a longitudinal study of hemoglobin changes and among the first evidence that hepcidin induces transient anemia and hypoferremia during KD’s acute inflammatory phase. PMID:27187366

THE SYNTHESIS OF LEAD PYROPHOSPHATE, PB2P2O7, IN WATER

EPA Science Inventory

Polyphosphates are used in the drinking water to prevent the precipitation of cations such as calcium and iron. The possible negative impact of using polyphosphates is the undesirable complexation of lead which could result in elevated lead levels in consumer’s tap water. Altho...

HFE C282Y/H63D compound heterozygotes are at low risk of hemochromatosis-related morbidity.

PubMed

Gurrin, Lyle C; Bertalli, Nadine A; Dalton, Gregory W; Osborne, Nicholas J; Constantine, Clare C; McLaren, Christine E; English, Dallas R; Gertig, Dorota M; Delatycki, Martin B; Nicoll, Amanda J; Southey, Melissa C; Hopper, John L; Giles, Graham G; Anderson, Gregory J; Olynyk, John K; Powell, Lawrie W; Allen, Katrina J

2009-07-01

The risk of hemochromatosis-related morbidity is unknown among HFE compound heterozygotes (C282Y/H63D). We used a prospective population-based cohort study to estimate the prevalence of elevated iron indices and hemochromatosis-related morbidity for compound heterozygotes. In all, 31,192 subjects of northern European descent were genotyped for HFE C282Y and H63D. An HFE-genotype stratified random sample of 1,438 subjects, followed for an average of 12 years to a mean age of 65 years, completed questionnaires and gave blood. Clinical examinations were blinded to HFE genotype. A total of 180 (84 males) clinically examined C282Y/H63D participants were compared with 330 (149 males) controls with neither HFE mutation; 132 (65 males) and 270 (122 males), respectively, had serum iron measures at both timepoints. Mean serum ferritin (SF) and transferrin saturation (TS) were significantly greater for male and female compound heterozygotes than for wild-types at baseline and follow-up (all P < 0.02) except for females who were premenopausal at baseline, where SF was similar in both genotype groups. For subjects with serum measures from both baseline and follow-up, mean SF and TS levels did not change significantly for men or for postmenopausal women, but for premenopausal women SF levels increased from 43 to 109 microg/L for compound heterozygotes and from 35 to 64 microg/L for wild-types (both P < 0.001). Male and female compound heterozygotes had a similar prevalence of hemochromatosis-related morbidity to wild-types. One of 82 males and zero of 95 females had documented iron overload-related disease. For male compound heterozygotes, mean iron indices do not change during middle age but for female compound heterozygotes menopause results in increased mean SF. Although compound heterozygotes might maintain elevated iron indices during middle age, documented iron overload-related disease is rare.

[The efficacy of phlebotomy with a low iron diet in the management of pulmonary iron overload].

PubMed

Fukuda, Tomoko; Kimura, Fumiaki; Watanabe, Yoichi; Yoshino, Tadasi; Kimura, Ikuro

2003-05-01

Numerous studies have shown that workers in ferriferous industries have an elevated risk of respiratory tract neoplasia and other airway diseases. Evidence is presented that iron is a carcinogenic and tissue toxic hazard as regarding the inhalation of ferriferous substances. Elimination of the inhaled iron and prevention from accumulation of iron in the lung seems to be very important. A 26-year-old man was admitted to our hospital complaining of right chest pain. He had worked as an arc welder for two years without a mask. A chest CT showed diffuse ground glass opacity in the bilateral lung fields. A transbronchial lung biopsy specimen showed numerous alveolar and interstitial iron-laden macrophages. A 200 ml phlebotomy was carried out biweekly in combination with a low iron diet (8 mg/day). When serum ferritin reached 20 ng/ml, phlebotomy was stopped. After that, serum ferritin level was kept at around 20 ng/ml with the low iron diet alone. A transbronchial lung biopsy was carried out again 7 months later and the specimen showed remarkable reduction in the number of iron-laden alveolar and interstitial macrophages. Phlebotomy in combination with a low iron diet might become a useful strategy in the management of pulmonary conditions associated with iron loading.

Impaired renal function and development in Belgrade rats

PubMed Central

Veuthey, Tania; Hoffmann, Dana; Vaidya, Vishal S.

2013-01-01

Belgrade rats carry a disabling mutation in the iron transporter divalent metal transporter 1 (DMT1). Although DMT1 plays a major role in intestinal iron absorption, the transporter is also highly expressed in the kidney, where its function remains unknown. The goal of this study was to characterize renal physiology of Belgrade rats. Male Belgrade rats died prematurely with ∼50% survival at 20 wk of age. Necropsy results indicated marked glomerular nephritis and chronic end-stage renal disease. By 15 wk of age, Belgrade rats displayed altered renal morphology associated with sclerosis and fibrosis. Creatinine clearance was significantly lower compared with heterozygote littermates. Urinary biomarkers of kidney injury, including albumin, fibrinogen, and kidney injury molecule-1, were significantly elevated. Pilot morphological studies suggest that nephrogenesis is delayed in Belgrade rat pups due to their low iron status and fetal growth restriction. Such defects in renal development most likely underlie the compromised renal metabolism observed in adult b/b rats. Belgrade rat kidney nonheme iron levels were not different from controls but urinary iron and transferrin levels were higher. These results further implicate an important role for the transporter in kidney function not only in iron reabsorption but also in glomerular filtration of the serum protein. PMID:24226520

Acetylcholinesterase-independent protective effects of huperzine A against iron overload-induced oxidative damage and aberrant iron metabolism signaling in rat cortical neurons.

PubMed

Tao, Ling-Xue; Huang, Xiao-Tian; Chen, Yu-Ting; Tang, Xi-Can; Zhang, Hai-Yan

2016-11-01

Iron dyshomeostasis is one of the primary causes of neuronal death in Alzheimer's disease (AD). Huperzine A (HupA), a natural inhibitor of acetylcholinesterase (AChE), is a licensed anti-AD drug in China and a nutraceutical in the United Sates. Here, we investigated the protective effects of HupA against iron overload-induced injury in neurons. Rat cortical neurons were treated with ferric ammonium citrate (FAC), and cell viability was assessed with MTT assays. Reactive oxygen species (ROS) assays and adenosine triphosphate (ATP) assays were performed to assess mitochondrial function. The labile iron pool (LIP) level, cytosolic-aconitase (c-aconitase) activity and iron uptake protein expression were measured to determine iron metabolism changes. The modified Ellman's method was used to evaluate AChE activity. HupA significantly attenuated the iron overload-induced decrease in neuronal cell viability. This neuroprotective effect of HupA occurred concurrently with a decrease in ROS and an increase in ATP. Moreover, HupA treatment significantly blocked the upregulation of the LIP level and other aberrant iron metabolism changes induced by iron overload. Additionally, another specific AChE inhibitor, donepezil (Don), at a concentration that caused AChE inhibition equivalent to that of HupA negatively, influenced the aberrant changes in ROS, ATP or LIP that were induced by excessive iron. We provide the first demonstration of the protective effects of HupA against iron overload-induced neuronal damage. This beneficial role of HupA may be attributed to its attenuation of oxidative stress and mitochondrial dysfunction and elevation of LIP, and these effects are not associated with its AChE-inhibiting effect.

Acetylcholinesterase-independent protective effects of huperzine A against iron overload-induced oxidative damage and aberrant iron metabolism signaling in rat cortical neurons

PubMed Central

Tao, Ling-xue; Huang, Xiao-tian; Chen, Yu-ting; Tang, Xi-can; Zhang, Hai-yan

2016-01-01

Aim: Iron dyshomeostasis is one of the primary causes of neuronal death in Alzheimer's disease (AD). Huperzine A (HupA), a natural inhibitor of acetylcholinesterase (AChE), is a licensed anti-AD drug in China and a nutraceutical in the United Sates. Here, we investigated the protective effects of HupA against iron overload-induced injury in neurons. Methods: Rat cortical neurons were treated with ferric ammonium citrate (FAC), and cell viability was assessed with MTT assays. Reactive oxygen species (ROS) assays and adenosine triphosphate (ATP) assays were performed to assess mitochondrial function. The labile iron pool (LIP) level, cytosolic-aconitase (c-aconitase) activity and iron uptake protein expression were measured to determine iron metabolism changes. The modified Ellman's method was used to evaluate AChE activity. Results: HupA significantly attenuated the iron overload-induced decrease in neuronal cell viability. This neuroprotective effect of HupA occurred concurrently with a decrease in ROS and an increase in ATP. Moreover, HupA treatment significantly blocked the upregulation of the LIP level and other aberrant iron metabolism changes induced by iron overload. Additionally, another specific AChE inhibitor, donepezil (Don), at a concentration that caused AChE inhibition equivalent to that of HupA negatively, influenced the aberrant changes in ROS, ATP or LIP that were induced by excessive iron. Conclusion: We provide the first demonstration of the protective effects of HupA against iron overload-induced neuronal damage. This beneficial role of HupA may be attributed to its attenuation of oxidative stress and mitochondrial dysfunction and elevation of LIP, and these effects are not associated with its AChE-inhibiting effect. PMID:27498774

Transcriptional response of Pasteurella multocida to defined iron sources.

PubMed

Paustian, Michael L; May, Barbara J; Cao, Dongwei; Boley, Daniel; Kapur, Vivek

2002-12-01

Pasteurella multocida was grown in iron-free chemically defined medium supplemented with hemoglobin, transferrin, ferritin, and ferric citrate as iron sources. Whole-genome DNA microarrays were used to monitor global gene expression over seven time points after the addition of the defined iron source to the medium. This resulted in a set of data containing over 338,000 gene expression observations. On average, 12% of P. multocida genes were differentially expressed under any single condition. A majority of these genes encoded P. multocida proteins that were involved in either transport and binding or were annotated as hypothetical proteins. Several trends are evident when the data from different iron sources are compared. In general, only two genes (ptsN and sapD) were expressed at elevated levels under all of the conditions tested. The results also show that genes with increased expression in the presence of hemoglobin did not respond to transferrin or ferritin as an iron source. Correspondingly, genes with increased expression in the transferrin and ferritin experiments were expressed at reduced levels when hemoglobin was supplied as the sole iron source. Finally, the data show that genes that were most responsive to the presence of ferric citrate did not follow a trend similar to that of the other iron sources, suggesting that different pathways respond to inorganic or organic sources of iron in P. multocida. Taken together, our results demonstrate that unique subsets of P. multocida genes are expressed in response to different iron sources and that many of these genes have yet to be functionally characterized.

Management strategies of iron accumulation in a captive population of black rhinoceroses (Diceros bicornis minor).

PubMed

Mylniczenko, Natalie D; Sullivan, Kathleen E; Corcoran, Michelle E; Fleming, Gregory J; Valdes, Eduardo V

2012-09-01

During routine health screens for black rhinoceroses (Diceros bicornis minor) in a captive setting, serum iron and ferritin were analyzed as well as total iron binding capacity and total iron saturation. Trends for ferritin and percent iron saturation showed steady increases since 2003 in four of four animals (three males; one female) with two animals (one male; one female) consistently showing higher elevations over conspecifics. The historical diet had been comprised of a commercial or in-house complete pelleted feed; several species of fresh browse, Bermuda grass, alfalfa and timothy hays, as well as enrichment and training items (apples, carrots, sweet potatoes, and a small amount of leafy greens and vegetables). In 2009, one of the three male rhinoceroses showed a threefold increase in ferritin and concurrently exhibited clinical signs of lethargy, decreased appetite, and disinterest in training. The lone female showed a twofold increase; she also became reproductively acyclic in the prior year. The male was immobilized for examination and phlebotomy. During the same time period, a new version of the complete pelleted feed, with a reduced amount of iron, was introduced. Subsequent to the diet change, the male's ferritin levels have consistently declined, and the female started cycling again. Even with these corrective steps to reduce iron levels, levels of iron saturation remained high, and ferritin levels were still above 1,500 ng/ml. Therapeutic phlebotomy was instituted via a rigorous training program that allowed phlebotomies over a 30-min time frame. This was possible because of a long-term training program for the animals, consistent training personnel, routine collection of samples on a monthly basis, and general comfort level of the animals in the restraint chute. The results of this integrated approach showed some significant improvements and an overall positive impact on the animals.

121. FRONT ELEVATION OF TELLURIDE IRON WORKS 2.5 BY 4FOOT ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

121. FRONT ELEVATION OF TELLURIDE IRON WORKS 2.5 BY 4-FOOT RETORT, USED TO FLASH MERCURY FROM GOLD. MERCURY VAPOR THEN CONDENSED ON INSIDE OF HOOD AND WAS COLLECTED FOR REUSE. - Shenandoah-Dives Mill, 135 County Road 2, Silverton, San Juan County, CO

Amyloid Precursor Protein and Alpha Synuclein Translation, Implications for Iron and Inflammation in Neurodegenerative diseases

PubMed Central

Cahill, Catherine M.; Lahiri, Debomoy K.; Huang, Xudong; Rogers, Jack T.

2014-01-01

Summary Recent studies that alleles in the hemochromatosis gene may accelerate the onset of Alzheimer's disease (AD) by five years have validated interest in the model in which metals (particularly iron) accelerate disease course. Biochemical and biophysical measurements demonstrated the presence of elevated levels of neurotoxic copper, zinc and iron in the brains of AD patients. Intracellular levels of amyloid precursor protein (APP) holoprotein were shown to be modulated via iron by a mechanism that is similar to the translation control of the ferritin L- and H mRNAs by Iron-responsive Element (IRE) RNA stem loops in their 5′untranslated regions (5′UTRs). Recently, we reported a putative IRE-like sequence to be present in the 5′UTR of the Parkinson's disease (PD) specific alpha synuclein (ASYN) transcript. ASYN encodes the non-Aβ component (NAC) of amyloid plaques. The demonstration of iron-dependent translation of APP mRNA, the involvement of metals in the plaque of AD patients and of increased iron in striatal neurons in the Substantia nigra (SN) of PD patients, have each encouraged the development of metal attenuating agents and iron chelators as a major new therapeutic strategy for the treatment of these neurodegenerative diseases. In the case of AD, metal based therapeutics may ultimately prove more cost effective than the use of an amyloid vaccine as the preferred anti-amyloid therapeutic strategy to ameliorate the cognitive decline of AD patients. PMID:19166904

Ceruloplasmin and hephaestin jointly protect the exocrine pancreas against oxidative damage by facilitating iron efflux.

PubMed

Chen, Min; Zheng, Jiashuo; Liu, Guohao; Xu, En; Wang, Junzhuo; Fuqua, Brie K; Vulpe, Chris D; Anderson, Gregory J; Chen, Huijun

2018-05-31

Little is known about the iron efflux from the pancreas, but it is likely that multicopper ferroxidases (MCFs) are involved in this process. We thus used hephaestin (Heph) and ceruloplasmin (Cp) single-knockout mice and Heph/Cp double-knockout mice to investigate the roles of MCFs in pancreatic iron homeostasis. We found that both HEPH and CP were expressed in the mouse pancreas, and that ablation of either MCF had limited effect on the pancreatic iron levels. However, ablation of both MCFs together led to extensive pancreatic iron deposition and severe oxidative damage. Perls' Prussian blue staining revealed that this iron deposition was predominantly in the exocrine pancreas, while the islets were spared. Consistent with these results, plasma lipase and trypsin were elevated in Heph/Cp knockout mice, indicating damage to the exocrine pancreas, while insulin secretion was not affected. These data indicate that HEPH and CP play mutually compensatory roles in facilitating iron efflux from the exocrine pancreas, and show that MCFs are able to protect the pancreas against iron-induced oxidative damage. Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.

The Prognostic Significance of Elevated Serum Ferritin Levels Prior to Transplantation in Patients With Lymphoma Who Underwent Autologous Hematopoietic Stem Cell Transplantation (autoHSCT): Role of Iron Overload.

PubMed

Sivgin, Serdar; Karamustafaoglu, Mehmet Fatih; Yildizhan, Esra; Zararsiz, Gokmen; Kaynar, Leylagul; Eser, Bulent; Cetin, Mustafa; Unal, Ali

2016-08-01

Hematopoietic stem cell transplantation is a common and preferred treatment of lymphomas in many centers. Our goal was to determine the association between pretransplant iron overload and survival in patients who underwent autologous hematopoietic stem cell transplantation (autoHSCT). A total of 165 patients with lymphoma, who underwent autoHSCT between the years of 2007 and 2014, were included in this study. Ferritin levels were used to determine iron status; the cut-off value was 500 ng/mL. The relationship between iron overload and survival was assessed by statistical analysis. The median ferritin level in the normal ferritin (ferritin < 500) group was 118 ng/mL (range, 9-494 ng/mL) and in the high-ferritin group (ferritin ≥ 500), it was 908 ng/mL (range, 503-4549 ng/mL). A total of 64 (38.8%) patients died during follow-up. Of these patients that died, 52 (81.25%) were in the high-ferritin group, and 12 (18.75%) were in the normal ferritin group (P ≤ .001). Twelve (14.1%) of 85 patients died in the normal ferritin group, and 52 (65.0%) of 80 patients died in the high-ferritin group. The overall mortality was significantly higher in the high-ferritin group (P < .001). The median overall survival was 42 months (range, 25-56 months) in the normal-ferritin group and20 months (range, 5-46) in the high-ferritin group. The difference between the groups was statistically significant (P < .001). The median disease-free survival was 39 months (range, 16-56) in the normal ferritin group and 10 months (range, 3-29) in the high-ferritin group. The difference between the groups was statistically significant (P < .001). Elevated serum ferritin levels might predict poorer survival in autoHSCT recipients. Copyright © 2016 Elsevier Inc. All rights reserved.

Phosphate inhibits in vitro Fe3+ loading into transferrin by forming a soluble Fe(III)-phosphate complex: a potential non-transferrin bound iron species.

PubMed

Hilton, Robert J; Seare, Matthew C; Andros, N David; Kenealey, Zachary; Orozco, Catalina Matias; Webb, Michael; Watt, Richard K

2012-05-01

In chronic kidney diseases, NTBI can occur even when total iron levels in serum are low and transferrin is not saturated. We postulated that elevated serum phosphate concentrations, present in CKD patients, might disrupt Fe(3+) loading into apo-transferrin by forming Fe(III)-phosphate species. We report that phosphate competes with apo-transferrin for Fe(3+) by forming a soluble Fe(III)-phosphate complex. Once formed, the Fe(III)-phosphate complex is not a substrate for donating Fe(3+) to apo-transferrin. Phosphate (1-10mM) does not chelate Fe(III) from diferric transferrin under the conditions examined. Complexed forms of Fe(3+), such as iron nitrilotriacetic acid (Fe(3+)-NTA), and Fe(III)-citrate are not susceptible to this phosphate complexation reaction and efficiently deliver Fe(3+) to apo-transferrin in the presence of phosphate. This reaction suggests that citrate might play an important role in protecting against Fe(III), phosphate interactions in vivo. In contrast to the reactions of Fe(3+) and phosphate, the addition of Fe(2+) to a solution of apo-transferrin and phosphate lead to rapid oxidation and deposition of Fe(3+) into apo-transferrin. These in vitro data suggest that, in principle, elevated phosphate concentrations can influence the ability of apo-transferrin to bind iron, depending on the oxidation state of the iron. Copyright © 2012 Elsevier Inc. All rights reserved.

Supplementation of iron in pulmonary hypertension: Rationale and design of a phase II clinical trial in idiopathic pulmonary arterial hypertension

PubMed Central

Howard, Luke S.G.E.; Watson, Geoffrey M.J.; Wharton, John; Rhodes, Christopher J.; Chan, Kakit; Khengar, Rajeshree; Robbins, Peter A.; Kiely, David G.; Condliffe, Robin; Elliott, Charlie A.; Pepke-Zaba, Joanna; Sheares, Karen; Morrell, Nicholas W.; Davies, Rachel; Ashby, Deborah; Gibbs, J. Simon R.; Wilkins, Martin R.

2013-01-01

Our aim is to assess the safety and potential clinical benefit of intravenous iron (Ferinject) infusion in iron deficient patients with idiopathic pulmonary arterial hypertension (IPAH). Iron deficiency in the absence of anemia (1) is common in patients with IPAH; (2) is associated with inappropriately raised levels of hepcidin, the key regulator of iron homeostasis; and (3) correlates with disease severity and worse clinical outcomes. Oral iron absorption may be impeded by reduced absorption due to elevated hepcidin levels. The safety and benefits of parenteral iron replacement in IPAH are unknown. Supplementation of Iron in Pulmonary Hypertension (SIPHON) is a Phase II, multicenter, double-blind, randomized, placebo-controlled, crossover clinical trial of iron in IPAH. At least 60 patients will be randomized to intravenous ferric carboxymaltose (Ferinject) or saline placebo with a crossover point after 12 weeks of treatment. The primary outcome will be the change in resting pulmonary vascular resistance from baseline at 12 weeks, measured by cardiac catheterization. Secondary measures include resting and exercise hemodynamics and exercise performance from serial bicycle incremental and endurance cardiopulmonary exercise tests. Other secondary measurements include serum iron indices, 6-Minute Walk Distance, WHO functional class, quality of life score, N-terminal pro-brain natriuretic peptide (NT-proBNP), and cardiac anatomy and function from cardiac magnetic resonance. We propose that intravenous iron replacement will improve hemodynamics and clinical outcomes in IPAH. If the data supports a potentially useful therapeutic effect and suggest this drug is safe, the study will be used to power a Phase III study to address efficacy. PMID:23662181

Daily propranolol administration reduces persistent injury-associated anemia following severe trauma and chronic stress

PubMed Central

Alamo, Ines G.; Kannan, Kolenkode B.; Bible, Letitia E.; Loftus, Tyler J.; Ramos, Harry; Efron, Philip A.; Mohr, Alicia M.

2017-01-01

Background Following severe trauma, patients develop a norepinephrine-mediated persistent, injury-associated anemia. This anemia is associated with suppression of bone marrow erythroid colony growth, along with decreased iron levels, and elevated erythropoietin (EPO) levels, which are insufficient to promote effective erythropoiesis. The impact of norepinephrine on iron regulators such as ferroportin, transferrin and transferrin receptor-1 (TFR-1) are unknown. Using a clinically relevant rodent model of lung contusion (LC), hemorrhagic shock (HS), and chronic stress (CS), we hypothesize that daily propranolol (BB), a non-selective beta-blocker, restores bone marrow function and improves iron homeostasis. Methods Male Sprague-Dawley rats were subjected to LCHS±BB and LCHS/CS±BB. BB was achieved with propranolol (10mg/kg) daily until the day of sacrifice. Hemoglobin (Hgb), plasma EPO, plasma hepcidin, bone marrow cellularity and bone marrow erythroid colony growth were assessed. RNA was isolated to measure transferrin, TFR-1 and ferroportin expression. Data is presented as mean±SD; *p<0.05 vs. untreated counterpart by t-test. Results The addition of CS to LCHS leads to persistent anemia on post-trauma day 7, while the addition of BB improved Hgb levels (LCHS/CS: 10.6±0.8 vs. LCHS/CS+BB: 13.9±0.4* g/dL). Daily BB use following LCHS/CS improved BM cellularity, CFU-GEMM, BFU-E and CFU-E colony growth. LCHS/CS+BB significantly reduced plasma EPO levels and increased plasma hepcidin levels on day 7. The addition of CS to LCHS resulted in decreased liver ferroportin expression as well as decreased bone marrow transferrin and TFR-1 expression, thus, blocking iron supply to erythroid cells. However, daily BB after LCHS/CS improved expression of all iron regulators. Conclusions Daily propranolol administration following LCHS/CS restored bone marrow function and improved anemia after severe trauma. In addition, iron regulators are significantly reduced following LCHS/CS, which may contribute to iron restriction after injury. However, daily propranolol administration after LCHS/CS improved iron homeostasis. Level of Evidence Level II, therapeutic study PMID:28099381

Grains of Nonferrous and Noble Metals in Iron-Manganese Formations and Igneous Rocks of Submarine Elevations of the Sea of Japan

NASA Astrophysics Data System (ADS)

Kolesnik, O. N.; Astakhova, N. V.

2018-01-01

Iron-manganese formations and igneous rocks of submarine elevations in the Sea of Japan contain overlapping mineral phases (grains) with quite identical morphology, localization, and chemical composition. Most of the grains conform to oxides, intermetallic compounds, native elements, sulfides, and sulfates in terms of the set of nonferrous, noble, and certain other metals (Cu, Zn, Sn, Pb, Ni, Mo, Ag, Pd, and Pt). The main conclusion that postvolcanic hydrothermal fluids are the key sources of metals is based upon a comparison of the data of electron microprobe analysis of iron-manganese formations and igneous rocks dredged at the same submarine elevations in the Sea of Japan.

Human ferritin for tumor detection and therapy.

PubMed

Fan, Kelong; Gao, Lizeng; Yan, Xiyun

2013-01-01

Ferritin, a major iron storage protein found in most living organisms, is composed of a 24-subunit protein cage with a hollow interior cavity. Serum ferritin serves as a critical marker to detect total body iron status. However, recent research reveals a number of novel functions of ferritin besides iron storage; for example, a ferritin receptor, transferrin receptor 1 (TfR1), has been identified and serum ferritin levels are found to be elevated in tumors. A particular new finding is that magnetoferritin nanoparticles, biomimetically synthesized using H-chain ferritin to form a 24-subunit cage with an iron oxide core, possess intrinsic dual functionality, the protein shell specifically targeting tumors and the iron oxide core catalyzing peroxidase substrates to produce a color reaction allowing visualization of tumor tissues. Here we attempt to summarize current research on ferritin, particularly newly identified functions related to tumors, in order to address current challenges and highlight future directions. Copyright © 2013 Wiley Periodicals, Inc.

A Survival Strategy for Pseudomonas aeruginosa That Uses Exopolysaccharides To Sequester and Store Iron To Stimulate Psl-Dependent Biofilm Formation

PubMed Central

Yu, Shan; Wei, Qing; Zhao, Tianhu; Guo, Yuan

2016-01-01

ABSTRACT Exopolysaccharide Psl is a critical biofilm matrix component in Pseudomonas aeruginosa, which forms a fiber-like matrix to enmesh bacterial communities. Iron is important for P. aeruginosa biofilm development, yet it is not clearly understood how iron contributes to biofilm development. Here, we showed that iron promoted biofilm formation via elevating Psl production in P. aeruginosa. The high level of iron stimulated the synthesis of Psl by reducing rhamnolipid biosynthesis and inhibiting the expression of AmrZ, a repressor of psl genes. Iron-stimulated Psl biosynthesis and biofilm formation held true in mucoid P. aeruginosa strains. Subsequent experiments indicated that iron bound with Psl in vitro and in biofilms, which suggested that Psl fibers functioned as an iron storage channel in P. aeruginosa biofilms. Moreover, among three matrix exopolysaccharides of P. aeruginosa, Psl is the only exopolysaccharide that can bind with both ferrous and ferric ion, yet with higher affinity for ferrous iron. Our data suggest a survival strategy of P. aeruginosa that uses exopolysaccharide to sequester and store iron to stimulate Psl-dependent biofilm formation. IMPORTANCE Pseudomonas aeruginosa is an environmental microorganism which is also an opportunistic pathogen that can cause severe infections in immunocompromised individuals. It is the predominant airway pathogen causing morbidity and mortality in individuals affected by the genetic disease cystic fibrosis (CF). Increased airway iron and biofilm formation have been proposed to be the potential factors involved in the persistence of P. aeruginosa in CF patients. Here, we showed that a high level of iron enhanced the production of the key biofilm matrix exopolysaccharide Psl to stimulate Psl-dependent biofilm formation. Our results not only make the link between biofilm formation and iron concentration in CF, but also could guide the administration or use of iron chelators to interfere with biofilm formation in P. aeruginosa in CF patients. Furthermore, our data also imply a survival strategy of P. aeruginosa under high-iron environmental conditions. PMID:27565622

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.

Arsenic rich iron plaque on macrophyte roots--an ecotoxicological risk?

PubMed

Taggart, M A; Mateo, R; Charnock, J M; Bahrami, F; Green, A J; Meharg, A A

2009-03-01

Arsenic is known to accumulate with iron plaque on macrophyte roots. Three to four years after the Aznalcóllar mine spill (Spain), residual arsenic contamination left in seasonal wetland habitats has been identified in this form by scanning electron microscopy. Total digestion has determined arsenic concentrations in thoroughly washed 'root+plaque' material in excess of 1000 mg kg(-1), and further analysis using X-ray absorption spectroscopy suggests arsenic exists as both arsenate and arsenite. Certain herbivorous species feed on rhizomes and bulbs of macrophytes in a wide range of global environments, and the ecotoxicological impact of consuming arsenic rich iron plaque associated with such food items remains to be quantified. Here, greylag geese which feed on Scirpus maritimus rhizome and bulb material in areas affected by the Aznalcóllar spill are shown to have elevated levels of arsenic in their feces, which may originate from arsenic rich iron plaque.

Effect of N-acetylcysteine administration on homocysteine level, oxidative damage to proteins, and levels of iron (Fe) and Fe-related proteins in lead-exposed workers.

PubMed

Kasperczyk, Sławomir; Dobrakowski, Michał; Kasperczyk, Aleksandra; Romuk, Ewa; Rykaczewska-Czerwińska, Monika; Pawlas, Natalia; Birkner, Ewa

2016-09-01

N-Acetylcysteine (NAC) could be included in protocols designed for the treatment of lead toxicity. Therefore, in this study, we decided to investigate the influence of NAC administration on homocysteine (Hcy) levels, oxidative damage to proteins, and the levels of iron (Fe), transferrin (TRF), and haptoglobin (HPG) in lead (Pb)-exposed workers. The examined population (n = 171) was composed of male employees who worked with Pb. They were randomized into four groups. Workers who were not administered any antioxidants, drugs, vitamins, or dietary supplements were classified as the reference group (n = 49). The remaining three groups consisted of workers who were treated orally with NAC at three different doses (1 × 200, 2 × 200, or 2 × 400 mg) for 12 weeks. After the treatment, blood Pb levels significantly decreased in the groups receiving NAC compared with the reference group. The protein concentration was not affected by NAC administration. In contrast, Hcy levels significantly decreased or showed a strong tendency toward lower values depending on the NAC dose. Levels of the protein carbonyl groups were significantly decreased in all of the groups receiving NAC. Conversely, glutamate dehydrogenase activity was significantly elevated in all of the groups receiving NAC, while the level of protein thiol groups was significantly elevated only in the group receiving 200 mg of NAC. Treatment with NAC did not significantly affect Fe and TRF levels, whereas HPG levels showed a tendency toward lower values. Treatment with NAC normalized the level of Hcy and decreased oxidative stress as measured by the protein carbonyl content; this effect occurred in a dose-dependent manner. Moreover, small doses of NAC elevated the levels of protein thiol groups. Therefore, NAC could be introduced as an alternative therapy for chronic Pb toxicity in humans. © The Author(s) 2015.

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

Mining legacy across a wetland landscape: high mercury in Upper Peninsula (Michigan) rivers, lakes, and fish.

PubMed

Kerfoot, W Charles; Urban, Noel R; McDonald, Cory P; Zhang, Huanxin; Rossmann, Ronald; Perlinger, Judith A; Khan, Tanvir; Hendricks, Ashley; Priyadarshini, Mugdha; Bolstad, Morgan

2018-04-25

A geographic enigma is that present-day atmospheric deposition of mercury in the Upper Peninsula of Michigan is low (48%) and that regional industrial emissions have declined substantially (ca. 81% reduction) relative to downstate. Mercury levels should be declining. However, state (MDEQ) surveys of rivers and lakes revealed elevated total mercury (THg) in Upper Peninsula waters and sediment relative to downstate. Moreover, Western Upper Peninsula (WUP) fish possess higher methyl mercury (MeHg) levels than Northern Lower Peninsula (NLP) fish. A contributing explanation for elevated THg loading is that a century ago the Upper Peninsula was a major industrial region, centered on mining. Many regional ores (silver, copper, zinc, massive sulfides) contain mercury in part per million concentrations. Copper smelters and iron furnace-taconite operations broadcast mercury almost continuously for 140 years, whereas mills discharged tailings and old mine shafts leaked contaminated water. We show that mercury emissions from copper and iron operations were substantial (60-650 kg per year) and dispersed over relatively large areas. Moreover, lake sediments in the vicinity of mining operations have higher THg concentrations. Sediment profiles from the Keweenaw Waterway show that THg accumulation increased 50- to 400-fold above modern-day atmospheric deposition levels during active mining and smelting operations, with lingering MeHg effects. High MeHg concentrations are geographically correlated with low pH and dissolved organic carbon (DOC), a consequence of biogeochemical cycling in wetlands, characteristic of the Upper Peninsula. DOC can mobilize metals and elevate MeHg concentrations. We argue that mercury loading from mining is historically superimposed upon strong regional wetland effects, producing a combined elevation of both THg and MeHg in the Western Upper Peninsula.

Arsenic in groundwater of Licking County, Ohio, 2012—Occurrence and relation to hydrogeology

USGS Publications Warehouse

Thomas, Mary Ann

2016-02-23

Arsenic concentrations were measured in samples from 168 domestic wells in Licking County, Ohio, to document arsenic concentrations in a wide variety of wells and to identify hydrogeologic factors associated with arsenic concentrations in groundwater. Elevated concentrations of arsenic (greater than 10.0 micrograms per liter [µg/L]) were detected in 12 percent of the wells (about 1 in 8). The maximum arsenic concentration of about 44 µg/L was detected in two wells in the same township.A subset of 102 wells was also sampled for iron, sulfate, manganese, and nitrate, which were used to estimate redox conditions of the groundwater. Elevated arsenic concentrations were detected only in strongly reducing groundwater. Almost 20 percent of the samples with iron concentrations high enough to produce iron staining (greater than 300 µg/L) also had elevated concentrations of arsenic.In groundwater, arsenic primarily occurs as two inorganic species—arsenite and arsenate. Arsenic speciation was determined for a subset of nine samples, and arsenite was the predominant species. Of the two species, arsenite is more difficult to remove from water, and is generally considered to be more toxic to humans.Aquifer and well-construction characteristics were compiled from 99 well logs. Elevated concentrations of arsenic (and iron) were detected in glacial and bedrock aquifers but were more prevalent in glacial aquifers. The reason may be that the glacial deposits typically contain more organic carbon than the Paleozoic bedrock. Organic carbon plays a role in the redox reactions that cause arsenic (and iron) to be released from the aquifer matrix. Arsenic concentrations were not significantly different for different types of bedrock (sandstone, shale, sandstone/shale, or other). However, arsenic concentrations in bedrock wells were correlated with two well-construction characteristics; higher arsenic concentrations in bedrock wells were associated with (1) shorter open intervals and (2) deeper open intervals, relative to the water level.The spatial distribution of arsenic concentrations was compared to hydrogeologic characteristics of Licking County. Elevated concentrations of arsenic (and iron) were associated with areas of flat topography and thick (greater than 100 feet),clay-rich glacial deposits. These characteristics are conducive to development of strongly reducing redox conditions, which can cause arsenic associated with iron oxyhydroxides in the aquifer matrix to be released to the groundwater.Hydrogeologic characteristics conducive to the development of strongly reducing groundwater are relatively wide-spread in the western part of Licking County, which is part of the Central Lowland physiographic province. In this area, a thick layer of clay-rich glacial deposits obscures the bedrock surface and creates flat to gently rolling landscape with poorly developed drainage networks. In the eastern part of the county, which is part of the Appalachian Plateaus physiographic province, the landscape includes steep-sided valleys and bedrock uplands. In this area, elevated arsenic concentrations were detected in buried valleys but not in the bedrock uplands, where glacial deposits are thin or absent. The observation that elevated concentrations of arsenic (and iron) were more prevalent in the western part of Licking County is true for both glacial and bedrock aquifers.In Licking County, thick, clay-rich glacial deposits (and elevated concentrations of arsenic) are associated with two hydrogeologic settings—buried valley and complex thick drift. Most wells in the buried-valley setting had low arsenic concentrations, but a few samples had very high concentrations (30–44 µg/L) and very reducing redox conditions (methanogenic and near-methanogenic). For wells in the complex-thick-drift setting, elevated arsenic concentrations are more prevalent, but the maximum concentration was lower (about 21 µg/L). Similar observations were made about arsenic concentrations in parts of southwestern Ohio.The hydrogeologic settings and characteristics associated with arsenic in Licking County also exist in other parts of Ohio. The statewide extent of these characteristics roughly corresponds to areas where elevated concentrations of arsenic are known to exist. This preliminary conceptual model can be tested and revised as additional wells are sampled for arsenic.

An innovative method for nondestructive analysis of cast iron artifacts at Hopewell Furnace National Historic Site, Pennsylvania

USGS Publications Warehouse

Sloto, R.A.; Helmke, M.F.

2011-01-01

Iron ore containing elevated concentrations of trace metals was smelted at Hopewell Furnace during its 113 years of operation (1771-1883). For this study, we sampled iron ore, cast iron furnace products, slag, soil, groundwater, streamflow, and streambed sediment to determine the fate of trace metals released into the environment during the iron-smelting process. Standard techniques were used to sample and analyze all media except cast iron. We analyzed the trace-metal content of the cast iron using a portable X-ray fluorescence spectrometer, which provided rapid, on-site, nondestructive analyses for 23 elements. The artifacts analyzed included eight cast iron stoves, a footed pot, and a kettle in the Hopewell Furnace museum. We measured elevated concentrations of arsenic, copper, lead, and zinc in the cast iron. Lead concentrations as great as 3,150 parts per million were measured in the stoves. Cobalt was detectable but not quantifiable because of interference with iron. Our study found that arsenic, cobalt, and lead were not released to soil or slag, which could pose a significant health risk to visitors and employees. Instead, our study demonstrates these heavy metals remained with the cast iron and were removed from the site.

Residual Myocardial Iron Following Intramyocardial Hemorrhage During the Convalescent Phase of Reperfused ST-Segment-Elevation Myocardial Infarction and Adverse Left Ventricular Remodeling.

PubMed

Bulluck, Heerajnarain; Rosmini, Stefania; Abdel-Gadir, Amna; White, Steven K; Bhuva, Anish N; Treibel, Thomas A; Fontana, Marianna; Ramlall, Manish; Hamarneh, Ashraf; Sirker, Alex; Herrey, Anna S; Manisty, Charlotte; Yellon, Derek M; Kellman, Peter; Moon, James C; Hausenloy, Derek J

2016-10-01

The presence of intramyocardial hemorrhage (IMH) in ST-segment-elevation myocardial infarction patients reperfused by primary percutaneous coronary intervention has been associated with residual myocardial iron at follow-up, and its impact on adverse left ventricular (LV) remodeling is incompletely understood and is investigated here. Forty-eight ST-segment-elevation myocardial infarction patients underwent cardiovascular magnetic resonance at 4±2 days post primary percutaneous coronary intervention, of whom 40 had a follow-up scan at 5±2 months. Native T1, T2, and T2* maps were acquired. Eight out of 40 (20%) patients developed adverse LV remodeling. A subset of 28 patients had matching T2* maps, of which 15/28 patients (54%) had IMH. Eighteen of 28 (64%) patients had microvascular obstruction on the acute scan, of whom 15/18 (83%) patients had microvascular obstruction with IMH. On the follow-up scan, 13/15 patients (87%) had evidence of residual iron within the infarct zone. Patients with residual iron had higher T2 in the infarct zone surrounding the residual iron when compared with those without. In patients with adverse LV remodeling, T2 in the infarct zone surrounding the residual iron was also higher than in those without (60 [54-64] ms versus 53 [51-56] ms; P=0.025). Acute myocardial infarct size, extent of microvascular obstruction, and IMH correlated with the change in LV end-diastolic volume (Pearson's rho of 0.64, 0.59, and 0.66, respectively; P=0.18 and 0.62, respectively, for correlation coefficient comparison) and performed equally well on receiver operating characteristic curve for predicting adverse LV remodeling (area under the curve: 0.99, 0.94, and 0.95, respectively; P=0.19 for receiver operating characteristic curve comparison). The majority of ST-segment-elevation myocardial infarction patients with IMH had residual myocardial iron at follow-up. This was associated with persistently elevated T2 values in the surrounding infarct tissue and adverse LV remodeling. IMH and residual myocardial iron may be potential therapeutic targets for preventing adverse LV remodeling in reperfused ST-segment-elevation myocardial infarction patients. © 2016 The Authors.

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.

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

Historical ground-water-flow patterns and trends in iron concentrations in the Potomac--Raritan--Magothy aquifer system in parts of Philadelphia, Pennsylvania, and Camden and Gloucester Counties, New Jersey

USGS Publications Warehouse

Sloto, Ronald A.

2003-01-01

The Potomac-Raritan-Magothy (PRM) aquifer system is an important sole-source ground-water supply in Camden and Gloucester Counties, N.J. Elevated iron concentrations are a persistent water-quality problem associated with ground water from the PRM. In Philadelphia, the PRM no longer is usable as a water supply because of highly elevated concentrations of iron (as high as 429 mg/L [milligrams per liter]), manganese (as high as 4 mg/L), and sulfate (as high as 1,720 mg/L). A strongly reducing environment in the PRM in south Philadelphia causes these constituents to be remobilized by reductive dissolution of the aquifer matrix.By the 1920s, ground-water pumping changed the natural ground-water-flow patterns, and ground water flowed toward pumping centers in Philadelphia. By 1940, recharge areas changed from the topographically high areas east of Trenton, N.J., to the outcrop area of the PRM in Philadelphia, and the Delaware River became a source of recharge instead of a point of ground-water discharge. By 1954, the cone of depression caused by pumping at the former Philadelphia Naval Ship Yard (PNSY) exceeded 50 feet below NGVD 29, and the direction of ground-water flow was from New Jersey toward Philadelphia. Because of highly elevated concentrations of iron and manganese, pumping at the former PNSY ceased in the mid-1960s. Beginning about 1951, increased ground-water withdrawals from the PRM in New Jersey reversed the hydraulic gradient so that ground-water flow was from Philadelphia toward New Jersey under the Delaware River, making Philadelphia a recharge area for the PRM aquifer system in parts of Camden and Gloucester Counties. By 1988, water levels in the lower aquifer of the PRM in New Jersey had declined to 103 feet below NAVD 88.In 1943, dissolved iron concentrations ranged from 0.07 to 0.6 mg/L at the former PNSY. By 1967 when the wells at the PNSY were abandoned, dissolved iron concentrations had reached 46 mg/L. Dissolved iron concentrations in water from industrial wells in Philadelphia increased from 0.17 mg/L in 1949 to 19 mg/L in 1979. The concentration of dissolved iron in water from wells screened in the lower aquifer in New Jersey also increased with time. By 1985, dissolved iron concentrations were as high as 16 mg/L for Eagle Point refinery wells.

Volcanism, Iron, and Phytoplankton in the Heard and McDonald Islands Region, Southern Indian Ocean

NASA Astrophysics Data System (ADS)

Coffin, M. F.; Arculus, R. J.; Bowie, A. R.; Chase, Z.; Robertson, R.; Trull, T. W.; Heobi in2016 v01 Shipboard Party, T.

2016-12-01

Phytoplankton supply approximately half of the oxygen in Earth's atmosphere, and iron supply limits the growth of phytoplankton in the anemic Southern Ocean. Situated entirely within the Indian Ocean sector of the Southern Ocean are Australia's only active subaerial volcanoes, Heard and McDonald islands (HIMI) on the central Kerguelen Plateau, a large igneous province. Widespread fields of submarine volcanoes, some of which may be active, extend for distances of up to several hundred kilometers from the islands. The predominantly eastward-flowing Antarctic Circumpolar Current sweeps across the central Kerguelen Plateau, and extensive blooms of phytoplankton are observed on the Plateau down-current of HIMI. The goal of RV Investigator voyage IN2016_V01, conducted in January/February 2016, is to test the hypothesis that hydrothermal fluids, which cool active submarine volcanoes in the HIMI region, ascend from the seafloor and fertilise surface waters with iron, thereby enhancing biological productivity beginning with phytoplankton. Significant initial shipboard results include: Documentation, for the first time, of the role of active HIMI and nearby submarine volcanoes in supplying iron to the Southern Ocean. Nearshore waters had elevated dissolved iron levels. Although biomass was not correspondingly elevated, fluorescence induction data indicated highly productive resident phytoplankton. Discovery of >200 acoustic plumes emanating from the seafloor and ascending up to tens of meters into the water column near HIMI. Deep tow camera footage shows bubbles rising from the seafloor in an acoustic plume field north of Heard Island. Mapping 1,000 km2 of uncharted seafloor around HIMI. Submarine volcanic edifices punctuate the adjacent seafloor, and yielded iron-rich rocks similar to those found on HIMI, respectively. Acoustic plumes emanating from some of these features suggest active seafloor hydrothermal systems.

Increased mitochondrial DNA deletions and copy number in transfusion-dependent thalassemia

PubMed Central

Calloway, Cassandra

2016-01-01

BACKGROUND. Iron overload is the primary cause of morbidity in transfusion-dependent thalassemia. Increase in iron causes mitochondrial dysfunction under experimental conditions, but the occurrence and significance of mitochondrial damage is not understood in patients with thalassemia. METHODS. Mitochondrial DNA (mtDNA) to nuclear DNA copy number (Mt/N) and frequency of the common 4977-bp mitochondrial deletion (ΔmtDNA4977) were quantified using a quantitative PCR assay on whole blood samples from 38 subjects with thalassemia who were receiving regular transfusions. RESULTS. Compared with healthy controls, Mt/N and ΔmtDNA4977 frequency were elevated in thalassemia (P = 0.038 and P < 0.001, respectively). ΔmtDNA4977 was increased in the presence of either liver iron concentration > 15 mg/g dry-weight or splenectomy, with the highest levels observed in subjects who had both risk factors (P = 0.003). Myocardial iron (MRI T2* < 20 ms) was present in 0%, 22%, and 46% of subjects with ΔmtDNA4977 frequency < 20, 20–40, and > 40/1 × 107 mtDNA, respectively (P = 0.025). Subjects with Mt/N values below the group median had significantly lower Matsuda insulin sensitivity index (5.76 ± 0.53) compared with the high Mt/N group (9.11 ± 0.95, P = 0.008). CONCLUSION. Individuals with transfusion-dependent thalassemia demonstrate age-related increase in mtDNA damage in leukocytes. These changes are markedly amplified by splenectomy and are associated with extrahepatic iron deposition. Elevated mtDNA damage in blood cells may predict the risk of iron-associated organ damage in thalassemia. FUNDING. This project was supported by Children’s Hospital & Research Center Oakland Institutional Research Award and by the National Center for Advancing Translational Sciences, NIH, through UCSF-CTSI grant UL1 TR000004. PMID:27583305

Examining potential side effects of therapeutic hypothermia in experimental intracerebral hemorrhage.

PubMed

Wowk, Shannon; Fagan, Kelly J; Ma, Yonglie; Nichol, Helen; Colbourne, Frederick

2017-08-01

Studies treating intracerebral hemorrhage (ICH) with therapeutic hypothermia (TH) have shown inconsistent benefits. We hypothesized that TH's anti-inflammatory effects may be responsible as inflammatory cells are essential for removing degrading erythrocytes. Here, we subjected rats to a collagenase-induced striatal ICH followed by whole-body TH (∼33℃ for 11-72 h) or normothermia. We used X-ray fluorescence imaging to spatially quantify total and peri-hematoma iron three days post-injury. At three and seven days, we measured non-heme iron levels. Finally, hematoma volume was quantified on one, three, and seven days. In the injured hemisphere, total iron levels were elevated ( p < 0.001) with iron increasing in the peri-hematoma region ( p = 0.007). Non-heme iron increased from three to seven days (p < 0.001). TH had no effect on any measure of iron ( p ≥ 0.479). At one and three days, TH did not affect hematoma volume ( p ≥ 0.264); however, at seven days there was a four-fold increase in hematoma volume in 40% of treated animals ( p = 0.032). Thus, even when TH does not interfere with initial increases in total and non-heme iron or its containment, TH can cause re-bleeding post-treatment. This serious complication could partly account for the intermittent protection previously observed. This also raises serious concerns for clinical usage of TH for ICH.

Heme Iron Concentrate and Iron Sulfate Added to Chocolate Biscuits: Effects on Hematological Indices of Mexican Schoolchildren.

PubMed

Quintero-Gutiérrez, Adrián Guillermo; González-Rosendo, Guillermina; Pozo, Javier Polo; Villanueva-Sánchez, Javier

2016-08-01

Food fortification is one of the most effective strategies for increasing iron intake in the population. A simple blind trial was conducted to compare the effect of 2 forms of iron fortification and assess the changes in hemoglobin and iron status indices among preschool children from rural communities. Hemoglobin was evaluated in 47 children aged 3-6 years old. For 72 days (10-week period), children ate Nito biscuits. Thirteen pupils with elevated hemoglobin levels were assigned to the biscuit control group, and pupils with hemoglobin equal to 13.5 mg/dL or less were randomly allocated to consume fortified biscuits with a heme iron concentrate (n = 15) or iron sulfate (n = 19). Changes in hemoglobin, plasma ferritin, and other hematological indices were evaluated with analysis of variance (ANOVA) for repeated measurements. Except mean corpuscular hemoglobin concentrations (+1.27 ± 2.25 g/dL), hematological indices increased significantly across the study: Mean corpuscular volume (+2.2 ± 1.0 f/dL), red blood cells (+0.30 ± 0.37 M/μL), mean corpuscular hemoglobin (+1.8 ± 1.74 pg), hemoglobin (+1.68 ± 0.91 g/dL), hematocrit (+3.43% ± 3.03%), and plasma ferritin (+18.38 ± 22.1 μg/L) were all p < 0.05. After 10 weeks, the adjusted effect of the iron-fortified chocolate biscuits in the hemoglobin levels was higher than the control group (+1.1 ± 0.2 g/dL) but no difference was found between consumers of fortified biscuits with heme iron concentrate or iron sulfate (+1.9 ± 0.2 g/dL and +2.0 ± 0.2 g/dL, respectively). Heme iron concentrate and iron sulfate were equally effective in increasing Hb levels and hematological indices. Processed foods were shown to be an effective, valuable, and admissible intervention to prevent anemia in preschool children.

Clinical and Laboratory Associations with Persistent Hyperferritinemia in 373 Black Hemochromatosis and Iron Overload Screening Study Participants.

PubMed

Barton, James C; Barton, J Clayborn; Adams, Paul C

2017-01-01

373 black participants had elevated screening and post-screening serum ferritin (SF) (> 300 μg/L men; > 200 μg/L women). We retrospectively studied SF and post-screening age; sex; body mass index; transferrin saturation (TS); ALT; AST; GGT; elevated C-reactive protein; ß-thalassemia; neutrophils; lymphocytes; monocytes; platelets; metacarpophalangeal joint hypertrophy; hepatomegaly; splenomegaly; diabetes; HFE H63D positivity; iron/alcohol intakes; and blood/erythrocyte transfusion units. Liver disease was defined as elevated ALT or AST. We computed correlations of SF and TS with: age; body mass index; ALT; AST; GGT; C-reactive protein; blood cell counts; and iron/alcohol. We compared participants with SF > 1,000 and ≤ 1,000 μg/L and performed regressions on SF. There were 237 men (63.5%). Mean age was 55 ± 13 (SD) y. 143 participants had liver disease (62 hepatitis B or C). There were significant correlations of SF: TS, ALT, AST, GGT, and monocytes (positive); and SF and TS with platelets (negative). 22 participants with SF > 1,000 μg/L had significantly higher median TS, ALT, and AST, and prevalences of anemia and transfusion > 10 units; and lower median platelets. Regression on SF revealed significant associations: TS; male sex; age; GGT; transfusion units (positive); and splenomegaly (negative) (p < 0.0001, 0.0016, 0.0281, 0.0025, 0.0001, and 0.0096, respectively). Five men with SF > 1,000 μg/L and elevated TS had presumed primary iron overload (hemochromatosis). Four participants had transfusion iron overload. Persistent hyperferritinemia in 373 black adults was associated with male sex, age, TS, GGT, and transfusion. 2.4% had primary iron overload (hemochromatosis) or transfusion iron overload.

Elevated Temperature Properties of Titanium Carbide Base Ceramals Containing Nickel or Iron

NASA Technical Reports Server (NTRS)

Cooper, A L; Colteryahn, L E

1951-01-01

Elevated-temperature properties of titanium carbide base ceramals containing nickel or iron were determined in oxidation, modulus of rupture, tensile strength, and thermal-shock resistance. These materials followed the general growth law and exhibited two stages in oxidation. The following tensile strengths were found at 2000 degrees F: 13.3 weight percent nickel, 16, 150 pounds per square inch; 11.8 weight percent iron, 12,500 pounds per square inch; unalloyed titanium carbide, 16,450 pounds per square inch. Nickel or iron additions to titanium carbide improved the thermal-shock resistance, nickel more. The path of fracture in tensile and thermal-shock specimens was found to progress approximately 50 percent intergranularly and 50 percent transgranularly.

Iron overload in HFE C282Y heterozygotes at first genetic testing: a strategy for identifying rare HFE variants.

PubMed

Aguilar-Martinez, Patricia; Grandchamp, Bernard; Cunat, Séverine; Cadet, Estelle; Blanc, François; Nourrit, Marlène; Lassoued, Kaiss; Schved, Jean-François; Rochette, Jacques

2011-04-01

Heterozygotes for the p.Cys282Tyr (C282Y) mutation of the HFE gene do not usually express a hemochromatosis phenotype. Apart from the compound heterozygous state for C282Y and the widespread p.His63Asp (H63D) variant allele, other rare HFE mutations can be found in trans on chromosome 6. We performed molecular investigation of the genes implicated in hereditary hemochromatosis in six patients who presented with iron overload but were simple heterozygotes for the HFE C282Y mutation at first genetic testing. Functional impairment of new variants was deduced from computational methods including molecular modeling studies. We identified four rare HFE mutant alleles, three of which have not been previously described. One mutation is a 13-nucleotide deletion in exon 6 (c.1022_1034del13, p.His341_Ala345 > LeufsX119), which is predicted to lead to an elongated and unstable protein. The second one is a substitution of the last nucleotide of exon 2 (c.340G > A, p.Glu114Lys) which modifies the relative solvent accessibility in a loop interface. The third mutation, p.Arg67Cys, also lies in exon 2 and introduces a destabilization of the secondary structure within a loop of the α1 domain. We also found the previously reported c.548T > C (p.Leu183Pro) missense mutation in exon 3. No other known iron genes were mutated. We present an algorithm at the clinical and genetic levels for identifying patients deserving further investigation. Conclusions Our results suggest that additional mutations in HFE may have a clinical impact in C282Y carriers. In conjunction with results from previously described cases we conclude that an elevated transferrin saturation level and elevated hepatic iron index should indicate the utility of searching for further HFE mutations in C282Y heterozygotes prior to other iron gene studies.

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

Effects of iron and iron chelation in vitro on mucosal oxidant activity in ulcerative colitis.

PubMed

Millar, A D; Rampton, D S; Blake, D R

2000-09-01

Reactive oxygen species may be pathogenic in ulcerative colitis. Oral iron supplements anecdotally exacerbate inflammatory bowel disease and iron levels are elevated in the inflamed mucosa. Mucosal iron may enhance hydroxyl ion production via Fenton chemistry. Conversely, the iron chelator, desferrioxamine, is reportedly beneficial in Crohn's disease. To assess the in vitro effects of exogenous iron and of iron chelators on the production of reactive oxygen species by colonic biopsies from normal control subjects and patients with ulcerative colitis. Luminol-amplified chemiluminescence was used to measure mucosal reactive oxygen species production both before and after addition in vitro of ferric citrate (100 microM), desferrioxamine (1 mM) and 1,10-phenanthroline (1 mM). Ferric citrate had no effect on the chemiluminescence produced by human colonic mucosa. However, desferrioxamine and phenanthroline reduced chemiluminescence by 47% (n=7, P=0.018) and by 26% (n=10, P=0.005), respectively, in inactive ulcerative colitis, and by 44% (n=9, P=0. 008) and 42% (n=11, P=0.006) in active disease. The lack of effect of ferric citrate suggests that sufficient free iron is already present in inflamed biopsies to drive the Fenton reaction maximally. The effects of desferrioxamine and 1,10-phenanthroline on the chemiluminescence of biopsies from patients with ulcerative colitis suggest that a clinical trial of topical iron chelation in active disease is indicated.

Deviation from Boltzmann distribution in excited energy levels of singly-ionized iron in an argon glow discharge plasma for atomic emission spectrometry

NASA Astrophysics Data System (ADS)

Zhang, Lei; Kashiwakura, Shunsuke; Wagatsuma, Kazuaki

2012-01-01

A Boltzmann plot for many iron ionic lines having excitation energies of 4.7-9.1 eV was investigated in an argon glow discharge plasma when the discharge parameters, such as the voltage/current and the gas pressure, were varied. A Grimm-style radiation source was employed in a DC voltage range of 400-800 V at argon pressures of 400-930 Pa. The plot did not follow a linear relationship over a wide range of the excitation energy, but it yielded a normal Boltzmann distribution in the range of 4.7-5.8 eV and a large overpopulation in higher-lying excitation levels of iron ion. A probable reason for this phenomenon is that excitations for higher excited energy levels of iron ion would be predominantly caused by non-thermal collisions with argon species, the internal energy of which is received by iron atoms for the ionization. Particular intense ionic lines, which gave a maximum peak of the Boltzmann plot, were observed at an excitation energy of ca. 7.7 eV. They were the Fe II 257.297-nm and the Fe II 258.111-nm lines, derived from the 3d54s4p 6P excited levels. The 3d54s4p 6P excited levels can be highly populated through a resonance charge transfer from the ground state of argon ion, because of good matching in the excitation energy as well as the conservation of the total spin before and after the collision. An enhancement factor of the emission intensity for various Fe II lines could be obtained from a deviation from the normal Boltzmann plot, which comprised the emission lines of 4.7-5.8 eV. It would roughly correspond to a contribution of the charge transfer excitation to the excited levels of iron ion, suggesting that the charge-transfer collision could elevate the number density of the corresponding excited levels by a factor of ca.104. The Boltzmann plots give important information on the reason why a variety of iron ionic lines can be emitted from glow discharge plasmas.

Decreased serum hepcidin, inflammation, and improved functional iron status six-months post-restrictive bariatric surgery.

USDA-ARS?s Scientific Manuscript database

Excess adiposity is associated with low-grade inflammation and decreased iron status. Iron depletion (ID) in obesity is thought to be mediated by an inflammation-induced increase in the body’s main regulator of iron homeostasis, hepcidin. Elevated hepcidin can result in ID as it prevents the release...

Analysis of high iron rice lines reveals new miRNAs that target iron transporters in roots

PubMed Central

Paul, Soumitra; Gayen, Dipak; Datta, Swapan K.; Datta, Karabi

2016-01-01

The present study highlights the molecular regulation of iron transport in soyFER1-overexpressing transgenic rice. Accumulation of iron in three different seed developmental stages, milk, dough, and mature, has been examined. The transgenic seeds of the milk stage showed significant augmentation of iron and zinc levels compared with wild-type seeds, and similar results were observed throughout the dough and mature stages. To investigate the regulation of iron transport, the role of miRNAs was studied in roots of transgenic rice. Sequencing of small RNA libraries revealed 153 known and 41 novel miRNAs in roots. Among them, 59 known and 14 novel miRNAs were found to be significantly expressed. miR166, miR399, and miR408 were identified as playing a vital role in iron uptake in roots of transgenic plants . Most importantly, four putative novel miRNAs, namely miR11, miR26, miR30, and miR31, were found to be down-regulated in roots of transgenic plants. For all these four novel miRNAs, natural resistance-associated macrophage protein 4 (NRAMP4), encoding a metal transporter, was predicted as a target gene. It is hypothesized that the NRAMP4 transporter is activated in roots of transgenic plants due to the lower abundance of its corresponding putative novel miRNAs. The relative transcript level of the NRAMP4 transcript was increased from 0.107 in the wild type to 65.24 and 55.39 in transgenic plants, which demonstrates the elevated amount of iron transport in transgenic plants. In addition, up-regulation of OsYSL15, OsFRO2, and OsIRT1 in roots also facilitates iron loading in transgenic seeds. PMID:27729476

Circulating Hepcidin-25 Is Reduced by Endogenous Estrogen in Humans.

PubMed

Lehtihet, Mikael; Bonde, Ylva; Beckman, Lena; Berinder, Katarina; Hoybye, Charlotte; Rudling, Mats; Sloan, John H; Konrad, Robert J; Angelin, Bo

2016-01-01

Hepcidin reduces iron absorption by binding to the intestinal iron transporter ferroportin, thereby causing its degradation. Although short-term administration of testosterone or growth hormone (GH) has been reported to decrease circulating hepcidin levels, little is known about how hepcidin is influenced in human endocrine conditions associated with anemia. We used a sensitive and specific dual-monoclonal antibody sandwich immunoassay to measure hepcidin-25 in patients (a) during initiation of in vitro fertilization when endogenous estrogens were elevated vs. suppressed, (b) with GH deficiency before and after 12 months substitution treatment, (c) with hyperthyroidism before and after normalization, and (d) with hyperprolactinemia before and after six months of treatment with a dopamine agonist. In response to a marked stimulation of endogenous estrogen production, median hepcidin levels decreased from 4.85 to 1.43 ng/mL (p < 0.01). Hyperthyroidism, hyperprolactinemia, or GH substitution to GH-deficient patients did not influence serum hepcidin-25 levels. In humans, gonadotropin-stimulated endogenous estrogen markedly decreases circulating hepcidin-25 levels. No clear and stable correlation between iron biomarkers and hepcidin-25 was seen before or after treatment of hyperthyroidism, hyperprolactinemia or growth hormone deficiency.

Circulating Hepcidin-25 Is Reduced by Endogenous Estrogen in Humans

PubMed Central

Lehtihet, Mikael; Bonde, Ylva; Beckman, Lena; Berinder, Katarina; Hoybye, Charlotte; Rudling, Mats; Sloan, John H.; Konrad, Robert J.; Angelin, Bo

2016-01-01

Objective Hepcidin reduces iron absorption by binding to the intestinal iron transporter ferroportin, thereby causing its degradation. Although short-term administration of testosterone or growth hormone (GH) has been reported to decrease circulating hepcidin levels, little is known about how hepcidin is influenced in human endocrine conditions associated with anemia. Research design and methods We used a sensitive and specific dual–monoclonal antibody sandwich immunoassay to measure hepcidin-25 in patients (a) during initiation of in vitro fertilization when endogenous estrogens were elevated vs. suppressed, (b) with GH deficiency before and after 12 months substitution treatment, (c) with hyperthyroidism before and after normalization, and (d) with hyperprolactinemia before and after six months of treatment with a dopamine agonist. Results In response to a marked stimulation of endogenous estrogen production, median hepcidin levels decreased from 4.85 to 1.43 ng/mL (p < 0.01). Hyperthyroidism, hyperprolactinemia, or GH substitution to GH-deficient patients did not influence serum hepcidin-25 levels. Conclusions In humans, gonadotropin-stimulated endogenous estrogen markedly decreases circulating hepcidin-25 levels. No clear and stable correlation between iron biomarkers and hepcidin-25 was seen before or after treatment of hyperthyroidism, hyperprolactinemia or growth hormone deficiency. PMID:26866603

Elevated serum ferritin - what should GPs know?

PubMed

Goot, Katie; Hazeldine, Simon; Bentley, Peter; Olynyk, John; Crawford, Darrell

2012-12-01

Elevated serum ferritin is commonly encountered in general practice. Ninety percent of elevated serum ferritin is due to noniron overload conditions, where venesection therapy is not the treatment of choice. This article aims to outline the role of the Australian Red Cross Blood Service Therapeutic Venesection program, to clarify the interpretation of the HFE gene test and iron studies, and to describe the steps in evaluating a patient with elevated serum ferritin. After exclusion of hereditary haemochromatosis, investigation of elevated serum ferritin involves identifying alcohol consumption, metabolic syndrome, obesity, diabetes, liver disease, malignancy, infection or inflammation as causative factors. Referral to a gastroenterologist, haematologist or physician with an interest in iron overload is appropriate if serum ferritin is >1000 µg/L or if the cause of elevated serum ferritin is still unclear.

Effect of Nitrates, Thiocyanates and Selenium on the Iron and Iodine Status of Postpartum Women.

PubMed

Bivolarska, Anelia V; Maneva, Ana I; Gatseva, Penka D; Katsarova, Mariana N

2016-09-01

To find correlations between high thiocyanate and nitrate levels and low selenium levels and the indicators of the iodine and iron status of postpartum women. The study included 41 mothers aged 26.4±5.9 yrs from Asenovgrad and nearby villages. Urinary iodine was determined by the Sandell-Kolthoff reaction and thiocyanate - by the interaction of these ions with acidic solution of KMnO4; for serum nitrates we used the colorimetric method; serum selenium was assessed by electro-thermal atomic-absorption spectrophotometry; thyroxin (FT4), the thyroid stimulating hormone (TSH), serum ferritin (SF), and serum transferrin receptor (sTfR) were determined using ELISA; Hb levels were determined by hematology analyzer. Assessing the iodine status, we found a negative correlation between the levels of iodine and thiocyanates in urine (R=-0.717, р<0.0001), a positive correlation between nitrates and TSH (R=0.487, р=0.003) and a negative correlation between nitrates and FT4 (R=-0.312, р=0.06). For the iron status, we found a negative correlation between nitrates and SF (R=-0.429, р=0.009) and between nitrates and Hb (R=-0.383, р=0.021). The Mann-Whitney U-test showed that in women with nitrate levels higher than the mean value there was low FT4 level (р=0.06), high TSH level (р=0.013), low Hb concentration (р=0.061) and low SF concentration (р=0.005). The combined effects of environmental factors (elevated nitrate levels and low selenium level) on the iodine and iron status are manifested by low concentrations of FT4 (р=0.033), Hb (р=0.06) and SF (р=0.05) and high level of TSH (р=0.05). In conclusion, we found that environmental factors, especially when combined, have a negative impact on the iron and iodine status of females.

