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Sample records for iron ferritin transferrin

  1. Serum iron, ferritin, transferrin and haptoglobin concentration variations during repeated show jumping competition in horse

    Directory of Open Access Journals (Sweden)

    Anna Assenza

    2016-01-01

    Full Text Available Modifications of the iron profile in athlete horses during two international three star (*** show jumping competitions performed in two consecutive weekends were evaluated. Serum iron, ferritin, transferrin, and haptoglobin were assessed in 12 well-trained Italian Saddle horses. Blood samplings were performed before the first day of competition (R1, within 10 min from the end of each competition (J1, J2 and on the day after competition (R2. The same plan was followed during the second weekend (J3, J4 and R3. One-way repeated measures analysis of variance (ANOVA was applied on obtained data, and a significant effect of exercise (P < 0.05 on all studied indices was found. These results suggest that serum iron, transferrin, ferritin and haptoglobin are responsive to intense exercise and could be considered important indicators that may give important information about the horse’s performance.

  2. Iron status of Filipino infants and preschoolers using plasma ferritin and transferrin receptor levels.

    Science.gov (United States)

    Kuizon, M D; Madriaga, J R; Desnacido, J A; Cheong, R L; Perlas, L A

    1996-06-01

    Iron status of 1,861 Filipino infants and preschoolers was evaluated by measurements of plasma ferritin (PF), transferrin receptor (TR) and hemoglobin (Hb). One group of subjects (Group I) consisted of all anemic subjects together with a systematic subsample from the Fourth National Nutrition Survey-Biochemical Phase. Results showed that depleted iron stores based on PF ( 8.5 mg/l) was present in higher proportion (80.0% and 73.7% for infants and preschoolers) which was comparable to the proportion of anemia (80.3%). In a subgroup of subjects from the Country Program for Children IV (Group 2) elevated TR was present in 61.4% of infants and 46.5% of preschoolers. A lower proportion of depleted iron stores of 22.7% in infants and 15.2% in preschoolers was observed. Correlation test showed that there was a closer relationship between Hb and TR (r = -0.42) than Hb and PF (r = 0.20) even if PF was expected to give a higher proportion of values below normal. The occurrence of anemia in the presence of elevated TR without any decrease in PF values suggest that the diagnostic ability of PF could be limited in the presence of infection. Therefore, future studies should include biochemical tests such as C-reactive proteins (CRP) to determine the extent of association between anemia and infection.

  3. Time- and cell-type specific changes in iron, ferritin, and transferrin in the gerbil hippocampal CA1 region after transient forebrain ischemia

    Directory of Open Access Journals (Sweden)

    Dae Young Yoo

    2016-01-01

    Full Text Available In the present study, we used immunohistochemistry and western blot analysis to examine changes in the levels and cellular localization of iron, heavy chain ferritin (ferritin-H, and transferrin in the gerbil hippocampal CA1 region from 30 minutes to 7 days following transient forebrain ischemia. Relative to sham controls, iron reactivity increased significantly in the stratum pyramidale and stratum oriens at 12 hours following ischemic insult, transiently decreased at 1-2 days and then increased once again within the CA1 region at 4-7 days after ischemia. One day after ischemia, ferritin-H immunoreactivity increased significantly in the stratum pyramidale and decreased at 2 days. At 4-7 days after ischemia, ferritin-H immunoreactivity in the glial components in the CA1 region was significantly increased. Transferrin immunoreactivity was increased significantly in the stratum pyramidale at 12 hours, peaked at 1 day, and then decreased significantly at 2 days after ischemia. Seven days after ischemia, Transferrin immunoreactivity in the glial cells of the stratum oriens and radiatum was significantly increased. Western blot analyses supported these results, demonstrating that compared to sham controls, ferritin H and transferrin protein levels in hippocampal homogenates significantly increased at 1 day after ischemia, peaked at 4 days and then decreased. These results suggest that iron overload-induced oxidative stress is most prominent at 12 hours after ischemia in the stratum pyramidale, suggesting that this time window may be the optimal period for therapeutic intervention to protect neurons from ischemia-induced death.

  4. Actinide uptake by transferrin and ferritin metalloproteins

    International Nuclear Information System (INIS)

    Den Auwer, C.; Llorens, I.; Moisy, Ph.; Vidaud, C.; Goudard, F.; Barbot, C.; Solari, P.L.; Funke, H.

    2005-01-01

    In order to better understand the mechanisms of actinide uptake by specific biomolecules, it is essential to explore the intramolecular interactions between the cation and the protein binding site. Although this has long been done for widely investigated transition metals, very few studies have been devoted to complexation mechanisms of actinides by active chelation sites of metalloproteins. In this field, X-ray absorption spectroscopy has been extensively used as a structural and electronic metal cation probe. The two examples that are presented here are related to two metalloproteins in charge of iron transport and storage in eukaryote cells: transferrin and ferritin. U(VI)O 2 2+ , Np(IV) and Pu(IV) have been selected because of their possible role as contaminant from the geosphere. (orig.)

  5. Aluminum stimulates uptake of non-transferrin bound iron and transferrin bound iron in human glial cells

    International Nuclear Information System (INIS)

    Kim, Yongbae; Olivi, Luisa; Cheong, Jae Hoon; Maertens, Alex; Bressler, Joseph P.

    2007-01-01

    Aluminum and other trivalent metals were shown to stimulate uptake of transferrin bound iron and nontransferrin bound iron in erytholeukemia and hepatoma cells. Because of the association between aluminum and Alzheimer's Disease, and findings of higher levels of iron in Alzheimer's disease brains, the effects of aluminum on iron homeostasis were examined in a human glial cell line. Aluminum stimulated dose- and time-dependent uptake of nontransferrin bound iron and iron bound to transferrin. A transporter was likely involved in the uptake of nontransferrin iron because uptake reached saturation, was temperature-dependent, and attenuated by inhibitors of protein synthesis. Interestingly, the effects of aluminum were not blocked by inhibitors of RNA synthesis. Aluminum also decreased the amount of iron bound to ferritin though it did not affect levels of divalent metal transporter 1. These results suggest that aluminum disrupts iron homeostasis in Brain by several mechanisms including the transferrin receptor, a nontransferrin iron transporter, and ferritin

  6. Iron, transferrin and myelinogenesis

    Energy Technology Data Exchange (ETDEWEB)

    Sergeant, C. E-mail: sergeant@cenbg.in2p3.fr; Vesvres, M.H.; Deves, G.; Baron, B.; Guillou, F

    2003-09-01

    Transferrin (Tf), the iron binding protein of vertebrates serum, is known to be synthesized by oligodendrocytes (Ols) in the central nervous system. It has been postulated that Tf is involved in Ols maturation and myelinogenesis. This link is particularly important in the understanding of a severe human pathology: the multiple sclerosis, which remains without efficient treatment. We generated transgenic mice containing the complete human Tf gene and extensive regulatory sequences from the 5{sup '} and 3{sup '} untranslated regions that specifically overexpress Tf in Ols. Brain cytoarchitecture of the transgenic mice appears to be normal in all brain regions examined, total myelin content is increased by 30% and motor coordination is significantly improved when compared with non-transgenic littermates. Tf role in the central nervous system may be related to its affinity for metallic cations. Normal and transgenic mice were used for determination of trace metals (iron, copper and zinc) and minerals (potassium and calcium) concentration in cerebellum and corpus callosum. The freeze-dried samples were prepared to allow proton-induced X-ray emission and Rutherford backscattering spectrometry analyses with the nuclear microprobe in Bordeaux. Preliminary results were obtained and carbon distribution was revealed as a very good analysis to distinguish precisely the white matter region. A comparison of metallic and mineral elements contents in brain between normal and transgenic mice shows that iron, copper and zinc levels remained constant. This result provides evidence that effects of Tf overexpression in the brain do not solely relate to iron transport.

  7. Iron, transferrin and myelinogenesis

    International Nuclear Information System (INIS)

    Sergeant, C.; Vesvres, M.H.; Deves, G.; Baron, B.; Guillou, F.

    2003-01-01

    Transferrin (Tf), the iron binding protein of vertebrates serum, is known to be synthesized by oligodendrocytes (Ols) in the central nervous system. It has been postulated that Tf is involved in Ols maturation and myelinogenesis. This link is particularly important in the understanding of a severe human pathology: the multiple sclerosis, which remains without efficient treatment. We generated transgenic mice containing the complete human Tf gene and extensive regulatory sequences from the 5 ' and 3 ' untranslated regions that specifically overexpress Tf in Ols. Brain cytoarchitecture of the transgenic mice appears to be normal in all brain regions examined, total myelin content is increased by 30% and motor coordination is significantly improved when compared with non-transgenic littermates. Tf role in the central nervous system may be related to its affinity for metallic cations. Normal and transgenic mice were used for determination of trace metals (iron, copper and zinc) and minerals (potassium and calcium) concentration in cerebellum and corpus callosum. The freeze-dried samples were prepared to allow proton-induced X-ray emission and Rutherford backscattering spectrometry analyses with the nuclear microprobe in Bordeaux. Preliminary results were obtained and carbon distribution was revealed as a very good analysis to distinguish precisely the white matter region. A comparison of metallic and mineral elements contents in brain between normal and transgenic mice shows that iron, copper and zinc levels remained constant. This result provides evidence that effects of Tf overexpression in the brain do not solely relate to iron transport

  8. Predicting C282Y Homozygote Genotype for Hemochromatosis Using Serum Ferritin and Transferrin Saturation Values from 44,809 Participants of the HEIRS Study

    Directory of Open Access Journals (Sweden)

    Andrew Lim

    2014-01-01

    Full Text Available INTRODUCTION: The simultaneous interpretation of serum ferritin level and transferrin saturation has been used as a clinical guide to diagnose genetic hemochromatosis. The Hemochromatosis and Iron Overload Screening (HEIRS Study screened 101,168 North American participants for serum ferritin level and transferrin saturation, and C282Y genotyping for the HFE gene.

  9. Improved differential diagnosis of anemia of chronic disease and iron deficiency anemia: a prospective multicenter evaluation of soluble transferrin receptor and the sTfR/log ferritin index.

    Science.gov (United States)

    Skikne, Barry S; Punnonen, Kari; Caldron, Paul H; Bennett, Michael T; Rehu, Mari; Gasior, Gail H; Chamberlin, Janna S; Sullivan, Linda A; Bray, Kurtis R; Southwick, Paula C

    2011-11-01

    Anemia of chronic disease (ACD) and iron deficiency anemia (IDA) are the most prevalent forms of anemia and often occur concurrently. Standard tests of iron status used in differential diagnosis are affected by inflammation, hindering clinical interpretation. In contrast, soluble transferrin receptor (sTfR) indicates iron deficiency and is unaffected by inflammation. Objectives of this prospective multicenter clinical trial were to evaluate and compare the diagnostic accuracy of sTfR and the sTfR/log ferritin index (sTfR Index) for differential diagnosis using the automated Access(®) sTfR assay (Beckman Coulter) and sTfR Index. We consecutively enrolled 145 anemic patients with common disorders associated with IDA and ACD. Subjects with IDA or ACD + IDA had significantly higher sTfR and sTfR Index values than subjects with ACD (P < 0.0001). ROC curves produced the following cutoffs for sTfR: 21 nmol/L (or 1.55 mg/L), and the sTfR Index: 14 (using nmol/L) (or 1.03 using mg/L). The sTfR Index was superior to sTfR (AUC 0.87 vs. 0.74, P < 0.0001). Use of all three parameters in combination more than doubled the detection of IDA, from 41% (ferritin alone) to 92% (ferritin, sTfR, sTfR Index). Use of sTfR and the sTfR Index improves detection of IDA, particularly in situations where routine markers provide equivocal results. Findings demonstrate a significant advantage in the simultaneous determination of ferritin, sTfR and sTfR Index. Obtaining a ferritin level alone may delay diagnosis of combined IDA and ACD. Copyright © 2011 Wiley-Liss, Inc.

  10. Changes in Serum Ferritin and Other Factors Associated with Iron Metabolism During Chronic Hyperbaric Exposure

    National Research Council Canada - National Science Library

    Gilman, Sara C; Hunter, Jr., W. L; Mooney, L. W

    1979-01-01

    .... during these simulated dives progressive and correlated increases in serum ferritin and iron occurred. No significant changes were observed in bilirubin, hemoglobin, neurloplasmia, transferrin, cooper, or total iron binding capacity...

  11. Effect of transferrin saturation on internal iron exchange

    International Nuclear Information System (INIS)

    Bergamaschi, G.; Eng, M.J.; Huebers, H.A.; Finch, C.A.

    1986-01-01

    Radioiron was introduced into the intestinal lumen to evaluate absorption, injected as nonviable red cells to evaluate reticuloendothelial (RE) processing of iron, and injected as hemoglobin to evaluate hepatocyte iron processing. Redistribution of iron through the plasma was evaluated in control animals and animals whose transferrin was saturated by iron infusion. Radioiron introduced into the lumen of the gut as ferrous sulfate and as transferrin-bound iron was absorbed about half as well in iron-infused animals, and absorbed iron was localized in the liver. The similar absorption of transferrin-bound iron suggested that absorption of ferrous iron occurred via the mucosal cell and did not enter by diffusion. The decrease in absorption was associated with an increase in mucosal iron and ferritin content produced by the iron infusion. An inverse relationship (r = -0.895) was shown between mucosal ferritin iron and absorption. When iron was injected as nonviable red cells, it was deposited predominantly in reticuloendothelial cells of the spleen. Return of this radioiron to the plasma was only 6% of that in control animals. While there was some movement of iron from spleen to liver, this could be accounted for by intravascular hemolysis. Injected hemoglobin tagged with radioiron was for the most part taken up and held by the liver. Some 13% initially localized in the marrow in iron-infused animals was shown to be storage iron unavailable for hemoglobin synthesis. These studies demonstrate the hepatic trapping of absorbed iron and the inability of either RE cell or hepatocyte to release iron in the transferrin-saturated animal

  12. Assessing the Association between Serum Ferritin, Transferrin Saturation, and C-Reactive Protein in Northern Territory Indigenous Australian Patients with High Serum Ferritin on Maintenance Haemodialysis

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    Sandawana William Majoni

    2017-01-01

    Full Text Available Objective. To determine the significance of high serum ferritin observed in Indigenous Australian patients on maintenance haemodialysis in the Northern Territory, we assessed the relationship between ferritin and transferrin saturation (TSAT as measures of iron status and ferritin and C-reactive protein (CRP as markers of inflammation. Methods. We performed a retrospective cohort analysis of data from adult patients (≥18 years on maintenance haemodialysis (>3 months from 2004 to 2011. Results. There were 1568 patients. The mean age was 53.9 (11.9 years. 1244 (79.3% were Indigenous. 44.2% (n=693 were male. Indigenous patients were younger (mean age [52.3 (11.1 versus 57.4 (15.2, p<0.001] and had higher CRP [14.7 mg/l (7–35 versus 5.9 mg/l (1.9–17.5, p<0.001], higher median serum ferritin [1069 µg/l (668–1522 versus 794.9 µg/l (558.5–1252.0, p<0.001], but similar transferrin saturation [26% (19–37 versus 28% (20–38, p=0.516]. We observed a small positive correlation between ferritin and TSAT (r2=0.11, p<0.001, no correlation between ferritin and CRP (r2 = 0.001, p<0.001, and positive association between high serum ferritin and TSAT (p<0.001, Indigenous ethnicity (p<0.001, urea reduction ratio (p=0.001, and gender (p<0.001 after adjustment in mixed regression analysis. Conclusion. Serum ferritin and TSAT may inadequately reflect iron status in this population. The high ferritin was poorly explained by inflammation.

  13. Using Soluble Transferrin Receptor and Taking Inflammation into Account When Defining Serum Ferritin Cutoffs Improved the Diagnosis of Iron Deficiency in a Group of Canadian Preschool Inuit Children from Nunavik

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    Huguette Turgeon O’Brien

    2016-01-01

    Full Text Available The prevalence of iron depletion, iron deficient erythropoiesis (IDE, and iron deficiency anemia (IDA was assessed in preschool Inuit children using soluble transferrin receptor (sTfR and traditional indicators of iron status while disregarding or taking inflammation into account when defining SF cutoffs. Iron depletion was defined as follows: (1 SF 5 mg/L, respectively. IDE corresponded to iron depletion combined with total iron binding capacity > 72 μmol/L and/or transferrin saturation < 16%. Iron depletion and IDE affected almost half of the children when accounting for inflammation, compared to one-third when the SF cutoff was defined regardless of CRP level (P<0.0001. The prevalence of IDE adjusted for inflammation (45.1% was very similar to the prevalence observed when sTfR was used as a sole marker of IDE (47.4%. The prevalence of anemia was 15%. The prevalence of IDA (IDE + hemoglobin < 110 g/L was higher when accounting for than when disregarding inflammation (8.0% versus 6.2%, P=0.083. Using sTfR and different SF cutoffs for children with versus without inflammation improved the diagnosis of iron depletion and IDE. Our results confirm that Inuit children are at particularly high risk for iron deficiency.

  14. Kinetics of Transferrin and Transferrin-Receptor during Iron Transport through Blood Brain Barrier

    Science.gov (United States)

    Khan, Aminul; Liu, Jin; Dutta, Prashanta

    2017-11-01

    Transferrin and its receptors play an important role during the uptake and transcytosis of iron by blood brain barrier (BBB) endothelial cells to maintain iron homeostasis in BBB endothelium and brain. In the blood side of BBB, ferric iron binds with the apo-transferrin to form holo-transferrin which enters the endothelial cell via transferrin receptor mediated endocytosis. Depending on the initial concentration of iron inside the cell endocytosed holo-transferrin can either be acidified in the endosome or exocytosed through the basolateral membrane. Acidification of holo-transferrin in the endosome releases ferrous irons which may either be stored and used by the cell or transported into brain side. Exocytosis of the holo-transferrin through basolateral membrane leads to transport of iron bound to transferrin into brain side. In this work, kinetics of internalization, recycling and exocytosis of transferrin and its receptors are modeled by laws of mass action during iron transport in BBB endothelial cell. Kinetic parameters for the model are determined by least square analysis. Our results suggest that the cell's initial iron content determines the extent of the two possible iron transport pathways, which will be presented in this talk Research reported in this publication was supported by the National Institute of General Medical Sciences of the National Institutes of Health under Award Number R01GM122081.

  15. Concentration-dependent sedimentation properties of ferritin: implications for estimation of iron contents of serum ferritins

    International Nuclear Information System (INIS)

    Niitsu, Y.; Adachi, C.; Takahashi, F.; Goto, Y.; Kohgo, Y.; Urushizaki, I.; Listowsky, I.

    1985-01-01

    Serum ferritins from various sources sedimented at lower densities than tissue ferritins in sucrose gradient centrifugation systems. The sedimentation patterns of ferritins, however, were shown to be dependent on the concentration of the protein; as the concentration decreased the protein appeared to sediment at lower densities. Thus, at the low concentration levels usually used for analysis of serum ferritin, tissue ferritins also sedimented in the same lower density regions. Iron labeling experiments indicated that the sedimentation changes upon dilution were not due to release of iron or was there any indication that the protein dissociated into subunits. The anomalous sedimentation behavior of serum ferritin should therefore not be interpreted in terms of its iron content. The disclosure that serum ferritins may have full complements of iron is counter to the prevalent view that serum ferritins are low iron forms and has potential implications with regard to the sources and possible function of this protein in the circulation

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

    Science.gov (United States)

    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

    2008-08-01

    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 microg/L (men), >200 microg/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 microg/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 microg/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 900 microg/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 microg/L in male C282Y homozygotes is predictive of moderately increased iron stores. Copyright 2008 Wiley-Liss, Inc.

  17. Competitive advantage of diferric transferrin in delivering iron to reticulocytes.

    Science.gov (United States)

    Huebers, H A; Csiba, E; Huebers, E; Finch, C A

    1983-01-01

    Radioiron- and radioiodine-labeled forms of human diferric and monoferric transferrin and apotransferrin, isolated by preparative isoelectric focusing, were used to define transferrin-iron uptake by human reticulocytes. In mixtures of human diferric and monoferric transferrin, the diferric molecule had a constant 7-fold advantage in delivering iron to reticulocytes, as compared with the 2-fold advantage when single solutions of mono- and diferric transferrins were compared. This was shown to be due to competitive interaction in iron delivery, probably at a common membrane-receptor binding site for transferrin. Apotransferrin did not interfere with the iron-donating process and its limited cellular uptake was inhibited in noncompetitive fashion by diferric transferrin. PMID:6572005

  18. Diagnostic relevance of radioiron-absorption-measurements and immunoradiometric serum-ferritin-assay in the evaluation of iron stores

    International Nuclear Information System (INIS)

    Heinrich, H.C.

    1978-01-01

    Negative iron balance and enhanced iron demand respectively causes deficient iron stores (prelatent iron deficiency) with increased iron absorption, later on decrease of serum iron and increase of transferrin (latent Fe deficiency) and at least iron deficient anemia (manifest iron deficiency). In prelatend iron deficiency diagnostic 59 Fe 2+ absorption is increased and the RES cells do not show storage iron cytochemically. In latent iron deficiency in addition serum iron, transferrin iron saturation and serum ferritin is decreased and hypochromic mikrocytic anemia completes the signs of manifest iron deficiency. Besides rare cases of primary hemochromatosis and marked hyperdasia of ineffective erythropoiesis in homocygotic beta-thalassemia, hereditary non-spherocytic hemolytic anemia caused by pyruvate kinase deficiency and some sideroblastic anemias increased 59 Fe 2+ absorption is a reliable measure of exhausted iron stores. In these exceptional cases differential diagnosis between sideroachrestic and siderosensitive iron deficiency anemia can be made by measurement of serum iron and serum ferritin respectively. The etiology of iron deficiency is to be cleared by measurement of 59 Fe absorption from 59 Fe 2+ and 59 Fe-marked meat with consecutive estimation of whole body 59 Fe elimination. Shortly after completion or during oral iron therapy serum ferritin concentration is not suitable to evaluate the content of iron stores. (orig.) [de

  19. Body iron and individual prophylaxis in pregnancy-should the iron dose be adjusted according to serum  ferritin?

    DEFF Research Database (Denmark)

    Milman, N; Byg, KE; Bergholt, T

    2006-01-01

    ferritin, serum soluble transferrin receptor (sTfR), haemoglobin] were recorded at 18, 32 and 39 weeks gestation and 8 weeks postpartum. Body iron was calculated using the serum sTfR/serum ferritin ratio. ID was defined by serum ferritin ...This study aims to evaluate iron prophylaxis in pregnant women from the individual aspect, i.e. according to serum ferritin levels at the beginning of pregnancy, and to assess which dose of iron would be adequate to prevent iron deficiency (ID) and iron deficiency anaemia (IDA) during pregnancy...... and postpartum. A randomised, double-blind study comprising 301 healthy Danish pregnant women allocated into four groups taking ferrous iron (as fumarate) in doses of 20 mg (n=74), 40 mg (n=76), 60 mg (n=77) and 80 mg (n=75) from 18 weeks gestation (inclusion) to 8 weeks postpartum. Iron status markers [serum...

  20. Erythroblast transferrin receptors and transferrin kinetics in iron deficiency and various anemias

    International Nuclear Information System (INIS)

    Muta, K.; Nishimura, J.; Ideguchi, H.; Umemura, T.; Ibayashi, H.

    1987-01-01

    To clarify the role of transferrin receptors in cases of altered iron metabolism in clinical pathological conditions, we studied: number of binding sites; affinity; and recycling kinetics of transferrin receptors on human erythroblasts. Since transferrin receptors are mainly present on erythroblasts, the number of surface transferrin receptors was determined by assay of binding of 125 I-transferrin and the percentage of erythroblasts in bone marrow mononuclear cells. The number of binding sites on erythroblasts from patients with an iron deficiency anemia was significantly greater than in normal subjects. Among those with an aplastic anemia, hemolytic anemia, myelodysplastic syndrome, and polycythemia vera compared to normal subjects, there were no considerable differences in the numbers of binding sites. The dissociation constants (Kd) were measured using Scatchard analysis. The apparent Kd was unchanged (about 10 nmol/L) in patients and normal subjects. The kinetics of endocytosis and exocytosis of 125 I-transferrin, examined by acid treatment, revealed no variations in recycling kinetics among the patients and normal subjects. These data suggest that iron uptake is regulated by modulation of the number of surface transferrin receptors, thereby reflecting the iron demand of the erythroblast

  1. Reference values for serum ferritin and percentage of transferrin saturation in Korean children and adolescents.

    Science.gov (United States)

    Oh, Hea Lin; Lee, Jun Ah; Kim, Dong Ho; Lim, Jung Sub

    2018-03-01

    Ferritin reference values vary by age, gender, and ethnicity. We aimed to determine reference values of serum ferritin (SF) and the percentage of transferrin saturation (TSAT) for Korean children and adolescents. We analyzed data from 2,487 participants (1,311 males and 1,176 females) aged 10-20 years from the Korea National Health and Nutrition Examination Survey (2010-2012). We calculated age- and gender-stratified means and percentile values for SF and TSAT. We first plotted mean SF and TSAT by gender and according to age. In males, mean SF tended to be relatively constant among participants aged 10 to 14 years, with an upward trend thereafter. Mean SF trended downward among female participants until the age of 15 years and remained constant thereafter. Thus, significant gender differences in ferritin exist from the age of 14 years. High levels of SF were associated with obesity, and lower SF levels were associated with anemia and menarche status. We established reference values of SF and TSAT according to age and gender. The reference values for SF calculated in this study can be used to test the association between SF values and other defined diseases in Korean children and adolescents.

  2. Monocyte transferrin-iron uptake in hereditary hemochromatosis

    International Nuclear Information System (INIS)

    Sizemore, D.J.; Bassett, M.L.

    1984-01-01

    Transferrin-iron uptake by peripheral blood monocytes was studied in vitro to test the hypothesis that the relative paucity of mononuclear phagocyte iron loading in hereditary hemochromatosis results from a defect in uptake of iron from transferrin. Monocytes from nine control subjects and 17 patients with hemochromatosis were cultured in the presence of 59Fe-labelled human transferrin. There was no difference in 59Fe uptake between monocytes from control subjects and monocytes from patients with hemochromatosis who had been treated by phlebotomy and who had normal body iron stores. However, 59Fe uptake by monocytes from iron-loaded patients with hemochromatosis was significantly reduced compared with either control subjects or treated hemochromatosis patients. It is likely that this was a secondary effect of iron loading since iron uptake by monocytes from treated hemochromatosis patients was normal. Assuming that monocytes in culture reflect mononuclear phagocyte iron metabolism in vivo, this study suggests that the relative paucity of mononuclear phagocyte iron loading in hemochromatosis is not related to an abnormality in transferrin-iron uptake by these cells

  3. Primary care requests for anaemia chemistry tests in Spain: potential iron, transferrin and folate over-requesting.

    Science.gov (United States)

    Salinas, Maria; López-Garrigós, Maite; Flores, Emilio; Leiva-Salinas, Carlos

    2017-09-01

    To study the regional variability of requests for anaemia chemistry tests in primary care in Spain and the associated economic costs of potential over-requesting. Requests for anaemia tests were examined in a cross-sectional study. Clinical laboratories from different autonomous communities (AACCs) were invited to report on primary care anaemia chemistry tests requested during 2014. Demand for iron, ferritin, vitamin B12 and folate tests per 1000 inhabitants and the ratios of the folate/vitamin B12 and transferrin/ferritin requests were compared between AACCs. We also calculated reagent costs and the number of iron, transferrin and folate tests and the economic saving if every AACC had obtained the results achieved by the AACC with best practice. 110 laboratories participated (59.8% of the Spanish population). More than 12 million tests were requested, resulting in reagent costs exceeding €16.5 million. The serum iron test was the most often requested, and the ferritin test was the most costly (over €7 million). Close to €4.5 million could potentially have been saved if iron, transferrin and folate had been appropriately requested (€6 million when extrapolated to the whole Spanish population). The demand for and expenditure on anaemia chemistry tests in primary care in Spain is high, with significant regional differences between different AACCs. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

  4. Assessment of iron status of Sudanese pregnant women by serum ferritin

    International Nuclear Information System (INIS)

    Eltayeb, E.A.; Khangi, F.A.; Satti, G.M.; Abu Salab, A.

    2004-03-01

    Eighty five normal pregnant women were included in the study at the start of the second trimester. Two blood samples were taken during the second trimester and two blood samples during the third trimester. The height of all subjects was measured. The weights of the subjects were under iron-supplementation throughout the gestation period. Sixty four normal non-parentage women were included in the study to serve as controls. Iron status was assessed for the groups with following parameters, haemoglobin (Hb), packed corpuscular volume (PCV), red blood cells count, peripheral blood film, mean corpuscular volume (MCV), mean cell haemoglobin (MCH), Mean haemoglobin concentration (MCH C), serum iron (Si), total iron binding capacity (T IBC), serum transferrin saturation (Ts) and serum ferritin (Sf). No significant difference was observed in the mean haemoglobin concentrations but the PCV of the non-pregnant women was higher than that of the pregnant women at different stages of gestation (p<0.05). MCV, MCH and MCH C values of the non-pregnant women were lower than those of the of the pregnant at different stages of gestation (p<0.05). Serum iron and transferrin saturation of the non-pregnant women were higher than those of the pregnant women, this difference was statistically significant at weeks (16-18) and (22-24) (p<0.05). Serum ferritin of the non-pregnant women was higher than that of the pregnant women and decreased continuously during the pregnancy, but this decrease was not statistically significant. Iron deficiency anaemia was observed in both pregnant and non-pregnant women. The best parameter that could be used as a marker for iron deficiency is serum ferritin. Iron supplementation s corrected for haemoglobin but not for iron status, but more studies were needed to cover this issue using different parameters.(Author)

  5. Acquisition of iron from transferrin regulates reticulocyte heme synthesis

    International Nuclear Information System (INIS)

    Ponka, P.; Schulman, H.M.

    1985-01-01

    Fe-salicylaldehyde isonicotinoylhydrazone (SIH), which can donate iron to reticulocytes without transferrin as a mediator, has been utilized to test the hypothesis that the rate of iron uptake from transferrin limits the rate of heme synthesis in erythroid cells. Reticulocytes take up 59 Fe from [ 59 Fe]SIH and incorporate it into heme to a much greater extent than from saturating concentrations of [ 59 Fe]transferrin. Also, Fe-SIH stimulates [2- 14 C]glycine into heme when compared to the incorporation observed with saturating levels of Fe-transferrin. In addition, delta-aminolevulinic acid does not stimulate 59 Fe incorporation into heme from either [ 59 Fe]transferrin or [ 59 Fe]SIH but does reverse the inhibition of 59 Fe incorporation into heme caused by isoniazid, an inhibitor of delta-aminolevulinic acid synthase. Taken together, these results suggest the hypothesis that some step(s) in the pathway of iron from extracellular transferrin to intracellular protoporphyrin limits the overall rate of heme synthesis in reticulocytes

  6. Iron induction of ferritin synthesis in soybean cell suspensions.

    Science.gov (United States)

    Proudhon, D; Briat, J F; Lescure, A M

    1989-06-01

    In animal cells specialized for iron storage, iron-induced accumulation of ferritin is known to result from a shift of stored mRNA from the ribonucleoprotein fraction to polysomes. Previous reports with bean leaves suggested that in plants iron induction of ferritin synthesis would result from a regulation at the transcriptional level (F van der Mark, F Bienfait, H van der Ende [1983] Biochem Biophys Res Commun 115:463-469). Soybean (Glycine max, cv Mandarin) cell suspension cultures have been used here to support these findings. Ferritin induction is obtained by addition of Fe-citrate to the culture medium. A good correlation is found between cellular iron content and the amount of ferritin accumulation. This protein accumulation corresponds to an increase of in vitro translatable ferritin mRNA. Addition of 4 micrograms actinomycin D per milliliter to the cultures inhibits completely in vivo RNA synthesis, whereas protein synthesis was poorly affected, at least for 24 hours. During the same time, this concentration of actinomycin D strongly inhibits the iron-induced synthesis of ferritin. These results show that in soybean cell cultures, the mechanism of regulation of ferritin synthesis in response to iron does not result from recruitment of preexisting mRNA. They confirm that in plant systems, ferritin synthesis results from increased transcription of the corresponding genes.

  7. IRON, ZINC, AND FERRITIN ACCUMULATION IN COMMON BEANS

    DEFF Research Database (Denmark)

    Urbanski, Dorian Fabian; Sørensen, Kirsten; Jurkiewicz, Anna Malgorzata

    Iron and zinc malnutrition are major threats to human health and development around the world. The World Health Organization states that over two billion people are affected by iron deficiency. In particular children and pregnant women in developing countries are affected by iron deficiency...... in mature seeds, but the ferritin protein was suggested to be the major iron storing protein in legumes [1]. Both iron and zinc localization, as well as speciation, can have an impact on their nutritional availability. We will present detailed information about iron, zinc, and ferritin distribution...

  8. Atomic absorption assessment of mineral iron quantity in ferritin

    International Nuclear Information System (INIS)

    Marinova, M.; Vladimirova, L.

    2009-01-01

    Possibilities for quantitative determination of the number of iron atoms in the mineral core of ferritin by atomic absorption spectroscopy (AAS) are investigated in the work. Different measurements with AAS show an iron content from 1000 up to 4500 atoms per molecule ferritin. This motivated us to investigate the amount of iron in the Horse Spleen Ferritin with atomic absorption spectroscopy under application of the Bulgarian standard BDS EN 14082/2003 Foodstuffs - Determination of trace elements - Determination of lead, cadmium, zinc, copper, iron and chromium by atomic absorption spectrometry (AAS) after dry ashing. The obtained results give approx. 1800 atoms per molecule Ferritin. It is in accordance with previous results, published by leading researchers. The investigation of the iron content with AAS under the use of the Bulgarian standard is a good opportunity to study many other objects of biological interest. (authors)

  9. The expression of ferritin, lactoferrin, transferrin receptor and solute carrier family 11A1 in the host response to BCG-vaccination and Mycobacterium tuberculosis challenge.

    Science.gov (United States)

    Thom, R E; Elmore, M J; Williams, A; Andrews, S C; Drobniewski, F; Marsh, P D; Tree, J A

    2012-05-02

    Iron is an essential cofactor for both mycobacterial growth during infection and for a successful protective immune response by the host. The immune response partly depends on the regulation of iron by the host, including the tight control of expression of the iron-storage protein, ferritin. BCG vaccination can protect against disease following Mycobacterium tuberculosis infection, but the mechanisms of protection remain unclear. To further explore these mechanisms, splenocytes from BCG-vaccinated guinea pigs were stimulated ex vivo with purified protein derivative from M. tuberculosis and a significant down-regulation of ferritin light- and heavy-chain was measured by reverse-transcription quantitative-PCR (P≤0.05 and ≤0.01, respectively). The mechanisms of this down-regulation were shown to involve TNFα and nitric oxide. A more in depth analysis of the mRNA expression profiles, including genes involved in iron metabolism, was performed using a guinea pig specific immunological microarray following ex vivo infection with M. tuberculosis of splenocytes from BCG-vaccinated and naïve guinea pigs. M. tuberculosis infection induced a pro-inflammatory response in splenocytes from both groups, resulting in down-regulation of ferritin (P≤0.05). In addition, lactoferrin (P≤0.002), transferrin receptor (P≤0.05) and solute carrier family 11A1 (P≤0.05), were only significantly down-regulated after infection of the splenocytes from BCG-vaccinated animals. The results show that expression of iron-metabolism genes is tightly regulated as part of the host response to M. tuberculosis infection and that BCG-vaccination enhances the ability of the host to mount an iron-restriction response which may in turn help to combat invasion by mycobacteria. Copyright © 2012 Elsevier Ltd. All rights reserved.

  10. Red cell ferritin and iron stores in chronic granulocytic leukemia

    International Nuclear Information System (INIS)

    Cermak, J.; Neuwirth, J.; Voglova, J.; Brabec, V.; Chrobak, L.

    1994-01-01

    Basic red cell ferritin was investigated in 28 patients with different phases of chronic granulocytic leukemia (GCL). Red cell ferritin was significantly decreased in remission after busulphan treatment and significantly elevated in the blast crisis as compared to healthy controls. Bone marrow stainable iron was decreased or absent in 86% of patients in the initial phase at the time of diagnosis and in 92% of those in remission. Red cell ferritin correlated with serum ferritin, however, serum ferritin level remained above normal range during all phases of the disease. A negative correlation between red cell ferritin and hemoglobin (Hb) (r = -0.605, p < 0.001) suggested that red cell ferritin level reflected the rate of iron utilization for heme synthesis. Decrease red cell iron observed in the remission may be explained by regression of dyserythropoiesis and by restoration of normal Hb synthesis after busulphan treatment. A progressive dyserythropoiesis in the blast crisis may lead to an increased red cell ferritin level. (author)

  11. Nonrandom distribution of iron in circulating human transferrin.

    Science.gov (United States)

    Zak, O; Aisen, P

    1986-07-01

    By combining the urea gel electrophoresis technique of Makey and Seal with Western immunoblotting, a method has been developed for analyzing the distribution of iron between the two sites of circulating human transferrin. The new method avoids exposure of samples to a nonphysiologic pH that may promote removal or redistribution of iron from the protein; this facilitates examination of multiple samples at one time. Analysis of 21 freshly drawn specimens from normal human subjects confirms previous reports that iron is not randomly distributed in the specific sites of transferrin. Rather, there is a considerable range in the ratio of occupancies of N-terminal and C-terminal sites (N:C ratio), from 0.31 to 6.87 in the present study, with the N-terminal site predominantly occupied in most subjects. The N:C ratio correlates modestly with serum iron concentration (r = .54). Possible flaws in studies indicating a random occupancy of the specific sites of circulating transferrin may lie in the low pH to which samples may be exposed during procedures based on isoelectric focusing or in drawing inferences from data considering only total monoferric transferrin rather than the two distinguishable monoferric species.

  12. Ferritin and iron levels in children with autistic disorder.

    Science.gov (United States)

    Hergüner, Sabri; Keleşoğlu, Fatih Mehmet; Tanıdır, Cansaran; Cöpür, Mazlum

    2012-01-01

    Iron has an important role on cognitive, behavioral, and motor development. High prevalence of iron deficiency has been reported in autism. The aim of this study was to investigate iron status in a group of children with autistic disorder. The sample was composed of 116 children between 3 and 16 years with a diagnosis of autistic disorder according to DSM-IV criteria. Serum ferritin, iron, hemoglobin, hematocrit, mean corpuscular volume, and red cell distribution width values were measured. We found that 24.1% of subjects had iron deficiency, and 15.5% had anemia. There was a significant positive correlation between age and ferritin and hematological measures. Results of this study confirmed that iron deficiency and anemia are common in children with autistic disorder. These findings suggest that ferritin levels should be measured in subjects with autism as a part of routine investigation.

  13. The role of serum transferrin receptor in the diagnosis of iron deficiency.

    Science.gov (United States)

    Remacha, A F; Sarda, M P; Parellada, M; Ubeda, J; Manteiga, R

    1998-11-01

    Iron deficiency anemia (IDA) is often associated with inflammatory disorders. The most conventional parameters of iron metabolism are therefore affected, making the evaluation of iron status difficult. Serum transferrin receptor (sTfR) levels are raised in iron deficiency but are not influenced by inflammatory changes. The aim of this study was to investigate the role of sTfR in differentiating IDA with inflammatory features. A diagnostic study of sTfR measured by immunoassay was carried out in IDA and anemia of chronic disorders (ACD). The cut-off points of sTfR and the ratio of sTfR/serum ferritin, which were obtained after comparing IDA and ACD, were applied to a group of 64 patients with mixed iron patterns (MIX) (16 with ACD and 48 with IDA). The best cut-off point of sTfR between IDA and ACD was 4.7 mg/L. Applying this cut-off to the MIX group, an efficiency of 87% was obtained (sensitivity 92% and specificity 81%). This level of sTfR correctly classified 53 out of 64 cases of the MIX group (83%). Using the ratio of sTfRx 100/serum ferritin, the best cut-off point was 8 (efficiency 100%), which correctly classified 62 out of 64 cases of the MIX group (97%). This study demonstrates that sTfR in conjunction with other iron parameters is very useful in iron deficiency evaluation, especially in hospital practice. Iron treatment should be considered in patients with mixed patterns of iron status, in which the diagnosis of IDA versus ACD is difficult, when the levels of sTfR exceed the cut-off point.

  14. Tissue-specific histochemical localization of iron and ferritin gene ...

    Indian Academy of Sciences (India)

    ficient and inappropriate diet is a severe nutritional problem. (Goto et al. 2001) that affects ... Ferritin is an iron storage protein which stores 4500 iron atoms in its central ... content in a high-economic-value indica rice variety (Oryza sativa L. cv.

  15. Serum Hepcidin and Soluble Transferrin Receptor in the Assessment of Iron Metabolism in Children on a Vegetarian Diet.

    Science.gov (United States)

    Ambroszkiewicz, Jadwiga; Klemarczyk, Witold; Mazur, Joanna; Gajewska, Joanna; Rowicka, Grażyna; Strucińska, Małgorzata; Chełchowska, Magdalena

    2017-12-01

    The aim of this study was to assess the effect of vegetarian diet on iron metabolism parameters paying special attention to serum hepcidin and soluble transferrin receptor (sTfR) concentrations in 43 prepubertal children (age range 4.5-9.0 years) on vegetarian and in 46 children on omnivorous diets. There were no significant differences according to age, weight, height, and body mass index (BMI) between vegetarian and omnivorous children. Vegetarians had similar intake of iron and vitamin B 12 and a significantly higher intake of vitamin C (p vegetarians. Hematologic parameters and serum iron concentrations were within the reference range in both groups of children. Serum transferrin levels were similar in all subjects; however, ferritin concentrations were significantly (p vegetarians than in omnivores. In children on a vegetarian diet, median hepcidin levels were lower (p vegetarians. We did not find significant associations with concentration of sTfR and selected biochemical, anthropometric, and dietary parameters in any of the studied groups of children. As hematologic parameters and iron concentrations in vegetarians and omnivores were comparable and ferritin level was lower in vegetarians, we suggest that inclusion of novel markers, in particular sTfR (not cofounded by inflammation) and hepcidin, can better detect subclinical iron deficiency in children following vegetarian diets.

  16. Initial Serum Ferritin Predicts Number of Therapeutic Phlebotomies to Iron Depletion in Secondary Iron Overload

    Science.gov (United States)

    Panch, Sandhya R.; Yau, Yu Ying; West, Kamille; Diggs, Karen; Sweigart, Tamsen; Leitman, Susan F.

    2014-01-01

    Background Therapeutic phlebotomy is increasingly used in patients with transfusional siderosis to mitigate organ injury associated with iron overload (IO). Laboratory response parameters and therapy duration are not well characterized in such patients. Methods We retrospectively evaluated 99 consecutive patients undergoing therapeutic phlebotomy for either transfusional IO (TIO, n=88; 76% had undergone hematopoietic transplantation) or non-transfusional indications (hyperferritinemia or erythrocytosis) (n=11). CBC, serum ferritin (SF), transferrin saturation, and transaminases were measured serially. Phlebotomy goal was an SF< 300 mcg/L. Results Mean SF prior to phlebotomy among TIO and nontransfusional subjects was 3,093 and 396 mcg/L, respectively. Transfusion burden in the TIO group was 94 ± 108 (mean ± SD) RBC units; about half completed therapy with 24 ± 23 phlebotomies (range 1–103). One-third was lost to follow-up. Overall, 15% had mild adverse effects, including headache, nausea, and dizziness, mainly during first phlebotomy. Prior transfusion burden correlated poorly with initial ferritin and total number of phlebotomies to target (NPT) in the TIO group. However, NPT was strongly correlated with initial SF (R2=0.8; p<0.0001) in both TIO and nontransfusional groups. ALT decreased significantly with serial phlebotomy in all groups (mean initial and final values, 61 and 39 U/L; p = 0.03). Conclusions Initial SF but not transfusion burden predicted number of phlebotomies to target in patients with TIO. Despite good treatment tolerance, significant losses to follow-up were noted. Providing patients with an estimated phlebotomy number and follow-up duration, and thus a finite endpoint, may improve compliance. Hepatic function improved with iron off-loading. PMID:25209879

  17. Serum ferritin in normal subjects and assessment of iron status during pregnancy

    International Nuclear Information System (INIS)

    Eltayeb, Ahmed Eltayeb

    1997-12-01

    This study was conducted with two main objectives;the estimation of serum ferritin level in normal subjects in khartoum area and the assessment of iron status during pregnancy at second and third trimesters. To fulfill the first objective,two hundred and sixty symptoms-free subjects were included in the study,103 males with ages ranging from 15 to 36 years and 157 females with ages ranging from 15 to 45 years.Serum ferritin was determined by radioimmunoassay (RIA). It was found that the mean concentration of male serum ferritin was much higher than that of the females. For the assessment of iron status during pregnancy,eighty five normal pregnant women were included in the study at the start of the second trimester.Two blood samples were taken during the second trimester and two blood samples during the third trimester. The height of all subjects was measured.The weights of the subjects were measured with each sample. All subjects were under iron-supplementations throughout the gestation period.Sixty four normal non pregnant women were included in the study to serve as controls. No significant difference was observed in the mean haemoglobin concentrations but the PCV of the non-pregnant women was higher than that of the pregnant women at different stages of gestation. MCV, MCH and MCHC values of the non-pregnant women were lower than those of the pregnant women at different stages of gestation. Serum iron and transferrin saturation of the non-pregnant women were higher than those of the pregnant women,this difference was statistically significant at weeks (16 -18) and weeks (22-24). Serum ferritin of the non-pregnant women was higher than that of the pregnant women and decreased continously during the prgnancy, but this decrease was not statistically significant. Iron deficiency anaemia was observed in both pregnant and non-pregnant women. The best parameter which could be used as a marker for iron deficiency is serum ferritin. Iron supplementations corrected for

  18. Serum ferritin in normal subjects and assessment of iron status during pregnancy

    Energy Technology Data Exchange (ETDEWEB)

    Eltayeb, Ahmed Eltayeb [Sudan Atomic Energy Commission, Khartoum (Sudan)

    1997-12-01

    This study was conducted with two main objectives;the estimation of serum ferritin level in normal subjects in khartoum area and the assessment of iron status during pregnancy at second and third trimesters. To fulfill the first objective,two hundred and sixty symptoms-free subjects were included in the study,103 males with ages ranging from 15 to 36 years and 157 females with ages ranging from 15 to 45 years.Serum ferritin was determined by radioimmunoassay (RIA). It was found that the mean concentration of male serum ferritin was much higher than that of the females. For the assessment of iron status during pregnancy,eighty five normal pregnant women were included in the study at the start of the second trimester.Two blood samples were taken during the second trimester and two blood samples during the third trimester. The height of all subjects was measured.The weights of the subjects were measured with each sample. All subjects were under iron-supplementations throughout the gestation period.Sixty four normal non pregnant women were included in the study to serve as controls. No significant difference was observed in the mean haemoglobin concentrations but the PCV of the non-pregnant women was higher than that of the pregnant women at different stages of gestation. MCV, MCH and MCHC values of the non-pregnant women were lower than those of the pregnant women at different stages of gestation. Serum iron and transferrin saturation of the non-pregnant women were higher than those of the pregnant women,this difference was statistically significant at weeks (16 -18) and weeks (22-24). Serum ferritin of the non-pregnant women was higher than that of the pregnant women and decreased continously during the prgnancy, but this decrease was not statistically significant. Iron deficiency anaemia was observed in both pregnant and non-pregnant women. The best parameter which could be used as a marker for iron deficiency is serum ferritin. Iron supplementations corrected for

  19. Serum hepcidin-25 may replace the ferritin index in the Thomas plot in assessing iron status in anemic patients.

    Science.gov (United States)

    Thomas, C; Kobold, U; Balan, S; Roeddiger, R; Thomas, L

    2011-04-01

    Biochemical markers of iron deficiency do not distinguish iron-deficient anemia (IDA) from the anemia of chronic disease (ACD) and the combined state of ACD/IDA. Serum hepcidin-25 might be a marker resolving this problem. We investigated the extent to which serum hepcidin-25 enables the differentiation of the states above in comparison with the ferritin index plot, the so-called Thomas plot [soluble transferrin receptor (sTfR)/log ferritin and the reticulocyte hemoglobin content (CHr)]. Serum hepcidin-25 was determined in 155 anemic patients who were classified as having latent iron deficiency (latent ID), IDA, ACD, or ACD/IDA using the ferritin index plot (Thomas plot). Hepcidin-25 was determined using an isotope-dilution micro-HPLC-tandem mass spectrometry method. The ability to discriminate among these states based on serum hepcidin-25 alone or in combination with the CHr was evaluated in a receiver operating characteristic curve analysis and a comparison with the recently established ferritin index plot. Serum hepcidin-25 correlated with ferritin and the ferritin index. Use of a hepcidin-25 cutoff level of ≤4 nmol/l allowed the differentiation of IDA from ACD and ACD/IDA. Furthermore, the discrimination of ACD/IDA from ACD required combination with CHr in a new plot (hepcidin-25 and the CHr). The hepcidin-25 plot and the ferritin index plot showed a good correspondence in the differentiation of iron states in patients with anemia. Patients with IDA can be differentiated from ACD and ACD/IDA but not ACD from ACD/IDA based on hepcidin-25 alone. The combination of hepcidin-25 with CHr in the hepcidin-25 plot was useful for the differentiation of the states above. © 2010 Blackwell Publishing Ltd.

  20. Iron exchange between transferrin molecules mediated by phosphate compounds and other cell metabolites.

    Science.gov (United States)

    Morgan, E H

    1977-08-25

    The ability of a large number of cellular metabolites to release iron from transferrin was investigated by measuring the rate at which they could mediate iron exchange between two types of transferrin. Rabbit transferrin labelled with 59Fe was incubated with human apotransferrin in the presence of the metabolites. After varying periods of incubation the human transferrin was separated from the rabbit transferrin by immunoprecipitation. GTP, 2,3-diphosphoglycerate, ATP, ADP and citrate produced the most rapid exchange of iron between the two types of transferrin, but many other compounds showed some degree of activity. Iron exchange mediated by the organic phosphates had the characteristics of a single first-order reaction and was sensitive to changes of incubation temperature and pH. The activation energy for the exchange reaction was approx. 13 kcal/mol. The rate of iron exchange from the oxalate - iron - transferrin complex was much lower than from bicarbonate - iron - transferrin. It is concluded that several organic phosphates have the capacity of releasing iron from transferrin. These compounds may represent the means by which the iron is released during the process of cellular uptake.