Daily propranolol administration reduces persistent injury-associated anemia after severe trauma and chronic stress.

PubMed

Alamo, Ines G; Kannan, Kolenkode B; Bible, Letitia E; Loftus, Tyler J; Ramos, Harry; Efron, Philip A; Mohr, Alicia M

2017-04-01

After severe trauma, patients develop a norepinephrine-mediated persistent, injury-associated anemia. This anemia is associated with suppression of bone marrow (BM) erythroid colony growth, along with decreased iron levels, and elevated erythropoietin (EPO) levels, which are insufficient to promote effective erythropoiesis. The impact of norepinephrine on iron regulators, such as ferroportin, transferrin, and transferrin receptor-1 (TFR-1), is unknown. Using a clinically relevant rodent model of lung contusion (LC), hemorrhagic shock (HS), and chronic stress (CS), we hypothesize that daily propranolol (BB), a nonselective β blocker, restores BM function and improves iron homeostasis. Male Sprague-Dawley rats were subjected to LCHS ± BB and LCHS/CS ± BB. BB was achieved with propranolol (10 mg/kg) daily until the day of sacrifice. Hemoglobin, plasma EPO, plasma hepcidin, BM cellularity and BM erythroid colony growth were assessed. RNA was isolated to measure transferrin, TFR-1 and ferroportin expression. Data are presented as mean ± SD; *p < 0.05 versus untreated counterpart by t test. The addition of CS to LCHS leads to persistent anemia on posttrauma day 7, while the addition of BB improved hemoglobin levels (LCHS/CS: 10.6 ± 0.8 vs. LCHS/CS + BB: 13.9 ± 0.4* g/dL). Daily BB use after LCHS/CS improved BM cellularity, colony-forming units granulocyte, erythrocyte, monocyte megakaryocyte, burst-forming unit erythroid and colony-forming unit erythroid cell colony growth. LCHS/CS + BB significantly reduced plasma EPO levels and increased plasma hepcidin levels on day 7. The addition of CS to LCHS resulted in decreased liver ferroportin expression as well as decreased BM transferrin and TFR-1 expression, thus, blocking iron supply to erythroid cells. However, daily BB after LCHS/CS improved expression of all iron regulators. Daily propranolol administration after LCHS/CS restored BM function and improved anemia after severe trauma. In addition, iron regulators are significantly reduced after LCHS/CS, which may contribute to iron restriction after injury. However, daily propranolol administration after LCHS/CS improved iron homeostasis.

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.

Iron, zinc, and copper in retinal physiology and disease.

PubMed

Ugarte, Marta; Osborne, Neville N; Brown, Laurence A; Bishop, Paul N

2013-01-01

The essential trace metals iron, zinc, and copper play important roles both in retinal physiology and disease. They are involved in various retinal functions such as phototransduction, the visual cycle, and the process of neurotransmission, being tightly bound to proteins and other molecules to regulate their structure and/or function or as unbound free metal ions. Elevated levels of "free" or loosely bound metal ions can exert toxic effects, and in order to maintain homeostatic levels to protect retinal cells from their toxicity, appropriate mechanisms exist such as metal transporters, chaperones, and the presence of certain storage molecules that tightly bind metals to form nontoxic products. The pathways to maintain homeostatic levels of metals are closely interlinked, with various metabolic pathways directly and/or indirectly affecting their concentrations, compartmentalization, and oxidation/reduction states. Retinal deficiency or excess of these metals can result from systemic depletion and/or overload or from mutations in genes involved in maintaining retinal metal homeostasis, and this is associated with retinal dysfunction and pathology. Iron accumulation in the retina, a characteristic of aging, may be involved in the pathogenesis of retinal diseases such as age-related macular degeneration (AMD). Zinc deficiency is associated with poor dark adaptation. Zinc levels in the human retina and RPE decrease with age in AMD. Copper deficiency is associated with optic neuropathy, but retinal function is maintained. The changes in iron and zinc homeostasis in AMD have led to the speculation that iron chelation and/or zinc supplements may help in its treatment. Copyright © 2013 Elsevier Inc. All rights reserved.

Concentration of heavy metals in drinking water of different localities in district east Karachi.

PubMed

Jaleel, M A; Noreen, R; Baseer, A

2001-01-01

Several heavy metals are present in drinking water that play important roles in the body provided their level remains within the specified range recommended by WHO. But now due to the industrialization and rapid urbanization, the problems of pollution have surfaced. This study was designed to ascertain the contents of some heavy metals and then their variations if any in drinking water in different localities of district East of Karachi, Pakistan. Drinking water samples were collected from different sources and localities of district East of Karachi. The concentration of the heavy metals i.e. Lead, Arsenic, Copper, Iron, Mercury, Chromium, Manganese, Nickel, Cadmium and Zinc were determined by Atomic Absorption Spectrophotometry. PH was estimated by pH meter. Total dissolved solids (TDS) were calculated by formula. These concentrations of heavy metals, pH and TDS were compared with the standards set by WHO. Concentrations of lead and nickel were found to be significantly elevated as compared to WHO recommended levels in all the three sources of water (Piped water, Hand pump water and Tanker water supply). Chromium was found to be raised in hand pump water. Arsenic and Mercury were not detected in any source of water. Copper, iron, manganese, cadmium and zinc were found to be within the safe limits in all the three sources of water. pH was found to be within the range of WHO recommended level in all the three sources of water. TDS was found to be elevated in hand pump water and tanker water. Concentrations of lead and nickel were found to be significantly elevated as compared to WHO recommended levels in all the three sources of water in district East of Karachi.

Regulation of type II transmembrane serine proteinase TMPRSS6 by hypoxia-inducible factors: new link between hypoxia signaling and iron homeostasis.

PubMed

Lakhal, Samira; Schödel, Johannes; Townsend, Alain R M; Pugh, Christopher W; Ratcliffe, Peter J; Mole, David R

2011-02-11

Hepcidin is a liver-derived hormone with a key role in iron homeostasis. In addition to iron, it is regulated by inflammation and hypoxia, although mechanisms of hypoxic regulation remain unclear. In hepatocytes, hepcidin is induced by bone morphogenetic proteins (BMPs) through a receptor complex requiring hemojuvelin (HJV) as a co-receptor. Type II transmembrane serine proteinase (TMPRSS6) antagonizes hepcidin induction by BMPs by cleaving HJV from the cell membrane. Inactivating mutations in TMPRSS6 lead to elevated hepcidin levels and consequent iron deficiency anemia. Here we demonstrate that TMPRSS6 is up-regulated in hepatic cell lines by hypoxia and by other activators of hypoxia-inducible factor (HIF). We show that TMPRSS6 expression is regulated by both HIF-1α and HIF-2α. This HIF-dependent up-regulation of TMPRSS6 increases membrane HJV shedding and decreases hepcidin promoter responsiveness to BMP signaling in hepatocytes. Our results reveal a potential role for TMPRSS6 in hepcidin regulation by hypoxia and provide a new molecular link between oxygen sensing and iron homeostasis.

Diabetes in HFE Hemochromatosis

PubMed Central

Acton, Ronald T.

2017-01-01

Diabetes in whites of European descent with hemochromatosis was first attributed to pancreatic siderosis. Later observations revealed that the pathogenesis of diabetes in HFE hemochromatosis is multifactorial and its clinical manifestations are heterogeneous. Increased type 2 diabetes risk in HFE hemochromatosis is associated with one or more factors, including abnormal iron homeostasis and iron overload, decreased insulin secretion, cirrhosis, diabetes in first-degree relatives, increased body mass index, insulin resistance, and metabolic syndrome. In p.C282Y homozygotes, serum ferritin, usually elevated at hemochromatosis diagnosis, largely reflects body iron stores but not diabetes risk. In persons with diabetes type 2 without hemochromatosis diagnoses, serum ferritin levels are higher than those of persons without diabetes, but most values are within the reference range. Phlebotomy therapy to achieve iron depletion does not improve diabetes control in all persons with HFE hemochromatosis. The prevalence of type 2 diabetes diagnosed today in whites of European descent with and without HFE hemochromatosis is similar. Routine iron phenotyping or HFE genotyping of patients with type 2 diabetes is not recommended. Herein, we review diabetes in HFE hemochromatosis and the role of iron in diabetes pathogenesis in whites of European descent with and without HFE hemochromatosis. PMID:28331855

Minerals in thalassaemia major patients: An overview.

PubMed

Ozturk, Zeynep; Genc, Gizem Esra; Gumuslu, Saadet

2017-05-01

Thalassaemia major (TM) is a hereditary blood disease characterised by reduced or absent production of beta globin chains. Erythrocyte transfusions are given to raise the haemoglobin level in patients with thalassaemia major. However, transfusions have been related to increased risk of iron overload and tissue damage related to excess iron. Both elevated oxidative stress due to iron overload and increased hemolysis lead to over utilisation of minerals required for antioxidant enzymes activities. Iron chelators have been used to prevent iron overload in thalassaemia major patients, but these chelators have the possibility of removing minerals from the body. Thalassaemia patients are more at risk for mineral deficiency because of increased oxidative stress and iron chelation therapies. Growth and maturational delay, cardiomyopathy, endocrinopathies and osteoporosis are the complications of thalassaemia. Minerals may play a particular role to prevent these complications. In the current review, we provide an overview of minerals including zinc (Zn), copper (Cu), selenium (Se), magnesium (Mg) and calcium (Ca) in thalassaemia major patients. We, also, underline that some complications of thalassaemia can be caused by an increased need for minerals or lack of the minerals. Copyright © 2017 Elsevier GmbH. All rights reserved.

Iron-Tolerant Cyanobacteria: Ecophysiology and Fingerprinting

NASA Technical Reports Server (NTRS)

Brown, I. I.; Mummey, D.; Lindsey, J.; McKay, D. S.

2006-01-01

Although the iron-dependent physiology of marine and freshwater cyanobacterial strains has been the focus of extensive study, very few studies dedicated to the physiology and diversity of cyanobacteria inhabiting iron-depositing hot springs have been conducted. One of the few studies that have been conducted [B. Pierson, 1999] found that cyanobacterial members of iron depositing bacterial mat communities might increase the rate of iron oxidation in situ and that ferrous iron concentrations up to 1 mM significantly stimulated light dependent consumption of bicarbonate, suggesting a specific role for elevated iron in photosynthesis of cyanobacteria inhabiting iron-depositing hot springs. Our recent studies pertaining to the diversity and physiology of cyanobacteria populating iron-depositing hot springs in Great Yellowstone area (Western USA) indicated a number of different isolates exhibiting elevated tolerance to Fe(3+) (up to 1 mM). Moreover, stimulation of growth was observed with increased Fe(3+) (0.02-0.4 mM). Molecular fingerprinting of unialgal isolates revealed a new cyanobacterial genus and species Chroogloeocystis siderophila, an unicellular cyanobacterium with significant EPS sheath harboring colloidal Fe(3+) from iron enriched media. Our preliminary data suggest that some filamentous species of iron-tolerant cyanobacteria are capable of exocytosis of iron precipitated in cytoplasm. Prior to 2.4 Ga global oceans were likely significantly enriched in soluble iron [Lindsay et al, 2003], conditions which are not conducive to growth of most contemporary oxygenic cyanobacteria. Thus, iron-tolerant CB may have played important physiological and evolutionary roles in Earths history.

Effects of iron on arsenic speciation and redox chemistry in acid mine water

USGS Publications Warehouse

Bednar, A.J.; Garbarino, J.R.; Ranville, J.F.; Wildeman, T.R.

2005-01-01

Concern about arsenic is increasing throughout the world, including areas of the United States. Elevated levels of arsenic above current drinking-water regulations in ground and surface water can be the result of purely natural phenomena, but often are due to anthropogenic activities, such as mining and agriculture. The current study correlates arsenic speciation in acid mine drainage and mining-influenced water with the important water-chemistry properties Eh, pH, and iron(III) concentration. The results show that arsenic speciation is generally in equilibrium with iron chemistry in low pH AMD, which is often not the case in other natural-water matrices. High pH mine waters and groundwater do not always hold to the redox predictions as well as low pH AMD samples. The oxidation and precipitation of oxyhydroxides deplete iron from some systems, and also affect arsenite and arsenate concentrations through sorption processes. ?? 2004 Elsevier B.V. All rights reserved.

Phytotoxin production in Aspergillus terreus is regulated by independent environmental signals

PubMed Central

Gressler, Markus; Meyer, Florian; Heine, Daniel; Hortschansky, Peter; Hertweck, Christian; Brock, Matthias

2015-01-01

Secondary metabolites have a great potential as pharmaceuticals, but there are only a few examples where regulation of gene cluster expression has been correlated with ecological and physiological relevance for the producer. Here, signals, mediators, and biological effects of terrein production were studied in the fungus Aspergillus terreus to elucidate the contribution of terrein to ecological competition. Terrein causes fruit surface lesions and inhibits plant seed germination. Additionally, terrein is moderately antifungal and reduces ferric iron, thereby supporting growth of A. terreus under iron starvation. In accordance, the lack of nitrogen or iron or elevated methionine levels induced terrein production and was dependent on either the nitrogen response regulators AreA and AtfA or the iron response regulator HapX. Independent signal transduction allows complex sensing of the environment and, combined with its broad spectrum of biological activities, terrein provides a prominent example of adapted secondary metabolite production in response to environmental competition. DOI: http://dx.doi.org/10.7554/eLife.07861.001 PMID:26173180

Behavior and Monoamine Deficits in Prenatal and Perinatal Iron Deficiency Are Not Corrected by Early Postnatal Moderate-Iron or High-Iron Diets in Rats12

PubMed Central

Unger, Erica L.; Hurst, Amy R.; Georgieff, Michael K.; Schallert, Tim; Rao, Raghavendra; Connor, James R.; Kaciroti, Niko; Lozoff, Betsy; Felt, Barbara

2012-01-01

Developmental iron deficiency anemia (IDA) causes brain and behavioral deficits in rodent models, which cannot be reversed when treated at periods equivalent to later infancy in humans. This study sought to determine whether earlier iron treatment can normalize deficits of IDA in rats and what iron dose is optimal. The offspring of dams with IDA during gestation were cross-fostered at postnatal d (P) 8 to dams receiving diets with 1 of 3 iron concentrations until weaning (P21): 0.003–0.01 g/kg [totally iron deficient (TID)]; 0.04 g/kg [formerly iron deficient (FID-40)]; or 0.4 g/kg (FID-400). Always iron-sufficient control dams (CN-40) received a 0.04-g/kg iron diet. At P21, TID pups received a 0.01 g iron/kg diet; all others received a 0.04 g iron/kg diet. Hematocrit and brain iron and monoamine concentrations were assessed at P21 and P100. Pup growth, development, activity, object recognition, hesitancy, and watermaze performance were evaluated. Regional brain iron was restored by iron treatment. Regional monoamine and metabolite concentrations were elevated in FID-40 rats and reduced in FID-400 and TID rats compared with CN-40 rats. FID-40 offspring had motor delays similar to TID during lactation and FID-400 rats had elevated thigmotaxis similar to TID rats at P25 and P100 in the spatial watermaze. In conclusion, iron treatment at P8 in rats did not normalize all monoamine or behavioral measures after early IDA. Moderate iron treatment improved adult behavior, but higher iron treatment caused brain and behavioral patterns similar to TID in the short and long term. PMID:22990465

Amyloid Precursor Protein Haploinsufficiency Preferentially Mediates Brain Iron Accumulation in Mice Transgenic for The Huntington's Disease Mutation.

PubMed

Berggren, Kiersten; Agrawal, Sonal; Fox, Julia A; Hildenbrand, Justin; Nelson, Ryan; Bush, Ashley I; Fox, Jonathan H

2017-01-01

Huntington's disease (HD) is an autosomal dominant disorder caused by a CAG expansion in the huntingtin gene that results in expression of mutant huntingtin protein. Iron accumulates in HD brain neurons. Amyloid precursor protein (APP) promotes neuronal iron export. However, the role of APP in brain iron accumulation in HD is unclear. To determine the effects of APP insufficiency on HD in YAC128 mice. We crossed APP hemizygous mice (APP+/-) with YAC128 mice that are transgenic (Tg) for human mutant huntingtin (hmHTT) to generate APP+/+ hmHTT-/-, APP+/- hmHTT-/-, APP+/+ hmHTT+/- and APP+/- hmHTT+/- progeny. Mice were evaluated for behavioral, biochemical and neuropathology HD outcomes at 2-12 months of age. APP heterozygosity decreased cortical APP 25% and 60% in non-Tg and Tg mice, respectively. Cerebral and striatal iron levels were increased by APP knockdown in Tg mice only. Nest-building behavior was decreased in Tg mice; APP knockdown decreased nest building in non-Tg but not Tg mice. Rota-rod endurance was decreased in Tg mice. APP+/- hHTT+/- mice demonstrated additional decreases in rota-rod endurance from 4-10 months of age. Tg mice had smaller striatal volumes and fewer striatal neurons but were not affected by APP knockdown. APP heterozygosity results in greater decreases of cortical APP in Tg versus non-Tg mice. Mutant huntingtin transgenic mice develop brain iron accumulation as a result of greater suppression of APP levels. Elevated brain iron in Tg mice was associated with a decline in motor endurance consistent with a disease promoting effect of iron in the YAC128 model of human HD.

The habenula and iron metabolism in cerebral mouse models of multiple sclerosis

PubMed Central

Sands, Scott A.; Tsau, Sheila; LeVine, Steven M.

2015-01-01

Iron accumulates in the CNS of patients with multiple sclerosis, but our understanding of the mechanism accounting for this accumulation is unclear. Mouse models of cerebral experimental autoimmune encephalomyelitis (EAE) in C57BL/6 and SJL mice were used together with a histochemical stain for iron and immunohistochemical stains for transferrin receptor, synaptophysin, iron regulatory protein 1 (IRP1) and/or IRP2 to investigate the role of disease activity on CNS iron metabolism. The expression of transferrin receptor, but not IRP1 or IRP2, increased in the medial habenula, which is adjacent to the third ventricle, in response to both types of cerebral EAE. In the habenula, the elevated expression of transferrin receptor in C57BL/6 mice with cerebral EAE was generally restricted to the medial habenula while the expression in SJL mice with cerebral EAE was more diffusely expressed. Iron levels were increased in all regions of the habenula in C57BL/6 mice with cerebral EAE, and in the medial and medial lateral but not the lateral habenula in SJL mice with cerebral EAE. Synaptophysin, which has been observed previously in endocytic vesicles together with the transferrin receptor, was concentrated at the medial habenula, but its levels did not increase with disease in C57BL/6 mice with cerebral EAE. Our results support the model that the medial habenula responds to disease activity by upregulating transferrin receptor to facilitate the movement of iron into the brain from the third ventricle, raising the possibility that a similar mechanism accounts for iron accumulation in deep gray matter structures in patients with multiple sclerosis. PMID:26362814

[Old and new iron parameters in iron metabolism and diagnostics].

PubMed

Graf, Lukas; Herklotz, Roberto; Huber, Andreas R; Korte, Wolfgang

2008-09-01

Iron is an element which is essential to life but also potentially toxic. Therefore, clever mechanisms exist in the human body for uptake, transport and storage of iron. Hepcidin, which seems to be the master protein for regulation of intestinal iron absorption, is known for a short time. The expression of hepcidin is not only influenced by iron levels but also by mediators of inflammation and growth factors of erythropoiesis. Hence hepcidin plays also a crucial role in the development of anemia of chronic disease and iron overload due to ineffective erythropoiesis. Serum ferritin is a reliable parameter to estimate the storage iron. It is an acute phase protein which is elevated during infections and inflammations, though. In these situations, measurement of soluble transferrin receptors is a useful tool to differentiate between iron deficiency and anemia of chronic disease. Newer parameters as erythrocyte zink protoporphyrin or percentage of hypochromic erythrocytes (%HYPO) are suited to detect a functional iron deficiency. Early diagnosis of iron overload is essential to prevent organ damage. Serum ferritin and transferrin are useful parameters to screen for iron overload. If no clear reason for a secondary iron overload can be found, the search for a hereditary haemochromatosis is recommended. Most of these hereditary haemochromatoses are a result of mutations in the HFE gene (homozygous state for Cys282Tyr or compound heterozygosity for Cys282Tyr/ His63Asp) which can be detected by PCR technique. Liver biopsy is still the gold standard for quantification of storage iron. However, a method of increasing importance for quantification of iron overload is magnetic resonance imaging with new approaches as for example T2*.

Impact of high iron intake on cognition and neurodegeneration in humans and in animal models: a systematic review

PubMed Central

Agrawal, Sonal; Berggren, Kiersten L.; Marks, Eileen; Fox, Jonathan H.

2017-01-01

Abstract Context Accumulation of brain iron is linked to aging and protein-misfolding neurodegenerative diseases. High iron intake may influence important brain health outcomes in later life. Objective The aim of this systematic review was to examine evidence from animal and human studies of the effects of high iron intake or peripheral iron status on adult cognition, brain aging, and neurodegeneration. Data Sources MEDLINE, Scopus, CAB Abstracts, the Cochrane Central Register of Clinical Trials, and OpenGrey databases were searched. Study Selection Studies investigating the effect of elevated iron intake at all postnatal life stages in mammalian models and humans on measures of adult brain health were included. Data Extraction Data were extracted and evaluated by two authors independently, with discrepancies resolved by discussion. Neurodegenerative disease diagnosis and/or behavioral/cognitive, biochemical, and brain morphologic findings were used to study the effects of iron intake or peripheral iron status on brain health. Risk of bias was assessed for animal and human studies. PRISMA guidelines for reporting systematic reviews were followed. Results Thirty-four preclinical and 14 clinical studies were identified from database searches. Thirty-three preclinical studies provided evidence supporting an adverse effect of nutritionally relevant high iron intake in neonates on brain-health-related outcomes in adults. Human studies varied considerably in design, quality, and findings; none investigated the effects of high iron intake in neonates/infants. Conclusions Human studies are needed to verify whether dietary iron intake levels used in neonates/infants to prevent iron deficiency have effects on brain aging and neurodegenerative disease outcomes. PMID:28505363

Ethnic and genetic factors of iron status in women of reproductive age.

PubMed

Gordeuk, Victor R; Brannon, Patsy M

2017-12-01

Background: African Americans are at increased risk of iron deficiency (ID) but also have higher serum ferritin (SF) concentrations than those of the general population. The Hemochromatosis and Iron Overload Screening (HEIRS) Study was a multicenter study of ethnically diverse participants that tested for the hemochromatosis ( HFE ) C282Y genotype and iron status. Objective: We sought to determine the prevalence and predictors of ID (SF concentration ≤15 μg/L) and elevated iron stores (SF concentration >300 μg/L) in HEIRS women of reproductive age (25-44 y). Design: The HEIRS Study was a cross-sectional study of iron status and HFE mutations in primary care patients at 5 centers in the United States and Canada. We analyzed data for women of reproductive age according to whether or not they were pregnant or breastfeeding at the time of the study. Results: ID was present in 12.5% of 20,080 nonpregnant and nonbreastfeeding women compared with 19.2% of 1962 pregnant or breastfeeding women ( P < 0.001). Asian American ethnicity (OR ≤0.9; P ≤ 0.049) and HFE C282Y (OR ≤0.84; P ≤ 0.060) were independently associated with a decreased risk of ID in nonpregnant and nonbreastfeeding women and in pregnant or breastfeeding women. Hispanic ethnicity (OR: 1.8; P < 0.001) and African American ethnicity (OR: 1.6; P < 0.001) were associated with an increased risk of ID in nonpregnant and nonbreastfeeding women. Elevated iron stores were shown in 1.7% of nonpregnant and nonbreastfeeding women compared with 0.7% of pregnant or breastfeeding women ( P = 0.001). HFE C282Y homozygosity had the most marked independent association with elevated iron stores in nonpregnant and nonbreastfeeding women and in pregnant or breastfeeding women (OR >49.0; P < 0.001), but African American ethnicity was also associated with increased iron stores in both groups of women (OR >2.0; P < 0.001). Asian American ethnicity (OR: 1.8; P = 0.001) and HFE C282Y heterozygosity (OR: 1.9; P = 0.003) were associated with increased iron stores in nonpregnant and nonbreastfeeding women. Conclusions: Both ID and elevated iron stores are present in women of reproductive age and are influenced by ethnicity and HFE C282Y. Efforts to optimize iron status should keep these findings in view. This study was registered at clinicaltrials.gov as NCT03276247. © 2017 American Society for Nutrition.

The role of myoglobin degradation in nephrotoxicity after rhabdomyolysis.

PubMed

Zorova, Ljubava D; Pevzner, Irina B; Chupyrkina, Anastasia A; Zorov, Savva D; Silachev, Denis N; Plotnikov, Egor Y; Zorov, Dmitry B

2016-08-25

The fate of myoglobin in renal cells was explored in an animal model of rhabdomyolysis known as the pathology highly related to oxidative stress resulting in impairment of renal functioning. The working hypothesis was that the proper degradation of myoglobin in rhabdomyolytic kidney can activate the reparative processes in the tissue. We found that incubation of myoglobin with kidney cells causes its accumulation in the cytoplasm. In rhabdomyolytic rats, the level of heme and free iron in cytoplasm and mitochondria of kidney cells is remarkably increased while inhibition of proteolysis results in further elevation of myoglobin content in the renal tissue. Heme oxygenase and ferritin levels were found to be increased in the kidney tissue at rhabdomyolysis and simulating conditions performed by i/v injection of myoglobin. In addition, the level of peroxidized lipids was high in rhabdomyolytic kidney and became even higher after inhibition of proteolysis by aprotinin. Elevated levels of carbonylated proteins were also observed after rhabdomyolysis, however, if prior to induction of rhabdomyolysis the injection of myoglobin was done, the level of carbonylated proteins dropped versus unprimed kidney tissue thus affording protection to the kidney against oxidative stress. Injection of myoglobin to the rat results in impairment of renal functioning and inhibition of myoglobin degradation in the rhabdomyolytic animal aggravates acute renal failure, demonstrating that degradation of myoglobin is somehow beneficial although it may result in undesired release of free iron which can participate in toxic redox cycling. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Landfill-stimulated iron reduction and arsenic release at the Coakley Superfund Site (NH).

PubMed

deLemos, Jamie L; Bostick, Benjamin C; Renshaw, Carl E; Stürup, Stefan; Feng, Xiahong

2006-01-01

Arsenic is a contaminant at more than one-third of all Superfund Sites in the United States. Frequently this contamination appearsto resultfrom geochemical processes rather than the presence of a well-defined arsenic source. Here we examine the geochemical processes that regulate arsenic levels at the Coakley Landfill Superfund Site (NH), a site contaminated with As, Cr, Pb, Ni, Zn, and aromatic hydrocarbons. Long-term field observations indicate that the concentrations of most of these contaminants have diminished as a result of treatment by monitored natural attenuation begun in 1998; however, dissolved arsenic levels increased modestly over the same interval. We attribute this increase to the reductive release of arsenic associated with poorly crystalline iron hydroxides within a glaciomarine clay layer within the overburden underlying the former landfill. Anaerobic batch incubations that stimulated iron reduction in the glaciomarine clay released appreciable dissolved arsenic and iron. Field observations also suggest that iron reduction associated with biodegradation of organic waste are partly responsible for arsenic release; over the five-year study period since a cap was emplaced to prevent water flow through the site, decreases in groundwater dissolved benzene concentrations at the landfill are correlated with increases in dissolved arsenic concentrations, consistent with the microbial decomposition of both benzene and other organics, and reduction of arsenic-bearing iron oxides. Treatment of contaminated groundwater increasingly is based on stimulating natural biogeochemical processes to degrade the contaminants. These results indicate that reducing environments created within organic contaminant plumes may release arsenic. In fact, the strong correlation (>80%) between elevated arsenic levels and organic contamination in groundwater systems at Superfund Sites across the United States suggests that arsenic contamination caused by natural degradation of organic contaminants may be widespread.

The Impact of Iron Adsorption on the Electronic and Photocatalytic Properties of the Zinc Oxide (0001) Surface: A First-Principles Study.

PubMed

Cheng, Jingsi; Wang, Ping; Hua, Chao; Yang, Yintang; Zhang, Zhiyong

2018-03-12

The structural stability, electronic structure, and optical properties of an iron-adsorbed ZnO (0001) surface with three high-symmetry adsorption sites are investigated with first-principle calculations on the basis of density functional theory and the Hubbard-U method. It is found that the iron adatom in the H₃ adsorption site of ZnO (0001) surface has the lowest adsorption energy of -5.665 eV compared with T₄ and Top sites. For the Top site, compared with the pristine ZnO (0001) surface, the absorption peak located at 1.17 eV has a red shift, and the elevation of the absorption coefficient is more pronounced in the visible-light region, because the Fe-related levels are introduced in the forbidden band and near the Fermi level. The electrostatic potential computation reveals that the work function of the ZnO (0001) surface is significantly decreased from 2.340 to 1.768 eV when iron is adsorbed on the Top site. Furthermore, the degradation mechanism based on the band structure is analyzed. It can be concluded that the adsorption of iron will promote the separation of photoinduced carriers, thus improving the photocatalytic activity of ZnO (0001) surface. Our study benefits research on the photocatalytic activity of ZnO and the utilization rate of solar energy.

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

Galvanic Corrosion of Lead by Iron (Oxyhydr)Oxides: Potential Impacts on Drinking Water Quality.

PubMed

Trueman, Benjamin F; Sweet, Gregory A; Harding, Matthew D; Estabrook, Hayden; Bishop, D Paul; Gagnon, Graham A

2017-06-20

Lead exposure via drinking water remains a significant public health risk; this study explored the potential effects of upstream iron corrosion on lead mobility in water distribution systems. Specifically, galvanic corrosion of lead by iron (oxyhydr)oxides was investigated. Coupling an iron mineral cathode with metallic lead in a galvanic cell increased lead release by 531 μg L -1 on average-a 9-fold increase over uniform corrosion in the absence of iron. Cathodes were composed of spark plasma sintered Fe 3 O 4 or α-Fe 2 O 3 or field-extracted Fe 3 O 4 and α-FeOOH. Orthophosphate immobilized oxidized lead as insoluble hydroxypyromorphite, while humic acid enhanced lead mobility. Addition of a humic isolate increased lead release due to uniform corrosion by 81 μg L -1 and-upon coupling lead to a mineral cathode-release due to galvanic corrosion by 990 μg L -1 . Elevated lead in the presence of humic acid appeared to be driven by complexation, with 208 Pb and UV 254 size-exclusion chromatograms exhibiting strong correlation under these conditions (R 2 average = 0.87). A significant iron corrosion effect was consistent with field data: lead levels after lead service line replacement were greater by factors of 2.3-4.7 at sites supplied by unlined cast iron distribution mains compared with the alternative, lined ductile iron.

Modeling Red Blood Cell and Iron Dynamics in Patients with Chronic Kidney Disease

DTIC Science & Technology

2012-02-10

level in the body. Most patients with CKD have elevated levels of inflammation due to CKD and the presence of other medical issues (e.g., diabetes ...Blood, 37 (1971), 725–732. [11] Chung-Che Chang, Yayan Chen, Kapil Modi , Omar Awar, Clarence P. Alfrey, and Lawrence Rice, Changes of red blood cell...National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, MD, 2008. [43] M. M. Udden, T. B. Driscoll, M

Tmprss6 is a genetic modifier of the Hfe-hemochromatosis phenotype in mice

PubMed Central

Whittlesey, Rebecca L.; Andrews, Nancy C.

2011-01-01

The hereditary hemochromatosis protein HFE promotes the expression of hepcidin, a circulating hormone produced by the liver that inhibits dietary iron absorption and macrophage iron release. HFE mutations are associated with impaired hepatic bone morphogenetic protein (BMP)/SMAD signaling for hepcidin production. TMPRSS6, a transmembrane serine protease mutated in iron-refractory iron deficiency anemia, inhibits hepcidin expression by dampening BMP/SMAD signaling. In the present study, we used genetic approaches in mice to examine the relationship between Hfe and Tmprss6 in the regulation of systemic iron homeostasis. Heterozygous loss of Tmprss6 in Hfe−/− mice reduced systemic iron overload, whereas homozygous loss caused systemic iron deficiency and elevated hepatic expression of hepcidin and other Bmp/Smad target genes. In contrast, neither genetic loss of Hfe nor hepatic Hfe overexpression modulated the hepcidin elevation and systemic iron deficiency of Tmprss6−/− mice. These results indicate that genetic loss of Tmprss6 increases Bmp/Smad signaling in an Hfe-independent manner that can restore Bmp/Smad signaling in Hfe−/− mice. Furthermore, these results suggest that natural genetic variation in the human ortholog TMPRSS6 might modify the clinical penetrance of HFE-associated hereditary hemochromatosis, raising the possibility that pharmacologic inhibition of TMPRSS6 could attenuate iron loading in this disorder. PMID:21355094

Subcutaneous adipose tissue from obese and lean adults does not release hepcidin, in vivo

USDA-ARS?s Scientific Manuscript database

Hepcidin is a small peptide that functions as the both the main regulator of systemic iron homeostasis, and as the link between host defense and iron metabolism. Elevated hepcidin is associated with reduced iron bioavailability, while low hepcidin concentrations are associated with increased dietary...

Serum ferritin concentrations and body iron stores in a multicenter, multiethnic primary-care population

PubMed Central

Gordeuk, Victor R.; Reboussin, David M.; McLaren, Christine E.; Barton, James C.; Acton, Ronald T.; McLaren, Gordon D.; Harris, Emily L.; Reiss, Jacob A.; Adams, Paul C.; Speechley, Mark; Phatak, Pradyumna D.; Sholinsky, Phyliss; Eckfeldt, John H.; Chen, Wen-Pin; Passmore, Leah; Dawkins, Fitzroy W.

2013-01-01

How often elevated serum ferritin in primary-care patients reflects increased iron stores (normally 0.8 g in men, 0.4 g in women) is not known. The Hereditary Hemochromatosis and Iron Overload Screening (HEIRS) study screened 101,168 primary-care participants (44% Caucasians, 27% African-Americans, 14% Asians/Pacific Islanders, 13% Hispanics, 2% others). Follow-up clinical evaluation was performed in 302 of 333 HFE C282Y homozygotes regardless of iron measures and 1,375 of 1,920 nonhomozygotes with serum ferritin >300 μg/L (men), >200 μg/L (women) and transferrin saturation >50% (men), >45% (women). Quantitative phlebotomy was conducted in 122 of 175 C282Y homozygotes and 122 of 1,102 nonhomozygotes with non-transfusional serum ferritin elevation at evaluation. The estimated prevalence in the Caucasian population of C282Y homozygotes with serum ferritin >900 μg/L at evaluation was 20 per 10,000 men and 4 per 10,000 women; this constellation was predictive of iron stores >4 g in men and >2 g in women. The estimated prevalence per 10,000 of non-C282Y homozygotes with serum ferritin >900 μg/L at evaluation was 7 among Caucasians, 13 among Hispanics, 20 among African Americans, and 38 among Asians and Pacific Islanders, and this constellation was predictive of iron stores >2 g but <4 g. In conclusion, serum ferritin >900 μg/L after initial elevations of both serum ferritin and transferrin saturation is predictive of mildly increased iron stores in multiple ethnic populations regardless of HFE genotype. Serum ferritin >900 μg/L in male C282Y homozygotes is predictive of moderately increased iron stores. PMID:18429050

FGF23 is correlated with iron status but not with inflammation and decreases after iron supplementation: a supplementation study

PubMed Central

2012-01-01

Background Recent studies have described relationships between iron status and fibroblast growth factor-23 (FGF23) but the possible confounding effects of inflammation on iron status have not been considered. The aims of this study were a) to consider a relationship between FGF23 and inflammation b) to identify relationships between iron status and FGF23 whilst correcting for inflammation and c) to assess the relationship between changes in FGF23 and iron status after supplementation. Study design and methodology Blood samples from an iron supplementation study in children (n=79) were collected at baseline and after 3 months supplementation with iron sulphate. The children were from a rural Gambian population where rates of iron deficiency and infection/inflammation are high. This study identified cross-sectional and longitudinal relationships between FGF23, inflammation (C-reactive protein (CRP)) and iron status (ferritin, haemoglobin, and zinc protoporphyrin). CRP ≥ 5 mg/dL was used to indicate inflammation and FGF23 ≥ 125 RU/mL was considered elevated. Results FGF23 was not significantly correlated with CRP. At baseline, all markers of iron status were significantly correlated with FGF23. Ferritin was the strongest independent inverse predictor of FGF23 in subjects with and without elevated CRP (coefficient (SE)): All subjects=−0.57 (0.12), R2=22.3%, P≤0.0001; subjects with CRP < 5 mg/dL=−0.89 (0.14), R2=38.9%, P≤0.0001. FGF23 was elevated in 28% of children at baseline and 16% post supplementation (P=0.1). Improved iron status was associated with a decrease in FGF23 concentration in univariate (ferritin =−0.41 (0.11), R2=14.1%, P=0.0004; haemoglobin=−2.22 (0.64), R2=12.5%, P=0.0008; zinc protoporphyrin=1.12 (0.26), R2=18.6%, P≤0.0001) and multivariate analysis (R2=33.1%; ferritin=−0.36 (0.10), P=0.0007, haemoglobin = −1.83 (0.61), P=0.004, zinc protoporphyrin=0.62 (0.26), P=0.02). Conclusions Iron status rather than inflammation is a negative predictor of plasma FGF23 concentration. Improvements in iron status following iron supplementation are associated with a significant decrease in FGF23 concentration. PMID:23098062

Study of oxidative stress biomarkers in chronic obstructive pulmonary disease and their correlation with disease severity in north Indian population cohort

PubMed Central

Bajpai, Jyoti; Prakash, Ved; Kant, Surya; Verma, Ajay Kumar; Srivastava, Anand; Bajaj, Darshan K; Ahmad, MK; Agarwal, Avinash

2017-01-01

Background: Oxidant-antioxidant imbalance forms a prime component in pathogenesis of chronic obstructive pulmonary disease (COPD). Studies of oxidative stress markers in South Asians were sparse. Methods: One hundred and eighty COPD patients and eighty healthy nonsmokers were enrolled in the study. Serum malondialdehyde (MDA) and iron levels were estimated for oxidative stress. Three antioxidant markers evaluated-catalase, superoxide dismutase (SOD), and serum copper. Patients on antioxidant therapy and with sepsis and chronic illness were excluded from the study. Results: The mean age of COPD patients was 59.29 ± 10.3 years. Serum levels of MDA and iron were significantly higher in COPD patients compared to controls (5.21 ± 1.9 vs. 0.71 ± 0.29 nmol MDA/ml, P = 0.0001 and 69.85 ± 85.49 vs. 79.32 ± 24.39 μg/dl, P = 0.0001, respectively). Mean level of all antioxidant enzymes catalase, SOD, and copper were significantly diminished in cases when compared to control population (P = 0.001). Levels of MDA and iron were found to be significantly elevated in higher Global Initiative for Chronic Obstructive Lung Disease (GOLD) classes (III, IV) when compared to lower GOLD Classes (I, II). The levels of serum antioxidants were significantly depleted in higher GOLD grades too. COPD patients who were male and smoked had significantly higher levels of oxidants and depleted antioxidant levels compared to female and nonsmoking compatriots. Serum MDA levels negatively correlated with forced expiratory volume 1 s and forced vital capacity (r = −0.19 and r = −0.21, P ≤ 0.01). The presence of a cough significantly correlated with higher levels of MDA and iron (P = 0.001). The levels of MDA negatively correlated with SOD and catalase levels. Conclusion: Oxidative markers (MDA and iron) are higher whereas antioxidants (catalase, copper, and SOD) are significantly reduced in patients of COPD. Serum MDA levels correlate with lung functions and disease severity. PMID:28671162

Metal-metal interaction mediates the iron induction of Drosophila MtnB

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

Qiang, Wenjia; Huang, Yunpeng; Wan, Zhihui

Metallothionein (MT) protein families are a class of small and universal proteins rich in cysteine residues. They are synthesized in response to heavy metal stresses to sequester the toxic ions by metal-thiolate bridges. Five MT family members, namely MtnA, MtnB, MtnC, MtnD and MtnE, have been discovered and identified in Drosophila. These five isoforms of MTs are regulated by metal responsive transcription factor dMTF-1 and play differentiated but overlapping roles in detoxification of metal ions. Previous researches have shown that Drosophila MtnB responds to copper (Cu), cadmium (Cd) and zinc (Zn). Interestingly in this study we found that Drosophila MtnBmore » expression also responds to elevated iron levels in the diet. Further investigations revealed that MtnB plays limited roles in iron detoxification, and the direct binding of MtnB to ferrous iron in vitro is also weak. The induction of MtnB by iron turns out to be mediated by iron interference of other metals, because EDTA at even a partial concentration of that of iron can suppress this induction. Indeed, in the presence of iron, zinc homeostasis is altered, as reflected by expression changes of zinc transporters dZIP1 and dZnT1. Thus, iron-mediated MtnB induction appears resulting from interrupted homeostasis of other metals such as zinc, which in turns induced MtnB expression. Metal-metal interaction may more widely exist than we expected. - Highlights: • Metallothionein B expression is regulated by iron in Drosophila melanogaster. • MtnB has limited physiological roles in iron detoxification. • Binding affinity of MtnB to iron is weak in vitro. • Induction of Drosophila MtnB by iron is mediated indirectly through metal-metal interaction.« less

Suppression of Iron-Regulatory Hepcidin by Vitamin D

PubMed Central

Bacchetta, Justine; Zaritsky, Joshua J.; Sea, Jessica L.; Chun, Rene F.; Lisse, Thomas S.; Zavala, Kathryn; Nayak, Anjali; Wesseling-Perry, Katherine; Westerman, Mark; Hollis, Bruce W.; Salusky, Isidro B.

2014-01-01

The antibacterial protein hepcidin regulates the absorption, tissue distribution, and extracellular concentration of iron by suppressing ferroportin-mediated export of cellular iron. In CKD, elevated hepcidin and vitamin D deficiency are associated with anemia. Therefore, we explored a possible role for vitamin D in iron homeostasis. Treatment of cultured hepatocytes or monocytes with prohormone 25-hydroxyvitamin D or active 1,25-dihydroxyvitamin D decreased expression of hepcidin mRNA by 0.5-fold, contrasting the stimulatory effect of 25-hydroxyvitamin D or 1,25-dihydroxyvitamin D on related antibacterial proteins such as cathelicidin. Promoter-reporter and chromatin immunoprecipitation analyses indicated that direct transcriptional suppression of hepcidin gene (HAMP) expression mediated by 1,25-dihydroxyvitamin D binding to the vitamin D receptor caused the decrease in hepcidin mRNA levels. Suppression of HAMP expression was associated with a concomitant increase in expression of the cellular target for hepcidin, ferroportin protein, and decreased expression of the intracellular iron marker ferritin. In a pilot study with healthy volunteers, supplementation with a single oral dose of vitamin D (100,000 IU vitamin D2) increased serum levels of 25D-hydroxyvitamin D from 27±2 ng/ml before supplementation to 44±3 ng/ml after supplementation (P<0.001). This response was associated with a 34% decrease in circulating levels of hepcidin within 24 hours of vitamin D supplementation (P<0.05). These data show that vitamin D is a potent regulator of the hepcidin-ferroportin axis in humans and highlight a potential new strategy for the management of anemia in patients with low vitamin D and/or CKD. PMID:24204002

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.

Effects of High Dietary HEME Iron and Radiation on Cardiovascular Function

NASA Technical Reports Server (NTRS)

Westby, Christian M.; Brown, A. K.; Platts, S. H.

2012-01-01

The radiation related health risks to astronauts is of particular concern to NASA. Data support that exposure to radiation is associated with a number of disorders including a heightened risk for cardiovascular diseases. Independent of radiation, altered nutrient status (e.g. high dietary iron) also increases ones risk for cardiovascular disease. However, it is unknown whether exposure to radiation in combination with high dietary iron further increases ones cardiovascular risk. The intent of our proposal is to generate compulsory data examining the combined effect of radiation exposure and iron overload on sensitivity to radiation injury to address HRP risks: 1) Risk Factor of Inadequate Nutrition; 2) Risk of Cardiac Rhythm Problems; and 3) Risk of Degenerative Tissue or other Health Effects from Space Radiation. Towards our goal we propose two distinct pilot studies using the following specific aims: Vascular Aim 1: To determine the short-term consequences of the independent and combined effects of exposure to gamma radiation and elevated body iron stores on measures of endothelial function and cell viability and integrity. We hypothesize that animals that have high body iron stores and are exposed to gamma radiation will show a greater reduction in endothelial dependent nitric oxid production and larger pathological changes in endothelial integrity than animals that have only 1 of those treatments (either high iron stores or exposure to gamma radiation). Vascular Aim 2: Identify and compare the effects of gamma radiation and elevated body iron stores on the genetic and epigenetic regulation of proteins associated with endothelial cell function. We hypothesize that modifications of epigenetic control and posttranslational expression of proteins associated with endothelial cell function will be differentially altered in rats with high body iron stores and exposed to gamma radiation compared to rats with only 1 type of treatment. Cardiac Aim 1: To determine the short-term consequences of the independent and combined effects of gamma radiation and elevated body iron stores on measures of cardiac structure. We hypothesize that modifications to cardiac structure and function will be greater in rats with high body iron stores and exposed to gamma radiation than in rats that have only 1 of those treatments. Cardiac Aim 2: Identify and compare the effects of gamma radiation and elevated body iron stores on the genetic and epigenetic regulation of proteins associated with cardiac structure and function. We hypothesize that modifications of epigenetic control and posttranslational expression of proteins associated with cardiac contractile function will be differentially altered in rats with high body iron stores and exposed to gamma radiation compared to rats with only 1 type of treatment.

The Association of Multiple Biomarkers of Iron Metabolism and Type 2 Diabetes - the EPIC-InterAct Study

PubMed Central

Podmore, Clara; Meidtner, Karina; Schulze, Matthias B; Scott, Robert A; Ramond, Anna; Butterworth, Adam S; Di Angelantonio, Emanuele; Danesh, John; Arriola, Larraitz; Barricarte, Aurelio; Boeing, Heiner; Clavel-Chapelon, Françoise; Cross, Amanda J; Dahm, Christina C; Fagherazzi, Guy; Franks, Paul W; Gavrila, Diana; Grioni, Sara; Gunter, Marc J; Gusto, Gaelle; Jakszyn, Paula; Katzke, Verena; Key, Timothy J; Kühn, Tilman; Mattiello, Amalia; Nilsson, Peter M; Olsen, Anja; Overvad, Kim; Palli, Domenico; Quirós, J. Ramón; Rolandsson, Olov; Sacerdote, Carlotta; Sánchez-Cantalejo, Emilio; Slimani, Nadia; Sluijs, Ivonne; Spijkerman, Annemieke MW; Tjonneland, Anne; Tumino, Rosario; van der A, Daphne L; van der Schouw, Yvonne T; Feskens, Edith JM; Forouhi, Nita G; Sharp, Stephen J; Riboli, Elio; Langenberg, Claudia; Wareham, Nicholas J

2016-01-01

Objective Observational studies show an association between ferritin and type 2 diabetes (T2D), suggesting a role of high iron stores for T2D development. However, ferritin is influenced by factors other than iron stores, which is less the case for other biomarkers of iron metabolism. We investigate associations of ferritin, transferrin saturation (TSAT), serum iron and transferrin with T2D incidence, to clarify the role of iron in the pathogenesis of T2D. Research and Design Methods The EPIC-InterAct study includes 12,403 incident T2D cases and a representative sub-cohort of 16,154 individuals from a European cohort with 3.99 million person-years of follow-up. We studied the prospective association of ferritin, TSAT, serum iron and transferrin with incident T2D in 11,052 cases and a random sub-cohort of 15,182 individuals and assessed whether these associations differed by subgroups of the population. Results Higher levels of ferritin and transferrin were associated with a higher risk of T2D [HR in men and women, respectively: 1.07 (95% CI: 1.01; 1.12) and 1.12 (1.05; 1.19) per 100 μg/L higher ferritin level; 1.11 (1.00; 1.24) and 1.22 (1.12; 1.33) per 0.5 g/L higher transferrin level] after adjustment for age, centre, BMI, physical activity, smoking status, education, hsCRP, ALT and GGT. Elevated TSAT (≥45% versus <45%) was associated with a lower risk of T2D in women [0.68 (0.54; 0.86)] but was not statistically significantly associated in men [0.90 (0.75; 1.08)]. Serum iron was not associated with T2D. The association of ferritin with T2D was stronger among leaner individuals (pinteraction<0.01). Conclusions The pattern of association of TSAT and transferrin with T2D suggests that the underlying relationship between iron stores and T2D is more complex than the simple link suggested by the association of ferritin with T2D. PMID:26861925

Bacteriophage PRD1 and silica colloid transport and recovery in an iron oxide-coated sand aquifer

USGS Publications Warehouse

Ryan, J.N.; Elimelech, M.; Ard, R.A.; Harvey, R.W.; Johnson, P.R.

1999-01-01

Bacteriophage PRD1 and silica colloids were co-injected into sewage- contaminated and uncontaminated zones of an iron oxide-coated sand aquifer on Cape Cod, MA, and their transport was monitored over distances up to 6 m in three arrays. After deposition, the attached PRD1 and silica colloids were mobilized by three different chemical perturbations (elevated pH, anionic surfactant, and reductant). PRD1 and silica colloids experienced less attenuation in the contaminated zone where adsorbed organic matter and phosphate may be hindering attachment of PRD1 and silica colloids to the iron oxide coatings. The PRD1 collision efficiencies agree well with collision efficiencies predicted by assuming favorable PRD1 deposition on iron oxide coatings for which the surface area coverage was measured by microprobe analysis of sediment thin sections. ?? potentials of the PRD1, silica colloids, and aquifer grains corroborated the transport results, indicating that electrostatic forces dominated the attachment of PRD1 and silica colloids. Elevated pH was the chemical perturbation most effective at mobilizing the attached PRD1 and silica colloids. Elevated surfactant concentration mobilized the attached PRD1 and silica colloids more effectively in the contaminated zone than in the uncontaminated zone.Bacteriophage PRD1 and silica colloids were co-injected into sewage-contaminated and uncontaminated zones of an iron oxide-coated sand aquifer on Cape Cod, MA, and their transport was monitored over distances up to 6 m in three arrays. After deposition, the attached PRD1 and silica colloids were mobilized by three different chemical perturbations (elevated pH, anionic surfactant, and reductant). PRD1 and silica colloids experienced less attenuation in the contaminated zone where adsorbed organic matter and phosphate may be hindering attachment of PRD1 and silica colloids to the iron oxide coatings. The PRD1 collision efficiencies agree well with collision efficiencies predicted by assuming favorable PRD1 deposition on iron oxide coatings for which the surface area coverage was measured by microprobe analysis of sediment thin sections. ?? potentials of the PRD1, silica colloids, and aquifer grains corroborated the transport results, indicating that electrostatic forces dominated the attachment of PRD1 and silica colloids. Elevated pH was the chemical perturbation most effective at mobilizing the attached PRD1 and silica colloids. Elevated surfactant concentration mobilized the attached PRD1 and silica colloids more effectively in the contaminated zone than in the uncontaminated zone.

Public health assessment for petitioned public health assessment, Old Douglas County Landfill (a/k/a Douglas County/Cedar Mountain Landfill), Douglasville, Douglas County, Georgia, Region 4: CERCLIS Number GAD984279232. Final report

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

NONE

The Old Douglas County Landfill in Douglasville, Georgia, operated from 1973 until 1987 as a municipal waste landfill. Existing landfill records specify that household wastes were received, however, industrial wastes are suspected to have been disposed at this landfill. The Agency for Toxic Substances and Disease Registry (ATSDR) concludes that private well water near the landfill is safe to drink. The surface water from Gothard`s Creek and the settling ponds on the landfill do not have chemicals present at levels of public health concern. The settling ponds on the landfill and parts of Gothard`s Creek contain elevated levels of lead,more » manganese, and iron in the sediment that are not harmfull to humans under typical exposure conditions. The soil located on- and off-site also had elevated levels of lead, manganese, and iron, however, these metals do not pose a threat to human health under typical exposure conditions. Currently, human contact with contaminants in soil, sediment, and surface water associated with Old Douglas County Landfill is not expected to result in adverse health effects. ATSDR determined that the methane monitoring locations and frequency at the landfill are inadequate to fully evaluate conditions at the perimeter of the landfill or near adjacent houses.« less

Neonatal hemochromatosis. Case series from Bahrain.

PubMed

Isa, Hasan M; Mohamed, Afaf M

2013-12-01

To review clinical presentations, diagnosis, response to treatment, and outcome of infants with neonatal hemochromatosis (NH). This is a retrospective review of all cases admitted to the Pediatric Department at Salmaniya Medical Center, Manama, Bahrain between March 2008 and May 2011. The diagnosis was based on serum iron and ferritin, alpha-fetoprotein levels (AFP), liver and buccal biopsies, and abdominal MRI scan. Ten patients (8 males and 2 females) were diagnosed with NH. Two patients were intrauterine growth restriction (IUGR) and 6 were preterm. The median birth weight was 1.700 grams. The median age at presentation was 16 days, and at diagnosis was 23 days. Two patients had positive consanguinity. Clinical presentations of the infants were hepatosplenomegaly (n=5), ascites (n=3), and hypoglycemia (n=6). All patients had raised ferritin levels, prolonged prothrombin time, and 9 patients had high serum iron and serum AFP. Abdominal MRI showed iron overload in the liver (n=8). Liver biopsies showed evidence of hemochromatosis (n=3). Buccal biopsies stained positive for iron (n=1). Eight patients received antioxidant therapy and survived. Two patients passed away. Neonatal hemochromatosis is a rare liver disease of newborns with a spectrum of clinical severity. Elevated serum ferritin and AFP support the diagnosis after excluding other causes of neonatal liver failure. The use of antioxidant therapy helps to improve the outcome.

Functional Investigation of Iron-Responsive Microsomal Proteins, including MirC, in Aspergillus fumigatus

PubMed Central

Mulvihill, Eoin D.; Moloney, Nicola M.; Owens, Rebecca A.; Dolan, Stephen K.; Russell, Lauren; Doyle, Sean

2017-01-01

The functionality of many microsome-associated proteins which exhibit altered abundance in response to iron limitation in Aspergillus fumigatus is unknown. Here, we generate and characterize eight gene deletion strains, and of most significance reveal that MirC (AFUA_2G05730) contributes to the maintenance of intracellular siderophore [ferricrocin (FC)] levels, augments conidiation, confers protection against oxidative stress, exhibits an intracellular localization and contributes to fungal virulence in the Galleria mellonella animal model system. FC levels were unaffected following deletion of all other genes encoding microsome-associated proteins. MirC does not appear to play a role in either siderophore export from, or uptake into, A. fumigatus. Label-free quantitative proteomic analysis unexpectedly revealed increased abundance of siderophore biosynthetic enzymes. In addition, increased expression of hapX (7.2 and 13.8-fold at 48 and 72 h, respectively; p < 0.001) was observed in ΔmirC compared to wild-type under iron-replete conditions by qRT-PCR. This was complemented by significantly elevated extracellular triacetylfusarinine C (TAFC; p < 0.01) and fusarinine C (FSC; p < 0.05) siderophore secretion. We conclude that MirC plays an important role in FC biosynthesis and contributes to the maintenance of iron homeostasis in A. fumigatus. PMID:28367141

10. DETAILED VIEW OF THE EAST ELEVATION. THE UPPER SET ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

10. DETAILED VIEW OF THE EAST ELEVATION. THE UPPER SET OF WINDOWS PROVIDE LIGHT FOR THE DELIVERY LEVEL. THE LOWER SETS OF WINDOWS PROVIDE LIGHT TO THREE STORY SPACE BENEATH THE DELIVERY LEVEL AND BEHIND THE ORE STORAGE BINS. NOTE THE ORE DELIVER TRESTLE AT THE TIME THE PHOTOGRAPH WAS TAKEN, THE MODERN CEMENT MIXER AND WHEELBARROWS WERE FOR THIS WORK. NOTE THE MORTAR BOXES ON THEIR SIDES. IT IS UNCLEAR IF THESE WERE FROM EARLIER STAMPS AT THIS MILL OR IF THEY WERE BROUGHT TO THE SITE FROM OTHER MILLS IN THE REGION. RISDON IRON WORKS IS CAST INTO THE MORTARS AND THEY ALSO BEAR A PLATE: WHITE, ROGERS AND CO. MILL WRIGHTS. - Standard Gold Mill, East of Bodie Creek, Northeast of Bodie, Bodie, Mono County, CA

Iron-tolerant Cyanobacteria as a Tool to Study Terrestrial and Extraterrestrial Iron Deposition

NASA Technical Reports Server (NTRS)

Brown, I. I.; Mummey, D.; Cooksey, K. E.; McKay, D. S.

2005-01-01

We are investigating biological mechanisms of terrestrial iron deposition as analogs for Martian hematite recently confirmed by. Possible terrestrial analogs include iron oxide hydrothermal deposits, rock varnish, iron-rich laterites, ferricrete soils, moki balls, and banded iron formations (BIFs). With the discovery of recent volcanic activity in the summit craters of five Martian volcanoes, renewed interest in the iron dynamics of terrestrial hydrothermal environments and associated microorganisms is warranted. In this study we describe a new genus and species of CB exhibiting elevated dissolved iron tolerance and the ability to precipitate hematite on the surface of their exopolymeric sheathes.

Method for producing iron-based catalysts

DOEpatents

Farcasiu, Malvina; Kaufman, Phillip B.; Diehl, J. Rodney; Kathrein, Hendrik

1999-01-01

A method for preparing an acid catalyst having a long shelf-life is provided comprising doping crystalline iron oxides with lattice-compatible metals and heating the now-doped oxide with halogen compounds at elevated temperatures. The invention also provides for a catalyst comprising an iron oxide particle having a predetermined lattice structure, one or more metal dopants for said iron oxide, said dopants having an ionic radius compatible with said lattice structure; and a halogen bound with the iron and the metal dopants on the surface of the particle.

Oral iron acutely elevates bacterial growth in human serum.

PubMed

Cross, James H; Bradbury, Richard S; Fulford, Anthony J; Jallow, Amadou T; Wegmüller, Rita; Prentice, Andrew M; Cerami, Carla

2015-11-23

Iron deficiency is the most common nutrient deficiency worldwide and routine supplementation is standard policy for pregnant mothers and children in most low-income countries. However, iron lies at the center of host-pathogen competition for nutritional resources and recent trials of iron administration in African and Asian children have resulted in significant excesses of serious adverse events including hospitalizations and deaths. Increased rates of malaria, respiratory infections, severe diarrhea and febrile illnesses of unknown origin have all been reported, but the mechanisms are unclear. We here investigated the ex vivo growth characteristics of exemplar sentinel bacteria in adult sera collected before and 4 h after oral supplementation with 2 mg/kg iron as ferrous sulfate. Escherichia coli, Yersinia enterocolitica and Salmonella enterica serovar Typhimurium (all gram-negative bacteria) and Staphylococcus epidermidis (gram-positive) showed markedly elevated growth in serum collected after iron supplementation. Growth rates were very strongly correlated with transferrin saturation (p < 0.0001 in all cases). Growth of Staphylococcus aureus, which preferentially scavenges heme iron, was unaffected. These data suggest that even modest oral supplements with highly soluble (non-physiological) iron, as typically used in low-income settings, could promote bacteremia by accelerating early phase bacterial growth prior to the induction of immune defenses.

Impact of high iron intake on cognition and neurodegeneration in humans and in animal models: a systematic review.

PubMed

Agrawal, Sonal; Berggren, Kiersten L; Marks, Eileen; Fox, Jonathan H

2017-06-01

Accumulation of brain iron is linked to aging and protein-misfolding neurodegenerative diseases. High iron intake may influence important brain health outcomes in later life. The aim of this systematic review was to examine evidence from animal and human studies of the effects of high iron intake or peripheral iron status on adult cognition, brain aging, and neurodegeneration. MEDLINE, Scopus, CAB Abstracts, the Cochrane Central Register of Clinical Trials, and OpenGrey databases were searched. Studies investigating the effect of elevated iron intake at all postnatal life stages in mammalian models and humans on measures of adult brain health were included. Data were extracted and evaluated by two authors independently, with discrepancies resolved by discussion. Neurodegenerative disease diagnosis and/or behavioral/cognitive, biochemical, and brain morphologic findings were used to study the effects of iron intake or peripheral iron status on brain health. Risk of bias was assessed for animal and human studies. PRISMA guidelines for reporting systematic reviews were followed. Thirty-four preclinical and 14 clinical studies were identified from database searches. Thirty-three preclinical studies provided evidence supporting an adverse effect of nutritionally relevant high iron intake in neonates on brain-health-related outcomes in adults. Human studies varied considerably in design, quality, and findings; none investigated the effects of high iron intake in neonates/infants. Human studies are needed to verify whether dietary iron intake levels used in neonates/infants to prevent iron deficiency have effects on brain aging and neurodegenerative disease outcomes. © The Author(s) 2017. Published by Oxford University Press on behalf of the International Life Sciences Institute.

[Marked hemosiderosis in myelodysplastic syndrome].

PubMed

Klinz, C

1999-01-29

A 68-year-old man was admitted because of symptoms of lumbar pain. He was known to have chronic anemia with ring sideroblasts and diabetes melitus and to be in heart failure. Three months before he had been given 7 units of red cell concentrate. On admission the outstanding features were brown discoloration of the skin, absent body hair, tachycardia, hepatomegaly and small testicles. He had a normocytic anemia, hyperglycemia and raised transaminases, hypogonadism and vitamin D3 deficiency. The serum levels of iron, transferrin saturation and feritin were markedly elevated. Liver iron content/g dried liver was 4.2 g (by biomagnetometer). Radiology of the lumbar vertebrae showed osteoporosis and sonography confirmed hepatomegaly. The known myelodysplastic syndrome (MDS) had fed to secondary hemosiderosis with heart failure, liver involvement, diabetes mellitus, hypogonadism and osteoporosis. Symptomatic treatment was unsuccessfully complemented by desferoxamine (up to 4 g/12 h) to release iron. But very good iron excretion was then achieved with deferiprone (3 x 1 g/d). The patient later died of the sequelae of hemosiderosis. Even when they have not required transfusions, patients with long-standing MDS should be examined regularly for the possible development of secondary hemosiderosis so that iron-chelating agents can be administered as needed.

Inadequate hepcidin serum concentrations predict incident type 2 diabetes mellitus.

PubMed

Pechlaner, Raimund; Weiss, Günter; Bansal, Sukhvinder; Mayr, Manuel; Santer, Peter; Pallhuber, Barbara; Notdurfter, Marlene; Bonora, Enzo; Willeit, Johann; Kiechl, Stefan

2016-02-01

Type 2 diabetes mellitus (T2DM) is closely associated with elevated body iron stores. The hormone hepcidin is the key regulator of iron homeostasis. Inadequately low hepcidin levels were recently reported in subjects with manifest T2DM. We investigated whether alterations of hepcidin levels precede the manifestation of T2DM and predict T2DM development independently of established risk conditions. This prospective population-based study included 675 subjects aged 50-89 years, 51.9% of whom were female. Hepcidin levels were measured by gold standard tandem mass spectrometry. Diabetes was diagnosed according to American Diabetes Association criteria, and incident diabetes was recorded between baseline in 2000 and 2010. The baseline hepcidin-to-ferritin ratio in subjects that subsequently developed diabetes during follow-up was reduced on average by 29.8% as compared with subjects with normal glucose tolerance (95% confidence interval, -50.7% to -0.2%; p = 0.049). After adjustment for age, sex, and serum ferritin, higher hepcidin levels were associated with reduced risk of incident diabetes (hazard ratio per 1-unit higher log2 hepcidin, 0.80; 95% confidence interval, 0.64-0.98; p = 0.035; 33 events). Additional adjustment for established diabetes risk factors and determinants of hepcidin concentration did not appreciably change these results (HR, 0.81; 95% CI, 0.66-0.99). Likewise, inadequately low hepcidin levels were also detected in subjects with prevalent T2DM (n = 76). Hepcidin levels that are inadequately low in relation to body iron stores are an independent predictor for incident T2DM and may contribute to diabetes-related tissue iron overload. Copyright © 2015 John Wiley & Sons, Ltd. Copyright © 2015 John Wiley & Sons, Ltd.

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

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.

Elevated moisture stimulates carbon loss from mineral soils by releasing protected organic matter.