  1. Abnormal iron metabolism and oxidative stress in mice expressing a mutant form of the ferritin light polypeptide gene

    Science.gov (United States)

    Barbeito, Ana G.; Garringer, Holly J.; Baraibar, Martin A.; Gao, Xiaoying; Arredondo, Miguel; Núñez, Marco T.; Smith, Mark A.; Ghetti, Bernardino; Vidal, Ruben

    2009-01-01

    Insertional mutations in exon 4 of the ferritin light chain (FTL) gene are associated with hereditary ferritinopathy (HF) or neuroferritinopathy, an autosomal dominant neurodegenerative disease characterized by progressive impairment of motor and cognitive functions. To determine the pathogenic mechanisms by which mutations in FTL lead to neurodegeneration, we investigated iron metabolism and markers of oxidative stress in the brain of transgenic (Tg) mice that express the mutant human FTL498-499InsTC cDNA. Compared with wild-type mice, brain extracts from Tg (FTL-Tg) mice showed an increase in the cytoplasmic levels of both FTL and ferritin heavy chain polypeptides, a decrease in the protein and mRNA levels of transferrin receptor-1, and a significant increase in iron levels. Transgenic mice also showed the presence of markers for lipid peroxidation, protein carbonyls, and nitrone–protein adducts in the brain. However, gene expression analysis of iron management proteins in the liver of Tg mice indicates that the FTL-Tg mouse liver is iron deficient. Our data suggest that disruption of iron metabolism in the brain has a primary role in the process of neurodegeneration in HF and that the pathogenesis of HF is likely to result from a combination of reduction in iron storage function and enhanced toxicity associated with iron-induced ferritin aggregates in the brain. PMID:19519778

  2. Ferritin gene transcription is regulated by iron in soybean cell cultures.

    Science.gov (United States)

    Lescure, A M; Proudhon, D; Pesey, H; Ragland, M; Theil, E C; Briat, J F

    1991-09-15

    Iron-regulated ferritin synthesis in animals is dominated by translational control of stored mRNA; iron-induced transcription of ferritin genes, when it occurs, changes the subunit composition of ferritin mRNA and protein and is coupled to translational control. Ferritins in plants and animals have evolved from a common progenitor, based on the similarity of protein sequence; however, sequence divergence occurs in the C termini; structure prediction suggests that plant ferritin has the E-helix, which, in horse ferritin, forms a large channel at the tetrameric interface. In contemporary plants, a transit peptide is encoded by ferritin mRNA to target the protein to plastids. Iron-regulated synthesis of ferritin in plants and animals appears to be very different since the 50- to 60-fold increases of ferritin protein, previously observed to be induced by iron in cultured soybean cells, is accompanied by an equivalent accumulation of hybridizable ferritin mRNA and by increased transcription of ferritin genes. Ferritin mRNA from iron-induced cells and the constitutive ferritin mRNA from soybean hypocotyls are identical. The iron-induced protein is translocated normally to plastids. Differences in animal ferritin structure coincide with the various iron storage functions (reserve for iron proteins and detoxification). In contrast, the constancy of structure of soybean ferritin, iron-induced and constitutive, coupled with the potential for vacuolar storage of excess iron in plants suggest that rapid synthesis of ferritin from a stored ferritin mRNA may not be needed in plants for detoxification of iron.

  3. Sequence analysis of dolphin ferritin H and L subunits and possible iron-dependent translational control of dolphin ferritin gene

    Directory of Open Access Journals (Sweden)

    Sasaki Yukako

    2008-10-01

    Full Text Available Abstract Background Iron-storage protein, ferritin plays a central role in iron metabolism. Ferritin has dual function to store iron and segregate iron for protection of iron-catalyzed reactive oxygen species. Tissue ferritin is composed of two kinds of subunits (H: heavy chain or heart-type subunit; L: light chain or liver-type subunit. Ferritin gene expression is controlled at translational level in iron-dependent manner or at transcriptional level in iron-independent manner. However, sequencing analysis of marine mammalian ferritin subunits has not yet been performed fully. The purpose of this study is to reveal cDNA-derived amino acid sequences of cetacean ferritin H and L subunits, and demonstrate the possibility of expression of these subunits, especially H subunit, by iron. Methods Sequence analyses of cetacean ferritin H and L subunits were performed by direct sequencing of polymerase chain reaction (PCR fragments from cDNAs generated via reverse transcription-PCR of leukocyte total RNA prepared from blood samples of six different dolphin species (Pseudorca crassidens, Lagenorhynchus obliquidens, Grampus griseus, Globicephala macrorhynchus, Tursiops truncatus, and Delphinapterus leucas. The putative iron-responsive element sequence in the 5'-untranslated region of the six different dolphin species was revealed by direct sequencing of PCR fragments obtained using leukocyte genomic DNA. Results Dolphin H and L subunits consist of 182 and 174 amino acids, respectively, and amino acid sequence identities of ferritin subunits among these dolphins are highly conserved (H: 99–100%, (99→98 ; L: 98–100%. The conserved 28 bp IRE sequence was located -144 bp upstream from the initiation codon in the six different dolphin species. Conclusion These results indicate that six different dolphin species have conserved ferritin sequences, and suggest that these genes are iron-dependently expressed.

  4. Second international round robin for the quantification of serum non-transferrin-bound iron and labile plasma iron in patients with iron-overload disorders

    NARCIS (Netherlands)

    de Swart, Louise; Hendriks, Jan C. M.; van der Vorm, Lisa N.; Cabantchik, Z. Ioav; Evans, Patricia J.; Hod, Eldad A.; Brittenham, Gary M.; Furman, Yael; Wojczyk, Boguslaw; Janssen, Mirian C. H.; Porter, John B.; Mattijssen, Vera E. J. M.; Biemond, Bart J.; MacKenzie, Marius A.; Origa, Raffaella; Galanello, Renzo; Hider, Robert C.; Swinkels, Dorine W.

    2016-01-01

    Non-transferrin-bound iron and its labile (redox active) plasma iron component are thought to be potentially toxic forms of iron originally identified in the serum of patients with iron overload. We compared ten worldwide leading assays (6 for non-transferrin-bound iron and 4 for labile plasma iron)

  5. Iron metabolism in BeWo chorion carcinoma cells. Transferrin-mediated uptake and release of iron

    NARCIS (Netherlands)

    van der Ende, A.; du Maine, A.; Simmons, C. F.; Schwartz, A. L.; Strous, G. J.

    1987-01-01

    Growing human choriocarcinoma BeWo b24 cells contain 1.5 X 10(6) functional cell surface transferrin binding sites and 2.0 X 10(6) intracellular binding sites. These cells rapidly accumulate iron at a rate of 360,000 iron atoms/min/cell. During iron uptake the transferrin and its receptor recycle at

  6. Relation between Serum Ferritin and Iron Parameters with Preeclampsia

    Directory of Open Access Journals (Sweden)

    Robabeh Taheripanah

    2007-06-01

    Full Text Available Objective: Preeclampsia is one of the most important complications of pregnancy that is associated with increased morbidity and mortality. The aim of this study was to investigate the relation between serum iron status and ferritin with pre-eclampsia. Materials and Methods: This case control study evaluated 33 preeclamptic patients and 33 normal pregnant women before parturition in Imam Hossein hospital, from March 2003 till March 2004. Anemia, diabetes and multiple pregnancies were excluded from the study. Blood samples were taken before delivery and patients with HELLP syndrome were considered separately.  Data were analyzed using the SPSS software and P value <0.05 was considered statistically significant. T-test, chi-square and Fisher exact test were used.  Results: The mean of serum iron level in case and control group was 79.9±32.4µg/dl and 88.6±40.8 µg/dl, respectively (NS. TIBC was 443.4±55.0 µmol/l and 383.7±63.6 µmol/l in normal patients and preeclamptics respectively (P = 0.002. Mean serum ferritin was 32.1±16.2 ng/dl in control group and 123.8±46.1 ng/dl in preeclamptics (P<0.001. No meaningful relation was observed between hematocrit, ferritin and iron. Conclusions: Ferritin increases and TIBC decreases in preeclampsia regardless of hepatic function. It seems that elevated serum ferritin (as an oxidative stress can accelerate vascular damage. So, routine iron supplementation in preeclamptic women is questationable.

  7. Iron release from ferritin and lipid peroxidation by radiolytically generated reducing radicals

    International Nuclear Information System (INIS)

    Reif, D.W.; Schubert, J.; Aust, S.D.

    1988-01-01

    Iron is involved in the formation of oxidants capable of damaging membranes, protein, and DNA. Using 137 Cs gamma radiation, we investigated the release of iron from ferritin and concomitant lipid peroxidation by radiolytically generated reducing radicals, superoxide and the carbon dioxide anion radical. Both radicals released iron from ferritin with similar efficiencies and iron mobilization from ferritin required an iron chelator. Radiolytically generated superoxide anion resulted in peroxidation of phospholipid liposomes as measured by malondialdehyde formation only when ferritin was included as an iron source and the released iron was found to be chelated by the phospholipid liposomes

  8. Iron status of pregnant Filipino women as measured by serum ferritin.

    Science.gov (United States)

    Perlas, L A; Kuizon, M D; Tajaon, R T; Desnacido, J A

    1992-12-01

    Iron status of pregnant women at different stages of pregnancy was evaluated by comparing values for hemoglobin (Hb), red cell indices, serum iron (SI), transferrin saturation (TS) and serum ferritin (SF) values with those of a group of non-pregnant women of comparable age and socio-economic status. Mean SF values on the second and third trimesters (9.3 +/- 2.60 ng/ml and 7.1 +/- 2.19 ng/ml) were significantly lower compared to that in the first trimester (22.6 +/- 2.20 ng/ml). These levels were also lower than that found in the non-pregnant controls. The trend was the same for TS. Hemoglobin levels of the pregnant subjects were significantly lower than those of the non-pregnant women. Prevalence of iron deficiency based on SF < 12.0 ng/ml and TS < 16.0% was highest at term and lowest during the first trimester indicating a decrease in iron stores as pregnancy progressed. Sensitivity for each of the iron parameters was computed, and it was found that for the diagnosis of iron deficiency in pregnant women, SF has a greater sensitivity than TS, SI, MCV and MCH.

  9. Changes in serum iron, total iron binding capacity and transferrin ...

    African Journals Online (AJOL)

    Background: Iron is a vital constituent of cells but in excess may be harmful and is associated with a raised risk for some malignant diseases including breast cancer. We aimed to study changes in iron profile in Sudanese females newly diagnosed with breast cancer. Methods: A case- control study in which serum iron, Total ...

  10. Transferrin receptor-1 and ferritin heavy and light chains in astrocytic brain tumors

    DEFF Research Database (Denmark)

    Rosager, Ann Mari; Sørensen, Mia D; Dahlrot, Rikke H

    2017-01-01

    Astrocytic brain tumors are the most frequent primary brain tumors. Treatment with radio- and chemotherapy has increased survival making prognostic biomarkers increasingly important. The aim of the present study was to investigate the expression and prognostic value of transferrin receptor-1 (TfR...

  11. Metallofullerenol Inhibits Cellular Iron Uptake by Inducing Transferrin Tetramerization.

    Science.gov (United States)

    Li, Jinxia; Xing, Xueqing; Sun, Baoyun; Zhao, Yuliang; Wu, Zhonghua

    2017-10-18

    Herein, A549 tumor cell proliferation was confirmed to be positively dependent on the concentration of Fe 3+ or transferrin (Tf). Gd@C 82 (OH) 22 or C 60 (OH) 22 effectively inhibited the iron uptake and the subsequent proliferation of A549 cells. The conformational changes of Tf mixed with FeCl 3 , GdCl 3 , C 60 (OH) 22 or Gd@C 82 (OH) 22 were obtained by SAXS. The results demonstrate that Tf homodimers can be decomposed into monomers in the presence of FeCl 3 , GdCl 3 or C 60 (OH) 22 , but associated into tetramers in the presence of Gd@C 82 (OH) 22 . The larger change of SAXS shapes between Tf+C 60 (OH) 22 and Tf+FeCl 3 implies that C 60 (OH) 22 is bound to Tf, blocking the iron-binding site. The larger deviation of the SAXS shape from a possible crystal structure of Tf tetramer implies that Gd@C 82 (OH) 22 is bound to the Tf tetramer, thus disturbing iron transport. This study well explains the inhibition mechanism of Gd@C 82 (OH) 22 and C 60 (OH) 22 on the iron uptake and the proliferation of A549 tumor cells and highlights the specific interactions of a nanomedicine with the target biomolecules in cancer therapy. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  12. An unusual case of iron deficiency anemia is associated with extremely low level of transferrin receptor.

    Science.gov (United States)

    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.

  13. The impact of maternal obesity on iron status, placental transferrin receptor expression and hepcidin expression in human pregnancy.

    Science.gov (United States)

    Garcia-Valdes, L; Campoy, C; Hayes, H; Florido, J; Rusanova, I; Miranda, M T; McArdle, H J

    2015-04-01

    Obesity is associated with decreased iron status, possibly due to a rise in hepcidin, an inflammatory protein known to reduce iron absorption. In animals, we have shown that maternal iron deficiency is minimised in the foetus by increased expression of placental transferrin receptor (pTFR1), resulting in increased iron transfer at the expense of maternal iron stores. This study examines the effect of obesity during pregnancy on maternal and neonatal iron status in human cohorts and whether the placenta can compensate for decreased maternal iron stores by increasing pTFR1 expression. A total of 240 women were included in this study. One hundred and fifty-eight placentas (Normal: 90; Overweight: 37; Obese: 31) were collected at delivery. Maternal iron status was measured by determining serum transferrin receptor (sTFR) and ferritin levels at 24 and 34 weeks and at delivery. Hepcidin in maternal and cord blood was measured by ELISA and pTFR1 in placentas by western blotting and real-time RT-PCR. Low iron stores were more common in obese women. Hepcidin levels (ng ml(-1)) at the end of the pregnancy were higher in obese than normal women (26.03±12.95 vs 18.00±10.77, PMaternal hepcidin levels were correlated with maternal iron status (sTFR r=0.2 P=0.025), but not with neonatal values. mRNA and protein levels of pTFR1 were both inversely related to maternal iron status. For mRNA and all women, sTFR r=0.2 P=0.044. Ferritin mRNA levels correlated only in overweight women r=-0.5 P=0.039 with hepcidin (r=0.1 P=0.349), irrespective of maternal body mass index (BMI). The data support the hypothesis that obese pregnant women have a greater risk of iron deficiency and that hepcidin may be a regulatory factor. Further, we show that the placenta responds to decreased maternal iron status by increasing pTFR1 expression.

  14. Evidence that transferrin supports cell proliferation by supplying iron for DNA synthesis

    International Nuclear Information System (INIS)

    Laskey, J.; Webb, I.; Schulman, H.M.; Ponka, P.

    1988-01-01

    Transferrin is essential for cell proliferation and it was suggested that it may trigger a proliferative response following its interaction with receptors, serving as a growth factor. However, since the only clearly defined function of transferrin is iron transport, it may merely serve as an iron donor. To further clarify this issue, the authors took advantage of an iron chelate, ferric salicylaldehyde isonicotinoyl hydrazone (Fe-SIH), which they developed and previously demonstrated to efficiently supply iron to cells without using physiological transferrin receptor pathway. As expected, they observed that blocking monoclonal antibodies against transferrin receptors inhibited proliferation of both Raji and murine erythroleukemia cells. This inhibited cell growth was rescued upon the addition of Fe-SIH which was also shown to deliver iron to Raji cells in the presence of blocking anti-transferrin receptor antibodies. Moreover, blocking anti-transferrin receptor antibodies inhibited [ 3 H]thymidine incorporation into DNA and this inhibition could be overcome by added Fe-SIH. In addition, Fe-SIH slightly stimulated, while SIH (an iron chelator) significantly inhibited, DNA synthesis in phytohemagglutinin-stimulated peripheral blood lymphocytes. Taken together, these results indicate that the only function of transferrin supporting cell proliferation is to supply cells with iron

  15. Magnetic resonance imaging of reconstructed ferritin as an iron-induced pathological model system

    Energy Technology Data Exchange (ETDEWEB)

    Balejcikova, Lucia [Institute of Experimental Physics SAS, Watsonova 47, 040 01 Kosice (Slovakia); Institute of Measurement Science SAS, Dubravska cesta 9, 841 04 Bratislava 4 (Slovakia); Strbak, Oliver [Institute of Measurement Science SAS, Dubravska cesta 9, 841 04 Bratislava 4 (Slovakia); Biomedical Center Martin, Jessenius Faculty of Medicine in Martin, Comenius University in Bratislava, Mala Hora 4, 036 01 Martin (Slovakia); Baciak, Ladislav [Faculty of Chemical and Food Technology STU, Radlinskeho 9, 812 37 Bratislava (Slovakia); Kovac, Jozef [Institute of Experimental Physics SAS, Watsonova 47, 040 01 Kosice (Slovakia); Masarova, Marta; Krafcik, Andrej; Frollo, Ivan [Institute of Measurement Science SAS, Dubravska cesta 9, 841 04 Bratislava 4 (Slovakia); Dobrota, Dusan [Biomedical Center Martin, Jessenius Faculty of Medicine in Martin, Comenius University in Bratislava, Mala Hora 4, 036 01 Martin (Slovakia); Kopcansky, Peter [Institute of Experimental Physics SAS, Watsonova 47, 040 01 Kosice (Slovakia)

    2017-04-01

    Iron, an essential element of the human body, is a significant risk factor, particularly in the case of its concentration increasing above the specific limit. Therefore, iron is stored in the non-toxic form of the globular protein, ferritin, consisting of an apoferritin shell and iron core. Numerous studies confirmed the disruption of homeostasis and accumulation of iron in patients with various diseases (e.g. cancer, cardiovascular or neurological conditions), which is closely related to ferritin metabolism. Such iron imbalance enables the use of magnetic resonance imaging (MRI) as a sensitive technique for the detection of iron-based aggregates through changes in the relaxation times, followed by the change in the inherent image contrast. For our in vitrostudy, modified ferritins with different iron loadings were prepared by chemical reconstruction of the iron core in an apoferritin shell as pathological model systems. The magnetic properties of samples were studied using SQUID magnetometry, while the size distribution was detected via dynamic light scattering. We have shown that MRI could represent the most advantageous method for distinguishing native ferritin from reconstructed ferritin which, after future standardisation, could then be suitable for the diagnostics of diseases associated with iron accumulation. - Highlights: • MRI is the sensitive technique for detecting iron-based aggregates. • Reconstructed Ferritin is suitable model system of iron-related disorders. • MRI allow distinguish of native ferritin from reconstructed ferritin. • MRI could be useful for diagnostics of diseases associated with iron accumulation.

  16. Tertiary structural changes and iron release from human serum transferrin.

    Science.gov (United States)

    Mecklenburg, S L; Donohoe, R J; Olah, G A

    1997-08-01

    Iron release from human serum transferrin was investigated by comparison of the extent of bound iron, measured by charge transfer absorption band intensity (465 nm), with changes observed by small-angle solution X-ray scattering (SAXS) for a series of equilibrated samples between pH 5.69 and 7.77. The phosphate buffers used in this study promote iron release at relatively high pH values, with an empirical pK of 6.9 for the convolved release from the two sites. The spectral data reveal that the N-lobe release is nearly complete by pH 7.0, while the C-lobe remains primarily metal-laden. Conversely, the radius of gyration, Rg, determined from the SAXS data remains constant between pH 7.77 and 7.05, and the evolution of Rg between its value observed for the diferric protein at pH 7.77 (31.2+/-0.2 A) and that of the apo protein at pH 5.69 (33.9+/-0.4 A) exhibits an empirical pK of 6.6. While Rg is effectively constant in the pH range associated with iron release from the N-lobe, the radius of gyration of cross-section, Rc, increases from 16.9+/-0.2 A to 17.6+/-0.2 A. Model simulations suggest that two different rotations of the NII domain relative to the NI domain about a hinge deep in the iron-binding cleft of the N-lobe, one parallel with and one perpendicular to the plane of the iron-binding site, can be significantly advanced relative to their holo protein positions while yielding constant Rg and increased Rc values consistent with the scattering data. Rotation of the CII domain parallel with the C-lobe iron-binding site plane can partially account for the increased Rg values measured at low pH; however, no reasonable combined repositioning of the NII and CII domains yields the experimentally observed increase in Rg.

  17. Central role for ferritin in the day/night regulation of iron homeostasis in marine phytoplankton

    Science.gov (United States)

    Botebol, Hugo; Lesuisse, Emmanuel; Šuták, Robert; Six, Christophe; Lozano, Jean-Claude; Schatt, Philippe; Vergé, Valérie; Kirilovsky, Amos; Morrissey, Joe; Léger, Thibaut; Camadro, Jean-Michel; Gueneugues, Audrey; Bowler, Chris; Blain, Stéphane; Bouget, François-Yves

    2015-01-01

    In large regions of the open ocean, iron is a limiting resource for phytoplankton. The reduction of iron quota and the recycling of internal iron pools are among the diverse strategies that phytoplankton have evolved to allow them to grow under chronically low ambient iron levels. Phytoplankton species also have evolved strategies to cope with sporadic iron supply such as long-term storage of iron in ferritin. In the picophytoplanktonic species Ostreococcus we report evidence from observations both in the field and in laboratory cultures that ferritin and the main iron-binding proteins involved in photosynthesis and nitrate assimilation pathways show opposite diurnal expression patterns, with ferritin being maximally expressed during the night. Biochemical and physiological experiments using a ferritin knock-out line subsequently revealed that this protein plays a central role in the diel regulation of iron uptake and recycling and that this regulation of iron homeostasis is essential for cell survival under iron limitation. PMID:26553998

  18. Investigation and management of a raised serum ferritin.

    Science.gov (United States)

    Cullis, Jonathan O; Fitzsimons, Edward J; Griffiths, William Jh; Tsochatzis, Emmanouil; Thomas, D Wayne

    2018-05-01

    Serum ferritin level is one of the most commonly requested investigations in both primary and secondary care. Whilst low serum ferritin levels invariably indicate reduced iron stores, raised serum ferritin levels can be due to multiple different aetiologies, including iron overload, inflammation, liver or renal disease, malignancy, and the recently described metabolic syndrome. A key test in the further investigation of an unexpected raised serum ferritin is the serum transferrin saturation. This guideline reviews the investigation and management of a raised serum ferritin level. The investigation and management of genetic haemochromatosis is not dealt with however and is the subject of a separate guideline. © 2018 John Wiley & Sons Ltd.

  19. Quantitating Iron in Serum Ferritin by Use of ICP-MS

    Science.gov (United States)

    Smith, Scott M.; Gillman, Patricia L.

    2003-01-01

    A laboratory method has been devised to enable measurement of the concentration of iron bound in ferritin from small samples of blood (serum). Derived partly from a prior method that depends on large samples of blood, this method involves the use of an inductively-coupled-plasma mass spectrometer (ICP-MS). Ferritin is a complex of iron with the protein apoferritin. Heretofore, measurements of the concentration of serum ferritin (as distinguished from direct measurements of the concentration of iron in serum ferritin) have been used to assess iron stores in humans. Low levels of serum ferritin could indicate the first stage of iron depletion. High levels of serum ferritin could indicate high levels of iron (for example, in connection with hereditary hemochromatosis an iron-overload illness that is characterized by progressive organ damage and can be fatal). However, the picture is complicated: A high level of serum ferritin could also indicate stress and/or inflammation instead of (or in addition to) iron overload, and low serum iron concentration could indicate inflammation rather than iron deficiency. Only when concentrations of both serum iron and serum ferritin increase and decrease together can the patient s iron status be assessed accurately. Hence, in enabling accurate measurement of the iron content of serum ferritin, the present method can improve the diagnosis of the patient s iron status. The prior method of measuring the concentration of iron involves the use of an atomic-absorption spectrophotometer with a graphite furnace. The present method incorporates a modified version of the sample- preparation process of the prior method. First, ferritin is isolated; more specifically, it is immobilized by immunoprecipitation with rabbit antihuman polyclonal antibody bound to agarose beads. The ferritin is then separated from other iron-containing proteins and free iron by a series of centrifugation and wash steps. Next, the ferritin is digested with nitric acid

  20. Pre-Altitude Serum Ferritin Levels and Daily Oral Iron Supplement Dose Mediate Iron Parameter and Hemoglobin Mass Responses to Altitude Exposure.

    Directory of Open Access Journals (Sweden)

    Andrew D Govus

    Full Text Available To investigate the influence of daily oral iron supplementation on changes in hemoglobin mass (Hbmass and iron parameters after 2-4 weeks of moderate altitude exposure.Hematological data collected from 178 athletes (98 males, 80 females exposed to moderate altitude (1,350-3,000 m were analysed using linear regression to determine how altitude exposure combined with oral iron supplementation influenced Hbmass, total iron incorporation (TII and blood iron parameters [ferritin and transferrin saturation (TSAT].Altitude exposure (mean ± s: 21 ± 3 days increased Hbmass by 1.1% [-0.4, 2.6], 3.3% [1.7, 4.8], and 4.0% [2.0, 6.1] from pre-altitude levels in athletes who ingested nil, 105 mg and 210 mg respectively, of oral iron supplement daily. Serum ferritin levels decreased by -33.2% [-46.9, -15.9] and 13.8% [-32.2, 9.7] from pre-altitude levels in athletes who supplemented with nil and 105 mg of oral iron supplement daily, but increased by 36.8% [1.3, 84.8] in athletes supplemented with 210 mg of oral iron daily. Finally, athletes who ingested either 105 mg or 210 mg of oral iron supplement daily had a greater TII compared with non-supplemented athletes (0 versus 105 mg: effect size (d = -1.88 [-2.56, -1.17]; 0 versus 210 mg: effect size (d = -2.87 [-3.88, -1.66].Oral iron supplementation during 2-4 weeks of moderate altitude exposure may enhance Hbmass production and assist the maintenance of iron balance in some athletes with low pre-altitude iron stores.

  1. The role of hepatic transferrin receptor 2 in the regulation of iron homeostasis in the body.

    Directory of Open Access Journals (Sweden)

    Christal A Worthen

    2014-03-01

    Full Text Available Fine tuning of body iron is required to prevent diseases such as iron-overload and anemia. The putative iron-sensor, transferrin receptor 2 (TfR2, is expressed in the liver and mutations in this protein result in the iron-overload disease Type III hereditary hemochromatosis (HH. With the loss of functional TfR2, the liver produces about two-fold less of the peptide hormone hepcidin, which is responsible for negatively regulating iron uptake from the diet. This reduction in hepcidin expression leads to the slow accumulation of iron in the liver, heart, joints, and pancreas and subsequent cirrhosis, heart disease, arthritis, and diabetes. TfR2 can bind iron-loaded transferrin in the bloodstream, and hepatocytes treated with transferrin respond with a two-fold increase in hepcidin expression through stimulation of the BMP-signaling pathway. Loss of functional TfR2 or its binding partner, the original HH protein (HFE, results in a loss of this transferrin-sensitivity. While much is known about the trafficking and regulation of TfR2, the mechanism of its transferrin-sensitivity through the BMP-signaling pathway is still not known.

  2. Iron Acquisition in Bacillus cereus: The Roles of IlsA and Bacillibactin in Exogenous Ferritin Iron Mobilization

    Science.gov (United States)

    Buisson, Christophe; Daou, Nadine; Kallassy, Mireille; Lereclus, Didier; Arosio, Paolo; Bou-Abdallah, Fadi; Nielsen Le Roux, Christina

    2014-01-01

    In host-pathogen interactions, the struggle for iron may have major consequences on the outcome of the disease. To overcome the low solubility and bio-availability of iron, bacteria have evolved multiple systems to acquire iron from various sources such as heme, hemoglobin and ferritin. The molecular basis of iron acquisition from heme and hemoglobin have been extensively studied; however, very little is known about iron acquisition from host ferritin, a 24-mer nanocage protein able to store thousands of iron atoms within its cavity. In the human opportunistic pathogen Bacillus cereus, a surface protein named IlsA (Iron-regulated leucine rich surface protein type A) binds heme, hemoglobin and ferritin in vitro and is involved in virulence. Here, we demonstrate that IlsA acts as a ferritin receptor causing ferritin aggregation on the bacterial surface. Isothermal titration calorimetry data indicate that IlsA binds several types of ferritins through direct interaction with the shell subunits. UV-vis kinetic data show a significant enhancement of iron release from ferritin in the presence of IlsA indicating for the first time that a bacterial protein might alter the stability of the ferritin iron core. Disruption of the siderophore bacillibactin production drastically reduces the ability of B. cereus to utilize ferritin for growth and results in attenuated bacterial virulence in insects. We propose a new model of iron acquisition in B. cereus that involves the binding of IlsA to host ferritin followed by siderophore assisted iron uptake. Our results highlight a possible interplay between a surface protein and a siderophore and provide new insights into host adaptation of B. cereus and general bacterial pathogenesis. PMID:24550730

  3. Iron acquisition in Bacillus cereus: the roles of IlsA and bacillibactin in exogenous ferritin iron mobilization.

    Directory of Open Access Journals (Sweden)

    Diego Segond

    2014-02-01

    Full Text Available In host-pathogen interactions, the struggle for iron may have major consequences on the outcome of the disease. To overcome the low solubility and bio-availability of iron, bacteria have evolved multiple systems to acquire iron from various sources such as heme, hemoglobin and ferritin. The molecular basis of iron acquisition from heme and hemoglobin have been extensively studied; however, very little is known about iron acquisition from host ferritin, a 24-mer nanocage protein able to store thousands of iron atoms within its cavity. In the human opportunistic pathogen Bacillus cereus, a surface protein named IlsA (Iron-regulated leucine rich surface protein type A binds heme, hemoglobin and ferritin in vitro and is involved in virulence. Here, we demonstrate that IlsA acts as a ferritin receptor causing ferritin aggregation on the bacterial surface. Isothermal titration calorimetry data indicate that IlsA binds several types of ferritins through direct interaction with the shell subunits. UV-vis kinetic data show a significant enhancement of iron release from ferritin in the presence of IlsA indicating for the first time that a bacterial protein might alter the stability of the ferritin iron core. Disruption of the siderophore bacillibactin production drastically reduces the ability of B. cereus to utilize ferritin for growth and results in attenuated bacterial virulence in insects. We propose a new model of iron acquisition in B. cereus that involves the binding of IlsA to host ferritin followed by siderophore assisted iron uptake. Our results highlight a possible interplay between a surface protein and a siderophore and provide new insights into host adaptation of B. cereus and general bacterial pathogenesis.

  4. Inactivation of transferrin iron binding capacity by the neutrophil myeloperoxidase system

    International Nuclear Information System (INIS)

    Clark, R.A.; Pearson, D.W.

    1989-01-01

    Human serum apotransferrin was exposed to the isolated myeloperoxidase-H2O2-halide system or to phorbol ester-activated human neutrophils. Such treatment resulted in a marked loss in transferrin iron binding capacity as well as concomitant iodination of transferrin. Each component of the cell-free system (myeloperoxidase, H2O2, iodide) or neutrophil system (neutrophils, phorbol ester, iodide) was required in order to observe these changes. In the cell-free system, the H2O2 requirement was fulfilled by either reagent H2O2 or the peroxide-generating system glucose oxidase plus glucose. Both loss of iron binding capacity and transferrin iodination by either the myeloperoxidase system or activated neutrophils were blocked by azide or catalase. The isolated peroxidase system had an acidic pH optimum, whereas the intact cell system was more efficient at neutral pH. The kinetics of changes in iron binding capacity and iodination closely paralleled one another, exhibiting t1/2 values of less than 1 min for the myeloperoxidase-H2O2 system, 3-4 min for the myeloperoxidase-glucose oxidase system, and 8 min for the neutrophil system. That the occupied binding site is protected from the myeloperoxidase system was suggested by (1) a failure to mobilize iron from iron-loaded transferrin, (2) an inverse correlation between initial iron saturation and myeloperoxidase-mediated loss of iron binding capacity, and (3) decreased myeloperoxidase-mediated iodination of iron-loaded versus apotransferrin. Since as little as 1 atom of iodide bound per molecule of transferrin was associated with substantial losses in iron binding capacity, there appears to be a high specificity of myeloperoxidase-catalyzed iodination for residues at or near the iron binding sites. Amino acid analysis of iodinated transferrin (approximately 2 atoms/molecule) demonstrated that iodotyrosine was the predominant iodinated species

  5. Internal distribution of excess iron and sources of serum ferritin in patients with thalassemia

    Energy Technology Data Exchange (ETDEWEB)

    Cazzola, M; Bergamaschi, G; Dezza, L; Borgna-Pignatti, C C; De Stefano, P; Bongo, I G; Avato, F [Pavia Univ. (Italy)

    1983-01-01

    Liver and spleen iron concentrations, serum ferritin level and binding of S-ferritin to concanavalin A (Con A) were measured in 12 patients with thalassemia major or intermedia at the time of splenectomy. All these subjects had increased liver iron concentration, most of them had hepatic fibrosis but none of them had histological evidence of chronic hepatitis. No patient had ascorbic acid deficiency. Serum ferritin concentration was increased in all cases, ranging from 266 to 5504 ..mu..g/l. In all but 2 subjects most of the protein did not bind to Con A, thus behaving as tissue ferritin. There were highly significant correlations between serum ferritin concentration, amount of blood transfused and liver iron concentration. On the average, iron concentration in the liver was about 3 times that in the spleen. The findings obtained suggest that in patients with thalassemia major or intermedia most of the iron is deposited in parenchymal tissues and most of the S-ferritin derives by leakage from the cytosol of iron-loaded parenchymal cells. S-ferritin is a valid index of liver iron overload in thalassemic patients witout complications such as viral hepatitis and/or ascorbic acid defiency.

  6. Internal distribution of excess iron and sources of serum ferritin in patients with thalassaemia

    International Nuclear Information System (INIS)

    Cazzola, M.; Bergamaschi, G.; Dezza, L.; Borgna-Pignatti, C.C.; De Stefano, P.; Bongo, I.G.; Avato, F.

    1983-01-01

    Liver and spleen iron concentrations, serum ferritin level and binding of S-ferritin to concanavalin A (Con A) were measured in 12 patients with thalassaemia major or intermedia at the time of splenectomy. All these subjects had increased liver iron concentration, most of them had hepatic fibrosis but none of them had histological evidence of chronic hepatitis. No patient had ascorbic acid deficiency. Serum ferritin concentration was increased in all cases, ranging from 266 to 5504 μg/l. In all but 2 subjects most of the protein did not bind to Con A, thus behaving as tissue ferritin. There were highly significant correlations between serum ferritin concentration, amount of blood transfused and liver iron concentration. On the avarage, iron concentration in the liver was about 3 times that in the spleen. The findings obtained suggest that in patients with thalassaemia major or intermedia most of the iron is deposited in parenchymal tissues and most of the S-ferritin derives by leakage from the cytosol of iron-loaded parenchymal cells. S-ferritin is a valid index of liver iron overload in thalassaemic patients witout complications such as viral hepatitis and/or ascorbic acid defiency. (author)

  7. Iron and ADHD: Time to Move beyond Serum Ferritin Levels

    Science.gov (United States)

    Donfrancesco, Renato; Parisi, Pasquale; Vanacore, Nicola; Martines, Francesca; Sargentini, Vittorio; Cortese, Samuele

    2013-01-01

    Objective: (a) To compare serum ferritin levels in a sample of stimulant-naive children with ADHD and matched controls and (b) to assess the association of serum ferritin to ADHD symptoms severity, ADHD subtypes, and IQ. Method: The ADHD and the control groups included 101 and 93 children, respectively. Serum ferritin levels were determined with…

  8. Purification and characterization of an iron-induced ferritin from soybean (Glycine max) cell suspensions.

    Science.gov (United States)

    Lescure, A M; Massenet, O; Briat, J F

    1990-11-15

    Ferric citrate induces ferritin synthesis and accumulation in soybean (Glycine max) cell suspension cultures [Proudhon, Briat & Lescure (1989) Plant Physiol. 90, 586-590]. This iron-induced ferritin has been purified from cells grown for 72 h in the presence of either 100 microM- or 500 microM-ferric citrate. It has a molecular mass of about 600 kDa and is built up from a 28 kDa subunit which is recognized by antibodies raised against pea (Pisum sativum) seed ferritin and it has the same N-terminal sequence as this latter, except for residue number 3, which is alanine in pea seed ferritin instead of valine in iron-induced soybean cell ferritin. It contains an average of 1800 atoms of iron per molecule whatever the ferric citrate concentration used to induce its synthesis. It is shown that the presence of 100 microM- or 500 microM-ferric citrate in the culture medium leads respectively to an 11- and 28-fold increase in the total intracellular iron concentration and to a 30- and 60-fold increase in the ferritin concentration. However, the percentage of iron stored in the mineral core of ferritin remains constant whatever the ferric citrate concentration used and represents only 5-6% of cellular iron.

  9. The iron content and ferritin contribution in fresh, dried, and toasted nori, Pyropia yezoensis.

    Science.gov (United States)

    Masuda, Taro; Yamamoto, Ami; Toyohara, Haruhiko

    2015-01-01

    Iron is one of the essential trace elements for humans. In this study, the iron contents in fresh, dried, and toasted nori (Pyropia yezoensis) were analyzed. The mean iron content of fresh, dried, and toasted nori were 19.0, 22.6, and 26.2 mg/100 g (dry weight), respectively. These values were superior to other food of plant origin. Furthermore, most of the iron in nori was maintained during processing, such as washing, drying, and toasting. Then, the form of iron in fresh, dried, and toasted nori was analyzed. As a result, an iron storage protein ferritin contributed to iron storage in raw and dried nori, although the precise rate of its contribution is yet to be determined, while ferritin protein cage was degraded in the toasted nori. It is the first report that verified the ferritin contribution to iron storage in such edible macroalgae with commercial importance.

  10. Kinetic, spectroscopic and chemical modification study of iron release from transferrin; iron(III) complexation to adenosine triphosphate

    International Nuclear Information System (INIS)

    Thompson, C.P.

    1985-01-01

    Amino acids other than those that serve as ligands have been found to influence the chemical properties of transferrin iron. The catalytic ability of pyrophosphate to mediate transferrin iron release to a terminal acceptor is largely quenched by modification non-liganded histine groups on the protein. The first order rate constants of iron release for several partially histidine modified protein samples were measured. A statistical method was employed to establish that one non-liganded histidine per metal binding domain was responsible for the reduction in rate constant. These results imply that the iron mediated chelator, pyrophosphate, binds directly to a histidine residue on the protein during the iron release process. EPR spectroscopic results are consistent with this interpretation. Kinetic and amino acid sequence studies of ovotransferrin and lactoferrin, in addition to human serum transferrin, have allowed the tentative assignment of His-207 in the N-terminal domain and His-535 in the C-terminal domain as the groups responsible for the reduction in rate of iron release. The above concepts have been extended to lysine modified transferrin. Complexation of iron(II) to adenosine triphosphate (ATP) was also studied to gain insight into the nature of iron-ATP species present at physiological pH. 31 P NMR spectra are observed when ATP is presented in large excess

  11. Blood Transfusion, Serum Ferritin, and Iron in Hemodialysis Patients in Africa

    Science.gov (United States)

    Kouegnigan Rerambiah, Leonard; Essola Rerambiah, Laurence; Mbourou Etomba, Armel; Mouguiama, Rose Marlène; Issanga, Phanie Brunelle; Biyoghe, Axel Sydney; Batchilili, Batchelili; Akone Assembe, Sylvestre; Djoba Siawaya, Joel Fleury

    2015-01-01

    Background and Objectives. There is no data analyzing the outcome of blood transfusions and oral iron therapy in patients with kidneys failure in sub-Saharan Africa. The present study aimed to fill that gap and assess the value of ferritin in the diagnosis of iron overload and deficiency. Design. From January to February 2012, we prospectively studied 85 hemodialysis patients (78% of males and 22% of females aged 20 to 79 years) attending the Gabonese National Hemodialysis Centre. Results. Correlation studies showed (a) a strong positive linear relationship between the number of blood transfusions and high serum ferritin in hemodialysis patient (Spearman r : 0.74; P value: 0.0001); (b) a weak association between the number of blood transfusions and serum iron concentrations (Spearman r : 0.32; P value: 0.04); (c) a weak association between serum ferritin and serum iron (Spearman r : 0.32; P value: 0.003). Also, the strength of agreement beyond chance between the levels of ferritin and iron in the serum was poor (κ = 0.14). The prevalence of iron overload was 10.6%, whereas the prevalence of iron deficiency was 2.3%, comparing (1) patients with a maximum of one transfusion not on iron therapy; (2) patients with a maximum of one transfusion on iron therapy; (3) polytransfused patients not on iron therapy; and (4) polytransfused patients on oral iron therapy. The “Kruskal-Wallis test” showed that ferritin levels varied significantly between the groups (P value: 0.0001). Conclusion. Serum ferritin is not reliable as a marker of iron overload. For patients undergoing regular transfusion we recommend routine serum ferritin measurement and yearly measurement of LIC. PMID:25685597

  12. Changes in Serum Ferritin and Other Factors Associated with Iron Metabolism During Chronic Hyperbaric Exposure

    Science.gov (United States)

    1979-03-01

    tech- jects prior to their participation included standard radio- ques , using- radioisotopes ("SFe and S"Tcm-- diphospho- graphic surveys for evidence of... es were apparent by the third dive day for iron and the iv than ABN. It is of interest that no VGE were heard ajt seventh dive day for ferrtin. No...source of the increased amounts of ferritin levels in acute bepatocellular damage from serum ferritin and iron found during these dives ap.- paracetamol

  13. The pupylation machinery is involved in iron homeostasis by targeting the iron storage protein ferritin.

    Science.gov (United States)

    Küberl, Andreas; Polen, Tino; Bott, Michael

    2016-04-26

    The balance of sufficient iron supply and avoidance of iron toxicity by iron homeostasis is a prerequisite for cellular metabolism and growth. Here we provide evidence that, in Actinobacteria, pupylation plays a crucial role in this process. Pupylation is a posttranslational modification in which the prokaryotic ubiquitin-like protein Pup is covalently attached to a lysine residue in target proteins, thus resembling ubiquitination in eukaryotes. Pupylated proteins are recognized and unfolded by a dedicated AAA+ ATPase (Mycobacterium proteasomal AAA+ ATPase; ATPase forming ring-shaped complexes). In Mycobacteria, degradation of pupylated proteins by the proteasome serves as a protection mechanism against several stress conditions. Other bacterial genera capable of pupylation such as Corynebacterium lack a proteasome, and the fate of pupylated proteins is unknown. We discovered that Corynebacterium glutamicum mutants lacking components of the pupylation machinery show a strong growth defect under iron limitation, which was caused by the absence of pupylation and unfolding of the iron storage protein ferritin. Genetic and biochemical data support a model in which the pupylation machinery is responsible for iron release from ferritin independent of degradation.

  14. Secreted glyceraldehye-3-phosphate dehydrogenase is a multifunctional autocrine transferrin receptor for cellular iron acquisition.

    Science.gov (United States)

    Sheokand, Navdeep; Kumar, Santosh; Malhotra, Himanshu; Tillu, Vikas; Raje, Chaaya Iyengar; Raje, Manoj

    2013-06-01

    The long held view is that mammalian cells obtain transferrin (Tf) bound iron utilizing specialized membrane anchored receptors. Here we report that, during increased iron demand, cells secrete the glycolytic enzyme glyceraldehyde-3-phosphate dehydrogenase (GAPDH) which enhances cellular uptake of Tf and iron. These observations could be mimicked by utilizing purified GAPDH injected into mice as well as when supplemented in culture medium of model cell lines and primary cell types that play a key role in iron metabolism. Transferrin and iron delivery was evaluated by biochemical, biophysical and imaging based assays. This mode of iron uptake is a saturable, energy dependent pathway, utilizing raft as well as non-raft domains of the cell membrane and also involves the membrane protein CD87 (uPAR). Tf internalized by this mode is also catabolized. Our research demonstrates that, even in cell types that express the known surface receptor based mechanism for transferrin uptake, more transferrin is delivered by this route which represents a hidden dimension of iron homeostasis. Iron is an essential trace metal for practically all living organisms however its acquisition presents major challenges. The current paradigm is that living organisms have developed well orchestrated and evolved mechanisms involving iron carrier molecules and their specific receptors to regulate its absorption, transport, storage and mobilization. Our research uncovers a hidden and primitive pathway of bulk iron trafficking involving a secreted receptor that is a multifunctional glycolytic enzyme that has implications in pathological conditions such as infectious diseases and cancer. Copyright © 2013 Elsevier B.V. All rights reserved.

  15. Targeted Delivery of Amoxicillin to C. trachomatis by the Transferrin Iron Acquisition Pathway.

    Directory of Open Access Journals (Sweden)

    Jun Hai

    Full Text Available Weak intracellular penetration of antibiotics makes some infections difficult to treat. The Trojan horse strategy for targeted drug delivery is among the interesting routes being explored to overcome this therapeutic difficulty. Chlamydia trachomatis, as an obligate intracellular human pathogen, is responsible for both trachoma and sexually transmitted diseases. Chlamydia develops in a vacuole and is therefore protected by four membranes (plasma membrane, bacterial inclusion membrane, and bacterial membranes. In this work, the iron-transport protein, human serum-transferrin, was used as a Trojan horse for antibiotic delivery into the bacterial vacuole. Amoxicillin was grafted onto transferrin. The transferrin-amoxicillin construct was characterized by mass spectrometry and absorption spectroscopy. Its affinity for transferrin receptor 1, determined by fluorescence emission titration [KaffTf-amox = (1.3 ± 1.0 x 108], is very close to that of transferrin [4.3 x 108]. Transmission electron and confocal microscopies showed a co-localization of transferrin with the bacteria in the vacuole and were also used to evaluate the antibiotic capability of the construct. It is significantly more effective than amoxicillin alone. These promising results demonstrate targeted delivery of amoxicillin to suppress Chlamydia and are of interest for Chlamydiaceae and maybe other intracellular bacteria therapies.

  16. Wheat ferritins: Improving the iron content of the wheat grain

    DEFF Research Database (Denmark)

    Borg, Søren; Brinch-Pedersen, Henrik; Tauris, Birgitte

    2012-01-01

    The characterization of the full complement of wheat ferritins show that the modern hexaploid wheat genome contains two ferritin genes, TaFer1 and TaFer2, each represented by three homeoalleles and placed on chromosome 5 and 4, respectively. The two genes are differentially regulated and expresse...

  17. Variability of ferritin measurements in chronic kidney disease; implications for iron management.

    Science.gov (United States)

    Ford, Bradley A; Coyne, Daniel W; Eby, Charles S; Scott, Mitchell G

    2009-01-01

    Serum ferritin levels are a proxy measure of iron stores; and existing guidelines for managing anemia in hemodialysis patients suggest that serum ferritin concentrations should be maintained at >200 ng/ml. The KDOQI recommendations further state there is insufficient evidence advocating routine intravenous iron when ferritin levels exceed 500 ng/ml. Here we determined the interassay differences and short-term intraindividual variability of serum ferritin measurements in patients on chronic hemodialysis to illustrate how these variances may affect treatment decisions. Intermethod variations of up to 150 ng/ml were found comparing six commonly used ferritin assays that evaluated thirteen pools of serum from hemodialysis and nonhemodialysis patients. The intraindividual variability for ferritin in 60 stable hemodialysis patients ranged between 2-62% measured over an initial two-week period and from 3-52% when factored over a six-week period. Our results suggests that single serum ferritin values should not be used to guide clinical decisions regarding treatment of chronic hemodialysis patients with intravenous iron due to significant analytical and intraindividual variability.

  18. Evaluation and association of serum iron and ferritin levels in children with dental caries.

    Science.gov (United States)

    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.

  19. Soluble transferrin receptor: a differentiating marker between iron deficiency anaemia and anaemia of chronic disorders

    International Nuclear Information System (INIS)

    Saboor, M.; Moinuddin, A.; Naureen, A.

    2012-01-01

    Background: Iron deficiency anaemia and anaemia of chronic disorders are the two major causes of microcytic and hypochromic anaemia. Many times the diagnosis of these conditions becomes difficult through conventional laboratory tests. Determination of soluble transferrin receptors is a helpful laboratory test for the differential diagnosis of these conditions. The study was conducted to evaluate the role of soluble transferrin receptors in the differential diagnosis between iron deficiency anaemia and anaemia of chronic disorders. Methods: A total of 80 blood samples were evaluated, i.e., 20 samples from normal adult male, 20 samples from normal adult female, 20 samples from iron deficiency anaemia group and 20 samples from patients with anaemia of chronic disorders. Soluble transferrin receptors were determined by ELISA technique using Quantikine IVD kit (R and D Systems). Results: There was significant difference in the levels of sTfR in iron deficiency anaemia and anaemia of chronic disorders. Statistically non-significant difference was observed between the levels of sTfR in patients with anaemia of chronic disorders as compared to normal control group. Conclusion: The sTfR determination can be used as a reliable differentiating marker in the diagnosis of iron deficiency anaemia and anaemia of chronic disorders. (author)

  20. Changes in iron levels, total iron binding capacity, transferrin saturation in race horses, before and after of physical exercise

    Directory of Open Access Journals (Sweden)

    Gláucia Abramovitc

    2014-09-01

    Full Text Available ABSTRACT. Abramovitc G., Parra A.C. & Fernandes W.R. [Changes in iron levels, total iron binding capacity, transferrin saturation in race horses, before and after of physical exercise]. Variação de níveis séricos de ferro, da capacidade total de ligação do ferro e da saturação da transferrina em equinos de corrida, antes e após exercício físico. Revista Brasileira de Medicina Veterinária, 36(3:289-293, 2014. Departamento de Clínica Médica, Faculdade de Medicina Veterinária e Zootecnia, Universidade de São Paulo, Rua Prof. Dr. Orlando Marques de Paiva 87, Cidade Universitária, Butantã, São Paulo, SP 05508-270, Brasil. Email: wilsonrf@usp.br The preparation of the horse for physical activities in competition is directly related to important factors such as nutrition, muscle adaptation and blood profile, related to the concentration of serum iron, total capacity total iron binding capacity (TIBC and saturation of transferrin. This study aimed to evaluate the influence of exercise in iron levels, the total iron and transferrin saturation in race horses. One hundred and eleven samples of blood serum were collected from Thoroughbred horses, from the Jockey Club of São Paulo, aged between 3 and 4 years old, male and female, clinically healthy, practitioners turf competition, in sand or grass. The samples were obtained before exercise (control time and 30 minutes after exercise (post exercise. These animals were submitted to gallop training, of high intensity and short duration for this research. As a result, it was observed that the serum concentration of iron (Fe showed a statistically significant lowering post-exercise, due to organic re-balance of iron, while TIBC (total iron binding capacity showed a clear and significant increase in their serum levels due to increased needs of iron during and after exercise. The percentage of transferrin saturation in serum was shown to be lower post-exercise, probably due to the recruitment of

  1. Soluble Transferrin Receptor - A Marker For Iron Deficiency; A Review

    African Journals Online (AJOL)

    Parameters for measuring iron deficiency have been established for decades and have served clinicians in the management of this nutritional disorder. The bone marrow still remains the gold standard in the final diagnosis of iron deficiency. However, researchers have been able to identify the dominating role of the ...