PubMed

Huang, Wenjuan; Hall, Steven J

2017-11-24

Moisture response functions for soil microbial carbon (C) mineralization remain a critical uncertainty for predicting ecosystem-climate feedbacks. Theory and models posit that C mineralization declines under elevated moisture and associated anaerobic conditions, leading to soil C accumulation. Yet, iron (Fe) reduction potentially releases protected C, providing an under-appreciated mechanism for C destabilization under elevated moisture. Here we incubate Mollisols from ecosystems under C 3 /C 4 plant rotations at moisture levels at and above field capacity over 5 months. Increased moisture and anaerobiosis initially suppress soil C mineralization, consistent with theory. However, after 25 days, elevated moisture stimulates cumulative gaseous C-loss as CO 2 and CH 4 to >150% of the control. Stable C isotopes show that mineralization of older C 3 -derived C released following Fe reduction dominates C losses. Counter to theory, elevated moisture may significantly accelerate C losses from mineral soils over weeks to months-a critical mechanistic deficiency of current Earth system models.

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.

The Challenges and Opportunities Associated with Biofortification of Pearl Millet (Pennisetum glaucum) with Elevated Levels of Grain Iron and Zinc

PubMed Central

Manwaring, Hanna R.; Bligh, H. F. J.; Yadav, Rattan

2016-01-01

Deficiencies of essential micronutrients such as iron and zinc are the cause of extensive health problems in developing countries. They adversely affect performance, productivity and are a major hindrance to economic development. Since many people who suffer from micronutrient deficiencies are dependent on staple crops to meet their dietary requirements, the development of crop cultivars with increased levels of micronutrients in their edible parts is becoming increasingly recognized as a sustainable solution. This is largely facilitated by genetics and genomic platforms. The cereal crop pearl millet (Pennisetum glaucum), is an excellent candidate for genetic improvement due to its ability to thrive in dry, semi-arid regions, where farming conditions are often unfavorable. Not only does pearl millet grow in areas where other crops such as maize and wheat do not survive, it contains naturally high levels of micronutrients, proteins and a myriad of other health benefitting characteristics. This review discusses the current status of iron and zinc deficiencies and reasons why interventions such as fortification, supplementation, and soil management are neither practicable nor affordable in poverty stricken areas. We argue that the most cost effective, sustainable intervention strategy is to biofortify pearl millet with enhanced levels of bioavailable iron and zinc. We discuss how naturally occurring genetic variations present in germplasm collections can be incorporated into elite, micronutrient rich varieties and what platforms are available to drive this research. We also consider the logistics of transgenic methods that could facilitate the improvement of the pearl millet gene pool. PMID:28066495

A case report of neonatal diabetes due to neonatal hemochromatosis.

PubMed

Cetinkaya, Semra; Kunak, Benal; Kara, Cengiz; Demirçeken, Fulya; Yarali, Neşe; Polat, Emine; Aycan, Zehra

2010-05-01

A 6-week-old girl, the first child of non-consanguineous parents, was admitted to the hospital for evaluation of vomiting. She was small for gestational age (1500 g). On admission, she weighed 1830 g, and appeared dehydrated. The blood glucose was 880 mg/dL. Insulin and C-peptide levels were <1 microIU/ml and 0.1 pmol/L, respectively. Antibodies of diabetes were negative. The serum triglyceride level was markedly elevated (5322 mg/dL). After a few days of insulin therapy, the triglyceride levels dramatically decreased, but cholestasis persisted. A liver biopsy revealed diffuse iron deposition and the diagnosis of neonatal hemochromatosis was established. In neonatal hemochromatosis, diabetes may occur as a result of iron deposition in the pancreas. The coexistence of neonatal diabetes secondary to neonatal hemochromatosis with a fatal course during the infancy period has not been previously reported. In this report, an infant with neonatal diabetes secondary to neonatal hemochromatosis is presented as the first case in the literature involving the coexistence of these two conditions.

Ferroportin (Q248H) mutations in African families with dietary iron overload.

PubMed

McNamara, Lynne; Gordeuk, Victor R; MacPhail, A Patrick

2005-12-01

Dietary iron overload found in sub-Saharan Africa might be caused by an interaction between dietary iron and an iron-loading gene. Caucasian people with ferroportin gene mutations have iron overload histologically similar to that found in African patients with iron overload. Ferroportin is also implicated in the hypoferremic response to inflammation. The prevalence of the ferroportin Q248H mutation, unique to African people, and its association with dietary iron overload, mean cell volume (MCV) and C-reactive protein (CRP) were examined in 19 southern African families. Polymerase chain reaction (PCR) and restriction enzyme digestion were used to identify the Q248H mutation. Statistical analysis was carried out to correlate the presence of the mutation with markers of iron overload and inflammation. We identified three (1.4%) Q248H homozygotes and 53 (24.1%) heterozygotes in the families examined in the present study. There was no increased prevalence of the mutation in index subjects or their families. Logistic regression showed significantly higher serum ferritin concentrations with the mutation. The mean cell volume (MCV) was significantly lower, and the serum CRP significantly higher in subjects who carried the mutation. The present study of 19 families with African iron overload failed to show evidence that the ferroportin (Q248H) mutation is responsible for the condition. Logistic regression, correcting for factors influencing iron status, did show increased ferritin levels in individuals with the mutation. The strong association with low MCV suggests the possibility that the ferroportin (Q248H) mutation might interfere with iron supply, whereas the elevated serum CRP might indicate that the ferroportin mutation influences the inflammatory response in African populations. Copyright 2005 Blackwell Publishing Asia Pty Ltd.

Role of vitamin C as an adjuvant therapy to different iron chelators in young β-thalassemia major patients: efficacy and safety in relation to tissue iron overload.

PubMed

Elalfy, Mohsen S; Saber, Maha M; Adly, Amira Abdel Moneam; Ismail, Eman A; Tarif, Mohamed; Ibrahim, Fatma; Elalfy, Omar M

2016-03-01

Vitamin C, as antioxidant, increases the efficacy of deferoxamine (DFO). To investigate the effects of vitamin C as an adjuvant therapy to the three used iron chelators in moderately iron-overloaded young vitamin C-deficient patients with β-thalassemia major (β-TM) in relation to tissue iron overload. This randomized prospective trial that included 180 β-TM vitamin C-deficient patients were equally divided into three groups (n = 60) and received DFO, deferiprone (DFP), and deferasirox (DFX). Patients in each group were further randomized either to receive vitamin C supplementation (100 mg daily) or not (n = 30). All patients received vitamin C (group A) or no vitamin C (group B) were followed up for 1 yr with assessment of transfusion index, hemoglobin, iron profile, liver iron concentration (LIC) and cardiac magnetic resonance imaging (MRI) T2*. Baseline vitamin C was negatively correlated with transfusion index, serum ferritin (SF), and LIC. After vitamin C therapy, transfusion index, serum iron, SF, transferrin saturation (Tsat), and LIC were significantly decreased in group A patients, while hemoglobin and cardiac MRI T2* were elevated compared with baseline levels or those in group B without vitamin C. The same improvement was found among DFO-treated patients post-vitamin C compared with baseline data. DFO-treated patients had the highest hemoglobin with the lowest iron, SF, and Tsat compared with DFP or DFX subgroups. Vitamin C as an adjuvant therapy possibly potentiates the efficacy of DFO more than DFP and DFX in reducing iron burden in the moderately iron-overloaded vitamin C-deficient patients with β-TM, with no adverse events. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

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

Is hepcidin a new cardiovascular risk marker in polycystic ovary syndrome?

PubMed

Gözdemir, Elif; Kaygusuz, Ikbal; Kafalı, Hasan

2013-01-01

Polycystic ovary syndrome (PCOS) is associated with reproductive and metabolic abnormalities and carries a number of cardiovascular risk factors. Low-grade chronic inflammation has been thought to play a role in the pathogenesis of atherosclerosis and PCOS patients have an increased rate of subclinical inflammation. In the present study, considering the major role that hepcidin plays in the regulation of iron metabolism and as an inflammatory marker, we investigated hepcidin in PCOS patients and its role in predicting cardiovascular disease (CVD) development. Forty patients with PCOS and 40 age- and body mass index-matched healthy controls were included in the study. Iron metabolites, insulin resistance (IR), inflammatory markers and hepcidin levels were analyzed. IR parameters, inflammatory markers, iron parameters and hepcidin levels were similar between the PCOS and control groups. While the inflammatory markers were significantly high in the overweight and obese PCOS subgroup, the hepcidin levels were also high but this elevation was not statistically significant. Obesity is the principle mechanism of chronic inflammation and IR in PCOS patients. C-reactive protein and interleukin-6 should be used to predict and follow the risk of CVD development in PCOS cases. Hepcidin may be used as an additional marker in the follow-up of PCOS patients in the future. Copyright © 2013 S. Karger AG, Basel.

Iron active electrode and method of making same

DOEpatents

Jackovitz, John F.; Seidel, Joseph; Pantier, Earl A.

1982-10-26

An iron active electrode and method of preparing same in which iron sulfate is calcined in an oxidizing atmosphere at a temperature in the range of from about 600.degree. C. to about 850.degree. C. for a time sufficient to produce an iron oxide with a trace amount of sulfate. The calcined material is loaded into an electrically conductive support and then heated in a reducing atmosphere at an elevated temperature to produce activated iron having a trace amount of sulfide which is formed into an electrode plate.

Role of Trace Elements for Oxidative Status and Quality of Human Sperm.

PubMed

Nenkova, Galina; Petrov, Lubomir; Alexandrova, Albena

2017-08-04

Oxidative stress affects sperm quality negatively. To maintain the pro/antioxidant balance, some metal ions (e.g. copper, zink, iron, selenium), which are co-factors of the antioxidant enzymes, are essential. However, iron and copper could act as prooxidants inducing oxidative damage of spermatozoa. To reveal a possible correlation between the concentrations of some metal ions (iron, copper, zinc, and selenium) in human seminal plasma, oxidative stress, assessed by malondialdehyde and total glutathione levels, and semen quality, assessed by the parameters count, motility, and morphology. Descriptive study. The semen analysis for volume, count, and motility was performed according to World Health Organization (2010) guidelines, using computer-assisted semen analysis. For the determination of spermatozoa morphology, a SpermBlue staining method was applied. Depending on their parameters, the sperm samples were categorized into normozoospermic, teratozoospermic, asthenoteratozoospermic, and oligoteratozoospermic. The seminal plasma content of iron, copper, zinc, and selenium was estimated by atomic absorption spectroscopy. The malondialdehyde and total glutathione levels were quantified spectrophotometrically. In the groups with poor sperm quality, the levels of Fe were higher, whereas those of Zn and Se were significantly lower than in the normozoospermic group. In all groups with poor sperm quality, increased levels of malondialdehyde and decreased glutathione levels were detected as evidence of oxidative stress occurrence. All these differences are most pronounced in the asthenoteratozoospermic group where values differ nearly twice as much compared to the normozoospermic group. The Fe concentration correlated positively with the malondialdehyde (r=0.666, p=0.018), whereas it showed a negative correlation with the level of total glutathione (r=-0.689, p=0.013). The total glutathione level correlated positively with the sperm motility (r=0.589, p=0.044). The elevated levels of Fe and the reduced Se levels are associated with sperm damage. The changes in the concentrations of the trace elements in human seminal plasma may be related to sperm quality since they are involved in the maintenance of the pro-/antioxidative balance in ejaculate.

Ratiometric Measurements of Adiponectin by Mass Spectrometry in Bottlenose Dolphins (Tursiops truncatus) with Iron Overload Reveal an Association with Insulin Resistance and Glucagon

PubMed Central

Neely, Benjamin A.; Carlin, Kevin P.; Arthur, John M.; McFee, Wayne E.; Janech, Michael G.

2013-01-01

High molecular weight (HMW) adiponectin levels are reduced in humans with type 2 diabetes and insulin resistance. Similar to humans with insulin resistance, managed bottlenose dolphins (Tursiops truncatus) diagnosed with hemochromatosis (iron overload) have higher levels of 2 h post-prandial plasma insulin than healthy controls. A parallel reaction monitoring assay for dolphin serum adiponectin was developed based on tryptic peptides identified by mass spectrometry. Using identified post-translational modifications, a differential measurement was constructed. Total and unmodified adiponectin levels were measured in sera from dolphins with (n = 4) and without (n = 5) iron overload. This measurement yielded total adiponectin levels as well as site specific percent unmodified adiponectin that may inversely correlate with HMW adiponectin. Differences in insulin levels between iron overload cases and controls were observed 2 h post-prandial, but not during the fasting state. Thus, post-prandial as well as fasting serum adiponectin levels were measured to determine whether adiponectin and insulin would follow similar patterns. There was no difference in total adiponectin or percent unmodified adiponectin from case or control fasting animals. There was no difference in post-prandial total adiponectin levels between case and control dolphins (mean ± SD) at 763 ± 298 and 727 ± 291 pmol/ml, respectively (p = 0.91); however, percent unmodified adiponectin was significantly higher in post-prandial cases compared to controls (30.0 ± 6.3 versus 17.0 ± 6.6%, respectively; p = 0.016). Interestingly, both total and percent unmodified adiponectin were correlated with glucagon levels in controls (r = 0.999, p  < 0.001), but not in cases, which is possibly a reflection of insulin resistance. Although total adiponectin levels were not significantly different, the elevated percent unmodified adiponectin follows a trend similar to HMW adiponectin reported for humans with metabolic disorders. PMID:24065958

High prevalence of anemia with lack of iron deficiency among women in rural Bangladesh: a role for thalassemia and iron in groundwater.

PubMed

Merrill, Rebecca D; Shamim, Abu Ahmed; Ali, Hasmot; Labrique, Alain B; Schulze, Kerry; Christian, Parul; West, Keith P

2012-01-01

Iron deficiency was absent in a recent population assessment of rural Bangladeshi women exhibiting anemia (57%), suggesting other causes of low hemoglobin. We assessed the relative influence on anemia of thalassemia, groundwater arsenic and iron, and diet among women of reproductive age living in rural Bangladesh. Women (n=207) sampled from a previous antenatal nutrient intervention trial in rural Bangladesh were visited during two seasons in 2008. Collected data included 7-day dietary and 24-hour drinking water intake recalls, 7-day morbidity recall, anthropometry, and drinking water arsenic and iron concentrations. Capillary blood was analyzed for iron (plasma ferritin, soluble transferrin receptor), inflammation (C-reactive protein) and thalassemia (β thalassemia and Hb E) status. In stratified, adjusted analyses, only parity was associated with anemia (odds ratio, OR (95% CI): 11.34 (1.94, 66.15)) for those with thalassemia (28% prevalent). In contrast, groundwater iron intake (>30 mg/d, 0.48 (0.24, 0.96)) and wasting (2.32 (1.17, 4.62)) were associated with anemia among those without thalassemia. Elevated groundwater arsenic (>50 μg/L, 12% of tubewells) and a diverse diet were unrelated to anemia regardless of thalassemia diagnosis (p>0.70 and >0.47, respectively). Among women in this typical rural Bangladeshi area, the prevalence of thalassemia was high and, unlike iron deficiency which was absent most likely due to high iron intake from groundwater, contributed to the risk of anemia. In such settings, the influence of environmental sources of iron and the role of thalassemias in contributing to anemia at the population level may be underappreciated.

The Association of Arsenic With Redox Conditions, Depth, and Ground-Water Age in the Glacial Aquifer System of the Northern United States

USGS Publications Warehouse

Thomas, Mary Ann

2007-01-01

More than 800 wells in the glacial aquifer system of the Northern United States were sampled for arsenic as part of U.S. Geological Survey National Water-Quality Assessment (NAWQA) studies during 1991-2003. Elevated arsenic concentrations (greater than or equal to 10 micrograms per liter) were detected in 9 percent of samples. Elevated arsenic concentrations were associated with strongly reducing conditions. Of the samples classified as iron reducing or sulfate reducing, arsenic concentrations were elevated in 19 percent. Of the methanogenic samples, arsenic concentrations were elevated in 45 percent. In contrast, concentrations of arsenic were elevated in only 1 percent of oxic samples. Arsenic concentrations were also related to ground-water age. Elevated arsenic concentrations were detected in 34 percent of old waters (recharged before 1953) as compared to 4 percent of young waters (recharged since 1953). For samples classified as both old and methanogenic, elevated arsenic concentrations were detected in 62 percent of samples, as compared to 1 percent for samples classified as young and oxic. Arsenic concentrations were also correlated with well depth and concentrations of several chemical constituents, including (1) constituents linked to redox processes and (2) anions or oxyanions that sorb to iron oxides. Observations from the glacial aquifer system are consistent with the idea that the predominant source of arsenic is iron oxides and the predominant mechanism for releasing arsenic to the ground water is reductive desorption or reductive dissolution. Arsenic is also released from iron oxides under oxic conditions, but on a more limited basis and at lower concentrations. Logistic regression was used to investigate the relative significance of redox, ground-water age, depth, and other water-quality constituents as indicators of elevated arsenic concentrations in the glacial aquifer system. The single variable that explained the greatest amount of variation in the data was redox. Multivariate models that included a redox variable overestimated the percentage of samples with elevated arsenic concentrations because, even though elevated arsenic concentrations were associated with strongly reducing samples, not all strongly reducing samples had elevated arsenic concentrations. Arsenic concentrations and redox conditions differed among four broad areas of the glacial aquifer system. For the East, Central, and West-Central north areas, there was a trend of increasing arsenic concentrations that corresponded to an increase in reducing conditions. For the West-Central south area, arsenic concentrations in oxic samples were higher than for the other areas, possibly because of high concentrations of orthophosphate, which is linked to desorption of arsenic from iron oxides under oxic conditions. The observed differences in arsenic concentrations among broad areas of the glacial aquifer system were generally consistent with a conceptual model developed by Smedley and Kinniburg, who studied or reviewed studies of widespread arsenic contamination in Bangladesh, India, China, Vietnam, Hungary, Argentina, northern Chile and the Southwestern United States.

Reduction of body iron in HFE-related haemochromatosis and moderate iron overload (Mi-Iron): a multicentre, participant-blinded, randomised controlled trial.

PubMed

Ong, Sim Y; Gurrin, Lyle C; Dolling, Lara; Dixon, Jeanette; Nicoll, Amanda J; Wolthuizen, Michelle; Wood, Erica M; Anderson, Gregory J; Ramm, Grant A; Allen, Katrina J; Olynyk, John K; Crawford, Darrell; Ramm, Louise E; Gow, Paul; Durrant, Simon; Powell, Lawrie W; Delatycki, Martin B

2017-12-01

The iron overload disorder hereditary haemochromatosis is most commonly caused by HFE p.Cys282Tyr homozygosity. In the absence of results from any randomised trials, current evidence is insufficient to determine whether individuals with hereditary haemochromatosis and moderately elevated serum ferritin, should undergo iron reduction treatment. This trial aimed to establish whether serum ferritin normalisation in this population improved symptoms and surrogate biomarkers. This study was a multicentre, participant-blinded, randomised controlled trial done at three centres in Australia. We enrolled people who were homozygous for HFE p.Cys282Tyr, aged between 18 and 70 years, with moderately elevated serum ferritin, defined as 300-1000 μg/L, and raised transferrin saturation. Participants were randomly assigned, via a computer-generated random number, to undergo either iron reduction by erythrocytapheresis (treatment group) or sham treatment by plasmapheresis (control group). Randomisation was stratified by baseline serum ferritin (<600 μg/L or ≥600 μg/L), sex, and study site. Erythrocytapheresis and plasmapheresis were done every 3 weeks, the number of procedures and volume of red cells or plasma removed determined on the basis of each patient's haemoglobin, haematocrit, and serum ferritin concentration, as well their height and weight. In the erythrocytapheresis group, the target was to reduce serum ferritin to less than 300 μg/L. The number of procedures for the control group was based on the initial serum ferritin and prediction of decrease in serum ferritin of approximately 120 μg/L per treatment. The primary outcome was patient-reported Modified Fatigue Impact Scale (MFIS) score, measured at baseline and before unblinding. Analyses were by intention to treat, including the safety analysis. The trial is registered with ClinicalTrials.gov, number NCT01631708, and has been completed. Between Aug 15, 2012, and June 9, 2016, 104 participants were randomly assigned to the treatment (n=54) and control (n=50) groups, of whom 94 completed the study (50 in the treatment group and 44 in the control group). Improvement in MFIS score was greater in the treatment group than in the control group (mean difference -6·3, 95% CI -11·1 to -1·4, p=0·013). There was a significant difference in the cognitive subcomponent (-3·6, -5·9 to -1·3, p=0·0030), but not in the physical (-1·90 -4·5 to 0·63, p=0·14) and psychosocial (-0·54, -1·2 to 0·11, p=0·10) subcomponents. No serious adverse events occurred in either group. One participant in the control group had a vasovagal event and 17 participants (14 in the treatment group and three in the control group) had transient symptoms assessed as related to hypovolaemia. Mild citrate reactions were more common in the treatment group (32 events [25%] in 129 procedures) compared with the control group (one event [1%] in 93 procedures). To our knowledge, this study is the first to objectively assess the consequences of iron removal in individuals with hereditary haemochromatosis and moderately elevated serum ferritin. Our results suggest that serum ferritin normalisation by iron depletion could be of benefit for all individuals with hereditary haemochromatosis and elevated serum ferritin levels. National Health and Medical Research Council (Australia). Copyright © 2017 Elsevier Ltd. All rights reserved.

METALLOPROTEINS DURING DEVELOPMENT OF WALKER-256 CARCINOSARCOMA RESISTANT PHENOTYPE.

PubMed

Chekhun, V F; Lozovska, Yu V; Burlaka, A P; Ganusevich, I I; Shvets, Yu V; Lukianova, N Yu; Todor, I M; Demash, D V; Pavlova, A A; Naleskina, L A

2015-01-01

The study was focused on the detection of changes in serum and tumor metal-containing proteins in animals during development ofdoxorubicin-resistant phenotype in malignant cells after 12 courses of chemotherapy. We found that on every stage of resistance development there was a significant increase in content of ferritin and transferrin proteins (which take part in iron traffick and storage) in Walker-256 carc'inosarcoma tissue. We observed decreased serumferritin levels at the beginning stage of the resistance development and significant elevation of this protein levels in the cases withfully developed resistance phenotype. Transferrin content showed changes opposite to that offerritin. During the development of resistance phenotype the tumor tissue also exhibited increased 'free iron' concentration that putatively correlate with elevation of ROS generation and levels of MMP-2 and MMP-9 active forms. The tumor non-protein thiol content increases gradually as well. The serum of animals with early stages of resistance phenotype development showed high ceruloplasmin activity and its significant reduction after loss of tumor sensitivity to doxorubicin. Therefore, the development of resistance phenotype in Walker-256 carcinosarcoma is accompanied by both the deregulation of metal-containing proteins in serum and tumor tissue and by the changes in activity of antioxidant defense system. Thus, the results of this study allow us to determine the spectrum of metal-containing proteins that are involved in the development of resistant tumor phenotype and that may be targeted for methods for doxorubicin sensitivity correction therapy.

Novel and rapid osteoporosis model established in zebrafish using high iron stress.

PubMed

Zhang, Wenjuan; Xu, Jingjin; Qiu, Juhui; Xing, Cencan; Li, Xiumin; Leng, Bo; Su, Yi; Lin, Jinmei; Lin, Jiaofen; Mei, Xuqiao; Huang, Yiqun; Pan, Yutian; Xue, Yu

2018-02-05

Osteoporosis is a global public health concern and, it can result from numerous pathogenic mechanisms, many of which are closely related with age, nutritional disorders, endocrine imbalance, or adverse drug side effects presented by glucocorticoids, heparin, and anti-epileptics. Given its wide range etiologies, it is crucial to establish an animal model of osteoporosis for use in screening potential drugs quickly and effectively. Previous research has reported that an accumulation of elevated iron in the body is an independent risk factor for osteoporosis. As such, we sought to use both zebrafish larvae and adults to model an osteoporosis phenotype using high iron stress (FAC, ferric ammonium citrate). Skeletal staining results suggested that iron-overload caused a significant decrease in bone calcification as well as severe developmental cartilage defects. In addition, osteoblast and cartilage-specific mRNA expression levels were downregulated after exposure to a high-iron environment. Most importantly, we demonstrated in both larval and adult fish that high iron-induced osteogenic defects were significantly rescued using alendronate (AL), a drug known to be effective against to human osteoporosis. Even more, the repair effect of AL was achieved by facilitating osteoblast differentiation and targeting Bmp signaling. Taken together, our findings propose an rapid and effective osteoporosis model, which could be used widely for future osteoporosis drug screening. Copyright © 2018 Elsevier Inc. All rights reserved.

Liver transplantation from a deceased donor with β-thalassemia intermedia is not contraindicated: A case report.

PubMed

Gumus, Ersin; Abbasoglu, Osman; Tanyel, Cahit; Gumruk, Fatma; Ozen, Hasan; Yuce, Aysel

2017-05-01

The use of extended criteria donors who might have previously been deemed unsuitable is an option to increase the organ supply for transplantation. This report presents a pediatric case of a successful liver transplantation from a donor with β-thalassemia intermedia. A patient, 6-year-old female, with a diagnosis of cryptogenic liver cirrhosis underwent deceased donor liver transplantation from a thalassemic donor. Extreme hyperferritinemia was detected shortly after transplantation. The most probable cause of hyperferritinemia was iron overload secondary to transplantation of a hemosiderotic liver. Hepatocellular injury due to acute graft rejection might have contributed to elevated ferritin levels by causing release of stored iron from the hemosiderotic liver graft. Iron chelation and phlebotomy therapies were started simultaneously in the early postoperative period to avoid iron-related organ toxicity and transplant failure. Follow-up with monthly phlebotomies after discharge yielded a favorable outcome with normal transplant functions. Thalassemia intermedia patients can be candidates of liver donors to decrease pretransplant waitlist mortality. After transplantation of a hemosiderotic liver, it is important to monitor the recipient in terms of iron overload and toxicity. Early attempts to lower iron burden including chelation therapy and/or phlebotomy should be considered to avoid organ toxicity and transplant failure. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

The effect of carboxydextran-coated superparamagnetic iron oxide nanoparticles on c-Jun N-terminal kinase-mediated apoptosis in human macrophages.

PubMed

Lunov, Oleg; Syrovets, Tatiana; Büchele, Berthold; Jiang, Xiue; Röcker, Carlheinz; Tron, Kyrylo; Nienhaus, G Ulrich; Walther, Paul; Mailänder, Volker; Landfester, Katharina; Simmet, Thomas

2010-07-01

Superparamagnetic iron oxide nanoparticles are frequently used for cell labeling or as diagnostic contrast media, yet studies analyzing their effects on immune cells remain scarce. Here we investigated how nanosized carboxydextran-coated superparamagnetic iron oxide (SPIO) and ultrasmall superparamagnetic iron oxide (USPIO) might affect human macrophages. Within 1 h, both SPIO and USPIO were rapidly taken up by macrophages. Confocal microscopy revealed that after 24 h the particles were almost exclusively localized within the lysosomal compartment. Continued cultivation of the macrophages for several days was associated with apoptosis induction caused by a long-lasting activation of the c-Jun N-terminal kinase (JNK) pathway. JNK activation was due to significantly elevated levels of reactive oxygen species, whereas no TNF-alpha was produced by the macrophages treated with nanoparticles. Compared to SPIO, USPIO induced more pronounced biochemical alterations and cytotoxicity, which could be antagonized by the JNK inhibitor V. Alternatively, treatment of macrophages with Trolox or N-acetyl-L-cysteine, two functionally different scavengers of reactive oxygen species, abolished both the JNK activation and the subsequent cytotoxic effects. These data indicate that nanosized superparamagnetic iron oxide-based contrast media exert cytotoxicity in human macrophages that can be functionally antagonized with radical scavengers. Copyright 2010 Elsevier Ltd. All rights reserved.

FRONT (SOUTH) ELEVATION, MIXER RUINS (CENTER) WITH STACKS (LEFT) AND ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

FRONT (SOUTH) ELEVATION, MIXER RUINS (CENTER) WITH STACKS (LEFT) AND POWER HOUSE (RIGHT). - Tennessee Coal & Iron Company, Ensley Works, Open Hearth Furnace (Ruins), West of Ensley commercial & residential districts, Birmingham, Jefferson County, AL

FRONT (SOUTH) ELEVATION, MIXER RUINS (CENTER) WITH STACKS (LEFT) AND ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

FRONT (SOUTH) ELEVATION, MIXER RUINS (CENTER) WITH STACKS (LEFT) AND POWER HOUSE (RIGHT - Tennessee Coal & Iron Company, Ensley Works, Open Hearth Furnace (Ruins), West of Ensley commercial & residential districts, Birmingham, Jefferson County, AL

2. WEST (FRONT) ELEVATION, LOOKING EAST, WITH SCALE (AND TOM ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

2. WEST (FRONT) ELEVATION, LOOKING EAST, WITH SCALE (AND TOM SHAW, S.C.ARCHIVES & HISTORY) - Cowpens Iron Furnace, 1000 feet East of County Road 34 & Cherokee Creek Bridge, Gaffney, Cherokee County, SC

Neonatal iron deficiency causes abnormal phosphate metabolism by elevating FGF23 in normal and ADHR mice.

PubMed

Clinkenbeard, Erica L; Farrow, Emily G; Summers, Lelia J; Cass, Taryn A; Roberts, Jessica L; Bayt, Christine A; Lahm, Tim; Albrecht, Marjorie; Allen, Matthew R; Peacock, Munro; White, Kenneth E

2014-02-01

Fibroblast growth factor 23 (FGF23) gain of function mutations can lead to autosomal dominant hypophosphatemic rickets (ADHR) disease onset at birth, or delayed onset following puberty or pregnancy. We previously demonstrated that the combination of iron deficiency and a knock-in R176Q FGF23 mutation in mature mice induced FGF23 expression and hypophosphatemia that paralleled the late-onset ADHR phenotype. Because anemia in pregnancy and in premature infants is common, the goal of this study was to test whether iron deficiency alters phosphate handling in neonatal life. Wild-type (WT) and ADHR female breeder mice were provided control or iron-deficient diets during pregnancy and nursing. Iron-deficient breeders were also made iron replete. Iron-deficient WT and ADHR pups were hypophosphatemic, with ADHR pups having significantly lower serum phosphate (p < 0.01) and widened growth plates. Both genotypes increased bone FGF23 mRNA (>50 fold; p < 0.01). WT and ADHR pups receiving low iron had elevated intact serum FGF23; ADHR mice were affected to a greater degree (p < 0.01). Iron-deficient mice also showed increased Cyp24a1 and reduced Cyp27b1, and low serum 1,25-dihydroxyvitamin D (1,25D). Iron repletion normalized most abnormalities. Because iron deficiency can induce tissue hypoxia, oxygen deprivation was tested as a regulator of FGF23, and was shown to stimulate FGF23 mRNA in vitro and serum C-terminal FGF23 in normal rats in vivo. These studies demonstrate that FGF23 is modulated by iron status in young WT and ADHR mice and that hypoxia independently controls FGF23 expression in situations of normal iron. Therefore, disturbed iron and oxygen metabolism in neonatal life may have important effects on skeletal function and structure through FGF23 activity on phosphate regulation. © 2014 American Society for Bone and Mineral Research.

Association of ferroportin Q248H polymorphism with elevated levels of serum ferritin in African-Americans in the Hemochromatosis and Iron Overload Screening (HEIRS) Study

PubMed Central

Rivers, Charles A.; Barton, James C.; Gordeuk, Victor R.; Acton, Ronald T.; Speechley, Mark R.; Snively, Beverly M.; Leiendecker-Foster, Catherine; Press, Richard D.; Adams, Paul C.; McLaren, Gordon D.; Dawkins, Fitzroy W.; McLaren, Christine E.; Reboussin, David M.

2007-01-01

The ferroportin (FPN1) Q248H polymorphism has been associated with increased serum ferritin (SF) levels in sub-Saharan Africans and in African Americans (AA). AA participants of the HEIRS Study who did not have HFE C282Y or H63D who had elevated initial screening SF (≥300 μg/L in men and ≥200 μg/L in women) (defined as cases) were frequency-matched to AA participants with normal SF (defined as controls) to investigate the association of the Q248H with elevated SF. 10.4% of cases and 6.7% of controls were Q248H heterozygotes (P = 0.257). Q248H homozygosity was observed in 0.5% of the cases and none of the controls. The frequency of Q248H was higher among men with elevated SF than among control men (P = 0.047); corresponding differences were not observed among women. This appeared to be unrelated to self-reports of a previous diagnosis of liver disease. Men with elevated SF were three times more likely than women with elevated SF to have Q248H (P = 0.012). There were no significant differences in Q248H frequencies in men and women control participants. We conclude that the frequency of the FPN1 Q248H polymorphism is greater in AA men with elevated SF than in those with normal SF. PMID:17276706

VAPOR PHASE MERCURY SORPTION BY ORGANIC SULFIDE MODIFIED BIMETALLIC IRON-COPPER NANOPARTICLE AGGREGATES

EPA Science Inventory

Novel organic sulfide modified bimetallic iron-copper nanoparticle aggregate sorbent materials have been synthesized for removing elemental mercury from vapor streams at elevated temperatures (120-140 °C). Silane based (disulfide silane and tetrasulfide silane) and alkyl sulfide ...

Iron storage in liver, bone marrow and splenic Gaucheroma reflects residual disease in type 1 Gaucher disease patients on treatment.

PubMed

Regenboog, Martine; Bohte, Anneloes E; Akkerman, Erik M; Stoker, Jaap; Hollak, Carla E M

2017-11-01

Gaucher disease (GD) is a lysosomal storage disorder characterized by the storage of glycosphingolipids in macrophages. Despite effective therapy, residual disease is present in varying degrees and may be associated with late complications, such as persistent bone or liver disease and increased cancer risk. Gaucher macrophages are capable of storing iron and locations of residual disease may thus be detectable with iron imaging. Forty type 1 GD (GD1) patients and 40 matched healthy controls were examined using a whole-body magnetic resonance imaging protocol consisting of standard sequences, allowing analysis of iron content per organ, expressed as R2* (Hz). Median R2* values were significantly elevated in GD1 patients as compared to healthy controls in liver [41 Hz (range 29-165) vs. 38 Hz (range 28-53), P < 0·01], femoral bone marrow [54 Hz (range 37-129) vs. 49 Hz (range 39-69), P = 0·036] and vertebral bone marrow (118 Hz (range 82-210) vs. 105 Hz (range 76-149), P < 0·01). In the spleen, primarily focal Gaucher lesions known as Gaucheroma were found to have increased R2* values. R2* values of liver, spleen and vertebral bone marrow strongly correlated with serum ferritin levels. GD1 patients with persistent hyperferritinaemia demonstrate increased iron levels in liver and bone marrow, which may carry a risk for liver fibrosis and cancer. © 2017 John Wiley & Sons Ltd.

Immune Status 'in Children with Beta Thalassemia' in Correlation 'with Iron Overload': Single Center Egyptian Study.

PubMed

Hagag, Adel A; Elgamsy, Mohamed A; El-Asy, Hassan M; Gamal, Rasha M; Elshahaby, Walid N; Abd Elbar, Enaam S

2016-01-01

'Beta thalassemia is inherited hemoglobin disorder resulting in chronic hemolytic anemia that requires lifelong transfusion therapy'. 'Repeated blood transfusions and RBCs hemolysis are the main causes of iron overload', which in addition to immune abnormalities, are common predisposing factors to infections in patients with thalassemia. The Aim of this Work: The aim of this work was to study immune status including T lymphocyte subsets and serum immunoglobulin levels 'in children with beta- thalassemia in correlation with iron overload'. The present 'study was conducted on 40 children with beta thalassemia major under follow up at Hematology Unit, Pediatric Department, Tanta University' 'including 24 males and 16 females with mean' age value of 9. 22 ± 3.9 years and 20 'healthy children of matched age and sex as a control group'. All children included in the study were subjected to; 'complete blood count, Hb electrophoresis, serum iron status', T cell subsets including CD3, CD4 and CD8 and serum immunoglobulin levels including IgM, IgA and IgG. 'Pallor and jaundice were the most common presenting' clinical manifestations. Infective episodes 'were significantly higher in patients' compared with controls. There were significantly lower Hb, MCV and MCH levels and significantly higher WBCs and platelets counts, reticulocytes and lymphocytes percentage in patients than controls and no significant differences in MCHC between patients and controls. Serum ferritin and iron were 'significantly higher but TIBC was significantly lower in' patients than controls. CD3, CD4 and IgM were significantly lower but CD8, IgG, and IgA 'were significantly higher in patients than controls' with negative correlation between CD3, CD4, IgM and ferritin and positive correlation between CD8, IgG, IgA and ferritin. Iron overload can affect humeral and cell mediated immunity in patients with beta thalassemia with reduction of IgM, CD3 and CD4 and elevation of CD8, IgG, and IgA. Regular follow up of patients with beta thalassemia for detection of iron overload as it affects humeral and cell mediated immunity. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Association of oxidative DNA damage, protein oxidation and antioxidant function with oxidative stress induced cellular injury in pre-eclamptic/eclamptic mothers during fetal circulation.

PubMed

Negi, Reena; Pande, Deepti; Karki, Kanchan; Kumar, Ashok; Khanna, Ranjana S; Khanna, Hari D

2014-02-05

Pre-eclampsia is a devastating multi system syndrome and a major cause of maternal, fetal, neonatal morbidity and mortality. Pre-eclampsia is associated with oxidative stress in the maternal circulation. To have an insight on the effect of pre-eclampsia/eclampsia on the neonates, the study was made to explore the oxidative status by quantification of byproducts generated during protein oxidation and oxidative DNA damage and deficient antioxidant activity in umbilical cord blood of pre-eclamptic/eclamptic mothers during fetal circulation. Umbilical cord blood during delivery from neonates born to 19 pre-eclamptic mothers, 14 eclamptic mothers and 18 normotensive mothers (uncomplicated pregnancy) as control cases was collected. 8-OHdG (8-hydroxy-2-deoxyguanosine), protein carbonyl, nitrite, catalase, non-enzymatic antioxidants (vitamin A, E, C), total antioxidant status and iron status were determined. Significant elevation in the levels of 8-OHdG, protein carbonyl, nitrite and iron along with decreased levels of catalase, vitamin A, E, C, total antioxidant status were observed in the umbilical cord blood of pre-eclamptic and eclamptic pregnancies. These parameters might be influential variables for the risk of free radical damage in infants born to pre-eclamptic/eclamptic pregnancies. Increased oxidative stress causes oxidation of DNA and protein which alters antioxidant function. Excess iron level and decreased unsaturated iron binding capacity may be the important factor associated with oxidative stress and contribute in the pathogenesis of pre-eclampsia/eclampsia which is reflected in fetal circulation. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Intake of meat, meat mutagens, and iron and the risk of breast cancer in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial.

PubMed

Ferrucci, L M; Cross, A J; Graubard, B I; Brinton, L A; McCarty, C A; Ziegler, R G; Ma, X; Mayne, S T; Sinha, R

2009-07-07

Epidemiological evidence on meat intake and breast cancer is inconsistent, with little research on potentially carcinogenic meat-related exposures. We investigated meat subtypes, cooking practices, meat mutagens, iron, and subsequent breast cancer risk. Among 52 158 women (aged 55-74 years) in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial, who completed a food frequency questionnaire, 1205 invasive breast cancer cases were identified. We estimated meat mutagen and haem iron intake with databases accounting for cooking practices. Using Cox proportional hazards regression, we calculated hazard ratios (HRs) and 95% confidence intervals (CIs) within quintiles of intake. Comparing the fifth to the first quintile, red meat (HR=1.23; 95% CI=1.00-1.51, P trend=0.22), the heterocyclic amine (HCA), 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx), (HR=1.26; 95% CI=1.03-1.55; P trend=0.12), and dietary iron (HR=1.25; 95% CI=1.02-1.52; P trend=0.03) were positively associated with breast cancer. We observed elevated, though not statistically significant, risks with processed meat, the HCA 2-amino-3,4,8-trimethylimidazo[4,5-f]quinoxaline (DiMeIQx), mutagenic activity, iron from meat, and haem iron from meat. In this prospective study, red meat, MeIQx, and dietary iron elevated the risk of invasive breast cancer, but there was no linear trend in the association except for dietary iron.

Model of radiation transmittance by inorganic fouling on UV reactor lamp sleeves.

PubMed

Wait, Isaac W; Blatchley, Ernest R

2010-11-01

The efficacy of UV disinfection of water depends on the ability of radiation to pass from UV lamps through the quartz sleeves that encase them; the accumulation of metal-containing foulants on sleeve surfaces inhibits disinfection by absorbing radiation that would otherwise be available for inactivation. In a series of experiments, the composition and quantity of sleeve foulants were studied relative to water chemistry and sleeve transmittance. Findings indicate that iron and calcium dominate fouling, with elevated fouling activity by iron, aluminum, manganese, and zinc. A regression-based modeling approach was used to characterize and quantify the effects of foulant metals on UV absorbance. The molar extinction coefficient for iron was found to be more than 3 times greater than that of calcium. Iron's relatively high activity in fouling reactions, elevated capacity to absorb UV, and reduced solubility under oxidizing conditions makes it a fouling precursor of particular concern, with respect to potential for sleeve fouling in UV reactors.

Physiological responses of coastal phytoplankton (Visakhapatnam, SW Bay of Bengal, India) to experimental copper addition.

PubMed

Biswas, Haimanti; Bandyopadhyay, Debasmita

2017-10-01

Trace amount of copper (Cu) is essential for many physiological processes; however, it can be potentially toxic at elevated levels. The impact of variable Cu concentrations on a coastal phytoplankton community was investigated along a coastal transect in SW Bay of Bengal. A small increase in Cu supply enhanced the concentrations of particulate organic carbon, particulate organic nitrogen, biogenic silica, total pigment, phytoplankton cell and total bacterial count. At elevated Cu levels all these parameters were adversely affected. δ 13 C POM and δ 15 N POC reflected a visible signature of both beneficial and toxic impacts of Cu supply. Skeletonema costatum, the dominant diatom species, showed higher tolerance to increasing Cu levels relative to Chaetoceros sp. Cyanobacteria showed greater sensitivity to copper than diatoms. The magnitude of Cu toxicity on the phytoplankton communities was inversely related to the distance from the coast. Co-enrichment of iron alleviated Cu toxicity to phytoplankton. Copyright © 2017 Elsevier Ltd. All rights reserved.

Is outdoor work associated with elevated rates of cerebrovascular disease mortality? A cohort study based on iron-ore mining.

PubMed

Björ, Ove; Jonsson, Håkan; Damber, Lena; Burström, Lage; Nilsson, Tohr

2016-01-01

A cohort study that examined iron ore mining found negative associations between cumulative working time employed underground and several outcomes, including mortality of cerebrovascular diseases. In this cohort study, and using the same group of miners, we examined whether work in an outdoor environment could explain elevated cerebrovascular disease rates. This study was based on a Swedish iron ore mining cohort consisting of 13,000 workers. Poisson regression models were used to generate smoothed estimates of standardized mortality ratios and adjusted rate ratios, both models by cumulative exposure time in outdoor work. The adjusted rate ratio between employment classified as outdoor work ≥25 years and outdoor work 0-4 years was 1.62 (95 % CI 1.07-2.42). The subgroup underground work ≥15 years deviated most in occurrence of cerebrovascular disease mortality compared with the external reference population: SMR (0.70 (95 % CI 0.56-0.85)). Employment in outdoor environments was associated with elevated rates of cerebrovascular disease mortality. In contrast, work in tempered underground employment was associated with a protecting effect.

Role of liver magnetic resonance imaging in hyperferritinaemia and the diagnosis of iron overload.

PubMed

Ruefer, Axel; Bapst, Christine; Benz, Rudolf; Bremerich, Jens; Cantoni, Nathan; Infanti, Laura; Samii, Kaveh; Schmid, Mathias; Vallée, Jean-Paul

2017-11-09

Hyperferritinaemia is a frequent clinical problem. Elevated serum ferritin levels can be detected in different genetic and acquired diseases and can occur with or without anaemia. It is therefore important to determine whether hyperferritinaemia is due to iron overload or due to a secondary cause. The main causes of iron overload are intestinal iron hyperabsorption disorders and transfusion-dependent disorders. Iron homeostasis and iron overload are quantified by different diagnostic approaches. The evaluation of serum ferritin and transferrin saturation is the first diagnostic step to identify the cause of hyperferritinaemia. The assessment of liver iron concentration by liver biopsy or magnetic resonance imaging (MRI) may guide the further diagnostic and therapeutic workup. Liver biopsy is invasive and poorly accepted by patients and should only be carried out in selected patients with hereditary haemochromatosis. As a non-invasive approach, MRI is considered the standard method to diagnose and to monitor both hepatic iron overload and the effectiveness of iron chelation therapy in many clinical conditions such as thalassaemia and myelodysplastic syndromes. Accurate evaluation and monitoring of iron overload has major implications regarding adherence, quality of life and prognosis. There are different technical MRI approaches to measuring the liver iron content. Of these, T2 and T2* relaxometry are considered the standard of care. MRI with cardiac T2* mapping is also suitable for the assessment of cardiac iron. Currently there is no consensus which technique should be preferred. The choice depends on local availability and patient population. However, it is important to use the same MRI technique in subsequent visits in the same patient to get comparable results. Signal intensity ratio may be a good adjunct to R2 and R2* methods as it allows easy visual estimation of the liver iron concentration. In this review a group of Swiss haematologists and radiologists give an overview of different conditions leading to primary or secondary iron overload and on diagnostic methods to assess hyperferritinaemia with a focus on the role of liver MRI. They summarise the standard practice in Switzerland on the use of liver iron concentration MRI as well as disease-specific guideline recommendations.

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

Estimation of Mineral and Trace Element Profile in Bubaline Milk Affected with Subclinical Mastitis.

PubMed

Singh, Mahavir; Yadav, Poonam; Sharma, Anshu; Garg, V K; Mittal, Dinesh

2017-04-01

The milk samples from buffaloes of Murrah breed at mid lactation stage, reared at an organised dairy farm, were screened for subclinical mastitis based on bacteriological examination and somatic cell count following International Dairy Federation criteria. Milk samples from subclinical mastitis infected and healthy buffaloes were analysed to evaluate physicochemical alterations in terms of protein, fat, pH, electrical conductivity, chloride, minerals (sodium, potassium and calcium) and trace elements (iron, zinc, copper and selenium). In the present study, protein, fat, zinc, iron, calcium and selenium content was significantly lower (P < 0.001), while pH and electrical conductivity were significantly higher in mastitic milk as compared to normal milk. Concentration of electrolytes mainly sodium and chloride significantly increased with higher somatic cell count in mastitic milk and to maintain osmolality; potassium levels decreased proportionately. Correlation matrix revealed significantly positive interdependences of somatic cell count with pH, electrical conductivity, sodium and chloride. However, protein, fat, calcium and potassium were correlated negatively with elevated somatic cell count in mastitic milk. It is concluded that udder infections resulting in elevated somatic cells may alter the mineral and trace element profile of milk, and magnitude of changes may have diagnostic and prognostic value.

Calcium-sensitive MRI contrast agents based on superparamagnetic iron oxide nanoparticles and calmodulin

PubMed Central

Atanasijevic, Tatjana; Shusteff, Maxim; Fam, Peter; Jasanoff, Alan

2006-01-01

We describe a family of calcium indicators for magnetic resonance imaging (MRI), formed by combining a powerful iron oxide nanoparticle-based contrast mechanism with the versatile calcium-sensing protein calmodulin and its targets. Calcium-dependent protein–protein interactions drive particle clustering and produce up to 5-fold changes in T2 relaxivity, an indication of the sensors' potency. A variant based on conjugates of wild-type calmodulin and the peptide M13 reports concentration changes near 1 μM Ca2+, suitable for detection of elevated intracellular calcium levels. The midpoint and cooperativity of the response can be tuned by mutating the protein domains that actuate the sensor. Robust MRI signal changes are achieved even at nanomolar particle concentrations (<1 μM in calmodulin) that are unlikely to buffer calcium levels. When combined with technologies for cellular delivery of nanoparticulate agents, these sensors and their derivatives may be useful for functional molecular imaging of biological signaling networks in live, opaque specimens. PMID:17003117

Calcium-sensitive MRI contrast agents based on superparamagnetic iron oxide nanoparticles and calmodulin.

PubMed

Atanasijevic, Tatjana; Shusteff, Maxim; Fam, Peter; Jasanoff, Alan

2006-10-03

We describe a family of calcium indicators for magnetic resonance imaging (MRI), formed by combining a powerful iron oxide nanoparticle-based contrast mechanism with the versatile calcium-sensing protein calmodulin and its targets. Calcium-dependent protein-protein interactions drive particle clustering and produce up to 5-fold changes in T2 relaxivity, an indication of the sensors' potency. A variant based on conjugates of wild-type calmodulin and the peptide M13 reports concentration changes near 1 microM Ca(2+), suitable for detection of elevated intracellular calcium levels. The midpoint and cooperativity of the response can be tuned by mutating the protein domains that actuate the sensor. Robust MRI signal changes are achieved even at nanomolar particle concentrations (<1 microM in calmodulin) that are unlikely to buffer calcium levels. When combined with technologies for cellular delivery of nanoparticulate agents, these sensors and their derivatives may be useful for functional molecular imaging of biological signaling networks in live, opaque specimens.

Alterations in sympathetic nerve traffic in genetic haemochromatosis before and after iron depletion therapy: a microneurographic study.

PubMed

Seravalle, Gino; Piperno, Alberto; Mariani, Raffaella; Pelloni, Irene; Facchetti, Rita; Dell'Oro, Raffaella; Cuspidi, Cesare; Mancia, Giuseppe; Grassi, Guido

2016-03-21

Haemochromatosis (HH) displays a number of circulatory alterations concurring at increase cardiovascular risk. Whether these include sympathetic abnormalities in unknown. In 18 males with primary HH (age: 42.3 ± 10.4 years, mean ± SD), clinic and beat-to-beat blood pressure (BP, Finapres), heart rate (HR, EKG), and muscle sympathetic nerve activity (MSNA, microneurography) traffic were measured in the iron overload state and after iron depletion therapy. Haemochromatosis patients displayed elevated serum iron indices while other haemodynamic and metabolic variables were superimposable to ones seen in 12 healthy subjects (C). Muscle sympathetic nerve activity was significantly greater in HH than C (64.8 ± 13.3 vs. 37.8 ± 6.7 bs/100 hb, P < 0.01). Iron depletion caused a significant reduction in serum ferritin, transferrin saturation, and MSNA (from 64.8 ± 13.3 to 39.2 ± 9.2 bs/100 hb, P < 0.01) and a significant improvement in baroreflex-MSNA modulation. This was paralleled by a significant increase in the high-frequency HR variability and by a significant reduction in the low-frequency systolic BP variability components. Before after iron depletion therapy, MSNA was significantly and directly related to transferrin saturation, liver iron concentration, and iron removed, while the MSNA reductions observed after the procedure were significantly and inversely related to the baroreflex-MSNA increases detected after iron depletion. In C, all variables remained unchanged following 1 month observation. These data provide the first evidence that in HH iron overload is associated with an hyperadrenergic state and a baroreflex alteration, which are reversed by iron depletion. These findings underline the importance of iron overload in modulating sympathetic activation, possibly participating at the elevated cardiovascular risk reported in HH. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2015. For permissions please email: journals.permissions@oup.com.

Ferritin for the Clinician

PubMed Central

Knovich, Mary Ann; Storey, Jonathan A.; Coffman, Lan G.; Torti, Suzy V.

2009-01-01

Ferritin, a major iron storage protein, is essential to iron homeostasis and is involved in a wide range of physiologic and pathologic processes. In clinical medicine, ferritin is predominantly utilized as a serum marker of total body iron stores. In cases of iron deficiency and overload, serum ferritin serves a critical role in both diagnosis and management. Elevated serum and tissue ferritin are linked to coronary artery disease, malignancy, and poor outcomes following stem cell transplantation. Ferritin is directly implicated in less common but potentially devastating human diseases including sideroblastic anemias, neurodegenerative disorders, and hemophagocytic syndrome. Additionally, recent research describes novel functions of ferritin independent of iron storage. PMID:18835072

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

The High Affinity Iron Permease is a Key Virulence Factor Required for Rhizopus oryzae Pathogenesis

USDA-ARS?s Scientific Manuscript database

Rhizopus oryzae is the most common cause of mucormycosis, an angioinvasive fungal infection that causes a >/=50% mortality rate despite first-line therapy. Clinical and animal model data clearly demonstrate that the presence of elevated available serum iron predisposes the host to mucormycosis. Th...

Phlebotomy improves histology in chronic hepatitis C males with mild iron overload

PubMed Central

Sartori, Massimo; Andorno, Silvano; Rossini, Angelo; Boldorini, Renzo; Bozzola, Cristina; Carmagnola, Stefania; Piano, Mario Del; Albano, Emanuele

2010-01-01

AIM: To investigate the usefulness of mild iron depletion and the factors predictive for histological improvement following phlebotomy in Caucasians with chronic hepatitis C (CHC). METHODS: We investigated 28 CHC Caucasians with persistently elevated serum aminotransferase levels and non responders to, or unsuitable for, antiviral therapy who underwent mild iron depletion (ferritin ≤ 70 ng/mL) by long-term phlebotomy. Histological improvement, as defined by at least one point reduction in the staging score or, in case of unchanged stage, as at least two points reduction in the grading score (Knodell), was evaluated in two subsequent liver biopsies (before and at the end of phlebotomy, 48 ± 16 mo apart). RESULTS: Phlebotomy showed an excellent safety profile. Histological improvement occurred in 12/28 phlebotomized patients. Only males responded to phlebotomy. At univariate logistic analysis alcohol intake (P = 0.034), high histological grading (P = 0.01) and high hepatic iron concentration (HIC) (P = 0.04) before treatment were associated with histological improvement. Multivariate logistic analysis showed that in males high HIC was the only predictor of histological improvement following phlebotomy (OR = 1.41, 95% CI: 1.03-1.94, P = 0.031). Accordingly, 12 out of 17 (70%) patients with HIC ≥ 20 μmol/g showed histological improvements at the second biopsy. CONCLUSION: Male CHC Caucasian non-responders to antiviral therapy with low-grade iron overload can benefit from mild iron depletion by long-term phlebotomy. PMID:20128028

Comparison of workers' perceptions toward work climate and health symptoms between ceramic and iron foundry workers.

PubMed

Majumder, Joydeep; Bagepally, Bhavani S; Shah, Priyanka; Kotadiya, Sanjay; Yadav, Suresh; Naha, Nibedita

2016-01-01

Workers exposed to heavy manual material handling (MMH) in a hot working environment succumb to severe physical stress and psychological stress. (1) Recognize the heat load at workplaces of ceramic industry and iron industry, and (2) comparatively examine the characteristics of self-reported physiological responses and heat-health perception among these workers. Cross-sectional prospective study. Workplace microclimate in the ceramic industry and iron industry was monitored. An ergonomic checklist and a questionnaire was used to record self-reported workers' perceptions toward heat stress at workplace (ceramic workers N = 321, iron foundry workers N = 253). The prevalence rates of subjective symptoms among workers of both the industries were compared. Chi-square test was used to examine the association between stressors and health complaints at a significance level set at P < 0.05. Iron foundries recorded higher mean ambient temperature (43.4 ± 3.7°C) and wet-bulb globe temperature (WGBT) index (31.5 ± 0.7°C) as compared to ceramic industries (39.9 ± 3.3°C and 28 ± 1.5°C, respectively). Heavy sweating, elevated body temperature, sleeplessness, excessive thirst, muscular discomforts, and fatigue were prime symptoms recorded among workers of both industries. Skin-related disorders (red face, dry skin, bumps, itching) were significantly higher among iron foundry workers, whereas sleeplessness, high blood pressure, heavy sweating, kidney stone, decreased urination, muscular discomforts, and fatigue were significantly more among ceramic workers. Young workers reported more sweating and fatigue than older workers. A hot work climate and heavy manual labor designate ceramic and iron industries as arduous. Direct contact with hot surface and continuous MMH in tandem with the mechanical pace of production process makes work in ceramic industries more difficult than iron foundries.

Double-blind randomized controlled trial of rolls fortified with microencapsulated iron.

PubMed

Barbosa, Teresa Negreira Navarro; Taddei, José Augusto de Aguiar Carrazedo; Palma, Domingos; Ancona-Lopez, Fábio; Braga, Josefina Aparecida Pellegrini

2012-01-01

To evaluate the impact of the fortification of rolls with microencapsulated iron sulfate with sodium alginate on the hemoglobin levels in preschoolers as compared to controls. Double-blind randomized controlled trial comprised of children aged 2 to 6 years with initial hemoglobin exceeding 9 g/dL from four not-for-profit daycares randomly selected in the city of São Paulo - Brazil. Children of 2 daycares (n = 88) received rolls with fortified wheat flour as the exposed group (EC) and children of 2 daycares (n = 85) received rolls without fortification as the control group (CG) over a 24-week period. Rolls with 4 mg iron each were offered once a day, five days a week. Hemoglobin concentrations were determined in capillary blood by HemoCue® at three moments of trial: baseline (Ml), after 12 and 24 weeks of intervention (M2, M3). Hemoglobin concentration presented significant increase up to M3 in EG (11.7-12.5-12.6 g/dL) and in CG (11.1-12.4-12.3 g/dL) with higher elevations in children initially with anemia. There was significant reduction in the occurrence of anemia from 22% to 9% in EG and from 47% to 8.2% in CG at M3. Rolls fortified with microencapsulated iron sulfate were well tolerated, increased hemoglobin levels and reduced the occurrence of anemia, but with no difference compared to the control group.

Elevated iron status and risk of gestational diabetes mellitus: A systematic review and meta-analysis.

PubMed

Fernández-Cao, José C; Aranda, Núria; Ribot, Blanca; Tous, Mònica; Arija, Victoria

2017-10-01

The aim of this systematic review and meta-analysis of observational studies was to assess the relationship between elevated iron status, measured as hemoglobin and ferritin levels, and the risk of gestational diabetes mellitus (GDM). The present study was recorded in PROSPERO (2013:CRD42013005717). The selected studies were identified through a systematic review of scientific literature published in The Cochrane Library and PubMed/MEDLINE databases from their inception until March 10, 2016, in addition to citation tracking and hand-searches. The search strategy of original articles combined several terms for hemoglobin, ferritin, pregnancy, and GDM. OR and 95% CI of the selected studies were used to identify associations between hemoglobin and/or ferritin levels with the risk of GDM. Summary estimates were calculated by combining inverse-variance using fixed-effects model. 2468 abstracts were initially found during the search. Of these, 11 with hemoglobin and/or ferritin data were selected for the meta-analyses. We observed that high hemoglobin (OR = 1.52; 95% CI: 1.23-1.88), as well as ferritin (OR = 2.09; 95% CI: 1.48-2.96) levels were linked to an increased risk of GDM. Low heterogeneity was observed in hemoglobin (I 2  = 33.3%, P = 0.151) and ferritin (I 2  = 0.7%, P = 0.418) meta-analyses, respectively. Publication bias was not appreciated. High hemoglobin or ferritin levels increase the risk of GDM by more than 50% and more than double, respectively, in the first and third trimester. Therefore, determining of hemoglobin or ferritin concentration in early pregnancy might be a useful tool for recognizing pregnant women at risk of GDM. © 2016 John Wiley & Sons Ltd.

Intake of meat, meat mutagens, and iron and the risk of breast cancer in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial

PubMed Central

Ferrucci, L M; Cross, A J; Graubard, B I; Brinton, L A; McCarty, C A; Ziegler, R G; Ma, X; Mayne, S T; Sinha, R

2009-01-01

Background: Epidemiological evidence on meat intake and breast cancer is inconsistent, with little research on potentially carcinogenic meat-related exposures. We investigated meat subtypes, cooking practices, meat mutagens, iron, and subsequent breast cancer risk. Methods: Among 52 158 women (aged 55–74 years) in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial, who completed a food frequency questionnaire, 1205 invasive breast cancer cases were identified. We estimated meat mutagen and haem iron intake with databases accounting for cooking practices. Using Cox proportional hazards regression, we calculated hazard ratios (HRs) and 95% confidence intervals (CIs) within quintiles of intake. Results: Comparing the fifth to the first quintile, red meat (HR=1.23; 95% CI=1.00–1.51, P trend=0.22), the heterocyclic amine (HCA), 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx), (HR=1.26; 95% CI=1.03–1.55; P trend=0.12), and dietary iron (HR=1.25; 95% CI=1.02–1.52; P trend=0.03) were positively associated with breast cancer. We observed elevated, though not statistically significant, risks with processed meat, the HCA 2-amino-3,4,8-trimethylimidazo[4,5-f]quinoxaline (DiMeIQx), mutagenic activity, iron from meat, and haem iron from meat. Conclusion: In this prospective study, red meat, MeIQx, and dietary iron elevated the risk of invasive breast cancer, but there was no linear trend in the association except for dietary iron. PMID:19513076

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

Astroglial and microglial contributions to iron metabolism disturbance in Parkinson's disease.

PubMed

Song, Ning; Wang, Jun; Jiang, Hong; Xie, Junxia

2018-03-01

Understandings of the disturbed iron metabolism in Parkinson's disease (PD) are largely from the perspectives of neurons. Neurodegenerative processes in PD trigger universal and conserved astroglial dysfunction and microglial activation. In this review, we start with astroglia and microglia in PD with an emphasis on their roles in spreading α-synuclein pathology, and then focus on their contributions in iron metabolism under normal conditions and the diseased state of PD. Elevated iron in the brain regions affects glial features, meanwhile, glial effects on neuronal iron metabolism are largely dependent on their releasing factors. These advances might be valuable for better understanding and modulating iron metabolism disturbance in PD. Copyright © 2018 Elsevier B.V. All rights reserved.

Incidentally Detected Transfusion-associated Iron Overload in 3 Children After Cancer Chemotherapy.

PubMed

Kuo, Dennis John; Bhagia, Pooja

2018-04-01

Iron overload is a potential long-term complication among cancer survivors who received transfusions during treatment. Although there are screening guidelines for iron overload in pediatric survivors of hematopoietic stem cell transplant, these do not call for screening of other pediatric oncology patients. In our practice we incidentally discovered 3 patients in a population of 168 cancer survivors over the span of 17 years who were treated for cancer without hematopoietic stem cell transplant who had iron overload. The 3 patients had elevated liver iron on magnetic resonance imaging T2* and 2 received therapeutic phlebotomy. These cases, and others like them, suggest that collaborative groups should consider revisiting the literature to establish screening and treatment guidelines for iron overload after cancer therapy.

Iron deficiency impairs developing hippocampal neuron gene expression, energy metabolism and dendrite complexity

PubMed Central

Bastian, Thomas W.; von Hohenberg, William C.; Mickelson, Daniel J.; Lanier, Lorene M.; Georgieff, Michael K.

2016-01-01

Iron deficiency (ID), with and without anemia, affects an estimated 2 billion people worldwide. ID is particularly deleterious during early-life brain development, leading to long-term neurological impairments, including deficits in hippocampus-mediated learning and memory. Neonatal rats with fetal/neonatal ID anemia (IDA) have shorter hippocampal CA1 apical dendrites with disorganized branching. ID-induced dendritic structural abnormalities persist into adulthood despite normalization of iron status. However, the specific developmental effects of neuronal iron loss on hippocampal neuron dendrite growth and branching are unknown. Embryonic hippocampal neuron cultures were chronically treated with deferoxamine (DFO, an iron chelator) beginning at 3 days in vitro (DIV). Levels of mRNA for Tfr1 and Slc11a2, iron-responsive genes involved in iron uptake, were significantly elevated in DFO-treated cultures at 11DIV and 18DIV, indicating a similar degree of neuronal ID as seen in rodent ID models. DFO treatment decreased mRNA levels for genes indexing dendritic and synaptic development (i.e., BdnfVI, Camk2a, Vamp1, Psd95, Cfl1, Pfn1, Pfn2, and Gda) and mitochondrial function (i.e., Ucp2, Pink1, and Cox6a1). At 18DIV, DFO reduced key aspects of energy metabolism including basal respiration, maximal respiration, spare respiratory capacity, ATP production, and glycolytic rate, capacity, and reserve. Sholl analysis revealed a significant decrease in distal dendritic complexity in DFO-treated neurons at both 11DIV and 18DIV. At 11DIV, the length of primary dendrites and the number and length of branches in DFO-treated neurons was reduced. By 18DIV, a partial recovery of dendritic branch number in DFO-treated neurons was counteracted by a significant reduction in the number and length of primary dendrites and length of branches. Our findings suggest that early neuronal iron loss, at least partially driven through altered mitochondrial function and neuronal energy metabolism, is responsible for the effects of fetal/neonatal ID and IDA on hippocampal neuron dendritic and synaptic maturation. Impairments in these neurodevelopmental processes likely underlie the negative impact of early life ID and IDA on hippocampus-mediated learning and memory. PMID:27669335

A new analytical approach to understanding nanoscale lead-iron interactions in drinking water distribution systems.