  2. Transferrin Receptor 2 Dependent Alterations of Brain Iron Metabolism Affect Anxiety Circuits in the Mouse

    Science.gov (United States)

    Pellegrino, Rosa Maria; Boda, Enrica; Montarolo, Francesca; Boero, Martina; Mezzanotte, Mariarosa; Saglio, Giuseppe; Buffo, Annalisa; Roetto, Antonella

    2016-01-01

    The Transferrin Receptor 2 (Tfr2) modulates systemic iron metabolism through the regulation of iron regulator Hepcidin (Hepc) and Tfr2 inactivation causes systemic iron overload. Based on data demonstrating Tfr2 expression in brain, we analysed Tfr2-KO mice in order to examine the molecular, histological and behavioural consequences of Tfr2 silencing in this tissue. Tfr2 abrogation caused an accumulation of iron in specific districts in the nervous tissue that was not accompanied by a brain Hepc response. Moreover, Tfr2-KO mice presented a selective overactivation of neurons in the limbic circuit and the emergence of an anxious-like behaviour. Furthermore, microglial cells showed a particular sensitivity to iron perturbation. We conclude that Tfr2 is a key regulator of brain iron homeostasis and propose a role for Tfr2 alpha in the regulation of anxiety circuits. PMID:27477597

  3. Evaluation of the influence of UV/IR radiation on iron release from ferritin

    International Nuclear Information System (INIS)

    Gritzkov, M.; Kochev, V.; Vladimirova, L

    2010-01-01

    In the present work the influence of UV/IR radiation on the iron-releasing process from ferritin is investigated. The ferritins are a family of iron-storing proteins playing a key role in the biochemical reactions between iron and oxygen-processes of exclusive importance for the existence of all living organisms. The iron is stored within the ferritin core in the form of insoluble crystals containing Fe(III). Therefore for its release, the mineral matrix has to be decomposed, usually through a reduction of Fe(III) to Fe(II). Our study considers the action of UV/IR radiation on the structure of the protein molecule. Eventual changes in the ferritin conformation under the irradiation could result in the change of channel forming regions responsible for the iron efflux. This can be assess by the quantity of Fe (II) obtained in a subsequent mobilization procedure evoked by exogenous reducing agents. In our case the content of the reduced iron is determined electrochemically by the method of potentiometric titration. As already was shown, this method promises to become highly useful for quantitative evaluation of released Fe 2+ . (Author)

  4. Determination of Non-Transferrin Bound Iron, Transferrin Bound Iron, Drug Bound Iron and Total Iron in Serum in a Rats after IV Administration of Sodium Ferric Gluconate Complex by Simple Ultrafiltration Inductively Coupled Plasma Mass Spectrometric Detection

    Directory of Open Access Journals (Sweden)

    Murali K. Matta

    2018-02-01

    Full Text Available A rapid, sensitive and specific ultrafiltration inductively-coupled plasma mass spectrometry method was developed and validated for the quantification of non-transferrin bound iron (NTBI, transferrin bound iron (TBI, drug bound iron (DI and total iron (TI in the same rat serum sample after intravenous (IV administration of iron gluconate nanoparticles in sucrose solution (Ferrlecit®. Ultrafiltration with a 30 kDa molecular cut-off filter was used for sample cleanup. Different elution solvents were used to separate each form of iron from sample serum. Isolated fractions were subjected to inductively-coupled mass spectrometric analysis after microwave digestion in 4% nitric acid. The reproducibility of the method was evaluated by precision and accuracy. The calibration curve demonstrated linearity from 5–500 ng/mL with a regression (r2 of more than 0.998. This method was effectively implemented to quantify rat pharmacokinetic study samples after intravenous administration of Ferrlecit®. The method was successfully applied to a pharmacokinetic (PK study of Ferrlecit in rats. The colloidal iron followed first order kinetics with half-life of 2.2 h and reached background or pre-dose levels after 12 h post-dosing. The drug shown a clearance of 0.31 mL/min/kg and volume of distribution of 0.05 L/kg. 19.4 ± 2.4 mL/h/kg.

  5. MRI contrast demonstration of antigen-specific targeting with an iron-based ferritin construct

    Energy Technology Data Exchange (ETDEWEB)

    Walsh, Edward G., E-mail: edward_walsh@brown.edu [Brown University, Department of Neuroscience (United States); Mills, David R. [Rhode Island Hospital/Warren Alpert Medical School of Brown University, Division of Hematology and Oncology, Department of Medicine (United States); Lim, Sierin; Sana, Barindra [Nanyang Technological University, Division of Bioengineering (Singapore); Brilliant, Kate E. [Rhode Island Hospital/Warren Alpert Medical School of Brown University, Division of Hematology and Oncology, Department of Medicine (United States); Park, William K. C. [Rhode Island Hospital, Department of Diagnostic Imaging (United States)

    2013-01-15

    A genetically modified ferritin has been examined for its properties as a tumor-selective magnetic resonance imaging (MRI) contrast agent. The engineered ferritin described herein was derived from Archaeoglobus fulgidus (AfFtn-AA), which stores a significantly greater quantity of iron than wild-type ferritins. Relaxivity measurements were taken at 3 Tesla of ferritin particles uniformly distributed in an agarose gel to assess relaxivities r{sub 1} and r{sub 2}. The r{sub 1} and r{sub 2} values of the uniformly distributed modified ferritin were significantly higher (r{sub 1} = 1,290 mM{sup -1} s{sup -1} and r{sub 2} = 5,740 mM{sup -1} s{sup -1}) than values observed for wild-type ferritin (e.g., horse spleen, r{sub 1} = 0.674 mM{sup -1} s{sup -1}, r{sub 2} = 95.54 mM{sup -1} s{sup -1}). The modified iron-enriched ferritin (14.5 nm diameter) was conjugated with a monoclonal antibody (10 nm length) against rat Necl-5, a cell surface glycoprotein overexpressed by many epithelial cancers. In vitro studies showed strong reactivity of the assembled nanoconjugate to transformed Necl-5 positive rat prostate epithelial cells. Furthermore, MRI demonstrated a significant T{sub 2} contrast with negligible T{sub 1} effect when bound to cells. These findings highlight the utility of the modified ferritin construct as a novel MRI contrast agent that can be manipulated to target antigen-specific tissues.

  6. Control of heme synthesis during Friend cell differentiation: role of iron and transferrin

    International Nuclear Information System (INIS)

    Laskey, J.D.; Ponka, P.; Schulman, H.M.

    1986-01-01

    In many types of cells the synthesis of σ-aminolevulinic acid (ALA) limits the rate of heme formation. However, results from this laboratory with reticulocytes suggest that the rate of iron uptake from 125 I-transferrin (Tf), rather than ALA synthase activity, limits the rate of heme synthesis in erythroid cells. To determine whether changes occur in iron metabolism and the control of heme synthesis during erythroid cell development Friend erythroleukemia cells induced to erythroid differentiation by dimethylsulfoxide (DMSO) were studied. While added ALA stimulated heme synthesis in uninduced Friend cells (suggesting ALA synthase is limiting) it did not do so in induced cells. Therefore the possibility was investigated that, in induced cells, iron uptake from Tf limits and controls heme synthesis. Several aspects of iron metabolism were investigated using the synthetic iron chelator salicylaldehyde isonicotinoyl hydrazone (SIH). Both induced and uninduced Friend cells take up and utilize Fe for heme synthesis directly from Fe-SIH without the involvement of transferrin and transferrin receptors and to a much greater extent than from saturating levels or 59 Fe-Tf (20 μM). Furthermore, in induced Friend cells 100 μM Fe-SIH stimulated 2- 14 C-glycine incorporation into heme up to 3.6-fold as compared to the incorporation observed with saturating concentrations of Fe-Tf. These results indicate that some step(s) in the pathway of iron from extracellular Tf to protoporphyrin, rather than the activity of ALA synthase, limits and controls the overall rate of heme and possibly hemoglobin synthesis in differentiating Friend erythroleukemia cells

  7. Serum-ferritin and iron absorption for the study of body iron stored in the Thai population

    International Nuclear Information System (INIS)

    Plehachinda, R.

    1984-05-01

    Measurements of serum ferritin by an ''in-house'' immunoradiometric assay (IRMA) method were used in conjunction with estimations of gastro-intestinal iron absorption from a standard test dose of ferrous ascorbate, measurements of blood haemoglobin and measurements of other haematological parameters to study body iron status in various population groups and to assess changes in body iron status after food-iron fortification. The IRMA method particularly covered the lower range of serum ferritin levels from 0.5 to 10 μg/litre, corresponding to iron deficiency. Quality control indicated satisfactory assay performance. In preliminary studies, serum ferritin level was found to be well correlated with gastro-intestinal iron absorption as an indicator of body iron status. Normal adult male subjects in Bangkok showed levels of 21-314 μg/litre and normal adult female levels of 13-173 μg/litre, in general agreement with values reported by other authors. Measurements were then extended to subjects in an area of north-eastern Thailand where iron-deficiency was common, to assess the effectiveness of food-iron fortification programmes. Measurements were also made on male blood donors in Bangkok, pregnant female subjects in Bangkok and north-eastern Thailand, school children in an area of southern Thailand where hookworm infestation was common and schoolchildren and adult female subjects in an area of northern Thailand where goitre was endemic. The results of all these studies are presented

  8. New insights into iron deficiency and iron deficiency anemia.

    Science.gov (United States)

    Camaschella, Clara

    2017-07-01

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

  9. Potentiometric assessment of iron release during ferritin reduction by exogenous agents.

    Science.gov (United States)

    Vladimirova, Lilia S; Kochev, Valery K

    2010-09-01

    This work studied the possibilities for quantitative determination of iron mobilization in connection with ferritin reduction by ascorbic acid (vitamin C) and sodium dithionite in vitro. The iron storage protein was incubated with an excess of reductant in aerobic conditions in the absence of complexing agents in the medium. The release of Fe(2+) was let to go to completion, and the overall content of Fe(2+) in the solution was evaluated with the aid of potentiometric titration using Ce(4+) as an oxidizing titrant. Results suggest a moderate iron efflux under the influence of the chosen reducing agents. Although such a reduction of the protein mineral core by dihydroxyfumarate contributes greatly to the iron mobilization, ferritin behavior with vitamin C and dithionite seems to be different. Although redox properties of dihydroxyfumarate are determined by hydroxyl groups similar to those of ascorbic acid, the two compounds differ significantly in structure, and this could be the basis for an explanation of the specificities in their interaction with ferritin. As revealed by the study, potentiometric titration promises to be a reliable tool for evaluation of the amount of Fe(2+) present in the solution as a result of the reduction of the ferritin's mineral core. 2010 Elsevier Inc. All rights reserved.

  10. Ferritin-iron increases killing of Chinese hamster ovary cells by X-irradiation

    International Nuclear Information System (INIS)

    Nelson, J.M.; Stevens, R.G.

    1992-01-01

    Stationary-phase Chinese hamster ovary cells were cultured in medium containing ferritin (∼19% iron by weight) added at concentrations ranging from 0 to 128 μg/ml. One set of cultures was unirradiated, another set exposed to 4.0 Gy of X-ray. Clonogenic cell survival was assessed in each set of cultures. In the absence of added ferritin, 4.0 Gy killed approximately 50% of the cells. In the absence of radiation, ferritin was not toxic at less than 48 μg/ml; above 48 μg/ml, toxicity increased with concentration. Apoferritin was not toxic at any concentration tested (up to 1000 μg/ml). Although 32 μg/ml ferritin, reflecting only a 3-6 fold increase in iron concentration over normal serum, was not toxic, it reduced survival of X-irradiated cells by an additional 75%. These results indicate that a sublethal concentration of ferritin can be a potent radiosensitizer. (Author)

  11. Studies on the 2-site immunoradiometric assay of serum ferritin and its applications for diagnosis of iron deficiency

    Energy Technology Data Exchange (ETDEWEB)

    Koseki, J.; Niitsu, Y. (Sapporo Medical Coll. (Japan). Cancer Research Inst.)

    1980-10-01

    The 2-site immunoradiometric assay using paper discs as a solid phase material was established for the measurement of serum ferritin. The standard curve was found the range from 0.5ng -- 500ng ferritin per ml and the sensitivity limit of the assay was 0.1ng ferritin per ml. The clinical value of serum ferritin assay was then investigated for diagnosis of iron deficiency. The mean serum ferritin concentrations of normal subjects were greater for males (119.8+-55.5ng/ml) than for females (56.5+-55.5ng/ml) although this sex difference was not distinct beyond the age of 45. All 15 patients with iron deficient anemia had serum ferritin concentrations below the normal range, whereas in other anemias including anemia associated with chronic inflammation, pernicious anemia, aplastic anemia, serum ferritin concentrations were normal or elevated. In 116 apparently normal subjects, 13.8% of total females had abnormally low serum ferritin concentrations with normal hemoglobin levels. The cytochrome c oxidase activity of peripheral leucocytes from those subjects were generally depleted. Most of them frequently suffered from easy fatigability, weakness, and dizziness and these complications were clearly relieved by the administration of iron. Measurement of serum ferritin was found to be quite useful for diagnosis and assessment of iron deficient states.

  12. Studies on the 2-site immunoradiometric assay of serum ferritin and its applications for diagnosis of iron deficiency

    International Nuclear Information System (INIS)

    Koseki, Junichi; Niitsu, Yoshiro

    1980-01-01

    The 2-site immunoradiometric assay using paper discs as a solid phase material was established for the measurement of serum ferritin. The standard curve was found the range from 0.5ng -- 500ng ferritin per ml and the sensitivity limit of the assay was 0.1ng ferritin per ml. The clinical value of serum ferritin assay was then investigated for diagnosis of iron deficiency. The mean serum ferritin concentrations of normal subjects were greater for males (119.8+-55.5ng/ml) than for females (56.5+-55.5ng/ml) although this sex difference was not distinct beyond the age of 45. All 15 patients with iron deficient anemia had serum ferritin concentrations below the normal range, whereas in other anemias including anemia associated with chronic inflammation, pernicious anemia, aplastic anemia, serum ferritin concentrations were normal oe elevated. In 116 apparently normal subjects, 13.8% of total females had abnormally low serum ferritin concentrations with normal hemoglobin levels. The cytochrome c oxidase activity of peripheral leucocytes from those subjects were generally depleted. Most of them frequently suffered from easy fatiguability, weakness, and dizziness and these complications were clearly relieved by the administration of iron. Measurement of serum ferritin was found to be quite useful for diagnosis and assessment of iron deficient states. (author)

  13. Neurodegeneration with inflammation is accompanied by accumulation of iron and ferritin in microglia and neurons.

    Science.gov (United States)

    Thomsen, Maj Schneider; Andersen, Michelle Vandborg; Christoffersen, Pia Rægaard; Jensen, Malene Duedal; Lichota, Jacek; Moos, Torben

    2015-09-01

    Chronic inflammation in the substantia nigra (SN) accompanies conditions with progressive neurodegeneration. This inflammatory process contributes to gradual iron deposition that may catalyze formation of free-radical mediated damage, hence exacerbating the neurodegeneration. This study examined proteins related to iron-storage (ferritin) and iron-export (ferroportin) (aka metal transporter protein 1, MTP1) in a model of neurodegeneration. Ibotenic acid injected stereotactically into the striatum leads to loss of GABAergic neurons projecting to SN pars reticulata (SNpr), which subsequently leads to excitotoxicity in the SNpr as neurons here become vulnerable to their additional glutamatergic projections from the subthalamic nucleus. This imbalance between glutamate and GABA eventually led to progressive shrinkage of the SNpr and neuronal loss. Neuronal cell death was accompanied by chronic inflammation as revealed by the presence of cells expressing ED1 and CD11b in the SNpr and the adjacent white matter mainly denoted by the crus cerebri. The SNpr also exhibited changes in iron metabolism seen as a marked accumulation of inflammatory cells containing ferric iron and ferritin with morphology corresponding to macrophages and microglia. Ferritin was detected in neurons of the lesioned SNpr in contrast to the non-injected side. Compared to non-injected rats, surviving neurons of the SNpr expressed ferroportin at unchanged level. Analyses of dissected SNpr using RT-qPCR showed a rise in ferritin-H and -L transcripts with increasing age but no change was observed in the lesioned side compared to the non-lesioned side, indicating that the increased expression of ferritin in the lesioned side occurred at the post-transcriptional level. Hepcidin transcripts were higher in the lesioned side in contrast to ferroportin mRNA that remained unaltered. The continuous entry of iron-containing inflammatory cells into the degenerating SNpr and their subsequent demise is probably

  14. Two kinds of ferritin protect ixodid ticks from iron overload and consequent oxidative stress.

    Directory of Open Access Journals (Sweden)

    Remil Linggatong Galay

    Full Text Available Ticks are obligate hematophagous parasites that have successfully developed counteractive means against their hosts' immune and hemostatic mechanisms, but their ability to cope with potentially toxic molecules in the blood remains unclear. Iron is important in various physiological processes but can be toxic to living cells when in excess. We previously reported that the hard tick Haemaphysalis longicornis has an intracellular (HlFER1 and a secretory (HlFER2 ferritin, and both are crucial in successful blood feeding and reproduction. Ferritin gene silencing by RNA interference caused reduced feeding capacity, low body weight and high mortality after blood meal, decreased fecundity and morphological abnormalities in the midgut cells. Similar findings were also previously reported after silencing of ferritin genes in another hard tick, Ixodes ricinus. Here we demonstrated the role of ferritin in protecting the hard ticks from oxidative stress. Evaluation of oxidative stress in Hlfer-silenced ticks was performed after blood feeding or injection of ferric ammonium citrate (FAC through detection of the lipid peroxidation product, malondialdehyde (MDA and protein oxidation product, protein carbonyl. FAC injection in Hlfer-silenced ticks resulted in high mortality. Higher levels of MDA and protein carbonyl were detected in Hlfer-silenced ticks compared to Luciferase-injected (control ticks both after blood feeding and FAC injection. Ferric iron accumulation demonstrated by increased staining on native HlFER was observed from 72 h after iron injection in both the whole tick and the midgut. Furthermore, weak iron staining was observed after Hlfer knockdown. Taken together, these results show that tick ferritins are crucial antioxidant molecules that protect the hard tick from iron-mediated oxidative stress during blood feeding.

  15. Iron and ferritin accumulate in separate cellular locations in Phaseolus seeds

    DEFF Research Database (Denmark)

    Cvitanich, Cristina; Przybylowicz, Wojciech J; Urbanski, Dorian Fabian

    2010-01-01

    and will assist in the production of staples with increased bioavailable iron. Results Here we reveal the distribution of iron in seeds of three Phaseolus species including thirteen genotypes of P. vulgaris, P. coccineus, and P. lunatus. We showed that high concentrations of iron accumulate in cells surrounding...... the provascular tissue of P. vulgaris and P. coccineus seeds. Using the Perls' Prussian blue method, we were able to detect iron in the cytoplasm of epidermal cells, cells near the epidermis, and cells surrounding the provascular tissue. In contrast, the protein ferritin that has been suggested as the major iron...... to P. vulgaris and P. coccineus, we did not observe iron accumulation in the cells surrounding the provascular tissues of P. lunatus cotyledons. A novel iron-rich genotype, NUA35, with a high concentration of iron both in the seed coat and cotyledons was bred from a cross between an Andean...

  16. Evidence for low molecular weight, non-transferrin-bound iron in rat brain and cerebrospinal fluid

    DEFF Research Database (Denmark)

    Moos, Torben; Morgan, Evan H.

    1998-01-01

    Neuroscience, blood-brain barrier, choroid plexus, interstitial fluid, transferrin receptor, uptake......Neuroscience, blood-brain barrier, choroid plexus, interstitial fluid, transferrin receptor, uptake...

  17. Iron- and ferritin-dependent reactive oxygen species distribution: impact on Arabidopsis root system architecture.

    Science.gov (United States)

    Reyt, Guilhem; Boudouf, Soukaina; Boucherez, Jossia; Gaymard, Frédéric; Briat, Jean-Francois

    2015-03-01

    Iron (Fe) homeostasis is integrated with the production of reactive oxygen species (ROS), and distribution at the root tip participates in the control of root growth. Excess Fe increases ferritin abundance, enabling the storage of Fe, which contributes to protection of plants against Fe-induced oxidative stress. AtFer1 and AtFer3 are the two ferritin genes expressed in the meristematic zone, pericycle and endodermis of the Arabidopsis thaliana root, and it is in these regions that we observe Fe stained dots. This staining disappears in the triple fer1-3-4 ferritin mutant. Fe excess decreases primary root length in the same way in wild-type and in fer1-3-4 mutant. In contrast, the Fe-mediated decrease of lateral root (LR) length and density is enhanced in fer1-3-4 plants due to a defect in LR emergence. We observe that this interaction between excess Fe, ferritin, and root system architecture (RSA) is in part mediated by the H2O2/O2·- balance between the root cell proliferation and differentiation zones regulated by the UPB1 transcription factor. Meristem size is also decreased in response to Fe excess in ferritin mutant plants, implicating cell cycle arrest mediated by the ROS-activated SMR5/SMR7 cyclin-dependent kinase inhibitors pathway in the interaction between Fe and RSA. Copyright © 2015 The Author. Published by Elsevier Inc. All rights reserved.

  18. Body iron is a contributor to oxidative damage of DNA

    DEFF Research Database (Denmark)

    Tuomainen, Tomi-Pekka; Loft, Steffen; Nyyssönen, Kristiina

    2007-01-01

    The transition metal iron is catalytically highly active in vitro, and not surprisingly, body iron has been suggested to promote oxidative stress in vivo. In the current analysis we studied the association of serum ferritin concentration and serum soluble transferrin receptor concentration.......17 (95% CI 0.08-0.26, P = 0.001), and serum soluble transferrin receptor to ferritin concentration ratio (TfR/ferritin) predicted the excretion rate at B = - 0.13 (95% CI - 0.21 to - 0.05, P = 0.002). Our data suggest that body iron contributes to excess oxidative stress already at non-iron overload...

  19. Studies on the mechanism of pyrophosphate-mediated uptake of iron from transferrin by isolated rat-liver mitochondria

    International Nuclear Information System (INIS)

    Konopka, K.; Romslo, I.; Bergen Univ.

    1981-01-01

    1. Respiring rat liver mitochondria accumulate iron released from transferrin by pyrophosphate. The amount of iron accumulated is 1-1.5 nmol mg protein -1 h -1 , or approximately 60% of the amount of iron mobilized from transferrin. 2. The uptake declines if respiration is inhibited, substrate is depleted, or the experiments are run under anaerobic conditions. Substrate, depletion and respiratory inhibitors are less inhibitory under anaerobic conditions. 3. More than 80% of the amount of iron accumulated by aerobic, actively respiring mitochondria can be chelated by bathophenanthroline sulphonate, and with deuteroporphyrin included, up to 30% of the amount of iron accumulated is recovered as deuteroheme. Iron accumulated by respiration-inhibited mitochondria under aerobic conditions is not available for heme synthesis. 4. With time the uptake of iron increases eightfold relative to the uptake of pyrophosphate. 5. The results are compatible with a model in which ferric iron is mobilized from transferrin by pyrophosphate, ferric iron pyrophosphate is bound to the mitochondria, iron is reduced, dissociates from pyrophosphate and is taken up by the mitochondria. Ferrous irons thus formed is available for heme synthesis. (orig.) [de

  20. Serum ferritin

    International Nuclear Information System (INIS)

    Rochna Viola, E.M.; Diaz de Domingo, N.B.; Lazarowski, A.

    1981-01-01

    Serum ferritin (SF) concentration as determined by the immunoradiometric method allows the direct measurement of a fraction of the body ferritin pool. In normal subjects, SF is an excellent index of body iron stores. In certain conditions associated with increased ferritin synthesis (such as liver disease, inflammation, malignancy, chronic disorders, ineffective erythropoiesis, or during ferrotherapy), SF may not accurately reflect body iron stores. In hyposideremic anemias SF concentration permits to differentiate those due to iron deficiency from those due to chronic disorders. With a good assay quality, subnormal SF levels are incontrovertible in the diagnosis of iron deficiency. SF determination has been investigated as possible tumor marker. When performed in combination with the alpha-fetoprotein assay, SF enhances the specificity of serodiagnosis of hepatoma. SF results must be interpreted bearing in mind the possible participation of circumstances that i) modify the body iron stores and ii) lead to increased ferritin synthesis. (author) [es

  1. Non-transferrin-bound iron (NTBI uptake by T lymphocytes: evidence for the selective acquisition of oligomeric ferric citrate species.

    Directory of Open Access Journals (Sweden)

    Joao Arezes

    Full Text Available Iron is an essential nutrient in several biological processes such as oxygen transport, DNA replication and erythropoiesis. Plasma iron normally circulates bound to transferrin. In iron overload disorders, however, iron concentrations exceed transferrin binding capacity and iron appears complexed with low molecular weight molecules, known as non-transferrin-bound iron (NTBI. NTBI is responsible for the toxicity associated with iron-overload pathologies but the mechanisms leading to NTBI uptake are not fully understood. Here we show for the first time that T lymphocytes are able to take up and accumulate NTBI in a manner that resembles that of hepatocytes. Moreover, we show that both hepatocytes and T lymphocytes take up the oligomeric Fe3Cit3 preferentially to other iron-citrate species, suggesting the existence of a selective NTBI carrier. These results provide a tool for the identification of the still elusive ferric-citrate cellular carrier and may also open a new pathway towards the design of more efficient iron chelators for the treatment of iron overload disorders.

  2. Rate of Iron Transfer Through the Horse Spleen Ferritin Shell Determined by the Rate of Formation of Prussian Blue and Fe-desferrioxamine Within the Ferritin Cavity

    Science.gov (United States)

    Zhang, Bo; Watt, Richard K.; Galvez, Natividad; Dominquez-Vera, Jose M.; Watt, Gerald D.

    2005-01-01

    Iron (2+ and 3+) is believed to transfer through the three-fold channels in the ferritin shell during iron deposition and release in animal ferritins. However, the rate of iron transit in and out through these channels has not been reported. The recent synthesis of [Fe(CN)(sub 6)](3-), Prussian Blue (PB) and desferrioxamine (DES) all trapped within the horse spleen ferritin (HoSF) interior makes these measurements feasible. We report the rate of Fe(2+) penetrating into the ferritin interior by adding external Fe(2+) to [Fe(CN)(sub 6)](3-) encapsulated in the HoSF interior and measuring the rate of formation of the resulting encapsulated PB. The rate at which Fe(2+) reacts with [Fe(CN)(sub 6)](3-) in the HoSF interior is much slower than the formation of free PB in solution and is proceeded by a lag period. We assume this lag period and the difference in rate represent the transfer of Fe(2+) through the HoSF protein shell. The calculated diffusion coefficient, D approx. 5.8 x 10(exp -20) square meters per second corresponds to the measured lag time of 10-20 s before PB forms within the HoSF interior. The activation energy for Fe(2+) transfer from the outside solution through the protein shell was determined to be 52.9 kJ/mol by conducting the reactions at 10 to approximately 40 C. The reaction of Fe(3+) with encapsulated [Fe(CN)6](4-) also readily forms PB in the HoSF interior, but the rate is faster than the corresponding Fe(2+) reaction. The rate for Fe(3+) transfer through the ferritin shell was confirmed by measuring the rate of the formation of Fe-DES inside HoSF and an activation energy of 58.4 kJ/mol was determined. An attempt was made to determine the rate of iron (2+ and 3+) transit out from the ferritin interior by adding excess bipyridine or DES to PB trapped within the HoSF interior. However, the reactions are slow and occur at almost identical rates for free and HoSF-encapsulated PB, indicating that the transfer of iron from the interior through the

  3. The distribution of iron between the metal-binding sites of transferrin human serum.

    Science.gov (United States)

    Williams, J; Moreton, K

    1980-02-01

    The Makey & Seal [(1976) Biochim. Biophys. Acta 453, 250--256] method of polyacrylamide-gel electrophoresis in buffer containing 6 M-urea was used to determine the distribution of iron between the N-terminal and C-terminal iron-binding sites of transferrin in human serum. In fresh serum the two sites are unequally occupied; there is preferential occupation of the N-terminal site. On incubation of the serum at 37 degrees C the preference of iron for the N-terminal site becomes more marked. On storage of serum at -15 degrees C the iron distribution changes so that there is a marked preference for the C-terminal site. Dialysis of serum against buffer at pH 7.4 also causes iron to be bound much more strongly by the C-terminal than by the N-terminal site. The original preference for the N-terminal site can be resroted to the dialysed serum by addition of the diffusible fraction.

  4. Iron Deposition and Ferritin Heavy Chain (Fth Localization in Rodent Teeth

    Directory of Open Access Journals (Sweden)

    Wen Xin

    2013-01-01

    Full Text Available Abstract Background An iron rich layer on the labial surface is characteristic of the enamel of rodent incisors. In order to address a role for iron content in continuously growing incisors during odontogenesis, we studied iron deposition patterns in enamel and dentine using Perls’ blue staining and ferritin heavy chain (Fth immunolocalization. Fth expression is regulated by iron level; therefore its localization can be used as a sensitive indicator for iron deposition. Results Sagittal sections of 4-week old rat incisors showed a gradual increase in iron level in the enamel organ from secretory to maturation stages. In addition, iron was detected in ameloblasts of erupting third molars of 4-week old rats, suggesting iron plays a role in both incisor and molar development. In odontoblasts, the presence of iron was demonstrated, and this is consistent with iron’s role in collagen synthesis. Using postnatal 3-, 6-, 9-day old mice, the spatial and temporal expression of Fth in tooth development again indicated the presence of iron in mature ameloblasts and odontoblasts. Conclusions While these data do not explain what functional role iron has in tooth formation, it does highlight a significant molecular activity associated with the formation of the rodent dentition.

  5. Iron environment in ferritin with large amounts of phosphate, from Azotobacter vinelandii and horse spleen, analyzed using Extended X-ray Absorption fine Structure (EXAFS)

    International Nuclear Information System (INIS)

    Rohrer, J.S.; Islam, Q.T.; Sayes, D.E.; Theil, E.C.; Watt, G.D.

    1990-01-01

    The iron core of proteins in the ferritin family displays structural variations that includes phosphate content was well as the number and the degree of ordering of the iron atoms. Earlier studies had shown that ferritin iron cores naturally high in phosphate, e.g., Azotobacter vinelandii (AV) ferritin had decreased long-range order. Here, the influence of phosphate on the local structure around iron in ferritin cores is reported, comparing the EXAFS of AV ferritin, reconstituted ferritin and native horse spleen ferritin. In contrast, when the phosphate content was high in AV ferritin and horse spleen ferritin reconstituted with phosphate, the average iron atom had five to six phosphorus neighbors at 3.17 angstrom. Moreover, the number of detectable iron neighbors was lower when phosphate was high or present during reconstitution and the interatomic distance was longer indicating that some phosphate bridges neighboring iron atoms. However, the decrease in the number of detectable iron-iron neighbors compared to HSF and the higher number of Fe-P interactions relative to Fe-Fe interactions suggest that some phosphate ligands were chain termini, or blocked crystal growth, and/or introduced defects which contributed both to the long-range disorder and to altered redox properties previously observed in AV ferritin

  6. Iron and ferritin dependent ROS distribution impact Arabidopsis root system architecture.

    Science.gov (United States)

    Reyt, Guilhem; Boudouf, Soukaina; Boucherez, Jossia; Gaymard, Frédéric; Briat, Jean-Franois

    2014-11-09

    Iron (Fe) homeostasis is integrated with the production of Reactive Oxygen Species (ROS) whose distribution at the root tip participates in the control of root growth. Excess Fe increases ferritin abundance, enabling the storage of Fe which contributes to protection of plants against Fe-induced oxidative stress. AtFer1 and AtFer3 are the two ferritin genes expressed in the meristematic zone, pericycle and endodermis of the Arabidopsis thaliana (Arabidopsis) root, and it is in these regions that we observe Fe stained dots. This staining disappears in the triple fer1-3-4 ferritin mutant. Fe excess decreases primary root length in the same way in wild-type and in fer1-3-4 mutant. In contrast, the Fe mediated decrease of lateral root (LR) length and density is enhanced in fer1-3-4 plants due to a defect in LR emergence. We observe that this interaction between excess Fe, ferritin and RSA is in part mediated by the H 2 O 2 /O 2 .- balance between the root cell proliferation and differentiation zones regulated by the UPB1 transcription factor. Further, meristem size is also decreased in response to Fe excess in ferritin mutant plants, implicating cell cycle arrest mediated by the ROS-activated SMR5/SMR7 cyclin-dependent kinase inhibitors pathway in the interaction between Fe and RSA. © The Author 2014. Published by the Molecular Plant Shanghai Editorial Office in association with Oxford University Press on behalf of CSPB and IPPE, SIBS, CAS.

  7. Iron-Restricted Diet Affects Brain Ferritin Levels, Dopamine Metabolism and Cellular Prion Protein in a Region-Specific Manner

    Directory of Open Access Journals (Sweden)

    Jessica M. V. Pino

    2017-05-01

    Full Text Available Iron is an essential micronutrient for several physiological functions, including the regulation of dopaminergic neurotransmission. On the other hand, both iron, and dopamine can affect the folding and aggregation of proteins related with neurodegenerative diseases, such as cellular prion protein (PrPC and α-synuclein, suggesting that deregulation of iron homeostasis and the consequential disturbance of dopamine metabolism can be a risk factor for conformational diseases. These proteins, in turn, are known to participate in the regulation of iron and dopamine metabolism. In this study, we evaluated the effects of dietary iron restriction on brain ferritin levels, dopamine metabolism, and the expression levels of PrPC and α-synuclein. To achieve this goal, C57BL/6 mice were fed with iron restricted diet (IR or with normal diet (CTL for 1 month. IR reduced iron and ferritin levels in liver. Ferritin reduction was also observed in the hippocampus. However, in the striatum of IR group, ferritin level was increased, suggesting that under iron-deficient condition, each brain area might acquire distinct capacity to store iron. Increased lipid peroxidation was observed only in hippocampus of IR group, where ferritin level was reduced. IR also generated discrete results regarding dopamine metabolism of distinct brain regions: in striatum, the level of dopamine metabolites (DOPAC and HVA was reduced; in prefrontal cortex, only HVA was increased along with the enhanced MAO-A activity; in hippocampus, no alterations were observed. PrPC levels were increased only in the striatum of IR group, where ferritin level was also increased. PrPC is known to play roles in iron uptake. Thus, the increase of PrPC in striatum of IR group might be related to the increased ferritin level. α-synuclein was not altered in any regions. Abnormal accumulation of ferritin, increased MAO-A activity or lipid peroxidation are molecular features observed in several neurological

  8. Enhanced iron and zinc accumulation in genetically engineered pineapple plants using soybean ferritin gene.

    Science.gov (United States)

    Mhatre, Minal; Srinivas, Lingam; Ganapathi, Thumballi R

    2011-12-01

    Pineapple (Ananas comosus L. Merr., cv. "Queen") leaf bases were transformed with Agrobacterium tumefaciens strain EHA 105 harboring the pSF and pEFESF plasmids with soybean ferritin cDNA. Four to eight percent of the co-cultivated leaf bases produced multiple shoots 6 weeks after transfer to Murashige and Skoog's medium supplemented with α-naphthalene acetic acid 1.8 mg/l, indole-3-butyric acid 2.0 mg/l, kinetin 2.0 mg/l, cefotaxime 400 mg/l, and kanamycin 50 mg/l. Putatively transformed shoots (1-2 cm) were selected and multiplied on medium of the same composition and elongated shoots (5 cm) were rooted on liquid rooting medium supplemented with cefotaxime 400 mg/l and kanamycin 100 mg/l. The rooted plants were analyzed through PCR, genomic Southern analysis, and reverse transcription PCR. The results clearly confirmed the integration and expression of soybean ferritin gene in the transformed plants. Atomic absorption spectroscopic analysis carried out with six independently transformed lines of pSF and pEFE-SF revealed a maximum of 5.03-fold increase in iron and 2.44-fold increase in zinc accumulation in the leaves of pSF-transformed plants. In pEFE-SF-transformed plants, a 3.65-fold increase in iron and 2.05-fold increase in zinc levels was observed. Few of the transgenic plants were hardened in the greenhouse and are being grown to maturity to determine the enhanced iron and zinc accumulation in the fruits. To the best of our knowledge this is the first report on the transformation of pineapple with soybean ferritin for enhanced accumulation of iron and zinc content in the transgenic plants.

  9. First comparative characterization of three distinct ferritin subunits from a teleost: Evidence for immune-responsive mRNA expression and iron depriving activity of seahorse (Hippocampus abdominalis) ferritins.

    Science.gov (United States)

    Oh, Minyoung; Umasuthan, Navaneethaiyer; Elvitigala, Don Anushka Sandaruwan; Wan, Qiang; Jo, Eunyoung; Ko, Jiyeon; Noh, Gyeong Eon; Shin, Sangok; Rho, Sum; Lee, Jehee

    2016-02-01

    Ferritins play an indispensable role in iron homeostasis through their iron-withholding function in living beings. In the current study, cDNA sequences of three distinct ferritin subunits, including a ferritin H, a ferritin M, and a ferritin L, were identified from big belly seahorse, Hippocampus abdominalis, and molecularly characterized. Complete coding sequences (CDS) of seahorse ferritin H (HaFerH), ferritin M (HaFerM), and ferritin L (HaFerL) subunits were comprised of 531, 528, and 522 base pairs (bp), respectively, which encode polypeptides of 177, 176, and 174 amino acids, respectively, with molecular masses of ∼20-21 kDa. Our in silico analyses demonstrate that these three ferritin subunits exhibit the typical characteristics of ferritin superfamily members including iron regulatory elements, domain signatures, and reactive centers. The coding sequences of HaFerH, M, and L were cloned and the corresponding proteins were overexpressed in a bacterial system. Recombinantly expressed HaFer proteins demonstrated detectable in vivo iron sequestrating (ferroxidase) activity, consistent with their putative iron binding capability. Quantification of the basal expression of these three HaFer sequences in selected tissues demonstrated a gene-specific ubiquitous spatial distribution pattern, with abundance of mRNA in HaFerM in the liver and predominant expression of HaFerH and HaFerL in blood. Interestingly, the basal expression of all three ferritin genes was found to be significantly modulated against pathogenic stress mounted by lipopolysaccharides (LPS), poly I:C, Streptococcus iniae, and Edwardsiella tarda. Collectively, our findings suggest that the three HaFer subunits may be involved in iron (II) homeostasis in big belly seahorse and that they are important in its host defense mechanisms. Copyright © 2016 Elsevier Ltd. All rights reserved.

  10. Low serum transferrin correlates with acute-on-chronic organ failure and indicates short-term mortality in decompensated cirrhosis.

    Science.gov (United States)

    Bruns, Tony; Nuraldeen, Renwar; Mai, Martina; Stengel, Sven; Zimmermann, Henning W; Yagmur, Eray; Trautwein, Christian; Stallmach, Andreas; Strnad, Pavel

    2017-02-01

    Iron represents an essential, but potentially harmful micronutrient, whose regulation has been associated with poor outcome in liver disease. Its homeostasis is tightly linked to oxidative stress, bacterial infections and systemic inflammation. To study the prognostic short-term significance of iron parameters in a cohort study of patients with decompensation of cirrhosis at risk of acute-on-chronic liver failure (ACLF). Ferritin, transferrin, iron, transferrin saturation (TSAT) and hepcidin were determined in sera from 292 German patients hospitalized for decompensation of cirrhosis with ascites, of which 78 (27%) had ACLF. Short-term mortality was prospectively assessed 30 and 90 days after inclusion. Transferrin concentrations were significantly lower, whereas ferritin and TSAT were higher in patients with ACLF compared to patients without ACLF (P≤.006). Transferrin, TSAT and ferritin differentially correlated with the severity of organ failure, active alcoholism and surrogates of systemic inflammation and macrophage activation. As compared with survivors, 30-day non-survivors displayed lower serum transferrin (P=.0003) and higher TSAT (P=.003), whereas 90-day non-survivors presented with higher ferritin (P=.03) and lower transferrin (P=.02). Lower transferrin (continuous or dichotomized at 87 mg/dL) and consecutively higher TSAT (continuous or dichotomized >41%) indicated increased mortality within 30 days and remained significant after adjustment for organ failure and inflammation in multivariate regression models and across subgroups of patients. Among the investigated indicators of iron metabolism, serum transferrin concentration was the best indicator of organ failure and an independent predictor of short-term mortality at 30 days. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  11. Iron stores in 70-year-old Danish men and women. Evaluation in 469 individuals by serum ferritin and hemoglobin

    DEFF Research Database (Denmark)

    Milman, N; Schultz-Larsen, K

    1994-01-01

    Iron status, including serum (S-) ferritin and hemoglobin (Hb) was assessed in a population survey of 469 old subjects (70 years of age; 254 men, 215 women); 7.9% of the participants had abnormal laboratory tests indicating diseases which might be connected with inappropriately high S-ferritin le......Iron status, including serum (S-) ferritin and hemoglobin (Hb) was assessed in a population survey of 469 old subjects (70 years of age; 254 men, 215 women); 7.9% of the participants had abnormal laboratory tests indicating diseases which might be connected with inappropriately high S......-ferritin levels. Men had a median S-ferritin of 114 micrograms/L, 5-95 percentile 28-373 micrograms/L; 2.4% had values depleted iron stores), 3.5% values from 15-30 micrograms/L (i.e., small iron stores), and 94.1% values > 30 micrograms/L (e.g., replete iron stores); 74.4% had values...

  12. Targeting higher ferritin concentrations with intravenous iron dextran lowers erythropoietin requirement in hemodialysis patients.

    Science.gov (United States)

    DeVita, M V; Frumkin, D; Mittal, S; Kamran, A; Fishbane, S; Michelis, M F

    2003-11-01

    Although clinical use of recombinant human erythropoietin (rHuEPO) since 1989 has improved anemia in most end-stage renal disease patients, there are still many hemodialysis patients unable to maintain an adequate hematocrit (HCT) without large doses of rHuEPO. This suggests that anemia is not solely a consequence of rHuEPO deficiency, but may be due to other factors including functional iron deficiency. Since the optimal prescription for iron replacement is not yet known, we evaluated the effect of intravenous iron dextran (IVFe) infusion on serum ferritin (SFer) concentration and rHuEPO dose. Our objective was to raise and maintain serum ferritin concentrations to 2 different levels above the National Kidney Foundation Dialysis Outcome Quality Initiative standard of 100 ng/ml to determine whether, and by what degree rHuEPO dose could be lowered. HD patients on i.v. rHuEPO with a SFer concentration > or = 70 ng/ml and an HCT of requirements.

  13. Analysis of iron storage proteins in chicken liver and spleen tissues in comparison with human liver ferritin by Moessbauer spectroscopy

    International Nuclear Information System (INIS)

    Oshtrakh, M.I.; Milder, O.B.; Semionkin, V.A.; Malakheeva, L.I.; Prokopenko, P.G.

    2006-01-01

    Characterization of iron storage proteins in liver and spleen from normal chicken and chicken with lymphoid leukemia in comparison with human liver ferritin were considered by Moessbauer spectroscopy (preliminary results). Small differences in Moessbauer hyperfine parameters for both normal and lymphoid leukemia chicken liver and spleen were observed. The value of quadrupole splitting for human liver ferritin was higher than those for chicken tissues. A decrease of iron content in lymphoid leukemia chicken tissues was also found, however, the reason of this fact (pathology or feeding) was not clear yet. (author)

  14. Antioxidant capacity of parsley cells (Petroselinum crispum L.) in relation to iron-induced ferritin levels and static magnetic field.

    Science.gov (United States)

    Rajabbeigi, Elham; Ghanati, Faezeh; Abdolmaleki, Parviz; Payez, Atefeh

    2013-12-01

    This study was aimed to evaluate antioxidant response of parsley cells to 21 ppm iron and static magnetic field (SMF; 30 mT). The activity of catalase (CAT) and ascorbate peroxidase (APX) and the contents of malonyldialdehyde, iron and ferritin were measured at 6 and 12 h after treatments. Exposure to SMF increased the activity of CAT in treated cells, while combination of iron and SMF treatments as well as iron supply alone decreased CAT activity, compared to that of control cells. Combination of SMF with iron treatment reduced iron content of the cells and ameliorated mal effect of iron on CAT activity. All treatments reduced APX activity; however, the content of total ascorbate increased in response to iron and SMF+iron. The results showed that among the components of antioxidant system of parsley cells, enhanced activity of CAT in SMF-treated cells and increase of ascorbate in SMF+Fe-treated ones were responsible for the maintenance of membranes integrity. Ferritin contents of SMF- and SMF+Fe-treated cells also decreased significantly 12 h after treatments, compared to those of the control cells. These results cast doubt on the proposed functions of ferritin as a putative reactive oxygen species detoxifying molecule.

  15. The physiological significance of transferrin microheterogeneity : an interpretation of the role of N-linked glycans in transferrin and iron metabolism /

    NARCIS (Netherlands)

    G. de Jong (Gerardus)

    1993-01-01

    textabstractThe starting point for this thesis was the observation that when attempts are made to separate monoferric transferrins from diferric transferrin by isoelectric focusing, in addition to what was thought to represent the pure monoferric transferrins, a great number of additional bands

  16. Can soluble transferrin receptor be used in diagnosing iron deficiency anemia and assessing iron response in infants with moderate acute malnutrition?

    Science.gov (United States)

    Büyükkaragöz, Bahar; Akgun, Necat A; Bulus, Ayse D; Durmus Aydogdu, Sultan; Bal, Cengiz

    2017-04-01

    To evaluate the efficacy of soluble transferrin receptor (sTfR) in diagnosing iron deficiency anemia (IDA) and evaluating iron response in infants with moderate acute malnutrition (MAM). Infants with hemoglobin (Hb) levels lower than threshold values for anemia for their ages and hypochromic/ microcytic anemia on peripheral smear were recruited. MAM was defined as weight/height z score iron parameters and sTfR were compared among 41 infants with MAM and anemia (MA group), 32 infants with anemia without MAM (group A), and healthy controls (n= 30). Following anemia and malnutrition treatment, tests were repeated. Besides hematological indices compatible with IDA, serum iron (Fe) and transferrin saturation (TS) were significantly lower, while transferrin was significantly higher in MA and A groups compared to controls (p 0.05) and significantly higher than controls (p iron treatment, sTfR decreased in both MA and A groups (p iron treatment, we believe that this parameter was not influenced by MAM or inflammation; and it alone can be used to detect IDA and monitor treatment response in infants with MAM.

  17. Study of the rhizobacterium Azospirillum brasilense Sp245 using Mössbauer spectroscopy with a high velocity resolution: Implication for the analysis of ferritin-like iron cores

    Science.gov (United States)

    Alenkina, I. V.; Oshtrakh, M. I.; Tugarova, A. V.; Biró, B.; Semionkin, V. A.; Kamnev, A. A.

    2014-09-01

    The results of a comparative study of two samples of the rhizobacterium Azospirillum brasilense (strain Sp245) prepared in different conditions and of human liver ferritin using Mössbauer spectroscopy with a high velocity resolution demonstrated the presence of ferritin-like iron (i.e. iron similar to that found in ferritin-like proteins) in the bacterium. Mössbauer spectra of these samples were fitted in two ways: as a rough approximation using a one quadrupole doublet fit (the homogeneous iron core model) and using a superposition of quadrupole doublets (the heterogeneous iron core model). Both results demonstrated differences in the Mössbauer parameters for mammalian ferritin and for bacterial ferritin-like iron. Moreover, some differences in the Mössbauer parameters were observed between the two samples of A. brasilense Sp245 related to the differences in their preparation conditions.

  18. Dopamine mediated iron release from ferritin is enhanced at higher temperatures: Possible implications for fever-induced Parkinson's disease

    International Nuclear Information System (INIS)

    Babincova, Melania; Babinec, Peter

    2005-01-01

    A new molecular mechanism is proposed to explain the pathogenesis of fever-induced Parkinson's disease. This proposal is based on dopamine and 6-hydroxydopamine-mediated free iron release from ferritin magnetic nanoparticles, which is enhanced at higher temperatures, and which may lead to substantial peroxidation and injury of lipid biomembranes of the substantia nigra in the brain

  19. A facile drug delivery system preparation through the interaction between drug and iron ion of transferrin

    International Nuclear Information System (INIS)

    Zhou, Lin; Liu, Jihua; Wei, Shaohua; Ge, Xuefeng; Zhou, Jiahong; Yu, Boyang; Shen, Jian

    2013-01-01

    Many anticancer drugs have the capability to form stable complex with metal ions. Based on such property, a simple method to combine these drugs with transferrin, through the interaction between drug and Fe ion of transferrin, to improve their anticancer activity, is proposed. To demonstrate this technique, the complex of photosensitive anticancer drug hypocrellin A and transferrin was prepared by such facile method. The results indicated that the complex of hypocrellin A and transferrin can stabilize in aqueous solution. In vitro studies have demonstrated the superior cancer cell uptake ability of hypocrellin A–transferrin complex to the free hypocrellin A. Significant damage to such drug-impregnated tumor cells was observed upon irradiation and the cancer cells killing ability of hypocrellin A–transferrin was stronger than the free hypocrellin A within a certain range of concentrations. The above results demonstrated the validity and potential of our proposed strategy to prepare the drug delivery system of this type of anti-cancer drugs and transferrin

  20. A facile drug delivery system preparation through the interaction between drug and iron ion of transferrin

    Energy Technology Data Exchange (ETDEWEB)

    Zhou, Lin [Nanjing Normal University, Jiangsu Key Laboratory Biofunctional Materials, Key Laboratory of Applied Photochemistry, Analysis and Testing Center, College of Chemistry and Materials Science (China); Liu, Jihua [China Pharmaceutical University, Department of Complex Prescription of TCM (China); Wei, Shaohua; Ge, Xuefeng; Zhou, Jiahong, E-mail: zhoujiahong@njnu.edu.cn [Nanjing Normal University, Jiangsu Key Laboratory Biofunctional Materials, Key Laboratory of Applied Photochemistry, Analysis and Testing Center, College of Chemistry and Materials Science (China); Yu, Boyang, E-mail: boyangyu59@163.com [China Pharmaceutical University, Department of Complex Prescription of TCM (China); Shen, Jian [Nanjing Normal University, Jiangsu Key Laboratory Biofunctional Materials, Key Laboratory of Applied Photochemistry, Analysis and Testing Center, College of Chemistry and Materials Science (China)

    2013-09-15

    Many anticancer drugs have the capability to form stable complex with metal ions. Based on such property, a simple method to combine these drugs with transferrin, through the interaction between drug and Fe ion of transferrin, to improve their anticancer activity, is proposed. To demonstrate this technique, the complex of photosensitive anticancer drug hypocrellin A and transferrin was prepared by such facile method. The results indicated that the complex of hypocrellin A and transferrin can stabilize in aqueous solution. In vitro studies have demonstrated the superior cancer cell uptake ability of hypocrellin A-transferrin complex to the free hypocrellin A. Significant damage to such drug-impregnated tumor cells was observed upon irradiation and the cancer cells killing ability of hypocrellin A-transferrin was stronger than the free hypocrellin A within a certain range of concentrations. The above results demonstrated the validity and potential of our proposed strategy to prepare the drug delivery system of this type of anti-cancer drugs and transferrin.