PubMed

Trueman, Benjamin F; Gagnon, Graham A

2016-07-05

High levels of iron in distributed drinking water often accompany elevated lead release from lead service lines and other plumbing. Lead-iron interactions in drinking water distribution systems are hypothesized to be the result of adsorption and transport of lead by iron oxide particles. This mechanism was explored using point-of-use drinking water samples characterized by size exclusion chromatography with UV and multi-element (ICP-MS) detection. In separations on two different stationary phases, high apparent molecular weight (>669 kDa) elution profiles for (56)Fe and (208)Pb were strongly correlated (average R(2)=0.96, N=73 samples representing 23 single-unit residences). Moreover, (56)Fe and (208)Pb peak areas exhibited an apparent linear dependence (R(2)=0.82), consistent with mobilization of lead via adsorption to colloidal particles rich in iron. A UV254 absorbance peak, coincident with high molecular weight (56)Fe and (208)Pb, implied that natural organic matter was interacting with the hypothesized colloidal species. High molecular weight UV254 peak areas were correlated with both (56)Fe and (208)Pb peak areas (R(2)=0.87 and 0.58, respectively). On average, 45% (std. dev. 10%) of total lead occurred in the size range 0.05-0.45 μm. Copyright © 2016 Elsevier B.V. All rights reserved.

Iron overload and HFE gene mutations in Czech patients with chronic liver diseases.

PubMed

Dostalikova-Cimburova, Marketa; Kratka, Karolina; Stransky, Jaroslav; Putova, Ivana; Cieslarova, Blanka; Horak, Jiri

2012-01-01

The aim of the study was to identify the prevalence of HFE gene mutations in Czech patients with chronic liver diseases and the influence of the mutations on iron status. The presence of HFE gene mutations (C282Y, H63D, and S65C) analyzed by the PCR-RFLP method, presence of cirrhosis, and serum iron indices were compared among 454 patients with different chronic liver diseases (51 with chronic hepatitis B, 122 with chronic hepatitis C, 218 with alcoholic liver disease, and 63 patients with hemochromatosis). Chronic liver diseases patients other than hemochromatics did not have an increased frequency of HFE gene mutations compared to controls. Although 33.3% of patients with hepatitis B, 43% of patients with hepatitis C, and 73.2% of patients with alcoholic liver disease had elevated transferrin saturation or serum ferritin levels, the presence of HFE gene mutations was not significantly associated with iron overload in these patients. Additionally, patients with cirrhosis did not have frequencies of HFE mutations different from those without cirrhosis. This study emphasizes the importance, not only of C282Y, but also of the H63D homozygous genetic constellation in Czech hemochromatosis patients. Our findings show that increased iron indices are common in chronic liver diseases but {\\it HFE} mutations do not play an important role in the pathogenesis of chronic hepatitis B, chronic hepatitis C, and alcoholic liver disease.

Iron chelation therapy: clinical effectiveness, economic burden and quality of life in patients with iron overload.

PubMed

Payne, Krista A; Rofail, Diana; Baladi, Jean-François; Viala, Muriel; Abetz, Linda; Desrosiers, Marie-Pierre; Lordan, Noreen; Ishak, Khajak; Proskorovsky, Irina

2008-08-01

This study of UK patients examines clinical, health-related quality of life (HRQOL) and economic outcomes associated with iron chelation therapy (ICT). Desferrioxamine (DFO) (Desferal; Novartis, Switzerland) and Deferiprone (Ferriprox; Apotex, Canada) are ICTs used to treat iron overload. DFO requires 8-to 12-hour infusions a minimum of five times per week. Deferiprone is administered in an oral daily regimen. Although pharmacologically efficacious, clinical effectiveness of ICT within the real-world setting is yet to be fully elucidated. A naturalistic cohort study of 60 patients (beta-thalassaemia, n=40; sickle cell disease, n=14; myelodysplastic syndromes, n=6; 63% female) receiving ICT in four UK treatment centres was conducted. Serum ferritin level data were abstracted from medical charts. Compliance, HRQOL, satisfaction and resource utilisation data were collected from interviews. Maximum ICT costs were estimated using the resource utilisation data associated with DFO. Mean serum ferritin levels, generally, remained elevated despite ICT. Compliance was suboptimal and HRQOL scores were lower than population norms. The total estimated mean weighted annual per-patient cost of DFO treatment was approximately pound19,000. DFO-related equipment, DFO drug, and home healthcare were estimated to account for 43%, 19% and 24% of costs, respectively. Other more minor components of total annual costs were for in-patient infusions, ICT home delivery services and monitoring costs. Generally, patients are not achieving target serum ferritin thresholds despite chronic treatment for iron overload. ICT appears to negatively impact HRQOL; compliance with ICT is poor; and, in the case of DFO, treatment costs well exceed the cost of DFO alone. These results suggest that current ICT in the real-world setting is suboptimal with respect to various clinical, HRQOL and economic outcomes.

Semaphorin4A Is Cytotoxic to Oligodendrocytes and Is Elevated in Microglia and Multiple Sclerosis

PubMed Central

Leitner, Dominique F.; Todorich, Bozho; Zhang, Xuesheng

2015-01-01

We have previously established that T cell immunoglobulin and mucin domain containing 2 (Tim2) is an H-ferritin receptor on oligodendrocytes (OLs). Tim2 also binds Semaphorin4A (Sema4A). Sema4A is expressed by lymphocytes, and its role in immune activation is known; however, its relationship to diseases that are known to have myelin damage has not been studied. In this study, we demonstrate that Sema4A is cytotoxic to OLs in culture: an effect accompanied by process collapse, membrane blebbing, and phosphatidylserine inversion. We further demonstrate that Sema4A preferentially binds to primary OLs but not astrocytes: an observation consistent with the lack of expression of Tim2 on astrocytes. We found that Sema4A protein levels are increased within multiple sclerosis plaques compared with normal-appearing white matter and that Sema4A induces lactate dehydrogenase release in a human OL cell line. The chief cellular source of Sema4A within the multiple sclerosis plaques appears to be infiltrating lymphocytes and microglia. Macrophages are known to express Sema4A, so we interrogated microglia as a potential source of Sema4A in the brain. We found that rat primary microglia express Sema4A which increased after lipopolysaccharide activation. Because activated microglia accumulate iron, we determined whether iron status influenced Sema4A and found that iron chelation decreased Sema4A and iron loading increased Sema4A in activated microglia. Overall, our data implicate Sema4A in the destruction of OLs and reveal that its expression is sensitive to iron levels. PMID:26024919

Dopamine elevates intracellular zinc concentration in cultured rat embryonic cortical neurons through the cAMP-nitric oxide signaling cascade.

PubMed

Hung, Hui-Hsing; Kao, Lung-Sen; Liu, Pei-Shan; Huang, Chien-Chang; Yang, De-Ming; Pan, Chien-Yuan

2017-07-01

Zinc ion (Zn 2+ ), the second most abundant transition metal after iron in the body, is essential for neuronal activity and also induces toxicity if the concentration is abnormally high. Our previous results show that exposure of cultured cortical neurons to dopamine elevates intracellular Zn 2+ concentrations ([Zn 2+ ] i ) and induces autophagosome formation but the mechanism is not clear. In this study, we characterized the signaling pathway responsible for the dopamine-induced elevation of [Zn 2+ ] i and the effect of [Zn 2+ ] i in modulating the autophagy in cultured rat embryonic cortical neurons. N,N,N',N'-tetrakis(2-pyridylmethyl)ethylenediamine (TPEN), a membrane-permeable Zn 2+ chelator, could rescue the cell death and suppress the autophagosome puncta number induced by dopamine. Dopamine treatment increased the lipidation level of the endogenous microtubule-associated protein 1A/1B-light chain 3 (LC3 II), an autophagosome marker. TPEN added 1h before, but not after, dopamine treatment suppressed the dopamine-induced elevation of LC3 II level. Inhibitors of the dopamine D1-like receptor, protein kinase A (PKA), and NOS suppressed the dopamine-induced elevation of [Zn 2+ ] i . PKA activators and NO generators directly increased [Zn 2+ ] i in cultured neurons. Through cell fractionation, proteins with m.w. values between 5 and 10kD were found to release Zn 2+ following NO stimulation. In addition, TPEN pretreatment and an inhibitor against PKA could suppress the LC3 II level increased by NO and dopamine, respectively. Therefore, our results demonstrate that dopamine-induced elevation of [Zn 2+ ] i is mediated by the D1-like receptor-PKA-NO pathway and is important in modulating the cell death and autophagy. Copyright © 2017 Elsevier Inc. All rights reserved.

Iron overload induced death of osteoblasts in vitro: involvement of the mitochondrial apoptotic pathway

PubMed Central

Dai, Zhipeng; Yang, Jingjing; Zheng, Jin

2016-01-01

Background Iron overload is recognized as a new pathogenfor osteoporosis. Various studies demonstrated that iron overload could induce apoptosis in osteoblasts and osteoporosis in vivo. However, the exact molecular mechanisms involved in the iron overload-mediated induction of apoptosis in osteoblasts has not been explored. Purpose In this study, we attempted to determine whether the mitochondrial apoptotic pathway is involved in iron-induced osteoblastic cell death and to investigate the beneficial effect of N-acetyl-cysteine (NAC) in iron-induced cytotoxicity. Methods The MC3T3-E1 osteoblastic cell line was treated with various concentrations of ferric ion in the absence or presence of NAC, and intracellular iron, cell viability, reactive oxygen species, functionand morphology changes of mitochondria and mitochondrial apoptosis related key indicators were detected by commercial kits. In addition, to further explain potential mechanisms underlying iron overload-related osteoporosis, we also assessed cell viability, apoptosis, and osteogenic differentiation potential in bone marrow-derived mesenchymal stemcells(MSCs) by commercial kits. Results Ferric ion demonstrated concentration-dependent cytotoxic effects on osteoblasts. After incubation with iron, an elevation of intracelluar labile iron levels and a concomitant over-generation of reactive oxygen species (ROS) were detected by flow cytometry in osteoblasts. Nox4 (NADPH oxidase 4), an important ROS producer, was also evaluated by western blot. Apoptosis, which was evaluated by Annexin V/propidium iodide staining, Hoechst 33258 staining, and the activation of caspase-3, was detected after exposure to iron. Iron contributed to the permeabilizatio of mitochondria, leading to the release of cytochrome C (cyto C), which, in turn, induced mitochondrial apoptosis in osteoblasts via activation of Caspase-3, up-regulation of Bax, and down-regulation of Bcl-2. NAC could reverse iron-mediated mitochondrial dysfunction and blocked the apoptotic events through inhibit the generation of ROS. In addition, iron could significantly promote apoptosis and suppress osteogenic differentiation and mineralization in bone marrow-derived MSCs. Conclusions These findings firstly demonstrate that the mitochondrial apoptotic pathway involved in iron-induced osteoblast apoptosis. NAC could relieved the oxidative stress and shielded osteoblasts from apoptosis casused by iron-overload. We also reveal that iron overload in bone marrow-derived MSCs results in increased apoptosis and the impairment of osteogenesis and mineralization. PMID:27843711

Phenocopy of warfarin syndrome in an infant born to a mother with sickle cell anemia and severe transfusional iron overload.

PubMed

Xie, Yi; Pivnick, Eniko K; Cohen, Harris L; Adams-Graves, Patricia E; Pourcyrous, Massroor; Aygun, Banu; Hankins, Jane S

2013-08-01

Neonatal chondrodysplasia punctata (CDP) is characterized by epiphyseal stippling and midfacial hypoplasia. CDP is usually inherited, but can be acquired because of maternal vitamin K deficiency. We describe an infant with CDP born to a teenager with sickle cell anemia and transfusional iron overload. The mother had severe liver fibrosis, elevated liver iron concentration (34 mg Fe/g), and coagulopathy, but no gestational use of warfarin. Fetal abnormalities were attributed to vitamin K deficiency secondary to liver dysfunction from iron toxicity. Treatment of iron overload among women with sickle cell anemia of childbearing potential is important to avoid possible CDP in newborns.

Biogeochemical and hydrological controls on fate and distribution of trace metals in oiled Gulf salt marshes

NASA Astrophysics Data System (ADS)

Keevan, J.; Natter, M.; Lee, M.; Keimowitz, A.; Okeke, B.; Savrda, C.; Saunders, J.

2011-12-01

On April 20, 2010, the drilling rig Deepwater Horizon exploded in the Gulf of Mexico, resulting in the release of approximately 5 million barrels of crude oil into the environment. Oil and its associated trace metals have been demonstrated to have a detrimental effect on coastal wetland ecosystems. Wetlands are particularly susceptible to oil contamination because they are composed largely of fine-grained sediments, which have a high capacity to adsorb organic matter and metals. The biogeochemical cycling of trace metals can be strongly influenced by microbial activity, specifically those of sulfate- and iron-reducing bacteria. Microbial activity may be enhanced by an increase in amounts of organic matter such as oil. This research incorporates an assessment of levels of trace metals and associated biogeochemical changes from ten coastal marshes in Alabama, Mississippi, and Louisiana. These sampling sites range in their pollution levels from pristine to highly contaminated. A total digestion analysis of wetland sediments shows higher concentrations of certain trace metals (e.g., Ni, Cu, Pb, Zn, Sr, Co, V, Ba, Hg, As) in heavily-oiled areas compared to less-affected and pristine sites. Due to chemical complexation among organic compounds and metals, crude oils often contain elevated levels (up to hundreds of mg/kg) of trace metals At the heavily-oiled Louisiana sites (e.g., Bay Jimmy, Bayou Dulac, Bay Batiste), elevated levels of metals and total organic carbon have been found in sediments down to depths of 30 cm. Clearly the contamination is not limited to shallow sediments and oil, along with various associated metals, may be invading into deeper (pre-industrial) portions of the marsh sediments. Pore-waters extracted from contaminated sediments are characterized by very high levels of reduced sulfur (up to 80 mg/kg), in contrast to fairly low ferrous iron concentrations (<0.02 mg/kg). The influx of oil into the wetlands might provide the initial substrate and carbon source for stimulating sulfate-reducing bacteria. The high sulfur levels, coupled with the low levels of iron, indicate that iron-reducing bacteria are outcompeted by sulfate reducers in oiled salt marshes. Moreover, pore-water pH values show a general increasing trend (ranging from 6.6 to 8.0) with depth, possibly reflecting the combined effects of bacterial sulfate reduction and saltwater intrusion at depth. Despite high levels of trace metals in bulk sediments, concentrations of trace metals dissolved in pore-waters are generally low. It is very likely that high organic matter content and bacterially-mediated sulfate reduction promote metal retention through the formation of sulfide solids. Framboidal pyrites, as well as other sulfides, have been identified, and are currently undergoing XRD, SEM, and EDAX analyses. Continued research is needed to monitor possible re-mobilization of trace metals in changing redox and biogeochemical conditions.

Magnetic susceptibility as a proxy for the hydrobiogeochemical cycling of iron within the water table fluctuation zone at hydrocarbon contaminated sites

NASA Astrophysics Data System (ADS)

Atekwana, E. A.; Enright, A.; Atekwana, E. A.; Beaver, C. L.; Rossbach, S.; Slater, L. D.; Ntarlagiannis, D.

2016-12-01

Sharp redox gradients are indicative of enhanced biogeochemical activity and occur at or near the water table. Hydrologic forcing drives changes in redox state and oxygen levels, enhancing the elemental cycling of metals, and coupling different biogeochemical cycles. These coupled hydrobiogeochemical cycles are often difficult to study in the field using geochemical and microbial proxies because of direct sampling limitations, the costs associated with these techniques, and because the dynamic nature of these processes complicates the interpretation of single time point measurements, which may not give accurate representations of prevailing conditions. Geophysical techniques can provide both the spatial and temporal resolution needed to elucidate these processes. Here we investigated the use of magnetic susceptibility (c) as a viable proxy for understanding the biogeochemical cycling of iron at several hydrocarbon contaminated sites where active intrinsic bioremediation is occurring. We performed borehole c logging using a Bartington c probe in the field as well as made c measurements on core samples retrieved from the field sites. Our results show the following: (1) in both sulfate-rich and sulfate-poor aquifers, excursions in c are coincident with zones of free product contamination and are limited to the water table fluctuation (smear) zone; (2) c values within the free product plume and contamination source zones are higher compared to values within the dissolved product plume; (3) high c coincides with zones of elevated Fe (II) and Fe (III) concentrations extracted from aquifer solids; and (4) the mixed valence magnetite and greigite were the dominant magnetic minerals. The c excursions are limited to the water table fluctuation zones because fluctuating water level conditions are hot beds for microbial activity due to the steep hydrocarbon and nutrients and consequently redox gradients. High water levels during periods of recharge favor anaerobic conditions enhancing iron reduction, while low water conditions during drought periods favor iron oxidation due to increased oxygen penetration. Such conditions favor mixed valent iron minerals such as magnetite and greigite. We conclude that c measurements are a low cost, rapid monitoring tool for assessing the elemental cycling of iron.

Arsenic in ground water in selected parts of southwestern Ohio, 2002-03

USGS Publications Warehouse

Thomas, Mary Ann; Schumann, Thomas L.; Pletsch, Bruce A.

2005-01-01

Arsenic concentrations were measured in 57 domestic wells in Preble, Miami, and Shelby Counties, in southwestern Ohio. The median arsenic concentration was 7.1 ?g/L (micrograms per liter), and the maximum was 67.6 ?g/L. Thirty-seven percent of samples had arsenic concentrations greater than the U.S. Environmental Protection Agency drinking-water standard of 10 ?g/L. Elevated arsenic concentrations (>10 ?g/L) were detected over the entire range of depths sampled (42 to 221 feet) and in each of three aquifer types, Silurian carbonate bedrock, glacial buried-valley deposits, and glacial till with interbedded sand and gravel. One factor common in all samples with elevated arsenic concentrations was that iron concentrations were greater than 1,000 ?g/L. The observed correlations of arsenic with iron and alkalinity are consistent with the hypothesis that arsenic was released from iron oxides under reducing conditions (by reductive dissolution or reductive desorption). Comparisons among the three aquifer types revealed some differences in arsenic occurrence. For buried-valley deposits, the median arsenic concentration was 4.6 ?g/L, and the maximum was 67.6 ?g/L. There was no correlation between arsenic concentrations and depth; the highest concentrations were at intermediate depths (about 100 feet). Half of the buried-valley samples were estimated to be methanic. Most of the samples with elevated arsenic concentrations also had elevated concentrations of dissolved organic carbon and ammonia. For carbonate bedrock, the median arsenic concentration was 8.0 ?g/L, and the maximum was 30.7 ?g/L. Arsenic concentrations increased with depth. Elevated arsenic concentrations were detected in iron- or sulfate-reducing samples. Arsenic was significantly correled with molybdenum, strontium, fluoride, and silica, which are components of naturally ocurring minerals. For glacial till with interbedded sand and gravel, half of the samples had elevated arsenic concentrations. The median was 11.4 ?g/L, and the maximum was 27.6 ?g/L. At shallow depths (<100 feet), this aquifer type had higher arsenic and iron concentrations than carbonate bedrock. It is not known whether these observed differences among aquifer types are related to variations in (1) arsenic content of the aquifer material, (2) organic carbon content of the aquifer material, (3) mechanisms of arsenic mobilization (or uptake), or (4) rates of arsenic mobilization (or uptake). A followup study that includes solid-phase analyses and geochemical modeling was begun in 2004 in northwestern Preble County.

Zinc transport by respiratory epithelial cells and interaction with iron homeostasis.

PubMed

Deng, Zhongping; Dailey, Lisa A; Soukup, Joleen; Stonehuerner, Jacqueline; Richards, Judy D; Callaghan, Kimberly D; Yang, Funmei; Ghio, Andrew J

2009-10-01

Despite recurrent exposure to zinc through inhalation of ambient air pollution particles, relatively little information is known about the homeostasis of this metal in respiratory epithelial cells. We describe zinc uptake and release by respiratory epithelial cells and test the postulate that Zn(2+) transport interacts with iron homeostasis in these same cells. Zn(2+) uptake after 4 and 8 h of exposure to zinc sulfate was concentration- and time-dependent. A majority of Zn(2+) release occurred in the 4 h immediately following cell exposure to ZnSO(4). Regarding metal importers, mRNA for Zip1 and Zip2 showed no change after respiratory epithelial cell exposure to zinc while mRNA for divalent metal transporter (DMT)1 increased. Western blot assay for DMT1 protein supported an elevated expression of this transport protein following zinc exposure. RT-PCR confirmed mRNA for the metal exporters ZnT1 and ZnT4 with the former increasing after ZnSO(4). Cell concentrations of ferritin increased with zinc exposure while oxidative stress, measured as lipid peroxides, was decreased supporting an anti-oxidant function for Zn(2+). Increased DMT1 expression, following pre-incubations of respiratory epithelial cells with TNF-alpha, IFN-gamma, and endotoxin, was associated with significantly decreased intracellular zinc transport. Finally, incubations of respiratory epithelial cells with both zinc sulfate and ferric ammonium citrate resulted in elevated intracellular concentrations of both metals. We conclude that exposure to zinc increases iron uptake by respiratory epithelial cells. Elevations in cell iron can possibly affect an increased expression of DMT1 and ferritin which function to diminish oxidative stress. Comparable to other metal exposures, changes in iron homeostasis may contribute to the biological effects of zinc in specific cells and tissues.

Association between ferritin and hepcidin levels and inflammatory status in patients with type 2 diabetes mellitus and obesity.

PubMed

Andrews, Mónica; Soto, Néstor; Arredondo-Olguín, Miguel

2015-01-01

The aim of this study was to determine the association between iron parameters and inflammation in obese individuals with and without type 2 diabetes mellitus (T2DM). We studied 132 obese individuals (OB), 60 individuals with T2DM, 106 obese individuals with T2DM (T2DOB), and 146 controls (C). All of were men aged >30 y. Biochemical, iron nutrition, and oxidative stress parameters were determined. Peripheral mononuclear cells were isolated and total RNA was extracted to quantify tumor necrosis factor (TNF)-α, nuclear factor (NF)-κB, interleukin (IL)-6, toll-like receptor (TLR)-2/4 and hepcidin by quantitative reverse transcription polymerase chain reaction. OB, T2DM, and T2DOB individuals had higher ferritin, retinol-binding protein 4, and thiobarbituric acid reactive substance (TBAR) levels than controls. T2DOB and T2DM individuals showed high high-sensitivity C-reactive protein (hsCRP) levels and OB with and without T2DM had elevated levels of serum hepcidin. Heme oxygenase activity was high in OB and T2DM and there were no differences observed in superoxide dismutase and glutathione parameters. A correlation between TBARS and ferritin in T2DOB was observed (r = 0.31; P < 0.006). Multiple linear regression analysis showed an association between diabetes and obesity with ferritin, TBARS, and hsCRP levels. The upper quartiles of ferritin, TBARS and hepcidin showed an adjusted odd ratio for T2DM of 1.782, 2.250, and 4.370, respectively. TNF-α, IL-6, hepcidin, NF-κB, TLR-2/4 mRNA abundances were increased in T2DM and T2DOB. Elevated hsCRP and hepcidin levels, and increased gene expression of TNF-α, IL-6, NF-κB, and TLR-2/4 in patients with diabetes, obesity, or both exacerbate and perpetuate the insulin resistance and inflammatory state. Copyright © 2015 Elsevier Inc. All rights reserved.

Distribution and Fate of Energetics on DoD Test and Training Ranges: Interim Report 5

DTIC Science & Technology

2005-04-01

aluminum, arsenic, and iron were naturally elevated (Ampleman et al. 2003). A cadmium concentration at 0.3 ppb was observed in one sample. Copper...copper concentration was twice the CCME criterion. Iron was also observed in the Shaver River sample at three times the CCME criterion. Concentrations...mainly in C-295, the first site visited. Copper and iron were found at high concentrations in almost all samples; however, only one or two samples showed

iron phase control during pressure leaching at elevated temperature

NASA Astrophysics Data System (ADS)

Fleuriault, Camille

Iron is a common contaminant encountered in most metal recovery operations, and particularly hydrometallurgical processes. For example, the Hematite Process uses autoclaves to precipitate iron oxide out of the leaching solution, while other metals are solubilized for further hydrometallurgical processing. In some cases, Basic Iron Sulfate (BIS) forms in place of hematite. The presence of BIS is unwanted in the autoclave discharge because it diminishes recovery and causes environmental matters. The focus of this master thesis is on the various iron phases forming during the pressure oxidation of sulfates. Artificial leaching solutions were produced from CuSO4, FeSO4 and H2SO4 in an attempt to recreate the matrix composition and conditions used for copper sulfides autoclaving. The following factors were investigated in order to determine which conditions hinder the formation of BIS: initial free acidity (5 -- 98 g/L), initial copper concentration (12.7 -- 63.5 g/L), initial iron concentration (16.7 -- 30.7 g/L) and initial iron oxidation state. There were three solid species formed in the autoclave: hematite, BIS and hydronium jarosite. The results show that free acid is the main factor influencing the composition of the residue. At an initial concentration of 22.3 g/L iron and no copper added, the upper limit for iron oxide formation is 41 g/L H2SO4. The increase of BIS content in the residue is not gradual and occurs over a change of a few grams per liter around the aforementioned limit. Increasing copper sulfate concentration in the solution hinders the formation of BIS. At 63.5g/L copper, the upper free acidity limit is increased to 61g/L. This effect seems to be related to the buffering action of copper sulfate, decreasing the overall acid concentration and thus extending the stability range of hematite. The effect of varying iron concentration on the precipitate chemistry is unclear. At high iron levels, the only noticeable effect was the inhibition of jarosite. The results were reported within a Cu-Fe-S ternary system and modeled. The modeling confirmed the experimental observations with the exception that increasing iron concentrations seem to promote BIS stability.

Altered iron metabolism, inflammation, transferrin receptors, and ferritin expression in non-small-cell lung cancer.

PubMed

Kukulj, Suzana; Jaganjac, Morana; Boranic, Milivoj; Krizanac, Simun; Santic, Zarko; Poljak-Blazi, Marija

2010-06-01

The involvement of iron and inflammation parameters on overall survival in non-small-cell lung cancer (NSCLC) patients was studied. Furthermore, transferrin receptors 1 (TfR1) and ferritin expression in tumor tissue, tumor stroma, and normal lung tissue were analyzed. Iron metabolism and inflammation parameters were determined by automated laboratory measurements at the time of diagnosis. TfR1 and ferritin expression were determined by immuno-histochemical methods. About 50% of patients survived 12 months only. At the time of diagnosis more than half of the patients had anemia and significantly elevated serum ferritin. Iron content of serum ferritin (ICF) was below the reference values in 90% of patients. Furthermore, ICF showed positive correlation with iron metabolic parameters and survival but negative correlation with serum ferritin and ESR. The expression of TfR1 and ferritin in tumor cells was observed in 88% or 62% of patients, respectively. Tumor stroma was TfR1 negative and sporadically ferritin positive. Tumor tissue ferritin expression showed negative correlation with serum iron and hematokrit (Ht), and positive correlation with ferritin, erythrocyte sedimentation rate (ESR), alpha-1 globulin, and alpha-2 globulin. Positive correlation was found between TfR1 expression in tumor tissue and alpha-globulin. The correlation between TfR1/ferritin expression in tumor tissue and ICF or survival was not observed. Therefore, we conclude that elevated serum ferritin in sera of NSCLC patients is the result of inflammation and oxidative stress rather than body iron overload. Higher expression of ferritin in tumor tissue may be the consequence of iron deficiency or local toxicity induced by environmental factors.

Siderophilic Cyanobacteria: Implications for Early Earth.

NASA Technical Reports Server (NTRS)

Brown, I. I.; Mummey, D.; Sarkisova, S.; Shen, G.; Bryant, D. A.; Lindsay, J.; Garrison, D.; McKay, D. S.

2006-01-01

Of all extant environs, iron-depositing hot springs (IDHS) may exhibit the greatest similarity to late Precambrian shallow warm oceans in regards to temperature, O2 gradients and dissolved iron and H2S concentrations. Despite the insights into the ecology, evolutionary biology, paleogeobiochemistry, and astrobiology examination of IDHS could potentially provide, very few studies dedicated to the physiology and diversity of cyanobacteria (CB) inhabiting IDHS have been conducted. Results. Here we describe the phylogeny, physiology, ultrastructure and biogeochemical activity of several recent CB isolates from two different greater Yellowstone area IDHS, LaDuke and Chocolate Pots. Phylogenetic analysis of 16S rRNA genes indicated that 6 of 12 new isolates examined couldn't be placed within established CB genera. Some of the isolates exhibited pronounced requirements for elevated iron concentrations, with maximum growth rates observed when 0.4-1 mM Fe(3+) was present in the media. In light of "typical" CB iron requirements, our results indicate that elevated iron likely represents a salient factor selecting for "siderophilicM CB species in IDHS. A universal feature of our new isolates is their ability to produce thick EPS layers in which iron accumulates resulting in the generation of well preserved signatures. In parallel, siderophilic CB show enhanced ability to etch the analogs of iron-rich lunar regolith minerals and impact glasses. Despite that iron deposition by CB is not well understood mechanistically, we recently obtained evidence that the PS I:PS II ratio is higher in one of our isolates than for other CB. Although still preliminary, this finding is in direct support of the Y. Cohen hypothesis that PSI can directly oxidize Fe(2+). Conclusion. Our results may have implications for factors driving CB evolutionary relationships and biogeochemical processes on early Earth and probably Mars.

Elevated expression of glutathione peroxidase in PC12 cells results in protection against methamphetamine but not MPTP toxicity.

PubMed

Hom, D G; Jiang, D; Hong, E J; Mo, J Q; Andersen, J K

1997-06-01

In vivo administration of either 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) or methamphetamine (MA) produces damage to the dopaminergic nervous system which may be due in part to the generation of reactive oxygen species (ROS). The resistance of superoxide dismutase (SOD) over-expressing transgenic mice to the effects of both MPTP and MA suggests the involvement of superoxide in the resulting neurotoxicity of both compounds. Superoxide can be converted by SOD to hydrogen peroxide, which itself can cause cellular degeneration by reacting with free iron to produce highly reactive hydroxyl radicals resulting in damage to proteins, nucleic acids and membrane phospholipids. Hydrogen peroxide has also been reported to be produced via inhibition of NADH dehydrogenase by MPP + formed during oxidation of MPTP by MAO-B and by dopamine auto-oxidation following MA-induced dopamine release from synaptic vesicles within nerve terminals. To test whether hydrogen peroxide is an important factor in the toxicity of either of these two neurotoxins, we created clonal PC12 lines expressing elevated levels of the hydrogen peroxide-reducing enzyme glutathione peroxidase (GSHPx). Elevation of GSHPx levels in PC12 was found to diminish the rise in ROS levels and lipid peroxidation resulting from MA but not MPTP treatment. Elevated levels of GSHPx also appeared to prevent decreases in transport-mediated dopamine uptake produced via MA administration as well as to attenuate toxin-induced cell loss as measured by either MTT reduction or LDH release. Our data, therefore, suggest that hydrogen peroxide production likely contributes to MA toxicity in dopaminergic neurons.

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.

Hematite-rich fracture fill at Meridiani Planum, Mars: Implications for fluid chemistry

NASA Astrophysics Data System (ADS)

Yen, Albert; Mittlefehldt, David; Morris, Richard; Gellert, Ralf

The Mars Exploration Rover Opportunity has been operating at the surface of Mars for over 2100 sols and has driven a distance of approximately 20 km. Throughout the traverse, outcrop rocks with margins and fracture fill resistant to erosion have been imaged and analyzed in detail by the Müssbauer (MB) spectrometer and the Alpha Particle X-ray Spectrometer (APXS). A recent APXS analysis of an outcrop block excavated by a young impact crater shows a coating with the highest concentration of iron measured by either rover, not including the iron-nickel meteorites. Texturally, this sample (referred to as "Chocolate Hills -Aloya") appears as a cemented collection of partially fragmented "blueberries." With the exception of an el-evated sulfur content, the elemental chemistry of this particular sample is entirely consistent with other analyses of hematite spherules at Merdiani Planum. As a result, it is difficult to determine whether this coating, which may have been filling a fracture in outcrop rocks prior to disruption by the impact, was simply an agglomeration of spherules or a result of a more complicated aqueous process. In contrast, a number of other fracture-filling exposures and erosion-resistant rinds have been analyzed by the APXS and MB instruments showing significant concentrations of iron in the form of hematite without the texture of spherule fragments. In one of these samples, a broken piece of fracture fill within Victoria crater referred to as "Dorsal," showed over 50% of the iron in hematite, the highest Mn concentration of any sample measured by the rovers, and elevated levels of Cl and Br. While the Fe:Mn ratio of the Dorsal analyses are comparable to that of Gusev and Meridiani basalts, it is clear that chemistry of this sample cannot be completely explained by a simple mixing of outcrop and blueberry compositions. A likely formation process for fracture fill and certain rinds involves the infiltration of iron-rich fluids post-dating the development of subsurface cracks. Mineral precipitates from these fluids resulted in hematite-rich zones within the outcrop rocks.

Assessment of oxidative stress and activities of antioxidant enzymes depicts the negative systemic effect of iron-containing fertilizers and plant phenolic compounds in the desert locust.

PubMed

Renault, David; Dorrah, Moataza A; Mohamed, Amr A; Abdelfattah, Eman A; Bassal, Taha T M

2016-11-01

For herbivore insects, digesting can be somewhat challenging, as the defense mechanisms evolved by plants, including the release of phenolics like the non-protein amino acid L-3,4-dihydroxyphenylalanine (L-DOPA), can cause fitness costs. In addition, industrial and agricultural activities have elevated the amounts of iron that can be found in nature and more particularly FeSO 4 that is used as fertilizer. Traces of iron can enhance the auto-oxidation of L-DOPA, in turn, generating reactive oxygen species (ROS) and consequently oxidative stress in insects. We examined the effects of the ion Fe 2+ (as FeSO 4 ) and L-DOPA on fifth instars of the desert locust Schistocerca gregaria. We measured the level of oxidative damage occurring to macromolecules (proteins and lipids) from midgut and thoracic tissues and assessed the activities of responsive antioxidant enzymes. Injected L-DOPA and redox-active metal iron generated ROS which caused oxidative damages to proteins and lipids to S. gregaria. The protein carbonyls and lipid peroxides present in tissue homogenates were elevated in treated insects. No synergism was observed when L-DOPA was co-injected with Fe 2+ . K m values of superoxide dismutase (SOD), glutathione reductase (GR), and glutathione peroxidase (GPx) were 4.3, 2.6, and 4.0 mM in thoracic muscles and 5.00, 2.43, and 1.66 mM in whole midgut for SOD, GR, and GPx, respectively, and 8.3 and 3.43 M for catalase (CAT) in the two tissues, respectively. These results suggest higher affinities of GPx and CAT to H 2 O 2 in midgut than in muscles. The time-course changes in activities of antioxidant enzymes and amounts of protein carbonyls and lipid peroxides showed fluctuating patterns, suggesting complex interactions among macromolecules, L-DOPA and FeSO 4 , and their degradation products. Our results demonstrated the stressful effects of L-DOPA and FeSO 4 , proving that iron-containing fertilizers are pollutants that can strongly affect S. gregaria.

Association between baseline serum hepcidin levels and infection in kidney transplant recipients: Potential role for iron overload.

PubMed

Fernández-Ruiz, Mario; Parra, Patricia; Ruiz-Merlo, Tamara; López-Medrano, Francisco; San Juan, Rafael; Polanco, Natalia; González, Esther; Andrés, Amado; Aguado, José María

2018-02-01

The liver-synthesized peptide hepcidin is a key regulator of iron metabolism and correlates with total iron stores. We analyzed the association between pre-transplant hepcidin-25 levels and infection after kidney transplantation (KT). Serum hepcidin-25 levels were measured at baseline by high-sensitivity ELISA in 91 patients undergoing KT at our institution between December 2011 and March 2013. The impact of this biomarker on the incidence of post-transplant infection (excluding lower urinary tract infection) during the first year was assessed by Cox regression. Mean hepcidin-25 level was 82.3 ± 67.4 ng/mL and strongly correlated with serum ferritin (Spearman's rho = 0.703; P < .001). There were no significant differences in hepcidin-25 levels between patients with or without overall infection (96.4 ± 67.5 vs 72.6 ± 66.7 ng/mL; P = .101). Such difference was evident for opportunistic (128.9 ± 75.0 vs 73.0 ± 62.3 ng/mL; P = .003) and, to a lesser extent, surgical-site infection (107.5 ± 73.3 vs 76.5 ± 65.2 ng/mL; P = .087). Patients with hepcidin-25 levels ≥72.5 ng/mL had higher 12-month cumulative incidence of overall infection (51.2% vs 29.2%; P = .032). After multivariate adjustment, hepcidin-25 ≥72.5 ng/mL acted as an independent risk factor for overall (adjusted hazard ratio [aHR] 3.86; 95% confidence interval [CI] 1.49-9.96; P = .005) and opportunistic infection (aHR 4.32; 95% CI 1.18-15.75; P = .027). Elevated baseline serum hepcidin-25 levels were associated with increased risk of infection after KT, suggesting a role for iron overload in the individual susceptibility to post-transplant infection. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Stress-induced behaviour in adult and old rats: effects of neonatal asphyxia, body temperature and chelation of iron.

PubMed

Rogalska, J; Caputa, M; Wentowska, K; Nowakowska, A

2006-11-01

Perinatal asphyxia in mammals leads to iron accumulation in the brain, which results in delayed neurobehavioural disturbances, including impaired learning and abnormal alertness over their entire life span. The aim of this investigation was to verify our hypothesis that newborn rats, showing reduced normal body temperature, are protected against neurotoxicity of the asphyxia up to senescence. Alertness was studied in adult and old male Wistar rats after exposure to critical neonatal anoxia: (i) at physiological neonatal body temperature of 33 degrees C, (ii) at body temperature elevated to 37 degrees C, or (iii) at body temperature elevated to 39 degrees C (the thermal conditions remained unchanged both during anoxia and for 2 h postanoxia). To elucidate the effect of iron-dependent postanoxic oxidative damage to the brain, half of the group (iii) was injected with deferoxamine, a chelator of iron. Postanoxic behavioural disturbances were recorded in open-field, elevated plus-maze, and sudden silence tests when the rats reached the age of 12 and 24 months. Open-field stress-induced motor activity was reduced in rats subjected to neonatal anoxia under hyperthermic conditions. In contrast, these rats were hyperactive in the plus-maze test. Both the plus-maze and sudden silence tests show reduced alertness of these rats to external stimuli signalling potential dangers. The behavioural disturbances were prevented by body temperature of 33 degrees C and by administration of deferoxamine.

Haematinic Deficiency and Macrocytosis in Middle-Aged and Older Adults

PubMed Central

Harrington, Janas; Cadogan, Sharon; Honari, Bahman; Perera, Kanthi; Fitzgerald, Anthony P.; Perry, Ivan J.; Cahill, Mary R.

2013-01-01

Objective To assess the prevalence and determinants of haematinic deficiency (lack of B12 folate or iron) and macrocytosis in blood from a national population-based study of middle-aged and older adults. Methods A cross-sectional study involving 1,207 adults aged ≥45 years, recruited from a sub-study of the Irish National Survey of Lifestyle Attitudes and Nutrition (SLÁN 2007). Participants completed a health and lifestyle questionnaire and a standard food frequency questionnaire. Non-fasting blood samples were obtained for measurement of full blood count and expert morphological assessment, serum ferritin, soluble transferrin receptor assay (sTfR), B12, folate and coeliac antibodies. Blood samples were also assayed for thyroid function (T4, TSH), liver function, aminotransferase (AST) and gamma-glutamyl transferase (GGT). Results The overall prevalence (95% C.I.) of anaemia (Hb <13.5g/dl men and 11.3 g/dl women) was 4.6% (2.9%–6.4%) in men and 1.0% (0.2%–1.9%) in women. Iron deficiency (ferritin <17ng/ml men and <11ng/ml in women) was detected in 6.3% of participants (3.7% in males and 8.7% in females, p<0.001). Based on both low ferritin and raised sTfR (>21nmol/ml) only 2.3% were iron-deficient. 3.0% and 2.7% were found to have low levels of serum folate (<2.3ng/ml) and serum B12 (<120ng/l) respectively. Clinically significant macrocytosis (MCV>99fl) was detected in 8.4% of subjects. Strong, significant and independent associations with macrocytosis were observed for lower social status, current smoking status, moderate to heavy alcohol intake, elevated GGT levels, deficiency of folate and vitamin B12, hypothyroidism and coeliac disease. The population attributable fraction (PAF) for macrocytosis associated with elevated GGT (25.0%) and smoking (24.6%) was higher than for excess alcohol intake (6.3%), folate deficiency (10.5%) or vitamin B12 (3.4%). Conclusions Haematinic deficiency and macrocytosis are common in middle-aged/older adults in Ireland. Macrocytosis is more likely to be attributable to an elevated GGT and smoking than vitamin B12 or folate deficiency. PMID:24244281

25. "CAST IRON HOWE TRUSS CARRYING PENNA STATE HIGHWAY ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

25. "CAST IRON HOWE TRUSS - CARRYING PENNA STATE HIGHWAY ROUTE #83 OVER READING CO. TRACKS - SOUTH OF READING, PENNA, Dwg. #6 - Sht. #1", dated November 20, 1956, shows partial side elevation of bridge truss, beginning at end post - Reading-Halls Station Bridge, U.S. Route 220, spanning railroad near Halls Station, Muncy, Lycoming County, PA

Hematite-Rich Fracture Fill at Meridiani Planum, Mars: Implications for Fluid Chemistry

NASA Technical Reports Server (NTRS)

Yen, Albert; Mittlefehldt, David W.; Morris, Richard V.; Gellert, Ralf

2010-01-01

The Mars Exploration Rover Opportunity has been operating at the surface of Mars for over 2100 sols and has driven a distance of approximately 20 km. Throughout the traverse, outcrop rocks with margins and fracture fill resistant to erosion have been imaged and analyzed in detail by the Moessbauer (MB) spectrometer and the Alpha Particle X-ray Spectrometer (APXS). A recent APXS analysis of an outcrop block excavated by a young impact crater shows a coating with the highest concentration of iron measured by either rover, not including the iron-nickel meteorites. Texturally, this sample (referred to as "Chocolate Hills -Aloya") appears as a cemented collection of partially fragmented \\blueberries." With the exception of an elevated sulfur content, the elemental chemistry of this particular sample is entirely consistent with other analyses of hematite spherules at Merdiani Planum. As a result, it is difficult to determine whether this coating, which may have been filling a fracture in outcrop rocks prior to disruption by the impact, was simply an agglomeration of spherules or a result of a more complicated aqueous process. In contrast, a number of other fracture-filling exposures and erosion-resistant rinds have been analyzed by the APXS and MB instruments showing significant concentrations of iron in the form of hematite without the texture of spherule fragments. In one of these samples, a broken piece of fracture fill within Victoria crater referred to as "Dorsal," showed over 50% of the iron in hematite, the highest Mn concentration of any sample measured by the rovers, and elevated levels of Cl and Br. While the Fe:Mn ratio of the Dorsal analyses are comparable to that of Gusev and Meridiani basalts, it is clear that chemistry of this sample cannot be completely explained by a simple mixing of outcrop and blueberry compositions

Arsenic Bioremediation by Biogenic Iron Oxides and Sulfides

PubMed Central

Couture, Raoul-Marie; Van Cappellen, Philippe; Corkhill, Claire L.; Charnock, John M.; Polya, David A.; Vaughan, David; Vanbroekhoven, Karolien; Lloyd, Jonathan R.

2013-01-01

Microcosms containing sediment from an aquifer in Cambodia with naturally elevated levels of arsenic in the associated groundwater were used to evaluate the effectiveness of microbially mediated production of iron minerals for in situ As remediation. The microcosms were first incubated without amendments for 28 days, and the release of As and other geogenic chemicals from the sediments into the aqueous phase was monitored. Nitrate or a mixture of sulfate and lactate was then added to stimulate biological Fe(II) oxidation or sulfate reduction, respectively. Without treatment, soluble As concentrations reached 3.9 ± 0.9 μM at the end of the 143-day experiment. However, in the nitrate- and sulfate-plus-lactate-amended microcosms, soluble As levels decreased to 0.01 and 0.41 ± 0.13 μM, respectively, by the end of the experiment. Analyses using a range of biogeochemical and mineralogical tools indicated that sorption onto freshly formed hydrous ferric oxide (HFO) and iron sulfide mineral phases are the likely mechanisms for As removal in the respective treatments. Incorporation of the experimental results into a one-dimensional transport-reaction model suggests that, under conditions representative of the Cambodian aquifer, the in situ precipitation of HFO would be effective in bringing groundwater into compliance with the World Health Organization (WHO) provisional guideline value for As (10 ppb or 0.13 μM), although soluble Mn release accompanying microbial Fe(II) oxidation presents a potential health concern. In contrast, production of biogenic iron sulfide minerals would not remediate the groundwater As concentration below the recommended WHO limit. PMID:23666325

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

Geoarchaeota: a new candidate phylum in the Archaea from high-temperature acidic iron mats in Yellowstone National Park

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

Kozubal, Mark; Romine, Margaret F.; Jennings, Ryan

Geothermal systems in Yellowstone National Park (YNP) provide an outstanding opportunity to understand the origin and evolution of metabolic processes necessary for life in extreme environments including low pH, high temperature, low oxygen and elevated concentrations of reduced iron. Previous phylogenetic studies of acidic ferric iron mats from YNP have revealed considerable diversity of uncultivated and undescribed archaea. The goal of this study was to obtain replicate de novo genome assemblies for a dominant archaeal population inhabiting acidic iron oxide mats in YNP. Detailed analysis of conserved ribosomal and informational processing genes indicate that the replicate assemblies represent a newmore » phylum-level lineage referred to here as 'novel archaeal group 1 (NAG1)'. The NAG1 organisms contain pathways necessary for the catabolism of peptides and complex carbohydrates as well as a bacterial-like Form I CO dehydrogenase complex likely used for energy conservation. Moreover, this novel population contains genes involved in metabolism of oxygen including a Type A heme copper oxidase, a bd-type terminal oxidase and a putative oxygen sensing protoglobin. NAG1 has a variety of unique bacterial-like cofactor biosynthesis and transport genes and a Type3-like CRISPR system. Discovery of NAG1 is critical to our understanding of microbial community structure and function in extant thermophilic iron mats of YNP, and will provide insight regarding the evolution of Archaea in early Earth environments that may have important analogues active in YNP today.« less

Lipocalin-2 Induces Cardiomyocyte Apoptosis by Increasing Intracellular Iron Accumulation*

PubMed Central

Xu, Guoxiong; Ahn, JinHee; Chang, SoYoung; Eguchi, Megumi; Ogier, Arnaud; Han, SungJun; Park, YoungSam; Shim, ChiYoung; Jang, YangSoo; Yang, Bo; Xu, Aimin; Wang, Yu; Sweeney, Gary

2012-01-01

Our objective was to determine whether lipocalin-2 (Lcn2) regulates cardiomyocyte apoptosis, the mechanisms involved, and the functional significance. Emerging evidence suggests that Lcn2 is a proinflammatory adipokine associated with insulin resistance and obesity-related complications, such as heart failure. Here, we used both primary neonatal rat cardiomyocytes and H9c2 cells and demonstrated for the first time that Lcn2 directly induced cardiomyocyte apoptosis, an important component of cardiac remodeling leading to heart failure. This was shown by detection of DNA fragmentation using TUNEL assay, phosphatidylserine exposure using flow cytometry to detect annexin V-positive cells, caspase-3 activity using enzymatic assay and immunofluorescence, and Western blotting for the detection of cleaved caspase-3. We also observed that Lcn2 caused translocation of the proapoptotic protein Bax to mitochondria and disruption of mitochondrial membrane potential. Using transient transfection of GFP-Bax, we confirmed that Lcn2 induced co-localization of Bax with MitoTracker® dye. Importantly, we used the fluorescent probe Phen Green SK to demonstrate an increase in intracellular iron in response to Lcn2, and depleting intracellular iron using an iron chelator prevented Lcn2-induced cardiomyocyte apoptosis. Administration of recombinant Lcn2 to mice for 14 days increased cardiomyocyte apoptosis as well as an acute inflammatory response with compensatory changes in cardiac functional parameters. In conclusion, Lcn2-induced cardiomyocyte apoptosis is of physiological significance and occurs via a mechanism involving elevated intracellular iron levels and Bax translocation. PMID:22117066

Hamp1 mRNA and plasma hepcidin levels are influenced by sex and strain but do not predict tissue iron levels in inbred mice.

PubMed

McLachlan, Stela; Page, Kathryn E; Lee, Seung-Min; Loguinov, Alex; Valore, Erika; Hui, Simon T; Jung, Grace; Zhou, Jie; Lusis, Aldons J; Fuqua, Brie; Ganz, Tomas; Nemeth, Elizabeta; Vulpe, Chris D

2017-11-01

Iron homeostasis is tightly regulated, and the peptide hormone hepcidin is considered to be a principal regulator of iron metabolism. Previous studies in a limited number of mouse strains found equivocal sex- and strain-dependent differences in mRNA and serum levels of hepcidin and reported conflicting data on the relationship between hepcidin ( Hamp1 ) mRNA levels and iron status. Our aim was to clarify the relationships between strain, sex, and hepcidin expression by examining multiple tissues and the effects of different dietary conditions in multiple inbred strains. Two studies were done: first, Hamp1 mRNA, liver iron, and plasma diferric transferrin levels were measured in 14 inbred strains on a control diet; and second, Hamp1 mRNA and plasma hepcidin levels in both sexes and iron levels in the heart, kidneys, liver, pancreas, and spleen in males were measured in nine inbred/recombinant inbred strains raised on an iron-sufficient or high-iron diet. Both sex and strain have a significant effect on both hepcidin mRNA (primarily a sex effect) and plasma hepcidin levels (primarily a strain effect). However, liver iron and diferric transferrin levels are not predictors of Hamp1 mRNA levels in mice fed iron-sufficient or high-iron diets, nor are the Hamp1 mRNA and plasma hepcidin levels good predictors of tissue iron levels, at least in males. We also measured plasma erythroferrone, performed RNA-sequencing analysis of liver samples from six inbred strains fed the iron-sufficient, low-iron, or high-iron diets, and explored differences in gene expression between the strains with the highest and lowest hepcidin levels. NEW & NOTEWORTHY Both sex and strain have a significant effect on both hepcidin mRNA (primarily a sex effect) and plasma hepcidin levels (primarily a strain effect). Liver iron and diferric transferrin levels are not predictors of Hamp1 mRNA levels in mice, nor are the Hamp1 mRNA and plasma hepcidin levels good predictors of tissue iron levels, at least in males. Copyright © 2017 the American Physiological Society.

Variation in heavy metals and microelements in South African medicinal plants obtained from street markets.

PubMed

Street, R A; Kulkarni, M G; Stirk, W A; Southway, C; Van Staden, J

2008-08-01

South African medicinal plants are traditionally harvested from a wide range of undisclosed locations by plant gatherers. Thus, there is a risk that plant material may be exposed to a variety of pollutants. The variation in five heavy metals (arsenic, cadmium, cobalt, nickel, and lead) and six essential elements (boron, copper, iron, manganese, molybdenum, and zinc) was determined in commonly used South African medicinal plants obtained from street markets. Elemental content was determined using inductively coupled plasma optical emission spectrophotometry. The reliability of the procedure was ensured by analysing a certified reference material. Medicinal plant samples contained arsenic and cadmium at levels exceeding the World Health Organization limits of 1 and 0.3 mg kg(-1) respectively. Lead and nickel were detected in all samples. Elevated iron and manganese levels were recorded in certain plant species. Multiple metal contamination of parts of medicinal plants gives grounds for concern. This study emphasizes the unsafe consequences of the South African practice of collecting medicinal plants from undisclosed locations and making these readily available to the public.

Iron isotopic fractionation between silicate mantle and metallic core at high pressure

PubMed Central

Liu, Jin; Dauphas, Nicolas; Roskosz, Mathieu; Hu, Michael Y.; Yang, Hong; Bi, Wenli; Zhao, Jiyong; Alp, Esen E.; Hu, Justin Y.; Lin, Jung-Fu

2017-01-01

The +0.1‰ elevated 56Fe/54Fe ratio of terrestrial basalts relative to chondrites was proposed to be a fingerprint of core-mantle segregation. However, the extent of iron isotopic fractionation between molten metal and silicate under high pressure–temperature conditions is poorly known. Here we show that iron forms chemical bonds of similar strengths in basaltic glasses and iron-rich alloys, even at high pressure. From the measured mean force constants of iron bonds, we calculate an equilibrium iron isotope fractionation between silicate and iron under core formation conditions in Earth of ∼0–0.02‰, which is small relative to the +0.1‰ shift of terrestrial basalts. This result is unaffected by small amounts of nickel and candidate core-forming light elements, as the isotopic shifts associated with such alloying are small. This study suggests that the variability in iron isotopic composition in planetary objects cannot be due to core formation. PMID:28216664

Coal fly ash as a source of iron in atmospheric dust.

PubMed

Chen, Haihan; Laskin, Alexander; Baltrusaitis, Jonas; Gorski, Christopher A; Scherer, Michelle M; Grassian, Vicki H

2012-02-21

Anthropogenic coal fly ash (FA) aerosol may represent a significant source of bioavailable iron in the open ocean. Few measurements have been made that compare the solubility of atmospheric iron from anthropogenic aerosols and other sources. We report here an investigation of iron dissolution for three FA samples in acidic aqueous solutions and compare the solubilities with that of Arizona test dust (AZTD), a reference material for mineral dust. The effects of pH, simulated cloud processing, and solar radiation on iron solubility have been explored. Similar to previously reported results on mineral dust, iron in aluminosilicate phases provides the predominant component of dissolved iron. Iron solubility of FA is substantially higher than of the crystalline minerals comprising AZTD. Simulated atmospheric processing elevates iron solubility due to significant changes in the morphology of aluminosilicate glass, a dominant material in FA particles. Iron is continuously released into the aqueous solution as FA particles break up into smaller fragments. These results suggest that the assessment of dissolved atmospheric iron deposition fluxes and their effect on the biogeochemistry at the ocean surface should be constrained by the source, environmental pH, iron speciation, and solar radiation.

Hemochromatosis and Vibrio vulnificus wound infections.

PubMed

Barton, James C; Acton, Ronald T

2009-10-01

There are several reports of persons with hemochromatosis and Vibrio vulnificus primary septicemia, but few accounts of persons with hemochromatosis and V. vulnificus wound infection. A 58-year-old white man developed infection of a forearm injury exposed to seawater in the Gulf of Mexico near the Alabama coast. At age 66, he was diagnosed to have hemochromatosis. Transferrin saturation was 89% and serum ferritin was 4761 pmol/L. HFE genotype was C282Y/C282Y. Serum levels of hepatic enzymes, glucose, IgG, IgA, and IgM, and blood levels of T, B, and natural killer cells were normal. We identified previous reports of only 2 similar cases: a woman from Alabama and a man from northern Australia. Mean age of the 3 subjects was 51 years at diagnosis of infection. Each had elevated serum iron measures or iron overload complications; both men were diagnosed to have hemochromatosis after they developed infection. Each of the 3 had recent exposure of a wound on an extremity to seawater, rapid development of a necrotizing soft tissue infection that required debridement and skin grafting, and positive wound or blood cultures. Each subject survived the infection. V. vulnificus wound infection occurs in some persons with hemochromatosis, but the risk of infection may be small. All patients with V. vulnificus infections should be evaluated for hemochromatosis, iron overload, and liver disorders.

Mechanistic and regulatory aspects of intestinal iron absorption

PubMed Central

Gulec, Sukru; Anderson, Gregory J.

2014-01-01

Iron is an essential trace mineral that plays a number of important physiological roles in humans, including oxygen transport, energy metabolism, and neurotransmitter synthesis. Iron absorption by the proximal small bowel is a critical checkpoint in the maintenance of whole-body iron levels since, unlike most other essential nutrients, no regulated excretory systems exist for iron in humans. Maintaining proper iron levels is critical to avoid the adverse physiological consequences of either low or high tissue iron concentrations, as commonly occurs in iron-deficiency anemia and hereditary hemochromatosis, respectively. Exquisite regulatory mechanisms have thus evolved to modulate how much iron is acquired from the diet. Systemic sensing of iron levels is accomplished by a network of molecules that regulate transcription of the HAMP gene in hepatocytes, thus modulating levels of the serum-borne, iron-regulatory hormone hepcidin. Hepcidin decreases intestinal iron absorption by binding to the iron exporter ferroportin 1 on the basolateral surface of duodenal enterocytes, causing its internalization and degradation. Mucosal regulation of iron transport also occurs during low-iron states, via transcriptional (by hypoxia-inducible factor 2α) and posttranscriptional (by the iron-sensing iron-regulatory protein/iron-responsive element system) mechanisms. Recent studies demonstrated that these regulatory loops function in tandem to control expression or activity of key modulators of iron homeostasis. In health, body iron levels are maintained at appropriate levels; however, in several inherited disorders and in other pathophysiological states, iron sensing is perturbed and intestinal iron absorption is dysregulated. The iron-related phenotypes of these diseases exemplify the necessity of precisely regulating iron absorption to meet body demands. PMID:24994858

5. Historic American Buildings Survey Photocopy of elevation drawing dated ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

5. Historic American Buildings Survey Photocopy of elevation drawing dated 1888 in office of First Coast Guard District, J. F. Kennedy Federal Building, Government Center, Boston, Mass. 02203 LIGHT-TOWER AT BOON ISLAND, MAINE SHOWING WROUGHT IRON WORK PROPOSED FOR ARRESTING VIBRATION OF LANTERN - Boon Island Light Tower, Cape Neddick, York County, ME

Comparison of workers’ perceptions toward work climate and health symptoms between ceramic and iron foundry workers

PubMed Central

Majumder, Joydeep; Bagepally, Bhavani S.; Shah, Priyanka; Kotadiya, Sanjay; Yadav, Suresh; Naha, Nibedita

2016-01-01

Background: Workers exposed to heavy manual material handling (MMH) in a hot working environment succumb to severe physical stress and psychological stress. Aims: (1) Recognize the heat load at workplaces of ceramic industry and iron industry, and (2) comparatively examine the characteristics of self-reported physiological responses and heat-health perception among these workers. Settings and Design: Cross-sectional prospective study. Materials and Methods: Workplace microclimate in the ceramic industry and iron industry was monitored. An ergonomic checklist and a questionnaire was used to record self-reported workers’ perceptions toward heat stress at workplace (ceramic workers N = 321, iron foundry workers N = 253). The prevalence rates of subjective symptoms among workers of both the industries were compared. Statistical Analysis: Chi-square test was used to examine the association between stressors and health complaints at a significance level set at P < 0.05. Results: Iron foundries recorded higher mean ambient temperature (43.4 ± 3.7°C) and wet-bulb globe temperature (WGBT) index (31.5 ± 0.7°C) as compared to ceramic industries (39.9 ± 3.3°C and 28 ± 1.5°C, respectively). Heavy sweating, elevated body temperature, sleeplessness, excessive thirst, muscular discomforts, and fatigue were prime symptoms recorded among workers of both industries. Skin-related disorders (red face, dry skin, bumps, itching) were significantly higher among iron foundry workers, whereas sleeplessness, high blood pressure, heavy sweating, kidney stone, decreased urination, muscular discomforts, and fatigue were significantly more among ceramic workers. Young workers reported more sweating and fatigue than older workers. Conclusions: A hot work climate and heavy manual labor designate ceramic and iron industries as arduous. Direct contact with hot surface and continuous MMH in tandem with the mechanical pace of production process makes work in ceramic industries more difficult than iron foundries. PMID:27390480

Novel multifunctional neuroprotective iron chelator-monoamine oxidase inhibitor drugs for neurodegenerative diseases: in vitro studies on antioxidant activity, prevention of lipid peroxide formation and monoamine oxidase inhibition.

PubMed

Zheng, Hailin; Gal, Shunit; Weiner, Lev M; Bar-Am, Orit; Warshawsky, Abraham; Fridkin, Mati; Youdim, Moussa B H

2005-10-01

Iron-dependent oxidative stress, elevated levels of iron and of monoamine oxidase (MAO)-B activity, and depletion of antioxidants in the brain may be major pathogenic factors in Parkinson's disease, Alzheimer's disease and related neurodegenerative diseases. Accordingly, iron chelators, antioxidants and MAO-B inhibitors have shown efficacy in a variety of cellular and animal models of CNS injury. In searching for novel antioxidant iron chelators with potential MAO-B inhibitory activity, a series of new iron chelators has been designed, synthesized and investigated. In this study, the novel chelators were further examined for their activity as antioxidants, MAO-B inhibitors and neuroprotective agents in vitro. Three of the selected chelators (M30, HLA20 and M32) were the most effective in inhibiting iron-dependent lipid peroxidation in rat brain homogenates with IC50 values (12-16 microM), which is comparable with that of desferal, a prototype iron chelator that is not has orally active. Their antioxidant activities were further confirmed using electron paramagnetic resonance spectroscopy. In PC12 cell culture, the three novel chelators at 0.1 microM were able to attenuate cell death induced by serum deprivation and by 6-hydroxydopamine. M30 possessing propargyl, the MAO inhibitory moiety of the anti-Parkinson drug rasagiline, displayed greater neuroprotective potency than that of rasagiline. In addition, in vitro, M30 was a highly potent non-selective MAO-A and MAO-B inhibitor (IC50 < 0.1 microM). However, HLA20 was more selective for MAO-B but had poor MAO inhibition, with an IC50 value of 64.2 microM. The data suggest that M30 and HLA20 might serve as leads in developing drugs with multifunctional activities for the treatment of various neurodegenerative disorders.

Distribution of trace metals at Hopewell Furnace National Historic Site, Berks and Chester Counties, Pennsylvania

USGS Publications Warehouse

Sloto, Ronald A.; Reif, Andrew G.

2011-01-01

Hopewell Furnace, located approximately 50 miles northwest of Philadelphia, was a cold-blast, charcoal iron furnace that operated for 113 years (1771 to 1883). The purpose of this study by the U.S. Geological Survey, in cooperation with the National Park Service, was to determine the distribution of trace metals released to the environment from an historical iron smelter at Hopewell Furnace National Historic Site (NHS). Hopewell Furnace used iron ore from local mines that contained abundant magnetite and accessory sulfide minerals enriched in arsenic, cobalt, copper, and other metals. Ore, slag, cast iron furnace products, soil, groundwater, stream base flow, streambed sediment, and benthic macroinvertebrates were sampled for this study. Soil samples analyzed in the laboratory had concentrations of trace metals low enough to meet Pennsylvania Department of Environmental Protection standards for non-residential use. Groundwater samples from the supply well met U.S. Environmental Protection Agency drinking-water regulations. Concentrations of metals in surface-water base flow at the five stream sampling sites were below continuous concentration criteria for protection of aquatic organisms. Concentrations of metals in sediment at the five stream sites were below probable effects level guidelines for protection of aquatic organisms except for copper at site HF-3. Arsenic, copper, lead, zinc, and possibly cobalt were incorporated into the cast iron produced by Hopewell Furnace. Manganese was concentrated in slag along with iron, nickel, and zinc. The soil near the furnace has elevated concentrations of chromium, copper, iron, lead, and zinc compared to background soil concentrations. Concentrations of toxic elements were not present at concentrations of concern in water, soil, or stream sediments, despite being elevated in ore, slag, and cast iron furnace products. The base-flow surface-water samples indicated good overall quality. The five sampled sites generally had low concentrations of nutrients and major ions but had elevated concentrations of iron, manganese, and strontium when compared to sites sampled in adjacent watersheds. The background site on Baptism Creek generally had the lowest concentrations and yields of constituents. Low concentrations of nutrients and major ions at all five sites indicate that measured concentrations can be attributed to general land use and geology and not to point sources. Streambed-sediment sampling results indicated higher concentrations of all metals except nickel at sites on French Creek compared to the background site on Baptism Creek. Concentrations of aluminum, cadmium, and nickel were highest in sediment from the sampling site upstream from Hopewell Furnace. The highest concentrations of arsenic, boron, cobalt, copper, iron, lead, manganese, mercury, and zinc were detected at the site just below Hopewell Furnace, which indicates that the source of these metals may be in Hopewell Furnace NHS. The invertebrate community at the background site on Baptism Creek was dominated by pollution sensitive taxa indicating a healthy, diverse benthic-macroinvertebrate community. Benthic-macroinvertebrate communities at sampling sites on French Creek indicated disturbed communities when compared to the background site on Baptism Creek and that the overall stream quality immediately above and below Hopewell Furnace NHS is degraded. The benthic-macroinvertebrate communities were dominated by pollution-tolerant taxa, and taxa were less diverse than at the background site. Habitat conditions at the upstream site on French Creek were good but were degraded at downstream sites on French Creek. The major habitat issues at these sites were related to a lack of stable substrate, erosion, and deposition. Water quality and streambed-sediment quality do not indicate that the degraded benthic-macroinvertebrate communities are the result of poor water quality. Habitat conditions (erosion and sedimentation) and physical alterations (water temperature) from the outfall of Hopewell Lake are the most likely causes of the impaired communities.

Characterization of iron metabolism and erythropoiesis in erythrocyte membrane defects and thalassemia traits.

PubMed

Sulovska, Lucie; Holub, Dusan; Zidova, Zuzana; Divoka, Martina; Hajduch, Marian; Mihal, Vladimir; Vrbkova, Jana; Horvathova, Monika; Pospisilova, Dagmar

2016-06-01

Erythropoiesis is closely related to iron metabolism in a balanced homeostasis. Analyses of diverse erythroid and iron metabolism disorders have shown that disrupted erythropoiesis negatively affects iron homeostasis and vice versa. The aim of this study was to characterize the relationship between erythropoietic activity and iron homeostasis in pediatric patients with erythrocyte membrane defects and thalassemia traits. Selected markers of erythropoietic activity (erythropoietin, soluble transferrin receptor - sTfR and growth differentiation factor 15) and iron status parameters (serum iron, ferritin and hepcidin) were evaluated in pediatric patients with erythrocyte membrane defects and thalassemia traits. The patients with erythrocyte membrane defects and thalassemia traits had altered iron homeostasis due to disturbed erythropoiesis. In comparison with healthy controls, they had a normal to low hepcidin/ferritin ratio and concomitantly elevated sTfR. The findings suggest that pediatric patients with erythrocyte membrane defects and thalassemia traits are more susceptible to iron overload than the general population and that the (hepcidin/ferritin)/sTfR ratio can be used to monitor any worsening of the disease.

Circulating ferritin concentrations and risk of type 2 diabetes in Japanese individuals.

PubMed

Akter, Shamima; Nanri, Akiko; Kuwahara, Keisuke; Matsushita, Yumi; Nakagawa, Tohru; Konishi, Maki; Honda, Toru; Yamamoto, Shuichiro; Hayashi, Takeshi; Noda, Mitsuhiko; Mizoue, Tetsuya

2017-07-01

Higher iron storage has been linked to an increased risk of type 2 diabetes, but little is known about the mediator of this association. Here, we prospectively investigated the association between circulating ferritin, a marker of iron storage, and the incidence of type 2 diabetes among Japanese individuals. The participants were 4,754 employees who attended a comprehensive health check-up in 2008-2009 and donated blood for the study. During 5 years of follow up, diabetes was identified based on plasma glucose, glycated hemoglobin and self-report. Two controls matched to each case on sex, age and date of check-up were randomly chosen using density sampling, giving 327 cases and 641 controls with ferritin measurement. Cox proportional hazards regression was used to estimate the hazard ratio while adjusting for a series of potential confounders or mediators. Elevated serum ferritin levels were associated with a significantly increased risk of type 2 diabetes, with the hazard ratio adjusted for known risk factors in the highest vs lowest quartile of 1.42 (95% confidence interval: 1.03-1.96). This association was unchanged after adjustment for C-reactive protein and adiponectin, but attenuated after adjustment for liver enzyme and insulin resistance (hazard ratio 1.04). The ferritin-diabetes association was confined to non-obese participants. These results suggest that elevated iron storage is associated with increased risk of type 2 diabetes in normal weight individuals, and that this association is partly mediated through liver dysfunction and resulting insulin resistance. © 2017 The Authors. Journal of Diabetes Investigation published by Asian Association for the Study of Diabetes (AASD) and John Wiley & Sons Australia, Ltd.

The iron-responsive microsomal proteome of Aspergillus fumigatus.

PubMed

Moloney, Nicola M; Owens, Rebecca A; Meleady, Paula; Henry, Michael; Dolan, Stephen K; Mulvihill, Eoin; Clynes, Martin; Doyle, Sean

2016-03-16

Aspergillus fumigatus is an opportunistic fungal pathogen. Siderophore biosynthesis and iron acquisition are essential for virulence. Yet, limited data exist with respect to the adaptive nature of the fungal microsomal proteome under iron-limiting growth conditions, as encountered during host infection. Here, we demonstrate that under siderophore biosynthetic conditions--significantly elevated fusarinine C (FSC) and triacetylfusarinine C (TAFC) production (p<0.0001), extensive microsomal proteome remodelling occurs. Specifically, a four-fold enrichment of transmembrane-containing proteins was observed with respect to whole cell lysates following ultracentrifugation-based microsomal extraction. Comparative label-free proteomic analysis of microsomal extracts, isolated following iron-replete and -deplete growth, identified 710 unique proteins. Scatterplot analysis (MaxQuant) demonstrated high correlation amongst biological replicates from each growth condition (Pearson correlation >0.96 within groups; biological replicates (n=4)). Quantitative and qualitative comparison revealed 231 proteins with a significant change in abundance between the iron-replete and iron-deplete conditions (p<0.05, fold change ≥ 2), with 96 proteins showing increased abundance and 135 with decreased abundance following iron limitation, including predicted siderophore transporters. Fluorescently labelled FSC was only sequestered following A. fumigatus growth under iron-limiting conditions. Interestingly, human sera exhibited significantly increased reactivity (p<0.0001) against microsomal protein extracts obtained following iron-deplete growth. The opportunistic fungal pathogen Aspergillus fumigatus must acquire iron to facilitate growth and pathogenicity. Iron-chelating non-ribosomal peptides, termed siderophores, mediate iron uptake via membrane-localised transporter proteins. Here we demonstrate for the first time that growth of A. fumigatus under iron-deplete conditions, concomitant with siderophore biosynthesis, leads to an extensive remodelling of the microsomal proteome which includes significantly altered levels of 231 constituent proteins (96 increased and 135 decreased in abundance), many of which have not previously been localised to the microsome. We also demonstrate the first synthesis of a fluorescent version of fusarinine C, an extracellular A. fumigatus siderophore, and its uptake and localization under iron-restricted conditions. This infers the use of an A. fumigatus siderophore as a 'Trojan horse' to potentiate the efficacy of anti-fungal drugs. Finally, in addition to revealing the Aspergillus-specific IgG reactivity in normal human sera against microsomal proteins, there appears to be a significantly increased reactivity against microsomal proteins obtained following iron-restricted growth. We hypothesise that iron-limiting environment in humans, which has evolved to nutritionally limit pathogen growth in vivo, may also alter the fungal microsomal proteome. Copyright © 2016 Elsevier B.V. All rights reserved.

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.

The use of nuclear muprobe techniques to study the chemistry of lacustrine sediments and particles

NASA Astrophysics Data System (ADS)

Grime, G. W.; Davison, W.

1993-05-01

The Oxford SPM has been used in two novel studies of lake chemistry: (a) The distribution of dissolved iron in sediment pore waters close to the sediment/water interface has been measured using the novel technique of diffusive equilibration in a thin film (DET). In this technique, which has a spatial resolution of < 1 mm, much less than that of competing techniques (1 cm), a thin layer of polyacrylamide gel is inserted into the sediment and after the rapid equilibration with the pore water, the gel is dried and fixed. The distribution of trace elements can then be measured using mubeam PIXE. Preliminary results have shown for the first time a subsurface maximum of Fe consistent with current theories of Fe dynamics. This paper presents some results obtained using the technique and discusses the limits on resolution and sensitivity, (b) Individual suspended lake particles (predominantly iron oxides and sulphides) have been analysed using point mubeam RBS and PIXE. Of particular interest in this study is the oxidation state of iron rich particles, so RBS with a 1 μm beam was used to determine the Fe: O stoichiometry of single particles. The particles were filtered from a depth of 14 m in Esthwaite Water in the English Lake District and handled in anoxic conditions until evacuation in the SPM sample chamber. Two distinct compositions of iron oxide were determined in clusters of about 5 μm diameter. Analysis by PIXE revealed that FeS was uniformly distributed in the particulate material and that it also contained elevated levels of Cu and Zn. This study was the first to demonstrate directly that discrete clusters of iron oxides are present in black particulate material which is commonly considered to comprise iron sulphides.

Dentate nucleus iron deposition is a potential biomarker for tremor-dominant Parkinson’s disease

PubMed Central

He, Naying; Huang, Pei; Ling, Huawei; Langley, Jason; Liu, Chunlei; Ding, Bei; Huang, Juan; Xu, Hongmin; Zhang, Yong; Zhang, Zhongping; Hu, Xiaoping; Chen, Shengdi; Yan, Fuhua

2016-01-01

Parkinson disease (PD) is a heterogeneous neurodegenerative disorder with variable clinicopathologic phenotypes and underlying neuropathologic mechanisms. Each clinical phenotype has a unique set of motor symptoms. Tremor is the most frequent initial motor symptom of PD and is the most difficult symptom to treat. The dentate nucleus (DN) is a deep iron rich nucleus in the cerebellum and may be involved in PD tremor. In this study, we test the hypothesis that DN iron may be elevated in tremor dominant PD patients using quantitative susceptibility mapping. Forty-three patients with PD [19 tremor dominant (TD)/24 akinetic-rigid dominant (AR)] and 48 healthy gender- and age-matched controls were recruited. Multi-echo gradient echo data were collected for each subject on a 3.0 T MR system. Inter-group susceptibility differences in bilateral DN were investigated and correlations of clinical features with susceptibility were also examined. In contrast to the AR group, the TD group was found to have increased susceptibility in the bilateral DN, when compared to healthy controls. In addition, susceptibility was positively correlated with tremor score in drug naive PD patients. These findings indicate that iron load within DN may make an important contribution to motor phenotypes in PD. Moreover, our results suggest that TD and AR phenotypes of PD can be differentiated on the basis of the susceptibility of the DN at least on the group level. PMID:27192177

Novel red cell indices indicating reduced availability of iron are associated with high erythropoietin concentration and low ph level in the venous cord blood of newborns.

PubMed

Ervasti, Mari; Sankilampi, Ulla; Heinonen, Seppo; Punnonen, Kari

2008-08-01

There is evidence that an elevated erythropoietin (EPO) concentration is associated with signs of iron deficient erythropoiesis. The aim of this study was to evaluate the iron status by means of novel cellular indices and serum iron markers and to determine whether these are associated with EPO and pH in the venous cord blood of 193 full-term newborns. There were positive correlations between EPO and the percentage of hypochromic red blood cells (%HYPOm) and reticulocytes (%HYPOr) [r = 0.45 (p < 0.001) and r = 0.56 (p < 0.001), respectively]. %HYPOm and %HYPOr also had negative correlations with pH [r = -0.53 (p = 0.001) and r = -0.46 (p = 0.001), respectively]. Newborns who had low pH (pH < or =7.15, n = 16) had significantly higher %HYPOm, %HYPOr, and serum transferrin receptor and transferrin concentrations in their cord blood than newborns with normal pH. Thus, in newborn cord blood, the higher number of red cells and reticulocytes with lower Hb content may have impaired the oxygen carrying capacity that has been a trigger for EPO production. Furthermore, signs of lower hemoglobinization of red cells are associated with low umbilical vein pH in the newborns, indicating an increased risk of birth asphyxia.

25. VIEW OF McGREGOR BRIDGE (18811936), CROSSING THE MERRIMACK RIVER ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

25. VIEW OF McGREGOR BRIDGE (1881-1936), CROSSING THE MERRIMACK RIVER AT BRIDGE STREET, LOOKING SOUTHEAST. NORTH ELEVATION OF DOUBLE-DECKED, THREE-SPAN DOUGLAS PATENT PARABOLIC IRON TRUSS ERECTED BY CORRUGATED METAL COMPANY (BERLIN IRON BRIDGE COMPANY, BERLIN, CT) From 'Bridge Street Bridge', photographer and date unknown. - Notre Dame Bridge, Spanning Merrimack River on Bridge Street, Manchester, Hillsborough County, NH

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

Elihn, K.; Landstroem, L.; Alm, O.

Iron nanoparticles enclosed in carbon shells were formed by laser-assisted chemical vapor decomposition of ferrocene (Fe(C{sub 5}H{sub 5}){sub 2}) vapor in Ar gas atmosphere. The particle size dependence on the total ambient gas pressure and on laser fluence of the pulsed ArF excimer laser was examined and, e.g., an effective size decrease of the iron core was observed at elevated laser fluences. Characterizations of the iron and carbon microstructures were performed by x-ray diffraction and transmission electron microscopy, while relative iron deposition rates were measured by x-ray fluorescence spectroscopy. Both {alpha}-Fe and {gamma}-Fe phases were found for the single crystallinemore » iron cores, surrounded by graphitic (inner) and amorphous (outer) carbon layers. The temperature rise of the laser-excited particles was also determined by optical spectroscopy of the emitted thermal radiation, which allowed an estimation of the iron loss of the nanoparticles due to evaporation. The estimated and measured iron losses are in good agreement.« less

Cysteine desulfurase Nfs1 and Pim1 protease control levels of Isu, the Fe-S cluster biogenesis scaffold.

PubMed

Song, Ji-Yoon; Marszalek, Jaroslaw; Craig, Elizabeth Anne

2012-06-26

Fe-S clusters are critical prosthetic groups for proteins involved in various critical biological processes. Before being transferred to recipient apo-proteins, Fe-S clusters are assembled on the highly conserved scaffold protein Isu, the abundance of which is regulated posttranslationally on disruption of the cluster biogenesis system. Here we report that Isu is degraded by the Lon-type AAA+ ATPase protease of the mitochondrial matrix, Pim1. Nfs1, the cysteine desulfurase responsible for providing sulfur for cluster formation, is required for the increased Isu stability occurring after disruption of cluster formation on or transfer from Isu. Physical interaction between the Isu and Nfs1 proteins, not the enzymatic activity of Nfs1, is the important factor in increased stability. Analysis of several conditions revealed that high Isu levels can be advantageous or disadvantageous, depending on the physiological condition. During the stationary phase, elevated Isu levels were advantageous, resulting in prolonged chronological lifespan. On the other hand, under iron-limiting conditions, high Isu levels were deleterious. Compared with cells expressing normal levels of Isu, such cells grew poorly and exhibited reduced activity of the heme-containing enzyme ferric reductase. Our results suggest that modulation of the degradation of Isu by the Pim1 protease is a regulatory mechanism serving to rapidly help balance the cell's need for critical iron-requiring processes under changing environmental conditions.

Impact of icebergs on net primary productivity in the Southern Ocean

NASA Astrophysics Data System (ADS)

Wu, Shuang-Ye; Hou, Shugui

2017-03-01

Productivity in the Southern Ocean (SO) is iron-limited, and supply of iron dissolved from aeolian dust is believed to be the main source from outside the marine environment. However, recent studies show that icebergs could provide a comparable amount of bioavailable iron to the SO as aeolian dust. In addition, small-scale areal studies suggest increased concentrations of chlorophyll, krill, and seabirds surrounding icebergs. Based on previous research, this study aims to examine whether iceberg occurrence has a significant impact on marine productivity at the scale of the SO, using remote sensing data of iceberg occurrences and ocean net primary productivity (NPP) covering the period 2002-2014. The impacts of both large and small icebergs are examined in four major ecological zones of the SO: the continental shelf zone (CSZ), the seasonal ice zone (SIZ), the permanent open ocean zone (POOZ), and the polar front zone (PFZ). We found that the presence of icebergs is associated with elevated levels of NPP, but the differences vary in different zones. Grid cells with small icebergs on average have higher NPP than other cells in most iron-deficient zones: 21 % higher for the SIZ, 16 % for the POOZ, and 12 % for the PFZ. The difference is relatively small in the CSZ where iron is supplied from meltwater and sediment input from the continent. In addition, NPP of grid cells adjacent to large icebergs on average is 10 % higher than that of control cells in the vicinity. The difference is larger at higher latitudes, where most large icebergs are concentrated. From 1992 to 2014, there is a significant increasing trend for both small and large icebergs. The increase was most rapid in the early 2000s and has leveled off since then. As the climate continues to warm, the Antarctic Ice Sheet is expected to experience increased mass loss as a whole, which could lead to more icebergs in the region. Based on our study, this could result in a higher level of NPP in the SO as a whole, providing a possible negative feedback for global warming in near future.

An analysis of the chemical and microbiological quality of ground water from boreholes and shallow wells in Zimbabwe

NASA Astrophysics Data System (ADS)

Moyo, N. A. G.

Groundwater from boreholes and shallow wells is a major source of drinking water in most rural areas of Zimbabwe. The quality of groundwater has been taken for granted and the status and the potential threats to groundwater quality have not been investigated on a large scale in Zimbabwe. A borehole and shallow well water quality survey was undertaken between January, 2009 and February, 2010 to determine the chemical and microbial aspects of drinking water in three catchment areas. Groundwater quality physico-chemical indicators used in this study were nitrates, chloride, water hardness, conductivity, alkalinity, total dissolved solids, iron, magnesium, manganese, potassium, calcium, fluoride, sulphates, sodium and pH. The microbiological indicators were total coliforms, faecal coliforms and heterotrophs. Principal component analysis (PCA) showed that most of the variation in ground water quality in all catchment areas is accounted for by Total Dissolved Solids (TDS), electrical conductivity (EC), sodium, bicarbonate and magnesium. The principal dissolved constituents in ground water are in the form of electrically charged ions. Nitrate is a significant problem as the World Health Organization recommended levels were exceeded in 36%, 37% and 22% of the boreholes in the Manyame, Mazowe and Gwayi catchment areas respectively. The nitrate levels were particularly high in commercial farming areas. Iron and manganese also exceeded the recommended levels. The probable source of high iron levels is the underlying geology of the area which is dominated by dolerites. Dolerites weather to give soils rich in iron and other mafic minerals. The high level of manganese is probably due to the lithology of the rock as well as mining activity in some areas. Water hardness is a problem in all catchment areas, particularly in the Gwayi catchment area where a value of 2550 mg/l was recorded in one borehole. The problems with hard water use are discussed. Chloride levels exceeded the recommended levels in a few areas under irrigation. Most of the chloride is probably from agricultural activity particularly the application of potassium chloride. Fluoride levels were particularly elevated in the Gwayi catchment area and this is because of the geology of the area. There was no evidence of microbial contamination in all the boreholes sampled as the total coliform, faecal coliforms, heterotrophs count was nil. However, severe microbial contamination was found in the wells especially those in clay areas.

[Changes in serum lipids in rats treated with oral cooper].

PubMed

Alarcón-Corredor, O M; Carnevalí de Tatá, E; Reinosa-Füller, J; Contreras, Y; Ramírez de Fernández, M; Yánez-Domínguez, C

2000-09-01

Disturbances in lipid metabolism during copper deficiency in rats are well recognized. Copper deficiency is associated with the spontaneous retention of hepatic iron. Previous studies have reported that hypercholesterolemia and hypertriglyceridemia are associated with elevated hepatic iron concentrations in copper deficient rats. There was a direct relationship between the magnitude of blood lipids and the concentration of hepatic iron. Based on these data, it has been hypothesized that iron was responsible for the development of lipemia of copper deficiency. In this study was determined the effect of increasing doses of Cu(10, 20 and 50 ppm) in the diet, on the serum total lipids, total cholesterol, triglycerides (triacylglicerols), phospholipids, non-esterified fatty acids (NEFA) and liver iron and zinc concentrations in normal rats. The results were compared with normal rats that received a balanced diet containing 0.6 and 6 ppm of Cu, respectively. The results show that Cu-supplement diminished the cholesterol and triglyceride serum levels, increased the level of phospholipids, NEFA and concomitantly decreased the hepatic concentrations of Fe and Zn. There was a statistically significant (p < 0.05) simple correlation between triglycerides and liver Fe (r = 0.917; R2 = 64.03%), cholesterol and liver Zn (r = 0.872; R2 = 76.07%), cholesterol and liver Fe (r = 0.995; R2 = 99.10%), liver Fe and liver Cu (r = -0.612), liver Fe and liver Zn (r = 0.837), liver Cu and liver Zn (r = -0.612), and serum triglycerides and liver Zn (r = 0.967). The mechanism(s) by which Fe and Zn determine these changes is not known; none of the enzymes that act in cholesterol and triglyceride metabolism and biosynthesis require Fe and/or Zn. The increase of NEFA is due to changes in the process of lipolysis and re-esterification of the fatty acids in blood. However, additional studies are needed for the precise mechanisms of this interrelationships to be clarified.

Nutrition Research: Basis for Station Requirements

NASA Technical Reports Server (NTRS)

Lane, Helen W.; Rice, Barbara; Smith, Scott M.

2011-01-01

Prior to the Shuttle program, all understanding of nutritional needs in space came from Skylab metabolic research. Because Shuttle flights were short, most less than 14 days, research focused on major nutritional issues: energy (calories), protein and amino acids, water and electrotypes, with some more general physiology studies that related to iron and calcium. Using stable isotope tracer studies and diet intake records, we found that astronauts typically did not consume adequate calories to meet energy expenditure. To monitor energy and nutrient intake status and provide feedback to the flight surgeon and the astronauts, the International Space Station (ISS) program implemented a weekly food frequency questionnaire and routine body mass measurements. Other Shuttle investigations found that protein turnover was higher during flight, suggesting there was increased protein degradation and probably concurrent increase in protein synthesis, and this occurred even in cases of adequate protein and caloric intake. These results may partially explain some of the loss of leg muscle mass. Fluid and electrolyte flight studies demonstrated that water intake, like energy intake, was lower than required. However, sodium intakes were elevated during flight and likely related to other concerns such as calcium turnover and other health-related issues. NASA is making efforts to have tasty foods with much lower salt levels to reduce sodium intake and to promote fluid intake on orbit. Red blood cell studies conducted on the Shuttle found decreased erythrogenesis and increased serum ferritin levels. Given that the diet is high in iron there may be iron storage health concerns, especially related to the role of iron in oxidative damage, complicated by the stress and radiation. The Shuttle nutrition research lead to new monitoring and research on ISS. These data will be valuable for future NASA and commercial crewed missions.

Pathways for arsenic from sediments to groundwater to streams: Biogeochemical processes in the Inner Coastal Plain, New Jersey, USA

USGS Publications Warehouse

Barringer, Julia L.; Mumford, Adam; Young, Lily Y.; Reilly, Pamela A.; Bonin, Jennifer L.; Rosman, Robert

2010-01-01

The Cretaceous and Tertiary sediments that underlie the Inner Coastal Plain of New Jersey contain the arsenic-rich mineral glauconite. Streambed sediments in two Inner Coastal Plain streams (Crosswicks and Raccoon Creeks) that traverse these glauconitic deposits are enriched in arsenic (15–25 mg/kg), and groundwater discharging to the streams contains elevated levels of arsenic (>80 μg/L at a site on Crosswicks Creek) with arsenite generally the dominant species. Low dissolved oxygen, low or undetectable levels of nitrate and sulfate, detectable sulfide concentrations, and high concentrations of iron and dissolved organic carbon (DOC) in the groundwater indicate that reducing environments are present beneath the streambeds and that microbial activity, fueled by the DOC, is involved in releasing arsenic and iron from the geologic materials. In groundwater with the highest arsenic concentrations at Crosswicks Creek, arsenic respiratory reductase gene (arrA) indicated the presence of arsenic-reducing microbes. From extracted DNA, 16s rRNA gene sequences indicate the microbial community may include arsenic-reducing bacteria that have not yet been described. Once in the stream, iron is oxidized and precipitates as hydroxide coatings on the sediments. Arsenite also is oxidized and co-precipitates with or is sorbed to the iron hydroxides. Consequently, dissolved arsenic concentrations are lower in streamwater than in the groundwater, but the arsenic contributed by groundwater becomes part of the arsenic load in the stream when sediments are suspended during high flow. A strong positive relation between concentrations of arsenic and DOC in the groundwater samples indicates that any process—natural or anthropogenic—that increases the organic carbon concentration in the groundwater could stimulate microbial activity and thus increase the amount of arsenic that is released from the geologic materials.

Effect of dietary cadmium on iron metabolism in growing rats.

PubMed

Crowe, A; Morgan, E H

1997-07-01

Little is known regarding the interactions between iron and cadmium during postnatal development. This study examined the effect of altered levels of dietary iron and cadmium loading on the distribution of cadmium and iron in developing rats ages 15, 21, and 63 days. The uptake of iron, transferrin, and cadmium into various organs was also examined using 59Fe, [125I]transferrin, and 109Cd. Dietary cadmium loading reduced packed cell volume and plasma iron and nonheme iron levels in the liver and kidneys, evidence of the inducement of an iron deficient state. Dietary iron loading was able to reverse these effects, suggesting that they were the result of impaired intestinal absorption of iron. Cadmium loading resulted in cadmium concentrations in the liver and kidneys up to 20 microg/g in rats age 63 days, while cadmium levels in the brain reached only 0.16 microg/g, indicating that the blood-brain barrier restricts the entry of cadmium into the brain. Iron loading had little effect on cadmium levels in the organs and cadmium feeding did not lower tissue iron levels in iron loaded animals. These results suggest that cadmium inhibits iron absorption only at low to normal levels of dietary iron and that at high levels of intake iron and cadmium are largely absorbed by other, noncompetitive mechanisms. It was shown that 109Cd is removed from the plasma extremely quickly irrespective of iron status and deposits mainly in the liver. One of the most striking effects of cadmium loading on iron metabolism was increased uptake of [125I]transferrin by the heart, possibly by disrupting the process of receptor-mediated endocytosis and recycling of transferrin by heart muscle.

Intravenous ferric carboxymaltose for the treatment of iron deficiency anemia

PubMed Central

Friedrisch, João Ricardo; Cançado, Rodolfo Delfini

2015-01-01

Nutritional iron deficiency anemia is the most common deficiency disorder, affecting more than two billion people worldwide. Oral iron supplementation is usually the first choice for the treatment of iron deficiency anemia, but in many conditions, oral iron is less than ideal mainly because of gastrointestinal adverse events and the long course needed to treat the disease and replenish body iron stores. Intravenous iron compounds consist of an iron oxyhydroxide core, which is surrounded by a carbohydrate shell made of polymers such as dextran, sucrose or gluconate. The first iron product for intravenous use was the high molecular weight iron dextran. However, dextran-containing intravenous iron preparations are associated with an elevated risk of anaphylactic reactions, which made physicians reluctant to use intravenous iron for the treatment of iron deficiency anemia over many years. Intravenous ferric carboxymaltose is a stable complex with the advantage of being non-dextran-containing and a very low immunogenic potential and therefore not predisposed to anaphylactic reactions. Its properties permit the administration of large doses (15 mg/kg; maximum of 1000 mg/infusion) in a single and rapid session (15-minute infusion) without the requirement of a test dose. The purpose of this review is to discuss some pertinent issues in relation to the history, pharmacology, administration, efficacy, and safety profile of ferric carboxymaltose in the treatment of patients with iron deficiency anemia. PMID:26670403

[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.

Surface-water and groundwater interactions in an extensively mined watershed, upper Schuylkill River, Pennsylvania, USA

USGS Publications Warehouse

Cravotta, Charles A.; Goode, Daniel J.; Bartles, Michael D.; Risser, Dennis W.; Galeone, Daniel G.

2014-01-01

Streams crossing underground coal mines may lose flow, while abandoned mine drainage (AMD) restores flow downstream. During 2005-12, discharge from the Pine Knot Mine Tunnel, the largest AMD source in the upper Schuylkill River Basin, had near-neutral pH and elevated concentrations of iron, manganese, and sulfate. Discharge from the tunnel responded rapidly to recharge but exhibited a prolonged recession compared to nearby streams, consistent with rapid infiltration and slow release of groundwater from the mine. Downstream of the AMD, dissolved iron was attenuated by oxidation and precipitation while dissolved CO2 degassed and pH increased. During high-flow conditions, the AMD and downstream waters exhibited decreased pH, iron, and sulfate with increased acidity that were modeled by mixing net-alkaline AMD with recharge or runoff having low ionic strength and low pH. Attenuation of dissolved iron within the river was least effective during high-flow conditions because of decreased transport time coupled with inhibitory effects of low pH on oxidation kinetics. A numerical model of groundwater flow was calibrated using groundwater levels in the Pine Knot Mine and discharge data for the Pine Knot Mine Tunnel and the West Branch Schuylkill River during a snowmelt event in January 2012. Although the calibrated model indicated substantial recharge to the mine complex took place away from streams, simulation of rapid changes in mine pool level and tunnel discharge during a high flow event in May 2012 required a source of direct recharge to the Pine Knot Mine. Such recharge produced small changes in mine pool level and rapid changes in tunnel flow rate because of extensive unsaturated storage capacity and high transmissivity within the mine complex. Thus, elimination of stream leakage could have a small effect on the annual discharge from the tunnel, but a large effect on peak discharge and associated water quality in streams.

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

Charged-Iron-Particles Found in Galactic Cosmic Rays are Potent Inducers of Epithelial Ovarian Tumors.

PubMed

Mishra, Birendra; Lawson, Gregory W; Ripperdan, Ryan; Ortiz, Laura; Luderer, Ulrike

2018-05-21

Astronauts traveling in deep space are exposed to high-charge and energy (HZE) particles from galactic cosmic rays. We have previously determined that irradiation of adult female mice with iron HZE particles induces DNA double-strand breaks, oxidative damage and apoptosis in ovarian follicles, causing premature ovarian failure. These effects occur at lower doses than with conventional photon irradiation. Ovarian failure with resultant loss of negative feedback and elevated levels of gonadotropin hormones is thought to play a role in the pathophysiology of ovarian cancer. Therefore, we hypothesized that charged-iron-particle irradiation induces ovarian tumorigenesis in mice. In this study, three-month-old female mice were exposed to 0 cGy (sham) or 50 cGy iron ions and aged to 18 months. The 50 cGy irradiated mice had increased weight gain with age and lack of estrous cycling, consistent with ovarian failure. A total of 47% and 7% of mice irradiated with 50 cGy had unilateral and bilateral ovarian tumors, respectively, whereas 14% of mice in the 0 cGy group had unilateral tumors. The tumors contained multiple tubular structures, which were lined with cells positive for the epithelial marker cytokeratin, and had few proliferating cells. In some tumors, packets of cells between the tubular structures were immunopositive for the granulosa cell marker FOXL2. Based on these findings, tumors were diagnosed as tubular adenomas or mixed tubular adenoma/granulosa cell tumors. In conclusion, charged-iron-particle-radiation induces ovarian tumors in mice, raising concerns about ovarian tumors as late sequelae of deep space travel in female astronauts.

Iron balance and iron supplementation for the female athlete: A practical approach.

PubMed

Pedlar, Charles R; Brugnara, Carlo; Bruinvels, Georgie; Burden, Richard

2018-03-01

Maintaining a positive iron balance is essential for female athletes to avoid the effects of iron deficiency and anaemia and to maintain or improve performance. A major function of iron is in the production of the oxygen and carbon dioxide carrying molecule, haemoglobin, via erythropoiesis. Iron balance is under the control of a number of factors including the peptide hormone hepcidin, dietary iron intake and absorption, environmental stressors (e.g. altitude), exercise, menstrual blood loss and genetics. Menstruating females, particularly those with heavy menstrual bleeding are at an elevated risk of iron deficiency. Haemoglobin concentration [Hb] and serum ferritin (sFer) are traditionally used to identify iron deficiency, however, in isolation these may have limited value in athletes due to: (1) the effects of fluctuations in plasma volume in response to training or the environment on [Hb], (2) the influence of inflammation on sFer and (3) the absence of sport, gender and individually specific normative data. A more detailed and longitudinal examination of haematology, menstrual cycle pattern, biochemistry, exercise physiology, environmental factors and training load can offer a superior characterisation of iron status and help to direct appropriate interventions that will avoid iron deficiency or iron overload. Supplementation is often required in iron deficiency; however, nutritional strategies to increase iron intake, rest and descent from altitude can also be effective and will help to prevent future iron deficient episodes. In severe cases or where there is a time-critical need, such as major championships, iron injections may be appropriate.

Antisense Inhibition of the Iron-Sulphur Subunit of Succinate Dehydrogenase Enhances Photosynthesis and Growth in Tomato via an Organic Acid–Mediated Effect on Stomatal Aperture[W][OA

PubMed Central

Araújo, Wagner L.; Nunes-Nesi, Adriano; Osorio, Sonia; Usadel, Björn; Fuentes, Daniela; Nagy, Réka; Balbo, Ilse; Lehmann, Martin; Studart-Witkowski, Claudia; Tohge, Takayuki; Martinoia, Enrico; Jordana, Xavier; DaMatta, Fábio M.; Fernie, Alisdair R.

2011-01-01

Transgenic tomato (Solanum lycopersicum) plants expressing a fragment of the Sl SDH2-2 gene encoding the iron sulfur subunit of the succinate dehydrogenase protein complex in the antisense orientation under the control of the 35S promoter exhibit an enhanced rate of photosynthesis. The rate of the tricarboxylic acid (TCA) cycle was reduced in these transformants, and there were changes in the levels of metabolites associated with the TCA cycle. Furthermore, in comparison to wild-type plants, carbon dioxide assimilation was enhanced by up to 25% in the transgenic plants under ambient conditions, and mature plants were characterized by an increased biomass. Analysis of additional photosynthetic parameters revealed that the rate of transpiration and stomatal conductance were markedly elevated in the transgenic plants. The transformants displayed a strongly enhanced assimilation rate under both ambient and suboptimal environmental conditions, as well as an elevated maximal stomatal aperture. By contrast, when the Sl SDH2-2 gene was repressed by antisense RNA in a guard cell–specific manner, changes in neither stomatal aperture nor photosynthesis were observed. The data obtained are discussed in the context of the role of TCA cycle intermediates both generally with respect to photosynthetic metabolism and specifically with respect to their role in the regulation of stomatal aperture. PMID:21307286

Polyvalent immunoglobulins with vitamin D3 and vitamin B12 in the treatment of Sjogren's syndrome in a vegetarian with stomatitis, glossodynia, xerostomia, and elevated antinuclear antibodies: Case report
.

PubMed

Cuny, Clemens; Vaerst, Barbara; Gabrielpillai, Jennis; Tahtali, Aykut; Balster, Sven; Lissner, Reinhard; Woodcock, Barry G

2018-01-01

Sjogren's syndrome, involving sicca symptoms with xerostomia, stomatitis, and considerable pain is a difficult-to-treat autoimmune disease where the treatment options are limited and, as in the case of methotrexate, have a low therapeutic index. This case report concerns a male patient, aged 75 years and vegetarian, with Sjogren's syndrome subsequently confirmed by salivary gland biopsy. Serum antinuclear antibodies (ANA) were elevated (1 : 320). Low serum vitamin B12 and iron levels could be improved after 20 days using vitamin B12 and iron oral supplements. Despite symptomatic treatment, xerostomia, glossitis, and glossodynia were still present, at times marked, after 12 months when the ANA titer was unchanged. Following treatment with an anti-inflammatory polyvalent immunoglobulin formulation (Lactobin^®N, 7 g daily), a bovine colostrum concentrate given orally in combination with oral vitamin D3 (2,000 IU daily), sicca symptoms and xerostomia progressively decreased and at day 750 were confined to occasional and minor glossitis of the upper lip. This case report demonstrates the satisfactory control of Sjogren's syndrome using oral polyvalent immunoglobulins with vitamin D3. In contrast to treatment options involving antimalarial drugs and methotrexate, there are no safety issues in patients tolerant to milk products.
.

Oral or parenteral iron supplementation to reduce deferral, iron deficiency and/or anaemia in blood donors.

PubMed

Smith, Graham A; Fisher, Sheila A; Doree, Carolyn; Di Angelantonio, Emanuele; Roberts, David J

2014-07-03

Iron deficiency is a significant cause of deferral in people wishing to donate blood. If iron removed from the body through blood donation is not replaced, then donors may become iron deficient. All donors are screened at each visit for low haemoglobin (Hb) levels. However, some deferred blood donors do not return to donate. Deferred first-time donors are even less likely to return. Interventions that reduce the risk of provoking iron deficiency and anaemia in blood donors will therefore increase the number of blood donations. Currently, iron supplementation for blood donors is not a standard of care in many blood services. A systematic review is required to answer specific questions regarding the efficacy and safety of iron supplementation in blood donors. To assess the efficacy and safety of iron supplementation to reduce deferral, iron deficiency and/or anaemia in blood donors. We ran the search on 18 November 2013. We searched Cochrane Injuries Group Specialised Register, CENTRAL, PubMed, MEDLINE (OvidSP), EMBASE (OvidSP), CINAHL (EBSCO Host) and six other databases. We also searched clinical trials registers and screened guidelines reference lists. Randomised controlled trials (RCTs) comparing iron supplementation versus placebo or control, oral versus parenteral iron supplementation, iron supplementation versus iron-rich food supplements, and different doses, treatment durations and preparations of iron supplementation in healthy blood donors. Autologous blood donors were excluded. We combined data using random-effects meta-analyses. We evaluated heterogeneity using the I(2) statistic; we explored considerable heterogeneity (I(2) > 75%) in subgroup analyses. We carried out sensitivity analyses to assess the impact of trial quality on the results. Thirty RCTs (4704 participants) met the eligibility criteria, including 19 comparisons of iron supplementation and placebo or control; one comparison of oral and parenteral iron supplementation; four comparisons of different doses of iron supplementation; one comparison of different treatment durations of iron supplementation; and 12 comparisons of different iron supplementation preparations.Many studies were of low or uncertain methodological quality and therefore at high or uncertain risk of bias. We therefore rated the quality of the evidence for our outcomes as moderate. There was a statistically significant reduction in deferral due to low haemoglobin in donors who received iron supplementation compared with donors who received no iron supplementation, both at the first donation visit after commencement of iron supplementation (risk ratio (RR) 0.34; 95% confidence interval (CI) 0.21 to 0.55; four studies; 1194 participants; P value < 0.0001) and at subsequent donations (RR 0.25; 95% CI 0.15 to 0.41; three studies; 793 participants; P value < 0.00001). Supplementation also resulted in significantly higher haemoglobin levels (mean difference (MD) 2.36 g/L; 95% CI 0.06 to 4.66; eight studies; 847 participants, P value =0.04), and iron stores, including serum ferritin (MD 13.98 ng/mL; 95% CI 8.92 to 19.03; five studies; 640 participants; P value < 0.00001) and transferrin saturation (MD 3.91%; 95% CI 2.02 to 5.80; four studies; 344 participants; P value < 0.0001) prior to further donation. The differences were maintained after subsequent donation(s).Adverse effects were widely reported and were more frequent in donors who received iron supplementation (RR 1.60; 95% CI 1.23 to 2.07; four studies; 1748 participants; P value = 0.0005). Adverse effects included constipation, diarrhoea, nausea, vomiting and taste disturbances, and some participants stopped treatment due to side effects. There is moderate quality evidence that rates of donor deferral due to low haemoglobin are considerably less in those taking iron supplements compared with those without iron supplementation, both at the first donation visit and at subsequent donation. Iron-supplemented donors also show elevated haemoglobin and iron stores. These beneficial effects are balanced by more frequent adverse events in donors who receive iron supplementation than in those who do not; this is likely to limit acceptability and compliance. The long-term effects of iron supplementation without measurement of iron stores are unknown. These considerations are likely to preclude widespread use of iron supplementation by tablets. Blood services may consider targeted use of supplementation in those at greatest risk of iron deficiency, personalised donation intervals and providing dietary advice.

Electronic properties and surface reactivity of SrO-terminated SrTiO3 and SrO-terminated iron-doped SrTiO3

PubMed Central

Staykov, Aleksandar; Tellez, Helena; Druce, John; Wu, Ji; Ishihara, Tatsumi; Kilner, John

2018-01-01

Abstract Surface reactivity and near-surface electronic properties of SrO-terminated SrTiO3 and iron doped SrTiO3 were studied with first principle methods. We have investigated the density of states (DOS) of bulk SrTiO3 and compared it to DOS of iron-doped SrTiO3 with different oxidation states of iron corresponding to varying oxygen vacancy content within the bulk material. The obtained bulk DOS was compared to near-surface DOS, i.e. surface states, for both SrO-terminated surface of SrTiO3 and iron-doped SrTiO3. Electron density plots and electron density distribution through the entire slab models were investigated in order to understand the origin of surface electrons that can participate in oxygen reduction reaction. Furthermore, we have compared oxygen reduction reactions at elevated temperatures for SrO surfaces with and without oxygen vacancies. Our calculations demonstrate that the conduction band, which is formed mainly by the d-states of Ti, and Fe-induced states within the band gap of SrTiO3, are accessible only on TiO2 terminated SrTiO3 surface while the SrO-terminated surface introduces a tunneling barrier for the electrons populating the conductance band. First principle molecular dynamics demonstrated that at elevated temperatures the surface oxygen vacancies are essential for the oxygen reduction reaction. PMID:29535797

Mortality of iron and steel workers in Korea.

PubMed

Park, Robert M; Ahn, Yeon-Soon; Stayner, Leslie T; Kang, Seong-Kyu; Jang, Jae-Kil

2005-09-01

The mortality experience of iron and steel workers from modern plants in developing countries has not been extensively described. Mortality at two Korean iron and steel manufacturing complexes was analyzed using Poisson regression methods with both direct and indirect standardization. Work histories were linked with a national mortality registry. Workers (44,974) hired beginning in 1968 were followed from 1992 to 2001. The 806 deaths observed during 10 years of follow-up comprised 2% of the population at risk and represented a large healthy worker effect (HWE) for all causes (SMR = 0.59, 95% CI = 0.55-0.63) and for cancer (SMR = 0.79, 95% CI = 0.70-0.90). Mortality at subsidiaries was considerably higher than at the parent plants (SRR = 1.71, 95% CI = 1.47-1.99). Relative mortality rates declined with employment duration: > 20 years had significantly reduced mortality (SRR = 0.59, 95% CI = 0.43-0.82) compared to duration < 1 year (test for trend: P = 0.0006). Fatal injury deaths in the first year were highly elevated (SMR = 3.10, 95% CI = 2.17-4.26) declining to less than that expected after 5 years. Cancer mortality was elevated in stainless steel production (SRR = 3.26, 95% CI = 1.37-6.49) and overall mortality was elevated for work in plant maintenance departments (SRR = 1.17, 95% CI = 1.00-1.37), particularly for fatal injuries (SRR = 1.67, 95% CI = 1.29-2.14). All-cause mortality increased with employment duration in the steel-production departments, as did fatal injuries in material handling/construction. This steelworker cohort exhibits excess mortality in some process areas. More detailed retrospective exposure assessment and future follow-up of this cohort will better define health risks in the modern iron and steel manufacturing.

Iron Mineral Catalyzed C-H Activation As a Potential Pathway for Halogenation Processes

NASA Astrophysics Data System (ADS)

Tubbesing, C.; Schoeler, H. F.; Benzing, K.; Krause, T.; Lippe, S.; Rudloff, M.

2014-12-01

Due to increasing drinking water demand of mankind and an expected climate change the impact of salt lakes and salt deserts will increase within the next decades. Furthermore, a rising sea level influences coastal areas like salt marshes and abets processes which will lead to elevated organohalogen formation. An additional increase of the global warming potential, of particle formation and stratospheric ozone depletion is expected. Understanding these multifaceted processes is essential for mankind to be prepared for these alterations of the atmosphere. For example, Keppler et al. (2000) described the production of volatile halogenated organic compounds via oxidation of organic matter driven by ferric iron. However, the formation of long-chained alkyl halides in salt lakes is yet undisclosed. Despite the relative "inertness" of alkanes a direct halogenation of these compounds might be envisaged. In 2005 Vaillancourt et al. discovered a nonheme iron enzyme which is able to halogenate organic compounds via generating the high valent ferryl cation as reaction center. Based on various publications about C-H activation (Bergman, 2007) we postulate a halogenation process in which an iron containing minerals catalyse the C-H bond cleavage of organic compounds in soils. The generated organic radicals are highly reactive towards halides connected to the iron complex. We suggest that next to diagenetically altered iron containing enzymes, minerals such as oxides, hydroxides and sulfides are involved in abiotic halogenation processes. We applied the amino acid methionine as organic model compound and soluble iron species as reactants. All samples were incubated in aqueous phases containing various NaCl concentrations. As a result various halogenated ethanes and ethenes were identified as reaction products. References Bergman, R. G. (2007) Nature, 446(7134) 391-393 Keppler, F., et al. (2000) Nature, 403(6767) 298-301 Vaillancourt, F. H., et al. (2005) Nature, 436(7054) 1191-1194

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

Responses to iron limitation in Hordeum vulgare L. as affected by the atmospheric CO2 concentration.

PubMed

Haase, S; Rothe, A; Kania, A; Wasaki, J; Römheld, V; Engels, C; Kandeler, E; Neumann, G

2008-01-01

Elevated atmospheric CO2 treatments stimulated biomass production in Fe-sufficient and Fe-deficient barley plants, both in hydroponics and in soil culture. Root/shoot biomass ratio was increased in severely Fe-deficient plants grown in hydroponics but not under moderate Fe limitation in soil culture. Significantly increased biomass production in high CO2 treatments, even under severe Fe deficiency in hydroponic culture, indicates an improved internal Fe utilization. Iron deficiency-induced secretion of PS in 0.5 to 2.5 cm sub-apical root zones was increased by 74% in response to elevated CO2 treatments of barley plants in hydroponics but no PS were detectable in root exudates collected from soil-grown plants. This may be attributed to suppression of PS release by internal Fe concentrations above the critical level for Fe deficiency, determined at final harvest for soil-grown barley plants, even without additional Fe supply. However, extremely low concentrations of easily plant-available Fe in the investigated soil and low Fe seed reserves suggest a contribution of PS-mediated Fe mobilization from sparingly soluble Fe sources to Fe acquisition of the soil-grown barley plants during the preceding culture period. Higher Fe contents in shoots (+52%) of plants grown in soil culture without Fe supply under elevated atmospheric CO2 concentrations may indicate an increased efficiency for Fe acquisition. No significant influence on diversity and function of rhizosphere-bacterial communities was detectable in the outer rhizosphere soil (0-3 mm distance from the root surface) by DGGE of 16S rRNA gene fragments and analysis of marker enzyme activities for C-, N-, and P-cycles.

Decreased Serum Hepcidin Concentration Correlates with Brain Iron Deposition in Patients with HBV-Related Cirrhosis

PubMed Central

Liu, Jian-Ying; He, Yi-Feng; Dai, Zhi; Chen, Cai-Zhong; Cheng, Wei-Zhong; Zhou, Jian; Wang, Xin

2013-01-01

Purpose Excessive brain iron accumulation contributes to cognitive impairments in hepatitis B virus (HBV)-related cirrhotic patients. The underlying mechanism remains unclear. Hepcidin, a liver-produced, 25-aminoacid peptide, is the major regulator of systemic iron metabolism. Abnormal hepcidin level is a key factor in some body iron accumulation or deficiency disorders, especially in those associated with liver diseases. Our study was aimed to explore the relationship between brain iron content in patients with HBV-related cirrhosis and serum hepcidin level. Methods Seventy HBV-related cirrhotic patients and forty age- sex-matched healthy controls were enrolled. Brain iron content was quantified by susceptibility weighted phase imaging technique. Serum hepcidin as well as serum iron, serum transferrin, ferritin, soluble transferrin receptor, total iron binding capacity, and transferrin saturation were tested in thirty cirrhotic patients and nineteen healthy controls. Pearson correlation analysis was performed to investigate correlation between brain iron concentrations and serum hepcidin, or other iron parameters. Results Cirrhotic patients had increased brain iron accumulation compared to controls in the left red nuclear, the bilateral substantia nigra, the bilateral thalamus, the right caudate, and the right putamen. Cirrhotic patients had significantly decreased serum hepcidin concentration, as well as lower serum transferring level, lower total iron binding capacity and higher transferrin saturation, compared to controls. Serum hepcidin level negatively correlated with the iron content in the right caudate, while serum ferritin level positively correlated with the iron content in the bilateral putamen in cirrhotic patients. Conclusions Decreased serum hepcidin level correlated with excessive iron accumulation in the basal ganglia in HBV-related cirrhotic patients. Our results indicated that systemic iron overload underlined regional brain iron repletion. Serum hepcidin may be a clinical biomarker for brain iron deposition in cirrhotic patients, which may have therapeutic potential. PMID:23776499

Remodulating effect of doxorubicin on the state of iron-containing proteins, and redox characteristics of tumor with allowance for its sensitivity to cytostatic agents.

PubMed

Chekhun, V F; Lozovska, Yu V; Burlaka, A P; Ganusevich, L I; Shvets, Yu V; Lukyanova, N Yu; Todor, I M; Tregubova, N A; Naleskina, L A

2016-01-01

The study was aimed at determining the changes of metal-containing proteins in blood serum and tumor tissue of animals with parental and doxorubicin-resistant strains of Walker-256 carcinosarcoma before and after the cytostatic administration. It has been shown that upon doxorubicin action the levels of total iron and transferrin in the tissues from the both groups of animals decreased while that of ferritine simultaneously increased with more pronounced pattern in the group of animals with resistant tumor strain. It has been shown that upon the action of doxorubicin in tumor tissue of animals with different sensitivity to the cytostatic there could be observed oppositely directed changes in the redox state of these cells that in turn determined the content of “ free iron” complexes, RO S generation and concentration of active forms of matrix metaloproteinase- 2 and matrix metaloproteinase-9, namely, the increase of these indexes in animals with parental strain and their decrease in animals with the resistant one. So, our study has demonstrated the remodulating effect of doxorubicin on the state of metal-containing proteins and redox characteristics of tumor dependent on its sensitivity to cytostatic, at the levels of the tumor and an organism. These data may serve as a criterion for the development of programs for the correction of malfunction of iron metabolism aimed at elevating tumor sensitivity to cytostatic agents.

Iron amendments to reduce bioaccessible arsenic.

PubMed

Cutler, William G; El-Kadi, Aly; Hue, Nguyen V; Peard, John; Scheckel, Kirk; Ray, Chittaranjan

2014-08-30

Former sugarcane lands on the Island of Hawaii have elevated levels of soil arsenic (As) from historical use of arsenical pesticides. The bioaccessible fraction of total As (AsTOT), a measure of the potential for human As uptake by incidental ingestion of soil, is used in the assessment of human health risk and the determination of the need for remedial action. Ferric chloride plus lime and ferrous sulfate plus lime were applied to As-contaminated soils in a field plot setting to determine the potential for reducing in vitro bioaccessible As (AsIVBA) by increasing As sequestration by the formation of additional iron (Fe) oxyhydroxides. The two Fe sources performed similarly in reducing AsIVBA over a 2-year observation period, with 30-41% reduction in AsIVBA for 0.25wt% Fe dosing (dry soil basis) and 59-63% reduction for 0.5wt% Fe dosing. Addition of phosphate (PO4) to treated and untreated soils caused a significant increase in AsIVBA. Iron-treated and control soils showed more than twice the AsIVBA after the addition of 1500mgPkg(-1). The cost of in situ treatment of As-contaminated soil with ferrous sulfate plus lime to lower AsIVBA was estimated to be an order of magnitude less than excavation and landfill disposal on the Island of Hawaii, making the technology a viable alternative when remedial action objectives were based on AsIVBA levels. Copyright © 2014 Elsevier B.V. All rights reserved.

[Effects of vitamin A supplementation on nutritional status of iron in healthy adults].

PubMed

Li, Zuwen; Fan, Ping; Deng, Gangbo; Du, Zhen; Shao, Zewei; Wang, Zhixu

2012-05-01

To investigate the effect of vitamin A (VA) supplementation on the nutritional status of iron in healthy adults. One hundred and fifteen healthy adults were recruited and divided randomly into four groups, with 28 or 29 adults in each group. VA supplements with different doses of retinyl acetate in capsules were given for 4-month. The equivalent doses of supplemented retinyl acetate were 600 microg/d, 400 microg/d, 200 microg/d and 0 microg/d (control) of retinol, respectively. The capsules were administered orally by double blind method. During the experiment, the subjects kept their usual dietary pattern but avoided high VA or pre-VA carotenoids foods from their diets. A 24-h dietary recall was carried out monthly on every subject. Before and after the intervention, the fast blood samples were collected from each subject, and were determined for hemoglobin concentration, levels of serum retinol, iron, ferrtin and transferrtin receptor. Total 108 subjects finished the experiment, with 27, 28, 27 and 26 persons left in group A, B, C and D, respectively. The subjects from each group had similar dietary intakes of energy nutrients, VA and iron (both were P > 0.05) during the experimental period. The serum retinol concentration of subjects from group A increased from 1.63 +/- 0.55 micromol/L of baseline to 1.93 +/-0.52 micromol/L at the end of the experiment (P < 0.05). The elevated value of serum retinol for group B and C were 0.29 micromol/L and 0.14 micromol/L (both were P < 0.05). There was no difference before and after the experiment for control group D (P > 0.05). There was no significant difference on Hb concentration before and after the experiment as well as between groups (all were P > 0.05). In subjects of group A, serum iron concentration increased (P < 0.05) and serum ferrtin and transferrtin receptor concentration decreased significantly (both were P < 0.05) after VA supplement intervention. No such changes were observed in group B and C (P < 0.05). It seems that the intervention of VA supplement with relative high dose of retinol at dietary level could enhance the iron status further in no-anemic healthy adults even without dietary iron supplementation.

Erythropoietin, Iron Depletion and Relative Thrombocytosis: A Possible Explanation for Hemoglobin-Survival Paradox in Chronic Kidney Disease

PubMed Central

Streja, Elani; Kovesdy, Csaba P; Greenland, Sander; Kopple, Joel D.; McAllister, Charles J; Nissenson, Allen R; Kalantar-Zadeh, Kamyar

2017-01-01

Background High doses of human recombinant erythropoietin (rHuEPO) to achieve hemoglobin levels above 13 g/dL in chronic kidney disease appear associated with elevated mortality. Study Design We conducted logistic regression and survival analyses in a retrospective cohort of maintenance hemodialysis (MHD) patients to examine the hypothesis that the induced iron depletion with resultant relative thrombocytosis may be a possible contributor to the link between the high rHuEPO dose associated hemoglobin ≥13 g/dL and mortality. Setting & Participants The national database of a large dialysis organization (DaVita) with 40,787 MHD patients during July to December 2001 and their survival up to July 2004 were examined. Predictors Hemoglobin level, platelet count and administered rHuEPO dose during each calendar quarter. Outcomes & other Measurements Case-mix adjusted 3-year all-cause mortality; and measures of iron stores including serum ferritin and iron saturation ratio (ISAT). Results Higher platelet count was associated with lower iron stores and higher prescribed rHuEPO dose. Compared to hemoglobin of 12-13 g/dL, hemoglobin ≥13 g/dL was associated with increased mortality in the presence of relative thrombocytosis, i.e., platelet count ≥300,000/μl, (case-mix adjusted death-rate ratio [RR]: 1.21, 95% confidence limits [CL]: 1.02–1.44, P=0.03) as opposed to the absence of relative thrombocytosis (RR: 1.04, 95% CL: 0.98–1.08, P=0.13). Prescribed rHuEPO dose >20,000 units/week was associated with higher likelihood of iron depletion (ISAT<20%) and relative thrombocytosis (case-mix adjusted odds ratio: 2.53 [CL: 2.37–2.69] and 1.36 [CL: 1.30–1.42], respectively, p<0.001) and increased mortality over 3 years (death-rate ratio of 1.59, CL: 1.54, 1.65, p<0.001). Limitations Our results may incorporate uncontrolled confounding. Achieved hemoglobin may have different mortality-predictability than targeted hemoglobin. Conclusions Iron depletion and associated relative thrombocytosis might contribute to increased mortality when administering high rHuEPO doses to achieve hemoglobin ≥13 g/dL in MHD patients. Randomized trials are needed to test these observational associations. PMID:18760517

EAST ELEVATION, LTV STEEL (FORMERLY REPUBLIC STEEL), 8" BAR MILL, ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

EAST ELEVATION, LTV STEEL (FORMERLY REPUBLIC STEEL), 8" BAR MILL, BUFFALO PLANT. VIEW LOOKING SOUTHWEST FROM ROLL SHOP. 8" BAR MILL DESIGNED AND BUILT BY DONNER STEEL CO. (PREDECESSOR OF REPUBLIC), 1919-1920. FOR DESCRIPTION OF ORIGINAL MILL SEE "IRON AGE", 116\\4 (23 JULY 1925): 201-204. - LTV Steel, 8-inch Bar Mill, Buffalo Plant, Buffalo, Erie County, NY

EXTERIOR VIEW, FRONT (NORTH) ELEVATION. THIS THREESTORY BRICK BUILDING WITH ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

EXTERIOR VIEW, FRONT (NORTH) ELEVATION. THIS THREE-STORY BRICK BUILDING WITH DEEPLY-BRACKETED AND OVERHANGING EAVES INCLUDES MULTIPLE BAYS CONSTRUCTED BEGINNING IN 1913 TO SERVE AS A 'CIVIC CENTER' FOR ACIPCO EMPLOYEES AND THEIR FAMILIES. THE BUILDING CURRENTLY INCLUDES THE TIME OFFICE, CAFETERIA, AND AUDITORIUM. - American Cast Iron Pipe Company, Service Building, 1501 Thirty-first Avenue North, Birmingham, Jefferson County, AL

45. DETAIL ELEVATION OF STAMP BATTERIES AND APRONS, LOOKING SOUTHEAST. ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

45. DETAIL ELEVATION OF STAMP BATTERIES AND APRONS, LOOKING SOUTHEAST. MORTARS, BOSSES, MOST SHOES, STEMS, TAPPETS, CAMS AND BULL WHEELS ARE CLEARLY VISIBLE ON THE UPPER MORTAR BLOCKS (BELOW CENTER) UNION IRON WORKS, SAN FRANCISCO C-L. SEE CA-290-18 FOR A SIMILAR B&W NEGATIVE. - Skidoo Mine, Park Route 38 (Skidoo Road), Death Valley Junction, Inyo County, CA

Nitrate-dependent iron oxidation limits iron transport in anoxic ocean regions

NASA Astrophysics Data System (ADS)

Scholz, Florian; Löscher, Carolin R.; Fiskal, Annika; Sommer, Stefan; Hensen, Christian; Lomnitz, Ulrike; Wuttig, Kathrin; Göttlicher, Jörg; Kossel, Elke; Steininger, Ralph; Canfield, Donald E.

2016-11-01

Iron is an essential element for life on Earth and limits primary production in large parts of the ocean. Oxygen-free continental margin sediments represent an important source of bioavailable iron to the ocean, yet little of the iron released from the seabed reaches the productive sea surface. Even in the anoxic water of oxygen minimum zones, where iron solubility should be enhanced, most of the iron is rapidly re-precipitated. To constrain the mechanism(s) of iron removal in anoxic ocean regions we explored the sediment and water in the oxygen minimum zone off Peru. During our sampling campaign the water column featured two distinct redox boundaries separating oxic from nitrate-reducing (i.e., nitrogenous) water and nitrogenous from weakly sulfidic water. The sulfidic water mass in contact with the shelf sediment contained elevated iron concentrations >300 nM. At the boundary between sulfidic and nitrogenous conditions, iron concentrations dropped sharply to <20 nM coincident with a maximum in particulate iron concentration. Within the iron gradient, we found an increased expression of the key functional marker gene for nitrate reduction (narG). Part of this upregulation was related to the activity of known iron-oxidizing bacteria. Collectively, our data suggest that iron oxidation and removal is induced by nitrate-reducing microbes, either enzymatically through anaerobic iron oxidation or by providing nitrite for an abiotic reaction. Given the important role that iron plays in nitrogen fixation, photosynthesis and respiration, nitrate-dependent iron oxidation likely represents a key-link between the marine biogeochemical cycles of nitrogen, oxygen and carbon.

Nutritional status of vegetarian children.

PubMed

Dwyer, J T; Dietz, W H; Andrews, E M; Suskind, R M

1982-02-01

Thirty-nine preschool children consuming different types of vegetarian diets were studied. Type and amount of carbohydrate, fat, protein, and amount of sodium and cholesterol provided by their diets were more like intakes suggested in the proposed Dietary Goals for the United States than to levels in usual diets of nonvegetarian children. Macrobiotic vegetarian children consumed less animal food than did other vegetarian children. The mean intake of vitamin D of macrobiotics was an eighth of the Recommended Dietary Allowance and mean serum alkaline phosphatase values were elevated. The mean intake of vitamin B12 levels were normal. Vegan macrobiotic children had the lowest intakes of vitamins B12 and D. Other vegetarians' mean intakes of these vitamins met the Recommended Dietary Allowance. Mean iron intakes of the vegetarians approximated the Recommended Dietary Allowance. Hematological indices were suggestive of mild iron deficiency anemia in a quarter of subjects. Serum cholesterol values were low for the group. Physical measurements were within normal limits and macrobiotic vegetarians were not smaller or leaner than other vegetarian children. The nutritional difficulties discovered could be corrected by careful planning of vegetarian children's diets while preserving the beneficial qualities of the diet in other respects.

Early signs of maternal iron deficiency do not influence the iron status of the newborn, but are associated with higher infant birthweight.

PubMed

Ervasti, Mari; Sankilampi, Ulla; Heinonen, Seppo; Punnonen, Kari

2009-01-01

To investigate the associations between maternal iron status, pregnancy outcome and newborn iron status using sensitive and specific red blood cell indices reflecting iron-deficient erythropoiesis. Cross-sectional study in Kuopio University Hospital, Finland. One hundred and ninety-two pregnant women and their full-term newborns (cord blood). Quartile analysis and Spearman correlations were used to investigate the associations of the iron status of pregnant women with that of their newborns, and with pregnancy outcome. Maternal and cord blood analysis including indices reflecting the hemoglobin (Hb) content of red blood cells as well as serum iron, transferrin saturation, transferrin receptor and ferritin. Gestational age, birthweight and placental weight. The highest quartile of the maternal percentage of hypochromic red blood cells (%HYPOm) indicating the lowest iron status was associated with a high birthweight and a long duration of pregnancy. The newborns in this group did not show any signs of iron deficiency even though the maternal %HYPOm was elevated. In a well-nourished maternal population, lower maternal iron status did not affect the iron accumulation on the fetal side. However, longer duration of pregnancy and growth of the fetus appeared to be associated with a lower amount of iron for Hb synthesis in maternal red blood cells, as reflected by the increased maternal %HYPOm, birthweight and length of gestation.

Association between functional iron deficiency and reactive thrombocytosis in hospitalised patients: a case-control study.

PubMed

Nicola, H; Ho, K M; Cordingley, F

2016-11-01

The association of deficiency in total body iron with an increased risk of reactive thrombocytosis is well known, but whether 'functional iron deficiency' is also associated with reactive thrombocytosis is unknown. This retrospective case-control study assessed the relationships between functional iron deficiency, reactive thrombocytosis and risk of thromboembolism. A total of 150 patients with reactive thrombocytosis (platelet count >400 x 10 9 /l) and 343 controls (platelet count <400 x 10 9 /l) were selected from the hospital laboratory database system. Patients with haematological disease or recent chemotherapy were excluded. Reactive thrombocytosis, infection, and an elevated C-reactive protein (CRP) concentration were all significantly more common in patients with functional iron deficiency than in those without functional iron deficiency (all P <0.01). After adjusting for infection and CRP concentration, functional iron deficiency was the only marker of iron status significantly associated with reactive thrombocytosis (odds ratio 1.66, 95% confidence interval 1.10-2.75; P =0.048). Thromboembolic events occurred in 32 patients (6.6%). This was not significantly associated with functional iron deficiency. Our results suggest that in patients without haematological malignancy or recent chemotherapy there might be a link between functional iron deficiency and reactive thrombocytosis. Whether treating patients with functional iron deficiency with intravenous iron corrects reactive thrombocytosis without inducing infection remains uncertain, but merits further investigation.

Treatment of Iron Deficiency in Women

PubMed Central

Breymann, C.; Römer, T.; Dudenhausen, J. W.

2013-01-01

Iron deficiency with and without anaemia is a common cause of morbidity, particularly in women. Iron deficiency is generally the result of an imbalance between iron loss and iron absorption. In women with symptoms suspicious for iron deficiency, it is important to confirm or exclude the suspicion using proper tests. The use of serum ferritin levels is considered the gold standard for diagnosis. Although the ideal ferritin levels are not unknown the current consent is that levels < 40 ng/ml indicate iron deficiency, which needs to be treated in symptomatic patients. However, symptoms can already occur at ferritin levels of < 100 ng/ml and treatment must be adapted to the individual patient. Iron supplementation is only indicated in symptomatic patients diagnosed with iron deficiency whose quality of life is affected. It is important to treat iron deficiency together with its causes or risk factors. For example, blood loss from hypermenorrhea should be reduced. Women also need to receive information about the benefits of an iron-rich diet. If oral treatment with iron supplements is ineffective, parenteral iron administration is recommended. PMID:26633902

Catalytic Transfer Hydrogenation of Furfural to Furfuryl Alcohol over Nitrogen-Doped Carbon-Supported Iron Catalysts.

PubMed

Li, Jiang; Liu, Jun-Ling; Zhou, Hong-Jun; Fu, Yao

2016-06-08

Iron-based heterogeneous catalysts, which were generally prepared by pyrolysis of iron complexes on supports at elevated temperature, were found to be capable of catalyzing the transfer hydrogenation of furfural (FF) to furfuryl alcohol (FFA). The effects of metal precursor, nitrogen precursor, pyrolysis temperature, and support on catalytic performance were examined thoroughly, and a comprehensive study of the reaction parameters was also performed. The highest selectivity of FFA reached 83.0 % with a FF conversion of 91.6 % under the optimal reaction condition. Catalyst characterization suggested that iron cations coordinated by pyridinic nitrogen functionalities were responsible for the enhanced catalytic activity. The iron catalyst could be recycled without significant loss of catalytic activity for five runs, and the destruction of the nitrogen-iron species, the presence of crystallized Fe2 O3 phase, and the pore structure change were the main reasons for catalyst deactivation. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Calcification response of Pleurochrysis carterae to iron concentrations in batch incubations: implication for the marine biogeochemical cycle

NASA Astrophysics Data System (ADS)

Zou, Xiang; Sun, Shiyong; Lin, Sen; Shen, Kexuan; Dong, Faqin; Tan, Daoyong; Nie, Xiaoqin; Liu, Mingxue; Wei, Jie

2017-12-01

Calcified coccolithophores, a diverse and widely distributed group of marine microalgae, produce biogenic calcite in the form of coccoliths located on the cell surface. Using batch incubations of the coccolithophorid Pleurochrysis carterae, we investigated the responses of this calcification process to iron concentrations by changing the iron supply in the initial culture media from a normal concentration to 1 ppm (parts per million), 5 ppm, and 10 ppm. Time-dependent measurements of cell population, production of inorganic carbon (coccoliths), and organic carbon (organic cellular components) showed that elevated iron supply in the growth medium of P. carterae stimulates carbon sequestration by increasing growth along enhanced photosynthetic activity and calcification. In addition, the acquired time-dependent UV-Vis and FT-IR spectra revealed that iron fertilization-enhanced coccolith calcification is accompanied by a crystalline phase transition from calcite to aragonite or amorphous phase. Our results suggest that iron concentration has a significant influence on the marine carbon cycle of coccolithophores.