  1. Immunocytochemical analysis of the subcellular distribution of ferritin in Imperata cylindrica (L.) Raeuschel, an iron hyperaccumulator plant.

    Science.gov (United States)

    de la Fuente, Vicenta; Rodríguez, Nuria; Amils, Ricardo

    2012-05-01

    Ferritin is of interest at the structural and functional level not only as storage for iron, a critical element, but also as a means to prevent cell damage produced by oxidative stress. The main objective of this work was to confirm by immunocytochemistry the presence and the subcellular distribution of the ferritin detected by Mösbauer spectroscopy in Imperata cylindrica, a plant which accumulates large amounts of iron. The localization of ferritin was performed in epidermal, parenchymal and vascular tissues of shoots and leaves of I. cylindrica. The highest density of immunolabeling in shoots appeared in the intracellular space of cell tissues, near the cell walls and in the cytoplasm. In leaves, ferritin was detected in the proximity of the dense network of the middle lamella of cell walls, following a similar path to that observed in shoots. Immunolabeling was also localized in chloroplasts. The abundance of immunogold labelling in mitochondria for I. cylindrica was rather low, probably because the study dealt with tissues from old plants. These results further expand the localization of ferritin in cell components other than chloroplasts and mitochondria in plants. Copyright © 2011 Elsevier GmbH. All rights reserved.

  2. Four variants in transferrin and HFE genes as potential markers of iron deficiency anaemia risk: an association study in menstruating women

    Directory of Open Access Journals (Sweden)

    Arroyo-Pardo Eduardo

    2011-10-01

    Full Text Available Abstract Background Iron deficiency anaemia is a worldwide health problem in which environmental, physiologic and genetic factors play important roles. The associations between iron status biomarkers and single nucleotide polymorphisms (SNPs known to be related to iron metabolism were studied in menstruating women. Methods A group of 270 Caucasian menstruating women, a population group at risk of iron deficiency anaemia, participated in the study. Haematological and biochemical parameters were analysed and 10 selected SNPs were genotyped by minisequencing assay. The associations between genetic and biochemical data were analysed by Bayesian Model Averaging (BMA test and decision trees. Dietary intake of a representative subgroup of these volunteers (n = 141 was assessed, and the relationship between nutrients and iron biomarkers was also determined by linear regression. Results Four variants, two in the transferrin gene (rs3811647, rs1799852 and two in the HFE gene (C282Y, H63D, explain 35% of the genetic variation or heritability of serum transferrin in menstruating women. The minor allele of rs3811647 was associated with higher serum transferrin levels and lower transferrin saturation, while the minor alleles of rs1799852 and the C282Y and H63D mutations of HFE were associated with lower serum transferrin levels. No association between nutrient intake and iron biomarkers was found. Conclusions In contrast to dietary intake, these four SNPs are strongly associated with serum transferrin. Carriers of the minor allele of rs3811647 present a reduction in iron transport to tissues, which might indicate higher iron deficiency anaemia risk, although the simultaneous presence of the minor allele of rs1799852 and HFE mutations appear to have compensatory effects. Therefore, it is suggested that these genetic variants might potentially be used as markers of iron deficiency anaemia risk.

  3. Body iron is a contributor to oxidative damage of DNA

    DEFF Research Database (Denmark)

    Tuomainen, T.P.; Loft, Steffen Huitfeldt; Nyyssonen, K.

    2007-01-01

    The transition metal iron is catalytically highly active in vitro, and not surprisingly, body iron has been suggested to promote oxidative stress in vivo. In the current analysis we studied the association of serum ferritin concentration and serum soluble transferrin receptor concentration...... with daily urinary 8-hydroxydeoxyguanosine excretion, a marker of oxidative stress, in 48 mildly dyslipidemic men in East Finland. In multivariate linear regression analyses allowing for age, smoking, body mass index and physical exercise, serum ferritin concentration predicted the excretion rate at B = 0.......17 (95% CI 0.08-0.26, P = 0.001), and serum soluble transferrin receptor to ferritin concentration ratio (TfR/ferritin) predicted the excretion rate at B = - 0.13 (95% CI - 0.21 to - 0.05, P = 0.002). Our data suggest that body iron contributes to excess oxidative stress already at non-iron overload...

  4. Iron, Anemia, and Iron Deficiency Anemia among Young Children in the United States

    OpenAIRE

    Gupta, Priya M.; Perrine, Cria G.; Mei, Zuguo; Scanlon, Kelley S.

    2016-01-01

    Iron deficiency and anemia are associated with impaired neurocognitive development and immune function in young children. Total body iron, calculated from serum ferritin and soluble transferrin receptor concentrations, and hemoglobin allow for monitoring of the iron and anemia status of children in the United States. The purpose of this analysis is to describe the prevalence of iron deficiency (ID), anemia, and iron deficiency anemia (IDA) among children 1–5 years using data from the 2007–201...

  5. Iron Deficiency Anemia in Adult Onset Still's Disease with a Serum Ferritin of 26,387 μg/L

    Directory of Open Access Journals (Sweden)

    Sheetal Patel

    2011-01-01

    Full Text Available Serum ferritin rises in the anemia of chronic inflammation reflecting increased iron storage and other changes mediated by inflammation. When iron deficiency coexists, the ferritin may not always decline into the subnormal range. We describe the rare interaction of iron deficiency with the extreme hyperferritinemia characteristic of adult onset Still's disease. The combination has clinical relevance and allows deductions about the presence of serum ferritin at 26,387 μg/L despite obvious iron depletion. The diagnosis of iron deficiency anemia was delayed and became fully obvious when her Still's disease remitted and serum ferritin decreased to 6.5 μg/L. The coexistence of iron deficiency should be considered when evaluating a patient with anemia of chronic inflammation even when the ferritin level is elevated several hundredfold. Further insights on ferritin metabolism in Still's disease are suggested by the likelihood that the patient's massive hyperferritinemia in the acute phase of Still's disease was almost entirely of the iron-free apoferritin form.

  6. Comparison of colorimetry and electrothermal atomic absorption spectroscopy for the quantification of non-transferrin bound iron in human sera.

    Science.gov (United States)

    Jittangprasert, Piyada; Wilairat, Prapin; Pootrakul, Pensri

    2004-12-01

    This paper describes a comparison of two analytical techniques, one employing bathophenanthrolinedisulfonate (BPT), a most commonly-used reagent for Fe (II) determination, as chromogen and an electrothermal atomic absorption spectroscopy (ETAAS) for the quantification of non-transferrin bound iron (NTBI) in sera from thalassemic patients. Nitrilotriacetic acid (NTA) was employed as the ligand for binding iron from low molecular weight iron complexes present in the serum but without removing iron from the transferrin protein. After ultrafiltration the Fe (III)-NTA complex was then quantified by both methods. Kinetic study of the rate of the Fe (II)-BPT complex formation for various excess amounts of NTA ligand was also carried out. The kinetic data show that a minimum time duration (> 60 minutes) is necessary for complete complex formation when large excess of NTA is used. Calibration curves given by colorimetric and ETAAS methods were linear over the range of 0.15-20 microM iron (III). The colorimetric and ETAAS methods exhibited detection limit (3sigma) of 0.13 and 0.14 microM, respectively. The NTBI concentrations from 55 thalassemic serum samples measured employing BPT as chromogen were statistically compared with the results determined by ETAAS. No significant disagreement at 95% confidence level was observed. It is, therefore, possible to select any one of these two techniques for determination of NTBI in serum samples of thalassemic patients. However, the colorimetric procedure requires a longer analysis time because of a slow rate of exchange of NTA ligand with BPT, leading to the slow rate of formation of the colored complex.

  7. Iron regulation of hepcidin despite attenuated Smad1,5,8 signaling in mice without transferrin receptor 2 or Hfe

    Science.gov (United States)

    Corradini, Elena; Rozier, Molly; Meynard, Delphine; Odhiambo, Adam; Lin, Herbert Y.; Feng, Qi; Migas, Mary C.; Britton, Robert S.; Babitt, Jodie L.; Fleming, Robert E.

    2011-01-01

    Background & Aims HFE and transferrin receptor 2 (TFR2) are each necessary for the normal relationship between body iron status and liver hepcidin expression. In murine Hfe and Tfr2 knockout models of hereditary hemochromatosis (HH), signal transduction to hepcidin via the bone morphogenetic protein 6 (Bmp6)/Smad1,5,8 pathway is attenuated. We examined the effect of dietary iron on regulation of hepcidin expression via the Bmp6/Smad1,5,8 pathway using mice with targeted disruption of Tfr2, Hfe, or both genes. Methods Hepatic iron concentrations and mRNA expression of Bmp6 and hepcidin were compared with wild-type mice in each of the HH models on standard or iron-loading diets. Liver phospho-Smad (P-Smad)1,5,8 and Id1 mRNA levels were measured as markers of Bmp/Smad signaling. Results While Bmp6 expression was increased, liver hepcidin and Id1 expression were decreased in each of the HH models compared with wild-type mice. Each of the HH models also demonstrated attenuated P-Smad1,5,8 levels relative to liver iron status. Mice with combined Hfe/Tfr2 disruption were most affected. Dietary iron loading increased hepcidin and Id1 expression in each of the HH models. Compared with wild-type mice, HH mice demonstrated attenuated (Hfe knockout) or no increases in P-Smad1,5,8 levels in response to dietary iron loading. Conclusions These observations demonstrate that Tfr2 and Hfe are each required for normal signaling of iron status to hepcidin via Bmp6/Smad1,5,8 pathway. Mice with combined loss of Hfe and Tfr2 up-regulate hepcidin in response to dietary iron loading without increases in liver BMP6 mRNA or steady-state P-Smad1,5,8 levels. PMID:21745449

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

    Science.gov (United States)

    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.

  9. Crystallization and preliminary X-ray diffraction analysis of iron regulatory protein 1 in complex with ferritin IRE RNA

    International Nuclear Information System (INIS)

    Selezneva, Anna I.; Cavigiolio, Giorgio; Theil, Elizabeth C.; Walden, William E.; Volz, Karl

    2006-01-01

    The iron regulatory protein IRP1 has been crystallized in a complex with ferritin IRE RNA and a complete data set has been collected to 2.8 Å resolution. Iron regulatory protein 1 (IRP1) is a bifunctional protein with activity as an RNA-binding protein or as a cytoplasmic aconitase. Interconversion of IRP1 between these mutually exclusive states is central to cellular iron regulation and is accomplished through iron-responsive assembly and disassembly of a [4Fe–4S] cluster. When in its apo form, IRP1 binds to iron responsive elements (IREs) found in mRNAs encoding proteins of iron storage and transport and either prevents translation or degradation of the bound mRNA. Excess cellular iron stimulates the assembly of a [4Fe–4S] cluster in IRP1, inhibiting its IRE-binding ability and converting it to an aconitase. The three-dimensional structure of IRP1 in its different active forms will provide details of the interconversion process and clarify the selective recognition of mRNA, Fe–S sites and catalytic activity. To this end, the apo form of IRP1 bound to a ferritin IRE was crystallized. Crystals belong to the monoclinic space group P2 1 , with unit-cell parameters a = 109.6, b = 80.9, c = 142.9 Å, β = 92.0°. Native data sets have been collected from several crystals with resolution extending to 2.8 Å and the structure has been solved by molecular replacement

  10. Iron nutrition in Indian women at different ages

    International Nuclear Information System (INIS)

    MacPhail, A.P.; Bothwell, T.H.; Torrance, J.D.; Derman, D.P.; Bezwoda, W.R.; Charlton, R.W.; Mayet, F.G.H.

    1981-01-01

    The iron status of 320 Indian women living in Chatsworth, Durban, who had volunteered for iron absorption studies, was assessed using a number of measurements. These included radio-iron absorption, the transferrin saturation, the serum ferritin concentration and the haemoglobin concentration. In the sample as a whole, the prevalence of iron deficiency anaemia (haemoglobin concentration smaller than 12 g/dl, with two or more abnormal measurements of iron status) was 14,4%. A further 26% had depleted iron stores (serum ferritin smaller than 12μg/l) and 8,4% also had evidence of iron-deficient erythropoiesis (serum ferritin smaller than 12μg/l and transferrin saturation below 16%). A profile of iron status based on the cumulative frequency distribution of iron stores showed that the sample with calculated median iron stores of 150 mg and lower and upper 10 percentiles of -355 mg and 655 mg respectively, was significantly more iron deficient than a sample of women studied in Washington State, USA. Of interest was the observation that all measurements of iron status were better in the older age groups, presumably as a result of the cessation of menstruation. In addition, there was evidence that the duration of menstruation, as volunteered in a brief history, had a significant effect on several measurements of iron status. This was particularly true of the serum ferritin concentration and radio-iron absorption, both of which reflect the size of the iron stores

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

    Science.gov (United States)

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

    2017-01-01

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

  12. Serum iron parameters in liver cirrhosis

    Science.gov (United States)

    Siregar, G. A.; Maail, W.

    2018-03-01

    The liver plays a fundamental role in iron homeostasis. Iron parameters change, especially ferritin, need to be evaluated in patients with liver cirrhosis. Serum ferritin could predict the prognosis of patients with decompensated cirrhosis since it reflects immunemediated and infectious stimuli. Ferritin could express the severity of liver disease and possible subsequent complications. Finally, it might reflect an iron overload condition resulting in significant morbidity and early mortality. 70 patients with decompensated liver cirrhosis divided into three Child-Pugh subgroups. Serum iron parameters include serum iron (SI), total iron binding capacity (TIBC) and ferritin was measured in these groups. From these 70 patients, 30 (42.9%) with HbsAg positive, 26 (37.1%) with anti-HCV positive and 14 (20%) with both HbsAg and anti-HCV positive. Of the 70 patients, 14 (20%) had CTP Class A cirrhosis, 17 (24.3%) had CTP Class B cirrhosis, and 39 (55.7%) had CTP C cirrhosis. The median (range) value of serum iron was 36 (10-345) μg/dl, TIBC was 160 (59-520) μg/dl, Ferritin was 253.5 (8-6078) ng/ml and the transferrin saturation was 22.9 (3.65-216.98) %.We found a significant difference in serum ferritin level with CTP score. Ferritin levels increased as Child-Pugh class progressed (p<0.001).

  13. [Iron status with particular consideration of soluble transferrin receptors in children and youth with gastritis, with or without Helicobacter pylori infection].

    Science.gov (United States)

    Mierzwa, Grazyna; Augustyńska, Beata; Czerwionka-Szaflarska, Mieczysława; Tyrakowski, Tomasz

    2006-09-01

    Role of Helicobacter pylori infection in chronic gastritis and gastric and/or duodenal ulcers is well known. Simultaneously there are some articles in literature considering H. pylori as a cause of extra-gastrointestinal illnesses such as atopic dermatitis, chronic urticaria or acne rosacea, hypotrophy, Schoenlein-Henoch disease, atherosclerosis or hypochromic anaemia. The aim of the study. was to asses iron status in aspect of plasmatic transferrin receptors concentration among children and youth with chronic gastritis with or without Helicobacter pylori infection. Forty one patients were included as a study group. Range of age was 9-18 years. All patients were diagnosed due to chronic abdominal pains. There were 13 males and 28 females. Blood was collected from every patient for blood cell count, iron, transferrin and transferrin receptors concentration (sTfR) assessment before endoscopy of upper gastrointestinal tract. Concentration of sTfR was higher than age norm among 29 (71%) of patients. Among patients with higher level of sTfR 20 (69%) had normal haemoglobin concentration and in this group 10 patients had H. pylori infection. During analysis of 12 patients with nornal level of sTfR normal haemoglobin concentration was found and among five of them H. pylori infection was stated. Among 21 patients without H. pylori infection 14 had normal level of sTfR and 7 had higher level of sTfR which means that 33% had hidden iron deficiency (involuntary of normal Hb concentrations). Among 15 of 20 patients with H. pylori infection level of sTfR was higher which means that 75% patients with infection had hidden iron deficiency (involuntary of normal Hb concentrations). Level of plasmatic transferrin receptors can be good and sensitive indicator of iron deficiency and can be helpful in differential diagnosis of hypochromic anaemia and anaemia caused by chronic illness including chronic gastritis with Helicobacter pylori infection.

  14. Comparative study of the iron cores in human liver ferritin, its pharmaceutical models and ferritin in chicken liver and spleen tissues using Moessbauer spectroscopy with a high velocity resolution

    Energy Technology Data Exchange (ETDEWEB)

    Alenkina, I.V.; Semionkin, V.A. [Faculty of Physical Techniques and Devices for Quality Control, Ural Federal University, Ekaterinburg (Russian Federation); Faculty of Experimental Physics, Ural Federal University, Ekaterinburg (Russian Federation); Oshtrakh, M.I. [Faculty of Physical Techniques and Devices for Quality Control, Ural Federal University, Ekaterinburg (Russian Federation); Klepova, Yu.V.; Sadovnikov, N.V. [Faculty of Physiology and Biotechnology, Ural State Agricultural Academy, Ekaterinburg, (Russian Federation); Dubiel, S.M. [Faculty of Physics and Applied Computer Science, AGH University of Science and Technology, Krakow (Poland)

    2011-07-01

    Full text: Application of the Moessbauer spectroscopy with a high velocity resolution (4096 channels) for a study of iron-containing biological species is of great interest. Improving the velocity resolution allows to reveal small variations in the electronic structure of iron, and to obtain hyperfine parameters with smaller instrumental (systematic) errors in comparison with measurements performed in 512 channels or less. It also allows a more reliable fitting of complex Moessbauer spectra. In the present study the Moessbauer spectroscopy with the high velocity resolution was used for a comparative analysis of ferritin and its pharmaceutically important models as well as iron storage proteins in a chicken liver and a spleen. The ferritin, an iron storage protein, consists of a nanosized polynuclear iron core formed by a ferrihydrite surrounded by a protein shell. Iron-polysaccharide complexes contain {beta}-FeOOH iron cores coated with various polysaccharides. The Moessbauer spectra of the ferritin and commercial products Imferon, MaltoferR and Ferrum Lek as well as those of the chicken liver and spleen tissues were measured with the high velocity resolution at 295 and 90 K. They were fitted using two models: (1) with a homogeneous iron core (an approximation using one quadrupole doublet), and (2) with a heterogeneous iron core (an approximation using several quadrupole doublets). The model (1) can be used as the first approximation fit to visualize small variations in the hyperfine parameters. Using this model, differences in the Moessbauer hyperfine parameters were obtained in both 295 and 90 K Moessbauer spectra. However, this model was considered as a rough approximation because the measured Moessbauer spectra had non-Lorentzian line shapes. Therefore, the spectra of the ferritin, Imferon, MaltoferR and Ferrum Lek as well as those of the liver and spleen tissues were fitted again using the model (2) in which a different number of the quadrupole doublets was

  15. The structural basis of transferrin sequestration by transferrin-binding protein B

    Energy Technology Data Exchange (ETDEWEB)

    Calmettes, Charles; Alcantara, Joenel; Yu, Rong-Hua; Schryvers, Anthony B.; Moraes, Trevor F. (Toronto); (Calgary)

    2012-03-28

    Neisseria meningitidis, the causative agent of bacterial meningitis, acquires the essential element iron from the host glycoprotein transferrin during infection through a surface transferrin receptor system composed of proteins TbpA and TbpB. Here we present the crystal structures of TbpB from N. meningitidis in its apo form and in complex with human transferrin. The structure reveals how TbpB sequesters and initiates iron release from human transferrin.

  16. Iron and zinc complexation in wild-type and ferritin-expressing wheat grain: implications for mineral transport into developing grain

    DEFF Research Database (Denmark)

    Neal, Andrew L; Geraki, Kalotina; Borg, Søren

    2013-01-01

    of modified complexation of both metals in transgenic grain overexpressing wheat ferritin. For zinc, there is a consistent doubling of the number of complexing phosphorus atoms. Although there is some EXAFS evidence for iron phytate in ferritin-expressing grain, there is also evidence of a structure lacking......We have used synchrotron-based X-ray fluorescence and absorption techniques to establish both metal distribution and complexation in mature wheat grains. In planta, extended X-ray absorption fine structure (EXAFS) spectroscopy reveals iron phytate and zinc phytate structures in aleurone cells...... of ferritin-expressing grains is quite different from that in wild-type grain. This may explain why the raised levels of minerals transported to the developing grain accumulate within the crease region of the transgenic grain....

  17. Vitreous Humor Changes Expression of Iron-Handling Proteins in Lens Epithelial Cells

    Science.gov (United States)

    Goralska, Malgorzata; Fleisher, Lloyd N.; McGahan, M. Christine

    2017-01-01

    Purpose In humans, vitrectomy is associated with development of nuclear cataracts. Iron catalyzes free radical formation causing oxidative damage, which is implicated in cataract formation. This study was designed to determine if vitreous humor, which can initiate differentiation of lens epithelial cells, would have an effect on iron-handling proteins. Methods Cultured canine lens epithelial cells were treated with collected canine vitreous humor. Lysates of treated and control cells were separated by SDS-PAGE. Ferritin H- and L-chains, transferrin receptor 1, and aquaporin 0 were immunodetected and quantitated with specific antibodies. Morphologic changes in treated cells were assessed. Results Treatment of lens epithelial cells with a 33% (vol/vol) solution of vitreous humor changed the morphology of lens cells and induced expression of aquaporin 0, a marker of fiber cell differentiation that was undetectable in control cells. Treatment did not modify the size of iron-handling proteins but significantly increased content of ferritin from 2.9- to 8.8-fold over control and decreased levels of transferrin receptor by 37% to 59%. Conclusions Vitreous humor may significantly limit iron uptake by transferrin/transferrin receptor pathway, and by increasing ferritin levels could profoundly increase the iron-storage capacity of ferritin in lens cells. Vitreous humor may play a significant protective role against iron-catalyzed oxidative damage of lens epithelial cells and therefore in the formation of cataracts. PMID:28245299

  18. Iron overload in very low birth weight infants: Serum Ferritin and adverse outcomes

    LENUS (Irish Health Repository)

    Barrett, M

    2011-11-01

    Adequate iron isessential for growth and haematpoiesis. Oral iron supplementation is the standard of care in VLBW infants. Post mortem evidence has confirmed significant iron overload. Excessive free iron has been associated with free radical formation and brain injury in term infants.

  19. Molecular characterization of the iron binding protein ferritin in Eisenia andrei earthworms

    Czech Academy of Sciences Publication Activity Database

    Procházková, Petra; Dvořák, Jiří; Šilerová, Marcela; Roubalová, Radka; Škanta, František; Halada, Petr; Bilej, Martin

    2011-01-01

    Roč. 485, č. 2 (2011), s. 73-80 ISSN 0378-1119 R&D Projects: GA ČR GA206/07/0378; GA ČR GD310/08/H077; GA AV ČR IAA600200704; GA MŠk 2B06155; GA MŠk LC07017 Institutional research plan: CEZ:AV0Z50200510 Keywords : Earthworms * Invertebrates * Ferritin Subject RIV: EC - Immunology Impact factor: 2.341, year: 2011

  20. Evidence for ferritin as dominant iron-bearing species in the rhizobacterium Azospirillum brasilense Sp7 provided by low-temperature/in-field Mössbauer spectroscopy.

    Science.gov (United States)

    Kovács, Krisztina; Kamnev, Alexander A; Pechoušek, Jiří; Tugarova, Anna V; Kuzmann, Ernő; Machala, Libor; Zbořil, Radek; Homonnay, Zoltán; Lázár, Károly

    2016-02-01

    For the ubiquitous diazotrophic rhizobacterium Azospirillum brasilense, which has been attracting the attention of researchers worldwide for the last 35 years owing to its significant agrobiotechnological and phytostimulating potential, the data on iron acquisition and its chemical speciation in cells are scarce. In this work, for the first time for azospirilla, low-temperature (at 80 K, 5 K, as well as at 2 K without and with an external magnetic field of 5 T) transmission Mössbauer spectroscopic studies were performed for lyophilised biomass of A. brasilense (wild-type strain Sp7 grown with (57)Fe(III) nitrilotriacetate complex as the sole source of iron) to enable quantitative chemical speciation analysis of the intracellular iron. In the Mössbauer spectrum at 80 K, a broadened quadrupole doublet of high-spin iron(III) was observed with a few percent of a high-spin iron(II) contribution. In the spectrum measured at 5 K, a dominant magnetically split component appeared with the parameters typical of ferritin species from other bacteria, together with a quadrupole doublet of a superparamagnetic iron(III) component and a similarly small contribution from the high-spin iron(II) component. The Mössbauer spectra recorded at 2 K (with or without a 5 T external field) confirmed the assignment of ferritin species. About 20% of total Fe in the dry cells of A. brasilense strain Sp7 were present in iron(III) forms superparamagnetic at both 5 and 2 K, i.e. either different from ferritin cores or as ferritin components with very small particle sizes.

  1. Increased iron sequestration in alveolar macrophages in chronic obstructive pulmonary disease.

    Directory of Open Access Journals (Sweden)

    Quentin Philippot

    Full Text Available Free iron in lung can cause the generation of reactive oxygen species, an important factor in chronic obstructive pulmonary disease (COPD pathogenesis. Iron accumulation has been implicated in oxidative stress in other diseases, such as Alzheimer's and Parkinson's diseases, but little is known about iron accumulation in COPD. We sought to determine if iron content and the expression of iron transport and/or storage genes in lung differ between controls and COPD subjects, and whether changes in these correlate with airway obstruction. Explanted lung tissue was obtained from transplant donors, GOLD 2-3 COPD subjects, and GOLD 4 lung transplant recipients, and bronchoalveolar lavage (BAL cells were obtained from non-smokers, healthy smokers, and GOLD 1-3 COPD subjects. Iron-positive cells were quantified histologically, and the expression of iron uptake (transferrin and transferrin receptor, storage (ferritin and export (ferroportin genes was examined by real-time RT-PCR assay. Percentage of iron-positive cells and expression levels of iron metabolism genes were examined for correlations with airflow limitation indices (forced expiratory volume in the first second (FEV1 and the ratio between FEV1 and forced vital capacity (FEV1/FVC. The alveolar macrophage was identified as the predominant iron-positive cell type in lung tissues. Furthermore, the quantity of iron deposit and the percentage of iron positive macrophages were increased with COPD and emphysema severity. The mRNA expression of iron uptake and storage genes transferrin and ferritin were significantly increased in GOLD 4 COPD lungs compared to donors (6.9 and 3.22 fold increase, respectively. In BAL cells, the mRNA expression of transferrin, transferrin receptor and ferritin correlated with airway obstruction. These results support activation of an iron sequestration mechanism by alveolar macrophages in COPD, which we postulate is a protective mechanism against iron induced oxidative

  2. Ferrokinetic Parameters and Regulation of Iron Metabolism in Patients with Chronic Inflammatory Bowel Diseases

    Directory of Open Access Journals (Sweden)

    T.Y. Boiko

    2014-11-01

    Full Text Available Article presents parameters of iron metabolism and cytokines (IL-6 and TNF-α in patients with chronic inflammatory bowel diseases (CIBD. The material for the study was the blood of 69 patients with CIBD and anemia and 26 — without anemia. We have studied the features of main ferrokinetic parameters — iron, total iron-binding capacity of serum, transferrin saturation, ferritin, transferrin receptor, erythropoietin, hepcidin depending on hemoglobin level and the type of anemia. The relationship of iron metabolism disorders with the level of proinflammatory cytokines (IL-6 and TNF-α is shown.

  3. Anemia and Iron Deficiency in Children With Potential Celiac Disease.

    Science.gov (United States)

    Repo, Marleena; Lindfors, Katri; Mäki, Markku; Huhtala, Heini; Laurila, Kaija; Lähdeaho, Marja-Leena; Saavalainen, Päivi; Kaukinen, Katri; Kurppa, Kalle

    2017-01-01

    Active screening for celiac disease frequently detects seropositive children with normal villous morphology (potential celiac disease). It remains unclear whether these subjects should be treated. We here investigated the prevalence of anemia and iron deficiency in children with potential and mucosal atrophy celiac disease. The prospective study involved 19 children with potential disease, 67 with partial or subtotal villous atrophy (P/SVA), and 16 with total villous atrophy (TVA). Twenty-three healthy children comprised the control group. The groups were compared for various clinical, histological, and laboratory parameters and hepcidin. The prevalence of abnormal parameters was as follows (controls, potential celiac disease, P/SVA, and TVA, respectively): anemia 0%, 15%, 22%, and 63%; low iron 5%, 0%, 14%, and 50%; increased transferrin receptor 1 5%, 16%, 20%, and 47%; low ferritin 0%, 21%, 35%, and 87%; and low transferrin saturation 10%, 11%, 41%, and 71%. One subject had low folate and none had low vitamin B12. The median values for hemoglobin, total iron, ferritin, and transferrin saturation were significantly lower and transferrin receptor 1 values higher in TVA group compared with other groups. After a median of 7 months on a gluten-free diet hemoglobin, total iron, ferritin, and albumin in children with P/SVA exceeded the baseline values in the potential celiac disease group. The development of anemia and iron deficiency in celiac disease is a continuum and may already be present in children with normal villous morphology, advocating an early diagnosis and possible dietary treatment of these patients.

  4. A case report of spontaneous mutation (C33>U) in the iron-responsive element of L-ferritin causing hyperferritinemia-cataract syndrome.

    LENUS (Irish Health Repository)

    Cao, Wei

    2010-01-15

    The hereditary hyperferritinemia cataract syndrome (HHCS) is an autosomal dominant disorder characterized by juvenile-onset cataracts and elevated serum ferritin levels. It is caused by mutation in the iron response element (IRE) within the 5\\'UTR of L-ferritin gene. The mutation results in a loss of post-transcriptional negative feedback exerted by the interaction between iron regulatory proteins 1, 2 (IRP1 and IRP2) and IRE, which leads to uncontrolled expression of L-ferritin. In this paper, we describe the molecular pathogenesis of non-hereditary hyperferritinemia cataract syndrome (non-H-HCS) in a patient with typical HHCS ocular lens morphology and high ferritin levels without obvious family history. Initial sequencing of the full-length L-ferritin cloned from genomic DNA demonstrated a mutation (C33>T) in the IRE of the affected patient but not in her unaffected family members. The mutation (C\\/T heterozygote) was also detected in cDNA derived from her blood mononuclear cells. Structure-prediction-modeling indicates that this mutation would significantly alter the secondary structure of the IRE, resulting in a loss of the interaction between IRP and IRE. By using IRP1\\/IRP2-human IgG1 Fc fusion proteins, we established a novel in vitro report system (modified ELISA) to verify impaired IRE\\/IRP binding. Both the C33>U and A40G mutations (the first identified mutation for HHCS) showed a dramatically decreased binding to IRP1\\/IRP2 protein, compared to the normal IRE RNA. Surprisingly, a decrease in L-ferritin mRNA levels was observed in the affected patient compared to controls suggesting a mechanism of transcriptional negative feedback by high intracellular L-ferritin protein levels not described heretofore. Taken together, spontaneous mutation in the IRE of L-ferritin may cause non-H-HCS by the same mechanism as HHCS. In addition, under abnormal circumstances, the protein level of L-ferritin may be principally controlled by post

  5. Regnase-1 Maintains Iron Homeostasis via the Degradation of Transferrin Receptor 1 and Prolyl-Hydroxylase-Domain-Containing Protein 3 mRNAs

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    Masanori Yoshinaga

    2017-05-01

    Full Text Available Iron metabolism is regulated by transcriptional and post-transcriptional mechanisms. The mRNA of the iron-controlling gene, transferrin receptor 1 (TfR1, has long been believed to be negatively regulated by a yet-unidentified endonuclease. Here, we show that the endonuclease Regnase-1 is critical for the degradation of mRNAs involved in iron metabolism in vivo. First, we demonstrate that Regnase-1 promotes TfR1 mRNA decay. Next, we show that Regnase-1−/− mice suffer from severe iron deficiency anemia, although hepcidin expression is downregulated. The iron deficiency anemia is induced by a defect in duodenal iron uptake. We reveal that duodenal Regnase-1 controls the expression of PHD3, which impairs duodenal iron uptake via HIF2α suppression. Finally, we show that Regnase-1 is a HIF2α-inducible gene and thus provides a positive feedback loop for HIF2α activation via PHD3. Collectively, these results demonstrate that Regnase-1-mediated regulation of iron-related transcripts is essential for the maintenance of iron homeostasis.

  6. Regnase-1 Maintains Iron Homeostasis via the Degradation of Transferrin Receptor 1 and Prolyl-Hydroxylase-Domain-Containing Protein 3 mRNAs.

    Science.gov (United States)

    Yoshinaga, Masanori; Nakatsuka, Yoshinari; Vandenbon, Alexis; Ori, Daisuke; Uehata, Takuya; Tsujimura, Tohru; Suzuki, Yutaka; Mino, Takashi; Takeuchi, Osamu

    2017-05-23

    Iron metabolism is regulated by transcriptional and post-transcriptional mechanisms. The mRNA of the iron-controlling gene, transferrin receptor 1 (TfR1), has long been believed to be negatively regulated by a yet-unidentified endonuclease. Here, we show that the endonuclease Regnase-1 is critical for the degradation of mRNAs involved in iron metabolism in vivo. First, we demonstrate that Regnase-1 promotes TfR1 mRNA decay. Next, we show that Regnase-1 -/- mice suffer from severe iron deficiency anemia, although hepcidin expression is downregulated. The iron deficiency anemia is induced by a defect in duodenal iron uptake. We reveal that duodenal Regnase-1 controls the expression of PHD3, which impairs duodenal iron uptake via HIF2α suppression. Finally, we show that Regnase-1 is a HIF2α-inducible gene and thus provides a positive feedback loop for HIF2α activation via PHD3. Collectively, these results demonstrate that Regnase-1-mediated regulation of iron-related transcripts is essential for the maintenance of iron homeostasis. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

  7. Current understanding of iron homeostasis.

    Science.gov (United States)

    Anderson, Gregory J; Frazer, David M

    2017-12-01

    Iron is an essential trace element, but it is also toxic in excess, and thus mammals have developed elegant mechanisms for keeping both cellular and whole-body iron concentrations within the optimal physiologic range. In the diet, iron is either sequestered within heme or in various nonheme forms. Although the absorption of heme iron is poorly understood, nonheme iron is transported across the apical membrane of the intestinal enterocyte by divalent metal-ion transporter 1 (DMT1) and is exported into the circulation via ferroportin 1 (FPN1). Newly absorbed iron binds to plasma transferrin and is distributed around the body to sites of utilization with the erythroid marrow having particularly high iron requirements. Iron-loaded transferrin binds to transferrin receptor 1 on the surface of most body cells, and after endocytosis of the complex, iron enters the cytoplasm via DMT1 in the endosomal membrane. This iron can be used for metabolic functions, stored within cytosolic ferritin, or exported from the cell via FPN1. Cellular iron concentrations are modulated by the iron regulatory proteins (IRPs) IRP1 and IRP2. At the whole-body level, dietary iron absorption and iron export from the tissues into the plasma are regulated by the liver-derived peptide hepcidin. When tissue iron demands are high, hepcidin concentrations are low and vice versa. Too little or too much iron can have important clinical consequences. Most iron deficiency reflects an inadequate supply of iron in the diet, whereas iron excess is usually associated with hereditary disorders. These disorders include various forms of hemochromatosis, which are characterized by inadequate hepcidin production and, thus, increased dietary iron intake, and iron-loading anemias whereby both increased iron absorption and transfusion therapy contribute to the iron overload. Despite major recent advances, much remains to be learned about iron physiology and pathophysiology. © 2017 American Society for Nutrition.

  8. Adaptation of transferrin protein and glycan synthesis

    NARCIS (Netherlands)

    G. de Jong (Gerard); W.L. van Noort (W.); R.A. Feelders (Richard); C.M.H. de Jeu-Jaspars (Nel); H.G. van Eijk (Henk)

    1992-01-01

    textabstractWe report the patterns of variability in transferrin structure in pregnancy, iron deficiency anemia, women using oral contraceptives, nonanaemic rheumatoid arthritis, iron deficient rheumatoid arthritis and anemia of the chronic diseases. Changes in microheterogeneity were assessed by

  9. Evaluation of iron deposits in the reticuloendothelial system using T2-relaxation rate of MRI. Relation with serum ferritin and Fe concentration

    International Nuclear Information System (INIS)

    Ootsuka, Kae; Togami, Izumi; Kitagawa, Takahiro

    1996-01-01

    MR imaging is a useful non-invasive technique to detect iron deposits in many organs, but it is difficult to evaluate quantitatively. This study was performed to determine the possibility whether T2 relaxation rate (1/T2) could quantify iron deposits in the reticuloendothelial system (liver, spleen and bone marrow) of 11 patients and four normal volunteers. A moderate correlation was obtained between T2-relaxation rate and the serum ferritin level. These results suggest that T2-relaxation rate may provide useful information for the repeated quantitative evaluation of patients with iron-overload-syndromes. (author)

  10. Deficiency of α-1-antitrypsin influences systemic iron homeostasis

    Directory of Open Access Journals (Sweden)

    Ghio AJ

    2013-01-01

    Full Text Available Andrew J Ghio,1 Joleen M Soukup,1 Judy H Richards,1 Bernard M Fischer,2 Judith A Voynow,2 Donald E Schmechel31US Environmental Protection Agency, Chapel Hill, NC, USA; 2Division of Pediatric Pulmonary Medicine, Department of Pediatrics,3Joseph and Kathleen Bryan Alzheimer Disease Research Center, Department of Medicine (Neurology, Duke University Medical Center, Durham, NC, USAAbstract: There is evidence that proteases and antiproteases participate in the iron homeostasis of cells and living systems. We tested the postulate that α-1 antitrypsin (A1AT polymorphism and the consequent deficiency of this antiprotease in humans are associated with a systemic disruption in iron homeostasis. Archived plasma samples from Alpha-1 Foundation (30 MM, 30 MZ, and 30 ZZ individuals were analyzed for A1AT, ferritin, transferrin, and C-reactive protein (CRP. Plasma samples were also assayed for metals using inductively coupled plasma atomic emission spectroscopy (ICPAES. Plasma levels of A1AT in MZ and ZZ individuals were approximately 60% and 20% of those for MM individuals respectively. Plasma ferritin concentrations in those with the ZZ genotype were greater relative to those individuals with either MM or MZ genotype. Plasma transferrin for MM, MZ, and ZZ genotypes showed no significant differences. Linear regression analysis revealed a significant (negative relationship between plasma concentrations of A1AT and ferritin while that between A1AT and transferrin levels was not significant. Plasma CRP concentrations were not significantly different between MM, MZ, and ZZ individuals. ICPAES measurement of metals confirmed elevated plasma concentrations of nonheme iron among ZZ individuals. Nonheme iron concentrations correlated (negatively with levels of A1AT. A1AT deficiency is associated with evidence of a disruption in iron homeostasis with plasma ferritin and nonheme iron concentrations being elevated among those with the ZZ genotype.Keywords: α-1

  11. Room-temperature susceptometry predicts biopsy-determined hepatic iron in patients with elevated serum ferritin.

    Science.gov (United States)

    Maliken, Bryan D; Avrin, William F; Nelson, James E; Mooney, Jody; Kumar, Sankaran; Kowdley, Kris V

    2012-01-01

    There is an ongoing clinical need for novel methods to measure hepatic iron content (HIC) noninvasively. Both magnetic resonance imaging (MRI) and superconducting quantum interference device (SQUID) methods have previously shown promise for estimation of HIC, but these methods can be expensive and are not widely available. Room-temperature susceptometry (RTS) represents an inexpensive alternative and was previously found to be strongly correlated with HIC estimated by SQUID measurements among patients with transfusional iron overload related to thalassemia. The goal of the current study was to examine the relationship between RTS and biochemical HIC measured in liver biopsy specimens in a more varied patient cohort. Susceptometry was performed in a diverse group of patients with hyperferritinemia due to hereditary hemochromatosis (HHC) (n = 2), secondary iron overload (n = 3), nonalcoholic fatty liver disease (NAFLD) (n = 2), and chronic viral hepatitis (n = 3) within one month of liver biopsy in the absence of iron depletion therapy. The correlation coefficient between HIC estimated by susceptometry and by biochemical iron measurement in liver tissue was 0.71 (p = 0.022). Variance between liver iron measurement and susceptometry measurement was primarily related to reliance on the patient's body-mass index (BMI) to estimate the magnetic susceptibility of tissue overlying the liver. We believe RTS holds promise for noninvasive measurement of HIC. Improved measurement techniques, including more accurate overlayer correction, may further improve the accuracy of liver susceptometry in patients with liver disease.

  12. Ferritin Assembly in Enterocytes of Drosophila melanogaster

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    Abraham Rosas-Arellano

    2016-02-01

    Full Text Available Ferritins are protein nanocages that accumulate inside their cavity thousands of oxidized iron atoms bound to oxygen and phosphates. Both characteristic types of eukaryotic ferritin subunits are present in secreted ferritins from insects, but here dimers between Ferritin 1 Heavy Chain Homolog (Fer1HCH and Ferritin 2 Light Chain Homolog (Fer2LCH are further stabilized by disulfide-bridge in the 24-subunit complex. We addressed ferritin assembly and iron loading in vivo using novel transgenic strains of Drosophila melanogaster. We concentrated on the intestine, where the ferritin induction process can be controlled experimentally by dietary iron manipulation. We showed that the expression pattern of Fer2LCH-Gal4 lines recapitulated iron-dependent endogenous expression of the ferritin subunits and used these lines to drive expression from UAS-mCherry-Fer2LCH transgenes. We found that the Gal4-mediated induction of mCherry-Fer2LCH subunits was too slow to effectively introduce them into newly formed ferritin complexes. Endogenous Fer2LCH and Fer1HCH assembled and stored excess dietary iron, instead. In contrast, when flies were genetically manipulated to co-express Fer2LCH and mCherry-Fer2LCH simultaneously, both subunits were incorporated with Fer1HCH in iron-loaded ferritin complexes. Our study provides fresh evidence that, in insects, ferritin assembly and iron loading in vivo are tightly regulated.

  13. 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.

    Science.gov (United States)

    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.

  14. Insulin resistance and serum parameters of iron status in type 2 diabetics

    International Nuclear Information System (INIS)

    Zafar, U.

    2011-01-01

    Background: Type 2 diabetes mellitus (T2DM) is a predominant public health concern worldwide, accounting for 90% of the cases of diabetes globally. Pathogenesis of T2DM involves insulin resistance, defective insulin secretion and increased glucose production by the liver. Subclinical haemochromatosis has been considered as one of the probable causes of insulin resistance and diabetes mellitus. The aim of this study was to determine and correlate insulin resistance and serum parameters of iron status (serum ferritin and transferrin saturation) in type 2 diabetics. Methods: It was a correlational study. This study was conducted on sixty male patients with type 2 diabetes mellitus. Fasting blood sample was taken from each subject and analysed for glucose, haemoglobin, insulin, iron, Total Iron Binding Capacity (TIBC) and ferritin. Insulin resistance was determined by HOMA-IR index. Transferrin saturation was calculated from serum iron and TIBC. Data was analysed using SPSS-17. Results: There was significant positive correlation between insulin resistance and transferrin saturation, but there was no significant correlation of insulin resistance with blood haemoglobin, serum iron and serum ferritin in type 2 diabetics. Conclusion: Correlation between insulin resistance and transferrin saturation reveals that iron has negative impact on insulin sensitivity in type 2 diabetics. (author)

  15. Ferritin levels, inflammatory biomarkers, and mortality in peripheral arterial disease: a substudy of the Iron (Fe) and Atherosclerosis Study (FeAST) Trial.

    Science.gov (United States)

    Depalma, Ralph G; Hayes, Virginia W; Chow, Bruce K; Shamayeva, Galina; May, Patricia E; Zacharski, Leo R

    2010-06-01

    This study delineated correlations between ferritin, inflammatory biomarkers, and mortality in a cohort of 100 cancer-free patients with peripheral arterial disease (PAD) participating in the Veterans Affairs (VA) Cooperative Study #410, the Iron (Fe) and Atherosclerosis Study (FeAST). FeAST, a prospective, randomized, single-blind clinical trial, tested the hypothesis that reduction of iron stores using phlebotomy would influence clinical outcomes in 1227 PAD patients randomized to iron reduction or control groups. The effects of statin administration were also examined in the Sierra Nevada Health Care (SNHC) cohort by measuring serum ferritin levels at entry and during the 6-year study period. No difference was documented between treatment groups in all-cause mortality and secondary outcomes of death plus nonfatal myocardial infarction and stroke. Iron reduction in the main study caused a significant age-related improvement in cardiovascular disease outcomes, new cancer diagnoses, and cancer-specific death. Tumor necrosis factor (TNF)-alpha, TNF-alpha receptors 1 and 2, interleukin (IL)-2, IL-6, IL-10, and high-sensitivity C reactive protein (hs-CRP) were measured at entry and at 6-month intervals for 6 years. Average levels of ferritin and lipids at entry and at the end of the study were compared. The clinical course and ferritin levels of 23 participants who died during the study were reviewed. At entry, mean age of entry was 67 +/- 9 years for the SNHCS cohort, comparable to FeAST and clinical and laboratory parameters were equivalent in substudy participants randomized to iron reduction (n = 51) or control (n = 49). At baseline, 53 participants on statins had slightly lower mean entry-level ferritin values (114.06 ng/mL; 95% confidence interval [CI] 93.43-134.69) vs the 47 off statins (127.62 ng/mL; 95% CI, 103.21-152.02). Longitudinal analysis of follow-up data, after adjusting for the phlebotomy treatment effect, showed that statin use was associated with

  16. Reference limits and behaviour of serum transferrin receptor in children 6-10 years of age.

    Science.gov (United States)

    Danise, P; Maconi, M; Morelli, G; Di Palma, A; Rescigno, G; Esposito, C; Avino, D; Talento, B

    2008-08-01

    Serum transferrin receptor (sTfR) originates mostly from erythroblasts and lesser from reticulocytes. The usefulness of sTfR has been implicated in several clinical situations, mainly as a marker of accelerated erythropoiesis or iron deficiency. The assessment of sTfR may be useful in the period of rapid growth during infancy, childhood and adolescence. We evaluated sTfR and the other quantitative and qualitative parameters of the erythropoiesis (Hb, MCV, CHr, Ret-He) and of the iron storage (serum ferritin, sTfR/ferritin index) in a total of 916 children aged 6-10 years. Children were divided into three groups: (A) healthy children, (B) with storage iron deficiency (serum ferritin 3.3). We determined reference intervals by sex and by age in healthy children. sTfR showed a slight but statistically significant age related increase but did not show significant sex differences. We compared sTfR and the other parameters investigated in the three groups of children. sTfR is not a decisive parameter that can be utilized alone in discriminating the border-line situations between normal and pathologic ones but can help in completing the panel of tests in iron deficiency and in thalassaemia Beta trait carriers.

  17. Relationship between high serum ferritin level and glaucoma in a South Korean population: the Kangbuk Samsung health study.

    Science.gov (United States)

    Gye, Hyo Jung; Kim, Joon Mo; Yoo, Chungkwon; Shim, Seong Hee; Won, Yu Sam; Sung, Ki Chul; Lee, Mi Yeon; Park, Ki Ho

    2016-12-01

    To investigate the association between serum ferritin levels and glaucoma in a South Korean population. This retrospective cross-sectional study included 164 029 subjects who underwent screening at Kangbuk Samsung Hospital Health Screening Center between August 2012 and July 2013. All subjects underwent a physical examination, answered sociodemographic and behavioural questions, and provided samples for laboratory analyses. A digital fundus photograph of both eyes was taken, and all photographs were reviewed by ophthalmologists. The ophthalmologists determined if an eye had glaucoma based on criteria set forth by the International Society of Geographical and Epidemiological Ophthalmology and the appearance of the retinal nerve fibre layer and optic disc. The mean serum ferritin level was 56.98 ng/mL in women and 223.82 ng/mL in men. After adjusting for age, serum iron, total iron-binding capacity (TIBC), transferrin saturation, white blood cell (WBC) count, high-sensitivity C-reactive protein (HsCRP) and total vitamin D level, males in the highest quartile for serum ferritin level had a higher OR for glaucoma than males in the lowest quartile (OR=1.176, 95% CI 1.030 to 1.342, p=0.016); we did not observe this relationship among women. Other markers of iron metabolism, such as iron level, transferrin saturation and TIBC, and inflammation measures, including WBC, HsCRP and total vitamin D, were not associated with glaucoma. High serum ferritin level was associated with a high risk of glaucoma in men, but not in women. Because serum ferritin is related to oxidative stress and inflammation, it might play a role in glaucoma development. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

  18. HFE Gene Mutations and Iron Status in 100 Healthy Polish Children.

    Science.gov (United States)

    Kaczorowska-Hac, Barbara; Luszczyk, Marcin; Antosiewicz, Jedrzej; Ziolkowski, Wieslaw; Adamkiewicz-Drozynska, Elzbieta; Mysliwiec, Malgorzata; Milosz, Ewa; Kaczor, Jan J

    2017-07-01

    Iron participates in oxygen transport, energetic, metabolic, and immunologic processes. There are 2 main causes of iron overload: hereditary hemochromatosis which is a primary cause, is a metabolic disorder caused by mutations of genes that control iron metabolism and secondary hemochromatosis caused by multitransfusions, chronic hemolysis, and intake of iron rich food. The most common type of hereditary hemochromatosis is caused by HFE gene mutation. In this study, we analyzed iron metabolism in 100 healthy Polish children in relation to their HFE gene status. The wild-type HFE gene was predominant being observed in 60 children (60%). Twenty-five children (25%), presented with heterozygotic H63D mutation, and 15 children (15%), presented with other mutations (heterozygotic C282Y and S65C mutation, compound heterozygotes C282Y/S65C, C282Y/H63D, H63D homozygote). The mean concentration of iron, the level of ferritin, and transferrin saturation were statistically higher in the group of HFE variants compared with the wild-type group. H63D carriers presented with higher mean concentration of iron, ferritin levels, and transferrin saturation compared with the wild-type group. Male HFE carriers presented with higher iron concentration, transferrin saturation, and ferritin levels than females. This preliminary investigation demonstrates allelic impact on potential disease progression from childhood.

  19. Studies of metal binding by the iron transport protein transferrin using time differential perturbed angular correlation spectroscopy

    International Nuclear Information System (INIS)

    Then, G.M.