Triumph and tragedy: anemia management in chronic kidney disease.

PubMed

Novak, James E; Szczech, Lynda A

2008-11-01

Recent trial data have resulted in a reevaluation of the management of anemia in chronic kidney disease, including the use of erythropoiesis-stimulating agents, intravenous iron, and novel pharmaceuticals. In this review, we evaluate the latest research on anemia management in chronic kidney disease. Clinical trials of erythropoiesis-stimulating agents indicate that targeting the complete correction of anemia in patients with chronic kidney disease results in a greater risk of morbidity and mortality despite improved hemoglobin and quality of life. Conversely, intravenous iron has been found effective and relatively well tolerated in treating anemia in chronic kidney disease, even in patients with elevated ferritin. New agents to manage anemia, including long-acting erythropoietin derivatives, are also in active development. Erythropoiesis-stimulating agents should be used to target hemoglobin 11-12 g/dl in patients with chronic kidney disease. Intravenous iron may be beneficial for patients with hemoglobin less than 11 g/dl and transferrin saturation less than 25% despite elevated ferritin (500-1200 ng/ml). An upcoming placebo-controlled trial of darbepoetin should help to define the role of erythropoiesis-stimulating agents in chronic kidney disease.

INFLAMMATORY MARKERS ASSOCIATED WITH TRAUMA AND INFECTION IN RED-TAILED HAWKS (BUTEO JAMAICENSIS) IN THE USA.

PubMed

Lee, Kelly A; Goetting, Valerie S; Tell, Lisa A

2015-10-01

Changes in inflammatory marker concentrations or activity can be used to monitor health and disease condition of domestic animals but have not been applied with the same frequency to wildlife. We measured concentrations or activity of six inflammatory markers (ceruloplasmin, haptoglobin, mannan-binding lectin-dependent complement [MBL/complement], unsaturated iron-binding capacity (UIBC) and total iron-binding capacity (TIBC), and plasma iron) in apparently healthy and sick or injured Red-tailed Hawks (Buteo jamaicensis). Haptoglobin and ceruloplasmin activities were consistently elevated in sick or injured hawks (2.1 and 2.5 times higher, respectively), and plasma iron concentrations decreased (0.46 times lower), relative to those of healthy birds. There were no differences between healthy and unhealthy hawks in TIBC and UIBC concentrations or MBL/complement activity. Therefore, haptoglobin, ceruloplasmin, and plasma iron would be useful inclusions in a panel of inflammatory markers for monitoring health in raptors.

Evaluation of the Effects of Iron Oxides on Soil Reducing Conditions and Methane Generation in Cambodian Wetland Rice Fields

NASA Astrophysics Data System (ADS)

Weaver, M.; Benner, S.; Fendorf, S.; Sampson, M.; Leng, M.

2007-12-01

Atmospheric concentrations of methane have been steadily increasing over the last 100 years, which has given rise to research of wetland rice fields, recently identified as a major anthropomorphic source of methane. Establishment of experimental soil pots, cultivating an aromatic early variety rice strain in the Kean Svay District of Cambodia, have recently been carried out to evaluate methods to minimize methane release by promoting redox buffering by iron oxides. In the first series of experiments, iron oxides were added to the soils and the rate of change in reducing conditions and methanogenesis onset was monitored. In the second series of experiments, plots are subject to periodic drying cycles to promote rejuvenation of buffering iron oxides. Initial results indicate a delay in the onset of methanogenesis, and overall methane generation, in plots where initial iron oxides concentrations are elevated.

Acidic Polysaccharide from Angelica sinensis Reverses Anemia of Chronic Disease Involving the Suppression of Inflammatory Hepcidin and NF-κB Activation.

PubMed

Wang, Kaiping; Wu, Jun; Cheng, Fang; Huang, Xiao; Zeng, Fang; Zhang, Yu

2017-01-01

Anemia of chronic disease (ACD) is the second most prevalent anemia and frequently occurs in patients with acute or chronic immune activation. In the current study, we evaluated the therapeutic efficacy of Angelica sinensis polysaccharide (ASP) against ACD in rats and the potential mechanisms involved. The results showed that ASP inhibited inflammatory hepcidin in both HepG2 cells and ACD rats by blocking the IL-6/STAT3 and BMP/SMAD pathways. In ACD rats, the administration of ASP increased ferroportin expression, mobilized iron from the liver and spleen, increased serum iron levels, caused an elevation of serum EPO, and effectively relieved the anemia. Furthermore, ASP inhibited NF- κ B p65 activation via the I κ B kinases- (IKKs-) I κ B α pathway, thereby reducing the secretion of interleukin-6 (IL-6) and TNF- α , which is known to inhibit erythropoiesis. Our findings indicate that ASP is a potential treatment option for patients suffering from ACD.

Age, gender, and hemispheric differences in iron deposition in the human brain: an in vivo MRI study.

PubMed

Xu, Xiaojun; Wang, Qidong; Zhang, Minming

2008-03-01

It is well known that iron accumulates in the brains of patients with various neurodegenerative diseases. To better understand disease-related iron changes, it is necessary to know the physiological distribution and accumulation of iron in the human brain. Studies have shown that brain iron levels increase with aging. However, the effects of gender and hemispheric laterality on iron accumulation and distribution are not well established. In this study, we estimated the brain iron levels in vivo in 78 healthy adults ranging in age 22 to 78 years using magnetic susceptibility-weighted phase imaging. The effects of age, gender, and hemispheric location on brain iron levels were evaluated within the framework of a general linear model. We found that the left hemisphere had higher iron levels than the right in the putamen, globus pallidus, substantia nigra, thalamus, and frontal white matter. We argue that the hemispheric asymmetry of iron content may underlie that of the dopaminergic system and may be related to motor lateralization in humans. In addition, significant age-related iron accumulation occurred in the putamen, red nucleus, and frontal white matter, but no gender-related differences in iron levels were detected. The results of this study extend our knowledge of the physiological distribution and accumulation of iron in the human brain.

Safety of long-term restrictive diets for peroxisomal disorders: vitamin and trace element status of patients treated for Adult Refsum Disease.

PubMed

Baldwin, E J; Harrington, D J; Sampson, B; Feher, M D; Wierzbicki, A S

2016-03-01

Adult Refsum's Disease (ARD) is caused by defects in the pathway for alpha-oxidation of phytanic acid (PA). Treatment involves restricting the dietary intake of phytanic acid by reducing the intake of dairy-derived fat. The adequacy of micronutrient intake in patients with ARD is unknown. Patients established on the Chelsea low-PA diet had general diet macronutrients, vitamins and trace elements assessed using 7-day-weighed intakes and serial 24-h recalls. Intakes were compared with biochemical assessments of nutritional status for haematinics (ferritin), trace elements (copper, zinc, iron, selenium), water- (vitamin B6 , B12 and folate) and fat-soluble vitamins (A, D, E and K). Eleven subjects (four women, seven men) were studied. Body mass index was 27 ± 5 kg/m(2) (range 19-38). All subjects had high sodium intakes (range 1873-4828 mg). Fat-soluble vitamin insufficiencies occurred in some individuals (vitamin A, n = 2; vitamin D, n = 6; vitamin E, n = 3; vitamin K, n = 10) but were not coincident. Vitamin B6 levels were normal or elevated (n = 6). Folate and 5-methyltetrahydrofolate concentrations were normal. Metabolic vitamin B12 insufficiency was suspected in four subjects based on elevated methylmalonic acid concentrations. Low copper and selenium intakes were noted in some subjects (n = 7, n = 2) but plasma levels were adequate. Iron, ferritin and zinc intakes and concentrations were normal. Subjects with ARD can be safely managed on the Chelsea low PA without routine micronutrient supplementation. Sodium intake should be monitored and reduced. Periodic nutritional screening may be necessary for fat-soluble vitamins, vitamin B12 , copper or selenium. © 2016 John Wiley & Sons Ltd.

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

Ferritin accumulation under iron scarcity in Drosophila iron cells.

PubMed

Mehta, A; Deshpande, A; Bettedi, L; Missirlis, F

2009-10-01

Ferritins are highly stable, multi-subunit protein complexes with iron-binding capacities that reach 4500 iron atoms per ferritin molecule. The strict dependence of cellular physiology on an adequate supply of iron cofactors has likely been a key driving force in the evolution of ferritins as iron storage molecules. The insect intestine has long been known to contain cells that are responsive to dietary iron levels and a specialized group of "iron cells" that always accumulate iron-loaded ferritin, even when no supplementary iron is added to the diet. Here, we further characterize ferritin localization in Drosophila melanogaster larvae raised under iron-enriched and iron-depleted conditions. High dietary iron intake results in ferritin accumulation in the anterior midgut, but also in garland (wreath) cells and in pericardial cells, which together filter the circulating hemolymph. Ferritin is also abundant in the brain, where levels remain unaltered following dietary iron chelation, a treatment that depletes ferritin from the aforementioned tissues. We attribute the stability of ferritin levels in the brain to the function of the blood-brain barrier that may shield this organ from systemic iron fluctuations. Most intriguingly, our dietary manipulations demonstrably iron-depleted the iron cells without a concomitant reduction in their production of ferritin. Therefore, insect iron cells may constitute an exception from the evolutionary norm with respect to iron-dependent ferritin regulation. It will be of interest to decipher both the physiological purpose served and the mechanism employed to untie ferritin regulation from cellular iron levels in this cell type.

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.

Effect of sewage sludge on formation of acidic ground water at a reclaimed coal mine

USGS Publications Warehouse

Cravotta, C.A.

1998-01-01

Data on rock, ground water, vadose water, and vadose gas chemistry were collected for two years after sewage sludge was applied at a reclaimed surface coal mine in Pennsylvania to determine if surface-applied sludge is an effective barrier to oxygen influx, contributes metals and nutrients to ground water, and promotes the acidification of ground water. Acidity, sulfate, and metals concentrations were elevated in the ground water (6- to 21-m depth) from spoil relative to unmined rock because of active oxidation of pyrite and dissolution of aluminosilicate, carbonate, and Mn-Fe-oxide minerals in the spoil. Concentrations of acidity, sulfate, metals (Fe, Mn, Al, Cd, Cu, Cr, Ni, Zn), and nitrate, and abundances of iron-oxidizing bacteria were elevated in the ground water from sludge-treated spoil relative to untreated spoil having a similar mineral composition; however, gaseous and dissolved oxygen concentrations did not differ between the treatments. Abundances of iron-oxidizing bacteria in the ground water samples were positively correlated with concentrations of ammonia, nitrate, acidity, metals, and sulfate. Concentrations of metals in vadose water samples (<5-m depth) from sludge-treated spoil (pH 5.9) were not elevated relative to untreated spoil (pH 4.4). In contrast, concentrations of nitrate were elevated in vadose water samples from sludge-treated spoil, frequently exceeding 10 mg/L. Downgradient decreases in nitrate to less than 3 mg/L and increases in sulfate concentrations in underlying ground water could result from oxidation of pyrite by nitrate. Thus, sewage sludge added to pyritic spoil can increase the growth of iron-oxidizing bacteria, the oxidation of pyrite, and the acidification of ground water. Nevertheless, the overall effects on ground water chemistry from the sludge were small and probably short-lived relative to the effects from mining only.

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

Dispersion and bioaccumulation of elements from an open-pit olivine mine in Southwest Greenland assessed using lichens, seaweeds, mussels and fish.

PubMed

Søndergaard, Jens

2013-08-01

This study investigated dispersion and bioaccumulation of mining-related elements from an open-pit olivine mine at Seqi in Southwest Greenland (64° N) using lichens (Flavocetraria nivalis), seaweeds (Fucus vesiculosus), mussels (Mytilus edulis) and fish (Myoxocephalus scorpius). The mine operated between 2005 and 2009, and samples were taken every year within a monitoring area 0-17 km from the mine during the period 2004-2011. A total of 46 elements were analysed in the samples. After mining began, highly elevated metal concentrations, especially nickel (Ni), chromium (Cr), iron (Fe) and cobalt (Co), were observed in lichens relative to pre-mining levels (up to a factor of 130) caused by dust dispersion from the mining activity. Elevated metal concentrations could be measured in lichens in distances up to ~5 km from the mine/ore treatment facility. Moderately elevated concentrations of Ni and Cr (up to a factor of 7) were also observed in seaweeds and mussels but only in close vicinity (<1 km) to the mine. Analyses of fish showed no significant changes in element composition. After mine closure, the elevated metal concentrations in lichens, seaweeds and mussels decreased markedly, and in 2011, significantly elevated metal concentrations could only be measured in lichens and only within a distance of 1 km from the mine.

[Liver enzymes elevation: etiologic study and efficiency of a single-act office visit].

PubMed

Bendezú García, Rogger Álvaro; Casado Martín, Marta; Lázaro Sáez, Marta; Patrón Román, Gustavo Óliver; Gálvez Miras, Alejandra; Rodríguez Laiz, Gonzalo P; González Sánchez, Mercedes; Vega Sáenz, José Luis

2013-01-01

Liver enzyme (LE) elevation is a common finding in routine blood analysis. There is very little information on the most prevalent causes of these alterations in our population. In addition, a number of tests and several visits to the specialist are required to reach a diagnosis. For these reasons, we designed a protocol to streamline the evaluation of patients with LE elevations in a single-act office visit. From March 2008 until June 2010, we studied all patients with incidental LE elevation (isolated transaminase elevation, combined elevation of alkaline phosphatase [FA] and gamma-glutamyl transpeptidase [GGT], or isolated elevation of GGT) who were referred by their primary care physicians. At the time of referral, a complete biochemistry analysis was performed (LE, viral serology, autoantibodies, ceruloplasmin, iron metabolism, alpha-1-antitrypsin and thyroid hormones) and the patients underwent an abdominal ultrasound scan on the day of the office evaluation by the hepatologist. A total of 427 patients were included in our study. The most common cause of transaminase elevation was non-alcoholic fatty liver disease (NAFLD) (40%), followed by alcohol intake (17%), and hepatitis C virus infection (13%). Elevated GGT levels were most commonly related to NAFLD (30%), closely followed by alcohol intake (27%), and hepatotoxicity (8%). Combined elevation of GGT and FA was associated with NAFLD (21%), alcohol (17%), and hepatotoxicity (11%). Self-limited elevation was seen in 9% of the patients and we could not identify a definite cause in 11%. A definitive diagnosis was reached in 79% of the patients. The single-act office visit has proven to be efficient, yielding a diagnosis in most of the patients. The most common cause of elevated LE was NAFLD. Transaminase elevation must be confirmed before a more thorough work-up is started. Copyright © 2013 Elsevier España, S.L. and AEEH y AEG. All rights reserved.

Hematinic deficiencies and pernicious anemia in oral mucosal disease patients with macrocytosis.

PubMed

Chang, Julia Yu-Fong; Wang, Yi-Ping; Wu, Yang-Che; Cheng, Shih-Jung; Chen, Hsin-Ming; Sun, Andy

2015-08-01

Macrocytosis is defined as having the mean corpuscular volume (MCV) ≥ 100 fL. This study assessed hematinic deficiencies and pernicious anemia (PA) in oral mucosal disease patients with macrocytosis. The blood hemoglobin (Hb), iron, vitamin B12, folic acid, and homocysteine concentrations and MCV in 60 oral mucosal disease patients with macrocytosis were measured and compared with the corresponding data in 120 age- and sex-matched healthy control participants. PA was defined by the World Health Organization (WHO) as having an Hb concentration < 13 g/dL for men and < 12 g/dL for women, an MCV ≥ 100 fL, a serum vitamin B12 level < 200 pg/mL, and serum gastric parietal cell antibody (GPCA) positivity. We found that 30 (50.0%), 7 (11.7%), 24 (40.0%), and three (5.0%) oral mucosal disease patients with macrocytosis had deficiencies of Hb (men < 13 g/dL, women < 12 g/dL), iron (< 60 μg/dL), vitamin B12 (< 200 pg/mL), and folic acid (< 4 mg/mL), respectively. Moreover, 38 (63.3%) and 16 (26.7%) macrocytosis patients had abnormally high blood homocysteine level (> 12.3 μM) and serum GPCA positivity, respectively. Macrocytosis patients had a significantly higher frequency of Hb, iron, or vitamin B12 deficiency, of abnormally elevated blood homocysteine level, and of GPCA positivity than healthy control participants (p < 0.001). However, only 16.7% of 60 macrocytosis patients were diagnosed as having PA by the WHO definition. Only 16.7% of oral mucosal disease patients with macrocytosis are discovered to have PA by the WHO definition. Copyright © 2015. Published by Elsevier B.V.

Dentate nucleus iron deposition is a potential biomarker for tremor-dominant Parkinson's disease.

PubMed

He, Naying; Huang, Pei; Ling, Huawei; Langley, Jason; Liu, Chunlei; Ding, Bei; Huang, Juan; Xu, Hongmin; Zhang, Yong; Zhang, Zhongping; Hu, Xiaoping; Chen, Shengdi; Yan, Fuhua

2017-04-01

Parkinson's disease (PD) is a heterogeneous neurodegenerative disorder with variable clinicopathologic phenotypes and underlying neuropathologic mechanisms. Each clinical phenotype has a unique set of motor symptoms. Tremor is the most frequent initial motor symptom of PD and is the most difficult symptom to treat. The dentate nucleus (DN) is a deep iron-rich nucleus in the cerebellum and may be involved in PD tremor. In this study, we test the hypothesis that DN iron may be elevated in tremor-dominant PD patients using quantitative susceptibility mapping. Forty-three patients with PD [19 tremor dominant (TD)/24 akinetic rigidity (AR) dominant] and 48 healthy gender- and age-matched controls were recruited. Multi-echo gradient echo data were collected for each subject on a 3.0-T MR system. Inter-group susceptibility differences in the bilateral DN were investigated and correlations of clinical features with susceptibility were also examined. In contrast with the AR-dominant group, the TD group was found to have increased susceptibility in the bilateral DN when compared with healthy controls. In addition, susceptibility was positively correlated with tremor score in drug-naive PD patients. These findings indicate that iron load within the DN may make an important contribution to motor phenotypes in PD. Moreover, our results suggest that TD and AR-dominant phenotypes of PD can be differentiated on the basis of the susceptibility of the DN, at least at the group level. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

Deferiprone attenuates inflammation and myocardial fibrosis in diabetic cardiomyopathy rats

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

Zou, Chunbo; Liu, Xiaogang; Xie, Rujuan

We attempted to investigate the therapeutic effects of deferiprone on DC rats and explore the underlying mechanism. Total 24 6-week-old male Wistar rats (weighing from 180 g to 220 g) were subjected to DC model construction and then randomly divided to three groups (8 rats per group): DC group, DC + 50 mg, and DC + 100 mg deferiprone treatment group. The 8 normal rats were considered as controls. After deferiprone treatment for 20 weeks, the blood samples were collected for the biochemical parameters test, including fasting glucose, HOMA-IR (homeostasis model assessment of the insulin resistance), serum iron, ferritin and transferrin saturation (TS). The oxidative stress was assessedmore » by detecting the level of malondialdehyde (MDA) and superoxide dismutase (SOD). Histopathologic changes were determined by Masson's trichrome staining and electron microscopy imaging. The expression levels of NF-κB (nuclear factor kappa B), COX2 (cytochrome c oxidase), tenascin C, collagen IV were measured by RT-PCR and western blotting. The expression of nitrotyrosine and MCP-1 (monocyte chemotactic protein 1) were determined by immunohistochemistry. Deferiprone treatment reduced iron deposition and IR in DC rats except for blood glucose. After deferiprone treatment, MDA level was significantly decreased and SOD level was increased significantly. The level of NF-κB, cyclooxygenase-2, tenascin C, collagen IV MCP-1 and nitrotyrosine were significantly reduced. There was no significant difference in the effect of deferiprone at 50 and 100 mg doses. Deferiprone showed therapeutic effects on DC by regulating the pro-inflammatory and pro-fibrotic factors. - Highlights: • The expression of serum iron, ferritin and TS were elevated in DC rats. • Oxidative stress related MDA and SOD were upregulated in DC rats. • NF-κB, COX2, tenascin C, collagen IV were accumulated in DC rats. • All the changes were reversed by deferiprone treatment.« less

The Phosphoinositide 3-Kinase Regulates Retrograde Trafficking of the Iron Permease CgFtr1 and Iron Homeostasis in Candida glabrata*

PubMed Central

Sharma, Vandana; Purushotham, Rajaram; Kaur, Rupinder

2016-01-01

The phosphoinositide 3-kinase (PI3K), which phosphorylates phosphatidylinositol and produces PI3P, has been implicated in protein trafficking, intracellular survival, and virulence in the pathogenic yeast Candida glabrata. Here, we demonstrate PI3-kinase (CgVps34) to be essential for maintenance of cellular iron homeostasis. We examine how CgVps34 regulates the fundamental process of iron acquisition, and underscore its function in vesicular trafficking as a central determinant. RNA sequencing analysis revealed iron homeostasis genes to be differentially expressed upon CgVps34 disruption. Consistently, the Cgvps34Δ mutant displayed growth attenuation in low- and high-iron media, increased intracellular iron content, elevated mitochondrial aconitase activity, impaired biofilm formation, and extenuated mouse organ colonization potential. Furthermore, we demonstrate for the first time that C. glabrata cells respond to iron limitation by expressing the iron permease CgFtr1 primarily on the cell membrane, and to iron excess via internalization of the plasma membrane-localized CgFtr1 to the vacuole. Our data show that CgVps34 is essential for the latter process. We also report that macrophage-internalized C. glabrata cells express CgFtr1 on the cell membrane indicative of an iron-restricted macrophage internal milieu, and Cgvps34Δ cells display better survival in iron-enriched medium-cultured macrophages. Overall, our data reveal the centrality of PI3K signaling in iron metabolism and host colonization. PMID:27729452

Iron excess in recreational marathon runners.

PubMed

Mettler, S; Zimmermann, M B

2010-05-01

Iron deficiency and anemia may impair athletic performance, and iron supplements are commonly consumed by athletes. However, iron overload should be avoided because of the possible long-term adverse health effects. We investigated the iron status of 170 male and female recreational runners participating in the Zürich marathon. Iron deficiency was defined either as a plasma ferritin (PF) concentration <15 microg/l (iron depletion) or as the ratio of the concentrations of transferrin receptor (sTfR) to PF (sTfR:log(PF) index) of > or =4.5 (functional iron deficiency). After excluding subjects with elevated C-reactive protein concentrations, iron overload was defined as PF >200 microg/l. Iron depletion was found in only 2 out of 127 men (1.6% of the male study population) and in 12 out of 43 (28.0%) women. Functional iron deficiency was found in 5 (3.9%) and 11 (25.5%) male and female athletes, respectively. Body iron stores, calculated from the sTfR/PF ratio, were significantly higher (P<0.001) among male compared with female marathon runners. Median PF among males was 104 microg/l, and the upper limit of the PF distribution in males was 628 microg/l. Iron overload was found in 19 out of 127 (15.0%) men but only 2 out of 43 in women (4.7%). Gender (male sex), but not age, was a predictor of higher PF (P<0.001). Iron depletion was present in 28% of female runners but in <2% of males, whereas one in six male runners had signs of iron overload. Although iron supplements are widely used by athletes in an effort to increase performance, our findings indicate excess body iron may be common in male recreational runners and suggest supplements should only be used if tests of iron status indicate deficiency.

The effect of iron balance on platelet counts in blood donors.

PubMed

Eder, Anne F; Yau, Yu Ying; West, Kamille

2017-02-01

Thrombocytosis (or, less commonly, thrombocytopenia) is associated with iron-deficiency anemia and resolves with iron therapy. Many volunteer blood donors have low iron stores, with or without anemia. Iron balance could affect platelet counts in blood donors. Whole blood donors deferred for finger-stick hemoglobin levels less than 12.5 g/dL were evaluated by complete blood count and serum iron panel before and after oral iron treatment. Group assignment for iron depletion was based on serum ferritin cutoffs of less than 20 µg/L for women and less than 30 µg/L for men or was based on changes in serum ferritin levels after iron replacement. Among 1273 Hb-deferred whole blood donors, 55% (619 of 1128) of the women and 70% (102 of 145) of the men were iron depleted. Iron-depleted donors had higher platelet counts compared with donors who had normal ferritin levels (women: 286 vs. 268 × 10 3 /µL; p < 0.0001; men: 246 vs. 222 × 10 3 /µL; p = 0.0454). Only 4.4% of iron-depleted donors had thrombocytosis (> 400 × 10 3 /µL) compared with 2.0% of donors who had normal ferritin levels (p = 0.017). Iron replacement decreased platelet counts in iron-depleted female donors (mean, -19,800/µL; interquartile range, 8000 to -45,000/μL), but not in donors who had normal or stable ferritin levels. The same trends were observed in male donors. Iron-depleted donors had higher platelet counts than donors who had adequate iron stores. Oral iron replacement decreased platelet counts on average by about 20,000/µL in iron-depleted donors but had no effect on platelet counts in donors who had normal or stable ferritin levels. Published 2016. This article is a U.S. Government work and is in the public domain in the USA.

Serum Iron and Haemoglobin Estimation in Oral Submucous Fibrosis and Iron Deficiency Anaemia: A Diagnostic Approach.

PubMed

Bhardwaj, Divya; Dinkar, Ajit D; Satoskar, Sujata K; Desai, Sapna Raut

2016-12-01

Oral Submucous Fibrosis (OSMF) is a premalignant condition with potential malignant behaviour characterized by juxta-epithelial fibrosis of the oral cavity. In the process of collagen synthesis, iron gets utilized, by the hydroxylation of proline and lysine, leading to decreased serum iron levels. The trace element like iron is receiving much attention in the detection of oral cancer and precancerous condition like OSMF as it was found to be significantly altered in these conditions. The aim of this study was to compare the haemoglobin and serum iron values of OSMF subjects with that of iron deficiency anaemia subjects. Total of 120 subjects were included, 40 subjects with the OSMF, 40 with the iron deficiency anemia without tobacco chewing habit, 40 healthy control subjects without OSMF and iron deficiency anaemia. A total of 5ml of venous blood was withdrawn from all the subjects and serum iron and haemoglobin levels were estimated for all the subjects. Estimation of iron was done using Ferrozine method and haemoglobin by Sahli's method. The statistical method applied were Kruskal Wallis, Mann Whitney and Pearson correlation coefficient test. There was a statistically significant difference in serum iron and haemoglobin level in all three groups (p<0.05). The serum iron level was lowest in OSMF group and haemoglobin was lowest in iron deficiency anaemia group. A progressive decrease in serum iron and haemoglobin levels from Stage I of OSMF to the Stage IV of OSMF was also observed. The iron deficiency anaemia group was not found to be suffering from OSMF in the absence of areca-nut or tobacco chewing habits, but OSMF patients with chewing habits were found to be suffering from iron deficiency anaemia. There is a progressive decrease in serum iron and haemoglobin levels from Stage I of OSMF to the Stage IV of OSMF so it can be used as an auxillary test in assessment of prognosis of the disease.

Characterization and treatment of water used for human consumption from six sources located in the Cameron/Tuba City abandoned uranium mining area.

PubMed

Orescanin, Visnja; Kollar, Robert; Nad, Karlo; Mikelic, Ivanka Lovrencic; Kollar, Iris

2011-01-01

The purpose of this research was the characterization and improvement of the quality of water used for human consumption of unregulated/regulated water sources located in the Cameron/Tuba City abandoned uranium mining area (NE Arizona, western edge of the Navajo Nation). Samples were collected at six water sources which included regulated sources: Wind Mill (Tank 3T-538), Badger Springs and Paddock Well as well as unregulated sources: Willy Spring, Water Wall and Water Hole. Samples taken from Wind Mill, Water Wall and Water Hole were characterized with high turbidity and color as well as high level of manganese, iron and nickel and elevated value of molybdenum. High level of iron was also found in Badger Spring, Willy Spring, and Paddock Well. These three water sources were also characterized with elevated values of fluoride and vanadium. Significant amounts of zinc were found in Water Wall and Water Hole samples. Water Wall sample was also characterized with high level of Cr(VI). Compared to primary or secondary Navajo Nation Environmental Protection Agency (NNEPA) water quality standard the highest enrichment was found for turbidity (50.000 times), color (up to 1.796 times) and manganese (71 times), Cr(VI) (17.5 times), iron (7.4 times) and arsenic (5.2 times). Activities of (226)Ra and (238)U in water samples were still in agreement with the maximum contaminant levels. In order to comply with NNEPA water quality standard water samples were subjected to electrochemical treatment. This method was selected due to its high removal efficiency for heavy metals and uranium, lower settlement time, production of smaller volume of waste mud and higher stability of waste mud compared to physico-chemical treatment. Following the treatment, concentrations of heavy metals and activities of radionuclides in all samples were significantly lower compared to NNEPA or WHO regulated values. The maximum removal efficiencies for color, turbidity, arsenic, manganese, molybdenum and nickel were 100.0%. Maximum removal percentage of Cu, F(-), V, Zn, (137)Cs, (226)Ra, (232)Th, (238)U were as follows: 98.0%; 82.7%; 99.9%; 95.6%; 75.0%; 76.9%; 80.0% and 99.2%. From the results presented it could be concluded that electrochemical treatment is a suitable approach for the purification of drinking water with complex mixture of contaminants, especially those with high turbidity and color.

Differing impact of the deletion of hemochromatosis-associated molecules HFE and transferrin receptor-2 on the iron phenotype of mice lacking bone morphogenetic protein 6 or hemojuvelin.

PubMed

Latour, Chloé; Besson-Fournier, Céline; Meynard, Delphine; Silvestri, Laura; Gourbeyre, Ophélie; Aguilar-Martinez, Patricia; Schmidt, Paul J; Fleming, Mark D; Roth, Marie-Paule; Coppin, Hélène

2016-01-01

Hereditary hemochromatosis, which is characterized by inappropriately low levels of hepcidin, increased dietary iron uptake, and systemic iron accumulation, has been associated with mutations in the HFE, transferrin receptor-2 (TfR2), and hemojuvelin (HJV) genes. However, it is still not clear whether these molecules intersect in vivo with bone morphogenetic protein 6 (BMP6)/mothers against decapentaplegic (SMAD) homolog signaling, the main pathway up-regulating hepcidin expression in response to elevated hepatic iron. To answer this question, we produced double knockout mice for Bmp6 and β2-microglobulin (a surrogate for the loss of Hfe) and for Bmp6 and Tfr2, and we compared their phenotype (hepcidin expression, Bmp/Smad signaling, hepatic and extrahepatic tissue iron accumulation) with that of single Bmp6-deficient mice and that of mice deficient for Hjv, alone or in combination with Hfe or Tfr2. Whereas the phenotype of Hjv-deficient females was not affected by loss of Hfe or Tfr2, that of Bmp6-deficient females was considerably worsened, with decreased Smad5 phosphorylation, compared with single Bmp6-deficient mice, further repression of hepcidin gene expression, undetectable serum hepcidin, and massive iron accumulation not only in the liver but also in the pancreas, the heart, and the kidneys. These results show that (1) BMP6 does not require HJV to transduce signal to hepcidin in response to intracellular iron, even if the loss of HJV partly reduces this signal, (2) another BMP ligand can replace BMP6 and significantly induce hepcidin expression in response to extracellular iron, and (3) BMP6 alone is as efficient at inducing hepcidin as the other BMPs in association with the HJV/HFE/TfR2 complex; they provide an explanation for the compensatory effect of BMP6 treatment on the molecular defect underlying Hfe hemochromatosis in mice. © 2015 by the American Association for the Study of Liver Diseases.

Modelling Systemic Iron Regulation during Dietary Iron Overload and Acute Inflammation: Role of Hepcidin-Independent Mechanisms.

PubMed

Enculescu, Mihaela; Metzendorf, Christoph; Sparla, Richard; Hahnel, Maximilian; Bode, Johannes; Muckenthaler, Martina U; Legewie, Stefan

2017-01-01

Systemic iron levels must be maintained in physiological concentrations to prevent diseases associated with iron deficiency or iron overload. A key role in this process plays ferroportin, the only known mammalian transmembrane iron exporter, which releases iron from duodenal enterocytes, hepatocytes, or iron-recycling macrophages into the blood stream. Ferroportin expression is tightly controlled by transcriptional and post-transcriptional mechanisms in response to hypoxia, iron deficiency, heme iron and inflammatory cues by cell-autonomous and systemic mechanisms. At the systemic level, the iron-regulatory hormone hepcidin is released from the liver in response to these cues, binds to ferroportin and triggers its degradation. The relative importance of individual ferroportin control mechanisms and their interplay at the systemic level is incompletely understood. Here, we built a mathematical model of systemic iron regulation. It incorporates the dynamics of organ iron pools as well as regulation by the hepcidin/ferroportin system. We calibrated and validated the model with time-resolved measurements of iron responses in mice challenged with dietary iron overload and/or inflammation. The model demonstrates that inflammation mainly reduces the amount of iron in the blood stream by reducing intracellular ferroportin transcription, and not by hepcidin-dependent ferroportin protein destabilization. In contrast, ferroportin regulation by hepcidin is the predominant mechanism of iron homeostasis in response to changing iron diets for a big range of dietary iron contents. The model further reveals that additional homeostasis mechanisms must be taken into account at very high dietary iron levels, including the saturation of intestinal uptake of nutritional iron and the uptake of circulating, non-transferrin-bound iron, into liver. Taken together, our model quantitatively describes systemic iron metabolism and generated experimentally testable predictions for additional ferroportin-independent homeostasis mechanisms.

Modelling Systemic Iron Regulation during Dietary Iron Overload and Acute Inflammation: Role of Hepcidin-Independent Mechanisms

PubMed Central

Sparla, Richard; Hahnel, Maximilian; Bode, Johannes; Muckenthaler, Martina U.; Legewie, Stefan

2017-01-01

Systemic iron levels must be maintained in physiological concentrations to prevent diseases associated with iron deficiency or iron overload. A key role in this process plays ferroportin, the only known mammalian transmembrane iron exporter, which releases iron from duodenal enterocytes, hepatocytes, or iron-recycling macrophages into the blood stream. Ferroportin expression is tightly controlled by transcriptional and post-transcriptional mechanisms in response to hypoxia, iron deficiency, heme iron and inflammatory cues by cell-autonomous and systemic mechanisms. At the systemic level, the iron-regulatory hormone hepcidin is released from the liver in response to these cues, binds to ferroportin and triggers its degradation. The relative importance of individual ferroportin control mechanisms and their interplay at the systemic level is incompletely understood. Here, we built a mathematical model of systemic iron regulation. It incorporates the dynamics of organ iron pools as well as regulation by the hepcidin/ferroportin system. We calibrated and validated the model with time-resolved measurements of iron responses in mice challenged with dietary iron overload and/or inflammation. The model demonstrates that inflammation mainly reduces the amount of iron in the blood stream by reducing intracellular ferroportin transcription, and not by hepcidin-dependent ferroportin protein destabilization. In contrast, ferroportin regulation by hepcidin is the predominant mechanism of iron homeostasis in response to changing iron diets for a big range of dietary iron contents. The model further reveals that additional homeostasis mechanisms must be taken into account at very high dietary iron levels, including the saturation of intestinal uptake of nutritional iron and the uptake of circulating, non-transferrin-bound iron, into liver. Taken together, our model quantitatively describes systemic iron metabolism and generated experimentally testable predictions for additional ferroportin-independent homeostasis mechanisms. PMID:28068331

Electroplating wastewater treatment by the combined electrochemical and ozonation methods.

PubMed

Orescanin, Visnja; Kollar, Robert; Mikelic, Ivanka Lovrencic; Nad, Karlo

2013-01-01

This article presents a pilot-plant study of the electroplating wastewater treatment by the processes of electroreduction with iron electrode plates, and electrocoagulation/ozonation with aluminum electrode set, followed by the process of ozonation. The initial effluent was found to be highly enriched in heavy metals and to possess the elevated levels of organic contaminants. The values of Cr(VI), Fe, Ni, Cu, Zn, Pb, TOC, and COD exceeded the upper permissible limits of 63, 220.2, 1.1, 7, 131.3, 1.7, 12.3, and 11.4 times, respectively. The heavy metal removal was forced either by the coagulation/flocculation using Fe(II), Fe(III), and Al(III) ions released into the treated solution by the electrochemical corrosion of the sacrificial iron and aluminum electrodes, or the precipitation of the metal hydroxides as well as co-precipitation with iron and aluminum hydroxides. The principle organic matter destruction mechanisms were ozone oxidation and the indirect oxidation with chlorine/hypochlorite formed by the anodic oxidation of chloride already present in the wastewater. Following the combined treatment, the removal efficiencies of Cr(VI), Fe, Ni, Cu, Zn, Pb, TOC, and COD were 99.94%, 100.00%, 95.86%, 98.66%, 99.97%, 96.81%, 93.24%, and 93.43%, respectively, thus complying with the regulated values.

Spectrophotometric Method for the Determination of Atmospheric Cr Pollution as a Factor to Accelerated Corrosion.

PubMed

Homa, Dereje; Haile, Ermias; Washe, Alemayehu P

2017-01-01

The effect of Cr(VI) pollution on the corrosion rate of corrugated iron roof samples collected from tanning industry areas was investigated through simulated laboratory exposure and spectrophotometric detection of Cr(III) deposit as a product of the reaction. The total level of Cr detected in the samples ranged from 113.892 ± 0.17 ppm to 53.05 ± 0.243 ppm and showed increasing trend as sampling sites get closer to the tannery and in the direction of tannery effluent stream. The laboratory exposure of a newly manufactured material to a simulated condition showed a relatively faster corrosion rate in the presence of Cr(VI) with concomitant deposition of Cr(III) under pH control. A significant ( P = 0.05) increase in the corrosion rate was also recorded when exposing scratched or stress cracked samples. A coupled redox process where Cr(VI) is reduced to a stable, immobile, and insoluble Cr(III) accompanying corrosion of the iron is proposed as a possible mechanism leading to the elevated deposition of the latter on the materials. In conclusion, the increased deposits of Cr detected in the corrugated iron roof samples collected from tanning industry zones suggested possible atmospheric Cr pollution as a factor to the accelerated corrosion of the materials.

Enhanced lipid accumulation and biodiesel production by oleaginous Chlorella protothecoides under a structured heterotrophic-iron (II) induction strategy.

PubMed

Li, Yuqin; Mu, Jinxiu; Chen, Di; Xu, Hua; Han, Fangxin

2015-05-01

A structured heterotrophic-iron (II) induction (HII) strategy was proposed to enhance lipid accumulation in oleaginous Chlorella protothecoides. C. protothecoides subjected to heterotrophic-iron (II) induction achieved a favorable lipid accumulation up to 62 % and a maximum lipid productivity of 820.17 mg/day, representing 2.78-fold and 3.64-fold increase respectively over heterotrophic cultivation alone. HII-induced cells produced significantly elevated levels of 16:0, 18:1(Δ9), and 18:2(Δ9,12) fatty acids (over 90 %). The lipid contents and plant lipid-like fatty acid compositions exhibit the potential of HII-induced C. protothecoides as biodiesel feedstock. Furthermore, 31 altered proteins in HII-induced algal cells were successfully identified. These differentially expressed proteins were assigned into nine molecular function categories, including carbohydrate metabolism, lipid biosynthesis, Calvin cycle, cellular respiration, photosynthesis, energy and transport, protein biosynthesis, regulate and defense, and unclassified. Analysis using the Kyoto encyclopedia of genes and genomes and gene ontology annotation showed that malic enzyme, acyltransferase, and ACP were key metabolic checkpoints found to modulate lipid accumulation in C. protothecoides. The results provided possible applications of HII cultivation strategy in other microalgal species and new possibilities in developing genetic and metabolic engineering microalgae for desirable lipid productivity.

Atmospheric carbon dioxide concentrations before 2.2 billion years ago

NASA Technical Reports Server (NTRS)

Rye, R.; Kuo, P. H.; Holland, H. D.

1995-01-01

The composition of the Earth's early atmosphere is a subject of continuing debate. In particular, it has been suggested that elevated concentrations of atmospheric carbon dioxide would have been necessary to maintain normal surface temperatures in the face of lower solar luminosity in early Earth history. Fossil weathering profiles, known as palaeosols, have provided semi-quantitative constraints on atmospheric oxygen partial pressure (pO2) before 2.2 Gyr ago. Here we use the same well studied palaeosols to constrain atmospheric pCO2 between 2.75 and 2.2 Gyr ago. The observation that iron lost from the tops of these profiles was reprecipitated lower down as iron silicate minerals, rather than as iron carbonate, indicates that atmospheric pCO2 must have been less than 10(-1.4) atm--about 100 times today's level of 360 p.p.m., and at least five times lower than that required in one-dimensional climate models to compensate for lower solar luminosity at 2.75 Gyr. Our results suggest that either the Earth's early climate was much more sensitive to increases in pCO2 than has been thought, or that one or more greenhouse gases other than CO2 contributed significantly to the atmosphere's radiative balance during the late Archaean and early Proterozoic eons.

The diacylglycerol acyltransferase Rv3371 of Mycobacterium tuberculosis is required for growth arrest and involved in stress-induced cell wall alterations.

PubMed

Rastogi, Shivangi; Singh, Amit Kumar; Chandra, Gyan; Kushwaha, Pragati; Pant, Garima; Singh, Kavita; Mitra, Kalyan; Sashidhara, Koneni V; Krishnan, Manju Y

2017-05-01

Triacylglycerol (TAG) is important to mycobacteria both as cell envelope component and energy reservoir. Mycobacterium tuberculosis (Mtb) genome encodes at least 15 putative TAG synthase (tgs)s. We report that one of these genes, Rv3371, specific to pathogenic mycobacteria, when expressed in M. smegmatis leads to modifications in colony morphotype, bacterial architecture, cell surface properties and elevated TAG levels. Rv3371 was found to largely localize in the cell membrane. The Rv3371 promoter is minimally active during exponential growth in vitro, however, is up-regulated under stationary phase, hypoxia, nutrient starvation, nitrosative stress, low iron, in IFN-γ activated macrophages and infected mice. The low iron-induced expression of Rv3371 is likely due to the de-repression by Rv1404, which is probably activated by ideR. An Rv3371 deletion mutant of Mtb showed impaired non-replicating persistence in vitro and altered sensitivity to anti-mycobacterial drugs. In low iron medium, the Rv3371 deletion mutant showed reduced formation of TAG containing extracellular vesicles. Therefore Rv3371 is likely involved in Mtb growth arrest and cell wall alterations during persistence. Copyright © 2017 Elsevier Ltd. All rights reserved.

Spectrophotometric Method for the Determination of Atmospheric Cr Pollution as a Factor to Accelerated Corrosion

PubMed Central

Homa, Dereje; Haile, Ermias

2017-01-01

The effect of Cr(VI) pollution on the corrosion rate of corrugated iron roof samples collected from tanning industry areas was investigated through simulated laboratory exposure and spectrophotometric detection of Cr(III) deposit as a product of the reaction. The total level of Cr detected in the samples ranged from 113.892 ± 0.17 ppm to 53.05 ± 0.243 ppm and showed increasing trend as sampling sites get closer to the tannery and in the direction of tannery effluent stream. The laboratory exposure of a newly manufactured material to a simulated condition showed a relatively faster corrosion rate in the presence of Cr(VI) with concomitant deposition of Cr(III) under pH control. A significant (P = 0.05) increase in the corrosion rate was also recorded when exposing scratched or stress cracked samples. A coupled redox process where Cr(VI) is reduced to a stable, immobile, and insoluble Cr(III) accompanying corrosion of the iron is proposed as a possible mechanism leading to the elevated deposition of the latter on the materials. In conclusion, the increased deposits of Cr detected in the corrugated iron roof samples collected from tanning industry zones suggested possible atmospheric Cr pollution as a factor to the accelerated corrosion of the materials. PMID:28469950

The iron chelator Dp44mT inhibits the proliferation of cancer cells but fails to protect from doxorubicin-induced cardiotoxicity in spontaneously hypertensive rats.

PubMed

Rao, V Ashutosh; Zhang, Jun; Klein, Sarah R; Espandiari, Parvaneh; Knapton, Alan; Dickey, Jennifer S; Herman, Eugene; Shacter, Emily B

2011-11-01

The iron chelator Dp44mT is a potent topoisomerase IIα inhibitor with novel anticancer activity. Doxorubicin (Dox), the current front-line therapy for breast cancer, induces a dose-limiting cardiotoxicity, in part through an iron-mediated pathway. We tested the hypothesis that Dp44mT can improve clinical outcomes of treatment with Dox by alleviating cardiotoxicity. The general cardiac and renal toxicities induced by Dox were investigated in the presence and absence of Dp44mT. The iron chelating cardioprotectant Dexrazoxane (Drz), which is approved for this indication, was used as a positive control. In vitro studies were carried out with H9c2 rat cardiomyocytes and in vivo studies were performed using spontaneously hypertensive rats. Testing of the GI(50) profile of Dp44mT in the NCI-60 panel confirmed activity against breast cancer cells. An acute, toxic dose of Dox caused the predicted cellular and cardiac toxicities, such as cell death and DNA damage in vitro and elevated cardiac troponin T levels, tissue damage, and apoptosis in vivo. Dp44mT alone caused insignificant changes in hematological and biochemical indices in rats, indicating that Dp44mT is not significantly cardiotoxic as a single agent. In contrast to Drz, Dp44mT failed to mitigate Dox-induced cardiotoxicity in vivo. We conclude that although Dp44mT is a potent iron chelator, it is unlikely to be an appropriate cardioprotectant against Dox-induced toxicity. However, it should continue to be evaluated as a potential anticancer agent as it has a novel mechanism for inhibiting the growth of a broad range of malignant cell types while exhibiting very low intrinsic toxicity to healthy tissues.

The Bradyrhizobium japonicum Ferrous Iron Transporter FeoAB Is Required for Ferric Iron Utilization in Free Living Aerobic Cells and for Symbiosis.

PubMed

Sankari, Siva; O'Brian, Mark R

2016-07-22

The bacterium Bradyrhizobium japonicum USDA110 does not synthesize siderophores for iron utilization in aerobic environments, and the mechanism of iron uptake within symbiotic soybean root nodules is unknown. An mbfA bfr double mutant defective in iron export and storage activities cannot grow aerobically in very high iron medium. Here, we found that this phenotype was suppressed by loss of function mutations in the feoAB operon encoding ferrous (Fe(2+)) iron uptake proteins. Expression of the feoAB operon genes was elevated under iron limitation, but mutants defective in either gene were unable to grow aerobically over a wide external ferric (Fe(3+)) iron (FeCl3) concentration range. Thus, FeoAB accommodates iron acquisition under iron limited and iron replete conditions. Incorporation of radiolabel from either (55)Fe(2+) or (59)Fe(3+) into cells was severely defective in the feoA and feoB strains, suggesting Fe(3+) reduction to Fe(2+) prior to traversal across the cytoplasmic membrane by FeoAB. The feoA or feoB deletion strains elicited small, ineffective nodules on soybean roots, containing few bacteria and lacking nitrogen fixation activity. A feoA(E40K) mutant contained partial iron uptake activity in culture that supported normal growth and established an effective symbiosis. The feoA(E40K) strain had partial iron uptake activity in situ within nodules and in isolated cells, indicating that FeoAB is the iron transporter in symbiosis. We conclude that FeoAB supports iron acquisition under limited conditions of soil and in the iron-rich environment of a symbiotic nodule. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

High-Iron Consumption Impairs Growth and Causes Copper-Deficiency Anemia in Weanling Sprague-Dawley Rats

PubMed Central

Ha, Jung-Heun; Doguer, Caglar; Wang, Xiaoyu; Flores, Shireen R.; Collins, James F.

2016-01-01

Iron-copper interactions were described decades ago; however, molecular mechanisms linking the two essential minerals remain largely undefined. Investigations in humans and other mammals noted that copper levels increase in the intestinal mucosa, liver and blood during iron deficiency, tissues all important for iron homeostasis. The current study was undertaken to test the hypothesis that dietary copper influences iron homeostasis during iron deficiency and iron overload. We thus fed weanling, male Sprague-Dawley rats (n = 6-11/group) AIN-93G-based diets containing high (~8800 ppm), adequate (~80) or low (~11) iron in combination with high (~183), adequate (~8) or low (~0.9) copper for 5 weeks. Subsequently, the iron- and copper-related phenotype of the rats was assessed. Rats fed the low-iron diets grew slower than controls, with changes in dietary copper not further influencing growth. Unexpectedly, however, high-iron (HFe) feeding also impaired growth. Furthermore, consumption of the HFe diet caused cardiac hypertrophy, anemia, low serum and tissue copper levels and decreased circulating ceruloplasmin activity. Intriguingly, these physiologic perturbations were prevented by adding extra copper to the HFe diet. Furthermore, higher copper levels in the HFe diet increased serum nonheme iron concentration and transferrin saturation, exacerbated hepatic nonheme iron loading and attenuated splenic nonheme iron accumulation. Moreover, serum erythropoietin levels, and splenic erythroferrone and hepatic hepcidin mRNA levels were altered by the dietary treatments in unanticipated ways, providing insight into how iron and copper influence expression of these hormones. We conclude that high-iron feeding of weanling rats causes systemic copper deficiency, and further, that copper influences the iron-overload phenotype. PMID:27537180

Does Iron Supplementation Improve Performance in Iron-Deficient Nonanemic Athletes?

PubMed

Rubeor, Amity; Goojha, Carmen; Manning, Jeffrey; White, Jordan

2018-05-01

Supplementing iron-deficient nonanemic (IDNA) athletes with iron to improve performance is a trend in endurance sports. To investigate the benefits of iron on performance, identify a ferritin level cutoff in IDNA athletes, and determine which iron supplementation regimens are most effective. A search of the PubMed, CINAHL, Embase, ERIC, and Cochrane databases was performed in 2014 including all articles. Citations of pertinent review articles were also searched. In 2017, the search was repeated. Inclusion criteria comprised studies of level 1 to 3 evidence, written in the English language, that researched iron supplementation in nonanemic athletes and reported performance outcomes. Systematic review. Level 3. The search terms used included athletic performance, resistance training, athletes, physical endurance, iron, iron deficiency, supplement, non-anemic, low ferritin, ferritin, ferritin blood level, athletes, and sports. A total of 1884 studies were identified through the initial database search, and 13 were identified through searching references of relevant review articles. A subsequent database search identified 46 studies. Following exclusions, 12 studies with a total of 283 participants were included. Supplementing IDNA athletes with iron improved performance in 6 studies (146 participants) and did not improve performance in the other 6 studies (137 participants). In the 6 studies that showed improved performance with iron supplementation, all used a ferritin level cutoff of ≤20 μg/L for treatment. Additionally, all studies that showed improved performance used oral iron as a supplement. The evidence is equivocal as to whether iron supplementation in IDNA athletes improves athletic performance. Supplementing athletes with ferritin levels <20 μg/L may be more beneficial than supplementing athletes with higher baseline ferritin levels.

Increase in type II collagen turnover after iron depletion in patients with hereditary haemochromatosis.

PubMed

Richette, Pascal; Eymard, Claire; Deberg, Michelle; Vidaud, Dominique; de Kerguenec, Caroline; Valla, Dominique; Vicaut, Eric; Bardin, Thomas; Henrotin, Yves

2010-04-01

To determine the effects of iron depletion on serum levels of joint biomarkers and on joint symptoms in patients with hereditary haemochromatosis (HH). Levels of biomarkers were measured in 18 patients with HH at the time of diagnosis and after iron depletion. The markers were type II collagen degradation (Coll2-1) and its nitrated form (Coll2-1NO(2)), type II procollagen synthesis (CPII), MPO, COMP and HA. For each patient, demographic data were collected and the global joint pain (visual analogue scale) was assessed before and after iron depletion by phlebotomy. A total of 18 patients [10 males; mean (s.d.) age 48 (11) years] were homozygous for the C282Y mutation. No patient had liver dysfunction. Ferritin level before iron removal was 627.5 (range 133-3276) microg/l, and duration of the iron depletion phase was 295 (70-670) days. Serum levels of both Coll2-1 and CPII were significantly increased from diagnosis after iron depletion: 80.1 (55.6-113.5) vs 96.0 (48.8-136.3) nM (P = 0.004) and 731.4 (374.2-1012.3) vs 812.8 (535.8-1165.6) ng/ml (P = 0.03), respectively. Levels of other biomarkers were not modified by iron depletion. Ferritin level, which at baseline was correlated with body iron store (r = 0.63; P = 0.008), was significantly correlated with HA level measured before iron depletion (r = 0.60; P = 0.01). Global joint pain was not correlated with ferritin concentration and did not significantly decrease after iron depletion: 43 (19-73) vs 36 (16-67) mm (P = 0.07). In patients with HH, cartilage homoeostasis is modified by iron excess and an increase in type II collagen turnover occurs after excess iron removal.

An unusual case of iron deficiency anemia is associated with extremely low level of transferrin receptor.

PubMed

Hao, Shuangying; Li, Huihui; Sun, Xiaoyan; Li, Juan; Li, Kuanyu

2015-01-01

A case study of a female patient, diagnosed with iron deficiency anemia, was unresponsive to oral iron treatment and only partially responsive to parenteral iron therapy, a clinical profile resembling the iron-refractory iron deficiency anemia (IRIDA) disorder. However, the patient failed to exhibit microcytic phenotype, one of the IRIDA hallmarks. Biochemical assays revealed that serum iron, hepcidin, interluekin 6, and transferrin saturation were within the normal range of references or were comparable to her non-anemic offspring. Iron contents in serum and red blood cells and hemoglobin levels were measured, which confirmed the partial improvement of anemia after parenteral iron therapy. Strikingly, serum transferrin receptor in patient was almost undetectable, reflecting the very low activity of bone-marrow erythropoiesis. Our data demonstrate that this is not a case of systemic iron deficiency, but rather cellular iron deficit due to the low level of transferrin receptor, particularly in erythroid tissue.

Application of the Systems Impact Assessment Model (SIAM) to Fishery Resource Issues in the Klamath River, California

USGS Publications Warehouse

Campbell, Sharon G.; Bartholow, John M.; Heasley, John

2010-01-01

At the request of two offices of the U.S. Fish and Wildlife Service (FWS) located in Yreka and Arcata, Calif., we applied the Systems Impact Assessment Model (SIAM) to analyze a variety of water management concerns associated with the Federal Energy Regulatory Commission (FERC) relicensing of the Klamath hydropower projects or with ongoing management of anadromous fish stocks in the mainstem Klamath River, Oregon and California. Requested SIAM analyses include predicted effects of reservoir withdrawal elevations, use of full active storage in Copco and Iron Gate Reservoirs to augment spring flows, and predicted spawning and juvenile outmigration timing of fall Chinook salmon. In an effort to further refine the analysis of spring flow effects on predicted fall Chinook production, additional SIAM analyses were performed for predicted response to spring flow release variability from Iron Gate Dam, high and low pulse flow releases, the predicted effects of operational constraints for both Upper Klamath Lake water surface elevations, and projected flow releases specified in the Klamath Project 2006 Operations Plan (April 10, 2006). Results of SIAM simulations to determine flow and water temperature relationships indicate that up to 4 degrees C of thermal variability can be attributed to flow variations, but the effect is seasonal. Much more of thermal variability can be attributed to air temperature variations, up to 6 degrees C. Reservoirs affect the annual thermal signature by delaying spring warming by about 3 weeks and fall cooling by about 2 weeks. Multi-level release outlets on Iron Gate Dam would have limited utility; however, if releases are small (700 cfs) and a near-surface and bottom-level outlet could be blended, then water temperature may be reduced by 2-4 degrees C for a 4-week period during September. Using the full active storage in Copco and Iron Gate Reservoir, although feasible, had undesirable ramifications such as earlier spring warming, loss of hydropower production, and inability to re-fill the reservoirs without causing shortages elsewhere in the system. Altering spawning and outmigration timing may be important management objectives for the salmon fishery, but difficult to implement. SIAM predicted benefits that might occur if water temperature was cooler in fall and spring emergence was advanced; however, model simulations were based on purely arbitrary thermal reductions. Spring flow variability did indicate that juvenile fall Chinook rearing habitat was the major biological 'bottleneck' for year class success. Rearing habitat is maximal in a range between 4,500 and 5,500 cfs below Iron Gate Dam. These flow levels are not typically provided by Klamath River system operations, except in very wet years. The incremental spring flow analysis provided insight into when and how long a pulse flow should occur to provide predicted fall Chinook salmon production increases. In general, March 15th - April 30th of any year was the period for pulse flows and 4000 cfs was the target flow release that provided near-optimal juvenile rearing habitat. Again, competition for water resources in the Klamath River Basin may make implementation of pulsed flows difficult.

Iron-overload injury and cardiomyopathy in acquired and genetic models is attenuated by resveratrol therapy.

PubMed

Das, Subhash K; Wang, Wang; Zhabyeyev, Pavel; Basu, Ratnadeep; McLean, Brent; Fan, Dong; Parajuli, Nirmal; DesAulniers, Jessica; Patel, Vaibhav B; Hajjar, Roger J; Dyck, Jason R B; Kassiri, Zamaneh; Oudit, Gavin Y

2015-12-07

Iron-overload cardiomyopathy is a prevalent cause of heart failure on a world-wide basis and is a major cause of mortality and morbidity in patients with secondary iron-overload and genetic hemochromatosis. We investigated the therapeutic effects of resveratrol in acquired and genetic models of iron-overload cardiomyopathy. Murine iron-overload models showed cardiac iron-overload, increased oxidative stress, altered Ca(2+) homeostasis and myocardial fibrosis resulting in heart disease. Iron-overload increased nuclear and acetylated levels of FOXO1 with corresponding inverse changes in SIRT1 levels in the heart corrected by resveratrol therapy. Resveratrol, reduced the pathological remodeling and improved cardiac function in murine models of acquired and genetic iron-overload at varying stages of iron-overload. Echocardiography and hemodynamic analysis revealed a complete normalization of iron-overload mediated diastolic and systolic dysfunction in response to resveratrol therapy. Myocardial SERCA2a levels were reduced in iron-overloaded hearts and resveratrol therapy restored SERCA2a levels and corrected altered Ca(2+) homeostasis. Iron-mediated pro-oxidant and pro-fibrotic effects in human and murine cardiomyocytes and cardiofibroblasts were suppressed by resveratrol which correlated with reduction in iron-induced myocardial oxidative stress and myocardial fibrosis. Resveratrol represents a clinically and economically feasible therapeutic intervention to reduce the global burden from iron-overload cardiomyopathy at early and chronic stages of iron-overload.

Iron-overload injury and cardiomyopathy in acquired and genetic models is attenuated by resveratrol therapy

PubMed Central

Das, Subhash K.; Wang, Wang; Zhabyeyev, Pavel; Basu, Ratnadeep; McLean, Brent; Fan, Dong; Parajuli, Nirmal; DesAulniers, Jessica; Patel, Vaibhav B.; Hajjar, Roger J.; Dyck, Jason R. B.; Kassiri, Zamaneh; Oudit, Gavin Y.

2015-01-01

Iron-overload cardiomyopathy is a prevalent cause of heart failure on a world-wide basis and is a major cause of mortality and morbidity in patients with secondary iron-overload and genetic hemochromatosis. We investigated the therapeutic effects of resveratrol in acquired and genetic models of iron-overload cardiomyopathy. Murine iron-overload models showed cardiac iron-overload, increased oxidative stress, altered Ca2+ homeostasis and myocardial fibrosis resulting in heart disease. Iron-overload increased nuclear and acetylated levels of FOXO1 with corresponding inverse changes in SIRT1 levels in the heart corrected by resveratrol therapy. Resveratrol, reduced the pathological remodeling and improved cardiac function in murine models of acquired and genetic iron-overload at varying stages of iron-overload. Echocardiography and hemodynamic analysis revealed a complete normalization of iron-overload mediated diastolic and systolic dysfunction in response to resveratrol therapy. Myocardial SERCA2a levels were reduced in iron-overloaded hearts and resveratrol therapy restored SERCA2a levels and corrected altered Ca2+ homeostasis. Iron-mediated pro-oxidant and pro-fibrotic effects in human and murine cardiomyocytes and cardiofibroblasts were suppressed by resveratrol which correlated with reduction in iron-induced myocardial oxidative stress and myocardial fibrosis. Resveratrol represents a clinically and economically feasible therapeutic intervention to reduce the global burden from iron-overload cardiomyopathy at early and chronic stages of iron-overload. PMID:26638758

Controversy on iron needs, intake levels, deficiency stigmata and benefits from iron supplementation

PubMed Central

Walker, Alexander R. P.

1969-01-01

At present there is considerable controversy over many aspects of iron nutrition, including: (1) iron needs and intake levels; (2) the bearing of iron intake on haematological levels; (3) iron deficiency anaemia and deficiency stigmata; and (4) iron therapy, prophylaxis, and the haematological and clinical benefits accruing. Differences of opinion prevail because of inadequacies of knowledge of the level of haemoglobin (or other parameter of iron status) below which unequivocal signs and symptoms of ill-health become manifest in the major proportion of those affected. Difficulties arise equally from lack of knowledge of the level of haemoglobin above which no clinical benefit, short-term or long-term, can be detected from iron supplementation. Clarification of the situation can be obtained only by carrying out the same meticulous and time-consuming procedures that have been used in respect of requirements and deficiency stigmata of other nutrients. Comprehensive iron depletion studies, real and simulated, and repletion studies, including the use of placebos, will be required. Epidemiological investigations bearing on haematological status and morbidity will also need to be undertaken, and include groups of subjects in both Western, and developing countries. PMID:4905446

Corrosion resistant coatings suitable for elevated temperature application

DOEpatents

Chan, Kwai S [San Antonio, TX; Cheruvu, Narayana Sastry [San Antonio, TX; Liang, Wuwei [Austin, TX

2012-07-31

The present invention relates to corrosion resistance coatings suitable for elevated temperature applications, which employ compositions of iron (Fe), chromium (Cr), nickel (Ni) and/or aluminum (Al). The compositions may be configured to regulate the diffusion of metals between a coating and a substrate, which may then influence coating performance, via the formation of an inter-diffusion barrier layer. The inter-diffusion barrier layer may comprise a face-centered cubic phase.

18. DETAIL ELEVATION OF STAMP BATTERIES AND APRONS, LOOKING SOUTHEAST. ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

18. DETAIL ELEVATION OF STAMP BATTERIES AND APRONS, LOOKING SOUTHEAST. MORTARS, BOSSES, MOST SHOES, STEMS, TAPPETS, CAMS AND BULL WHEELS ARE CLEARLY VISIBLE AND INTACT. NAMEPLATE CASTING IS CLEARLY VISIBLE ON THE UPPER MORTAR BLOCKS (BELOW CENTER) UNION IRON WORKS, SAN FRANCISCO C-L, SEE CA-290-45 (CT) FOR A SIMILAR COLOR TRANSPARENCY. - Skidoo Mine, Park Route 38 (Skidoo Road), Death Valley Junction, Inyo County, CA

Iron Biofortification and Homeostasis in Transgenic Cassava Roots Expressing the Algal Iron Assimilatory Gene, FEA1

PubMed Central

Ihemere, Uzoma E.; Narayanan, Narayanan N.; Sayre, Richard T.

2012-01-01

We have engineered the tropical root crop cassava (Manihot esculenta) to express the Chlamydomonas reinhardtii iron assimilatory gene, FEA1, in its storage roots with the objective of enhancing the root nutritional qualities. Iron levels in mature cassava storage roots were increased from 10 to 36 ppm in the highest iron accumulating transgenic lines. These iron levels are sufficient to meet the minimum daily requirement for iron in a 500 g meal. Significantly, the expression of the FEA1 gene in storage roots did not alter iron levels in leaves. Transgenic plants also had normal levels of zinc in leaves and roots consistent with the specific uptake of ferrous iron mediated by the FEA1 protein. Relative to wild-type plants, fibrous roots of FEA1 expressing plants had reduced Fe (III) chelate reductase activity consistent with the more efficient uptake of iron in the transgenic plants. We also show that multiple cassava genes involved in iron homeostasis have altered tissue-specific patterns of expression in leaves, stems, and roots of transgenic plants consistent with increased iron sink strength in transgenic roots. These results are discussed in terms of strategies for the iron biofortification of plants. PMID:22993514

Hypobaric Hypoxia Regulates Brain Iron Homeostasis in Rats.

PubMed

Li, Yaru; Yu, Peng; Chang, Shi-Yang; Wu, Qiong; Yu, Panpan; Xie, Congcong; Wu, Wenyue; Zhao, Baolu; Gao, Guofen; Chang, Yan-Zhong

2017-06-01

Disruption of iron homeostasis in brain has been found to be closely involved in several neurodegenerative diseases. Recent studies have reported that appropriate intermittent hypobaric hypoxia played a protective role in brain injury caused by acute hypoxia. However, the mechanisms of this protective effect have not been fully understood. In this study, Sprague-Dawley (SD) rat models were developed by hypobaric hypoxia treatment in an altitude chamber, and the iron level and iron related protein levels were determined in rat brain after 4 weeks of treatment. We found that the iron levels significantly decreased in the cortex and hippocampus of rat brain as compared to that of the control rats without hypobaric hypoxia treatment. The expression levels of iron storage protein L-ferritin and iron transport proteins, including transferrin receptor-1 (TfR1), divalent metal transporter 1 (DMT1), and ferroportin1 (FPN1), were also altered. Further studies found that the iron regulatory protein 2 (IRP2) played a dominant regulatory role in the changes of iron hemostasis, whereas iron regulatory protein 1 (IRP1) mainly acted as cis-aconitase. These results, for the first time, showed the alteration of iron metabolism during hypobaric hypoxia in rat models, which link the potential neuroprotective role of hypobaric hypoxia treatment to the decreased iron level in brain. This may provide insight into the treatment of iron-overloaded neurodegenerative diseases. J. Cell. Biochem. 118: 1596-1605, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Water-quality assessment of the upper Illinois River Basin in Illinois, Indiana, and Wisconsin; major and trace elements in water, sediment, and biota, 1978-90

USGS Publications Warehouse

Fitzpatrick, F.A.; Scudder, B.C.; Crawford, J.K.; Schmidt, A.R.; Sieverling, J.B.

1995-01-01

The distribution of 22 major and trace elements was examined in water, sediment, and biota in the upper Illinois River Basin in Illinois, Indiana, and Wisconsin as part of a pilot National Water-Quality Assessment project done by the U.S. Geological Survey from 1987 through 1990. The 22 elements are aluminum, antimony, arsenic, barium, beryllium, boron, cadmium, chromium, cobalt, copper, iron, lead, manganese, mercury, molybdenum, nickel, phosphorus, selenium, silver, strontium, vanadium, and zinc. Concentrations of U.S. Environmental Protection Agency (USEPA) priority pollutants among the 22 elements were elevated in the Chicago area in all three aquatic components (water, sediment, and biota). Further, some of the priority pollutants also were found at elevated concentrations in biota in agricultural areas in the basin. Cadmium, chromium, copper, iron, lead, mercury, silver, and zinc concentrations in water exceeded USEPA acute or chronic water-quality criteria at several sites in the Chicago area. Correlations among concentra- tions of elements in water, sediment, and biota were found, but the correlation analysis was hindered by the large proportion of observations less than the minimum reporting level in water. Those sites where water-quality criteria were sometimes exceeded were not always the same sites where concentrations in biota were the largest. This relation indicates that accumulation of these pollutants in biota is confounded by complex geochemical and biological processes that differ throughout the upper Illinois River Basin.

LIVER ULTRASONOGRAPHY IN DOLPHINS: USE OF ULTRASONOGRAPHY TO ESTABLISH A TECHNIQUE FOR HEPATOBILIARY IMAGING AND TO EVALUATE METABOLIC DISEASE-ASSOCIATED LIVER CHANGES IN BOTTLENOSE DOLPHINS (TURSIOPS TRUNCATUS).

PubMed

Seitz, Kelsey E; Smith, Cynthia R; Marks, Stanley L; Venn-Watson, Stephanie K; Ivančić, Marina

2016-12-01

The objective of this study was to establish a comprehensive technique for ultrasound examination of the dolphin hepatobiliary system and apply this technique to 30 dolphins to determine what, if any, sonographic changes are associated with blood-based indicators of metabolic syndrome (insulin greater than 14 μIU/ml or glucose greater than 112 mg/dl) and iron overload (transferrin saturation greater than 65%). A prospective study of individuals in a cross-sectional population with and without elevated postprandial insulin levels was performed. Twenty-nine bottlenose dolphins ( Tursiops truncatus ) in a managed collection were included in the final data analysis. An in-water ultrasound technique was developed that included detailed analysis of the liver and pancreas. Dolphins with hyperinsulinemia concentrations had larger livers compared with dolphins with nonelevated concentrations. Using stepwise, multivariate regression including blood-based indicators of metabolic syndrome in dolphins, glucose was the best predictor of and had a positive linear association with liver size (P = 0.007, R 2 = 0.24). Bottlenose dolphins are susceptible to metabolic syndrome and associated complications that affect the liver, including fatty liver disease and iron overload. This study facilitated the establishment of a technique for a rapid, diagnostic, and noninvasive ultrasonographic evaluation of the dolphin liver. In addition, the study identified ultrasound-detectable hepatic changes associated primarily with elevated glucose concentration in dolphins. Future investigations will strive to detail the pathophysiological mechanisms for these changes.

Effects of Iron Supplementation and Activity on Serum Iron Depletion and Hemoglobin Levels in Female Athletes

ERIC Educational Resources Information Center

Cooter, G. Rankin; Mowbray, Kathy W.

1978-01-01

Research revealed that a four-month basketball training program did not significantly alter serum iron, total iron binding capacity, hemoglobin, and percent saturation levels in female basketball athletes. (JD)

Serum Iron and Haemoglobin Estimation in Oral Submucous Fibrosis and Iron Deficiency Anaemia: A Diagnostic Approach

PubMed Central

Dinkar, Ajit D; Satoskar, Sujata K; Desai, Sapna Raut

2016-01-01

Introduction Oral Submucous Fibrosis (OSMF) is a premalignant condition with potential malignant behaviour characterized by juxta-epithelial fibrosis of the oral cavity. In the process of collagen synthesis, iron gets utilized, by the hydroxylation of proline and lysine, leading to decreased serum iron levels. The trace element like iron is receiving much attention in the detection of oral cancer and precancerous condition like OSMF as it was found to be significantly altered in these conditions. Aim The aim of this study was to compare the haemoglobin and serum iron values of OSMF subjects with that of iron deficiency anaemia subjects. Materials and Methods Total of 120 subjects were included, 40 subjects with the OSMF, 40 with the iron deficiency anemia without tobacco chewing habit, 40 healthy control subjects without OSMF and iron deficiency anaemia. A total of 5ml of venous blood was withdrawn from all the subjects and serum iron and haemoglobin levels were estimated for all the subjects. Estimation of iron was done using Ferrozine method and haemoglobin by Sahli’s method. The statistical method applied were Kruskal Wallis, Mann Whitney and Pearson correlation coefficient test. Results There was a statistically significant difference in serum iron and haemoglobin level in all three groups (p<0.05). The serum iron level was lowest in OSMF group and haemoglobin was lowest in iron deficiency anaemia group. A progressive decrease in serum iron and haemoglobin levels from Stage I of OSMF to the Stage IV of OSMF was also observed. The iron deficiency anaemia group was not found to be suffering from OSMF in the absence of areca-nut or tobacco chewing habits, but OSMF patients with chewing habits were found to be suffering from iron deficiency anaemia. Conclusion There is a progressive decrease in serum iron and haemoglobin levels from Stage I of OSMF to the Stage IV of OSMF so it can be used as an auxillary test in assessment of prognosis of the disease. PMID:28209005

Prevalence of unexplained anaemia in Inuit men and Inuit post-menopausal women in Northern Labrador: International Polar Year Inuit Health Survey.

PubMed

Jamieson, Jennifer A; Weiler, Hope A; Kuhnlein, Harriet V; Egeland, Grace M

2016-06-27

To identify correlates of hemoglobin (Hb) and anaemia unexplained by iron deficiency (UA) in Canadian Inuit adults. A cross-sectional survey assessed diet, demographic information, anthropometry, fasting Hb, ferritin, soluble transferrin receptor (on a subset), high-sensitivity C-reactive protein (hs-CRP) in serum, red blood cell (RBC) fatty acid composition, blood lead, and antibodies to Helicobacter pylori in non-pregnant, Inuit adults (n = 2550), ≥18 years of age from randomly selected households in 36 Inuit communities in Inuvialuit Settlement Region, Nunavut Territory and Nunatsiavut of Northern Labrador, Canada. Hb concentrations were lower and UA prevalence higher in Inuit men after 50 years of age. Rate of anaemia was constant among Inuit women but changed from primarily iron deficiency anaemia pre-menopause, to primarily UA in post-menopause. Low education levels and hs-CRP were associated with increased risk of UA. For Inuit men, % RBC eicosapentaenoic acid (EPA) and elevated blood lead were also associated with increased risk of UA. Frequency of traditional food intake was positively associated with Hb. Age patterns and regional variation of anaemia suggest that ethnicity-related physiological differences cannot explain anaemia prevalence for Inuit. High RBC EPA status, inflammation and infections, and lower education levels may contribute to the prevalence of anaemia in this population, which is not related to iron status. Thus, traditional lifestyle may protect Inuit from nutritional anaemia but contribute to lower Hb through environmental exposures. The clinical significance of UA for older Inuit adults requires further investigation, as the prevalence represents a moderate public health problem.

Seasonal and spatial variations in microbial activity at various phylogenetic resolutions at a groundwater - surface water interface.

PubMed

Yu, Ran; Smets, Barth F; Gan, Ping; MacKay, Allison A; Graf, Joerg

2014-05-01

We investigated the seasonal and spatial variation in activity and density of the metabolically active in situ microbial community (AIMC) at a landfill leachate-impacted groundwater - surface water interface (GSI). A series of AIMC traps were designed and implemented for AIMC sampling and microbial activity and density examinations. Measurements were made not only at the level of bacterial domain but also at the levels of alphaproteobacterial Rhizobiales order and gammaproteobacterial Pseudomonas genus, both of which included a large number of iron-oxidizing bacteria as revealed from previous analysis. Consistently higher microbial activities with less variation in depth were measured in the AIMC traps than in the ambient sediments. Flood disturbance appeared to control AIMC activity distributions at the gradually elevated GSI. The highest AIMC activities were generally obtained from locations closest to the free surface water boundary except during the dry season when microbial activities were similar across the entire GSI. A clone library of AIMC 16S rRNA genes was constructed, and it confirmed the predominant role of the targeted alphaproteobacterial group in AIMC activity and composition. This taxon constituted 2%-14% of all bacteria with similar activity distribution profiles. The Pseudomonas group occupied only 0.1‰-0.5‰ of the total bacterial density, but its activity was 27 times higher than the bacterial average. Of the 16S rRNA sequences in the AIMC clone library, 7.5% were phylogenetically related to putative IOB, supporting the occurrence and persistence of active microbial iron oxidation across the studied iron-rich GSI ecosystem.

Hepcidin regulation in wild-type and Hfe knockout mice in response to alcohol consumption: evidence for an alcohol-induced hypoxic response.

PubMed

Heritage, Mandy L; Murphy, Therese L; Bridle, Kim R; Anderson, Gregory J; Crawford, Darrell H G; Fletcher, Linda M

2009-08-01

Expression of Hamp1, the gene encoding the iron regulatory peptide hepcidin, is inappropriately low in HFE-associated hereditary hemochromatosis and Hfe knockout mice (Hfe(-/-)). Since chronic alcohol consumption is also associated with disturbances in iron metabolism, we investigated the effects of alcohol consumption on hepcidin mRNA expression in Hfe(-/-) mice. Hfe(-/-) and C57BL/6 (wild-type) mice were pair-fed either an alcohol liquid diet or control diet for up to 8 weeks. The mRNA levels of hepcidin and ferroportin were measured at the mRNA level by RT-PCR and protein expression of hypoxia inducible factor-1 alpha (HIF-1alpha) was measured by western blot. Hamp1 mRNA expression was significantly decreased and duodenal ferroportin expression was increased in alcohol-fed wild-type mice at 8 weeks. Time course experiments showed that the decrease in hepcidin mRNA was not immediate, but was significant by 4 weeks. Consistent with the genetic defect, Hamp1 mRNA was decreased and duodenal ferroportin mRNA expression was increased in Hfe(-/-) mice fed on the control diet compared with wild-type animals and alcohol further exacerbated these effects. HIF-1alpha protein levels were elevated in alcohol-fed wild-type animals compared with controls. Alcohol may decrease Hamp1 gene expression independently of the HFE pathway possibly via alcohol-induced hypoxia.

Nitrosative Stress and Apoptosis by Intravenous Ferumoxytol, Iron Isomaltoside 1000, Iron Dextran, Iron Sucrose, and Ferric Carboxymaltose in a Nonclinical Model.

PubMed

Toblli, J E; Cao, G; Giani, J F; Dominici, F P; Angerosa, M

2015-07-01

Iron is involved in the formation as well as in the scavenging of reactive oxygen and nitrogen species. Thus, iron can induce as well as inhibit both oxidative and nitrosative stress. It also has a key role in reactive oxygen and nitrogen species-mediated apoptosis. We assessed the differences in tyrosine nitration and caspase 3 expression in the liver, heart, and kidneys of rats treated weekly with intravenous ferumoxytol, iron isomaltoside 1000, iron dextran, iron sucrose and ferric carboxymaltose (40 mg iron/kg body weight) for 5 weeks. Nitrotyrosine was quantified in tissue homogenates by Western blotting and the distribution of nitrotyrosine and caspase 3 was assessed in tissue sections by immunohistochemistry. Ferric carboxymaltose and iron sucrose administration did not result in detectable levels of nitrotyrosine or significant levels of caspase 3 vs. control in any of the tissue studied. Nitrotyrosine and caspase 3 levels were significantly (p<0.01) increased in all assessed organs of animals treated with iron dextran and iron isomaltoside 1000, as well as in the liver and kidneys of ferumoxytol-treated animals compared to isotonic saline solution (control). Nitrotyrosine and caspase 3 levels were shown to correlate positively with the amount of Prussian blue-detectable iron(III) deposits in iron dextran- and iron isomaltoside 1000-treated rats but not in ferumoxytol-treated rats, suggesting that iron dextran, iron isomaltoside 1000 and ferumoxytol induce nitrosative (and oxidative) stress as well as apoptosis via different mechanism(s). © Georg Thieme Verlag KG Stuttgart · New York.

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

Genetically engineered Escherichia coli Nissle 1917 synbiotic counters fructose-induced metabolic syndrome and iron deficiency.

PubMed

Chaudhari, Archana Somabhai; Raghuvanshi, Ruma; Kumar, G Naresh

2017-06-01

Consumption of fructose leads to metabolic syndrome, but it is also known to increase iron absorption. Present study investigates the effect of genetically modified Escherichia coli Nissle 1917 (EcN) synbiotic along with fructose on non-heme iron absorption. Charles foster rats weighing 150-200 g were fed with iron-deficient diet for 2 months. Probiotic treatment of EcN (pqq) and EcN (pqq-glf-mtlK) was given once per week, 10 9  cells after 2 months with fructose in drinking water. Iron levels, blood, and liver parameters for oxidative stress, hyperglycemia, and dyslipidemia were estimated. Transferrin-bound iron levels in the blood decreased significantly after 10 weeks of giving iron-deficient diet. Probiotic treatment of EcN (pqq-glf-mtlK) and fructose together led to the restoration of normal transferrin-bound iron levels and blood and hepatic antioxidant levels as compared to iron-deficient control group. The probiotic also led to the restoration of body weight along with levels of serum and hepatic lipid, blood glucose, and antioxidant in the blood and liver as compared to iron-deficient control group. Restoration of liver injury marker enzymes was also seen. Administration of EcN-producing PQQ and mannitol dehydrogenase enzyme together with fructose led to increase in the transferrin-bound iron levels in the blood and amelioration of consequences of metabolic syndrome caused due to fructose consumption.

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.

1. Historic American Buildings Survey E. W. Russell, Photographer, September ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

1. Historic American Buildings Survey E. W. Russell, Photographer, September 15, 1936 SIDNEY SMITH PLACE - 203 GOVERNMENT ST., FRONT ELEVATION - Sidney Smith House (Iron Gate & Balcony), 203 Government Street, Mobile, Mobile County, AL

Ameliorating role of rutin on oxidative stress induced by iron overload in hepatic tissue of rats.

PubMed

Aziza, Samy Ali Hussein; Azab, Mohammed El-Said; El-Shall, Soheir Kamal

2014-08-01

Iron is an essential element that participates in several metabolic activities of cells; however, excess iron is a major cause of iron-induced oxidative stress and several human diseases. Natural flavonoids, as rutin, are well-known antioxidants and could be efficient protective agents. Therefore, the present study was undertaken to evaluate the protective influence of rutin supplementation to improve rat antioxidant systems against IOL-induced hepatic oxidative stress. Sixty male albino rats were randomly divided to three equal groups. The first group, the control, the second group, iron overload group, the third group was used as iron overload+rutin group. Rats received six doses of ferric hydroxide polymaltose (100 mg kg(-1) b.wt.) as one dose every two days, by intraperitoneal injections (IP) and administrated rutin (50 mg kg(-1) b.wt.) as one daily oral dose until the sacrificed day. Blood samples for serum separation and liver tissue specimens were collected three times, after three, four and five weeks from the onset of the experiment. Serum iron profiles total iron, Total Iron Binding Capacity (TIBC), Unsaturated Iron Binding Capacity (UIBC), transferrin (Tf) and Transferrin Saturation% (TS%)}, ferritin, albumin, total Protein, total cholesterol, triacylglycerols levels and aspartate aminotransferase (AST) and alanine aminotransferase (ALT) activities were determined. Moreover, total iron in the liver, L-malondialdehyde (L-MDA), glutathione (GSH), Nitric Oxide (NO) and Total Nucleic Acid (TNA) levels and glutathione peroxidase (GPx), catalase (CAT) and superoxide dismutase (SOD) activities were also determined. The obtained results revealed that, iron overload (IOL) resulted in significant increase in serum iron, TIBC, Tf, TS% and ferritin levels and AST and ALT activities and also increased liver iron, L-MDA and NO levels. Meanwhile, it decreased serum UIBC, total cholesterol, triacylglycerols, albumin, total protein and liver GSH, TNA levels and Gpx, CAT and SOD activities when compared with the control group. Rutin administration to iron-overloaded rats resulted in significant decrease in serum total iron, TIBC, Tf, TS%, ferritin levels and AST and ALT activities and liver total iron, L-MDA and NO levels with significant increases in serum UIBC, albumin, total protein and total cholesterol levels and in liver GSH, CAT and SOD activities compared with the IOL group. This study provides in vivo evidence that rutin administration can improve the antioxidant defense systems against IOL-induced hepatic oxidative stress in rats. This protective effect in liver of iron-loaded rats may be due to both antioxidant and metal chelation activities.

Response of acid mobilization of iron-containing mineral dust to improvement of air quality projected in the future

NASA Astrophysics Data System (ADS)

Ito, A.; Xu, L.

2014-04-01

Acidification of dust aerosols may increase aerosol iron (Fe) solubility, which is linked to mineral properties. Combustion aerosols can also elevate aerosol iron solubility when aerosol loading is low. Here, we use an atmospheric chemical transport model to investigate the deposition of filterable iron and its response to changes in anthropogenic emissions of both combustion aerosols and precursor gases. By introducing three classes of iron-containing minerals into the detailed aerosol chemistry model, we provide a theoretical examination of the effects of different dissolution behaviors on the acid mobilization of iron. Comparisons of modeled Fe dissolution curves with the measured dissolution rates for African, east Asian, and Australian dust samples show overall good agreement under acidic conditions. The improved treatment of Fe in mineral dust and its dissolution scheme results in reasonable predictive capability for iron solubility over the oceans in the Northern Hemisphere. Our model results suggest that the improvement of air quality projected in the future will lead to a decrease of the filterable iron deposition from iron-containing mineral dust to the eastern North Pacific due to less acidification in Asian dust, which is mainly associated with the reduction of nitrogen oxides (NOx) emissions. These results could have important implications for iron fertilization of phytoplankton growth, and highlight the necessity of improving the process-based quantitative understanding of the response of the chemical modification in iron-containing minerals to environmental changes.

[Efficacy and safety of deferasirox in aplastic anemia patients with iron overload: a single arm, multi-center,prospective study in China].

PubMed

Shi, Jun; Chang, Hong; Zhang, Li; Shao, Yinqi; Nie, Neng; Zhang, Jing; Huang, Jinbo; Zhang, Li; Tang, Xudong; Quan, Richeng; Zheng, Chunmei; Xiao, Haiyan; Hu, Dengming; Hu, Lingyan; Liu, Feng; Zhou, Yongming; Zheng, Yizhou; Zhang, Fengkui

2016-01-01

To explore the efficacy and safety of deferasirox in aplastic anemia (AA)patients with iron overload. A single arm, multi- center, prospective, open- label study was conducted to evaluate absolute change in serum ferritin (SF)from baseline to 12 months of deferasirox administration, initially at a dose of 20 mg·kg(-1)·d(-1), and the safety in 64 AA patients with iron overload. All patients started their deferasirox treatment with a daily dose of 20 mg · kg(-1) ·d(-1). The mean actual dose was (18.6±3.60) mg · kg(-1)·d(-1). The median SF decreased from 4 924 (2 718- 6 765)μg/L at baseline (n=64) to 3 036 (1 474- 5 551)μg/L at 12 months (n=23) with the percentage change from baseline as 38%. A median SF decrease of 651 (126-2 125)μg/L was observed at the end of study in 23 patients who completed 12 months' treatment, the median SF level decreased by 1 167(580-4 806)μg/L [5 271(3 420-8 278)μg/L at baseline; 3 036(1 474-5 551)μg/L after 12 months' treatment; the percentage change from baseline as 42% ] after 12 months of deferasirox treatment. The most common adverse events (AEs) were increased serum creatinine levels (40.98%), gastrointestinal discomfort (40.98%), elevated liver transaminase (ALT: 21.31%; AST: 13.11%)and proteinuria (24.59%). The increased serum creatinine levels were reversible and non-progressive. Of 38 patients with concomitant cyclosporine use, 12(31.8%)patients had two consecutive values >ULN, 10(26.3%)patients had two consecutive values >1.33 baseline values, but only 1(2.6%)patient's serum creatinine increased more than 1.33 baseline values and exceeded ULN. For both AST and ALT, no patients experienced two post- baseline values >5 ×ULN or >10 × ULN during the whole study. In AA patients with low baseline PLT count (less than 50 × 10(9)/L), there was no decrease for median PLT level during 12 months' treatment period. AA patients with iron overload could achieve satisfactory efficacy of iron chelation by deferasirox treatment. The drug was well tolerated with a clinically manageable safety profile and no major adverse events.

Mathematical modeling of the dynamic storage of iron in ferritin

PubMed Central

2010-01-01

Background Iron is essential for the maintenance of basic cellular processes. In the regulation of its cellular levels, ferritin acts as the main intracellular iron storage protein. In this work we present a mathematical model for the dynamics of iron storage in ferritin during the process of intestinal iron absorption. A set of differential equations were established considering kinetic expressions for the main reactions and mass balances for ferritin, iron and a discrete population of ferritin species defined by their respective iron content. Results Simulation results showing the evolution of ferritin iron content following a pulse of iron were compared with experimental data for ferritin iron distribution obtained with purified ferritin incubated in vitro with different iron levels. Distinctive features observed experimentally were successfully captured by the model, namely the distribution pattern of iron into ferritin protein nanocages with different iron content and the role of ferritin as a controller of the cytosolic labile iron pool (cLIP). Ferritin stabilizes the cLIP for a wide range of total intracellular iron concentrations, but the model predicts an exponential increment of the cLIP at an iron content > 2,500 Fe/ferritin protein cage, when the storage capacity of ferritin is exceeded. Conclusions The results presented support the role of ferritin as an iron buffer in a cellular system. Moreover, the model predicts desirable characteristics for a buffer protein such as effective removal of excess iron, which keeps intracellular cLIP levels approximately constant even when large perturbations are introduced, and a freely available source of iron under iron starvation. In addition, the simulated dynamics of the iron removal process are extremely fast, with ferritin acting as a first defense against dangerous iron fluctuations and providing the time required by the cell to activate slower transcriptional regulation mechanisms and adapt to iron stress conditions. In summary, the model captures the complexity of the iron-ferritin equilibrium, and can be used for further theoretical exploration of the role of ferritin in the regulation of intracellular labile iron levels and, in particular, as a relevant regulator of transepithelial iron transport during the process of intestinal iron absorption. PMID:21047430

Mathematical modeling of the dynamic storage of iron in ferritin.

PubMed

Salgado, J Cristian; Olivera-Nappa, Alvaro; Gerdtzen, Ziomara P; Tapia, Victoria; Theil, Elizabeth C; Conca, Carlos; Nuñez, Marco T

2010-11-03

Iron is essential for the maintenance of basic cellular processes. In the regulation of its cellular levels, ferritin acts as the main intracellular iron storage protein. In this work we present a mathematical model for the dynamics of iron storage in ferritin during the process of intestinal iron absorption. A set of differential equations were established considering kinetic expressions for the main reactions and mass balances for ferritin, iron and a discrete population of ferritin species defined by their respective iron content. Simulation results showing the evolution of ferritin iron content following a pulse of iron were compared with experimental data for ferritin iron distribution obtained with purified ferritin incubated in vitro with different iron levels. Distinctive features observed experimentally were successfully captured by the model, namely the distribution pattern of iron into ferritin protein nanocages with different iron content and the role of ferritin as a controller of the cytosolic labile iron pool (cLIP). Ferritin stabilizes the cLIP for a wide range of total intracellular iron concentrations, but the model predicts an exponential increment of the cLIP at an iron content > 2,500 Fe/ferritin protein cage, when the storage capacity of ferritin is exceeded. The results presented support the role of ferritin as an iron buffer in a cellular system. Moreover, the model predicts desirable characteristics for a buffer protein such as effective removal of excess iron, which keeps intracellular cLIP levels approximately constant even when large perturbations are introduced, and a freely available source of iron under iron starvation. In addition, the simulated dynamics of the iron removal process are extremely fast, with ferritin acting as a first defense against dangerous iron fluctuations and providing the time required by the cell to activate slower transcriptional regulation mechanisms and adapt to iron stress conditions. In summary, the model captures the complexity of the iron-ferritin equilibrium, and can be used for further theoretical exploration of the role of ferritin in the regulation of intracellular labile iron levels and, in particular, as a relevant regulator of transepithelial iron transport during the process of intestinal iron absorption.

Angiotensin II promotes iron accumulation and depresses PGI₂ and NO synthesis in endothelial cells: effects of losartan and propranolol analogs.

PubMed

Mak, I Tong; Landgraf, Kenneth M; Chmielinska, Joanna J; Weglicki, William B

2012-10-01

Angiotensin may promote endothelial dysfunction through iron accumulation. To research this, bovine endothelial cells (ECs) were incubated with iron (30 µmol·L⁻¹) with or without angiotensin II (100 nmol·L⁻¹). After incubation for 6 h, it was observed that the addition of angiotensin enhanced EC iron accumulation by 5.1-fold compared with a 1.8-fold increase for cells incubated with iron only. This enhanced iron uptake was attenuated by losartan (100 nmol·L⁻¹), d-propranolol (10 µmol·L⁻¹), 4-HO-propranolol (5 µmol·L⁻¹), and methylamine, but not by vitamin E or atenolol. After 6 h of incubation, angiotensin plus iron provoked intracellular oxidant formation (2'7'-dichlorofluorescein diacetate (DCF-DA) fluorescence) and elevated oxidized glutathione; significant loss of cell viability occurred at 48 h. Stimulated prostacyclin release decreased by 38% (6 h) and NO synthesis was reduced by 41% (24 h). Both oxidative events and functional impairment were substantially attenuated by losartan or d-propranolol. It is concluded that angiotensin promoted non-transferrin-bound iron uptake via AT-1 receptor activation, leading to EC oxidative functional impairment. The protective effects of d-propranolol and 4-HO-propranolol may be related to their lysosomotropic properties.

Are there anamnestic risk factors for iron deficiency in pregnancy? Results from a feasibility study.

PubMed

Kirschner, Wolf; Dudenhausen, Joachim W; Henrich, Wolfgang

2016-04-01

The conditions of iron deficiency are highly incident in pregnancy with elevated risks for preterm birth and low birth weight. In our recent study, we found 6% of participants having anemia, whereas between 39% and 47% showed iron deficiency without anemia. In many countries in prenatal care solely hemoglobin (Hb) measurement is applied. For the gynecologists till date there is no indication to determine other markers (e.g., serum-ferritin). As iron deficiency results from an imbalance between intake and loss of iron, our aim was to find out if the risk of iron deficiency conditions can be estimated by a diet history protocol as well as questionnaires to find about iron loss. We found that the risk of having iron deficiency in upper gestational week (>=21) increased by a factor of five. Thus, additional diagnostics should be done in this group by now. Using the questionnaire as a screening instrument, we further estimated the probability of disease in terms of a positive likelihood ratio (LR+). The positive LR for the group below 21th week of gestation is 1.9 thus, increasing the post-test probability to 52% from 36% as before. Further research based on higher sample sizes will show if the ratios can be increased further.

The Role of Eating Habits on the Iron Status of Pregnant Women.

PubMed

Bivolarska, Anelia V; Gatseva, Penka D; Maneva, Ana I

2016-01-01

This study highlights the relationship between some eating habits and iron status during pregnancy. The study included 219 healthy pregnant women aged 27.6 ± 5.7 years from southern Bulgaria. Subjects' iron status was assessed on the basis of the following iron indicators: hemoglobin (Hb), serum ferritin (SF), serum transferrin receptor (sTfR), and body iron index (mg/kg). Severe anemia among the women from southern Bulgaria was not observed. Advanced pregnancy and some eating habits are factors that deteriorate iron status. Women who had consumed fish at least 3 times a week had lower levels of sTfR (р = 0.008), higher levels of SF (р = 0.05), and lower levels of body iron (р = 0.018). Frequent legume consumption was related to increased levels of sTfR (р = 0.036). Pregnant women with a high frequency of coffee consumption had lower values of body iron (р < 0.0001). Women who had consumed cow's milk at least 3 times a week had lower levels of SF (р = 0.026) and body iron (р = 0.042). Regular consumption of fish and legumes, rarely drinking coffee, and milk consumption during the intervals between food intake are conditions for optimization of iron status during pregnancy.

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

Evaluation and association of serum iron and ferritin levels in children with dental caries.

PubMed

Venkatesh Babu, N S; Bhanushali, Parin Vasant

2017-01-01

Iron deficiency anemia accounts for 90% of all types of anemia in the world. Although the prevalence has declined in recent years, it remains an important pediatric public health problem. Iron deficiency has also been associated with dental caries. It impairs salivary gland function causing reduced salivary secretion and buffering capacity leading to increased caries activity. The aim of the study is to explore an association between dental caries and serum levels of iron and ferritin in children aged 3-12 years. Subjectsand Methods: The study group included 120 children, hospitalized for uncomplicated medical problems. Blood reports were evaluated to determine serum iron and ferritin levels. Dental caries experience was assessed using deft index. The collected data were tabulated and analyzed using Student's t-test and Pearson's correlation coefficient. Out of 120 children, 38 children showed low serum iron levels of which 31 children had dental caries and nine out of 15 children in the high serum iron level group showed dental caries. High ferritin levels were seen in three children among which two children were caries-free and only one child had a low ferritin level who also had a positive deft score. Based on the results, it was concluded that there is an inverse association between serum iron levels and dental caries whereas there is no association between serum ferritin levels and dental caries.

Ferritin Elevation and Improved Responsiveness to Erythropoiesis-Stimulating Agents in Patients on Ferric Citrate Hydrate.

PubMed

Yokoyama, Keitaro; Fukagawa, Masafumi; Akiba, Takashi; Nakayama, Masaaki; Otoguro, Toshiya; Yamada, Kana; Nagamine, Yasuo; Fishbane, Steven; Hirakata, Hideki

2017-05-01

In hemodialysis patients on ferric citrate hydrate, the increase in ferritin level is mainly due to the administration of the compound. We investigated possible other factors associated with ferritin level and how erythropoietin resistance index and erythropoiesis in those patients were affected. We looked at ferritin-elevating factors using data from a Japanese phase III long-term clinical trial of ferric citrate hydrate. The factors with a strong association with ferritin levels at week 28 were selected by the process of variable selection. In addition, selected factors were analyzed by Mixed Model for Repeated Measurement. Subjects were divided into 3 groups by quantiles (

Iron metabolism in patients with anorexia nervosa: elevated serum hepcidin concentrations in the absence of inflammation.

PubMed

Papillard-Marechal, Solesne; Sznajder, Marc; Hurtado-Nedelec, Margarita; Alibay, Yasmin; Martin-Schmitt, Caroline; Dehoux, Monique; Westerman, Mark; Beaumont, Carole; Chevallier, Bertrand; Puy, Herve; Stheneur, Chantal

2012-03-01

Only a few studies based on small cohorts have been carried out on iron status in anorexia nervosa (AN) patients. The aim of this study was to evaluate the role of hepcidin in hyperferritinemia in AN adolescents. Twenty-seven adolescents hospitalized for AN in the pediatric inpatient unit of Ambroise Paré Academic Hospital were enrolled in the study. The control group comprised 11 patients. Hematologic variables and markers of iron status, including serum hepcidin, were measured before and after nutritional rehabilitation. The mean age of patients was 14.4 y. Except for 2 AN patients and 1 control patient, all patients presented normal hemoglobin, vitamin B-12, and folate concentrations. Markers of inflammation and cytokines were normal throughout the study. None of the muscular lysis markers were elevated. Most AN patients had normal serum iron concentrations on admission. Serum ferritin concentrations were significantly higher in patients than in control subjects (198 compared with 49 μg/L, respectively; P < 0.001). The median hepcidin concentration was significantly higher in AN patients than in the control group (186.5 compared with 39.5 μg/L, respectively; P = 0.002). There was a highly significant correlation between ferritinemia and serum hepcidin concentrations (P < 0.0001). After nutritional rehabilitation, a significant reduction was observed (P = 0.004) in serum ferritin. Serum hepcidin analyzed in a smaller number of patients also returned to within the normal range. Hepcidin and ferritin concentrations were higher in the serum of AN patients, without any evidence of iron overload or inflammation. These concentrations returned to normal after nutritional rehabilitation. These results suggest that nutritional stress induced by malnourishment in the hepatocyte could be yet another mechanism that regulates hepcidin.

Characteristics of participants with self-reported hemochromatosis or iron overload at HEIRS Study initial screening

PubMed Central

Barton, James C.; Acton, Ronald T.; Leiendecker-Foster, Catherine; Lovato, Laura; Adams, Paul C.; Eckfeldt, John H.; McLaren, Christine E.; Reiss, Jacob A.; McLaren, Gordon D.; Reboussin, David M.; Gordeuk, Victor R.; Speechley, Mark R.; Press, Richard D.; Dawkins, Fitzroy W.

2013-01-01

There are few descriptions of young adults with self-reported hemochromatosis or iron overload (H/IO). We analyzed initial screening data in 7,343 HEmochromatosis and IRon Overload Screening (HEIRS) Study participants ages 25–29 years, including race/ethnicity and health information; transferrin saturation (TS) and ferritin (SF) measurements; and HFE C282Y and H63D genotypes. We used denaturing high-pressure liquid chromatography and sequencing to detect mutations in HJV, TFR2, HAMP, SLC40A1, and FTL. Fifty-one participants reported previous H/IO; 23 (45%) reported medical conditions associated with H/IO. Prevalences of reports of arthritis, diabetes, liver disease or liver cancer, heart failure, fertility problems or impotence, and blood relatives with H/IO were significantly greater in participants with previous H/IO reports than in those without. Only 7.8% of the 51 participants with previous H/IO reports had elevated TS; 13.7% had elevated SF. Only one participant had C282Y homozygosity. Three participants aged 25–29 years were heterozygous for potentially deleterious mutations in HFE2, TFR2, and HAMP promoter, respectively. Prevalences of self-reported conditions, screening iron phenotypes, and C282Y homozygosity were similar in 1,165 participants aged 30 years or greater who reported previous H/IO. We conclude that persons who report previous H/IO diagnoses in screening programs are unlikely to have H/IO phenotypes or genotypes. Previous H/IO reports in some participants could be explained by treatment that induced iron depletion before initial screening, misdiagnosis, or participant misunderstanding of their physician or the initial screening questionnaire. PMID:17726683

Appraising the Role of Iron in Brain Aging and Cognition: Promises and Limitations of MRI Methods

PubMed Central

Daugherty, Ana M; Raz, Naftali

2015-01-01

Age-related increase in frailty is accompanied by a fundamental shift in cellular iron homeostasis. By promoting oxidative stress, the intracellular accumulation of non-heme iron outside of binding complexes contributes to chronic inflammation and interferes with normal brain metabolism. In the absence of direct non-invasive biomarkers of brain oxidative stress, iron accumulation estimated in vivo may serve as its proxy indicator. Hence, developing reliable in vivo measurements of brain iron content via magnetic resonance imaging (MRI) is of significant interest in human neuroscience. To date, by estimating brain iron content through various MRI methods, significant age differences and age-related increases in iron content of the basal ganglia have been revealed across multiple samples. Less consistent are the findings that pertain to the relationship between elevated brain iron content and systemic indices of vascular and metabolic dysfunction. Only a handful of cross-sectional investigations have linked high iron content in various brain regions and poor performance on assorted cognitive tests. The even fewer longitudinal studies indicate that iron accumulation may precede shrinkage of the basal ganglia and thus predict poor maintenance of cognitive functions. This rapidly developing field will benefit from introduction of higher-field MRI scanners, improvement in iron-sensitive and -specific acquisition sequences and post-processing analytic and computational methods, as well as accumulation of data from long-term longitudinal investigations. This review describes the potential advantages and promises of MRI-based assessment of brain iron, summarizes recent findings and highlights the limitations of the current methodology. PMID:26248580

AMD-like retinopathy associated with intravenous iron

PubMed Central

Song, Delu; Kanu, Levi N.; Li, Yafeng; Kelly, Kristen L.; Bhuyan, Rupak K.; Aleman, Tomas; Morgan, Jessica I. W.; Dunaief, Joshua L.

2016-01-01

Iron accumulation in the retina is associated with the development of age-related macular degeneration (AMD). IV iron is a common method to treat iron deficiency anemia in adults, and its retinal manifestations have not hitherto been identified. To assess whether IV iron formulations can be retina-toxic, we generated a mouse model for iron-induced retinal damage. Male C57BL/6J mice were randomized into groups receiving IV iron-sucrose (+Fe) or 30% sucrose (−Fe). Iron levels in neurosensory retina (NSR), retinal pigment epithelium (RPE), and choroid were assessed using immunofluorescence, quantitative PCR, and the Perls’ iron stain. Iron levels were most increased in the RPE and choroid while levels in the NSR did not differ significantly in +Fe mice compared to controls. Eyes from +Fe mice shared histological features with AMD, including Bruch’s membrane (BrM) thickening with complement C3 deposition, as well as RPE hypertrophy and vacuolization. This focal degeneration correlated with areas with high choroidal iron levels. Ultrastructural analysis provided further detail of the RPE/photoreceptor outer segment vacuolization and Bruch’s membrane thickening. Findings were correlated with a clinical case of a 43-year-old patient who developed numerous retinal drusen, the hallmark of AMD, within 11 months of IV iron therapy. Our results suggest that IV iron therapy may have the potential to induce or exacerbate a form of retinal degeneration. This retinal degeneration shares features with AMD, indicating the need for further study of AMD risk in patients receiving IV iron treatment. PMID:27565570

Too much is bad--an appraisal of phytotoxicity of elevated plant-beneficial heavy metal ions.

PubMed

Anjum, Naser A; Singh, Harminder P; Khan, M Iqbal R; Masood, Asim; Per, Tasir S; Negi, Asha; Batish, Daizy R; Khan, Nafees A; Duarte, Armando C; Pereira, Eduarda; Ahmad, Iqbal

2015-03-01

Heavy metal ions such as cobalt (Co), copper (Cu), iron (Fe), manganese (Mn), molybdenum (Mo), nickel (Ni), and zinc (Zn) are considered essential/beneficial for optimal plant growth, development, and productivity. However, these ions readily impact functions of many enzymes and proteins, halt metabolism, and exhibit phytotoxicity at supra-optimum supply. Nevertheless, the concentrations of these heavy metal ions are increasing in agricultural soils worldwide via both natural and anthropogenic sources that need immediate attention. Considering recent breakthroughs on Co, Cu, Fe, Mn, Mo, Ni, and Zn in soil-plant system, the present paper: (a) overviews the status in soils and their uptake, transport, and significance in plants; (b) critically discusses their elevated level-mediated toxicity to both plant growth/development and cell/genome; (c) briefly cross talks on the significance of potential interactions between previous plant-beneficial heavy metal ions in plants; and (d) highlights so far unexplored aspects in the current context.

Quality of water in the alluvial aquifer, American Bottoms, East St Louis, Illinois

USGS Publications Warehouse

Voelker, David C.

1984-01-01

Ground-water levels in the American Bottoms regions around East St. Louis, Illinois, have risen several feet since the early 1970's. Artificial dewatering of the aquifer by increased pumping is being investigated by the U.S. Army Corps of Engineers to alleviate economic and health concerns resulting from elevated ground-water levels. A ground-water quality evaluation is necessary for selecting a feasible dewatering scheme. Analyses of water samples from 63 wells show that except for iron, manganese, and dissolved solids, constituent concentrations do not exceed Illinois water-quality standards. The waters are primarily of the calcium-magnesium-bicarbonate type with some calcium-sulfate type water. Iron concentrations ranged from less than 3 to 82,000 micrograms per liter, manganese from 5 to 5,300 micrograms per liter, and dissolved solids from 140 to 3,000 milligrams per liter. These constituent concentrations exceed Illinois ' public water supply, effluent, and general water-quality standards in most samples and analysis indicates the concentrations are representative of the ambient water quality. Concentrations of nitrite + nitrate nitrogen fluoride, zinc, lead, and sulfate also exceeded Illinois water-quality standards in a few samples. Concentrations of organic pesticides, polychlorinated biphenyls, and polychlorinated naphthalenes were below analytical detection limits. (USGS)

Structure-property relationships in oxide-dispersed iron-beryllia alloys

NASA Technical Reports Server (NTRS)

Wolf, S.; Grant, N. J.

1977-01-01

Two BeO dispersed iron alloys containing about 2.5 and 5.5 v/o dispersoid were produced by attritting, internally oxidizing, and extruding dilute, prealloyed Fe-Be powders. As-extruded alloys were given various thermomechanical treatments involving room temperature swaging and annealing above and below the allotropic transformation temperature. The elevated temperature rupture strengths were measured and correlated with changes in structure; strengthening trends were examined in the light of proposed models for such strengthening. The results obtained showed that the elevated temperature strength was determined by the oxide interparticle spacing (IPS) in recrystallized material and IPS as well as prior deformation in swaged specimens. In fact, a parametric correlation was found between rupture strength values in the longitudinal direction with prestrain during swaging. The overall pattern in strength and microstructural observations were more consistent with a strength-stored energy (substructure) dependence than a strength-grain shape (grain aspect ratio) relation.

Evaluation of Thermal Stability of Ausferrite in Austempered Ductile Iron Using Differential Scanning Calorimetry

NASA Astrophysics Data System (ADS)

Warsinski, Karl C.

Austempered Ductile Iron (ADI) is prone to changes in microstructure and mechanical properties when exposed to elevated service temperatures. Differential Scanning Calorimetry has been used to evaluate the stabilizing effects of copper, nickel, molybdenum, and cobalt on the ausferrite structure. Previous studies have conflated the effects of various alloy additions, and little effort has been made to systematically catalog the effects of individual elements. The focus of the current research has been to identify alloying elements that more strongly stabilize the ausferrite structure in order to improve service life of ADI at elevated temperatures. Nickel has been shown to have a moderate stabilizing effect, while copper and molybdenum cause a much sharper increase in activation energy. Cobalt has a high stabilizing effect at 0.5% addition by weight, but a further increase to 2.36% results in a slight decrease in activation energy.

Iron-based alloy and nitridation treatment for PEM fuel cell bipolar plates

DOEpatents

Brady, Michael P [Oak Ridge, TN; Yang, Bing [Oak Ridge, TN; Maziasz, Philip J [Oak Ridge, TN

2010-11-09

A corrosion resistant electrically conductive component that can be used as a bipolar plate in a PEM fuel cell application is composed of an alloy substrate which has 10-30 wt. % Cr, 0.5 to 7 wt. % V, and base metal being Fe, and a continuous surface layer of chromium nitride and vanadium nitride essentially free of base metal. A oxide layer of chromium vanadium oxide can be disposed between the alloy substrate and the continuous surface nitride layer. A method to prepare the corrosion resistant electrically conductive component involves a two-step nitridization sequence by exposing the alloy to a oxygen containing gas at an elevated temperature, and subsequently exposing the alloy to an oxygen free nitrogen containing gas at an elevated temperature to yield a component where a continuous chromium nitride layer free of iron has formed at the surface.

Effect of oral calcium disodium EDTA on iron absorption in a human model of iron overdose.

PubMed

Matteucci, Michael J; Habibe, Michael; Robson, Kristie; Baldassano, Accursia A; Riffenburgh, Robert H; Tanen, David A

2006-01-01

Anecdotal case reports and animal models have suggested that the administration of CaNa2EDTA (EDTA) may be effective in reducing the absorption of iron after an oral iron overdose. We designed this study to determine the effect of orally administrated EDTA with or without activated charcoal (AC) on iron absorption after a mild iron ingestion in healthy human volunteers. A randomized, crossover study was conducted in eight healthy human volunteers. All subjects ingested 5 mg/kg of elemental iron in the form of ferrous sulfate. One hour post ingestion, subjects were randomized to receive 35 mg/kg EDTA, EDTA plus 50 grams of AC, or water. Serial iron levels were obtained at baseline and every hour for the first 6 hours, then at 8, 12, and 24 hours. A 2-week washout was used between study arms. The Kruskal-Wallis test was used for the following comparisons between treatment groups: baseline serum iron levels, area under time-concentration curves (AUCs) from baseline to 12 hours and baseline to 24 hours, and peak iron levels. Baseline serum iron levels did not differ among the three treatment groups (p = 0.844). AUCs were not different among groups (p = 0.746 for 12 hr, p = 0.925 for 24 hr). AUC medians (with 95% binomial confidence bounds) for control, EDTA, EDTA + AC groups, respectively, for 12 hr were: 2813 (2298, 3561), 2570 (1669, 3476), and 2654 (2125, 3600); and for 24 hr were: 4083 (3488,5314), 4139 (2666, 5547), and 4274 (3336, 5577). Peak serum iron levels did not differ among treatment groups (p = 0.481). Peak iron level medians in microg/dL (with 95% binomial confidence bounds) were for control: 329 (253, 382), for EDTA: 271 (184, 375), and for EDTA + AC: 285 (229, 352). Orally administered EDTA did not significantly reduce iron absorption when administered 1 hour post iron ingestion during the 12 or 24-hour period following the ingestion of 5 mg/kg of elemental iron in healthy human volunteers.

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.

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.

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

A rare case of iron-pill induced gastritis in a female teenager: A case report and a review of the literature.

PubMed

Meliţ, Lorena Elena; Mărginean, Cristina Oana; Mocanu, Simona; Mărginean, Maria Oana

2017-07-01

The treatment of iron-deficiency anemia with oral iron supplements can present side-effects on the GI tract mucosa including necrosis, ulceration, or ischemia. The particular endoscopic findings and the histopathological exam will establish the diagnosis of erosive gastritis with iron deposits in the gastric mucosa. We present the case of a 14-year-old female admitted in our clinic for upper digestive hemorrhage, nausea, melena, and abdominal pain. Her personal history revealed iron deficiency anemia receiving oral iron supplements for approximately 2 weeks. The laboratory tests at the moment of admission pointed out anemia, increased level of serum iron, increased liver transaminases, a decreased level of ferritin, but with normal levels of both total iron-binding capacity and transferrin. The eso-gastro-duodenoscopy revealed multiple brown deposits on the surface of the gastric mucosa and multiple hemorrhagic lesions, under the aspect of erosions all over the gastric mucosa, but more severe in the antral part, and the histopathological exam confirmed the presence of iron deposits at this level. Iron-pill induced gastritis is a rare, under-diagnosed entity that can be present even at pediatric ages with potential severe clinical impact.

Iron metabolism in critically ill patients developing anemia of inflammation: a case control study.

PubMed

Boshuizen, Margit; Binnekade, Jan M; Nota, Benjamin; van de Groep, Kirsten; Cremer, Olaf L; Tuinman, Pieter R; Horn, Janneke; Schultz, Marcus J; van Bruggen, Robin; Juffermans, Nicole P

2018-05-02

Anemia occurring as a result of inflammatory processes (anemia of inflammation, AI) has a high prevalence in critically ill patients. Knowledge on changes in iron metabolism during the course of AI is limited, hampering the development of strategies to counteract AI. This case control study aimed to investigate iron metabolism during the development of AI in critically ill patients. Iron metabolism in 30 patients who developed AI during ICU stay was compared with 30 septic patients with a high Hb and 30 non-septic patients with a high Hb. Patients were matched on age and sex. Longitudinally collected plasma samples were analyzed for levels of parameters of iron metabolism. A linear mixed model was used to assess the predictive values of the parameters. In patients with AI, levels of iron, transferrin and transferrin saturation showed an early decrease compared to controls with a high Hb, already prior to the development of anemia. Ferritin, hepcidin and IL-6 levels were increased in AI compared to controls. During AI development, erythroferrone decreased. Differences in iron metabolism between groups were not influenced by APACHE IV score. The results show that in critically ill patients with AI, iron metabolism is already altered prior to the development of anemia. Levels of iron regulators in AI differ from septic controls with a high Hb, irrespective of disease severity. AI is characterized by high levels of hepcidin, ferritin and IL-6 and low levels of iron, transferrin and erythroferrone.

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.

Tracer test with As(V) under variable redox conditions controlling arsenic transport in the presence of elevated ferrous iron concentrations

USGS Publications Warehouse

Hohn, R.; Isenbeck-Schroter, M.; Kent, D.B.; Davis, J.A.; Jakobsen, R.; Jann, S.; Niedan, V.; Scholz, C.; Stadler, S.; Tretner, A.

2006-01-01

To study transport and reactions of arsenic under field conditions, a small-scale tracer test was performed in an anoxic, iron-reducing zone of a sandy aquifer at the USGS research site on Cape Cod, Massachusetts, USA. For four weeks, a stream of groundwater with added As(V) (6.7????M) and bromide (1.6??mM), was injected in order to observe the reduction of As(V) to As(III). Breakthrough of bromide (Br-), As(V), and As(III) as well as additional parameters characterizing the geochemical conditions was observed at various locations downstream of the injection well over a period of 104??days. After a short lag period, nitrate and dissolved oxygen from the injectate oxidized ferrous iron and As(V) became bound to the freshly formed hydrous iron oxides. Approximately one week after terminating the injection, anoxic conditions had been reestablished and increases in As(III) concentrations were observed within 1??m of the injection. During the observation period, As(III) and As(V) were transported to a distance of 4.5??m downgradient indicating significant retardation by sorption processes for both species. Sediment assays as well as elevated concentrations of hydrogen reflected the presence of As(V) reducing microorganisms. Thus, microbial As(V) reduction was thought to be one major process driving the release of As(III) during the tracer test in the Cape Cod aquifer. ?? 2006 Elsevier B.V. All rights reserved.

Potent Synergistic Effect of Doxycycline with Fluconazole against Candida albicans Is Mediated by Interference with Iron Homeostasis

PubMed Central

2012-01-01

Doxycycline was found to act synergistically with the antifungal fluconazole against Candida albicans. Combination with doxycycline converts fluconazole from fungistatic to fungicidal, prevents the onset of drug resistance, and is also effective against a clinical isolate characterized by elevated resistance to fluconazole. Investigation of the interactions between the two drugs by way of checkerboard assays indicated that doxycycline had an influence on the MIC for fluconazole, as defined by CLSI standards, only at high concentrations (200 μg/ml). However, lower concentrations were effective at eliminating residual cell growth at supra-MICs of fluconazole. Using MIC-0, defined as a drug combination resulting in optically clear wells, as an endpoint, doxycycline was found to be synergistic with fluconazole at a concentration as low as 25 μg/ml, with a fractional inhibitory concentration index of <0.5. Doxycycline-mediated growth inhibition can be reversed by externally added iron, indicating that iron depletion may account for the synergism. Consistently, we confirmed old literature data about iron-chelating activity of doxycycline. Synergism of fluconazole with doxycycline does not appear to be mediated by calcineurin, since doxycycline further aggravates the susceptibility to fluconazole of mutants lacking the catalytic or the regulatory subunits of calcineurin. Growth in the presence of fluconazole and doxycycline is restored by an elevated dosage of ERG11 in Saccharomyces cerevisiae but not in C. albicans, despite the full competence of the pathogen's protein to act as a suppressor in baker's yeast. PMID:22564841

Haemochromatosis in a Brazilian tapir (Tapirus terrestris) in an Australian zoo.

PubMed

Peters, A; Raidal, S R; Blake, A H; Atkinson, M M; Atkinson, P R; Eggins, G P

2012-01-01

A 23-year-old Brazilian, or lowland, tapir with a 6-month history of loss of body condition developed clinical signs and laboratory findings consistent with liver failure. The animal was euthanased and a diagnosis of hepatic haemochromatosis was made based on histopathology. Two other healthy tapirs in the same collection had chronically elevated serum and tissue iron concentrations. The excessive accumulation of iron in tissues with resultant tissue damage (i.e. haemochromatosis) has been reported in a range of captive species. This and other reported cases of haemochromatosis in the Brazilian tapir would suggest that this condition is an important consideration in the management of this species in zoos. Further research into the endogenous regulation of iron metabolism, especially the role of hepcidin, in tapirs and other species at risk of iron storage disorders may be helpful in the prevention of this condition. © 2012 The Authors. Australian Veterinary Journal © 2012 Australian Veterinary Association.

Association of hair iron levels with creativity and psychological variables related to creativity

PubMed Central

Takeuchi, Hikaru; Taki, Yasuyuki; Sekiguchi, Atsushi; Nouchi, Rui; Kotozaki, Yuka; Nakagawa, Seishu; Miyauchi, Carlos M.; Iizuka, Kunio; Yokoyama, Ryoichi; Shinada, Takamitsu; Yamamoto, Yuki; Hanawa, Sugiko; Araki, Tsuyoshi; Hashizume, Hiroshi; Kunitoki, Keiko; Sassa, Yuko; Kawashima, Ryuta

2013-01-01

Creativity generally involves the conception of original and valuable ideas. Previous studies have suggested an association between creativity and the dopaminergic system, and that physical activity facilitates creativity. Iron plays a key role in the dopaminergic system and physical activity. Here, we newly investigated the associations between hair iron levels and creativity, dopamine-related traits and states [novelty seeking, extraversion, and vigor (motivational state)], as well as the physical activity level. In the present study, we addressed this issue by performing a hair mineral analysis to determine iron levels and a behavioral creativity test of divergent thinking and related psychological measures among young adults (254 men, 88 women; mean age 20.79 ± 2.03 years). Iron levels did not show any significant association with creativity but displayed significant positive associations with novelty seeking, extraversion, and physical activity level. These results may be partly congruent with the notion that iron plays a key role in the dopaminergic system and imply that iron is important for traits and physical activity, which facilitate creativity. Future interventional or longitudinal studies are warranted to identify any causal effects. PMID:24385960

The Statin–Iron Nexus: Anti-Inflammatory Intervention for Arterial Disease Prevention

PubMed Central

DePalma, Ralph G.; Shamayeva, Galina; Chow, Bruce K.

2013-01-01

Objectives. We postulated the existence of a statin–iron nexus by which statins improve cardiovascular disease outcomes at least partially by countering proinflammatory effects of excess iron stores. Methods. Using data from a clinical trial of iron (ferritin) reduction in advanced peripheral arterial disease, the Iron and Atherosclerosis Study, we compared effects of ferritin levels versus high-density lipoprotein to low-density lipoprotein ratios (both were randomization variables) on clinical outcomes in participants receiving and not receiving statins. Results. Statins increased high-density lipoprotein to low-density lipoprotein ratios and reduced ferritin levels by noninteracting mechanisms. Improved clinical outcomes were associated with lower ferritin levels but not with improved lipid status. Conclusions. There are commonalities between the clinical benefits of statins and the maintenance of physiologic iron levels. Iron reduction may be a safe and low-cost alternative to statins. PMID:23409890

Iron-chelating effect of silymarin in patients with β-thalassemia major: A crossover randomised control trial.

PubMed

Darvishi-Khezri, Hadi; Salehifar, Ebrahim; Kosaryan, Mehrnoush; Karami, Hossein; Mahdavi, Mohammadreza; Alipour, Abbas; Aliasgharian, Aily

2018-03-01

This study aimed to determine the potential iron-chelating effects of silymarin in patients with β-thalassemia major receiving standard iron-chelation therapy. We evaluated whether addition of silymarin to standard iron-chelation therapy could improve iron burden markers and liver and cardiac function in these patients, via a placebo-controlled, crossover clinical study. Silymarin (140 mg) or placebo were administered thrice daily to all patients (n = 82) for 12 weeks, and after a 2-week washout period, patients were crossed over to the other groups. Silymarin efficacy was assessed by measuring serum iron level, ferritin level, total iron-binding capacity and liver and cardiac function on magnetic resonance imaging. Silymarin treatment resulted in a negative change in the serum iron and ferritin levels and a positive change in the total iron-binding capacity levels (treatment effect, p < .001, p = .06, and p = .05, respectively). Silymarin treatment led to positive changes in cardiac and liver function in both treatment sequences of study; however, this was not statistically significant. There was a negative change in liver iron concentration in both treatment sequences (treatment effect, p = .02). In conclusion, combined iron-chelation and silymarin therapy was effective for improving the iron-burden status in patients with β-thalassemia major. Copyright © 2017 John Wiley & Sons, Ltd.

Estrogen regulates hepcidin expression via GPR30-BMP6-dependent signaling in hepatocytes.

PubMed

Ikeda, Yasumasa; Tajima, Soichiro; Izawa-Ishizawa, Yuki; Kihira, Yoshitaka; Ishizawa, Keisuke; Tomita, Shuhei; Tsuchiya, Koichiro; Tamaki, Toshiaki

2012-01-01

Hepcidin, a liver-derived iron regulatory protein, plays a crucial role in iron metabolism. It is known that gender differences exist with respect to iron storage in the body; however, the effects of sex steroid hormones on iron metabolism are not completely understood. We focused on the effects of the female sex hormone estrogen on hepcidin expression. First, ovariectomized (OVX) and sham-operated mice were employed to investigate the effects of estrogen on hepcidin expression in an in vivo study. Hepcidin expression was decreased in the livers of OVX mice compared to the sham-operated mice. In OVX mice, bone morphologic protein-6 (BMP6), a regulator of hepcidin, was also found to be downregulated in the liver, whereas ferroportin (FPN), an iron export protein, was upregulated in the duodenum. Both serum and liver iron concentrations were elevated in OVX mice relative to their concentrations in sham-operated mice. In in vitro studies, 17β-estradiol (E(2)) increased the mRNA expression of hepcidin in HepG2 cells in a concentration-dependent manner. E(2)-induced hepatic hepcidin upregulation was not inhibited by ICI 182720, an inhibitor of the estrogen receptor; instead, hepcidin expression was increased by ICI 182720. E(2) and ICI 182720 exhibit agonist actions with G-protein coupled receptor 30 (GPR30), the 7-transmembrane estrogen receptor. G1, a GPR30 agonist, upregulated hepcidin expression, and GPR30 siRNA treatment abolished E(2)-induced hepcidin expression. BMP6 expression induced by E(2) was abolished by GPR30 silencing. Finally, both E(2) and G1 supplementation restored reduced hepatic hepcidin and BMP6 expression and reversed the augmentation of duodenal FPN expression in the OVX mice. In contrast, serum hepcidin was elevated in OVX mice, which was reversed in these mice with E(2) and G1. Thus, estrogen is involved in hepcidin expression via a GPR30-BMP6-dependent mechanism, providing new insight into the role of estrogen in iron metabolism.

Fob1 and Fob2 Proteins Are Virulence Determinants of Rhizopus oryzae via Facilitating Iron Uptake from Ferrioxamine

PubMed Central

Liu, Mingfu; Lin, Lin; Gebremariam, Teclegiorgis; Luo, Guanpingsheng; Skory, Christopher D.; French, Samuel W.; Chou, Tsui-Fen; Edwards, John E.; Ibrahim, Ashraf S.

2015-01-01

Dialysis patients with chronic renal failure receiving deferoxamine for treating iron overload are uniquely predisposed for mucormycosis, which is most often caused by Rhizopus oryzae. Although the deferoxamine siderophore is not secreted by Mucorales, previous studies established that Rhizopus species utilize iron from ferrioxamine (iron-rich form of deferoxamine). Here we determined that the CBS domain proteins of Fob1 and Fob2 act as receptors on the cell surface of R. oryzae during iron uptake from ferrioxamine. Fob1 and Fob2 cell surface expression was induced in the presence of ferrioxamine and bound radiolabeled ferrioxamine. A R. oryzae strain with targeted reduced Fob1/Fob2 expression was impaired for iron uptake, germinating, and growing on medium with ferrioxamine as the sole source of iron. This strain also exhibited reduced virulence in a deferoxamine-treated, but not the diabetic ketoacidotic (DKA), mouse model of mucormycosis. The mechanism by which R. oryzae obtains iron from ferrioxamine involves the reductase/permease uptake system since the growth on ferrioxamine supplemented medium is associated with elevated reductase activity and the use of the ferrous chelator bathophenanthroline disulfonate abrogates iron uptake and growth on medium supplemented with ferrioxamine as a sole source of iron. Finally, R. oryzae mutants with reduced copies of the high affinity iron permease (FTR1) or with decreased FTR1 expression had an impaired iron uptake from ferrioxamine in vitro and reduced virulence in the deferoxamine-treated mouse model of mucormycosis. These two receptors appear to be conserved in Mucorales, and can be the subject of future novel therapy to maintain the use of deferoxamine for treating iron-overload. PMID:25974051

The Iron Metallome in Eukaryotic Organisms

PubMed Central

Dlouhy, Adrienne C.; Outten, Caryn E.

2013-01-01

This chapter is focused on the iron metallome in eukaryotes at the cellular and subcellular level, including properties, utilization in metalloproteins, trafficking, storage, and regulation of these processes. Studies in the model eukaryote Saccharomyces cerevisiae and mammalian cells will be highlighted. The discussion of iron properties will center on the speciation and localization of intracellular iron as well as the cellular and molecular mechanisms for coping with both low iron bioavailability and iron toxicity. The section on iron metalloproteins will emphasize heme, iron-sulfur cluster, and non-heme iron centers, particularly their cellular roles and mechanisms of assembly. The section on iron uptake, trafficking, and storage will compare methods used by yeast and mammalian cells to import iron, how this iron is brought into various organelles, and types of iron storage proteins. Regulation of these processes will be compared between yeast and mammalian cells at the transcriptional, post-transcriptional, and post-translational levels. PMID:23595675

Red meat intake in chronic kidney disease patients: Two sides of the coin.

PubMed

Mafra, Denise; Borges, Natalia A; Cardozo, Ludmila Ferreira Medeiros de Franca; Anjos, Juliana S; Black, Ana Paula; Moraes, Cristiane; Bergman, Peter; Lindholm, Bengt; Stenvinkel, Peter

2018-02-01

Red meat is an important dietary source of high biological value protein and micronutrients such as vitamins, iron, and zinc that exert many beneficial functions. However, high consumption of animal protein sources, especially red meat, results in an increased intake of saturated fat, cholesterol, iron, and salt, as well as an excessive acid load. Red meat intake may lead to an elevated production of uremic toxins by the gut microbiota, such as trimethylamine n-oxide (TMAO), indoxyl sulfate, and p-cresyl sulfate. These uremic toxins are associated with increased risk for cardiovascular (CV) mortality. Limiting the intake of red meat in patients with chronic kidney disease (CKD) thus may be a good strategy to reduce CV risk, and may slow the progression of kidney disease. In the present review, we discuss the role of red meat in the diet of patients with CKD. Additionally, we report on a pilot study that focused on the effect of a low-protein diet on TMAO plasma levels in nondialysis CKD patients. Copyright © 2017 Elsevier Inc. All rights reserved.

Radon exposure and cancers other than lung cancer in Swedish iron miners.

PubMed Central

Darby, S C; Radford, E P; Whitley, E

1995-01-01

Data are presented on the risks of cancers other than lung cancer in a cohort of iron miners from northern Sweden occupationally exposed to elevated levels of the radioactive gas radon. Compared with rates for the four northernmost counties of Sweden, mortality was increased for all cancers other than lung cancer (ratio of observed to expected deaths 1.21, 95% confidence interval 1.03-1.41), stomach cancer (ratio of observed to expected deaths 1.45, 95% confidence interval 1.04-1.98), and rectal cancer (ratio of observed to expected deaths 1.94, 95% confidence interval 1.03-3.31). Despite these overall increases, mortality was not significantly associated with cumulative exposure to radon, either for all cancers other than lung cancer or for any site of cancer other than lung cancer individually. However, the data from this cohort on its own have limited power; and for several sites of cancer the data in this study would be consistent with a radon-related increase. Further study of cancers other than lung cancer in populations exposed to radon is required. PMID:7614946

Plasma Ferritin and Hepcidin Are Lower at 4 Months Postpartum among Women with Elevated C-Reactive Protein or α1-Acid Glycoprotein.