    1987-01-01

    The binding of the transition metal hafnium to transferrin was studied under various chemical conditions using time differential perturbed γγ angular correlation spectroscopy (TDPAC). Observing the electric quadrupole interaction of the 181 Hf probe nuclei size and symmetry of the electric field gradient induced by the ligands of the metal ions can be determined. The experimental data suggest how homogeneous the binding conditions are and to which extend relaxation phenomena are involved. Due to the excellent time resolution obtained with new BaF 2 detectors the quadrupole coupling parameters of 181 Hf-transferrin could be determined very accurately. Under nearly physiological conditions different binding configurations were quantitatively characterized by spectroscopic means and distinguished with high specificity. (orig./PW) [de

  20. Serum levels of iron in Sør-Varanger, Northern Norway--an iron mining municipality.

    Science.gov (United States)

    Broderstad, Ann R; Smith-Sivertsen, Tone; Dahl, Inger Marie S; Ingebretsen, Ole Christian; Lund, Eiliv

    2006-12-01

    The purpose of this study was to investigate iron status in a population with a high proportion of miners in the northernmost part of Norway. Cross-sectional, population-based study performed in order to investigate possible health effects of pollution in the population living on both sides of the Norwegian-Russian border. All individuals living in the community of Sør-Varanger were invited for screening in 1994. In 2000, blood samples from 2949 participants (response rate 66.8 %), age range 30-69 years, were defrosted. S-ferritin and transferrin saturation were analysed in samples from 1548 women and 1401 men. About 30 % (n = 893) were employed in the iron mining industry, 476 of whom were miners and 417 had other tasks in the company. Type and duration of employment and time since last day of work at the company were used as indicators of exposure. Both s-ferritin levels and transferrin saturation were higher in men than in women. S-ferritin increased with increasing age in women, while the opposite was true for men. Iron deficiency occurred with higher frequencies in women (16 %) than in men (4 %). Iron overload was uncommon in both sexes. Adjustment for smoking and self-reported pulmonary diseases did not show any effect on iron levels. Miners had non-significant higher mean s-ferritin and transferrin saturation than non-miners. Neither duration, nor time since employment in the mine, had any impact on iron status. Our analyses did not show any associations between being a miner in the iron mining industry and serum iron levels compared to the general population.

  1. Correlations between abnormal iron metabolism and non-motor symptoms in Parkinson's disease.

    Science.gov (United States)

    Xu, Wu; Zhi, Yan; Yuan, Yongsheng; Zhang, Bingfeng; Shen, Yuting; Zhang, Hui; Zhang, Kezhong; Xu, Yun

    2018-07-01

    Despite a growing body of evidence suggests that abnormal iron metabolism plays an important role in the pathogenesis of Parkinson's disease (PD), few studies explored its role in non-motor symptoms (NMS) of PD. The present study aimed to investigate the relationship between abnormal iron metabolism and NMS of PD. Seventy PD patients and 64 healthy controls were consecutively recruited to compare serum iron, ceruloplasmin, ferritin, and transferrin levels. We evaluated five classic NMS, including depression, anxiety, pain, sleep disorder, and autonomic dysfunction in PD patients using the Hamilton Depression Scale (HAMD), the Hamilton Anxiety Scale (HAMA), the short form of the McGill Pain Questionnaire, the Pittsburgh Sleep Quality Index and the Scale for Outcomes in Parkinson's disease for Autonomic Symptoms, respectively. Hierarchical multiple regression analysis was used to investigate the correlations between abnormal iron metabolism and NMS. No differences in serum ceruloplasmin and ferritin levels were examined between PD patients and healthy controls, but we observed significantly decreased serum iron levels and increased serum transferrin levels in PD patients in comparison with healthy controls. After eliminating confounding factors, HAMD scores and HAMA scores were both negatively correlated with serum iron levels and positively correlated with serum transferrin levels. In summary, abnormal iron metabolism might play a crucial role in the pathogenesis of depression and anxiety in PD. Serums levels of iron and transferrin could be peripheral markers for depression and anxiety in PD.

  2. A RhABF2/Ferritin module affects rose (Rosa hybrida) petal dehydration tolerance and senescence by modulating iron levels.

    Science.gov (United States)

    Liu, Jitao; Fan, Youwei; Zou, Jing; Fang, Yiqun; Wang, Linghao; Wang, Meng; Jiang, Xinqiang; Liu, Yiqing; Gao, Junping; Zhang, Changqing

    2017-12-01

    Plants often develop the capacity to tolerate moderate and reversible environmental stresses, such as drought, and to re-establish normal development once the stress has been removed. An example of this phenomenon is provided by cut rose (Rosa hybrida) flowers, which experience typical reversible dehydration stresses during post-harvest handling after harvesting at the bud stages. The molecular mechanisms involved in rose flower dehydration tolerance are not known, however. Here, we characterized a dehydration- and abscisic acid (ABA)-induced ferritin gene (RhFer1). Dehydration-induced free ferrous iron (Fe 2+ ) is preferentially sequestered by RhFer1 and not transported outside of the petal cells, to restrict oxidative stresses during dehydration. Free Fe 2+ accumulation resulted in more serious oxidative stresses and the induction of genes encoding antioxidant enzyme in RhFer1-silenced petals, and poorer dehydration tolerance was observed compared with tobacco rattle virus (TRV) controls. We also determined that RhABF2, an AREB/ABF transcription factor involved in the ABA signaling pathway, can activate RhFer1 expression by directly binding to its promoter. The silencing of RhABF2 decreased dehydration tolerance and disrupted Fe homeostasis in rose petals during dehydration, as did the silencing of RhFer1. Although both RhFer1 and Fe transporter genes are induced during flower natural senescence in plants, the silencing of RhABF2 or RhFer1 accelerates the petal senescence processes. These results suggest that the regulatory module RhABF2/RhFer1 contributes to the maintenance of Fe levels and enhances dehydration tolerance through the action of RhFer1 locally sequestering free Fe 2+ under dehydration conditions, and plays synergistic roles with transporter genes during flower senescence. © 2017 The Authors The Plant Journal © 2017 John Wiley & Sons Ltd.

  3. Effects of hemochromatosis and transferrin gene mutations on peripheral iron dyshomeostasis in Mild Cognitive Impairment and Alzheimer’s and Parkinson’s diseases

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    Stefania eMariani

    2013-08-01

    Full Text Available Deregulation of iron metabolism has been observed in patients with neurodegenerative diseases. We have carried out a molecular analysis investigating the interaction between iron specific gene variants [transferrin (TF, P589S, hemochromatosis (HFE C282Y and H63D], iron biochemical variables [iron, Tf, ceruloplasmin (Cp, Cp:Tf ratio and % of Tf saturation (% Tf-sat] Impairment (MCI, 78 Parkinson’s disease (PD patients and 139 healthy controls to investigate mechanisms of iron regulation or toxicity. No difference in genetic variant distributions between patients and controls was found in our Italian sample, but the stratification for the APOE e4 allele revealed that among the APOE e4 carriers was higher the frequency of those carriers of at least a mutated TF P589S allele. Decreased Tf in both AD and MCI and increased Cp:Tf ratio in AD vs. controls were detected. A multinomial logistic regression model revealed that increased iron and Cp:Tf ratio and being man instead of woman increased the risk of having PD, that increased values of Cp:Tf ratio corresponded to a 4-fold increase of the relative risk of having MCI, while higher Cp levels were protective for PD and MCI. Our study has some limitations: the small size of the sample, one ethnic group considered, the rarity of some alleles which prevent the statistical power of some genetic analysis. Even though they need confirmation in larger cohorts, our data suggest the hypothesis that deregulation of iron metabolism, in addition to other factors, has some effect on the PD disease risk.

  4. 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.

    Science.gov (United States)

    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.

  5. Iron status in obese women.

    Science.gov (United States)

    Stankowiak-Kulpa, Hanna; Kargulewicz, Angelika; Styszyński, Arkadiusz; Swora-Cwynar, Ewelina; Grzymisławski, Marian

    2017-12-23

    A decreased concentration of iron, and consecutively haemoglobin, ferritin and decreased level of saturated transferrin, were observed in obese individuals more often than in healthy subjects. The purpose of this study was to determine whether iron, ferritin, transferrin saturation are significantly diminished in obese female patients compared to non-obese counterparts, and whether excess adiposity and inflammation were associated with depleted iron. Female patients (n=48) diagnosed with obesity (BMI > 30 kg/m2), aged 18-40 were accepted for the study. A control group (n=30) encompassed normal weight women, aged 18-30. All obese women obtained an individually adjusted dietary plan with an energy content of 1,500 kcal. Blood glucose, insulin, lipids, ferritin, TIBC and iron concentrations were assayed in serum twice, initially and after 8 weeks of dieting. The obese women at the initial evaluation, in comparison to non-obese control women, were characterized by a significantly lower mean red blood cell volume (MCV; 84.2±12.4 vs. 91.3±9.3 fL; piron level (92.6±42.4 vs. 119.8±44.0 μg/dL; piron homeostasis. Weight loss leads to decrease in the CRP level, but it does not change haematologic parameters in the period of 8 weeks.

  6. Serum transferrin receptor in polycythemia.

    Science.gov (United States)

    Manteiga, R; Remacha, A F; Sardà, M P; Ubeda, J

    1998-10-01

    We measured serum transferrin receptor (sTfR) levels in 22 patients with polycythemia vera and in 26 cases of secondary polycythemia. In our study, raised sTfR levels in both polycythemia groups were related to iron deficiency.

  7. Electron-beam-induced reduction of Fe3+ in iron phosphate dihydrate, ferrihydrite, haemosiderin and ferritin as revealed by electron energy-loss spectroscopy

    International Nuclear Information System (INIS)

    Pan, Ying-Hsi; Vaughan, Gareth; Brydson, Rik; Bleloch, Andrew; Gass, Mhairi; Sader, Kasim; Brown, Andy

    2010-01-01

    The effect of high-energy electron irradiation on ferritin/haemosiderin cores (in an iron-overloaded human liver biopsy), its mineral analogue; six-line ferrihydrite (6LFh), and iron phosphate dihydrate (which has similar octahedral ferric iron to oxygen coordination to that in ferrihydrite and ferritin/haemosiderin cores) has been investigated using electron energy-loss spectroscopy (EELS). Fe L 2,3 -ionisation edges were recorded on two types of electron microscope: a 200 keV transmission electron microscope (TEM) and a 100 keV scanning transmission electron microscope (STEM), in order to investigate the damage mechanisms in operation and to establish a methodology for minimum specimen alteration during analytical electron microscopic characterisation. A specimen damage mechanism dominated by radiolysis that results in the preferential loss of iron co-ordinating ligands (O, OH and H 2 O) is discussed. The net result of irradiation is structural re-organisation and reduction of iron within the iron hydroxides. At sufficiently low electron fluence and particularly in the lower incident energy, finer probe diameter STEM, the alteration is shown to be minimal. All the materials examined exhibit damage which as a function of cumulative fluence is best fitted by an inverse power-law, implying that several chemical and structural changes occur in response to the electron beam and we suggest that these are governed by secondary processes arising from the primary ionisation event. This work affirms that electron fluence and current density should be considered when measuring mixed valence ratios with EELS.

  8. Electron-beam-induced reduction of Fe{sup 3+} in iron phosphate dihydrate, ferrihydrite, haemosiderin and ferritin as revealed by electron energy-loss spectroscopy

    Energy Technology Data Exchange (ETDEWEB)

    Pan, Ying-Hsi; Vaughan, Gareth; Brydson, Rik [Institute for Materials Research, SPEME, University of Leeds, Leeds LS2 9JT (United Kingdom); Bleloch, Andrew; Gass, Mhairi [SuperSTEM, Daresbury Laboratories, Warrington WA4 4AD (United Kingdom); Sader, Kasim [Institute for Materials Research, SPEME, University of Leeds, Leeds LS2 9JT (United Kingdom); SuperSTEM, Daresbury Laboratories, Warrington WA4 4AD (United Kingdom); Brown, Andy, E-mail: a.p.brown@leeds.ac.uk [Institute for Materials Research, SPEME, University of Leeds, Leeds LS2 9JT (United Kingdom)

    2010-07-15

    The effect of high-energy electron irradiation on ferritin/haemosiderin cores (in an iron-overloaded human liver biopsy), its mineral analogue; six-line ferrihydrite (6LFh), and iron phosphate dihydrate (which has similar octahedral ferric iron to oxygen coordination to that in ferrihydrite and ferritin/haemosiderin cores) has been investigated using electron energy-loss spectroscopy (EELS). Fe L{sub 2,3}-ionisation edges were recorded on two types of electron microscope: a 200 keV transmission electron microscope (TEM) and a 100 keV scanning transmission electron microscope (STEM), in order to investigate the damage mechanisms in operation and to establish a methodology for minimum specimen alteration during analytical electron microscopic characterisation. A specimen damage mechanism dominated by radiolysis that results in the preferential loss of iron co-ordinating ligands (O, OH and H{sub 2}O) is discussed. The net result of irradiation is structural re-organisation and reduction of iron within the iron hydroxides. At sufficiently low electron fluence and particularly in the lower incident energy, finer probe diameter STEM, the alteration is shown to be minimal. All the materials examined exhibit damage which as a function of cumulative fluence is best fitted by an inverse power-law, implying that several chemical and structural changes occur in response to the electron beam and we suggest that these are governed by secondary processes arising from the primary ionisation event. This work affirms that electron fluence and current density should be considered when measuring mixed valence ratios with EELS.

  9. Decreased serum hepcidin concentration correlates with brain iron deposition in patients with HBV-related cirrhosis.

    Directory of Open Access Journals (Sweden)

    Dong Lin

    Full Text Available 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

  10. Association of Increased Serum Ferritin With Impaired Muscle Strength/Quality in Hemodialysis Patients.

    Science.gov (United States)

    Nakagawa, Chie; Inaba, Masaaki; Ishimura, Eiji; Yamakawa, Tomoyuki; Shoji, Shigeichi; Okuno, Senji

    2016-07-01

    We reported previously that muscle quality and muscle strength provide clinically relevant predictors for better survival in hemodialysis patients. Iron overload might impair muscle function by its accumulation in muscle in such patients. Serum ferritin, a marker for body iron store, was examined for its association with handgrip strength (HGS) and muscle quality which was defined as the ratio of HGS to arm lean mass measured with dual-energy X-ray absorptiometry. In 300 Japanese hemodialysis patients, age, hemodialysis duration, body mass index, and serum albumin were 58.0 ±12.0 (mean ± standard deviation) years, 4.2 (1.8-10.4) (median [25th-75th percentile]) years, 20.4 ± 2.8 kg/m(2), 4.0 ± 0.3 g/dL, respectively. Hemoglobin and hematocrit were 8.9 ± 1.2 g/dL, and 28.8 ± 3.9%, respectively, whereas transferrin saturation and serum ferritin were 29.8 ± 11.0% and 100 (54-172) ng/mL, respectively. Serum ferritin significantly correlated in a positive manner with the total dose of iron orally administered during the previous 6 months (r = 0.185, P = .0013). HGS and muscle quality were 23.1 ± 10.4 kg and 11.6 ± 3.8 kg/kg, respectively. In multivariate analysis to elucidate the factors associated with HGS and muscle quality in 300 hemodialysis patients, which included transferrin saturation and log serum ferritin, in addition to age, gender, hemodialysis duration, the presence/absence of diabetes, body mass index as independent variables, log serum ferritin emerged as a significant and independent factor which associated in a negative fashion with HGS (β = -0.091, P = .0395) and tendency toward negative association with muscle quality (β = -0.100, P = .0754). In summary, the present study demonstrated the significant association of serum ferritin with HGS and muscle quality in hemodialysis patients and thus suggested that we should be careful of iron overload to avoid its possible harmful effect on muscle in such patients. Copyright © 2016 National Kidney

  11. Evaluation of the Efficiency of the Reticulocyte Hemoglobin Content on Diagnosis for Iron Deficiency Anemia in Chinese Adults

    Directory of Open Access Journals (Sweden)

    Jie Cai

    2017-05-01

    Full Text Available Our aim was to evaluate the cut-off value and efficiency of using reticulocyte hemoglobin content as a marker to diagnose iron deficiency anemia in Chinese adults. 140 adults who needed bone marrow aspiration for diagnosis at the hematology department of the Peking Union Medical College Hospital were enrolled according to the inclusive and exclusive criteria. Venous blood samples were collected to detect complete blood count, including hemoglobin, reticulocyte hemoglobin content, hematocrit, mean cellular volume, corpuscular hemoglobin concentration, hemoglobin content, free erythrocyte protoporphyrin; iron indexes of serum ferritin, serum transferrin receptor, and unsaturated iron-binding capacity; and inflammation markers of C-reactive protein and α-acid glycoprotein. Bone marrow samples were obtained for the bone marrow iron staining, which was used as the standard for the evaluation of iron status in this study. Subjects were divided into three groups according to hemoglobin levels and bone marrow iron staining results: the IDA (iron deficiency anemia group, the NIDA (non-iron deficiency anemia group, and the control group. The differences of the above-mentioned indexes were compared among the three groups and the effect of inflammation was also considered. The cut-off value of reticulocyte hemoglobin content was determined by receiver operation curves. The IDA group (n = 56 had significantly lower reticulocyte hemoglobin content, mean cellular volume, corpuscular hemoglobin concentration, hemoglobin content, and serum ferritin; and higher free erythrocyte protoporphyrin, unsaturated iron-binding capacity, and serum transferrin receptor (p < 0.05 compared with the NIDA group (n = 38 and control group (n = 46. Hematocrit, serum ferritin, and unsaturated iron-binding capacity were significantly affected by inflammation while reticulocyte hemoglobin content and other parameters were not. The cut-off value of reticulocyte hemoglobin content for

  12. Low transferrin saturation is associated with impaired fasting glucose and insulin resistance in the South Korean adults: the 2010 Korean National Health and Nutrition Examination Survey.

    Science.gov (United States)

    Park, R J; Moon, J D

    2015-05-01

    The associations of transferrin saturation with diabetes have not been well evaluated and conflicting results have been reported. The purpose of this study is to examine the association of iron indices (serum ferritin and transferrin saturation) with risk of impaired fasting glucose and insulin resistance. We conducted a cross-sectional study in 2413 individuals (1150 men and 1263 women) aged 20-50 years who participated in the 2010 Korean National Health and Nutrition Examination Survey. Participants were free of diabetes, malignancy, liver cirrhosis, chronic renal failure, anaemia, pregnancy and menopause. Fasting plasma glucose, insulin and the homeostasis model assessment of insulin resistance (HOMA-IR) were measured as the outcomes. Impaired fasting glucose was more prevalent in the highest compared with the lowest serum ferritin quartile among men (odds ratio [OR], 1.97; 95% confidence interval [CI], 1.20-3.24) after adjustment for multiple covariates. Following the same adjustment, impaired fasting glucose was less prevalent in the highest compared with the lowest transferrin saturation quartile among men (OR, 0.45; 95% CI, 0.25-0.80) and women (OR, 0.33; 95% CI, 0.14-0.77). Moreover, a higher ferritin level was significantly associated with higher HOMA-IR after adjusting for confounders in men. Lower transferrin saturation was also significantly associated with higher insulin levels and HOMA-IR in both sexes. Lower transferrin saturations were associated with an increased risk of impaired fasting glucose and insulin resistance among general South Korean population. © 2014 The Authors. Diabetic Medicine © 2014 Diabetes UK.

  13. Iron Therapy in Patients with Heart Failure and Iron Deficiency: Review of Iron Preparations for Practitioners.

    Science.gov (United States)

    Drozd, Marcin; Jankowska, Ewa A; Banasiak, Waldemar; Ponikowski, Piotr

    2017-06-01

    In patients with heart failure (HF), iron deficiency (ID) correlates with decreased exercise capacity and poor health-related quality of life, and predicts worse outcomes. Both absolute (depleted iron stores) and functional (where iron is unavailable for dedicated tissues) ID can be easily evaluated in patients with HF using standard laboratory tests (assessment of serum ferritin and transferrin saturation). Intravenous iron therapy in iron-deficient patients with HF and reduced ejection fraction has been shown to alleviate HF symptoms and improve exercise capacity and quality of life. In this paper, we provide information on how to diagnose ID in HF. Further we discuss pros and cons of different iron preparations and discuss the results of major trials implementing iron supplementation in HF patients, in order to provide practical guidance for clinicians on how to manage ID in patients with HF.

  14. NCOA4 Deficiency Impairs Systemic Iron Homeostasis

    Directory of Open Access Journals (Sweden)

    Roberto Bellelli

    2016-01-01

    Full Text Available The cargo receptor NCOA4 mediates autophagic ferritin degradation. Here we show that NCOA4 deficiency in a knockout mouse model causes iron accumulation in the liver and spleen, increased levels of transferrin saturation, serum ferritin, and liver hepcidin, and decreased levels of duodenal ferroportin. Despite signs of iron overload, NCOA4-null mice had mild microcytic hypochromic anemia. Under an iron-deprived diet (2–3 mg/kg, mice failed to release iron from ferritin storage and developed severe microcytic hypochromic anemia and ineffective erythropoiesis associated with increased erythropoietin levels. When fed an iron-enriched diet (2 g/kg, mice died prematurely and showed signs of liver damage. Ferritin accumulated in primary embryonic fibroblasts from NCOA4-null mice consequent to impaired autophagic targeting. Adoptive expression of the NCOA4 COOH terminus (aa 239–614 restored this function. In conclusion, NCOA4 prevents iron accumulation and ensures efficient erythropoiesis, playing a central role in balancing iron levels in vivo.

  15. Ferritin associates with marginal band microtubules

    International Nuclear Information System (INIS)

    Infante, Anthony A.; Infante, Dzintra; Chan, M.-C.; How, P.-C.; Kutschera, Waltraud; Linhartova, Irena; Muellner, Ernst W.; Wiche, Gerhard; Propst, Friedrich

    2007-01-01

    We characterized chicken erythrocyte and human platelet ferritin by biochemical studies and immunofluorescence. Erythrocyte ferritin was found to be a homopolymer of H-ferritin subunits, resistant to proteinase K digestion, heat stable, and contained iron. In mature chicken erythrocytes and human platelets, ferritin was localized at the marginal band, a ring-shaped peripheral microtubule bundle, and displayed properties of bona fide microtubule-associated proteins such as tau. Red blood cell ferritin association with the marginal band was confirmed by temperature-induced disassembly-reassembly of microtubules. During erythrocyte differentiation, ferritin co-localized with coalescing microtubules during marginal band formation. In addition, ferritin was found in the nuclei of mature erythrocytes, but was not detectable in those of bone marrow erythrocyte precursors. These results suggest that ferritin has a function in marginal band formation and possibly in protection of the marginal band from damaging effects of reactive oxygen species by sequestering iron in the mature erythrocyte. Moreover, our data suggest that ferritin and syncolin, a previously identified erythrocyte microtubule-associated protein, are identical. Nuclear ferritin might contribute to transcriptional silencing or, alternatively, constitute a ferritin reservoir

  16. Iron metabolism in critically ill patients developing anemia of inflammation: a case control study.

    Science.gov (United States)

    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.

  17. Relationship between Serum Iron Profile and Blood Groups among the Voluntary Blood Donors of Bangladesh.

    Science.gov (United States)

    Hoque, M M; Adnan, S D; Karim, S; Al-Mamun, M A; Faruki, M A; Islam, K; Nandy, S

    2016-04-01

    Blood donation results in a substantial iron loss and subsequent mobilization from body stores. Chronic iron deficiency is a well-recognized complication of regular blood donation. The present study conducted to compare the level of serum ferritin, serum iron, total iron binding capacity (TIBC) and percentage transferrin saturation in different ABO and Rhesus type blood groups among the voluntary blood donors of Bangladesh. The present prospective study included 100 healthy voluntary donors attending at Department of Blood Transfusion, Dhaka Medical College, Dhaka between the periods of July 2013 to Jun 2014. From each donor 10mL venous blood sample was taken and divided into heparinized and non-heparinized tubes for determination of hemoglobin (Hb), hematocrit (Hct), serum iron (SI), total iron binding capacity (TIBC) and serum ferritin by standard laboratory methods. Percentage of transferrin saturation (TS) calculated from serum iron and TIBC. Data were analyzed with SPSS (version 16) software and comparisons between groups were made using student's t-test and one way ANOVA. In the present study mean±SD of age of the respondents was 27.2±6.5 years with a range of 18 to 49 years and 81.0% were male and 19.0% were female. Among the donors 18.0% had blood group A, 35.0% had blood group B, 14.0% had blood group AB and 33.0% had blood group O. Among the donors 91.0% had rhesus positive and 9.0% had rhesus negative. Donors with blood group O had lowest haemoglobin, serum iron and transferring saturation levels. Donors with blood group A had highest TIBC level. Donors with blood group B had lowest serum ferritin level. An independent samples 't' test showed statistically significant difference in serum ferritin and percentage transferrin saturation between blood group AB and blood group O and in percentage transferrin saturation between blood group B and blood group O. One way ANOVA showed that there is no significant difference in haemoglobin, serum iron, serum

  18. Hemin inhibits internalization of transferrin by reticulocytes and promotes phosphorylation of the membrane transferrin receptor

    International Nuclear Information System (INIS)

    Cox, T.M.; O'Donnell, M.W.; Aisen, P.; London, I.M.

    1985-01-01

    Addition of hemin to reticulocytes inhibits incorporation of iron from transferrin. Heme also regulates protein synthesis in immature erythroid cells through its effects on phosphorylation of the initiation factor eIF-2. The authors have examined its effects on endocytosis of iron-transferrin and phosphorylation of the transferrin receptor. Hemin reduced iron transport but increased cell-associated transferrin. During uptake of 125 I-labeled transferrin in the steady state, the use of a washing technique to dissociate bound transferrin on the cell membrane showed that radioligand accumulated on the surface of hemin-treated cells. Receptor phosphorylation was investigated by immunoprecipitation of reticulocyte extracts after metabolic labeling with [ 32 P]P/sub i/. In the absence of ligand, phosphorylated receptor was chiefly localized on cell stroma. Exposure to transferrin increased cytosolic phosphorylated receptor from 15-30% to approximately 50% of the total, an effect overcome by hemin treatment. The findings suggest a possible relationship of phosphorylation to endocytosis of the transferrin receptor in reticulocytes

  19. Diagnosis of Iron-Deficiency Anemia in Chronic Kidney Disease.

    Science.gov (United States)

    Bahrainwala, Jehan; Berns, Jeffrey S

    2016-03-01

    Anemia is a common and clinically important consequence of chronic kidney disease (CKD). It is most commonly a result of decreased erythropoietin production by the kidneys and/or iron deficiency. Deciding on the appropriate treatment for anemia associated with CKD with iron replacement and erythropoietic-stimulating agents requires an ability to accurately diagnose iron-deficiency anemia. However, the diagnosis of iron-deficiency anemia in CKD patients is complicated by the relatively poor predictive ability of easily obtained routine serum iron indices (eg, ferritin and transferrin saturation) and more invasive gold standard measures of iron deficiency (eg, bone marrow iron stores) or erythropoietic response to supplemental iron. In this review, we discuss the diagnostic utility of currently used serum iron indices and emerging alternative markers of iron stores. Copyright © 2016 Elsevier Inc. All rights reserved.

  20. Disruptive chemical doping in a ferritin-based iron oxide nanoparticle to decrease r2 and enhance detection with T1-weighted MRI.

    Science.gov (United States)

    Clavijo Jordan, M Veronica; Beeman, Scott C; Baldelomar, Edwin J; Bennett, Kevin M

    2014-01-01

    Inorganic doping was used to create flexible, paramagnetic nanoparticle contrast agents for in vivo molecular magnetic resonance imaging (MRI) with low transverse relaxivity (r2). Most nanoparticle contrast agents formed from superparamagnetic metal oxides are developed with high r2. While sensitive, they can have limited in vivo detection due to a number of constraints with T2 or T2*-weighted imaging. T1-weighted imaging is often preferred for molecular MRI, but most T1-shortening agents are small chelates with low metal payload or are nanoparticles that also shorten T2 and limit the range of concentrations detectable with T1-weighting. Here we used tungsten and iron deposition to form doped iron oxide crystals inside the apoferritin cavity to form a WFe nanoparticle with a disordered crystal and un-coupled atomic magnetic moments. The atomic magnetic moments were thus localized, resulting in a principally paramagnetic nanoparticle. The WFe nanoparticles had no coercivity or saturation magnetization at 5 K and sweeping up to ± 20,000 Oe, while native ferritin had a coercivity of 3000 Oe and saturation at ± 20,000 Oe. This tungsten-iron crystal paramagnetism resulted in an increased WFe particle longitudinal relaxivity (r1) of 4870 mm(-1) s(-1) and a reduced transverse relaxivity (r2) of 9076 mm(-1) s(-1) compared with native ferritin. The accumulation of the particles was detected with T1-weighted MRI in concentrations from 20 to 400 nm in vivo, both injected in the rat brain and targeted to the rat kidney glomerulus. The WFe apoferritin nanoparticles were not cytotoxic up to 700 nm particle concentrations, making them potentially important for targeted molecular MRI. Copyright © 2014 John Wiley & Sons, Ltd.

  1. Evaluation of the Efficiency of the Reticulocyte Hemoglobin Content on Diagnosis for Iron Deficiency Anemia in Chinese Adults.

    Science.gov (United States)

    Cai, Jie; Wu, Meng; Ren, Jie; Du, Yali; Long, Zhangbiao; Li, Guoxun; Han, Bing; Yang, Lichen

    2017-05-02

    Our aim was to evaluate the cut-off value and efficiency of using reticulocyte hemoglobin content as a marker to diagnose iron deficiency anemia in Chinese adults. 140 adults who needed bone marrow aspiration for diagnosis at the hematology department of the Peking Union Medical College Hospital were enrolled according to the inclusive and exclusive criteria. Venous blood samples were collected to detect complete blood count, including hemoglobin, reticulocyte hemoglobin content, hematocrit, mean cellular volume, corpuscular hemoglobin concentration, hemoglobin content, free erythrocyte protoporphyrin; iron indexes of serum ferritin, serum transferrin receptor, and unsaturated iron-binding capacity; and inflammation markers of C-reactive protein and α-acid glycoprotein. Bone marrow samples were obtained for the bone marrow iron staining, which was used as the standard for the evaluation of iron status in this study. Subjects were divided into three groups according to hemoglobin levels and bone marrow iron staining results: the IDA (iron deficiency anemia) group, the NIDA (non-iron deficiency anemia) group, and the control group. The differences of the above-mentioned indexes were compared among the three groups and the effect of inflammation was also considered. The cut-off value of reticulocyte hemoglobin content was determined by receiver operation curves. The IDA group ( n = 56) had significantly lower reticulocyte hemoglobin content, mean cellular volume, corpuscular hemoglobin concentration, hemoglobin content, and serum ferritin; and higher free erythrocyte protoporphyrin, unsaturated iron-binding capacity, and serum transferrin receptor ( p iron-binding capacity were significantly affected by inflammation while reticulocyte hemoglobin content and other parameters were not. The cut-off value of reticulocyte hemoglobin content for diagnosing iron deficiency anemia was 27.2 pg, with a sensitivity of 87.5% and a specificity of 92.9%. The cut-off values for

  2. Transferrin metabolism in alcoholic liver disease

    International Nuclear Information System (INIS)

    Potter, B.J.; Chapman, R.W.; Nunes, R.M.; Sorrentino, D.; Sherlock, S.

    1985-01-01

    The metabolism of transferrin was studied using purified 125 I-labeled transferrin in 11 alcoholic patients; six with fatty liver and five with cirrhosis. Six healthy subjects whose alcohol intake was les than 40 gm daily were studied as a control group. There were no significant differences in the mean fractional catabolic rate and plasma volume in the alcoholic groups when compared with control subjects. A significantly decreased mean serum transferrin concentration was found in the alcoholic cirrhotic patients (1.8 +/- 0.3 gm per liter vs. 2.9 +/- 0.2; p less than 0.01), resulting from diminished total body synthesis (0.9 +/- 0.2 mg per kg per hr vs. 1.8 +/- 0.2; p less than 0.01). In contrast, in the patients with alcoholic fatty liver, the mean total body transferrin synthesis (2.4 +/- 0.3 mg per kg per hr) was significantly increased when compared with controls (p less than 0.05). For all the alcoholic patients, the serum transferrin correlated with transferrin synthesis (r = +0.70; p less than 0.01) but the serum iron did not. These results suggest that, in alcoholic cirrhosis, transferrin synthesis is decreased, probably reflecting diminished synthetic capacity by the liver. In contrast, in patients with alcoholic fatty liver, transferrin turnover is accelerated

  3. The association of markers of oxidative-inflammatory status with malnutrition in hemodialysis patients with serum ferritin lower than 500 ng/mL

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    Simone Gonçalves de Almeida

    2013-03-01

    Full Text Available INTRODUCTION: Enhanced inflammatory-oxidative status is well established in chronic kidney disease. OBJECTIVE: The objective of this study was to evaluate the oxidative- inflammatory status and iron indices in patients undergoing maintenance hemodialysis (HD with serum ferritin lower than 500ng/mL, and to correlate them with nutritional status. METHOD: In a cross-sectional survey 35 HD patients (23 with normal nutritional status, 12 with Protein-Energy-Wasting syndrome, PEW, and healthy volunteers (n = 35 were studied. Serum concentration of iron, ferritin, transferrin saturation, malondialdehyde (MDA, protein carbonyl (PC, high-sensitive serum C -reactive protein (hs-CRP and blood counts were determined. The nutritional status was determined by anthropometric and biochemical criteria. RESULTS: HD patients showed low values of hemoglobin and higher values of ferritin, MDA and PC when compared with healthy volunteers. HD subjects with PEW had higher values of PC and hs-PCR as compared to HD patients with normal nutritional status. A multiple logistic regression analysis showed that the independent variables PC (Wald Statistic 4.25, p = 0.039 and hs-CRP (Wald Statistic 4.83, p = 0.028 where related with the patients' nutritional condition. CONCLUSION: In HD patients with serum ferritin below 500 ng/mL was observed one association of the markers of oxidative stress and inflammation with poor nutritional status independently of serum ferritin, gender and age.

  4. Iron status determination in pregnancy using the Thomas plot.

    Science.gov (United States)

    Weyers, R; Coetzee, M J; Nel, M

    2016-04-01

    Physiological changes during pregnancy affect routine tests for iron deficiency. The reticulocyte haemoglobin equivalent (RET-He) and serum-soluble transferrin receptor (sTfR) assay are newer diagnostic parameters for the detection of iron deficiency, combined in the Thomas diagnostic plot. We used this plot to determine the iron status of pregnant women presenting for their first visit to an antenatal clinic in Bloemfontein, South Africa. Routine laboratory tests (serum ferritin, full blood count and C-reactive protein) and RET-He and sTfR were performed. The iron status was determined using the Thomas plot. For this study, 103 pregnant women were recruited. According to the Thomas plot, 72.8% of the participants had normal iron stores and erythropoiesis. Iron-deficient erythropoiesis was detected in 12.6%. A third of participants were anaemic. Serum ferritin showed excellent sensitivity but poor specificity for detecting depleted iron stores. HIV status had no influence on the iron status of the participants. Our findings reiterate that causes other than iron deficiency should be considered in anaemic individuals. When compared with the Thomas plot, a low serum ferritin is a sensitive but nonspecific indicator of iron deficiency. The Thomas plot may provide useful information to identify pregnant individuals in whom haematologic parameters indicate limited iron availability for erythropoiesis. © 2015 John Wiley & Sons Ltd.

  5. Iron status markers in 224 indigenous Greenlanders

    DEFF Research Database (Denmark)

    Milman, N; Byg, K E; Mulvad, G

    2001-01-01

    OBJECTIVE: To evaluate iron status in indigenous Greenlanders and its relationship to gender, age and intake of traditional Greenlandic foods. Methods: Serum ferritin, serum transferrin saturation and haemoglobin were evaluated in a population survey in 1993-1994 comprising 224 Greenlandic...... of living. Consumption of traditional foods was assessed by questionnaire. RESULTS: Intake of traditional foods was more prevalent among elderly than among young individuals and more frequent in Uummannaq than in Ilulissat and Nuuk. Ferritin levels were higher in men than in women (p....06; women, r(s)=0.73, ptraditional foods was correlated with ferritin in men (r(s)=0.29, p=0.01) and women (r(s)=0.40, p

  6. Study of ferritin nanoparticles

    International Nuclear Information System (INIS)

    Lancok, A.; Kohout, J.; Volfova, L.; Miglierini, M.

    2015-01-01

    Moessbauer spectrometry confirms the presence of hematite, ferrihydrite and maghemite/magnetite in ferritin derived from human spleen tissues. The minerals are present in a form of small (about 4-5 nm in size) grains with highly disordered structure. Consequently, at room temperature all agglomerates of ferritin nanoparticles show non-magnetic behaviour. Magnetic states are revealed at low enough temperatures below the so-called blocking temperature. Employing Moessbauer effect measurements, the latter was determined to be of 16 K for the human spleen. Structural features of these tissues were studied by TEM technique. Employing 57 Fe nuclei as local probes both structural and magnetic features of the biological materials were investigated by Moessbauer spectrometry. It was possible to identify iron atoms and their neighbours. (authors)

  7. Preferential Iron Trafficking Characterizes Glioblastoma Stem-like Cells

    DEFF Research Database (Denmark)

    Schonberg, David L; Miller, Tyler E; Wu, Qiulian

    2015-01-01

    Glioblastomas display hierarchies with self-renewing cancer stem-like cells (CSCs). RNA sequencing and enhancer mapping revealed regulatory programs unique to CSCs causing upregulation of the iron transporter transferrin, the top differentially expressed gene compared with tissue......, to propagate and form tumors in vivo. Depleting ferritin disrupted CSC mitotic progression, through the STAT3-FoxM1 regulatory axis, revealing an iron-regulated CSC pathway. Iron is a unique, primordial metal fundamental for earliest life forms, on which CSCs have an epigenetically programmed, targetable...

  8. Dietary Iron Intake and Serum Ferritin Concentration in 213 Patients Homozygous for the HFEC282Y Hemochromatosis Mutation

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    Victor R Gordeuk

    2012-01-01

    Full Text Available BACKGROUND: HFEC282Y homozygotes have an increased risk for developing increased iron stores and related disorders. It is controversial whether dietary iron restrictions should be recommended to such individuals.

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

    Science.gov (United States)

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

    2017-12-01

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

  10. Ceruloplasmin/Transferrin Ratio Changes in Alzheimer's Disease

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    Rosanna Squitti

    2011-01-01

    Full Text Available The link between iron and Alzheimer's disease (AD has been mainly investigated with a focus on the local accumulation of this metal in specific areas of the brain that are critical for AD. In the present study, we have instead looked at systemic variations of markers of iron metabolism. We measured serum levels of iron, ceruloplasmin, and transferrin and calculated the transferrin saturation and the ceruloplasmin to transferrin ratio (Cp/Tf. Cp/Tf and transferrin saturation increased in AD patients. Cp/Tf ratios also correlated positively with peroxide levels and negatively with serum iron concentrations. Elevated values of ceruloplasmin, peroxides, and Cp/Tf inversely correlated with MMSE scores. Isolated medial temporal lobe atrophy positively correlated with Cp/Tf and negatively with serum iron. All these findings indicate that the local iron accumulation found in brain areas critical for AD should be viewed in the frame of iron systemic alterations.

  11. The effect of nutrition knowledge and dietary iron intake on iron status in young women.

    Science.gov (United States)

    Leonard, Alecia J; Chalmers, Kerry A; Collins, Clare E; Patterson, Amanda J

    2014-10-01

    Previous research on the relationships between general nutrition knowledge and dietary intake, and dietary iron intake and iron status has produced inconsistent results. Currently, no study has focused on knowledge of dietary iron and its effect on dietary iron intake. This study aimed to determine whether nutrition knowledge of iron is related to dietary iron intake in young women, and subsequently whether greater knowledge and intake translates into better iron status. A cross-sectional assessment of nutrition knowledge of iron, dietary iron intake and iron status was conducted in women aged 18-35 years living in Newcastle, NSW, Australia. Iron status was assessed by serum ferritin, haemoglobin, soluble transferrin receptor and alpha-1-glycoprotein. One hundred and seven women (27.8 ± 4.7 years) completed the nutrition knowledge questionnaire and FFQ. Of these, 74 (70%) also had biomarkers of iron status measured. Mean iron intake was 11.2 ± 3.8 mg/day. There was no association between nutrition knowledge score and whether the women met the RDI for iron (F (1, 102) = .40, P = .53). A positive correlation was shown between nutrition knowledge score and iron intake (mg/day) (r = 0.25, P = .01). Serum ferritin was positively associated with the frequency of flesh food intake (r = .27 P = .02). Vegetarians (including partial vegetarians) had significantly lower serum ferritin levels than non-vegetarians (F (1, 71) = 7.44, P = .01). Significant positive correlations found between higher flesh food intake and biomarkers of iron status suggest that educating non-vegetarians about the benefits of increased flesh food consumption and vegetarians about dietary iron enhancers and inhibitors may have potential for addressing the high rates of iron deficiency among young women. Crown Copyright © 2014. Published by Elsevier Ltd. All rights reserved.

  12. Kinetic Studies of Iron Deposition Catalyzed by Recombinant Human Liver Heavy, and Light Ferritins and Azotobacter Vinelandii Bacterioferritin Using O2 and H2O2 as Oxidants

    Science.gov (United States)

    Bunker, Jared; Lowry, Thomas; Davis, Garrett; Zhang, Bo; Brosnahan, David; Lindsay, Stuart; Costen, Robert; Choi, Sang; Arosio, Paolo; Watt, Gerald D.

    2005-01-01

    The discrepancy between predicted and measured H2O2 formation during iron deposition with recombinant heavy human liver ferritin (rHF) was attributed to reaction with the iron protein complex [Biochemistry 40 (2001) 10832-10838]. This proposal was examined by stopped-flow kinetic studies and analysis for H2O2 production using (1) rHF, and Azotobacter vinelandii bacterial ferritin (AvBF), each containing 24 identical subunits with ferroxidase centers; (2) site-altered rHF mutants with functional and dysfunctional ferroxidase centers; and (3) rccombinant human liver light ferritin (rLF), containing 110 ferroxidase center. For rHF, nearly identical pseudo-first-order rate constants of 0.18 per second at pH 7.5 were measured for Fe(2+) oxidation by both O2 and H2O2, but for rLF, the rate with O2 was 200-fold slower than that for H2O2 (k-0.22 per second). A Fe(2+)/O2 stoichiometry near 2.4 was measured for rHF and its site altered forms, suggesting formation of H2O2. Direct measurements revealed no H2O2 free in solution 0.5-10 min after all Fe(2+) was oxidized at pH 6.5 or 7.5. These results are consistent with initial H2O2 formation, which rapidly reacts in a secondary reaction with unidentified solution components. Using measured rate constants for rHF, simulations showed that steady-state H2O2 concentrations peaked at 14 pM at approx. 600 ms and decreased to zero at 10-30 s. rLF did not produce measurable H2O2 but apparently conducted the secondary reaction with H2O2. Fe(2+)/O2 values of 4.0 were measured for AvBF. Stopped-flow measurements with AvBF showed that both H2O2 and O2 react at the same rate (k=0.34 per second), that is faster than the reactions with rHF. Simulations suggest that AvBF reduces O2 directly to H2O without intermediate H2O2 formation.

  13. Magnetism in plant and mammalian ferritin

    International Nuclear Information System (INIS)

    Bauminger, E.R.; Nowik, I.

    1989-01-01

    A rich variety of magnetic phenomena is observed in Moessbauer studies of ferritin. Depending on the amount of iron in the horse spleen ferritin core, a paramagnetic relaxation spectrum, or quadrupole split doublet or a magnetically split sextet showing superparamagnetism, are obtained at 4.1 K. Moessbauer studies of the recently prepared iron loaded concanavalin A yield hyperfine parameters identical to those found previously in mammalian ferritin, yet show the existence of larger iron aggregates. Due to the larger particle size it is possible to follow the magnetic hyperfine field and to obtain the magnetic ordering temperature as 240 K. This is exactly the Neel temperature of ferrihydrite, thus establishing that this is indeed the iron compound in the ferritin core. (orig.)

  14. The importance of the stem cell marker prominin-1/CD133 in the uptake of transferrin and in iron metabolism in human colon cancer Caco-2 cells.

    Directory of Open Access Journals (Sweden)

    Erika Bourseau-Guilmain

    Full Text Available As the pentaspan stem cell marker CD133 was shown to bind cholesterol and to localize in plasma membrane protrusions, we investigated a possible function for CD133 in endocytosis. Using the CD133 siRNA knockdown strategy and non-differentiated human colon cancer Caco-2 cells that constitutively over-expressed CD133, we provide for the first time direct evidence for a role of CD133 in the intracellular accumulation of fluorescently labeled extracellular compounds. Assessed using AC133 monoclonal antibody, CD133 knockdown was shown to improve Alexa488-transferrin (Tf uptake in Caco-2 cells but had no impact on FITC-dextran or FITC-cholera-toxin. Absence of effect of the CD133 knockdown on Tf recycling established a role for CD133 in inhibiting Tf endocytosis rather than in stimulating Tf exocytosis. Use of previously identified inhibitors of known endocytic pathways and the positive impact of CD133 knockdown on cellular uptake of clathrin-endocytosed synthetic lipid nanocapsules supported that CD133 impact on endocytosis was primarily ascribed to the clathrin pathway. Also, cholesterol extraction with methyl-β-cyclodextrine up regulated Tf uptake at greater intensity in the CD133(high situation than in the CD133(low situation, thus suggesting a role for cholesterol in the inhibitory effect of CD133 on endocytosis. Interestingly, cell treatment with the AC133 antibody down regulated Tf uptake, thus demonstrating that direct extracellular binding to CD133 could affect endocytosis. Moreover, flow cytometry and confocal microscopy established that down regulation of CD133 improved the accessibility to the TfR from the extracellular space, providing a mechanism by which CD133 inhibited Tf uptake. As Tf is involved in supplying iron to the cell, effects of iron supplementation and deprivation on CD133/AC133 expression were investigated. Both demonstrated a dose-dependent down regulation here discussed to the light of transcriptional and post

  15. Distinguishing ferritin from apoferritin using magnetic force microscopy

    International Nuclear Information System (INIS)

    Nocera, Tanya M; Zeng, Yuzhi; Agarwal, Gunjan

    2014-01-01

    Estimating the amount of iron-replete ferritin versus iron-deficient apoferritin proteins is important in biomedical and nanotechnology applications. This work introduces a simple and novel approach to quantify ferritin by using magnetic force microscopy (MFM). We demonstrate how high magnetic moment probes enhance the magnitude of MFM signal, thus enabling accurate quantitative estimation of ferritin content in ferritin/apoferritin mixtures in vitro. We envisage MFM could be adapted to accurately determine ferritin content in protein mixtures or in small aliquots of clinical samples. (fast track communication)

  16. Distinguishing ferritin from apoferritin using magnetic force microscopy

    Science.gov (United States)

    Nocera, Tanya M.; Zeng, Yuzhi; Agarwal, Gunjan

    2014-11-01

    Estimating the amount of iron-replete ferritin versus iron-deficient apoferritin proteins is important in biomedical and nanotechnology applications. This work introduces a simple and novel approach to quantify ferritin by using magnetic force microscopy (MFM). We demonstrate how high magnetic moment probes enhance the magnitude of MFM signal, thus enabling accurate quantitative estimation of ferritin content in ferritin/apoferritin mixtures in vitro. We envisage MFM could be adapted to accurately determine ferritin content in protein mixtures or in small aliquots of clinical samples.

  17. SERUM IRON PARAMETERS IN ALCOHOLIC CIRRHOSIS, CRYPTOGENIC CIRRHOSIS, CHRONIC HEPATITIS B AND CHRONIC HEPATITIS C

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    Sajeevan K. C

    2016-11-01

    Full Text Available BACKGROUND Regular monitoring of serum iron parameters is helpful for assessing the severity of alcoholic liver disease. Assessment of serum iron parameters are used for screening hereditary haemochromatosis in chronic liver disease. Serum iron parameters in chronic liver disease have not been clearly described in most of the studies. The aim of this study was to assess the serum iron, Total Iron Binding Capacity (TIBC, transferrin saturation and ferritin levels in common chronic liver disease like alcoholic cirrhosis, cryptogenic cirrhosis, chronic hepatitis C and chronic hepatitis B. MATERIALS AND METHODS 110 consecutive patients with chronic liver disease admitted to the Gastroenterology Department, Government Medical College, Kozhikode were selected for the study. The categories of chronic liver disease included in our study were alcoholic cirrhosis (Group I, n = 40, cryptogenic cirrhosis (Group II, n = 30, chronic hepatitis C (Group III, n = 20 and chronic hepatitis B (Group IV, n = 20. Serum iron, ferritin, total iron binding capacity and transferrin saturation were estimated in the fasting sample. Statistical Analysis- Analysis was performed using nonparametric Kruskal-Wallis and Bonferroni test to assess statistical significance of difference of continuous variables among and between groups, respectively. The results were considered statistically significant at the level of p <0.05. RESULTS The serum iron level was normal and total iron binding capacity was low in all the four groups of chronic liver disease. Serum ferritin and transferrin saturation were significantly higher in alcoholic cirrhosis in comparison with cryptogenic cirrhosis and chronic hepatitis B, but was not statistically significant in comparison with chronic hepatitis C. CONCLUSION We observed irregularities in iron status in patients with alcoholic cirrhosis, cryptogenic cirrhosis, chronic hepatitis C and chronic hepatitis B.

  18. Iron status and its relations with oxidative damage and bone loss during long-duration space flight on the International Space Station.

    Science.gov (United States)

    Zwart, Sara R; Morgan, Jennifer L L; Smith, Scott M

    2013-07-01

    Increases in stored iron and dietary intake of iron during space flight have raised concern about the risk of excess iron and oxidative damage, particularly in bone. The objectives of this study were to perform a comprehensive assessment of iron status in men and women before, during, and after long-duration space flight and to quantify the association of iron status with oxidative damage and bone loss. Fasting blood and 24-h urine samples were collected from 23 crew members before, during, and after missions lasting 50 to 247 d to the International Space Station. Serum ferritin and body iron increased early in flight, and transferrin and transferrin receptors decreased later, which indicated that early increases in body iron stores occurred through the mobilization of iron to storage tissues. Acute phase proteins indicated no evidence of an inflammatory response during flight. Serum ferritin was positively correlated with the oxidative damage markers 8-hydroxy-2'-deoxyguanosine (r = 0.53, P < 0.001) and prostaglandin F2α (r = 0.26, P < 0.001), and the greater the area under the curve for ferritin during flight, the greater the decrease in bone mineral density in the total hip (P = 0.031), trochanter (P = 0.006), hip neck (P = 0.044), and pelvis (P = 0.049) after flight. Increased iron stores may be a risk factor for oxidative damage and bone resorption.

  19. Iron supplementation is positively associated with increased serum ferritin levels in 9-month-old Danish infants

    DEFF Research Database (Denmark)

    Gondolf, Ulla Holmboe; Tetens, Inge; Michaelsen, Kim Fleischer

    2013-01-01

    recommendation (>400 ml Fe-fortified formula or 8 mg Fe/d) is associated with more favourable levels of Fe status indicators compared to those not following the recommendation. A random sample of 9-month-old infants living in Copenhagen was established and 312 healthy term infants were examined at 9·1 (sd 0......Fe deficiency is still common in infancy, even in affluent societies, and has prompted Fe fortification of food products and use of Fe supplements in many populations. In the present study, we tested the hypothesis that Fe status among 9-month-old infants following the Danish Fe supplementation......·3) months of age. Blood samples were available from 278 infants. Overall, twenty infants (7·8 %) had Fe deficiency (serum ferritin

  20. Effect of short-term intravenous ascorbic acid on reducing ferritin in hemodialysis patients.

    Science.gov (United States)

    Jalalzadeh, M; Shekari, E; Mirzamohammadi, F; Ghadiani, M H

    2012-05-01

    Resistance to recombinant erythropoietin (rEPO) in hemodialysis patients may be due to inadequate iron recruitment and defect in iron use. In this cross over randomized clinical trial, 30 hemodialysis patients with serum ferritin levels of ≥500 ng/ml, hemoglobin ≤11.0 g/dl, and transferrin saturation (TSAT) of 20% or less were administrated intravenous iron (50-100 mg/wk) and rEPO (120-360 U/kg/wk) for 6 months. Patients were excluded if there was a clear explanation for rEPO hyporesponsiveness. Patients were divided into two groups. Group1 received standard care and 500 mg of intravenous ascorbic acid (IVAA) with each dialysis session in the first week of each month for a total of 3 months. Group 2 received standard care only. After 2 month washout period, groups were crossed over. Each month hemoglobin (Hb) was assessed. Iron, TIBC (transferrin iron binding capacity), TSAT, iPTH (intact parathyroid hormone), liver enzymes, albumin and cholesterol levels were measured every 3 months. After 3 months of intervention, Hb significantly increased from 10.11 to 12.19 g/dl (P <0 0.001; 95% confidence interval [CI] 2.7-1.4) and TSAT increased from 18.9 to 28.1% (P = 0.008; 95% CI 0.09-3), while ferritin and serum iron declined significantly from 1391 to 938 ng/ml (P = 0.001; 95% CI 216-689), 97.2 to 64.6 (P = 0.001; 95% CI 14.8-50.4) in the study group. Change of Hb over time in IVAA group was significant (P < 0.0005). There were significant differences between two groups in change of Hb level over time (P < 0.0005) and treatment effect (P = 0.002). Baseline laboratory tests were similar in the two groups and there was no carry over effect at phase 2. We showed that low amount of IVAA could reduce ferritin level and enhance Hb and TSAT, suggesting improved iron utilization.

  1. Role of Breastfeeding and Complementary Food on Hemoglobin and Ferritin Levels in a Cambodian Cross-Sectional Sample of Children Aged 3 to 24 Months.

    Directory of Open Access Journals (Sweden)

    Anika Reinbott

    Full Text Available Iron deficiency derives from a low intake of dietary iron, poor absorption of iron, and high requirements due to growth as well as blood loss. An estimated number of about 50% of all anemia may be attributed to iron deficiency among young children in Cambodia.A cross-sectional survey was conducted in rural Cambodia in September 2012. Villages in pre-selected communes were randomly chosen using stunting as a primary indicator of nutritional status. In total, 928 randomly selected households with children aged 3-23 months were included. Hemoglobin, ferritin, soluble transferrin receptor (sTfR, and retinol binding protein (RBP were assessed from capillary blood samples. In addition, length/height and weight of mothers and children were taken and data on dietary diversity was collected. A child feeding index (CFI was created. Associations between biomarkers of iron and vitamin A status and nutritional status or food intake were explored.Anemia prevalence was highest among 6- to 12-months-olds (71%. Ferritin and sTfR inversely correlated and were significantly associated with hemoglobin concentrations. The consumption of animal source foods (ASF significantly impacts on the interaction between ferritin, sTfR and hemoglobin. Concentrations of RBP were significantly higher in children who had received a vitamin A supplement. The CFI was associated with sTfR and hemoglobin. Lower length and weight were associated with lower ferritin levels and showed an indirect effect on hemoglobin through ferritin.Nutrition programs targeting children under 2 years of age need to focus on the preparation of complementary foods with high nutrient density to sustainably prevent micronutrient deficiency and generally improve nutritional status. Future assessments of the micronutrient status should include identification of hemoglobinopathies and parasitic infections to better understand all causes of anemia in Cambodian infants and young children.German Clinical Trials

  2. Serum vitamin B12, folic acid and ferritin levels in patients with migraine

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    Abdullah Acar

    2011-06-01

    Full Text Available OBJECTIVE: It has been reported that disability due to migraine may be reduced with homocysteine-lowering treatment including folic acid and vitamin B12. In addition, recently the periaqueductal gray matter iron deposits have been found to be increased in migraine patients. There are few studies regarding vitamin B12, folic acid, ferritin and transferrin levels in patients with migraine. The aims of this study was to measure vitamin B12, folic acid, ferritin and transferrin levels in patients with migraine and compare them with the control group. METHODS: Fifty-one consecutive newly diagnosed migraine patients who did not receive any vitamin supplement medication were enrolled. The study group consisted of 51 patients, suffering from migraine with aura (n= 23 and migraine without aura (n= 28. The control group consisted of 28 healthy participants without history of headache, anemia and vitamin supplement. Serum vitamin B12, folic acid, ferritin and transferin levels were measured using a chemiluminescence method. RESULTS: Migraine patients had significantly lower concentrations of vitamin B12 and folic acid compared with the healthy controls (for vitamin B12; 215.6±133.7 pg/ml vs. 289.9±12 pg/ml, respectively, p=0.005; for folic acid; 6.74 ± 4.31 pg/ml vs. 8.47 ± 1.85 pg/ml, respectively, p=0.048. The vitamin B12 levels were found to be significantly lower during attacks in migraine patients than in interictal periods (177.3 ± 139.2 pg/ml vs 252.5 ± 119.5 pg/ml, p=0.043. There were no differences in folic acid, ferritin, and transferritin levels between during attacks and in interictal period of patients with migraine (p>0.05. The ferritin levels were found to be significantly lower during attacks in migraine patients than in interictal periods (43.4 ± 41.1 mg/ml, vs 75.4 ± 51.7, mg/ml, p=0.018. CONCLUSION: Migraine patients had lower serum vitamin B12 and folic acid levels than healthy subjects. These findings supported that vitamin B12

  3. Serum ferritin in recurrent oral ulceration

    International Nuclear Information System (INIS)

    Challacombe, S.J.; Scully, C.; Keevil, B.; Lehner, T.

    1983-01-01

    A sensitive radio-assay for ferritin was developed and used to examine serum ferritin levels in 105 patients with recurrent oral ulceration (ROU), 41 patients with Behcet's syndrome (BS), 42 with other ulcerative oral lesions, 35 patients with non-ulcerative oral lesions and in 78 controls. Ferritin levels increased with age and were significantly higher in males than females. The mean ferritin concentrations in male patients with ROU, BS or with other oral ulcers were significantly reduced in comparison with controls, and in female patients were significantly reduced in those with major aphthous ulcers. The prevalence of low serum ferritin levels was about 8% in patients with ROU, 15% in BS and 9.5% in patients with other ulcerative oral lesions, compared with less than 3% in patients with non-ulcerative oral disorders and in controls. Most of the iron-deficient patients were female. Serum ferritin levels did not directly correlate with serum iron levels and may be a more accurate indicator of iron deficiency. Furthermore, serum ferritin can distinguish between patients with true iron deficiency and those with secondary sideropenia. It is suggested that in a small number of patients, oral ulceration may be a presenting sign of iron deficiency, and that in a further small proportion of patients, ROU already present will be exacerbated by concurrent iron deficiency. Both groups will show a therapeutic response to correction of the iron deficiency. The results suggest that serum ferritin levels are a useful part of the haematological investigatons in patients with ROU. (author)

  4. Low iron stores are related to higher blood concentrations of manganese, cobalt and cadmium in non-smoking, Norwegian women in the HUNT 2 study

    Energy Technology Data Exchange (ETDEWEB)

    Margrete Meltzer, Helle, E-mail: helle.margrete.meltzer@fhi.no [Division of Environmental Medicine, Department of Food Safety and Nutrition, Norwegian Institute of Public Health, PO Box 4404 Nydalen, N-0403 Oslo (Norway); Lise Brantsaeter, Anne [Division of Environmental Medicine, Department of Food Safety and Nutrition, Norwegian Institute of Public Health, PO Box 4404 Nydalen, N-0403 Oslo (Norway); Borch-Iohnsen, Berit [Institute of Basic Medical Sciences, Department of Nutrition, University of Oslo, PO Box 1046 Blindern, N-0316 Oslo (Norway); Ellingsen, Dag G. [National Institute of Occupational Health, PO Box 8149 Dep, N-0033 Oslo (Norway); Alexander, Jan [Division of Environmental Medicine, Department of Food Safety and Nutrition, Norwegian Institute of Public Health, PO Box 4404 Nydalen, N-0403 Oslo (Norway); Thomassen, Yngvar [National Institute of Occupational Health, PO Box 8149 Dep, N-0033 Oslo (Norway); Stigum, Hein [Division of Epidemiology, Department of Chronic Diseases, Norwegian Institute of Public Health, PO Box 4404 Nydalen, N-0403 Oslo (Norway); Ydersbond, Trond A. [Statistics Norway, P.Box 8131 Dep, N-0033 Oslo (Norway)

    2010-07-15

    Low iron (Fe) stores may influence absorption or transport of divalent metals in blood. To obtain more knowledge about such associations, the divalent metal ions cadmium (Cd), manganese (Mn), cobalt (Co), copper (Cu), zinc (Zn) and lead (Pb) and parameters of Fe metabolism (serum ferritin, haemoglobin (Hb) and transferrin) were investigated in 448 healthy, menstruating non-smoking women, age 20-55 years (mean 38 years), participating in the Norwegian HUNT 2 study. The study population was stratified for serum ferritin: 257 were iron-depleted (serum ferritin <12 {mu}g/L) and 84 had iron deficiency anaemia (serum ferritin <12 {mu}g/L and Hb<120 g/L). The low ferritin group had increased blood concentrations of Mn, Co and Cd but normal concentrations of Cu, Zn and Pb. In multiple regression models, ferritin emerged as the main determinant of Mn, Co and Cd (p<0.001), while no significant associations with Cu, Zn and Pb were found. Adjusted r{sup 2} for the models were 0.28, 0.48 and 0.34, respectively. Strong positive associations between blood concentrations of Mn, Co and Cd were observed, also when controlled for their common association with ferritin. Apart from these associations, the models showed no significant interactions between the six divalent metals studied. Very mild anaemia (110{<=}Hb<120 g/L) did not seem to have any effect independent of low ferritin. Approximately 26% of the women with iron deficiency anaemia had high concentrations of all of Mn, Co and Cd as opposed to 2.3% of iron-replete subjects. The results confirm that low serum ferritin may have an impact on body kinetics of certain divalent metal ions, but not all. Only a fraction of women with low iron status exhibited an increased blood concentration of divalent metals, providing indication of complexities in the body's handling of these metals.

  5. Low iron stores are related to higher blood concentrations of manganese, cobalt and cadmium in non-smoking, Norwegian women in the HUNT 2 study

    International Nuclear Information System (INIS)

    Margrete Meltzer, Helle; Lise Brantsaeter, Anne; Borch-Iohnsen, Berit; Ellingsen, Dag G.; Alexander, Jan; Thomassen, Yngvar; Stigum, Hein; Ydersbond, Trond A.

    2010-01-01

    Low iron (Fe) stores may influence absorption or transport of divalent metals in blood. To obtain more knowledge about such associations, the divalent metal ions cadmium (Cd), manganese (Mn), cobalt (Co), copper (Cu), zinc (Zn) and lead (Pb) and parameters of Fe metabolism (serum ferritin, haemoglobin (Hb) and transferrin) were investigated in 448 healthy, menstruating non-smoking women, age 20-55 years (mean 38 years), participating in the Norwegian HUNT 2 study. The study population was stratified for serum ferritin: 257 were iron-depleted (serum ferritin 2 for the models were 0.28, 0.48 and 0.34, respectively. Strong positive associations between blood concentrations of Mn, Co and Cd were observed, also when controlled for their common association with ferritin. Apart from these associations, the models showed no significant interactions between the six divalent metals studied. Very mild anaemia (110≤Hb<120 g/L) did not seem to have any effect independent of low ferritin. Approximately 26% of the women with iron deficiency anaemia had high concentrations of all of Mn, Co and Cd as opposed to 2.3% of iron-replete subjects. The results confirm that low serum ferritin may have an impact on body kinetics of certain divalent metal ions, but not all. Only a fraction of women with low iron status exhibited an increased blood concentration of divalent metals, providing indication of complexities in the body's handling of these metals.

  6. The influence of iron status and genetic polymorphisms in the HFE gene on the risk for postoperative complications after bariatric surgery: a prospective cohort study in 1,064 patients

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    Freedman-Weiss Mollie

    2011-01-01

    Full Text Available Abstract Background Gastric bypass surgery is a highly effective therapy for long-term weight loss in severely obese patients, but carries significant perioperative risks including infection, wound dehiscence, and leaks from staple breakdown. Iron status can affect immune function and wound healing, thus may influence peri-operative complications. Common mutations in the HFE gene, the gene responsible for the iron overload disorder hereditary hemochromatosis, may impact iron status. Methods We analyzed 1064 extremely obese Caucasian individuals who underwent open and laparoscopic Roux-n-Y gastric bypass surgery at the Geisinger Clinic. Serum iron, ferritin, transferrin, and iron binding capacity were measured pre-operatively. All patients had intra-operative liver biopsies and were genotyped for the C282Y and H63D mutations in the HFE gene. Associations between surgical complications and serum iron measures, HFE gene status, and liver iron histology were determined. Results We found that increased serum iron and transferrin saturation were present in patients with any post-operative complication, and that increased serum ferritin was also increased in patients with major complications. Increased serum transferrin saturation was also associated with wound complications in open RYGB, and transferrin saturation and ferritin with prolonged lengths of stay. The presence of 2 or more HFE mutations was associated with overall complications as well as wound complications in open RYGB. No differences were found in complication rates between those with stainable liver iron and those without. Conclusion Serum iron status and HFE genotype may be associated with complications following RYGB surgery in the extremely obese.

  7. Serum Ferritin Levels Are Lower in Children With Tic Disorders Compared with Children Without Tics: A Cross-Sectional Study.

    Science.gov (United States)

    Avrahami, Matan; Barzilay, Ran; HarGil, Miki; Weizman, Abraham; Watemberg, Nathan

    2017-03-01

    Alteration in peripheral iron indices has been reported in a number of movement disorders, particularly Parkinson's disease. We hypothesized that iron stores may be diminished in children at an early stage of tic disorder. Using data retrieved from electronic medical records, we compared serum ferritin levels, an indicator of body iron store balance, in drug-naive children diagnosed for the first time with tic disorder (study group; N = 47, 32 boys/15 girls, aged 8.66 ± 3.17 years) compared to age- and sex-matched children with headaches (comparison group, n = 100, 62 boys/38 girls, aged 9.51 ± 3.15 years) treated in the same pediatric neurological clinic. Mean serum ferritin levels were significantly lower (-32%, p = 0.01) in the tic disorder group compared to the headache group. No significant differences were detected in circulatory hemoglobin, iron, transferrin, and platelet count between the two groups. Our findings suggest that body iron stores may be reduced in children with recent-onset tic disorder.

  8. Iron-Binding Protein Degradation by Cysteine Proteases of Naegleria fowleri

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    Moisés Martínez-Castillo

    2015-01-01

    Full Text Available Naegleria fowleri causes acute and fulminant primary amoebic meningoencephalitis. This microorganism invades its host by penetrating the olfactory mucosa and then traveling up the mesaxonal spaces and crossing the cribriform plate; finally, the trophozoites invade the olfactory bulbs. During its invasion, the protozoan obtains nutrients such as proteins, lipids, carbohydrates, and cationic ions (e.g., iron, calcium, and sodium from the host. However, the mechanism by which these ions are obtained, particularly iron, is poorly understood. In the present study, we evaluated the ability of N. fowleri to degrade iron-binding proteins, including hololactoferrin, transferrin, ferritin, and hemoglobin. Zymography assays were performed for each substrate under physiological conditions (pH 7 at 37°C employing conditioned medium (CM and total crude extracts (TCEs of N. fowleri. Different degradation patterns with CM were observed for hololactoferrin, transferrin, and hemoglobin; however, CM did not cause ferritin degradation. In contrast, the TCEs degraded only hololactoferrin and transferrin. Inhibition assays revealed that cysteine proteases were involved in this process. Based on these results, we suggest that CM and TCEs of N. fowleri degrade iron-binding proteins by employing cysteine proteases, which enables the parasite to obtain iron to survive while invading the central nervous system.

  9. Assessment of iron deficiency in pregnant women by determining iron status

    International Nuclear Information System (INIS)

    Raza, N.; Munazza, B.; Ayub, M.; Sarwar, I

    2011-01-01

    Background: Pregnant women constitute a high risk group for iron deficiency. Maternal iron deficiency and particularly iron deficiency anaemia may be associated with detrimental effects on maternal and infant function and particularly with a higher risk of preterm delivery and delivery of low birth weight neonates. Objective of this study was to assess and compare the iron status of normal healthy non-pregnant women with that of pregnant women of Hazara Division. Methods: This study was conducted at Faculty of Health Sciences, Hazara University, and Ayub Medical College, Abbottabad from first March to /31 August 2006. Altogether 120 women, 90 pregnant at various stages of pregnancy and 30 non-pregnant women as control group were included in this study by convenience sampling. Their iron status was assessed by determination of haemoglobin (Hb), Serum ferritin, Serum-iron, Total Iron Binding Capacity (TIBC), Unsaturated Iron Binding Capacity (UIBC), and Percentage saturation of transferrin. Data generated on these variables were subjected to ANOVA and correlation analysis. Results: The salient finding of this study is a significant decrease in Hb, Serum ferritin, Serum iron, percentage saturation of transferrin and a significant increase in values of TIBC and a pronounced increase in UIBC in second and third trimester compared to first trimester in iron deficient pregnant women. The mean values of Hb, SF, and Fe/TIBC% were significantly lower in the cases than in the control and significantly higher values of TIBC and UIBC were observed in the cases compared to controls. Significant correlations were observed for TIBC, UIBC and Fe/TIBC% against serum iron in different trimesters of pregnancy. Conclusion: A high percentage of the pregnant women are iron deficient due to factors such as high parity, poor dietary habits and socioeconomic status. (author)

  10. HBsAg carrier status and the association between gestational diabetes with increased serum ferritin concentration in Chinese women.

    Science.gov (United States)

    Lao, Terence T; Tse, Ka-Yu; Chan, Louis Y; Tam, Kar-Fai; Ho, Lai-Fong

    2003-11-01

    To determine whether the high prevalence of hepatitis B surface antigen (HBsAg) carriage in our population can explain the previous observation of an association between increased maternal serum ferritin concentration and gestational diabetes in Hong Kong Chinese women. A retrospective study was performed on 767 nonanemic women with singleton pregnancy who had iron status assessed at 28-30 weeks. The result of the routine antenatal HBsAg screening was retrieved from patient records. The HBsAg-positive and -negative groups were compared for maternal characteristics, prevalence of gestational diabetes in the third trimester, prevalence of high serum ferritin and iron concentrations, and transferrin saturation, which is defined as a value in the highest quartile established by the measurements obtained from the HBsAg-negative group. The incidences of oral glucose tolerance test and gestational diabetes were significantly increased in the HBsAg-positive group. The HBsAg-positive women with gestational diabetes had significantly increased prevalence of high serum ferritin compared with the HBsAg-negative women, irrespective of the latter's gestational diabetes status. Multiple logistic regression analysis confirmed the independent association between HBsAg carrier status with gestational diabetes (relative risk 3.51, 95% CI 1.83-6.73) but excluded high ferritin as an independent factor. Our results indicate that maternal HBsAg carriage could explain in part the association between increased serum ferritin concentration with gestational diabetes in Hong Kong Chinese women, and that HBsAg carrier status is an independent risk factor for gestational diabetes.

  11. Ferritin Test

    Science.gov (United States)

    ... normal" values. By comparing your test results with reference values, you and your healthcare provider can see if ... along with other iron tests , when a routine complete blood count (CBC) shows that a person's hemoglobin and hematocrit ...

  12. ESA Hyporesponsiveness Is Associated with Adverse Events in Maintenance Hemodialysis (MHD Patients, But Not with Iron Storage.

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    Takahiro Kuragano

    Full Text Available It has been reported that hyporesponsiveness to erythropoiesis-stimulating agent (ESA is associated with adverse events in patients on maintenance hemodialysis (MHD. However, it has not been determined whether higher iron storage is associated with an improved response, including better survival, to ESA.We measured serum ferritin, hemoglobin (Hb, and transferrin saturation (TSAT levels every three months for two years in 1,095 MHD patients. The weekly dose of ESA to Hb ratio was also calculated as an index of ESA responsiveness (ERI.A significant correlation (p280; however, serum ferritin and TSAT levels did not predict a higher ERI. In the time-dependent Cox hazard model, the risk for a composite event in the patients with a high ERI (≥280 and a high ferritin level (≥100 ng/mL was significantly greater (hazard ratio [HR], 2.09, P = 0.033 than that for patients with a high ERI and a low ferritin (<100 ng/mL level.Hb was dependent upon ferritin levels in patients with ferritin levels <50 ng/mL but not in patients with ferritin levels ≥50 ng/mL. Patients with hyporesponsiveness to ESA had a greater risk of composite events, but ERI was unrelated to iron storage.

  13. Could the erythrocyte indices or serum ferritin predict the therapeutic response to a trial with oral iron during pregnancy? Results from the Accuracy study for Maternal Anaemia diagnosis (AMA).

    Science.gov (United States)

    Bresani Salvi, Cristiane Campello; Braga, Maria Cynthia; Figueirôa, José Natal; Batista Filho, Malaquias

    2016-08-12

    Treatment of maternal iron-deficiency anaemia can reduce risks of prematurity and low birth weight; hence a reliable diagnosis of maternal iron needs is critical. However, erythrocyte indices and serum ferritin have shown a weak correlation with iron status during pregnancy. This study verified the accuracy of those tests to predict the responsiveness to a therapeutic test with oral iron as reference standard for iron deficiency in pregnant women. A prospective diagnostic study phase 3 was conducted in a single prenatal care center in Northeast Brazil. Between August 2011 and October 2012 a consecutive sampling included 187 women in their 2(nd)-3(rd) trimesters of low-risk pregnancy and having anaemia (haemoglobin <11.0 g/dL). Until December 2012, 139 women completed a trial with daily pills of ferrous sulfate (40 mg of iron), during 23 to 125 days. Haemoglobin (Hb), other erythrocyte indices and ferritin (index-tests) were assessed pre-treatment by automated analyzers. Hb was performed also post-treatment to assess the therapeutic response by its post-pretreatment differences. We estimated sensitivity (Se), specificity (Sp), predictive values (PV), likelihood ratios (LR), diagnostic Odds Ratio (OR), area under Receiver Operating Characteristic curve (AUC), accuracy ratio and agreement coefficient of the index-tests against an increase of at least 0.55 Hb Z-score (reference standard test). We calculated the Z-scores according to the reference population from Centers for Disease Control and Prevention. Hb had a mean increase of 0.24 Z-score after 30 iron pills (p 0.013). All index-tests demonstrated PV- above 70 %, PV+ around 40 %, LR around 1.0, and AUC of 0.5 to 0.6. Hb and haematocrit had Se of 50 % (95 % CI 40 to 70); and Sp of 59 % (95 % CI 43 to 74) and 47 % (95 % CI 38 to 57), respectively. Ferritin, Mean Corpuscular Volume, Mean Corpuscular Haemoglobin, Mean Corpuscular Haemoglobin Concentration and Red blood cell Distribution Width had Se below 40

  14. Human macrophage hemoglobin-iron metabolism in vitro

    International Nuclear Information System (INIS)

    Custer, G.; Balcerzak, S.; Rinehart, J.

    1982-01-01

    An entirely in vitro technique was employed to characterize hemoglobin-iron metabolism by human macrophages obtained by culture of blood monocytes and pulmonary alveolar macrophages. Macrophages phagocytized about three times as many erythrocytes as monocytes and six times as many erythrocytes as pulmonary alveolar macrophages. The rate of subsequent release of 59 Fe to the extracellular transferrin pool was two- to fourfold greater for macrophages as compared to the other two cell types. The kinetics of 59 Fe-transferrin release were characterized by a relatively rapid early phase (hours 1-4) followed by a slow phase (hours 4-72) for all three cell types. Intracellular movement of iron was characterized by a rapid shift from hemoglobin to ferritin that was complete with the onset of the slow phase of extracellular release. A transient increase in 59 Fe associated with an intracellular protein eluting with transferrin was also observed within 1 hour after phagocytosis. The process of hemoglobin-iron release to extracellular transferrin was inhibited at 4 degrees C but was unaffected by inhibitory of protein synthesis, glycolysis, microtubule function, and microfilament function. These data emphasize the rapidity of macrophage hemoglobin iron metabolism, provide a model for characterization of this process in vitro, and in general confirm data obtained utilizing in vivo animal models

  15. Iron Status in Chronic Heart Failure: Impact on Symptoms, Functional Class and Submaximal Exercise Capacity.

    Science.gov (United States)

    Enjuanes, Cristina; Bruguera, Jordi; Grau, María; Cladellas, Mercé; Gonzalez, Gina; Meroño, Oona; Moliner-Borja, Pedro; Verdú, José M; Farré, Nuria; Comín-Colet, Josep

    2016-03-01

    To evaluate the effect of iron deficiency and anemia on submaximal exercise capacity in patients with chronic heart failure. We undertook a single-center cross-sectional study in a group of stable patients with chronic heart failure. At recruitment, patients provided baseline information and completed a 6-minute walk test to evaluate submaximal exercise capacity and exercise-induced symptoms. At the same time, blood samples were taken for serological evaluation. Iron deficiency was defined as ferritin < 100 ng/mL or transferrin saturation < 20% when ferritin is < 800 ng/mL. Additional markers of iron status were also measured. A total of 538 heart failure patients were eligible for inclusion, with an average age of 71 years and 33% were in New York Heart Association class III/IV. The mean distance walked in the test was 285 ± 101 meters among those with impaired iron status, vs 322 ± 113 meters (P=.002). Symptoms during the test were more frequent in iron deficiency patients (35% vs 27%; P=.028) and the most common symptom reported was fatigue. Multivariate logistic regression analyses showed that increased levels of soluble transferrin receptor indicating abnormal iron status were independently associated with advanced New York Heart Association class (P < .05). Multivariable analysis using generalized additive models, soluble transferrin receptor and ferritin index, both biomarkers measuring iron status, showed a significant, independent and linear association with submaximal exercise capacity (P=.03 for both). In contrast, hemoglobin levels were not significantly associated with 6-minute walk test distance in the multivariable analysis. In patients with chronic heart failure, iron deficiency but not anemia was associated with impaired submaximal exercise capacity and symptomatic functional limitation. Copyright © 2015 Sociedad Española de Cardiología. Published by Elsevier España, S.L.U. All rights reserved.

  16. Iron status and reproduction in US women: National Health and Nutrition Examination Survey, 1999-2006.

    Directory of Open Access Journals (Sweden)

    Elizabeth M Miller

    Full Text Available Women experience significant changes in iron status throughout their reproductive lifespans. While this is evident in regions with high rates of malnutrition and infectious disease, the extent of reproductive-related changes is less well known in countries with low rates of iron deficiency anemia, such as the United States. The goal of this study is determine the relationship between women's reproductive variables (pregnancy, parity, currently breastfeeding, regular menstruation, hormonal contraceptive use, and age at menarche and iron status (hemoglobin, ferritin, transferrin receptor, and % transferrin saturation using an anthropological framework for interpreting the results. Data from women aged 18-49 were taken from the 1999-2006 US NHANES, a nationally representative cross-sectional sample of US women. Using multiple imputation and complex survey statistics, women's reproductive variables were regressed against indicators of iron status. Pregnant women had significantly poorer iron status, by most indicators, than non-pregnant women. All biomarkers demonstrated significantly lower iron levels with increasing parity. Women who were having regular periods had iron indicators that suggested decreased iron levels, while women who used hormonal contraceptives had iron indicators that suggested increased iron levels. Despite relatively good iron status and widespread availability of iron-rich foods in the US, women still exhibit patterns of iron depletion across several reproductive variables of interest. These results contribute to an ecological approach to iron status that seeks to understand variation in iron status, with the hopes that appropriate, population-specific recommendations can be developed to improve women's health.

  17. Alternative expression of vacuolar iron transporter and ferritin genes leads to blue/purple coloration of flowers in tulip cv. 'Murasakizuisho'.

    Science.gov (United States)

    Shoji, Kazuaki; Momonoi, Kazumi; Tsuji, Tosiaki

    2010-02-01

    Flowers of tulip cv. 'Murasakizuisho' have a purple perianth except for the bottom region, which is blue in color even though it has the same anthocyanin, delphinidin 3-O-rutinoside, as the entire perianth. The development of the blue coloration in the perianth bottom is due to complexation by anthocyanin, flavonol and iron (Fe), as well as a vacuolar iron transporter, TgVit1. Although transient expression of TgVit1 in the purple cells led to a color change to light blue, the coloration of the transformed cells did not coincide with the dark blue color of the cells of the perianth bottom. We thought that another factor is required for the blue coloration of the cells of perianth bottom. To examine the effect of ferritin (FER), an Fe storage protein, on blue color development, we cloned an FER gene (TgFER1) and performed expression analyses. TgFER1 transcripts were found in the cells located in the upper region of the petals along with purple color development by anthocyanin and were not found in the blue cells of the perianth bottom. This gene expression is in contrast to that of TgVit1, expressed only in the cells of the perianth bottom. Co-expression of TgVIT1 and TgFER-RNAi, constructed for suppressing endogenous TgFER1 by RNA interference (RNAi), changed the purple petal cells to a dark blue color similar to that of the natural perianth bottom. These results strongly suggest that TgVit1 expression and TgFER1 suppression are critical for the development of blue color in the perianth bottom.

  18. Bioavailability and the mechanisms of intestinal absorption of iron from ferrous ascorbate and ferric polymaltose in experimental animals

    International Nuclear Information System (INIS)

    Johnson, G.; Jacobs, P.

    1990-01-01

    The comparative bioavailability from matching quantities of iron in the form of ferrous ascorbate or ferric polymaltose was defined in rats. Studies were carried out in the intact animals under basal conditions and also when requirements for this metal were either increased or decreased by manipulating stores or erythropoietic activity. No significant difference was found in the total quantity of iron absorbed from either salt or complex under any of these circumstances, suggesting that the mucosal mechanism regulating the overall process was common to both. However, the rate of transfer from the lumen into portal blood was distinctive, reaching a maximum with salt at 30 min compared to 24 h for the complex. To explore the possibility that iron from the two sources was initially handled by different subcellular pathways, the radiolabeled compounds were instilled into loops of bowel that had been isolated between ligatures in vivo. Enterocytes were harvested and fractionated, and incorporation into ferritin and transferrin was determined using RIA. From salt, iron appeared rapidly in duodenal but not ileal ferritin, whereas mucosal transferrin increased under conditions of stimulated absorption, suggesting that this protein may act as a shuttle for the metal. In contrast, iron from polymaltose showed a cumulative incorporation into duodenal ferritin over time that correlated with iron absorption, defined by the appearance of radiolabel in the serum and in the carcass; a similar pattern was demonstrable in ileal mucosal cells. Conversely, binding of iron to transferrin was minimal. No iron polymaltose was found within the mucosal cells. It is suggested that the low rate of iron transfer from this ferric complex may reflect its extracellular breakdown in the lumen of the gastrointestinal tract

  19. Role of androgen-mediated enhancement of erythropoiesis in the increased body iron stores of patients with polycystic ovary syndrome.

    Science.gov (United States)

    Escobar-Morreale, Héctor F; Luque-Ramírez, Manuel

    2011-04-01

    To determine whether androgen excess contributes to the increased body iron stores of polycystic ovary syndrome (PCOS) by stimulating erythropoietic activity, by measuring serum soluble transferrin receptor (sTfR) concentrations and its ratio to ferritin levels in patients with PCOS, as surrogate markers of erythropoietic activity and of the appropriateness of cellular iron demands for the total body iron contents, respectively. Case-control study. Academic hospital. One hundred-four patients with PCOS and 100 controls without androgen excess. Blood sampling and oral glucose tolerance test. Serum sTfR and ferritin concentrations, as well as indexes of androgen excess, inflammation, obesity, and insulin and glucose metabolism. Serum ferritin levels increased in women presenting with PCOS, obesity, and/or abnormal glucose tolerance, but these disorders did not influence sTfR concentrations. The sTfR/ferritin ratio decreased with obesity and abnormal glucose tolerance, and its logarithm correlated inversely with body mass index, free T, and C-reactive protein levels and directly with the insulin sensitivity and disposition indexes. A stepwise multiple regression analysis indicated that the changes in the insulin sensitivity index explained 7% of the variability of the logarithm of sTfR/ferritin ratio. Increased serum ferritin levels in patients with PCOS are associated with a reduction in insulin sensitivity but do not result from a putative enhancement of erythropoiesis by androgen excess. Copyright © 2011 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

  20. HO-1-mediated macroautophagy: a mechanism for unregulated iron deposition in aging and degenerating neural tissues.

    Science.gov (United States)

    Zukor, Hillel; Song, Wei; Liberman, Adrienne; Mui, Jeannie; Vali, Hojatollah; Fillebeen, Carine; Pantopoulos, Kostas; Wu, Ting-Di; Guerquin-Kern, Jean-Luc; Schipper, Hyman M

    2009-05-01

    Oxidative stress, deposition of non-transferrin iron, and mitochondrial insufficiency occur in the brains of patients with Alzheimer disease (AD) and Parkinson disease (PD). We previously demonstrated that heme oxygenase-1 (HO-1) is up-regulated in AD and PD brain and promotes the accumulation of non-transferrin iron in astroglial mitochondria. Herein, dynamic secondary ion mass spectrometry (SIMS) and other techniques were employed to ascertain (i) the impact of HO-1 over-expression on astroglial mitochondrial morphology in vitro, (ii) the topography of aberrant iron sequestration in astrocytes over-expressing HO-1, and (iii) the role of iron regulatory proteins (IRP) in HO-1-mediated iron deposition. Astroglial hHO-1 over-expression induced cytoplasmic vacuolation, mitochondrial membrane damage, and macroautophagy. HO-1 promoted trapping of redox-active iron and sulfur within many cytopathological profiles without impacting ferroportin, transferrin receptor, ferritin, and IRP2 protein levels or IRP1 activity. Thus, HO-1 activity promotes mitochondrial macroautophagy and sequestration of redox-active iron in astroglia independently of classical iron mobilization pathways. Glial HO-1 may be a rational therapeutic target in AD, PD, and other human CNS conditions characterized by the unregulated deposition of brain iron.

  1. The relationship between body iron stores and blood and urine cadmium concentrations in US never-smoking, non-pregnant women aged 20-49 years

    International Nuclear Information System (INIS)

    Gallagher, Carolyn M.; Chen, John J.; Kovach, John S.

    2011-01-01

    Background: Cadmium is a ubiquitous environmental pollutant associated with increased risk of leading causes of mortality and morbidity in women, including breast cancer and osteoporosis. Iron deficiency increases absorption of dietary cadmium, rendering women, who tend to have lower iron stores than men, more susceptible to cadmium uptake. We used body iron, a measure that incorporates both serum ferritin and soluble transferrin receptor, as recommended by the World Health Organization, to evaluate the relationships between iron status and urine and blood cadmium. Methods: Serum ferritin, soluble transferrin receptor, urine and blood cadmium values in never-smoking, non-pregnant, non-lactating, non-menopausal women aged 20-49 years (n=599) were obtained from the 2003-2008 National Health and Nutrition Examination Surveys. Body iron was calculated from serum ferritin and soluble transferrin receptor, and iron deficiency defined as body iron <0 mg/kg. Robust linear regression was used to evaluate the relationships between body iron and blood and urine cadmium, adjusted for age, race, poverty, body mass index, and parity. Results: Per incremental (mg/kg) increase in body iron, urine cadmium decreased by 0.003 μg/g creatinine and blood cadmium decreased by 0.014 μg/L. Iron deficiency was associated with 0.044 μg/g creatinine greater urine cadmium (95% CI=0.020, 0.069) and 0.162 μg/L greater blood cadmium (95% CI=0.132, 0.193). Conclusions: Iron deficiency is a risk factor for increased blood and urine cadmium among never-smoking, pre-menopausal, non-pregnant US women, independent of age, race, poverty, body mass index and parity. Expanding programs to detect and correct iron deficiency among non-pregnant women merits consideration as a potential means to reduce the risk of cadmium associated diseases. - Highlights: → Body iron was calculated from serum ferritin and soluble transferrin receptor. → Body iron was inversely associated with blood and urine cadmium

  2. The relationship between body iron stores and blood and urine cadmium concentrations in US never-smoking, non-pregnant women aged 20-49 years

    Energy Technology Data Exchange (ETDEWEB)

    Gallagher, Carolyn M., E-mail: 2crgallagher@optonline.net [PhD Program in Population Health and Clinical Outcomes Research, Stony Brook University, NY (United States) and Department of Preventive Medicine, Stony Brook University, Z-8036, Level 3, HSC, Stony Brook, NY 11794-8036 (United States); Chen, John J.; Kovach, John S. [Department of Preventive Medicine, Stony Brook University, Z-8036, Level 3, HSC, Stony Brook, NY 11794-8036 (United States)

    2011-07-15

    Background: Cadmium is a ubiquitous environmental pollutant associated with increased risk of leading causes of mortality and morbidity in women, including breast cancer and osteoporosis. Iron deficiency increases absorption of dietary cadmium, rendering women, who tend to have lower iron stores than men, more susceptible to cadmium uptake. We used body iron, a measure that incorporates both serum ferritin and soluble transferrin receptor, as recommended by the World Health Organization, to evaluate the relationships between iron status and urine and blood cadmium. Methods: Serum ferritin, soluble transferrin receptor, urine and blood cadmium values in never-smoking, non-pregnant, non-lactating, non-menopausal women aged 20-49 years (n=599) were obtained from the 2003-2008 National Health and Nutrition Examination Surveys. Body iron was calculated from serum ferritin and soluble transferrin receptor, and iron deficiency defined as body iron <0 mg/kg. Robust linear regression was used to evaluate the relationships between body iron and blood and urine cadmium, adjusted for age, race, poverty, body mass index, and parity. Results: Per incremental (mg/kg) increase in body iron, urine cadmium decreased by 0.003 {mu}g/g creatinine and blood cadmium decreased by 0.014 {mu}g/L. Iron deficiency was associated with 0.044 {mu}g/g creatinine greater urine cadmium (95% CI=0.020, 0.069) and 0.162 {mu}g/L greater blood cadmium (95% CI=0.132, 0.193). Conclusions: Iron deficiency is a risk factor for increased blood and urine cadmium among never-smoking, pre-menopausal, non-pregnant US women, independent of age, race, poverty, body mass index and parity. Expanding programs to detect and correct iron deficiency among non-pregnant women merits consideration as a potential means to reduce the risk of cadmium associated diseases. - Highlights: {yields} Body iron was calculated from serum ferritin and soluble transferrin receptor. {yields} Body iron was inversely associated with blood

  3. Iron Status and Inflammation in Early Stages of Chronic Kidney Disease

    Directory of Open Access Journals (Sweden)

    Ewelina Łukaszyk

    2015-06-01

    Full Text Available Background/Aims: One of the most common causes of anemia of chronic disease (ACD is chronic kidney disease. The main pathomechanism responsible for ACD is subclinical inflammation. The key element involved in iron metabolism is hepcidin, however, studies on new indices of iron status are in progress.The aim of the study was to assess the iron status in patients in early stages of chronic kidney disease, iron correlation with inflammation parameters and novel biomarkers of iron metabolism. Methods: The study included 69 patients. Standard laboratory measurements were used to measure the iron status, complete blood count, fibrinogen, prothrombin index, C-reactive protein concentration (CRP, creatinine, urea, uric acid. Commercially available kits were used to measure high-sensitivity CRP, interleukin 6 (IL-6, hepcidin-25, hemojuvelin, soluble transferrin receptor (sTfR, growth differentiation factor-15 (GDF-15 and zonulin. Results: Absolute iron deficiency was present in 17% of the patients, functional iron deficiency was present in 12% of the patients. Functional iron deficiency was associated with significantly higher serum levels of fibrinogen, ferritin, transferrin saturation, total iron binding capacity, hepcidin and older age relative to patients with absolute iron deficiency. In comparison with patients without iron deficiency, patients with functional iron deficiency were older, with lower prothrombin index, higher fibrinogen, CRP, hsCRP, sTfR, GDF-15, urea and lower eGFR. Hepcidin was predicted by markers of inflammation:ferritin, fibrinogen and IL-6. Conclusion: Inflammation is correlated with iron status. Novel biomarkers of iron metabolism might be useful to distinguish iron deficiency anemia connected with inflammation and absolute iron deficiency.

  4. The characteristics of transferrin variants by carbohydrate-deficient transferrin tests using capillary zone electrophoresis.

    Science.gov (United States)

    Yoo, Gilsung; Kim, Juwon; Yoon, Kap Joon; Lee, Jong-Han

    2018-04-17

    Transferrin is the major plasma transport protein for iron. We aimed to investigate the characteristics of transferrin variant by carbohydrate-deficient transferrin (CDT) test using capillary zone electrophoresis. We retrospectively analyzed the CDT tests of 2449 patients from March 2009 to May 2017 at a tertiary hospital in Korea. CDT was quantified using a Capillarys 2 system (Sebia, Lisses, France) by capillary zone electrophoresis. The characteristics of variant transferrin patterns using electropherogram of CDT tests were analyzed. Seventy-seven (3.1%) patients were classified as variant transferrin. Mean age of these patients was 51.8 years, and the male-to-female ratio was 3.5:1. The most common variants were the BC variants (n = 37), followed by the CD variants (n = 27), unclear patterns (n = 7), BD variants (n = 3), CC variants (n = 2), misclassification (n = 1). In the variant Tf group, the most common disease was alcoholic liver cirrhosis (n = 22, 28.6%), followed by the toxic effects of substances (n = 17, 22.1%), and mental and behavioral disorders attributable to alcohol (n = 11, 14.3%). Nonvariant group showed a predominance of the toxic substance effects (n = 880, 37.1%), a personal history of suicide attempts (n = 634, 26.7%), and mental and behavioral disorders due to alcohol (n = 336, 14.2%). We analyzed the basic characteristics of variant transferrin by CDT tests using capillary zone electrophoresis. The prevalence of variant transferrin was 3.1% of the study subjects. Male patients, alcohol abusers, and liver cirrhosis patients predominated in the variant transferrin population. Further prospective studies are warranted to elucidate variant transferrin in clinical practice. © 2018 Wiley Periodicals, Inc.

  5. Laboratory methodologies for indicators of iron status: strengths, limitations, and analytical challenges.

    Science.gov (United States)

    Pfeiffer, Christine M; Looker, Anne C

    2017-12-01

    Biochemical assessment of iron status relies on serum-based indicators, such as serum ferritin (SF), transferrin saturation, and soluble transferrin receptor (sTfR), as well as erythrocyte protoporphyrin. These indicators present challenges for clinical practice and national nutrition surveys, and often iron status interpretation is based on the combination of several indicators. The diagnosis of iron deficiency (ID) through SF concentration, the most commonly used indicator, is complicated by concomitant inflammation. sTfR concentration is an indicator of functional ID that is not an acute-phase reactant, but challenges in its interpretation arise because of the lack of assay standardization, common reference ranges, and common cutoffs. It is unclear which indicators are best suited to assess excess iron status. The value of hepcidin, non-transferrin-bound iron, and reticulocyte indexes is being explored in research settings. Serum-based indicators are generally measured on fully automated clinical analyzers available in most hospitals. Although international reference materials have been available for years, the standardization of immunoassays is complicated by the heterogeneity of antibodies used and the absence of physicochemical reference methods to establish "true" concentrations. From 1988 to 2006, the assessment of iron status in NHANES was based on the multi-indicator ferritin model. However, the model did not indicate the severity of ID and produced categorical estimates. More recently, iron status assessment in NHANES has used the total body iron stores (TBI) model, in which the log ratio of sTfR to SF is assessed. Together, sTfR and SF concentrations cover the full range of iron status. The TBI model better predicts the absence of bone marrow iron than SF concentration alone, and TBI can be analyzed as a continuous variable. Additional consideration of methodologies, interpretation of indicators, and analytic standardization is important for further

  6. Nitric oxide-mediated modulation of iron regulatory proteins: implication for cellular iron homeostasis.

    Science.gov (United States)

    Kim, Sangwon; Ponka, Prem

    2002-01-01

    Iron regulatory proteins (IRP1 and IRP2) control the synthesis of transferrin receptors (TfR) and ferritin by binding to iron-responsive elements (IREs) that are located in the 3' untranslated region (UTR) and the 5' UTR of their respective mRNAs. Cellular iron levels affect binding of IRPs to IREs and consequently expression of TfR and ferritin. Moreover, NO(.), a redox species of nitric oxide that interacts primarily with iron, can activate IRP1 RNA-binding activity resulting in an increase in TfR mRNA levels and a decrease in ferritin synthesis. We have shown that treatment of RAW 264.7 cells (a murine macrophage cell line) with NO(+) (nitrosonium ion, which causes S-nitrosylation of thiol groups) resulted in a rapid decrease in RNA-binding of IRP2, followed by IRP2 degradation, and these changes were associated with a decrease in TfR mRNA levels and a dramatic increase in ferritin synthesis. Moreover, we demonstrated that stimulation of RAW 264.7 cells with lipopolysaccharide (LPS) and interferon-gamma (IFN-gamma) increased IRP1 binding activity, whereas RNA-binding of IRP2 decreased and was followed by a degradation of this protein. Furthermore, the decrease of IRP2 binding/protein levels was associated with a decrease in TfR mRNA levels and an increase in ferritin synthesis in LPS/IFN-gamma-treated cells, and these changes were prevented by inhibitors of inducible nitric oxide synthase. These results suggest that NO(+)-mediated degradation of IRP2 plays a major role in iron metabolism during inflammation.

  7. Iron homeostasis and its disruption in mouse lung in iron deficiency and overload.

    Science.gov (United States)

    Giorgi, Gisela; D'Anna, María Cecilia; Roque, Marta Elena

    2015-10-01

    What is the central question of this study? The aim was to explore the role and hitherto unclear mechanisms of action of iron proteins in protecting the lung against the harmful effects of iron accumulation and the ability of pulmonary cells to mobilize iron in iron deficiency. What is the main finding and its importance? We show that pulmonary hepcidin appears not to modify cellular iron mobilization in the lung. We propose pathways for supplying iron to the lung in iron deficiency and for protecting the lung against iron excess in iron overload, mediated by the co-ordinated action of iron proteins, such as divalent metal transporter 1, ZRT-IRE-like-protein 14, transferrin receptor, ferritin, haemochromatosis-associated protein and ferroportin. Iron dyshomeostasis is associated with several forms of chronic lung disease, but its mechanisms of action remain to be elucidated. The aim of the present study was to determine the role of the lung in whole-animal models with iron deficiency and iron overload, studying the divalent metal transporter 1 (DMT1), ZRT-IRE-like protein 14 (ZIP14), transferrin receptor (TfR), haemochromatosis-associated protein (HFE), hepcidin, ferritin and ferroportin (FPN) expression. In each model, adult CF1 mice were divided into the following groups (six mice per group): (i) iron-overload model, iron saccharate i.p. and control group (iron adequate), 0.9% NaCl i.p.; and (ii) iron-deficiency model, induced by repeated bleeding, and control group (sham operated). Proteins were assessed by immunohistochemistry and Western blot. In control mice, DMT1 was localized in the cytoplasm of airway cells, and in iron deficiency and overload it was in the apical membrane. Divalent metal transporter 1 and TfR increased in iron deficiency, without changes in iron overload. ZRT-IRE-like protein 14 decreased in airway cells in iron deficiency and increased in iron overload. In iron deficiency, HFE and FPN were immunolocalized close to the apical membrane

  8. The prevalence of anemia and iron deficiency is more common in breastfed infants than their mothers in Bhaktapur, Nepal.

    Science.gov (United States)

    Chandyo, R K; Henjum, S; Ulak, M; Thorne-Lyman, A L; Ulvik, R J; Shrestha, P S; Locks, L; Fawzi, W; Strand, T A

    2016-04-01

    Iron deficiency anemia is a widespread public health problem, particularly in low- and middle-income countries. Maternal iron status around and during pregnancy may influence infant iron status. We examined multiple biomarkers to determine the prevalence of iron deficiency and anemia among breastfed infants and explored its relationship with maternal and infant characteristics in Bhaktapur, Nepal. In a cross-sectional survey, we randomly selected 500 mother-infant pairs from Bhaktapur municipality. Blood was analyzed for hemoglobin, ferritin, total iron-binding capacity, transferrin receptors and C-reactive protein. The altitude-adjusted prevalence of anemia was 49% among infants 2-6-month-old (hemaglobin (Hb) Iron deficiency anemia, defined as anemia and serum ferritin anemia (Hb iron stores. Significant predictors of infant iron status and anemia were infant age, sex and duration of exclusive breastfeeding and maternal ferritin concentrations. Our findings suggest that iron supplementation in pregnancy is likely to have resulted in a low prevalence of postpartum anemia. The higher prevalence of anemia and iron deficiency among breastfed infants compared with their mothers suggests calls for intervention targeting newborns and infants.

  9. Helicobacter pylori infection and serum ferritin

    DEFF Research Database (Denmark)

    Berg, Gabriele; Bode, G; Blettner, M

    2001-01-01

    OBJECTIVE: Helicobacter pylori may possibly affect the iron metabolism by occult bleeding, impaired absorption of non-hem iron, and by scavenging hem iron or ferritin, as some studies have suggested. The aim of this study was to analyze the association between H. pylori infection and serum ferritin...... in 1987/1988. The examination included a detailed questionnaire on medical history and lifestyle factors, a 7-day food record, and blood samples. Infection with H. pylori was measured serologically by ELISA and Westernblot. RESULTS: In total, 39.2% of 1806 persons aged 18 to 89 yr included in the study...... were H. pylori positive, of whom 57.6% had an infection with a CagA-positive H. pylori strain. Age- and sex-adjusted geometric mean of ferritin was 54.5 microg/dl among H. pylori-infected compared with 63.8 microg/dl among uninfected persons. A multiple linear regression model with log...