PubMed

Jorgensen, Josh M; Yang, Zhenyu; Lönnerdal, Bo; Chantry, Caroline J; Dewey, Kathryn G

2017-06-01

Background: Ferritin and hepcidin are markers of iron status that typically increase during inflammation or infection. The postpartum period is a physiologically unique life stage in which the relations between these proteins and other markers of inflammation have not been extensively studied. Objective: We aimed to determine whether 2 markers of inflammation [high-sensitivity C-reactive protein (CRP) and α1-acid glycoprotein (AGP)] were associated with ferritin or hepcidin in postpartum women in California. Methods: This is a secondary analysis of a randomized controlled iron-intervention trial. Plasma CRP, AGP, ferritin, and hepcidin were analyzed at 2 and 17 wk postpartum in 114 lactating women. We examined Pearson correlation coefficients between all biomarkers at both time points and differences in mean values of ferritin and hepcidin between those with and without elevated CRP and/or AGP. Results: At 2 and 17 wk postpartum, 58% and 26% of women had CRP >5 mg/L and 78% and 29% had AGP >1 g/L, respectively. Neither CRP nor AGP was significantly correlated with ferritin ( r = 0.07 and -0.06; n = 114 at 2 wk; -0.14 and -0.14; n = 95 at 17 wk) or hepcidin ( r = 0.18 and -0.03 at 2 wk; -0.05 and -0.14 at 17 wk; P > 0.05 for all). At 2 wk, geometric mean plasma ferritin and hepcidin concentrations did not differ between women with and without elevated CRP or AGP ( P > 0.5), but at 17 wk women with elevated CRP or AGP had lower mean (95% CI) ferritin and hepcidin than did women without either elevated CRP or AGP [ferritin: 30.3 ng/mL (23.4, 39.1 ng/mL) compared with 40.2 ng/mL (32.9, 49.2 ng/mL); P < 0.01; hepcidin: 44.3 ng/mL (32.3, 60.9 ng/mL) compared with 67.6 ng/mL (56.1, 81.5 ng/mL); P = 0.02]. Conclusion: Lower ferritin and hepcidin among women with elevated CRP or AGP at 17 wk postpartum suggests that these markers of iron status react differently to physiologic immune activation than to pathologic inflammatory states. © 2017 American Society for Nutrition.

Calcium in drinking water: effect on iron stores in Danish blood donors-results from the Danish Blood Donor Study.

PubMed

Rigas, Andreas S; Ejsing, Benedikte H; Sørensen, Erik; Pedersen, Ole B; Hjalgrim, Henrik; Erikstrup, Christian; Ullum, Henrik

2018-06-01

Studies confirm that calcium inhibits iron absorption. Danish tap water comes from groundwater, which contains varying amounts of calcium depending on the subsoil. We investigated the association of calcium in drinking water with iron levels in Danish blood donors. We used data on Danish blood donors including dietary and lifestyle habits, blood donation history, and physiologic characteristics including measures of ferritin levels along with information on area of residence from The Danish Blood Donor Study. Data on calcium levels in groundwater ("water hardness") were obtained through the Geological Survey of Denmark and Greenland. We performed multiple linear and logistic regression analyses to evaluate the effect of water hardness on ferritin levels and risk of having iron deficiency (defined as ferritin levels <15 ng/mL), stratified by sex. There was a significant negative association between water hardness and ferritin levels in both men and women. Risk of iron deficiency was correspondingly increased in both men (odds ratio [OR], 1.55; 95% confidence interval [CI], 1.14-2.12) and women (OR, 1.20; 95% CI, 1.03-1.40) with increasing water hardness. In analyses restricted to individuals who received supplemental iron tablets no significant association between groundwater hardness and ferritin levels was observed. As measured by ferritin levels, residential drinking water calcium content is associated with blood donors- iron levels and risk of iron deficiency. However, effect sizes are small. © 2018 AABB.

Serum Iron Levels and the Risk of Parkinson Disease: A Mendelian Randomization Study

PubMed Central

Gögele, Martin; Lill, Christina M.; Bertram, Lars; Do, Chuong B.; Eriksson, Nicholas; Foroud, Tatiana; Myers, Richard H.; Nalls, Michael; Keller, Margaux F.; Benyamin, Beben; Whitfield, John B.; Pramstaller, Peter P.; Hicks, Andrew A.; Thompson, John R.; Minelli, Cosetta

2013-01-01

Background Although levels of iron are known to be increased in the brains of patients with Parkinson disease (PD), epidemiological evidence on a possible effect of iron blood levels on PD risk is inconclusive, with effects reported in opposite directions. Epidemiological studies suffer from problems of confounding and reverse causation, and mendelian randomization (MR) represents an alternative approach to provide unconfounded estimates of the effects of biomarkers on disease. We performed a MR study where genes known to modify iron levels were used as instruments to estimate the effect of iron on PD risk, based on estimates of the genetic effects on both iron and PD obtained from the largest sample meta-analyzed to date. Methods and Findings We used as instrumental variables three genetic variants influencing iron levels, HFE rs1800562, HFE rs1799945, and TMPRSS6 rs855791. Estimates of their effect on serum iron were based on a recent genome-wide meta-analysis of 21,567 individuals, while estimates of their effect on PD risk were obtained through meta-analysis of genome-wide and candidate gene studies with 20,809 PD cases and 88,892 controls. Separate MR estimates of the effect of iron on PD were obtained for each variant and pooled by meta-analysis. We investigated heterogeneity across the three estimates as an indication of possible pleiotropy and found no evidence of it. The combined MR estimate showed a statistically significant protective effect of iron, with a relative risk reduction for PD of 3% (95% CI 1%–6%; p = 0.001) per 10 µg/dl increase in serum iron. Conclusions Our study suggests that increased iron levels are causally associated with a decreased risk of developing PD. Further studies are needed to understand the pathophysiological mechanism of action of serum iron on PD risk before recommendations can be made. Please see later in the article for the Editors' Summary PMID:23750121

Lower serum hepcidin and greater parenchymal iron in nonalcoholic fatty liver disease patients with C282Y HFE mutations

PubMed Central

Nelson, James E.; Brunt, Elizabeth M.; Kowdley, Kris V.

2012-01-01

Hepcidin regulation is linked to both iron and inflammatory signals and may influence iron loading in nonalcoholic steatohepatitis (NASH). The aim of this study was to examine the relationships among HFE genotype, serum hepcidin level, hepatic iron deposition and histology in nonalcoholic fatty liver disease (NAFLD). SNP genotyping for C282Y (rs1800562) and H63D (rs1799945) HFE mutations was performed in 786 adult subjects in the NASH Clinical Research Network (CRN). Clinical, histologic, and laboratory data were compared using nonparametric statistics and multivariate logistic regression. NAFLD patients with C282Y, but not H63D mutations, had lower median serum hepcidin levels (57 vs 65 ng/ml, p=0.01) and higher mean hepatocellular (HC) iron grades (0.59 vs 0.28, p<0.001), compared to wild type (WT) subjects. Subjects with hepatic iron deposition had higher serum hepcidin levels than subjects without iron for all HFE genotypes (p<0.0001). Hepcidin levels were highest among patients with mixed HC/reticuloendothelial system cell (RES) iron deposition. H63D mutations were associated with higher steatosis grades and NAFLD activity scores (OR≥1.4, CI >1.0≤2.5, p≤0.041), compared to WT, but not with either HC or RES iron. NAFLD patients with C282Y mutations had less ballooning or NASH (OR ≤0.62, 95% CI >0.39<0.94, p≤0.024) compared to WT subjects. Conclusions Presence of C282Y mutations in patients with NAFLD is associated with greater HC iron deposition and decreased serum hepcidin levels and there is a positive relationship between hepatic iron stores and serum hepcidin level across all HFE genotypes. These data suggest that body iron stores are the major determinant of hepcidin regulation in NAFLD regardless of HFE genotype. A potential role for H63D mutations in NAFLD pathogenesis is possible through iron-independent mechanisms. PMID:22611049

19. Historic American Buildings Survey E. W. Russell, Photographer, May ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

19. Historic American Buildings Survey E. W. Russell, Photographer, May 7, 1936 SOUTH ELEVATION (REAR) SHOWING ROUND IRON COLUMN AND SQUARE STUCCO COLUMN - Spring Hill College, Main Building, Old Shell Road, Spring Hill, Mobile County, AL

Iron aluminide alloys with improved properties for high temperature applications

DOEpatents

McKamey, Claudette G.; Liu, Chain T.

1990-01-01

An improved iron aluminide alloy of the DO.sub.3 type that has increased room temperature ductility and improved high elevated temperature strength. The alloy system further is resistant to corrosive attack in the environments of advanced energy corrosion systems such as those using fossil fuels. The resultant alloy is relatively inexpensive as contrasted to nickel based and high nickel steels currently utilized for structural components. The alloy system consists essentially of 26-30 at. % aluminum, 0.5-10 at. % chromium, 0.02-0.3 at. % boron plus carbon, up to 2 at. % molybdenum, up to 1 at. % niobium, up to 0.5 at. % zirconium, up to 0.1 at. % yttrium, up to 0.5 at. % vanadium and the balance iron.

Iron aluminide alloys with improved properties for high temperature applications

DOEpatents

McKamey, C.G.; Liu, C.T.

1990-10-09

An improved iron aluminide alloy of the DO[sub 3] type is described that has increased room temperature ductility and improved high elevated temperature strength. The alloy system further is resistant to corrosive attack in the environments of advanced energy conversion systems such as those using fossil fuels. The resultant alloy is relatively inexpensive as contrasted to nickel based and high nickel steels currently utilized for structural components. The alloy system consists essentially of 26--30 at. % aluminum, 0.5--10 at. % chromium, 0.02--0.3 at. % boron plus carbon, up to 2 at. % molybdenum, up to 1 at. % niobium, up to 0.5 at. % zirconium, up to 0.1 at. % yttrium, up to 0.5 at. % vanadium and the balance iron. 3 figs.

Remediation of arsenic-contaminated groundwater using media-injected permeable reactive barriers with a modified montmorillonite: sand tank studies.

PubMed

Luo, Ximing; Liu, Haifei; Huang, Guoxin; Li, Ye; Zhao, Yan; Li, Xu

2016-01-01

A modified montmorillonite (MMT) was prepared using an acid activation-sodium activation-iron oxide coating method to improve the adsorption capacities of natural MMTs. For MMT, its interlamellar distance increased from 12.29 to 13.36 Å, and goethite (α-FeOOH) was intercalated into its clay layers. Two novel media-injected permeable reactive barrier (MI-PRB) configurations were proposed for removing arsenic from groundwater. Sand tank experiments were conducted to investigate the performance of the two MI-PRBs: Tank A was filled with quartz sand. Tank B was packed with quartz sand and zero-valent iron (ZVI) in series, and the MMT slurry was respectively injected into them to form reactive zones. The results showed that for tank A, total arsenic (TA) removal of 98.57% was attained within the first 60 mm and subsequently descended slowly to 88.84% at the outlet. For tank B, a similar spatial variation trend was observed in the quartz sand layer, and subsequently, TA removal increased to ≥99.80% in the ZVI layer. TA removal by MMT mainly depended on both surface adsorption and electrostatic adhesion. TA removal by ZVI mainly relied on coagulation/precipitation and adsorption during the iron corrosion. The two MI-PRBs are feasible alternatives for in situ remediation of groundwater with elevated As levels.

Effect of the Ginger Derivative, 6-Shogaol, on Ferritin Levels in Patients With Low to Intermediate-1-Risk Myelodysplastic Syndrome-A Small, Investigative Study.

PubMed

Golombick, Terry; Diamond, Terrence H; Manoharan, Arumugam; Ramakrishna, Rajeev; Badmaev, Vladimir

2017-01-01

Myelodysplastic syndrome (MDS) is a heterogeneous group of clonal stem cell disorders characterized by dysplastic and ineffective hematopoiesis and peripheral cytopenias. Elevated serum ferritin (SF) is often observed in nontransfused, lower risk MDS. It has been reported that ineffective erythropoiesis enhances iron absorption in MDS through downregulation of hepcidin and its prohormones such that SF rises. To determine the effect of 6-shogaol, a dehydration derivative of ginger, known to have hepatoprotective and chemotherapeutic activity, on 6 early-stage, transfusion-independent patients with MDS, 3 of whom had raised levels of SF. Six patients with MDS with low or intermediate-1 subtypes, as defined by the International Prognostic Scoring System (IPSS), were recruited into the study and were administered 1 gel capsule daily containing 20 mg ginger extract standardized for 20% 6-shogaol. Blood and urine samples were collected and various markers monitored at regular intervals. 6-shogaol caused a decrease in SF levels in 3 of 6 patients with early MDS (50%) whose SF levels were elevated at the start of the study. Our findings suggest upregulation of hepcidin and its prohormones, possibly through an improvement in liver function. In light of the encouraging results in this small, investigative study, we are planning a larger study to confirm the beneficial effect of 6-shogaol in patients with raised ferritin levels due to ineffective erythropoiesis.

Effect of the Ginger Derivative, 6-Shogaol, on Ferritin Levels in Patients With Low to Intermediate-1–Risk Myelodysplastic Syndrome—A Small, Investigative Study

PubMed Central

Golombick, Terry; Diamond, Terrence H; Manoharan, Arumugam; Ramakrishna, Rajeev; Badmaev, Vladimir

2017-01-01

Background: Myelodysplastic syndrome (MDS) is a heterogeneous group of clonal stem cell disorders characterized by dysplastic and ineffective hematopoiesis and peripheral cytopenias. Elevated serum ferritin (SF) is often observed in nontransfused, lower risk MDS. It has been reported that ineffective erythropoiesis enhances iron absorption in MDS through downregulation of hepcidin and its prohormones such that SF rises. Aim: To determine the effect of 6-shogaol, a dehydration derivative of ginger, known to have hepatoprotective and chemotherapeutic activity, on 6 early-stage, transfusion-independent patients with MDS, 3 of whom had raised levels of SF. Method: Six patients with MDS with low or intermediate-1 subtypes, as defined by the International Prognostic Scoring System (IPSS), were recruited into the study and were administered 1 gel capsule daily containing 20 mg ginger extract standardized for 20% 6-shogaol. Blood and urine samples were collected and various markers monitored at regular intervals. Results: 6-shogaol caused a decrease in SF levels in 3 of 6 patients with early MDS (50%) whose SF levels were elevated at the start of the study. Our findings suggest upregulation of hepcidin and its prohormones, possibly through an improvement in liver function. Discussion: In light of the encouraging results in this small, investigative study, we are planning a larger study to confirm the beneficial effect of 6-shogaol in patients with raised ferritin levels due to ineffective erythropoiesis. PMID:29147080

Lead-iron phosphate glass as a containment medium for the disposal of high-level nuclear wastes

DOEpatents

Boatner, L.A.; Sales, B.C.

1984-04-11

Disclosed are lead-iron phosphate glasses containing a high level of Fe/sub 2/O/sub 3/ for use as a storage medium for high-level radioactive nuclear waste. By combining lead-iron phosphate glass with various types of simulated high-level nuclear waste

Mössbauer Spectra of Mouse Hearts Reveal Age-dependent Changes in Mitochondrial and Ferritin Iron Levels.

PubMed

Wofford, Joshua D; Chakrabarti, Mrinmoy; Lindahl, Paul A

2017-03-31

Cardiac function requires continuous high levels of energy, and so iron, a critical player in mitochondrial respiration, is an important component of the heart. Hearts from 57 Fe-enriched mice were evaluated by Mössbauer spectroscopy. Spectra consisted of a sextet and two quadrupole doublets. One doublet was due to residual blood, whereas the other was due to [Fe 4 S 4 ] 2+ clusters and low-spin Fe II hemes, most of which were associated with mitochondrial respiration. The sextet was due to ferritin; there was no evidence of hemosiderin, a ferritin decomposition product. Iron from ferritin was nearly absent in young hearts, but increased steadily with age. EPR spectra exhibited signals similar to those of brain, liver, and human cells. No age-dependent EPR trends were apparent. Hearts from HFE -/- mice with hemochromatosis contained slightly more iron overall than controls, including more ferritin and less mitochondrial iron; these differences typify slightly older hearts, perhaps reflecting the burden due to this disease. HFE -/- livers were overloaded with ferritin but had low mitochondrial iron levels. IRP2 -/- hearts contained less ferritin than controls but normal levels of mitochondrial iron. Hearts of young mice born to an iron-deficient mother contained normal levels of mitochondrial iron and no ferritin; the heart from the mother contained low ferritin and normal levels of mitochondrial iron. High-spin Fe II ions were nearly undetectable in heart samples; these were evident in brains, livers, and human cells. Previous Mössbauer spectra of unenriched diseased human hearts lacked mitochondrial and blood doublets and included hemosiderin features. This suggests degradation of iron-containing species during sample preparation. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

Iron Reduces M1 Macrophage Polarization in RAW264.7 Macrophages Associated with Inhibition of STAT1.

PubMed

Gan, Zhen-Shun; Wang, Qian-Qian; Li, Jia-Hui; Wang, Xu-Liang; Wang, Yi-Zhen; Du, Hua-Hua

2017-01-01

Iron metabolism in inflammation has been mostly characterized in macrophages exposed to pathogens or inflammatory conditions. The aim of this study is to investigate the cross-regulatory interactions between M1 macrophage polarization and iron metabolism. Firstly, we characterized the transcription of genes related to iron homeostasis in M1 RAW264.7 macrophages stimulated by IFN- γ . The molecular signature of M1 macrophages showed high levels of iron storage (ferritin), a low level of iron export (ferroportin), and changes of iron regulators (hepcidin and transferrin receptors), which favour iron sequestration in the reticuloendothelial system and are benefit for inflammatory disorders. Then, we evaluated the effect of iron on M1 macrophage polarization. Iron significantly reduced mRNA levels of IL-6, IL-1 β , TNF- α , and iNOS produced by IFN- γ -polarized M1 macrophages. Immunofluorescence analysis showed that iron also reduced iNOS production. However, iron did not compromise but enhanced the ability of M1-polarized macrophages to phagocytose FITC-dextran. Moreover, we demonstrated that STAT1 inhibition was required for reduction of iNOS and M1-related cytokines production by the present of iron. Together, these findings indicated that iron decreased polarization of M1 macrophages and inhibited the production of the proinflammatory cytokines. The results expanded our knowledge about the role of iron in macrophage polarization.

Dissolved and particulate trace metal micronutrients under the McMurdo Sound seasonal sea ice: basal sea ice communities as a capacitor for iron

PubMed Central

Noble, Abigail E.; Moran, Dawn M.; Allen, Andrew E.; Saito, Mak A.

2013-01-01

Dissolved and particulate metal concentrations are reported from three sites beneath and at the base of the McMurdo Sound seasonal sea ice in the Ross Sea of Antarctica. This dataset provided insight into Co and Mn biogeochemistry, supporting a previous hypothesis for water column mixing occurring faster than scavenging. Three observations support this: first, Mn-containing particles with Mn/Al ratios in excess of the sediment were present in the water column, implying the presence of bacterial Mn-oxidation processes. Second, dissolved and labile Co were uniform with depth beneath the sea ice after the winter season. Third, dissolved Co:PO3−4 ratios were consistent with previously observed Ross Sea stoichiometry, implying that over-winter scavenging was slow relative to mixing. Abundant dissolved Fe and Mn were consistent with a winter reserve concept, and particulate Al, Fe, Mn, and Co covaried, implying that these metals behaved similarly. Elevated particulate metals were observed in proximity to the nearby Islands, with particulate Fe/Al ratios similar to that of nearby sediment, consistent with a sediment resuspension source. Dissolved and particulate metals were elevated at the shallowest depths (particularly Fe) with elevated particulate P/Al and Fe/Al ratios in excess of sediments, demonstrating a sea ice biomass source. The sea ice biomass was extremely dense (chl a >9500 μg/L) and contained high abundances of particulate metals with elevated metal/Al ratios. A hypothesis for seasonal accumulation of bioactive metals at the base of the McMurdo Sound sea ice by the basal algal community is presented, analogous to a capacitor that accumulates iron during the spring and early summer. The release and transport of particulate metals accumulated at the base of the sea ice by sloughing is discussed as a potentially important mechanism in providing iron nutrition during polynya phytoplankton bloom formation and could be examined in future oceanographic expeditions. PMID:24790953

Dissolved and particulate trace metal micronutrients under the McMurdo Sound seasonal sea ice: basal sea ice communities as a capacitor for iron

NASA Astrophysics Data System (ADS)

Noble, Abigail; Saito, Mak; Moran, Dawn; Allen, Andrew

2013-10-01

Dissolved and particulate metal concentrations are reported from three sites beneath and at the base of the McMurdo Sound seasonal sea ice in the Ross Sea of Antarctica. This dataset provided insight into Co and Mn biogeochemistry, supporting a previous hypothesis for water column mixing occurring faster than scavenging. Three observations support this: first, Mn-containing particles with Mn/Al ratios in excess of the sediment were present in the water column, implying the presence of bacterial Mn-oxidation processes. Second, dissolved and labile Co were uniform with depth beneath the sea ice after the winter season. Third, dissolved Co:PO43- ratios were consistent with previously observed Ross Sea stoichiometry, implying that over-winter scavenging was slow relative to mixing. Abundant dissolved Fe and Mn were consistent with a winter reserve concept, and particulate Al, Fe, Mn, and Co covaried, implying that these metals behaved similarly. Elevated particulate metals were observed in proximity to the nearby Islands, with particulate Fe/Al ratios similar to that of nearby sediment, consistent with a sediment resuspension source. Dissolved and particulate metals were elevated at the shallowest depths (particularly Fe) with elevated particulate P/Al and Fe/Al ratios in excess of sediments, demonstrating a sea ice biomass source. The sea ice biomass was extremely dense (chl a >9500 μg/L) and contained high abundances of particulate metals with elevated metal/Al ratios. A hypothesis for seasonal accumulation of bioactive metals at the base of the McMurdo Sound sea ice by the basal algal community is presented, analogous to a capacitor that accumulates iron during the spring and early summer. The release and transport of particulate metals accumulated at the base of the sea ice by sloughing is discussed as a potentially important mechanism in providing iron nutrition during polynya phytoplankton bloom formation and could be examined in future oceanographic expeditions.

The effects of maternal iron deficiency on infant fibroblast growth factor-23 and mineral metabolism

PubMed Central

Braithwaite, V.S.; Prentice, A.; Darboe, M.K.; Prentice, A.M.; Moore, S.E.

2016-01-01

Fibroblast growth factor-23 (FGF23), a phosphate(Phos)-regulating hormone, is abnormally elevated in hypophosphataemic syndromes and an elevated FGF23 is a predictor of mortality in kidney disease. Recent findings suggest iron deficiency as a potential mediator of FGF23 expression and murine studies have shown in utero effects of maternal iron deficiency on offspring FGF23 and phosphate metabolism. Our aim was to investigate the impact of maternal iron status on infant FGF23 and mineral metabolites over the first 2 years of life. Infants born to mothers with normal (NIn = 25,) and low (LIn = 25) iron status during pregnancy, from a mother-infant trial (ISRCTN49285450) in rural Gambia, West Africa, had blood and plasma samples analysed at 12, 24, 52, 78 and 104 weeks (wk) of age. Circulating intact-FGF23 (I-FGF23), Phos, total alkaline phosphatase (TALP) and haemoglobin (Hb) decreased and estimated glomerular filtration rate increased over time [all P ≤ 0.0001)]. C-terminal-FGF23 (C-FGF23) and TALP were significantly higher in LI compared with NI, from 52 wk for C-FGF23 [Beta coefficient (SE) 18.1 (0.04) %, P = 0.04] and from 24 wk for TALP [44.7 (29.6) U/L, P = 0.04]. Infant Hb was the strongest negative predictor of C-FGF23 concentration [− 21% (4%) RU/mL, P ≤ 0.0001], Phos was the strongest positive predictor of I-FGF23 [32.0(3.9) pg/mL, P ≤ 0.0001] and I-FGF23 did not predict C-FGF23 over time [− 0.5% (0.5%), P = 0.3]. In conclusion, this study suggests that poor maternal iron status is associated with a higher infant C-FGF23 and TALP but similar I-FGF23 concentrations in infants and young children. These findings further highlight the likely public health importance of preventing iron deficiency during pregnancy. Whether or not children who are born to iron deficient mothers have persistently high concentrations of these metabolites and are more likely to be at risk of impaired bone development and pre-disposed to rickets requires further research. PMID:26453792

Mineral Levels in Thalassaemia Major Patients Using Different Iron Chelators.

PubMed

Genc, Gizem Esra; Ozturk, Zeynep; Gumuslu, Saadet; Kupesiz, Alphan

2016-03-01

The goal of the present study was to determine the levels of minerals in chronically transfused thalassaemic patients living in Antalya, Turkey and to determine mineral levels in groups using different iron chelators. Three iron chelators deferoxamine, deferiprone and deferasirox have been used to remove iron from patients' tissues. There were contradictory results in the literature about minerals including selenium, zinc, copper, and magnesium in thalassaemia major patients. Blood samples from the 60 thalassaemia major patients (the deferoxamine group, n = 19; the deferiprone group, n = 20 and the deferasirox group, n = 21) and the controls (n = 20) were collected. Levels of selenium, zinc, copper, magnesium, and iron were measured, and all of them except iron showed no significant difference between the controls and the patients regardless of chelator type. Serum copper levels in the deferasirox group were lower than those in the control and deferoxamine groups, and serum magnesium levels in the deferasirox group were higher than those in the control, deferoxamine and deferiprone groups. Iron levels in the patient groups were higher than those in the control group, and iron levels showed a significant correlation with selenium and magnesium levels. Different values of minerals in thalassaemia major patients may be the result of different dietary intake, chelator type, or regional differences in where patients live. That is why minerals may be measured in thalassaemia major patients at intervals, and deficient minerals should be replaced. Being careful about levels of copper and magnesium in thalassaemia major patients using deferasirox seems to be beneficial.

PhybalSIT — Fatigue Assessment and Life Time Calculation of the Ductile Cast Iron EN-GJS-600 at Ambient and Elevated Temperatures

NASA Astrophysics Data System (ADS)

Jost, Benjamin; Klein, Marcus; Eifler, Dietmar

This paper focuses on the ductile cast iron EN-GJS-600 which is often used for components of combustion engines. Under service conditions, those components are mechanically loaded at different temperatures. Therefore, this investigation targets at the fatigue behavior of EN-GJS-600 at ambient and elevated temperatures. Light and scanning electron microscopic investigations were done to characterize the sphericity of the graphite as well as the ferrite, pearlite and graphite fraction. At elevated temperatures, the consideration of dynamic strain ageing effects is of major importance. In total strain increase, temperature increase and constant total strain amplitude tests, the plastic strain amplitude, the stress amplitude, the change in temperature and the change in electrical resistance were measured. The measured values depend on plastic deformation processes in the bulk of the specimens and at the interfaces between matrix and graphite. The fatigue behavior of EN-GJS-600 is dominated by cyclic hardening processes. The physically based fatigue life calculation "PHYBALSIT" (SIT = strain increase test) was developed for total strain controlled fatigue tests. Only one temperature increase test is necessary to determine the temperature interval of pronounced dynamic strain ageing effects.

Monoamine metabolites, iron induced seizures, and the anticonvulsant effect of tannins.

PubMed

Kabuto, H; Yokoi, I; Mori, A

1992-06-01

Intracortical injections of iron ions have been shown to induce recurrent seizures and epileptic discharges in the EEG. (-)-Epigallocatechin (EGC) and (-)-epigallocatechin-3-O-gallate (EGCG), isolated from green tea leaves, have been reported to prevent or diminish the occurrence of epileptic discharges induced by iron ions, and to inhibit catechol-O-methyltransferase. Iron ions significantly increased DOPAC and HVA levels in the intrastriatal perfusate 140 and 180 minutes, respectively, after injection. EGC and EGCG inhibited the increases induced by iron ions. Furthermore, EGCG decreased the HVA level in the perfusate 200 minutes after injection whether or not iron ions were injected. Iron ions had no effect on the 5-HIAA level, and EGC and EGCG raised it. These results suggest that formation of an epileptic focus induced by iron ions might be accompanied by activation of dopaminergic neurons, and that EGC and EGCG inhibit that hyperactivity.

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.

Bmp6 Regulates Retinal Iron Homeostasis and Has Altered Expression in Age-Related Macular Degeneration

PubMed Central

Hadziahmetovic, Majda; Song, Ying; Wolkow, Natalie; Iacovelli, Jared; Kautz, Leon; Roth, Marie-Paule; Dunaief, Joshua L.

2011-01-01

Iron-induced oxidative stress causes hereditary macular degeneration in patients with aceruloplasminemia. Similarly, retinal iron accumulation in age-related macular degeneration (AMD) may exacerbate the disease. The cause of retinal iron accumulation in AMD is poorly understood. Given that bone morphogenetic protein 6 (Bmp6) is a major regulator of systemic iron, we examined the role of Bmp6 in retinal iron regulation and in AMD pathogenesis. Bmp6 was detected in the retinal pigment epithelium (RPE), a major site of pathology in AMD. In cultured RPE cells, Bmp6 was down-regulated by oxidative stress and up-regulated by iron. Intraocular Bmp6 protein injection in mice up-regulated retinal hepcidin, an iron regulatory hormone, and altered retinal labile iron levels. Bmp6−/− mice had age-dependent retinal iron accumulation and degeneration. Postmortem RPE from patients with early AMD exhibited decreased Bmp6 levels. Because oxidative stress is associated with AMD pathogenesis and down-regulates Bmp6 in cultured RPE cells, the diminished Bmp6 levels observed in RPE cells in early AMD may contribute to iron build-up in AMD. This may in turn propagate a vicious cycle of oxidative stress and iron accumulation, exacerbating AMD and other diseases with hereditary or acquired iron excess. PMID:21703414

Artificial intelligence models for predicting iron deficiency anemia and iron serum level based on accessible laboratory data.

PubMed

Azarkhish, Iman; Raoufy, Mohammad Reza; Gharibzadeh, Shahriar

2012-06-01

Iron deficiency anemia (IDA) is the most common nutritional deficiency worldwide. Measuring serum iron is time consuming, expensive and not available in most hospitals. In this study, based on four accessible laboratory data (MCV, MCH, MCHC, Hb/RBC), we developed an artificial neural network (ANN) and an adaptive neuro-fuzzy inference system (ANFIS) to diagnose the IDA and to predict serum iron level. Our results represent that the neural network analysis is superior to ANFIS and logistic regression models in diagnosing IDA. Moreover, the results show that the ANN is likely to provide an accurate test for predicting serum iron levels with high accuracy and acceptable precision.

Transfusional iron overload in children with sickle cell anemia on chronic transfusion therapy for secondary stroke prevention.

PubMed

Kwiatkowski, Janet L; Cohen, Alan R; Garro, Julian; Alvarez, Ofelia; Nagasubramanian, Ramamorrthy; Sarnaik, Sharada; Thompson, Alexis; Woods, Gerald M; Schultz, William; Mortier, Nicole; Lane, Peter; Mueller, Brigitta; Yovetich, Nancy; Ware, Russell E

2012-02-01

Chronic transfusion reduces the risk of recurrent stroke in children with sickle cell anemia (SCA) but leads to iron loading. Management of transfusional iron overload in SCA has been reported as suboptimal [1], but studies characterizing monitoring and treatment practices for iron overload in children with SCA, particularly in recent years with the expansion of chelator options, are lacking. We investigated the degree of iron loading and treatment practices of 161 children with SCA receiving transfusions for a history of stroke who participated in the Stroke with Transfusions Changing to Hydroxyurea (SWiTCH) trial. Data obtained during screening, including past and entry liver iron concentration (LIC) measurements, ferritin values, and chelation were analyzed. The mean age at enrollment was 12.9 ± 4 years and the mean duration of transfusion was 7 ± 3.8 years. Baseline LIC (median 12.94 mg/g dw) and serum ferritin (median 3,164 ng/mL) were elevated. Chelation therapy was initiated after a mean of 2.6 years of transfusions. At study entry, 137 were receiving chelation, most of whom (90%) were receiving deferasirox. This study underscores the need for better monitoring of iron burden with timely treatment adjustments in chronically transfused children with SCA.

Anchorage of iron hydro(oxide) nanoparticles onto activated carbon to remove As(V) from water.

PubMed

Nieto-Delgado, Cesar; Rangel-Mendez, Jose Rene

2012-06-01

The adsorption of arsenic (V) by granular iron hydro(oxides) has been proven to be a reliable technique. However, due to the low mechanical properties of this material, it is difficult to apply it in full scale water treatment. Hence, the aim of this research is to develop a methodology to anchor iron hydro(oxide) nanoparticles onto activated carbon, in which the iron hydro(oxide) nanoparticles will give the activated carbon an elevated active surface area for arsenic adsorption and also help avoid the blockage of the activated carbon pores. Three activated carbons were modified by employing the thermal hydrolysis of iron as the anchorage procedure. The effects of hydrolysis temperature (60-120 °C), hydrolysis time (4-16 h), and FeCl(3) concentration (0.4-3 mol Fe/L) were studied by the surface response methodology. The iron content of the modified samples ranged from 0.73 to 5.27%, with the higher end of the range pertaining to the carbons with high oxygen content. The materials containing smaller iron hydro(oxide) particles exhibited an enhanced arsenic adsorption capacity. The best adsorbent material reported an arsenic adsorption capacity of 4.56 mg As/g at 1.5 ppm As at equilibrium and pH 7. Copyright © 2012 Elsevier Ltd. All rights reserved.

Aeshnid dragonfly larvae as bioindicators of methylmercury contamination in aquatic systems impacted by elevated sulfate loading

USGS Publications Warehouse

Jeremiason, Jeffrey D.; Reiser, T. K.; Weitz, R. A.; Berndt, M.E.; Aiken, George R.

2016-01-01

Methylmercury (MeHg) levels in dragonfly larvae and water were measured over two years in aquatic systems impacted to varying degrees by sulfate releases related to iron mining activity. This study examined the impact of elevated sulfate loads on MeHg concentrations and tested the use of MeHg in dragonfly larvae as an indicator of MeHg levels in a range of aquatic systems including 16 river/stream sites and two lakes. MeHg concentrations in aeshnid dragonfly larvae were positively correlated (R2 = 0.46, p < 0.01) to peak MeHg concentrations in the dissolved phase for the combined years of 2012 and 2013. This relation was strong in 2012 (R2 = 0.85, p < 0.01), but showed no correlation in 2013 (R2 = 0.02, p > 0.05). MeHg in dragonfly larvae were not elevated at the highest sulfate sites, but rather the reverse was generally observed. Record rainfall events in 2012 and above average rainfall in 2013 likely delivered the majority of Hg and MeHg to these systems via interflow and activated groundwater flow through reduced sediments. As a result, the impacts of elevated sulfate releases due to mining activities were not apparent in these systems where little of the sulfate is reduced. Lower bioaccumulation factors for MeHg in aeshnid dragonfly larvae were observed with increasing dissolved organic carbon (DOC) concentrations. This finding is consistent with previous studies showing that MeHg in high DOC systems is less bioavailable; an equilibrium model shows that more MeHg being associated with DOC rather than algae at the base of the food chain readily explains the lower bioaccumulation factors.

Iron regulatory proteins and their role in controlling iron metabolism.

PubMed

Kühn, Lukas C

2015-02-01

Cellular iron homeostasis is regulated by post-transcriptional feedback mechanisms, which control the expression of proteins involved in iron uptake, release and storage. Two cytoplasmic proteins with mRNA-binding properties, iron regulatory proteins 1 and 2 (IRP1 and IRP2) play a central role in this regulation. Foremost, IRPs regulate ferritin H and ferritin L translation and thus iron storage, as well as transferrin receptor 1 (TfR1) mRNA stability, thereby adjusting receptor expression and iron uptake via receptor-mediated endocytosis of iron-loaded transferrin. In addition splice variants of iron transporters for import and export at the plasma-membrane, divalent metal transporter 1 (DMT1) and ferroportin are regulated by IRPs. These mechanisms have probably evolved to maintain the cytoplasmic labile iron pool (LIP) at an appropriate level. In certain tissues, the regulation exerted by IRPs influences iron homeostasis and utilization of the entire organism. In intestine, the control of ferritin expression limits intestinal iron absorption and, thus, whole body iron levels. In bone marrow, erythroid heme biosynthesis is coordinated with iron availability through IRP-mediated translational control of erythroid 5-aminolevulinate synthase mRNA. Moreover, the translational control of HIF2α mRNA in kidney by IRP1 coordinates erythropoietin synthesis with iron and oxygen supply. Besides IRPs, body iron absorption is negatively regulated by hepcidin. This peptide hormone, synthesized and secreted by the liver in response to high serum iron, downregulates ferroportin at the protein level and thereby limits iron absorption from the diet. Hepcidin will not be discussed in further detail here.

Uranium fate in wetland mesocosms: Effects of plants at two iron loadings with different pH values.

PubMed

Koster van Groos, Paul G; Kaplan, Daniel I; Chang, Hyun-Shik; Seaman, John C; Li, Dien; Peacock, Aaron D; Scheckel, Kirk G; Jaffé, Peter R

2016-11-01

Small-scale continuous flow wetland mesocosms (∼0.8 L) were used to evaluate how plant roots under different iron loadings affect uranium (U) mobility. When significant concentrations of ferrous iron (Fe) were present at circumneutral pH values, U concentrations in root exposed sediments were an order of magnitude greater than concentrations in root excluded sediments. Micro X-ray absorption near-edge structure (μ-XANES) spectroscopy indicated that U was associated with the plant roots primarily as U(VI) or U(V), with limited evidence of U(IV). Micro X-ray fluorescence (μ-XRF) of plant roots suggested that for high iron loading at circumneutral pH, U was co-located with Fe, perhaps co-precipitated with root Fe plaques, while for low iron loading at a pH of ∼4 the correlation between U and Fe was not significant, consistent with previous observations of U associated with organic matter. Quantitative PCR analyses indicated that the root exposed sediments also contained elevated numbers of Geobacter spp., which are likely associated with enhanced iron cycling, but may also reduce mobile U(VI) to less mobile U(IV) species. Copyright © 2016 Elsevier Ltd. All rights reserved.

Infant anaemia is associated with infection, low birthweight and iron deficiency in rural Bangladesh.

PubMed

Eneroth, Hanna; Persson, Lars-Åke; El Arifeen, Shams; Ekström, Eva-Charlotte

2011-02-01

To estimate the prevalence of infant anaemia and its association with iron deficiency, growth, infection and other micronutrient deficiencies. Using data from MINIMat, a randomized maternal food and micronutrient supplementation trial, we assessed the associations between anaemia (haemoglobin < 105 g/L) in 580 infants at 6 months and deficiencies of iron, vitamin A, vitamin B12, zinc and folate, infection and anthropometric indices. Variables associated with anaemia in bivariate analyses were evaluated in logistic regression models, adjusting for potential confounders. Anaemia was found in 46% of the infants, and among these, 28% had iron deficiency (plasma ferritin <9 μg/L). Elevated C-reactive protein (>10mg/L) (OR = 2.7, 95% CI: 1.6, 4.7), low birthweight (OR = 2.3, 95% CI: 1.5, 3.5) and iron deficiency (OR = 2.2, 95% CI: 1.4, 3.6) were independently associated with increased risk for anaemia. We also observed a seasonal variation in anaemia not mediated through the other factors studied. In a cohort in rural Bangladesh, anaemia at age 6 months was common and associated with infection, low birthweight and iron deficiency. © 2010 The Author(s)/Acta Paediatrica © 2010 Foundation Acta Paediatrica.

Pathophysiology of transfusional iron overload: contrasting patterns in thalassemia major and sickle cell disease.

PubMed

Porter, John B

2009-01-01

The pathophysiological consequences of transfusional iron overload largely reflect the pattern of excess iron distribution and include cardiomyopathy, endocrinopathy, cirrhosis, and hepatocellular carcinoma. Since the introduction of desferrioxamine (DFO) in the late 1970s, these complications have fallen substantially but approximately half of the chelated adult patients with thalassemia major (TM) still show evidence of increased myocardial iron loading by MRI. An understanding of the factors that determine the propensity to extrahepatic iron distribution may be a key to minimizing the pathophysiological consequences of transfusional iron overload. Transfused patients with sickle cell disease (SCD) appear less likely to develop these extrahepatic complications, possibly because plasma nontransferrin-bound iron (NTBI) levels are typically lower than in TM patients at matched levels of iron loading. Other mechanisms that may reduce the extrahepatic iron distribution in SCD include raised plasma hepcidin due to chronic inflammation, lower growth differentiation factor 15 (GDF15) levels because of less ineffective erythropoiesis (IE), and induction of heme oxygenase (HO1) by intravascular hemolysis. Further understanding of these mechanisms may help in designing strategies to decrease extrahepatic iron distribution in TM.

High Iron Levels Are Associated with Increased Malaria Risk in Infants during the First Year of Life in Benin.

PubMed

Moya-Alvarez, Violeta; Cottrell, Gilles; Ouédraogo, Smaila; Accrombessi, Manfred; Massougbodgi, Achille; Cot, Michel

2017-08-01

The World Health Organization (WHO) estimates that 40% of children in low-income countries are anemic. Therefore, iron supplements are recommended by WHO in areas with high anemia rates. However, some studies have set into question the benefits of iron supplementation in malaria-endemic regions. In Benin, a west African country with high prevalence of anemia and malaria, no iron supplements are given systematically to infants so far despite the WHO recommendations. In this context, we wanted to investigate the effect of iron levels during the first year of life on malarial risk in Benin considering complementary risk factors. We followed 400 women and their offspring between January 2010 and June 2012 in Allada (Benin). Environmental, obstetric, and numerous clinical, maternal, and infant risk factors were considered. In multilevel models, high iron levels were significantly associated with the risk of a positive blood smear (adjusted odds ratio = 2.90, P < 0.001) and Plasmodium falciparum parasitemia (beta estimate = 0.38, P < 0.001). Infants with iron levels in the lowest quartile were less likely to have a positive blood smear ( P < 0.001), and the risk increased with higher iron levels. Our results appeal for additional evaluation of the effect of different doses of iron supplements on the infant health status, including malaria incidence. Thus, the health status of infants should be compared between cohorts where iron is given either for prevention or anemia treatment, to better understand the effect of iron supplements on infant health.

Absolute and functional iron deficiency in professional athletes during training and recovery.

PubMed

Reinke, Simon; Taylor, William R; Duda, Georg N; von Haehling, Stephan; Reinke, Petra; Volk, Hans-Dieter; Anker, Stefan D; Doehner, Wolfram

2012-04-19

Iron deficiency (ID) is one of the most important metabolic dysfunctions. Athletic performance depends on oxygen transport and mitochondrial efficiency, thus on optimal iron balance. We hypothesised that physical extremes result in ID in elite athletes and that the short recovery period may be insufficient to allow a lasting replenishment of iron reserves. Iron metabolism was examined in 20 elite rowing athletes and 10 professional soccer players at the end of a competitive season, after recuperation and during pre-season training. Absolute ID values were defined as ferritin <30 μg/L, functional ID as ferritin 30-99 μg/L or 100-299 μg/L+transferrin saturation <20%. At the end of season, 27% of all athletes had absolute ID and 70% showed functional ID. Absolute iron depletion was not generally restored after recuperation and observed at all time points in 14% of the athletes. Although athletes with initially low ferritin levels showed a slight increase during recuperation (p<0.09), these increases remained within borderline levels. Furthermore, 10% showed borderline haemoglobin levels, suggestive of mild anaemia, as defined by the World Health Organisation. A significant proportion of professional athletes have ID, independent of the training mode. Although recuperation seems to allow a certain recovery of iron storage, particularly in athletes with initially low ferritin levels, this retrieval was insufficient to fully normalise reduced iron levels. Therefore, iron status should be carefully monitored during the various training and competitive periods in elite athletes. An adequate iron supplementation may be needed to maintain balanced iron stores. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

A study to establish whether food-based approaches can improve serum iron levels in child-bearing aged women.

PubMed

Bokhari, F; Derbyshire, E; Li, W; Brennan, C S; Stojceska, V

2012-02-01

Iron-deficiency anaemia is particularly prevalent in pregnancy. The present study aimed to determine whether functional bread containing teff flour (i.e. naturally rich in iron) could be an alternative way of improving iron status. However, before testing whether its consumption can improve pregnancy iron status, the bio-availability of iron was determined in a sample of nonpregnant women. Fifty-eight women (20-50 years) were recruited from the University. Blood samples were taken at baseline to assess iron status and participants were screened to account for other factors affecting iron status. Twenty-four participants (haemoglobin 9.5-14.0g dL(-1) ) were recruited to take part in the intervention and allocated to five groups: (i) control bread (CB); (ii) teff bread (TB); (iii) TB+level 1 phytase (TB+P1); (iv) TB+level 2 phytase (TB+P2); or (v) a supplement containing 10 mg of ferrous sulphate. Venous blood samples were taken before the intervention and after 180-210min, aiming to determine changes in serum iron. Consuming three or four slices of TB provided statistically significantly more iron (7.6mg) than CB (5.1mg) (P<0.001). Because participants were fasted, serum iron levels declined in all bread groups (average -1.5μm), although the smallest reduction was observed in the TB+P2 group (-0.3 μm). The area-under-the-curve from baseline to 210min was lower in the TB+P2 (-78.8μmol min L(-1) ) group compared to the other bread interventions, indicating higher levels of iron absorption in this group. The results obtained in the present study show that TB consumption may help to maintain serum iron levels, especially when phytase is added. The findings from the study also demonstrate there may be potential to further improve the bio-availability of iron from non-haem food sources. © 2011 Manchester Metropolitan University. Journal of Human Nutrition and Dietetics © 2011 The British Dietetic Association Ltd.

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.

Ferric Citrate Decreases Fibroblast Growth Factor 23 and Improves Erythropoietin Responsiveness in Hemodialysis Patients.

PubMed

Maruyama, Noriaki; Otsuki, Tomoyasu; Yoshida, Yoshinori; Nagura, Chinami; Kitai, Maki; Shibahara, Nami; Tomita, Hyoe; Maruyama, Takashi; Abe, Masanori

2018-06-06

Serum phosphate and vitamin D receptor activator regulate fibroblast growth factor 23 (FGF23), and iron may modulate FGF23 metabolism. The aim of the present study was to elucidate the effects of ferric citrate hydrate and lanthanum carbohydrate on serum FGF23 levels in hemodialysis patients. This prospective, open-label, multicenter study enrolled 60 patients on hemodialysis treated with lanthanum carbonate. Patients were randomly assigned to 2 groups: those switching from lanthanum carbonate to ferric citrate hydrate (ferric citrate group, n = 30) or those continuing lanthanum carbonate (control group, n = 30). Patients were monitored for 24 weeks. Endpoints included changes in FGF23, phosphate, and the dose of erythropoiesis stimulating agent (ESA), erythropoietin responsiveness index (ERI), and adverse events. FGF-23 levels were significantly lower in the ferric citrate group compared with the levels in the control group (change from baseline -6,160 vs. -1,118 pg/mL; p = 0.026). There were no significant changes in serum calcium, phosphate, and intact parathyroid hormone levels in either group. The ferric citrate group had significantly increased serum iron, ferritin, and transferrin saturation. Hemoglobin levels were significantly elevated, and the dose of ESA was significantly decreased in the ferric citrate group but not in the control group. ERI and the dose of intravenous saccharated ferric oxide were significantly lower in the ferric citrate group compared with those of the control group (p = 0.015 and p = 0.002). In patients on hemodialysis, 24-week treatment with ferric citrate hydrate resulted in significant reduction in FGF23 and ERI independently of serum phosphate level. © 2018 S. Karger AG, Basel.

Erythrocyte transfusions and serum prohepcidin levels in premature newborns with anemia of prematurity.

PubMed

Yapakçi, Ece; Ecevit, Ayşe; Gökmen, Zeynel; Tarcan, Aylin; Ozbek, Namik

2009-11-01

Hepcidin is a regulatory peptide hormone acts by limiting intestinal iron absorption and promoting iron retention. Determining the level of hepcidin in anemia of prematurity might be important in preventing iron overload. This study aimed to determine serum levels of prohepcidin in newborns with anemia of prematurity, to assess the effect of a single erythrocyte transfusion on serum prohepcidin levels, and to determine the possible relationships between prohepcidin levels and serum iron and complete blood count parameters. Nineteen premature newborns with anemia of prematurity who had been treated with erythrocyte transfusions were included in this study. Just before, and 48 hours after, each transfusion, venous blood samples were collected from patients. Serum prohepcidin levels before and after erythrocyte transfusion were 206.5+/-27.3 and 205.7+/-47.1 ng/mL, respectively; no statistically significant differences were found. No significant differences existed before or after transfusion regarding serum total iron and ferritin levels, iron-binding capacity, or mean corpuscular hemoglobin concentration. No significant correlations existed between serum prohepcidin levels and other parameters, either before or after transfusions. Our results showed that there were no statistically significant differences between serum prohepcidin levels before and after a single erythrocyte transfusion in premature newborns.

Iron release from the Lucky Iron Fish®: safety considerations.

PubMed

Armstrong, Gavin R; Dewey, Cate E; Summerlee, Alastair Js

2017-01-01

The principal objective was to explore in greater detail safety issues with regard to the use of the Lucky Iron Fish® (fish) as a treatment for iron deficiency and iron deficiency anaemia in women in rural Cambodia. Experiments were done to determine: (1) purity of the iron in the fish by mass spectroscopy; (2) release of iron and contaminants released during boiling in water using inductive-ly-coupled plasma optical emission spectroscopy; (3) the impact of cooking time, acidity and number of fish in acidified water and two types of Khmer soups; and (4) drinkability of the water after boiling with different num-bers of fish. The fish is composed primarily of ferrous iron with less than 12% non-ferrous iron. Contaminants were either not detectable or levels were below the acceptable standards set by the World Health Organization. The length of time boiling the fish and the acidity of the water increased iron release but even with 5 fish boiled for 60 minutes, iron levels only approached levels where side effects are observed. Boiling one fish in water did not affect the perception of colour, smell or taste of the water but boiling in water with two or more fish resulted in the water being unpalatable which further limits the potential for iron toxicity from using the fish. The results suggest that the Lucky Iron Fish™ may be a safe treatment for iron deficiency.

Inflammation-induced effects on iron-related proteins in splenic macrophages and the liver in mice.

PubMed

Sukumaran, Abitha; Venkatraman, Aparna; Jacob, Molly

2012-06-15

Anemia of inflammation is characterized by disturbances in systemic iron homeostasis. In order to better understand the events involved, we carried out a time-course study on the effects of acute and chronic inflammation on iron-related proteins in mouse splenic macrophages and the liver. Mice were sacrificed at various time points ranging from 0 h up to 4 weeks after induction of inflammation with turpentine oil. Expression levels of iron-related proteins in the splenic macrophages and liver were determined. Iron levels in the serum, spleen and liver were also measured. Hepatic hepcidin was found to be induced in response to inflammation. In the macrophages, expression levels of ferroportin and TfR1 were decreased at some of the time points. The expression of hepatic TfR1 and ferritin was significantly higher at the early time points. Ferritin levels in the liver decreased progressively thereafter; this was associated with significantly higher ferroportin expression in the liver, despite high levels of hepcidin, suggesting that hepcidin may not regulate ferroportin levels in the liver, unlike in the macrophages. The effects of hepcidin, thus, appeared to be tissue-specific. Serum iron levels were decreased initially; these then rose and were associated with decreasing iron levels in the liver and spleen. Thus, inflammation affected the expression levels of many proteins involved in iron homeostasis in splenic macrophages and the liver, with differences seen in the effects at these 2 sites. These effects are likely to contribute to the development of anemia of inflammation. Copyright © 2012 Elsevier Inc. All rights reserved.

Transfusional iron burden and liver toxicity after bone marrow transplantation for acute myelogenous leukemia and hemoglobinopathies.

PubMed

Jastaniah, Wasil; Harmatz, Paul; Pakbaz, Zahra; Fischer, Roland; Vichinsky, Elliott; Walters, Mark C

2008-02-01

While it is appropriate to treat transfusional iron overload to limit end-organ injury after bone marrow transplantation (BMT) for beta-thalassemia major (TM), this approach after BMT for sickle cell disease (SCD) and hematological malignancies has not been studied. Fifteen children with SCD (n = 4), TM (n = 6), or acute myelogenous leukemia (AML, n = 5) underwent HLA-identical sibling BMT between 2000 and 2003. Prospective evaluations of iron biomarkers were performed and the three groups were compared. The pre-BMT duration and volume of RBC transfusions varied among the three groups, but baseline ferritin and liver iron concentration (LIC) were similar. In contrast, liver histology differed. Liver inflammation was present in four TM patients and portal fibrosis was observed in five TM and one SCD patient. Hepatic veno-occlusive disease (VOD) developed in 5 of 15 patients. VOD was not associated with age, ferritin, ALT, or transfusions, but an association with liver inflammation and elevated LIC was suggested. Phlebotomy was performed in five patients after BMT. Changes in LIC were minimal in non-phlebotomized patients (P = 0.02). Iron biomarkers demonstrated significant iron overload before BMT in patients with malignant and non-malignant disorders. However, iron overload was associated with liver inflammation and VOD primarily in TM patients. The clinical significance of iron overload in patients after BMT remains uncertain, but this is the first study to suggest that VOD may be associated with transfusional iron burden. (c) 2007 Wiley-Liss, Inc.

Iron homeostasis and toxicity in retinal degeneration.

PubMed

He, Xining; Hahn, Paul; Iacovelli, Jared; Wong, Robert; King, Chih; Bhisitkul, Robert; Massaro-Giordano, Mina; Dunaief, Joshua L

2007-11-01

Iron is essential for many metabolic processes but can also cause damage. As a potent generator of hydroxyl radical, the most reactive of the free radicals, iron can cause considerable oxidative stress. Since iron is absorbed through diet but not excreted except through menstruation, total body iron levels buildup with age. Macular iron levels increase with age, in both men and women. This iron has the potential to contribute to retinal degeneration. Here we present an overview of the evidence suggesting that iron may contribute to retinal degenerations. Intraocular iron foreign bodies cause retinal degeneration. Retinal iron buildup resulting from hereditary iron homeostasis disorders aceruloplasminemia, Friedreich's ataxia, and panthothenate kinase-associated neurodegeneration cause retinal degeneration. Mice with targeted mutation of the iron exporter ceruloplasmin have age-dependent retinal iron overload and a resulting retinal degeneration with features of age-related macular degeneration (AMD). Post mortem retinas from patients with AMD have more iron and the iron carrier transferrin than age-matched controls. Over the past 10 years much has been learned about the intricate network of proteins involved in iron handling. Many of these, including transferrin, transferrin receptor, divalent metal transporter-1, ferritin, ferroportin, ceruloplasmin, hephaestin, iron-regulatory protein, and histocompatibility leukocyte antigen class I-like protein involved in iron homeostasis (HFE) have been found in the retina. Some of these proteins have been found in the cornea and lens as well. Levels of the iron carrier transferrin are high in the aqueous and vitreous humors. The functions of these proteins in other tissues, combined with studies on cultured ocular tissues, genetically engineered mice, and eye exams on patients with hereditary iron diseases provide clues regarding their ocular functions. Iron may play a role in a broad range of ocular diseases, including glaucoma, cataract, AMD, and conditions causing intraocular hemorrhage. While iron deficiency must be prevented, the therapeutic potential of limiting iron-induced ocular oxidative damage is high. Systemic, local, or topical iron chelation with an expanding repertoire of drugs has clinical potential.

Meteor Crater, AZ

NASA Image and Video Library

2002-03-12

The Barringer Meteorite Crater (also known as "Meteor Crater") is a gigantic hole in the middle of the arid sandstone of the Arizona desert. A rim of smashed and jumbled boulders, some of them the size of small houses, rises 50 m above the level of the surrounding plain. The crater itself is nearly a 1500 m wide, and 180 m deep. When Europeans first discovered the crater, the plain around it was covered with chunks of meteoritic iron - over 30 tons of it, scattered over an area 12 to 15 km in diameter. Scientists now believe that the crater was created approximately 50,000 years ago. The meteorite which made it was composed almost entirely of nickel-iron, suggesting that it may have originated in the interior of a small planet. It was 50 m across, weighed roughly 300,000 tons, and was traveling at a speed of 65,000 km per hour. This ASTER 3-D perspective view was created by draping an ASTER bands 3-2-1image over a digital elevation model from the US Geological Survey National Elevation Dataset. This image was acquired on May 17, 2001 by the Advanced Spaceborne Thermal Emission and Reflection Radiometer (ASTER) on NASA's Terra satellite. With its 14 spectral bands from the visible to the thermal infrared wavelength region, and its high spatial resolution of 15 to 90 meters (about 50 to 300 feet), ASTER will image Earth for the next 6 years to map and monitor the changing surface of our planet. http://photojournal.jpl.nasa.gov/catalog/PIA03490

[Effect of atmospheric CO2 concentration and nitrogen application level on absorption and transportation of nutrient elements in oilseed rape].

PubMed

Wang, Wen-ming; Zhang, Zhen-hua; Song, Hai-xing; Liu, Qiang; Rong, Xiang-min; Guan, Chun-yun; Zeng, Jing; Yuan, Dan

2015-07-01

Effect of elevated atmospheric-CO2 (780 µmol . mol-1) on the absorption and transportation of secondary nutrient elements (calcium, magnesium, sulphur) and micronutrient elements (iron, manganese, zinc, molybdenum and boron) in oilseed rape at the stem elongation stage were studied by greenhouse simulated method. Compared with the ambient CO2 condition, the content of Zn in stem was increased and the contents of other nutrient elements were decreased under the elevated atmospheric-CO2 with no nitrogen (N) application; the contents of Ca, S, B and Zn were increased, and the contents of Mg, Mn, Mo and Fe were decreased under the elevated atmospheric CO2 with N application (0.2 g N . kg-1 soil); except the content of Mo in leaf was increased, the contents of other nutrient elements were decreased under the elevated atmospheric-CO2 with two levels of N application. Compared with the ambient CO2 condition, the amounts of Ca and S relative to the total amount of secondary nutrient elements in stem and the amounts of B and Zn relative to the total amount of micronutrient elements in stem were increased under the elevated-CO2 treatment with both levels of N application, and the corresponding values of Mg, Fe, Mn and Mo were decreased; no-N application treatment increased the proportion of Ca distributed into the leaves, and the proportion of Mg distributed into leaves was increased by the normal-N application level; the proportions of Mn, Zn and Mo distributed into the leaves were increased at both N application levels. Without N application, the elevation of atmospheric CO2 increased the transport coefficients of SFe, Mo and SS,B, but decreased the transport coefficients of SMg,Fe, SMg, Mn and SS,Fe, indicating the proportions of Mo, S transported into the upper part of plant tissues was higher than that of Fe, and the corresponding value of B was higher than that observed for S, the corresponding value of Mg was higher than that of Fe and Mn. Under normal-N application, the elevation of atmospheric CO2 increased the transport coefficients of SMg,Fe, SMg,Mn and SS,B, but decreased the transport coefficients of SCa, Mg, SFe,Mo and SS,Fe indicating the proportions of Fe, Mn and Ca transported into the upper part of plant tissues was higher than that of Mg; the corresponding value of B was higher than that observed for S, the corresponding value of Fe was higher than that of Mo, and the corresponding value of S was higher than that of Fe.

Iron

MedlinePlus

... too little iron, you may develop iron deficiency anemia. Causes of low iron levels include blood loss, poor diet, or an inability to absorb enough iron from foods. People at higher risk of having too little iron are young children and women who are pregnant or have periods. ...

Reassessment of Iron Biomarkers for Prediction of Dialysis Iron Overload: An MRI Study

PubMed Central

Rostoker, Guy; Griuncelli, Mireille; Loridon, Christelle; Magna, Théophile; Machado, Gabrielle; Drahi, Gilles; Dahan, Hervé; Janklewicz, Philippe; Cohen, Yves

2015-01-01

Background and Objectives Iron overload among hemodialysis patients was previously considered rare but is now an increasingly recognized clinical situation. We analyzed correlations between iron biomarkers and the liver iron concentration (LIC) measured by magnetic resonance imaging (MRI), and examined their diagnostic accuracy for iron overload. Design, Setting, Participants and Measurements We performed a prospective cross-sectional study from 31 January 2005 to 31 August 2013 in the dialysis centre of a French community-based private hospital. A cohort of 212 hemodialysis patients free of overt inflammation or malnutrition, were treated for anemia with parenteral iron-sucrose and an erythropoesis-stimulating agent, in keeping with current clinical guidelines. Blinded measurements of hepatic iron stores were performed by T1 and T2* contrast MRI, and relationships were analysed using Spearman’s coefficient, logistic regression and receiver-operator characteristic (ROC) curves. Results Among the biological markers, only serum ferritin showed a strong correlation with LIC (rho= 0.52, 95% CI: 0.41-0.61, p< 0.0001, Spearman test). In logistic analysis, only serum ferritin correctly classified the overall cohort into patients with normal liver iron stores (LIC ≤ 50 μmol/g) and those with elevated liver iron stores (LIC > 50 μmol/g) (odds ratio 1.007; 95% CI: 1.004-1.010). Serum ferritin was the iron biomarker with the best discriminatory capacity in ROC curves analysis (area under the curve (AUC) = 0.767; 95% CI: 0.698-0.835). The optimal serum ferritin cutoffs were 160 μg/L for LIC > 50 μmol/g (mild iron overload) and 290 μg/L for LIC > 200 μmol/g (severe iron overload). Conclusions For clinical purposes, serum ferritin correctly reflects liver iron stores, as assessed by MRI, in hemodialysis patients without overt inflammation or malnutrition. These results strongly suggest that current ferritin target values should be lowered to avoid iron overload. Trial Registration ISRCTN Registry 80100088 PMID:26182077

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

Validation and Potential Mechanisms of Red Cell Distribution Width as a Prognostic Marker in Heart Failure

PubMed Central

ALLEN, LARRY A.; FELKER, G. MICHAEL; MEHRA, MANDEEP R.; CHIONG, JUN R.; DUNLAP, STEPHANIE H.; GHALI, JALAL K.; LENIHAN, DANIEL J.; OREN, RON M.; WAGONER, LYNNE E.; SCHWARTZ, TODD A.; ADAMS, KIRKWOOD F.

2014-01-01

Background: Adverse outcomes have recently been linked to elevated red cell distribution width (RDW) in heart failure. Our study sought to validate the prognostic value of RDW in heart failure and to explore the potential mechanisms underlying this association. Methods and Results: Data from the Study of Anemia in a Heart Failure Population (STAMINA-HFP) registry, a prospective, multicenter cohort of ambulatory patients with heart failure supported multivariable modeling to assess relationships between RDW and outcomes. The association between RDW and iron metabolism, inflammation, and neurohormonal activation was studied in a separate cohort of heart failure patients from the United Investigators to Evaluate Heart Failure (UNITE-HF) Biomarker registry. RDW was independently predictive of outcome (for each 1% increase in RDW, hazard ratio for mortality 1.06, 95% CI 1.01-1.12; hazard ratio for hospitalization or mortality 1.06; 95% CI 1.02-1.10) after adjustment for other covariates. Increasing RDW correlated with decreasing hemoglobin, increasing interleukin-6, and impaired iron mobilization. Conclusions: Our results confirm previous observations that RDW is a strong, independent predictor of adverse outcome in chronic heart failure and suggest elevated RDW may indicate inflammatory stress and impaired iron mobilization. These findings encourage further research into the relationship between heart failure and the hematologic system. PMID:20206898

Validation and potential mechanisms of red cell distribution width as a prognostic marker in heart failure.

PubMed

Allen, Larry A; Felker, G Michael; Mehra, Mandeep R; Chiong, Jun R; Dunlap, Stephanie H; Ghali, Jalal K; Lenihan, Daniel J; Oren, Ron M; Wagoner, Lynne E; Schwartz, Todd A; Adams, Kirkwood F

2010-03-01

Adverse outcomes have recently been linked to elevated red cell distribution width (RDW) in heart failure. Our study sought to validate the prognostic value of RDW in heart failure and to explore the potential mechanisms underlying this association. Data from the Study of Anemia in a Heart Failure Population (STAMINA-HFP) registry, a prospective, multicenter cohort of ambulatory patients with heart failure supported multivariable modeling to assess relationships between RDW and outcomes. The association between RDW and iron metabolism, inflammation, and neurohormonal activation was studied in a separate cohort of heart failure patients from the United Investigators to Evaluate Heart Failure (UNITE-HF) Biomarker registry. RDW was independently predictive of outcome (for each 1% increase in RDW, hazard ratio for mortality 1.06, 95% CI 1.01-1.12; hazard ratio for hospitalization or mortality 1.06; 95% CI 1.02-1.10) after adjustment for other covariates. Increasing RDW correlated with decreasing hemoglobin, increasing interleukin-6, and impaired iron mobilization. Our results confirm previous observations that RDW is a strong, independent predictor of adverse outcome in chronic heart failure and suggest elevated RDW may indicate inflammatory stress and impaired iron mobilization. These findings encourage further research into the relationship between heart failure and the hematologic system. Copyright (c) 2010 Elsevier Inc. All rights reserved.