  10. Oxidative modification of ferritin induced by methylglyoxal

    Directory of Open Access Journals (Sweden)

    Sung Ho An

    2012-03-01

    Full Text Available Methylglyoxal (MG was identified as an intermediate innon-enzymatic glycation and increased levels were reported inpatients with diabetes. In this study, we evaluated the effects ofMG on the modification of ferritin. When ferritin wasincubated with MG, covalent crosslinking of the proteinincreased in a time- and MG dose-dependent manner.Reactive oxygen species (ROS scavengers, N-acetyl-L-cysteineand thiourea suppressed the MG-mediated ferritinmodification. The formation of dityrosine was observed inMG-mediated ferritin aggregates and ROS scavengers inhibitedthe formation of dityrosine. During the reaction betweenferritin and MG, the generation of ROS was increased as afunction of incubation time. These results suggest that ROSmay play a role in the modification of ferritin by MG. Thereaction between ferritin and MG led to the release of ironions from the protein. Ferritin exposure to MG resulted in aloss of arginine, histidine and lysine residues. It was assumedthat oxidative damage to ferritin caused by MG may induce anincrease in the iron content in cells, which is deleterious tocells. This mechanism, in part, may provide an explanation orthe deterioration of organs under diabetic conditions. [BMBreports 2012; 45(3: 147-152

  11. TIBC, UIBC and Transferrin

    Science.gov (United States)

    ... circulating and stored iron may eventually lead to iron deficiency anemia (decreased hemoglobin and hematocrit , smaller and paler red ... results of each can help identify iron deficiency, iron deficiency anemia, or too much iron in the body (overload). ...

  12. Immunoradiometric assay for ferritin in human serum

    International Nuclear Information System (INIS)

    Leyland, M.J.; Ganguli, P.C.; Blower, D.; Delamore, I.W.

    1975-01-01

    A sensitiv specific and precise immunoradiometric assay for ferritin has been developed. Ferritin was measured in the serum of 160 hospital controls, 101 females (118 plus/minus 9 μg/l) and 59 males (189 plus/minus 16 μg/l). This difference was statistically significant. In 28 patients with untreated iron deficiency anemia, serum ferritin concentration (6.1plus/minus 0.7 μg/l) was significantly lower than in the controls, but it was within the normal range in 14 cases of polycythaemia vera treated by repeated phlebotomy. In 4 patients with primary haemachromatosis (2884 plus/minus 56 μg/l), 25 with secondary iron overload states (5702 plus/minus 1235 μg/l) and 8 with haemolytic anaemia (1612 plus/minus 605 μg/l), serum ferritin levels were markedly elevated. In 14 cases of transfusional siderosis there was a highly significant correlation between serum ferritin concentration and units of blood transfused. A circadian rhythmin serum ferritin concentration was observed in 7 healthy subjects. (author)

  13. Nutritional Immunity Triggers the Modulation of Iron Metabolism Genes in the Sub-Antarctic Notothenioid Eleginops maclovinus in Response to Piscirickettsia salmonis

    Directory of Open Access Journals (Sweden)

    Danixa Martínez

    2017-09-01

    Full Text Available Iron deprivation is a nutritional immunity mechanism through which fish can limit the amount of iron available to invading bacteria. The aim of this study was to evaluate the modulation of iron metabolism genes in the liver and brain of sub-Antarctic notothenioid Eleginops maclovinus challenged with Piscirickettsia salmonis. The specimens were inoculated with two P. salmonis strains: LF-89 (ATCC® VR-1361™ and Austral-005 (antibiotic resistant. Hepatic and brain samples were collected at intervals over a period of 35 days. Gene expression (by RT-qPCR of proteins involved in iron storage, transport, and binding were statistically modulated in infected fish when compared with control counterparts. Specifically, the expression profiles of the transferrin and hemopexin genes in the liver, as well as the expression profiles of ferritin-M, ferritin-L, and transferrin in the brain, were similar for both experimental groups. Nevertheless, the remaining genes such as ferritin-H, ceruloplasmin, hepcidin, and haptoglobin presented tissue-specific expression profiles that varied in relation to the injected bacterial strain and sampling time-point. These results suggest that nutritional immunity could be an important immune defense mechanism for E. maclovinus against P. salmonis injection. This study provides relevant information for understanding iron metabolism of a sub-Antarctic notothenioid fish.

  14. A composite mouse model of aplastic anemia complicated with iron overload.

    Science.gov (United States)

    Wu, Dijiong; Wen, Xiaowen; Liu, Wenbin; Xu, Linlong; Ye, Baodong; Zhou, Yuhong

    2018-02-01

    Iron overload is commonly encountered during the course of aplastic anemia (AA), but no composite animal model has been developed yet, which hinders drug research. In the present study, the optimal dosage and duration of intraperitoneal iron dextran injection for the development of an iron overload model in mice were explored. A composite model of AA was successfully established on the principle of immune-mediated bone marrow failure. Liver volume, peripheral hemogram, bone marrow pathology, serum iron, serum ferritin, pathological iron deposition in multiple organs (liver, bone marrow, spleen), liver hepcidin, and bone morphogenetic protein 6 (BMP6), SMAD family member 4 (SMAD4) and transferrin receptor 2 (TfR2) mRNA expression levels were compared among the normal control, AA, iron overload and composite model groups to validate the composite model, and explore the pathogenesis and features of iron overload in this model. The results indicated marked increases in iron deposits, with significantly increased liver/body weight ratios as well as serum iron and ferritin in the iron overload and composite model groups as compared with the normal control and AA groups (Poverload and AA was successfully established, and AA was indicated to possibly have a critical role in abnormal iron metabolism, which promoted the development of iron deposits.

  15. Iron overload patients with unknown etiology from national survey in Japan.

    Science.gov (United States)

    Ikuta, Katsuya; Hatayama, Mayumi; Addo, Lynda; Toki, Yasumichi; Sasaki, Katsunori; Tatsumi, Yasuaki; Hattori, Ai; Kato, Ayako; Kato, Koichi; Hayashi, Hisao; Suzuki, Takahiro; Kobune, Masayoshi; Tsutsui, Miyuki; Gotoh, Akihiko; Aota, Yasuo; Matsuura, Motoo; Hamada, Yuzuru; Tokuda, Takahiro; Komatsu, Norio; Kohgo, Yutaka

    2017-03-01

    Transfusion is believed to be the main cause of iron overload in Japan. A nationwide survey on post-transfusional iron overload subsequently led to the establishment of guidelines for iron chelation therapy in this country. To date, however, detailed clinical information on the entire iron overload population in Japan has not been fully investigated. In the present study, we obtained and studied detailed clinical information on the iron overload patient population in Japan. Of 1109 iron overload cases, 93.1% were considered to have occurred post-transfusion. There were, however, 76 cases of iron overload of unknown origin, which suggest that many clinicians in Japan may encounter some difficulty in correctly diagnosing and treating iron overload. Further clinical data were obtained for 32 cases of iron overload of unknown origin; median of serum ferritin was 1860.5 ng/mL. As occurs in post-transfusional iron overload, liver dysfunction was found to be as high as 95.7% when serum ferritin levels exceeded 1000 ng/mL in these patients. Gene mutation analysis of the iron metabolism-related genes in 27 cases of iron overload with unknown etiology revealed mutations in the gene coding hemojuvelin, transferrin receptor 2, and ferroportin; this indicates that although rare, hereditary hemochromatosis does occur in Japan.

  16. Iron Homeostasis in Mycobacterium tuberculosis: Mechanistic Insights into Siderophore-Mediated Iron Uptake

    Science.gov (United States)

    2016-01-01

    Mycobacterium tuberculosis requires iron for normal growth but faces a limitation of the metal ion due to its low solubility at biological pH and the withholding of iron by the mammalian host. The pathogen expresses the Fe3+-specific siderophores mycobactin and carboxymycobactin to chelate the metal ion from insoluble iron and the host proteins transferrin, lactoferrin, and ferritin. Siderophore-mediated iron uptake is essential for the survival of M. tuberculosis, as knockout mutants, which were defective in siderophore synthesis or uptake, failed to survive in low-iron medium and inside macrophages. But as excess iron is toxic due to its catalytic role in the generation of free radicals, regulation of iron uptake is necessary to maintain optimal levels of intracellular iron. The focus of this review is to present a comprehensive overview of iron homeostasis in M. tuberculosis that is discussed in the context of mycobactin biosynthesis, transport of iron across the mycobacterial cell envelope, and storage of excess iron. The clinical significance of the serum iron status and the expression of the iron-regulated protein HupB in tuberculosis (TB) patients is presented here, highlighting the potential of HupB as a marker, notably in extrapulmonary TB cases. PMID:27402628

  17. Transferrin saturation ratio and risk of total and cardiovascular mortality in the general population.

    LENUS (Irish Health Repository)

    Stack, A G

    2014-08-01

    The transferrin saturation (TSAT) ratio is a commonly used indicator of iron deficiency and iron overload in clinical practice but precise relationships with total and cardiovascular mortality are unclear.

  18. Comparative analysis of iron homeostasis in sub-Saharan African children with sickle cell disease and their unaffected siblings

    Directory of Open Access Journals (Sweden)

    Selma eGomez

    2016-02-01

    Full Text Available Iron is an essential trace element subject to tight regulation to ensure adequate running of biological processes. In sub-Saharan Africa where hemoglobinopathies are common, iron homeostasis is likely to be impaired by these conditions. Here we assessed and compared key serum proteins associated with iron metabolism between sub-Saharan African children with sickle cell disease (SCD and their unaffected siblings. Complete blood counts and serum concentrations of four key proteins involved in iron regulation (ferritin, transferrin, sTfR and hepcidin were measured for 73 children with SCD and 68 healthy siblings in Benin, West Africa. We found significant differences in concentration of transferrin, sTfR and ferritin between the two groups. Hepcidin concentrations were found at unusually high concentrations but did not differ among the two groups. We found a significant negative correlation between hepcidin levels and both MCH and MCV in the SCD group and report that sTfR concentrations show a correlation with MCV and MHC in opposite directions in the two groups. These results highlight the unusually high levels of hepcidin in the Beninese population and the patterns of differential iron homeostasis taking place under sickle cell disease status. These results lay the foundation for a systematic evaluation of the underlying mechanisms deregulating iron homeostasis in populations with SCD or high prevalence of iron deficiency.

  19. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... iron in your body is low. For this reason, other iron tests are also done. Ferritin measure ... iron is needed, such as childhood and pregnancy. Good sources of iron are meat, poultry, fish, and ...

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

    Science.gov (United States)

    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 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.

  1. Computational modeling and analysis of iron release from macrophages.

    Directory of Open Access Journals (Sweden)

    Alka A Potdar

    2014-07-01

    Full Text Available A major process of iron homeostasis in whole-body iron metabolism is the release of iron from the macrophages of the reticuloendothelial system. Macrophages recognize and phagocytose senescent or damaged erythrocytes. Then, they process the heme iron, which is returned to the circulation for reutilization by red blood cell precursors during erythropoiesis. The amount of iron released, compared to the amount shunted for storage as ferritin, is greater during iron deficiency. A currently accepted model of iron release assumes a passive-gradient with free diffusion of intracellular labile iron (Fe2+ through ferroportin (FPN, the transporter on the plasma membrane. Outside the cell, a multi-copper ferroxidase, ceruloplasmin (Cp, oxidizes ferrous to ferric ion. Apo-transferrin (Tf, the primary carrier of soluble iron in the plasma, binds ferric ion to form mono-ferric and di-ferric transferrin. According to the passive-gradient model, the removal of ferrous ion from the site of release sustains the gradient that maintains the iron release. Subcellular localization of FPN, however, indicates that the role of FPN may be more complex. By experiments and mathematical modeling, we have investigated the detailed mechanism of iron release from macrophages focusing on the roles of the Cp, FPN and apo-Tf. The passive-gradient model is quantitatively analyzed using a mathematical model for the first time. A comparison of experimental data with model simulations shows that the passive-gradient model cannot explain macrophage iron release. However, a facilitated-transport model associated with FPN can explain the iron release mechanism. According to the facilitated-transport model, intracellular FPN carries labile iron to the macrophage membrane. Extracellular Cp accelerates the oxidation of ferrous ion bound to FPN. Apo-Tf in the extracellular environment binds to the oxidized ferrous ion, completing the release process. Facilitated-transport model can

  2. Biosynthesis, isolation and characterization of {sup 57}Fe-enriched Phaseolus vulgaris ferritin after heterologous expression in Escherichia coli

    Energy Technology Data Exchange (ETDEWEB)

    Hoppler, Matthias [ETH Zurich, Laboratory of Human Nutrition, Zurich (Switzerland); Meile, Leo [ETH Zurich, Laboratory of Food Biotechnology, Zurich (Switzerland); Walczyk, Thomas [National University of Singapore, Department of Chemistry and Department of Biochemistry, Singapore (Singapore)

    2008-01-15

    Ferritin is the major iron storage protein in the biosphere. Iron stores of an organism are commonly assessed by measuring the concentration of the protein shell of the molecule in fluids and tissues. The amount of ferritin-bound iron, the more desirable information, still remains inaccessible owing to the lack of suitable techniques. Iron saturation of ferritin is highly variable, with a maximum capacity of 4,500 iron atoms per molecule. This study describes the direct isotopic labeling of a complex metalloprotein in vivo by biosynthesis, in order to measure ferritin-bound iron by isotope dilution mass spectrometry. [{sup 57}Fe]ferritin was produced by cloning and overexpressing the Phaseolus vulgaris ferritin gene pfe in Escherichia coli in the presence of {sup 57}FeCl{sub 2}. Recombinant ferritin was purified in a fully assembled form and contained approximately 1,000 iron atoms per molecule at an isotopic enrichment of more than 95% {sup 57}Fe. We did not find any evidence of species conversion of the isotopic label for at least 5 months of storage at -20 C. Transfer efficiency of enriched iron into [{sup 57}Fe]ferritin of 20% was sufficient to be economically feasible. Negligible amounts of non-ferritin-bound iron in the purified [{sup 57}Fe]ferritin solution allows for use of this spike for quantification of ferritin-bound iron by isotope dilution mass spectrometry. (orig.)

  3. Maxi- and mini-ferritins: minerals and protein nanocages.

    Science.gov (United States)

    Bevers, Loes E; Theil, Elizabeth C

    2011-01-01

    Ferritins synthesize ferric oxide biominerals and are central to all life for concentrating iron and protection against oxidative stress from the ferrous and oxidant chemistry. The ferritin protein nanocages and biomineral synthesis are discussed in terms of wide biological distribution of the maxi-ferritins (24 subunit ± heme) and mini-ferritins (Dps) (12 subunit), conservations of the iron/oxygen catalytic sites in the protein cages, mineral formation (step i. Fe(II) entry and binding, step ii. O(2) or H(2)O(2) binding and formation of transition intermediates, step iii. release of differric oxo mineral precursors from active sites, step iv. nucleation and mineralization) properties of the minerals, and protein control of mineral dissolution and release of Fe(II). Pores in ferritin protein cages control iron entry for mineralization and iron exit after mineral dissolution. The relationship between phosphate or the presence of catalytically inactive subunits (animal L subunits) and ferritin iron mineral disorder is developed based on new information about contributions of ferritin protein cage structure to nucleation in protein cage subunit channels that exit close enough to those of other subunits and exiting mineral nuclei to facilitate bulk mineral formation. How and where protons move in and out of the protein during mineral synthesis and dissolution, how ferritin cage assembly with 12 or 24 subunits is encoded in the widely divergent ferritin amino acid sequences, and what is the role of the protein in synthesis of the bulk mineral are all described as problems requiring new approaches in future investigations of ferritin biominerals.

  4. Anemia and Iron Status Among Different Body Size Phenotypes in Chinese Adult Population: a Nation-Wide, Health and Nutrition Survey.

    Science.gov (United States)

    Li, Jiang; Xiao, Cheng; Yang, Hui; Zhou, Yun; Wang, Rui; Cao, Yongtong

    2017-12-09

    Previous studies have shown that there is a controversial relationship between iron homeostasis and obesity. This study aims to explore the relationship of anemia and iron status with different body size phenotypes in adult Chinese population. Using information on iron status-related parameters and lifestyle data from 8462 participants of the 2009 wave of China Health and Nutrition Survey (2009 CHNS), we performed multivariable logistic regression analyses to estimate the odds ratios (ORs) for the risk of anemia and iron parameters according to different body size phenotypes. Participants with higher body mass index (BMI) had a lower anemia prevalence with significant trends in both metabolic status groups (P different metabolic status groups and in different body size phenotypes, respectively. The ORs for higher ferritin and transferrin increased across different body size phenotypes in both genders, and for sTfR/log ferritin index decreased (P < 0.01 for trend). This association was still statistically significant after adjustment for multiple confounders. We found an inverse association of BMI levels with the prevalence of anemia and strong association of serum ferritin and transferrin with higher risk of obesity or overweight in both metabolic status groups.

  5. LABILE IRON IN CELLS AND BODY FLUIDS . Physiology, Pathology and Pharmacology

    Directory of Open Access Journals (Sweden)

    Zvi Ioav Cabantchik

    2014-03-01

    Full Text Available In living systems iron appears predominantly associated with proteins, but can also be detected in forms referred as labile iron, which denotes the combined redox properties of iron and its amenability to exchange between ligands, including chelators. The labile cell iron (LCI composition varies with metal concentration and substances with chelating groups but also with pH and the redox potential. Although physiologically in the lower µM range, LCI plays a key role in cell iron economy as cross-roads of metabolic pathways. LCI levels are continually regulated by an iron-responsive machinery that balances iron uptake versus deposition into ferritin. However, LCI rises aberrantly in some cell types due to faulty cell utilization pathways or infiltration by pathological iron forms that are found in hemosiderotic plasma. As LCI attains pathological levels, it can catalyze reactive O species (ROS formation that, at particular threshold, can surpass cellular anti-oxidant capacities and seriously damage its constituents. While in normal plasma and interstitial fluids, virtually all iron is securely carried by circulating transferrin (that renders iron essentially non-labile, in systemic iron overload (IO, the total plasma iron binding capacity is often surpassed by a massive iron influx from hyperabsorptive gut or from erythrocyte overburdened spleen and/or liver. As plasma transferrin approaches iron saturation, labile plasma iron (LPI emerges in forms that can infiltrate cells by unregulated routes and raise LCI to toxic levels. Despite the limited knowledge available on LPI speciation in different types and degrees of iron overload, LPI measurements can be and are in fact used for identifying systemic IO and for initiating/adjusting chelation regimens to attain full-day LPI protection. A recent application of labile iron assay is the detection of labile components in iv iron formulations per se as well as in plasma (LPI following parenteral iron

  6. Multiple post-transcriptional regulatory mechanisms in ferritin gene expression

    International Nuclear Information System (INIS)

    Mattia, E.; Den Blaauwen, J.; Van Renswoude, J.; Ashwell, G.

    1989-01-01

    The authors have investigated the mechanisms involved in the regulation of ferritin biosynthesis in K562 human erythroleukemia cells during prolonged exposure to iron. They show that, upon addition of hemin (an efficient iron donor) to the cell culture, the rate of ferritin biosynthesis reaches a maximum after a few hours and then decreases. During a 24-hr incubation with the iron donor the concentrations of total ferritin heavy (H) and light (L) subunit mRNAs rise 2- to 5-fold and 2- to 3-fold, respectively, over the control values, while the amount of the protein increases 10- to 30-fold. The hemin-induced increment in ferritin subunit mRNA is not prevented by deferoxamine, suggesting that it is not directly mediated by chelatable iron. In vitro nuclear transcription analyses performed on nuclei isolated from control cells and cells grown in the presence of hemin indicate that the rates of synthesis of H- and L-subunit mRNAs remain constant. They conclude that iron-induced ferritin biosynthesis is governed by multiple post-transcriptional regulatory mechanisms. They propose that exposure of cells to iron leads to stabilization of ferritin mRNAs, in addition to activation and translation of stored H-and L-subunit mRNAs

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

    Science.gov (United States)

    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.

  8. Impact of daily consumption of iron fortified ready-to-eat cereal and pumpkin seed kernels (Cucurbita pepo) on serum iron in adult women.

    Science.gov (United States)

    Naghii, Mohammad Reza; Mofid, Mahmood

    2007-01-01

    Iron deficiency, anemia, is the most prevalent nutritional problem in the world today. The objective of this study was to consider the effectiveness of consumption of iron fortified ready-to-eat cereal and pumpkin seed kernels as two sources of dietary iron on status of iron nutrition and response of hematological characteristics of women at reproductive ages. Eight healthy female, single or non pregnant subjects, aged 20-37 y consumed 30 g of iron fortified ready-to-eat cereal (providing 7.1 mg iron/day) plus 30 g of pumpkin seed kernels (providing 4.0 mg iron/day) for four weeks. Blood samples collected on the day 20 of menstrual cycles before and after consumption and indices of iron status such as reticulocyte count, hemoglobin (Hb), hematocrit (Ht), serum ferritin, iron, total iron-binding capacity (TIBC), transferrin and transferrin saturation percent were determined. Better response for iron status was observed after consumption period. The statistical analysis showed a significant difference between the pre and post consumption phase for higher serum iron (60 +/- 22 vs. 85 +/- 23 ug/dl), higher transferrin saturation percent (16.8 +/- 8.0 vs. 25.6 +/- 9.0%), and lower TIBC (367 +/- 31 vs. 339 +/- 31 ug/dl). All individuals had higher serum iron after consumption. A significant positive correlation (r=0.981, p=0.000) between the differences in serum iron levels and differences in transferrin saturation percentages and a significant negative correlation (r=-0.916, pfoods contribute to maintaining optimal nutritional status and minimizing the likelihood of iron insufficiencies and use of fortified ready-to-eat cereals is a common strategy. The results showed that adding another food source of iron such as pumpkin seed kernels improves the iron status. Additional and longer studies using these two food products are recommended to further determine the effect of iron fortification on iron nutrition and status among the target population, and mainly in young

  9. Laboratory assessment of iron status in pregnancy.

    LENUS (Irish Health Repository)

    Walsh, Thomas

    2012-02-01

    BACKGROUND: Efforts to improve maternal nutrition during pregnancy prompted an observational study of the occurrence of maternal iron deficiency and its laboratory diagnosis in almost 500 pregnancies. METHODS: In this longitudinal study, the biochemical and haematological iron indices of women (n=492) attending a prenatal clinic in a Dublin maternity hospital were assessed at first booking (mean 15.9 weeks), and after 24 weeks, and 36 weeks of gestation. Full blood counts were measured. Serum ferritin (SF), zinc protoporphyrin (ZPP), and transferrin receptor (sTfR) concentrations were assayed and transferrin receptor index (sTfR-Index) was calculated. The occurrence of low values and their diagnostic values were considered. RESULTS: A high occurrence iron deficiency (ID) at first booking (SF<12 mug\\/L) had increased over six-fold by 24 weeks, and all biochemical iron indices reflected progressive iron depletion right up to term. The WHO recommended anaemia "cut-off" (Hb<110 g\\/L) was insensitive to biochemical iron deficiency at booking, missing over 90% of the low SF values (SF<12 mug\\/L) which were mostly associated with much higher Hb levels. CONCLUSIONS: This study stresses the importance of including a biochemical index of iron status in prenatal screening and supports SF as the best indicator of biochemical ID overall. sTfR was insensitive to iron deficiency in early pregnancy, whereas the sTfR-Index, as a ratio, has the potential to distinguish between ID and physiological anaemia, and may offer stability in the assessment of iron stores from early pregnancy to full term. A policy of early screening of both Hb and SF concentrations is recommended as the minimum requirement for surveillance of maternal iron status in pregnancy.

  10. The contribution of diet and genotype to iron status in women: a classical twin study.

    Science.gov (United States)

    Fairweather-Tait, Susan J; Guile, Geoffrey R; Valdes, Ana M; Wawer, Anna A; Hurst, Rachel; Skinner, Jane; Macgregor, Alexander J

    2013-01-01

    This is the first published report examining the combined effect of diet and genotype on body iron content using a classical twin study design. The aim of this study was to determine the relative contribution of genetic and environmental factors in determining iron status. The population was comprised of 200 BMI- and age-matched pairs of MZ and DZ healthy twins, characterised for habitual diet and 15 iron-related candidate genetic markers. Variance components analysis demonstrated that the heritability of serum ferritin (SF) and soluble transferrin receptor was 44% and 54% respectively. Measured single nucleotide polymorphisms explained 5% and selected dietary factors 6% of the variance in iron status; there was a negative association between calcium intake and body iron (p = 0.02) and SF (p = 0.04).

  11. Iron concentrations in breast milk and selected maternal factors of human milk bank donors.

    Science.gov (United States)

    Mello-Neto, Julio; Rondó, Patrícia H C; Morgano, Marcelo A; Oshiiwa, Marie; Santos, Mariana L; Oliveira, Julicristie M

    2010-05-01

    The aim of this study was to evaluate the relationship between iron concentration in mature breast milk and characteristics of 136 donors of a Brazilian milk bank. Iron, vitamin A, zinc, and copper concentrations were assessed in human milk and maternal blood. Data were collected on maternal anthropometrics, obstetric, socioeconomic, demographic, and lifestyle factors. Iron, zinc, and copper in milk and zinc and copper in blood were detected by spectrophotometry. Vitamin A in milk and blood was determined by high-performance liquid chromatography. Hemoglobin was measured by electronic counting and serum iron and ferritin by colorimetry and chemoluminescence, respectively. Transferrin and ceruloplasmin were determined by nephelometry. According to multivariate linear regression analysis, iron in milk was positively associated with vitamin A in milk and with smoking but negatively associated with timing of breast milk donation (P milk of Brazilian donors may be influenced by nutritional factors and smoking.

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

    Science.gov (United States)

    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.

  13. Serum ferritin and stomach cancer risk among A-bomb survivors

    International Nuclear Information System (INIS)

    Akiba, Suminori; Neriishi, Kazuo; Blot, W.J.; Kabuto, Michinori; Stevens, R.G.; Kato, Hiroo; Land, C.E.

    1990-02-01

    Using stored serum samples collected from 1970-72 and/or from 1977-79, serum ferritin, transferrin, and ceruloplasmin levels were immunologically determined for 233 stomach cancer and 84 lung cancer cases diagnosed from 1973-83 and for 385 matched controls from a fixed population of Hiroshima and Nagasaki atomic bomb survivors. Elevated stomach cancer risk was associated with low serum ferritin levels, with more than a threefold excess among those in the lowest quintile as compared to the highest ferritin quintile. The average serum ferritin concentration was 8% lower in the stomach cancer cases than in the controls. Risk did not vary with the time between blood collection and stomach cancer onset, remaining high among those with low ferritin levels five or more years before cancer diagnosis. Low ferritin combined with achlorhydria, diagnosed about 10 years before the blood collection and up to 25 years before cancer diagnosis, was an exceptionally strong marker of increased stomach cancer risk. No effect of transferrin or ceruloplasmin independent of ferritin was observed on gastric cancer risk. Lung cancer risk was not related to these three serum proteins. (author)

  14. HFE gene mutation is a risk factor for tissue iron accumulation in hemodialysis patients.

    Science.gov (United States)

    Turkmen, Ercan; Yildirim, Tolga; Yilmaz, Rahmi; Hazirolan, Tuncay; Eldem, Gonca; Yilmaz, Engin; Aybal Kutlugun, Aysun; Altindal, Mahmut; Altun, Bulent

    2017-07-01

    HFE gene mutations are responsible from iron overload in general population. Studies in hemodialysis patients investigated the effect of presence of HFE gene mutations on serum ferritin and transferrin saturation (TSAT) with conflicting results. However effect of HFE mutations on iron overload in hemodialysis patients was not previously extensively studied. 36 hemodialysis patients (age 51.3 ± 15.6, (18/18) male/female) and 44 healthy control subjects included in this cross sectional study. Hemoglobin, ferritin, TSAT in the preceding 2 years were recorded. Iron and erythropoietin (EPO) administered during this period were calculated. Iron accumulation in heart and liver was detected by MRI. Relationship between HFE gene mutation, hemoglobin, iron parameters and EPO doses, and tissue iron accumulation were determined. Iron overload was detected in nine (25%) patients. Hemoglobin, iron parameters, weekly EPO doses, and monthly iron doses of patients with and without iron overload were similar. There was no difference between control group and hemodialysis patients with respect to the prevalence of HFE gene mutations. Iron overload was detected in five of eight patients who had HFE gene mutations, but iron overload was present in 4 of 28 patients who had no mutations (P = 0.01). Hemoglobin, iron parameters, erythropoietin, and iron doses were similar in patients with and without gene mutations. HFE gene mutations remained the main determinant of iron overload after multivariate logistic regression analysis (P = 0.02; OR, 11.6). Serum iron parameters were not adequate to detect iron overload and HFE gene mutation was found to be an important risk factor for iron accumulation. © 2017 International Society for Hemodialysis.

  15. Ameliorating role of rutin on oxidative stress induced by iron overload in hepatic tissue of rats.

    Science.gov (United States)

    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

  16. Synthesis and characterization of human transferrin-stabilized gold nanoclusters

    International Nuclear Information System (INIS)

    Le Guevel, Xavier; Schneider, Marc; Daum, Nicole

    2011-01-01

    Human transferrin has been biolabelled with gold nanoclusters (Au NCs) using a simple, fast and non-toxic method. These nanocrystals ( em = 695 nm). Structural investigation and photophysical measurements show a high population of clusters formed of 22-33 gold atoms covalently bound to the transferrin. In solutions with pH ranging from 5 to 10 and in buffer solutions (PBS, HEPES), those biolabelled proteins exhibit a good stability. No significant quenching effect of the fluorescent transferrin has been detected after iron loading of iron-free transferrin (apoTf) and in the presence of a specific polyclonal antibody. Additionally, antibody-induced agglomeration demonstrates no alteration in the protein activity and the receptor target ability. MTT and Vialight Plus tests show no cytotoxicity of these labelled proteins in cells (1 μg ml -1 -1 mg ml -1 ). Cell line experiments (A549) indicate also an uptake of the iron loaded fluorescent proteins inside cells. These remarkable data highlight the potential of a new type of non-toxic fluorescent transferrin for imaging and targeting.

  17. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... red meat, salmon, iron-fortified breads and cereals, peas, tofu, dried fruits, and dark green leafy vegetables. ... stored iron has been used. Ferritin is a protein that helps store iron in your body. Reticulocyte ...

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

    Science.gov (United States)

    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 (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

  19. Assay of serum ferritin by two different radioimmunometric methods and its clinical significance

    International Nuclear Information System (INIS)

    Kaltwasser, J.P.; Werner, E.; Gesellschaft fuer Strahlen- und Umweltforschung m.b.H., Frankfurt am Main

    1977-01-01

    Serum ferritin was measured by two different radioimmunometric methods a) the Addison assay, b) a commercial radioimmunoassay. Iron storage in the body was determined using 59 Fe. A dose correlation was found between serum ferritin and iron storage in the body. (AJ) [de

  20. Efficacy of a microencapsulated iron pyrophosphate-fortified fruit juice: a randomised, double-blind, placebo-controlled study in Spanish iron-deficient women.

    Science.gov (United States)

    Blanco-Rojo, Ruth; Pérez-Granados, Ana M; Toxqui, Laura; González-Vizcayno, Carmen; Delgado, Marco A; Vaquero, M Pilar

    2011-06-01

    Fe-deficiency anaemia is a worldwide health problem. We studied the influence of consuming an Fe-fortified fruit juice on Fe status in menstruating women. A randomised, double-blind, placebo-controlled study of 16 weeks of duration was performed. Subjects were randomised into two groups: the P group (n 58) or the F group (n 64), and consumed, as a supplement to their usual diet, 500 ml/d of a placebo fruit juice or an Fe-fortified fruit juice, respectively. The Fe-fortified fruit juice, containing microencapsulated iron pyrophosphate, provided 18 mg Fe/d (100 % of the RDA). At baseline and monthly, dietary intake, body weight and Fe parameters were determined: total erythrocytes, haematocrit, mean corpuscular volume (MCV), red blood cell distribution width (RDW), Hb, serum Fe, serum ferritin, serum transferrin, transferrin saturation, soluble transferrin receptor (sTfR) and zinc protoporphyrin (ZnPP). The fruit juice consumption involved increased intake of carbohydrates and vitamin C, and increased BMI within normal limits. Ferritin was higher in the F group after week 4 (P juice improves Fe status and may be used to prevent Fe-deficiency anaemia.

  1. Effects of exercise on the markers of iron status in serum of cross-country skiers

    Directory of Open Access Journals (Sweden)

    J Malczewska-Lenczowska

    2010-12-01

    Full Text Available The study aim was to assess the within-subject, day-to-day variability for ferritin and soluble transferrin receptor (sTfR concentrations in serum of 6 female and 8 male cross-country skiers aged 16-18 years under a regular training regimen throughout 8 consecutive days. The concentrations of iron status variables and creatine kinase (CK activities were adjusted to plasma volume changes. Mean ferritin concentrations were 30.6 • 1.142[sup]±1[/sup] and 22.6 • 1.167[sup]±1[/sup] μg/l for men and women, respectively, the average within-subject, mean day-to-day variability coefficients (CV being 13.4% in men and 15.2% in women. Mean sTfR was 2.14 • 1.050[sup]±1[/sup] and 2.62 • 1.047[sup]±1[/sup] mg/l, respectively, and mean day-to-day CV 6.5% and 4.6%. Mean CV for sTfR/logFerr were 6.0% and 7.4%, respectively. Neither index correlated with training loads or CK activities. Thus, the training performed once daily had no significant effect on ferritin concentrations on the following morning, so ferritin alone may prove insufficient in detecting iron deficiency in endurance athletes. The low variability of sTfR under endurance loads made it useful in detecting iron deficiency together with ferritin and the sTfR/logFerr index. Adjusting the concentrations of ferritin and sTfR by changes in plasma volume might be recommendable for endurance athletes.

  2. New Insights on Iron Study in Myelodysplasia

    Directory of Open Access Journals (Sweden)

    Noha M. El Husseiny

    2014-12-01

    Full Text Available OBJECTIVE: Hepcidin plays a pivotal role in iron homeostasis. It is predominantly produced by hepatocytes and inhibits iron release from macrophages and iron uptake by intestinal epithelial cells. Competitive ELISA is the current method of choice for the quantification of serum hepcidin because of its lower detection limit, low costs, and high throughput. This study aims to discuss the role of hepcidin in the pathogenesis of iron overload in recently diagnosed myelodysplasia (MDS cases. METHODS: The study included 21 recently diagnosed MDS patients and 13 healthy controls. Ferritin, hepcidin, and soluble transferrin receptor (sTFR were measured in all subjects. RESULTS: There were 7 cases of hypocellular MDS, 8 cases of refractory cytopenia with multilineage dysplasia, and 6 cases of refractory anemia with excess blasts. No difference was observed among the 3 MDS subtypes in terms of hepcidin, sTFR, and ferritin levels (p>0.05. Mean hepcidin levels in the MDS and control groups were 55.8±21.5 ng/mL and 19.9±2.6 ng/ mL, respectively. Mean sTFR was 45.7±8.8 nmol/L in MDS patients and 31.1±5.6 nmol/L in the controls. Mean ferritin levels were significantly higher in MDS patients than in controls (539.14±83.5 ng/mL vs. 104.6±42.9 ng/mL, p0.05. CONCLUSION: Hepcidin may not be the main cause of iron overload in MDS. Further studies are required to test failure of production or peripheral unresponsiveness to hepcidin in MDS cases.

  3. Reference Values of Reticulocyte Hemoglobin Content and Their Relation With Other Indicators of Iron Status in Healthy Children.

    Science.gov (United States)

    López-Ruzafa, Encarnación; Vázquez-López, Maria A; Lendinez-Molinos, Francisco; Poveda-González, Juan; Galera-Martínez, Rafael; Bonillo-Perales, Antonio; Martín-González, Manuel

    2016-10-01

    Reticulocyte hemoglobin content (CHr) is considered an indicator of functional iron deficiency, but is understudied in children. The goals of this study are to determine the reference intervals for CHr in healthy children, and their relation with iron parameters, erythropoiesis, and individual conditions. A total of 902 children without iron deficiency, aged 1 to 11 years were analyzed in a cross-sectional study. Besides a physical examination of the subjects and a questionnaire completed by their parents, the complete blood count, serum transferrin receptor, ferritin, transferrin saturation, erythrocyte protoporphyrin, serum erythropoietin, C-reactive protein, and CHr levels were measured. Changes in CHr, iron status, and erythropoiesis at different age intervals were analyzed and linear multiple regression was used to identify the factors that determine CHr variability. Mean value obtained for CHr was 30.9±1.8 pg (P2.5-P97.5: 26.9 to 34.3 pg), but the influence of age on CHr (the values increased with age) and on the iron parameters justified the establishment of different reference ranges. In addition to age, nutritional status, hematologic measurements, reticulocytes, transferrin saturation, and erythrocyte protoporphyrin accounted for 39% of CHr variability.

  4. Iron insufficiency compromises motor neurons and their mitochondrial function in Irp2-null mice

    KAUST Repository

    Jeong, Suh Young; Crooks, Daniel R.; Wilson-Ollivierre, Hayden; Ghosh, Manik C.; Sougrat, Rachid; Lee, Jaekwon; Cooperman, Sharon; Mitchell, James B.; Beaumont, Carole; Rouault, Tracey A.

    2011-01-01

    Genetic ablation of Iron Regulatory Protein 2 (Irp2, Ireb2), which post-transcriptionally regulates iron metabolism genes, causes a gait disorder in mice that progresses to hind-limb paralysis. Here we have demonstrated that misregulation of iron metabolism from loss of Irp2 causes lower motor neuronal degeneration with significant spinal cord axonopathy. Mitochondria in the lumbar spinal cord showed significantly decreased Complex I and II activities, and abnormal morphology. Lower motor neurons appeared to be the most adversely affected neurons, and we show that functional iron starvation due to misregulation of iron import and storage proteins, including transferrin receptor 1 and ferritin, may have a causal role in disease. We demonstrated that two therapeutic approaches were beneficial for motor neuron survival. First, we activated a homologous protein, IRP1, by oral Tempol treatment and found that axons were partially spared from degeneration. Secondly, we genetically decreased expression of the iron storage protein, ferritin, to diminish functional iron starvation. These data suggest that functional iron deficiency may constitute a previously unrecognized molecular basis for degeneration of motor neurons in mice.

  5. Iron insufficiency compromises motor neurons and their mitochondrial function in Irp2-null mice

    KAUST Repository

    Jeong, Suh Young

    2011-10-07

    Genetic ablation of Iron Regulatory Protein 2 (Irp2, Ireb2), which post-transcriptionally regulates iron metabolism genes, causes a gait disorder in mice that progresses to hind-limb paralysis. Here we have demonstrated that misregulation of iron metabolism from loss of Irp2 causes lower motor neuronal degeneration with significant spinal cord axonopathy. Mitochondria in the lumbar spinal cord showed significantly decreased Complex I and II activities, and abnormal morphology. Lower motor neurons appeared to be the most adversely affected neurons, and we show that functional iron starvation due to misregulation of iron import and storage proteins, including transferrin receptor 1 and ferritin, may have a causal role in disease. We demonstrated that two therapeutic approaches were beneficial for motor neuron survival. First, we activated a homologous protein, IRP1, by oral Tempol treatment and found that axons were partially spared from degeneration. Secondly, we genetically decreased expression of the iron storage protein, ferritin, to diminish functional iron starvation. These data suggest that functional iron deficiency may constitute a previously unrecognized molecular basis for degeneration of motor neurons in mice.

  6. Iron insufficiency compromises motor neurons and their mitochondrial function in Irp2-null mice.

    Directory of Open Access Journals (Sweden)

    Suh Young Jeong

    Full Text Available Genetic ablation of Iron Regulatory Protein 2 (Irp2, Ireb2, which post-transcriptionally regulates iron metabolism genes, causes a gait disorder in mice that progresses to hind-limb paralysis. Here we have demonstrated that misregulation of iron metabolism from loss of Irp2 causes lower motor neuronal degeneration with significant spinal cord axonopathy. Mitochondria in the lumbar spinal cord showed significantly decreased Complex I and II activities, and abnormal morphology. Lower motor neurons appeared to be the most adversely affected neurons, and we show that functional iron starvation due to misregulation of iron import and storage proteins, including transferrin receptor 1 and ferritin, may have a causal role in disease. We demonstrated that two therapeutic approaches were beneficial for motor neuron survival. First, we activated a homologous protein, IRP1, by oral Tempol treatment and found that axons were partially spared from degeneration. Secondly, we genetically decreased expression of the iron storage protein, ferritin, to diminish functional iron starvation. These data suggest that functional iron deficiency may constitute a previously unrecognized molecular basis for degeneration of motor neurons in mice.

  7. Iron deficiency was not the major cause of anemia in rural women of reproductive age in Sidama zone, southern Ethiopia: A cross-sectional study.

    Science.gov (United States)

    Gebreegziabher, Tafere; Stoecker, Barbara J

    2017-01-01

    Anemia, which has many etiologies, is a moderate/severe public health problem in young children and women of reproductive age in many developing countries. The aim of this study was to investigate prevalence of iron deficiency, anemia, and iron deficiency anemia using multiple biomarkers and to evaluate their association with food insecurity and food consumption patterns in non-pregnant women from a rural area of southern Ethiopia. A cross-sectional study was conducted in 202 rural women of reproductive age in southern Ethiopia. Anthropometrics and socio-demographic data were collected. A venipuncture blood sample was analyzed for hemoglobin (Hb) and for biomarkers of iron status. Biomarkers were skewed and were log transformed before analysis. Mean, median, Pearson's correlations and ordinary least-squares regressions were calculated. Median (IQR) Hb was 138 (127, 151) g/L. Based on an altitude-adjusted (1708 m) cutoff of 125 g/L for Hb, 21.3% were anemic. Plasma ferritin was 1.0 g/L; four women (2%) had > 5 mg/L of C-reactive protein (CRP). Of the 43 women who were anemic, 23.3% (10 women) had depleted iron stores based on plasma ferritin. Three of these had elevated soluble transferrin receptors (sTfR). Hemoglobin (Hb) concentration was negatively correlated with sTfR (r = -0.24, p = 0.001), and positively correlated with ferritin (r = 0.17, p = 0.018), plasma iron (r = 0.15, p = 0.046), transferrin saturation (TfS) (r = 0.15, p = 0.04) and body iron (r = 0.14, p = 0.05). Overall prevalence of iron deficiency anemia was only 5%. Iron deficiency anemia was not prevalent in the study population, despite the fact that anemia would be classified as a moderate public health problem.

  8. Efficacy of iron fortification compared to iron supplementation among Vietnamese schoolchildren.

    Science.gov (United States)

    Thi Le, Huong; Brouwer, Inge D; Burema, Jan; Nguyen, Khan Cong; Kok, Frans J

    2006-12-05

    The effect of iron fortification is generally assumed to be less than iron supplementation; however, the magnitude of difference in effects is not known. The present study aims to compare the efficacy of these two strategies on anaemia and iron status. After screening on low Hb, 425 anaemic children in six primary schools in Tam Nong district of Phu Tho province were included in a randomized, placebo-controlled trial comparing two groups receiving iron fortified instant noodles or iron supplementation for 6 months and a control group, with children in all groups having been dewormed. Blood samples were collected before and after intervention for haemoglobin, serum ferritin (SF), serum transferrin receptor (TfR), C-reactive protein (CRP), and haemoglobinopathies analysis. Regression analysis was used to assess the effect of iron fortification and iron supplementation on haemoglobin concentration, SF, TfR, body iron, and anaemic status as outcome variables. The improvement of haemoglobin, SF, and body iron level in the group receiving iron fortification was 42% (2.6 g/L versus 6.2 g/L), 20% (23.5 microg/L versus 117.3 microg/L), and 31.3% (1.4 mg/kg versus 4.4 mg/kg) of that in the iron supplementation group. The prevalence of anaemia dropped to 15.1% in the control group, with an additional reduction of anaemia of 8.5% in the iron supplementation group. The additional reduction due to iron fortification was 5.4%, which amounts to well over 50% of the impact of supplementation. In conclusion, the efficacy of iron fortification based on reduction of prevalence of anaemia, and on the change in haemoglobin level, is about half of the maximum impact of supplementation in case of optimal compliance. Thus, in a population of anaemic children with mild iron deficiency, iron fortification should be the preferred strategy to combat anaemia.

  9. Efficacy of iron fortification compared to iron supplementation among Vietnamese schoolchildren

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    Nguyen Khan

    2006-12-01

    Full Text Available Abstract The effect of iron fortification is generally assumed to be less than iron supplementation; however, the magnitude of difference in effects is not known. The present study aims to compare the efficacy of these two strategies on anaemia and iron status. After screening on low Hb, 425 anaemic children in six primary schools in Tam Nong district of Phu Tho province were included in a randomized, placebo-controlled trial comparing two groups receiving iron fortified instant noodles or iron supplementation for 6 months and a control group, with children in all groups having been dewormed. Blood samples were collected before and after intervention for haemoglobin, serum ferritin (SF, serum transferrin receptor (TfR, C-reactive protein (CRP, and haemoglobinopathies analysis. Regression analysis was used to assess the effect of iron fortification and iron supplementation on haemoglobin concentration, SF, TfR, body iron, and anaemic status as outcome variables. The improvement of haemoglobin, SF, and body iron level in the group receiving iron fortification was 42% (2.6 g/L versus 6.2 g/L, 20% (23.5 μg/L versus 117.3 μg/L, and 31.3% (1.4 mg/kg versus 4.4 mg/kg of that in the iron supplementation group. The prevalence of anaemia dropped to 15.1% in the control group, with an additional reduction of anaemia of 8.5% in the iron supplementation group. The additional reduction due to iron fortification was 5.4%, which amounts to well over 50% of the impact of supplementation. In conclusion, the efficacy of iron fortification based on reduction of prevalence of anaemia, and on the change in haemoglobin level, is about half of the maximum impact of supplementation in case of optimal compliance. Thus, in a population of anaemic children with mild iron deficiency, iron fortification should be the preferred strategy to combat anaemia.

  10. The Iron Status of Sickle Cell Anaemia Patients in Ilorin, North Central Nigeria

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    Musa A. Sani

    2015-01-01

    Full Text Available Objectives. Sickle cell anaemia (SCA is one of the commonest genetic disorders in the world. It is characterized by anaemia, periodic attacks of thrombotic pain, and chronic systemic organ damage. Recent studies have suggested that individuals with SCA especially from developing countries are more likely to be iron deficient rather than have iron overload. The study aims to determine the iron status of SCA patients in Ilorin, Nigeria. Methods. A cross-sectional study of 45 SCA patients in steady state and 45 non-SCA controls was undertaken. FBC, blood film, sFC, sTfR, and sTfR/log sFC index were done on all subjects. Results. The mean patients’ serum ferritin (589.33 ± 427.61 ng/mL was significantly higher than the mean serum ferritin of the controls (184.53 ± 119.74 ng/mL. The mean serum transferrin receptor of the patients (4.24 ± 0.17 μg/mL was higher than that of the controls (3.96 ± 0.17 μg/mL (p=0.290. The mean serum transferrin receptor (sTfR/log serum ferritin index of the patients (1.65 ± 0.27 μg/mL was significantly lower than that of the control (1.82 ± 0.18 μg/mL (p=0.031. Conclusion. Iron deficiency is uncommon in SCA patients and periodic monitoring of the haematological, biochemical, and clinical features for iron status in SCA patients is advised.

  11. c-Myc over-expression in Ramos Burkitt's lymphoma cell line predisposes to iron homeostasis disruption in vitro

    International Nuclear Information System (INIS)

    Habel, Marie-Eve; Jung, Daniel

    2006-01-01

    Burkitt's lymphoma is an aggressive B-cell neoplasm resulting from deregulated c-myc expression. We have previously shown that proliferation of Burkitt's lymphoma cell lines such as Ramos is markedly reduced by iron treatment. It has been shown that iron induces expression of c-myc which, owing to its transcriptional regulatory functions, regulates genes involved in iron metabolism. Transient enhancement of c-myc expression by iron could increase the expression of genes involved in iron incorporation, which could lead to an accumulation of intracellular free iron. Here, we have investigated whether cells with a high basal level of c-Myc were more likely to accumulate free iron. Our results suggest that the basal level of c-Myc in Ramos cells is twofold higher than what is seen in HL-60 cells. Moreover, in Ramos cells, where c-Myc is expressed at a high level, H-ferritin expression is down-regulated, transferrin receptor (CD71) expression is increased, and ferritin translation is inhibited. These modifications in iron metabolism, resulting from the strong basal expression of c-Myc, and amplified by iron addition, could lead to a disruption in homeostasis and consequently to growth arrest

  12. Crystallographic study of the inorganic part of the ferritin molecule

    International Nuclear Information System (INIS)

    Lawrence, J.J.

    1969-01-01

    Diffraction data given by ferritin core, essentially made up of an iron hydroxide, let us propose, for hypothesis, a hexagonal unit cell (a = 11.79 Angstrom c = 9.90 Angstrom). This product cannot be identified with any known iron hydroxide but its diffraction diagram shows some similarities with that δ FeOOH. (author) [fr

  13. Total mortality by transferrin saturation levels: two general population studies and a metaanalysis

    DEFF Research Database (Denmark)

    Ellervik, Christina; Tybjærg-Hansen, Anne; Nordestgaard, Børge G

    2011-01-01

    There is evidence for increased mortality in patients with clinically overt hereditary hemochromatosis. Whether increased transferrin saturation (TS), as a proxy for iron overload is associated with increased mortality in the general population is largely unknown.......There is evidence for increased mortality in patients with clinically overt hereditary hemochromatosis. Whether increased transferrin saturation (TS), as a proxy for iron overload is associated with increased mortality in the general population is largely unknown....

  14. Hepcidin Response to Iron Therapy in Patients with Non-Dialysis Dependent CKD: An Analysis of the FIND-CKD Trial.

    Science.gov (United States)

    Gaillard, Carlo A; Bock, Andreas H; Carrera, Fernando; Eckardt, Kai-Uwe; Van Wyck, David B; Bansal, Sukhvinder S; Cronin, Maureen; Meier, Yvonne; Larroque, Sylvain; Roger, Simon D; Macdougall, Iain C

    2016-01-01

    Hepcidin is the key regulator of iron homeostasis but data are limited regarding its temporal response to iron therapy, and response to intravenous versus oral iron. In the 56-week, open-label, multicenter, prospective, randomized FIND-CKD study, 626 anemic patients with non-dialysis dependent chronic kidney disease (ND-CKD) and iron deficiency not receiving an erythropoiesis stimulating agent were randomized (1:1:2) to intravenous ferric carboxymaltose (FCM), targeting higher (400-600μg/L) or lower (100-200μg/L) ferritin, or to oral iron. Serum hepcidin levels were measured centrally in a subset of 61 patients. Mean (SD) baseline hepcidin level was 4.0(3.5), 7.3(6.4) and 6.5(5.6) ng/mL in the high ferritin FCM (n = 17), low ferritin FCM (n = 16) and oral iron group (n = 28). The mean (SD) endpoint value (i.e. the last post-baseline value) was 26.0(9.1),15.7(7.7) and 16.3(11.0) ng/mL, respectively. The increase in hepcidin from baseline was significantly smaller with low ferritin FCM or oral iron vs high ferritin FCM at all time points up to week 52. Significant correlations were found between absolute hepcidin and ferritin values (r = 0.65, p<0.001) and between final post-baseline increases in both parameters (r = 0.70, p<0.001). The increase in hepcidin levels over the 12-month study generally mirrored the cumulative iron dose in each group. Hepcidin and transferrin saturation (TSAT) absolute values showed no correlation, although there was an association between final post-baseline increases (r = 0.42, p<0.001). Absolute values (r = 0.36, p = 0.004) and final post-baseline increases of hepcidin and hemoglobin (p = 0.30, p = 0.030) correlated weakly. Baseline hepcidin levels were not predictive of a hematopoietic response to iron therapy. In conclusion, hepcidin levels rose in response to either intravenous or oral iron therapy, but the speed and extent of the rise was greatest with intravenous iron targeting a higher ferritin level. However neither the

  15. Iron deficiency in chronic systolic heart failure(indic study

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    Sunil Verma

    2016-01-01

    Full Text Available Background: Chronic systolic heart failure (HF is characterized by the left ventricular dysfunction, exercise intolerance and is associated with neurohormonal activation that affects several organs such as kidney and skeletal muscle. Anemia is common in HF and may worsen symptoms. Iron deficiency (ID is also common in HF patients with or without anemia. Iron is the key cofactor in oxidative metabolism in skeletal muscle and the Krebs cycle. There is a paucity of data regarding iron metabolism in chronic systolic HF in India. Methods: IroN Deficiency In CHF study (INDIC is an observational study that investigated forty chronic heart failure patients for the presence of ID. Serum ferritin (micrograms per liter, serum iron (micrograms per liter, total iron binding capacity (micrograms per liter, transferring (milligrams per deciliter, and transferrin saturation were measured to assess iron status. Results: There were 67.5% (27/40 patients who had ID with a mean serum ferritin level of 76.4 μg/L. Of the 27 iron deficient patients, 22 (55% had an absolute ID, and 5 had a functional ID. Eight out of 27 of the iron deficient patients were anemic (20% of the total cohort, 30% of the iron deficient patients. Anemia was seen in 6 other patients, which was possibly anemia of chronic disease. There was a trend for more advanced New York Heart Association (NYHA class (NYHA III and NYHA IV patients with ID (37.4% vs. 30.77%, P = 0.697. Conclusion: In our study, ID was very common, affecting more than half of the patients with systolic HF. Absolute ID was the most common cause of ID and patients with ID had a tendency to have advanced NYHA class. Our study also demonstrated that ID can occur in the absence of anemia (iron depletion.

  16. STUDY OF WOMEN'S IRON-DEFICIENCY ANAEMIA IN REPRODUCTIVE AGE REFERRED TO OBSTETRIC AND GYNECOLOGY CENTER OF HOSPITAL

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    H. R. Sadeghipour Roudsari

    1996-07-01

    Full Text Available We studied the prevalence of iron-deficiency anaemia in women of reproductive age, between 15 to 49, with a mean age of 31-56±1.34 years, attending Mirzakoochak khan Hospital OB. GYN. Center for routine gynecological and obstetrical examination. We compa'tred mean values for the serum tests and haematological data and investigated etiological factors such as age, marital status, education, spouse's education, occupation, spouse's occuption, number of days of menstrual bleeding, severity of menstrual bleeding, pregnancy status, number of pregnancies, number of deliveries, intervals between successive pregnancies, ami smoking status, as probable causes of iron-deficiency anaemia in women. Moreover the relevance between occurance of iron-deficiency anaemia or ferritin serum level to etiological factors and diagnostic laboratory tests arc analyzed. A serum diagnosis of iron-deficiency was accepted on the basis of one or more of the following test results: serum ferritin levels below 12 figf with or without transferrin saturation below 16%. For the purpose of this study anaemia was difind as haemoglobin (Hb below 12 gdf . Women have been classified into two groups of anaemic Vs normal according to the diagnosis. Prevalence of anaemia among 41 subjects with complete laboratory results was 36.58%. Moreover, the probability of occurance of iron-deficiency anaemia, in general population was fount! to be 33.3%. As a result a significant relationship was observed between occurance of iron-deficiency anaemia and diagnostic laboratory tests including serum ferritin, serum iron, total iron-binding capacity (TIBC, transferring saturation (%, Hb, haematocrit (Hct, mean corpuscular haemoglobin (MCH, mean corpuscular volume (MCV, mean corpuscular haemoglobin concentration (MCHC, and etiological factors such as number of days of menstrual bleeding, severity of menstrual bleeding. Same relationship was observed between serum ferritin levels and

  17. HFE gene mutations and iron status of Brazilian blood donors.

    Science.gov (United States)

    Santos, P C J L; Cançado, R D; Terada, C T; Rostelato, S; Gonzales, I; Hirata, R D C; Hirata, M H; Chiattone, C S; Guerra-Shinohara, E M

    2010-01-01

    Mutations of the HFE and TFR2 genes have been associated with iron overload. HFE and TFR2 mutations were assessed in blood donors, and the relationship with iron status was evaluated. Subjects (N = 542) were recruited at the Hemocentro da Santa Casa de São Paulo, São Paulo, Brazil. Iron status was not influenced by HFE mutations in women and was independent of blood donation frequency. In contrast, men carrying the HFE 282CY genotype had lower total iron-binding capacity (TIBC) than HFE 282CC genotype carriers. Men who donated blood for the first time and were carriers of the HFE 282CY genotype had higher transferrin saturation values and lower TIBC concentrations than those with the homozygous wild genotype for the HFE C282Y mutation. Moreover, in this group of blood donors, carriers of HFE 63DD plus 63HD genotypes had higher serum ferritin values than those with the homozygous wild genotype for HFE H63D mutation. Multiple linear regression analysis showed that HFE 282CY leads to a 17.21% increase (P = 0.018) and a 83.65% decrease (P = 0.007) in transferrin saturation and TIBC, respectively. In addition, serum ferritin is influenced by age (3.91%, P = 0.001) and the HFE 63HD plus DD genotype (55.84%, P = 0.021). In conclusion, the HFE 282Y and 65C alleles were rare, while the HFE 63D allele was frequent in Brazilian blood donors. The HFE C282Y and H63D mutations were associated with alterations in iron status in blood donors in a gender-dependent manner.

  18. HFE gene mutations and iron status of Brazilian blood donors

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    P.C.J.L. Santos

    2010-01-01

    Full Text Available Mutations of the HFE and TFR2 genes have been associated with iron overload. HFE and TFR2 mutations were assessed in blood donors, and the relationship with iron status was evaluated. Subjects (N = 542 were recruited at the Hemocentro da Santa Casa de São Paulo, São Paulo, Brazil. Iron status was not influenced by HFE mutations in women and was independent of blood donation frequency. In contrast, men carrying the HFE 282CY genotype had lower total iron-binding capacity (TIBC than HFE 282CC genotype carriers. Men who donated blood for the first time and were carriers of the HFE 282CY genotype had higher transferrin saturation values and lower TIBC concentrations than those with the homozygous wild genotype for the HFE C282Y mutation. Moreover, in this group of blood donors, carriers of HFE 63DD plus 63HD genotypes had higher serum ferritin values than those with the homozygous wild genotype for HFE H63D mutation. Multiple linear regression analysis showed that HFE 282CY leads to a 17.21% increase (P = 0.018 and a 83.65% decrease (P = 0.007 in transferrin saturation and TIBC, respectively. In addition, serum ferritin is influenced by age (3.91%, P = 0.001 and the HFE 63HD plus DD genotype (55.84%, P = 0.021. In conclusion, the HFE 282Y and 65C alleles were rare, while the HFE 63D allele was frequent in Brazilian blood donors. The HFE C282Y and H63D mutations were associated with alterations in iron status in blood donors in a gender-dependent manner.

  19. Ferritin-Templated Quantum-Dots for Quantum Logic Gates

    Science.gov (United States)

    Choi, Sang H.; Kim, Jae-Woo; Chu, Sang-Hyon; Park, Yeonjoon; King, Glen C.; Lillehei, Peter T.; Kim, Seon-Jeong; Elliott, James R.

    2005-01-01

    Quantum logic gates (QLGs) or other logic systems are based on quantum-dots (QD) with a stringent requirement of size uniformity. The QD are widely known building units for QLGs. The size control of QD is a critical issue in quantum-dot fabrication. The work presented here offers a new method to develop quantum-dots using a bio-template, called ferritin, that ensures QD production in uniform size of nano-scale proportion. The bio-template for uniform yield of QD is based on a ferritin protein that allows reconstitution of core material through the reduction and chelation processes. One of the biggest challenges for developing QLG is the requirement of ordered and uniform size of QD for arrays on a substrate with nanometer precision. The QD development by bio-template includes the electrochemical/chemical reconsitution of ferritins with different core materials, such as iron, cobalt, manganese, platinum, and nickel. The other bio-template method used in our laboratory is dendrimers, precisely defined chemical structures. With ferritin-templated QD, we fabricated the heptagonshaped patterned array via direct nano manipulation of the ferritin molecules with a tip of atomic force microscope (AFM). We also designed various nanofabrication methods of QD arrays using a wide range manipulation techniques. The precise control of the ferritin-templated QD for a patterned arrangement are offered by various methods, such as a site-specific immobilization of thiolated ferritins through local oxidation using the AFM tip, ferritin arrays induced by gold nanoparticle manipulation, thiolated ferritin positioning by shaving method, etc. In the signal measurements, the current-voltage curve is obtained by measuring the current through the ferritin, between the tip and the substrate for potential sweeping or at constant potential. The measured resistance near zero bias was 1.8 teraohm for single holoferritin and 5.7 teraohm for single apoferritin, respectively.

  20. Effects of transferrin on aromatase activity in porcine granulosa cells in vitro.

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    Małgorzata Duda

    2009-01-01

    Full Text Available Proliferating cells have an absolute requirement for iron, which is delivered by transferrin with subsequent intracellular transport via the transferrin receptor. Recent studies have reported that transferrin plays a crucial role in the local regulation of ovarian function, apart from its iron-binding characteristic. Therefore, the present study was undertaken to explore the possible role of transferrin in porcine granulosa cells function by examining its influence on aromatase activity, the most important indicator of follicular cell differentiation. In the first series of studies, pig granulosa cells isolated from small, immature follicles were cultured in the presence of transferrin alone (10 microg/ml or 100 microg/ml or with the addition of FSH (100ng/ml. The second series of studies was undertaken to determine transferrin-stimulated granulosa cells ability to aromatize exogenous testosterone (1x10(-7M. One hour after the establishment of cultures an aromatase inhibitor CGS16949A was added to test its influence on estradiol production. After 48 hours, cultures were terminated and cells were processed for immunocytochemical staining of aromatase. Media were frozen for further estradiol level analysis. Positive immunostaining for aromatase was found in all granulosa cell cultures. The intensity of immunostaining was always stronger in cultures supplemented with FSH whereas the addition of transferrin had no effect. Granulosa cells in vitro synthesized the highest amount of estradiol after the addition of FSH and exogenous testosterone as measured radioimmunologically. Concomitant treatment with FSH and transferrin caused an inhibition of FSH-stimulated aromatase activity. The production of estradiol also declined in the presence of FSH, testosterone and transferrin. This study demonstrates that transferrin had a dose-dependent inhibitory effect on FSH-stimulated aromatase activity, which was confirmed by radioimmunoassay. Our results indicate

  1. Reduced ferritin levels in individuals with non-O blood group

    DEFF Research Database (Denmark)

    Rigas, Andreas S; Berkfors, Adam A; Pedersen, Ole B

    2017-01-01

    stores expressed as ferritin levels. STUDY DESIGN AND METHODS: Ferritin levels were measured at least once for 30,595 Danish Blood Donor Study participants. Linear regression analyses were performed with the ABO blood group as explanatory variable and adjusted for age, number of donations 3 years before......BACKGROUND: Genomewide association studies have reported alleles in the ABO locus to be associated with ferritin levels. These studies warrant the investigation of a possible association between the ABO blood group and ferritin levels. We aimed to explore if ABO blood group is associated with iron...... blood group was associated with a ferritin level of less than 15 ng/mL. RESULTS: Non-O blood group donors had lower ferritin levels than blood group O donors, regardless of sex. Accordingly, risk of ferritin level of less than 15 ng/mL was increased for individuals with non-O blood group compared with O...

  2. THE EFFECT OF HAEMOCHROMATOSIS MUTATION ON IRON OVERLOAD IN THALASSAEMIA MAJOR PATIENTS

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    Tapas Ranjan Behera

    2016-11-01

    Full Text Available BACKGROUND Haemochromatosis is a genetic form of iron overload due to a defective HFE gene. Secondary iron overload is the main complication in transfusion-dependent thalassaemia major patients. This study aims at evaluating the degree of iron overload in β-thalassaemia major patients with and without HFE mutations (C282Y, H63D and S65C. MATERIALS AND METHODS A descriptive observational study was conducted including fifty diagnosed -thalassaemia major cases. Detailed clinical history and iron profile was estimated. DNA analysis by PCR-RFLP method for HFE gene mutations was performed. RESULTS After DNA analysis of all the thalassaemia major cases, two groups were identified, one with HFE gene mutation and other without HFE gene mutation. Iron profile of both the groups (with and without HFE gene mutation was estimated and compared. Only H63D mutation (out of three HFE gene mutations was detected in 16% cases (8 out of 50 cases, which comprised the group with mutation. Comparison of iron parameters between two groups (with and without HFE gene mutation showed significant difference in percent transferrin saturation (p=0.02, while other iron parameters (serum iron and serum ferritin did not show significant difference. CONCLUSION No significant difference between serum ferritin values (a marker of iron overload of groups with and without mutation (mean ferritin level 4641±2166 ng/mL and 4170±2461 ng/mL, respectively was found (p=0.61, in a patient population in whom transfusion protocol and proper chelation regimen was followed.

  3. Ferritin gene organization: differences between plants and animals suggest possible kingdom-specific selective constraints.

    Science.gov (United States)

    Proudhon, D; Wei, J; Briat, J; Theil, E C

    1996-03-01

    Ferritin, a protein widespread in nature, concentrates iron approximately 10(11)-10(12)-fold above the solubility within a spherical shell of 24 subunits; it derives in plants and animals from a common ancestor (based on sequence) but displays a cytoplasmic location in animals compared to the plastid in contemporary plants. Ferritin gene regulation in plants and animals is altered by development, hormones, and excess iron; iron signals target DNA in plants but mRNA in animals. Evolution has thus conserved the two end points of ferritin gene expression, the physiological signals and the protein structure, while allowing some divergence of the genetic mechanisms. Comparison of ferritin gene organization in plants and animals, made possible by the cloning of a dicot (soybean) ferritin gene presented here and the recent cloning of two monocot (maize) ferritin genes, shows evolutionary divergence in ferritin gene organization between plants and animals but conservation among plants or among animals; divergence in the genetic mechanism for iron regulation is reflected by the absence in all three plant genes of the IRE, a highly conserved, noncoding sequence in vertebrate animal ferritin mRNA. In plant ferritin genes, the number of introns (n = 7) is higher than in animals (n = 3). Second, no intron positions are conserved when ferritin genes of plants and animals are compared, although all ferritin gene introns are in the coding region; within kingdoms, the intron positions in ferritin genes are conserved. Finally, secondary protein structure has no apparent relationship to intron/exon boundaries in plant ferritin genes, whereas in animal ferritin genes the correspondence is high. The structural differences in introns/exons among phylogenetically related ferritin coding sequences and the high conservation of the gene structure within plant or animal kingdoms of the gene structure within plant or animal kingdoms suggest that kingdom-specific functional constraints may

  4. The impact of H63D HFE gene carriage on hemoglobin and iron status in children.

    Science.gov (United States)

    Barbara, Kaczorowska-Hac; Marcin, Luszczyk; Jedrzej, Antosiewicz; Wieslaw, Ziolkowski; Elzbieta, Adamkiewicz-Drozynska; Malgorzata, Mysliwiec; Ewa, Milosz; Jacek, Kaczor Jan

    2016-12-01

    The molecular mechanism that regulates iron homeostasis is based on a network of signals, which reflect on the iron requirements of the body. Hereditary hemochromatosis is a heterogenic metabolic syndrome which is due to unchecked transfer of iron into the bloodstream and its toxic effects on parenchymatous organs. It is caused by the mutation of genes that encode proteins that help hepcidin to monitor serum iron. These proteins include the human hemochromatosis protein -HFE, transferrin-receptor 2, hemojuvelin in rare instances, and ferroportin. HFE-related hemochromatosis is the most frequent form of the disease. Interestingly, the low penetrance of polymorphic HFE genes results in rare clinical presentation of the disease, predominantly in middle-aged males. Taking into account the wide dispersion of HFE mutation in our population and also its unknown role in heterozygotes, we analyzed the impact of H63D HFE carriage in the developmental age, with respect to gender, on the iron status and hemoglobin concentration of carriers in comparison to those of wild-type HFE gene (12.7 ± 3.07 years, 42 boys and 41 girls). H63D carriers presented higher blood iron, transferrin saturation, and ferritin concentration than wild-type probands (p HFE heterozygotes.

  5. Differential transferrin expression in placentae from normal and abnormal pregnancies: a pilot study

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    Bukovsky Antonin

    2008-07-01

    Full Text Available Abstract Background The placenta is an important site for iron metabolism in humans. It transfers iron from the mother to the fetus. One of the major iron transport proteins is transferrin, which is a blood plasma protein crucial for iron uptake. Its localization and expression may be one of the markers to distinguish placental dysfunction. Methods In the experimental study we used antibody preparation, mass spectrometric analysis, biochemical and immunocytochemical methods for characterization of transferrin expression on the human choriocarcinoma cell line JAR (JAR cells, placental lysates, and cryostat sections. Newly designed monoclonal antibody TRO-tf-01 to human transferrin was applied on human placentae from normal (n = 3 and abnormal (n = 9 pregnancies. Results Variations of transferrin expression were detected in villous syncytiotrophoblast, which is in direct contact with maternal blood. In placentae from normal pregnancies, the expression of transferrin in the syncytium was significantly lower (p Conclusion These observations suggest that in the case of abnormal pregnancies, the fetus may require higher levels of transferrin in order to prevent iron depletion due to the stress from the placental dysfunction.

  6. Impact of multi-micronutrient fortified rice on hemoglobin, iron and vitamin A status of Cambodian schoolchildren

    DEFF Research Database (Denmark)

    Perignon, Marlene; Fiorentino, Marion; Khov, Kuong

    2016-01-01

    In Cambodia, micronutrient deficiencies remain a critical public health problem. Our objective was to evaluate the impact of multi-micronutrient fortified rice (MMFR) formulations, distributed through a World Food Program school-meals program (WFP-SMP), on the hemoglobin concentrations and iron......Rice) or unfortified rice (placebo) six days a week for six months. Four additional schools not participating in WFP-SMP were randomly selected as controls. A total of 2440 schoolchildren (6–16 years old) participated in the biochemical study. Hemoglobin, iron status, estimated using inflammation-adjusted ferritin...... and transferrin receptors concentrations, and VA status, assessed using inflammation-adjusted retinol-binding protein concentration, were measured at the baseline, as well as at three and six months. Baseline prevalence of anemia, depleted iron stores, tissue iron deficiency, marginal VA status and VA deficiency...

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

    Science.gov (United States)

    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 1.5 × ULN, including steatosis, fibrosis, hepatocellular ballooning, and diagnosis of NASH (P 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.

  8. Lethal Cardiomyopathy in Mice Lacking Transferrin Receptor in the Heart

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    Wenjing Xu

    2015-10-01

    Full Text Available Both iron overload and iron deficiency have been associated with cardiomyopathy and heart failure, but cardiac iron utilization is incompletely understood. We hypothesized that the transferrin receptor (Tfr1 might play a role in cardiac iron uptake and used gene targeting to examine the role of Tfr1 in vivo. Surprisingly, we found that decreased iron, due to inactivation of Tfr1, was associated with severe cardiac consequences. Mice lacking Tfr1 in the heart died in the second week of life and had cardiomegaly, poor cardiac function, failure of mitochondrial respiration, and ineffective mitophagy. The phenotype could only be rescued by aggressive iron therapy, but it was ameliorated by administration of nicotinamide riboside, an NAD precursor. Our findings underscore the importance of both Tfr1 and iron in the heart, and may inform therapy for patients with heart failure.

  9. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... may be diagnosed with iron-deficiency anemia if you have low iron or ferritin levels in your blood. More testing may be needed to rule out other types of anemia. Tests for gastrointestinal ...

  10. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... have less hemoglobin than normal. Hemoglobin is a protein inside red blood cells that carries oxygen from ... stored iron has been used. Ferritin is a protein that helps store iron in your body. Reticulocyte ...

  11. Aqueous humor ferritin in hereditary hyperferritinemia cataract syndrome.

    Science.gov (United States)

    Lenzhofer, Markus; Schroedl, Falk; Trost, Andrea; Kaser-Eichberger, Alexandra; Wiedemann, Helmut; Strohmaier, Clemens; Hohensinn, Melchior; Strasser, Michael; Muckenthaler, Martina U; Grabner, Guenther; Aigner, Elmar; Reitsamer, Herbert A

    2015-04-01

    Hereditary hyperferritinemia cataract syndrome (HHCS) is a rare autosomal dominant hereditary disease, characterized by hyperferritinemia but with absence of body iron excess and early onset of bilateral cataracts. Although 5- to 20-fold increased serum ferritin concentrations have been reported in HHCS patients, data of ferritin levels in aqueous humor have not been obtained. We therefore aimed to investigate the ferritin levels in aqueous humor and serum and further present histological and ultrastructural data of the lens. During cataract extraction and intraocular lens implantation, aqueous humor and lens aspirate of a 37-year-old HHCS patient were obtained from both eyes. Ferritin levels in serum and aqueous humor were quantitatively analyzed via immunoassays in the HHCS patient and healthy control subjects (n = 6). Lens aspirate in HHCS was analyzed histologically and at the ultrastructural level. Further, genetic mutation screening by polymerase chain reaction and DNA sequencing in blood was performed. Serum ferritin levels in the control group were 142.2 ± 38.7 μg/L, whereas in the HHCS patient, this parameter was excessively increased (1086 μg/L). Analysis of ferritin in aqueous humor revealed 6.4 ± 3.8 μg/L in normal control subjects and 146.3 μg/L (OD) and 160.4 μg/L (OS) in the HHCS patient. DNA analysis detected a C>A mutation on position +18, a T>G mutation on position +22, a T>C mutation on position +24, and a T>G polymorphism on position +26 in the iron-responsive element of the light-chain ferritin (L-ferritin) gene. In the HHCS patient, a 23-fold (OD) to 25-fold (OS) increased aqueous humor ferritin level was detected. Therefore, the formation of bilateral cataract in HHCS is most likely a result of elevated aqueous humor ferritin. In addition, a novel mutation in this rare disease in the iron-responsive element of L-ferritin gene is reported.

  12. Cloning and characterization of transferrin cDNA and rapid detection of transferrin gene polymorphism in rainbow trout (Oncorhynchus mykiss).

    Science.gov (United States)

    Tange, N; Jong-Young, L; Mikawa, N; Hirono, I; Aoki, T

    1997-12-01

    A cDNA clone of rainbow trout (Oncorhynchus mykiss) transferrin was obtained from a liver cDNA library. The 2537-bp cDNA sequence contained an open reading frame encoding 691 amino acids and the 5' and 3' noncoding regions. The amino acid sequences at the iron-binding sites and the two N-linked glycosylation sites, and the cysteine residues were consistent with known, conserved vertebrate transferrin cDNA sequences. Single N-linked glycosylation sites existed on the N- and C-lobe. The deduced amino acid sequence of the rainbow trout transferrin cDNA had 92.9% identities with transferrin of coho salmon (Oncorhynchus kisutch); 85%, Atlantic salmon (Salmo salar); 67.3%, medaka (Oryzias latipes); 61.3% Atlantic cod (Gadus morhua); and 59.7%, Japanese flounder (Paralichthys olivaceus). The long and accurate polymerase chain reaction (LA-PCR) was used to amplify approximately 6.5 kb of the transferrin gene from rainbow trout genomic DNA. Restriction fragment length polymorphisms (RFLPs) of the LA-PCR products revealed three digestion patterns in 22 samples.

  13. The Effect of Iron Status on Risk of Coronary Artery Disease: A Mendelian Randomization Study-Brief Report.

    Science.gov (United States)

    Gill, Dipender; Del Greco M, Fabiola; Walker, Ann P; Srai, Surjit K S; Laffan, Michael A; Minelli, Cosetta

    2017-09-01

    Iron status is a modifiable trait that has been implicated in cardiovascular disease. This study uses the Mendelian randomization technique to investigate whether there is any causal effect of iron status on risk of coronary artery disease (CAD). A 2-sample Mendelian randomization approach is used to estimate the effect of iron status on CAD risk. Three loci (rs1800562 and rs1799945 in the HFE gene and rs855791 in TMPRSS6 ) that are each associated with serum iron, transferrin saturation, ferritin, and transferrin in a pattern suggestive of an association with systemic iron status are used as instruments. SNP (single-nucleotide polymorphism)-iron status association estimates are based on a genome-wide association study meta-analysis of 48 972 individuals. SNP-CAD estimates are derived by combining the results of a genome-wide association study meta-analysis of 60 801 CAD cases and 123 504 controls with those of a meta-analysis of 63 746 CAD cases and 130 681 controls obtained from Metabochip and genome-wide association studies. Combined Mendelian randomization estimates are obtained for each marker by pooling results across the 3 instruments. We find evidence of a protective effect of higher iron status on CAD risk (iron odds ratio, 0.94 per SD unit increase; 95% confidence interval, 0.88-1.00; P =0.039; transferrin saturation odds ratio, 0.95 per SD unit increase; 95% confidence interval, 0.91-0.99; P =0.027; log-transformed ferritin odds ratio, 0.85 per SD unit increase; 95% confidence interval, 0.73-0.98; P =0.024; and transferrin odds ratio, 1.08 per SD unit increase; 95% confidence interval, 1.01-1.16; P =0.034). This Mendelian randomization study supports the hypothesis that higher iron status reduces CAD risk. These findings may highlight a therapeutic target. © 2017 American Heart Association, Inc.

  14. Relation between serum lipoperoxide concentrations and iron or copper status over one year in Cuban adult men

    Energy Technology Data Exchange (ETDEWEB)

    Arnaud, J.; Renversez, J.C.; Favier, A.E. [Dept. de Biologie Integree, CHUG, Grenoble (France); Fleites, P.; Perez-Cristia, R. [Centro national de Toxicologia (CENATOX), La Habana (Cuba); Chassagne, M.; Barnouin, J. [INRA, Unite d' Ecopathologie, Saint Genes Champanelle (France); Verdura, T. [Inst. Finlay, La Lisa, La Habana (Cuba); Garcia, I.G. [Inst. de Farmacia y Alimentos, La Coronela, La Lisa, Ciudad de la Habana (Cuba); Tressol, J.C. [INRA, Unite maladies metaboliques et micronutriments, Saint Genes Champanelle (France)

    2001-07-01

    The aims of this study were to determine the relations between iron and copper status and lipid peroxidation at different periods over one year in low-income and low-energy intake healthy subjects. The study was conducted in 199 middle-aged healthy Cuban men from March 1995 to February 1996. Iron status was assessed by the determination of serum ferritin, transferrin saturation, whole blood hemoglobin and iron intakes. Copper status was evaluated by the determination of serum copper and copper intakes. Serum thiobarbituric acid substances (TBARS) determination was used as an index of lipid peroxidation. Rank correlations were observed between serum TBARS concentrations and iron or copper status indices at different periods. In period 3 (end of the rainy season), serum TBARS and ferritin concentrations were maximum whereas blood hemoglobin levels and iron intake were minimum. Serum TBARS concentrations were significantly higher than the reference values of the laboratory whereas, iron and copper status were within the reference ranges. These results suggested that iron and copper status may be associated with lipid peroxidation in subjects without metal overloads and that variations over the year needed to be taken in account. (orig.)

  15. Expression of Iron-Related Proteins Differentiate Non-Cancerous and Cancerous Breast Tumors

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    Sara Pizzamiglio

    2017-02-01

    Full Text Available We have previously reported hepcidin and ferritin increases in the plasma of breast cancer patients, but not in patients with benign breast disease. We hypothesized that these differences in systemic iron homeostasis may reflect alterations in different iron-related proteins also play a key biochemical and regulatory role in breast cancer. Thus, here we explored the expression of a bundle of molecules involved in both iron homeostasis and tumorigenesis in tissue samples. Enzyme-linked immunosorbent assay (ELISA or reverse-phase protein array (RPPA, were used to measure the expression of 20 proteins linked to iron processes in 24 non-cancerous, and 56 cancerous, breast tumors. We found that cancerous tissues had higher level of hepcidin than benign lesions (p = 0.012. The univariate analysis of RPPA data highlighted the following seven proteins differentially expressed between non-cancerous and cancerous breast tissue: signal transducer and transcriptional activator 5 (STAT5, signal transducer and activator of transcription 3 (STAT3, bone morphogenetic protein 6 (BMP6, cluster of differentiation 74 (CD74, transferrin receptor (TFRC, inhibin alpha (INHA, and STAT5_pY694. These findings were confirmed for STAT5, STAT3, BMP6, CD74 and INHA when adjusting for age. The multivariate statistical analysis indicated an iron-related 10-protein panel effective in separating non-cancerous from cancerous lesions including STAT5, STAT5_pY694, myeloid differentiation factor 88 (MYD88, CD74, iron exporter ferroportin (FPN, high mobility group box 1 (HMGB1, STAT3_pS727, TFRC, ferritin heavy chain (FTH, and ferritin light chain (FTL. Our results showed an association between some iron-related proteins and the type of tumor tissue, which may provide insight in strategies for using iron chelators to treat breast cancer.

  16. Urinary hepcidin level as an early predictor of iron deficiency in children: A case control study

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    Gharib Amal F

    2011-08-01

    Full Text Available Abstract Background The ideal screening test would be capable of identifying iron deficiency in the absence of anemia. We tried to detect role of urinary hepcidin-25 level in early prediction of iron deficiency in children. Methods This is a case control study performed on 100 children in Hematology Unit of Pediatric Department, Zagazig University Hospital, Egypt. Our study included 25 cases of iron deficiency (ID stage-1 (iron depletion, 25 cases ID stage-2 (iron-deficient erythropoiesis, 25 cases ID stage-3 (iron deficiency anemia and 25 healthy children as a control group. Estimation of iron status parameters was done. Urinary hepcidin-25 level was detected. Results Urinary hepcidin-25 level was significantly lower in all stages of iron deficiency than in control group, more significant reduction in its level was observed with the progress in severity of iron deficiency. Urinary hepcidin showed significant positive correlation with hemoglobin, mean corpuscular volume, hematocrit value, serum iron and ferritin and transferrin saturation. In contrary, it showed significant negative correlation with serum transferrin and total iron binding capacity. Urinary hepcidin at cutoff point ≤0.94 nmol/mmol Cr could Predict ID stage-1 with sensitivity 88% and specificity 88%. Cutoff point ≤0.42 nmol/mmol Cr could predict ID stage-2 with sensitivity 96% and specificity 92%. Cutoff point ≤0.08 nmol/mmol Cr could Predict ID stage-3 with Sensitivity 96% and specificity 100%. Conclusions We can conclude that detection of urinary hepcidin-25 level was a simple and non invasive test and could predict iron deficiency very early, before appearance of hematological affections.

  17. The effect of glycosylation on the transferrin structure: A molecular dynamic simulation analysis.

    Science.gov (United States)

    Ghanbari, Z; Housaindokht, M R; Bozorgmehr, M R; Izadyar, M

    2016-09-07

    Transferrins have been defined by the highly cooperative binding of iron and a carbonate anion to form a Fe-CO3-Tf ternary complex. As such, the layout of the binding site residues affects transferrin function significantly; In contrast to N-lobe, C-lobe binding site of the transferrin structure has been less characterized and little research which surveyed the interaction of carbonate with transferrin in the C-lobe binding site has been found. In the present work, molecular dynamic simulation was employed to gain access into the molecular level understanding of carbonate binding site and their interactions in each lobe. Residues responsible for carbonate binding of transferrin structure were pointed out. In addition, native human transferrin is a glycoprotein that two N-linked complex glycan chains located in the C-lobe. Usually, in the molecular dynamic simulation for simplifying, glycan is removed from the protein structure. Here, we explore the effect of glycosylation on the transferrin structure. Glycosylation appears to have an effect on the layout of the binding site residue and transferrin structure. On the other hand, sometimes the entire transferrin formed by separated lobes that it allows the results to be interpreted in a straightforward manner rather than more parameters required for full length protein. But, it should be noted that there are differences between the separated lobe and full length transferrin, hence, a comparative analysis by the molecular dynamic simulation was performed to investigate such structural variations. Results revealed that separation in C-lobe caused a significant structural variation in comparison to N-lobe. Consequently, the separated lobes and the full length one are different, showing the importance of the interlobe communication and the impact of the lobes on each other in the transferrin structure. Copyright © 2016 Elsevier Ltd. All rights reserved.

  18. Clinical Significance of Reticulocyte Hemoglobin Content in the Diagnosis of Iron Deficiency Anemia

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    Mustafa Karagülle

    2013-06-01

    Full Text Available OBJECTIVE: The aim of this study was to evaluate the clinical significance of reticulocyte hemoglobin content (CHr in the diagnosis of iron deficiency anemia (IDA and to compare it with other conventional iron parameters. METHODS: A total of 32 female patients with IDA (serum hemoglobin 120 g/L and serum ferritin <20 ng/mL were enrolled. RESULTS: CHr was 24.95±3.92 pg in female patients with IDA and 29.93±2.96 pg in female patients with iron deficiency. CHr showed a significant positive correlation with hemoglobin, mean corpuscular volume, mean corpuscular hemoglobin, mean corpuscular hemoglobin concentration, serum iron, and transferrin saturation and a significant negative correlation with transferrin and total iron-binding capacity. The cut-off value of CHr for detecting IDA was 29 pg. CONCLUSION: Our data demonstrate that CHr is a useful parameter that can be confidently used in the diagnosis of IDA, and a CHr cut-off value of 29 pg predicts IDA.

  19. Altered erythropoiesis and iron metabolism in carriers of thalassemia

    Science.gov (United States)

    Guimarães, Jacqueline S.; Cominal, Juçara G.; Silva-Pinto, Ana Cristina; Olbina, Gordana; Ginzburg, Yelena Z.; Nandi, Vijay; Westerman, Mark; Rivella, Stefano; de Souza, Ana Maria

    2014-01-01

    The thalassemia syndromes (α- and β-thalassemia) are the most common and frequent disorders associated with ineffective erythropoiesis. Imbalance of α- or β-globin chain production results in impaired red blood cell synthesis, anemia and more erythroid progenitors in the blood stream. While patients affected by these disorders show definitive altered parameters related to erythropoiesis, the relationship between the degree of anemia, altered erythropoiesis and dysfunctional iron metabolism have not been investigated in both α-thalassemia carriers (ATC) and β-thalassemia carriers (BTC). Here we demonstrate that ATC have a significantly reduced hepcidin and increased soluble transferrin receptor levels but relatively normal hematological findings. In contrast, BTC have several hematological parameters significantly different from controls, including increased soluble transferrin receptor and erythropoietin levels. These changings in both groups suggest an altered balance between erythropoiesis and iron metabolism. The index sTfR/log ferrin and (hepcidin/ferritin)/sTfR are respectively increased and reduced relative to controls, proportional to the severity of each thalassemia group. In conclusion, we showed in this study, for the first time in the literature, that thalassemia carriers have altered iron metabolism and erythropoiesis. PMID:25307880

  20. The Study of HFE Genotypes and Its Expression Effect on Iron Status of Iranian Haemochromatosis, Iron Deficiency Anemia Patients, Iron-Taker and Non Iron-Taker Controls.

    Science.gov (United States)

    Beiranvand, Elham; Abediankenari, Saeid; Rostamian, Mosayeb; Beiranvand, Behnoush; Naazeri, Saeed

    2015-01-01

    The role of HFE gene mutations or its expression in regulation of iron metabolism of hereditary haemochromatosis (HH) patients is remained controversial. Therefore here the correlation between two common HFE genotype (p.C282Y, p.H63D) and HFE gene expression with iron status in HH, iron deficiency anemia (IDA) and healthy Iranian participants was studied. For this purpose genotype determination was done by polymerase chain reaction--restriction fragment length polymorphism (PCR-RFLP). Real-Time PCR was applied for evaluation of HFE gene expression. Biochemical parameters and iron consumption were also assessed. Homozygote p.H63D mutation was seen in all HH patients and p.C282Y was not observed in any member of the population. A significant correlation was observed between serum ferritin (SF) level and gender or age of HH patients. p.H63D homozygote was seen to be able to significantly increase SF and transferrin saturation (TS) level without affecting on liver function. Our results also showed that iron consumption affects on TS level increasing. HFE gene expression level of IDA patients was significantly higher than other groups. Also the HFE gene expression was negatively correlated with TS. Finally, the main result of our study showed that loss of HFE function in HH is not derived from its gene expression inhibition and much higher HFE gene expression might lead to IDA. However we propose repeating of the study for more approval of our finding.

  1. Iron deficiency in blood donors

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    Rodolfo Delfini Cançado

    Full Text Available CONTEXT: Blood donation results in a substantial loss of iron (200 to 250 mg at each bleeding procedure (425 to 475 ml and subsequent mobilization of iron from body stores. Recent reports have shown that body iron reserves generally are small and iron depletion is more frequent in blood donors than in non-donors. OBJECTIVE: The aim of this study was to evaluate the frequency of iron deficiency in blood donors and to establish the frequency of iron deficiency in blood donors according to sex, whether they were first-time or multi-time donors, and the frequency of donations per year. DESIGN: From September 20 to October 5, 1999, three hundred blood donors from Santa Casa Hemocenter of São Paulo were studied. DIAGNOSTIC TESTS: Using a combination of biochemical measurements of iron status: serum iron, total iron-binding capacity, transferrin saturation index, serum ferritin and the erythrocyte indices. RESULTS: The frequency of iron deficiency in blood donors was 11.0%, of whom 5.5% (13/237 were male and 31.7% (20/63 female donors. The frequency of iron deficiency was higher in multi-time blood donors than in first-time blood donors, for male blood donors (7.6% versus 0.0%, P < 0.05 and female ones (41.5% versus 18.5%, P < 0.05. The frequency of iron deficiency found was higher among the male blood donors with three or more donations per year (P < 0.05 and among the female blood donors with two or more donations per year (P < 0.05. CONCLUSIONS: We conclude that blood donation is a very important factor for iron deficiency in blood donors, particularly in multi-time donors and especially in female donors. The high frequency of blood donors with iron deficiency found in this study suggests a need for a more accurate laboratory trial, as hemoglobin or hematocrit measurement alone is not sufficient for detecting and excluding blood donors with iron deficiency without anemia.

  2. Low prevalence of iron deficiency anemia between 1981 and 2010 in Chilean women of childbearing age.

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    Israel Ríos-Castillo

    2013-09-01

    Full Text Available Objective. To determine the prevalence of anemia and iron status among Chilean women of childbearing age between 1981 and 2010. Materials and methods. Calculation of the prevalence of anemia and iron status was based on multiple cross-sectional iron absorption studies performed in 888 women during this period of time. All studies included measurements of hemoglobin, mean corpuscular volume, zinc protoporphyrin, percentage of transferrin saturation and serum ferritin. Data were grouped by decade (1981-1990,1991-2000, and 2001-2010. Results. Prevalence of anemia for these decades was 9, 6 and 10%, respectively (p=NS. Iron deficiency anemia was the main cause of anemia in all periods (55, 85 and 75%, respectively; p=NS. A high prevalence of women with normal iron status was observed for all periods (64, 69, and 67, respectively; p=NS. Prevalence of iron deficiency without anemia in 1981-1990, 1991-2000 and 2001-2010 was 7, 20 and 12%, respectively (p menor que 0.05. Finally, prevalence of iron depleted stores was 20, 6 and 10%, respectively (p menor que 0.05. Conclusions. Prevalence of iron deficiency anemia in Chilean women of childbearing age was mild between 1981 and 2010. More than 60% of childbearing age women presented normal iron status in all periods. However, prevalence of iron depleted stores was moderate during 1981-1990, and was mild during 1991-2000 and 2001-2010.

  3. Influence of artistic gymnastics on iron nutritional status and exercise-induced hemolysis in female athletes.

    Science.gov (United States)

    Sureira, Thaiz Mattos; Amancio, Olga Silverio; Pellegrini Braga, Josefina Aparecida

    2012-08-01

    This study evaluates the relationship between body iron losses and gains in artistic gymnastics female athletes. It shows that despite the low iron intake and exercise-induced hemolysis, iron deficiency or iron-deficiency anemia does not occur, but partial changes in the hematological profile do. The hypothesis that gymnasts' nutritional behavior contributes to anemia, which may be aggravated by exercise-induced hemolysis, led to this cross-sectional study, conducted with 43 female artistic gymnasts 6-16 yr old. The control group was formed by 40 nontraining girls, paired by age. Hemogram, serum iron, ferritin, soluble transferrin receptor, haptoglobin, total and fractional bilirubin, Type I urine, and parasitologic and occult fecal blood tests were evaluated. The athletes presented mean hematimetric and serum iron values (p = .020) higher than those of the control group. The bilirubin result discarded any hemolytic alteration in both groups. The haptoglobin results were lower in the athlete group (p = .002), confirming the incidence of exercise-induced hemolysis. Both groups presented low iron intake. The results suggest that artistic gymnastics practice leads to exercise-induced hemolysis and partially changes the hematological profile, although not causing iron deficiency or iron-deficiency anemia, even in the presence of low iron intake.

  4. Iron Stores of Breastfed Infants during the First Year of Life

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    Ekhard E. Ziegler

    2014-05-01

    Full Text Available The birth iron endowment provides iron for growth in the first months of life. We describe the iron endowment under conditions of low dietary iron supply. Subjects were infants participating in a trial of Vitamin D supplementation from 1 to 9 months. Infants were exclusively breastfed at enrollment but could receive complementary foods from 4 months but not formula. Plasma ferritin (PF and transferrin receptor (TfR were determined at 1, 2, 4, 5.5, 7.5, 9 and 12 months. At 1 month PF ranged from 38 to 752 µg/L and was only weakly related to maternal PF. PF declined subsequently and flattened out at 5.5 months. PF of females was significantly higher than PF of males except at 12 months. TfR increased with age and was inversely correlated with PF. PF and TfR tracked strongly until 9 months. Iron deficiency (PF < 10 µg/L began to appear at 4 months and increased in frequency until 9 months. Infants with ID were born with low iron endowment. We concluded that the birth iron endowment is highly variable in size and a small endowment places infants at risk of iron deficiency before 6 months. Boys have smaller iron endowments and are at greater risk of iron deficiency than girls.

  5. Excessive Iron Availability Caused by Disorders of Interleukin-10 and Interleukin-22 Contributes to High Altitude Polycythemia

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    Yun-Sheng Liu

    2018-05-01

    Full Text Available Background: Because the pathogenesis of high altitude polycythemia (HAPC is unclear, the aim of the present study was to explore whether abnormal iron metabolism is involved in the pathogenesis of HAPC and the possible cause.Methods: We examined the serum levels of iron, total iron binding capacity, soluble transferrin receptor (sTfR, ferritin, and hepcidin as well as erythropoietin (EPO and inflammation-related cytokines in 20 healthy volunteers at sea level, 36 healthy high-altitude migrants, and 33 patients with HAPC. Mice that were exposed to a simulated hypoxic environment at an altitude of 5,000 m for 4 weeks received exogenous iron or intervention on cytokines, and the iron-related and hematological indices of peripheral blood and bone marrow were detected. The in vitro effects of some cytokines on hematopoietic cells were also observed.Results: Iron mobilization and utilization were enhanced in people who had lived at high altitudes for a long time. Notably, both the iron storage in ferritin and the available iron in the blood were elevated in patients with HAPC compared with the healthy high-altitude migrants. The correlation analysis indicated that the decreased hepcidin may have contributed to enhanced iron availability in HAPC, and decreased interleukin (IL-10 and IL-22 were significantly associated with decreased hepcidin. The results of the animal experiments confirmed that a certain degree of iron redundancy may promote bone marrow erythropoiesis and peripheral red blood cell production in hypoxic mice and that decreased IL-10 and IL-22 stimulated iron mobilization during hypoxia by affecting hepcidin expression.Conclusion: These data demonstrated, for the first time, that an excess of obtainable iron caused by disordered IL-10 and IL-22 was involved in the pathogenesis of some HAPC patients. The potential benefits of iron removal and immunoregulation for the prevention and treatment of HAPC deserve further research.

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

    Science.gov (United States)

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

    2018-07-01

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

  7. Regulation of iron metabolism during Neisseria meningitidis infection in mice

    Energy Technology Data Exchange (ETDEWEB)

    Letendre, E.D.

    1984-01-01

    Bacterial invasion of vertebrates triggers a marked reduction in the levels of iron associated with the plasma transferrin (Tf) pool. This hypoferremic response has been regarded as a host attempt to withhold essential iron from the invading pathogen. The exact nature of the mechanisms involved remains obscure. The kinetics of iron processing by the RE system were studied by labeling the RE compartments with /sup 59/Fe-labeled denatured red blood cells. Uptake and redistribution of the label indicated the RE-processed iron was not returned to the plasma Tf pool during the hypoferremia. Fractionation of hepatic cellular compartments showed that this impaired release of iron resulted from a preferential incorporation of home-derived iron into the intracellular ferritin pool and this produces the hypoferremia. The role of ceruloplasmin (ferroxidase I,EC.1.16.3.1) (Cp) in iron metabolism during meningococcal infection was investigated. Plasma Cp ferroxidase activity was found to increase greatly in mice during the convalescence phase.

  8. Iron stores in regular blood donors in Lagos, Nigeria

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    Adediran A

    2013-06-01

    Full Text Available Adewumi Adediran,1 Ebele I Uche,2 Titilope A Adeyemo,1 Dapus O Damulak,3 Akinsegun A Akinbami,4 Alani S Akanmu1 1Department of Hematology and Blood Transfusion, University of Lagos, Lagos, Nigeria; 2Department of Hematology and Blood Transfusion, Lagos University Teaching Hospital, Lagos, Nigeria; 3Department of Hematology and Blood Transfusion, Jos University Teaching Hospital, Jos, Nigeria; 4Department of Hematology and Blood Transfusion, Lagos State University, Ikeja, Nigeria Background: Apart from challenging the bone marrow to increase its red cell production, thereby producing more blood for the donor, regular blood donation has been shown to have several benefits, one of which is preventing accumulation of body iron which can cause free radical formation in the body. This study was carried out to assess body iron stores in regular blood donors. Methods: A total of 52 regular (study and 30 first-time (control volunteer blood donors were studied prospectively. Twenty milliliters of venous blood was drawn from each subject, 5 mL of which was put into sodium ethylenediamine tetra-acetic acid specimen bottles for a full blood count, including red blood cell indices. The remaining sample was allowed to clot in a plain container, and the serum was then retrieved for serum ferritin, serum iron, and serum transferrin receptor measurement by enzyme-linked immunosorbent assay. Results: Mean hemoglobin and packed cell volume in the study group (13.47 ± 2.36 g/dL and 42.00 ± 7.10, respectively, P = 0.303 were not significantly higher than in the control group (12.98 ± 1.30 g/dL and 39.76 ± 4.41, respectively, P = 0.119. Mean serum ferritin was 102.46 ± 80.26 ng/mL in the control group and 41.46 ± 40.33 ng/mL in the study group (P = 0.001. Mean serum ferritin for women in the study group (28.02 ± 25.00 ng/mL was significantly lower than for women in the control group (56.35 ± 34.03 ng/mL, P = 0.014. Similarly, men in the study group had a lower

  9. A Protein-Based Ferritin Bio-Nanobattery

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    Gerald D. Watt

    2012-01-01

    Full Text Available Nanostructured materials are increasingly important for the construction of electrochemical energy storage devices that will meet the needs of portable nanodevices. Here we describe the development of a nanoenergy storage system based on inorganic mineral phases contained in ferritin proteins. The electrochemical cell consists of an anode containing ~2000 iron atoms as Fe(OH2 in the hollow protein interior of ferritin and a cathode containing ~2000 of Co(OH3 in a separate ferritin molecule. The achieved initial voltage output from a combination of Fe2+- and Co3+-ferritins adsorbed on gold electrodes was ~500 mV, while a combination of Fe2+- and Co3+-ferritins immobilized on gold produced a voltage of 350–405 mV. When fully discharged, Fe(OH3 and Co(OH2 are the products of a single electron transfer per metal atom from anode to cathode. The spent components can be regenerated by chemical or electrochemical methods restoring battery function. The properties of ferritins are presented and their unique characteristics are described, which have led to the development of a functional bio-nanobattery.

  10. Comparison of iron status and insulin resistance between non-diabetic offspring of type 2 diabetics and non-diabetic offspring of non-diabetics

    International Nuclear Information System (INIS)

    Zafar, U.; Qureshi, H.J.

    2015-01-01

    Insulin resistance is positively correlated with body iron. It is unclear whether iron is a cause or an outcome of insulin resistance. Insulin resistance precedes type 2 diabetes mellitus. Offspring of type 2 diabetics are insulin resistant as compared to those of the non-diabetics. The present study was designed to compare and correlate insulin resistance with iron parameters (including serum ferritin, transferrin saturation and blood haemoglobin) in non-diabetic offspring of type 2 diabetics and non-diabetic offspring of non-diabetics. Methods: It was a cross-sectional study, conducted on one hundred and twenty male subjects 20-40 years of age. They were divided into two groups, each group having 60 subjects. Group A included non-diabetic offspring of type 2 diabetics, while Group B included non-diabetic offspring of non-diabetics. Fasting blood sample was taken and examined for glucose, haemoglobin, insulin, iron, TIBC and ferritin. Data was analysed by SPSS-17. Results: Insulin resistance and iron parameters were significantly higher (p<0.05) in non-diabetic offspring of type 2 diabetics as compared to those of the non-diabetics. There was significant positive correlation (p=0.027) between insulin resistance and serum iron in non-diabetic offspring of type 2 diabetics. There was also significant positive correlation between insulin resistance and serum iron, transferrin saturation and haemoglobin in non-diabetic offspring of non-diabetics. Conclusion: Non-diabetic offspring of type 2 diabetics have iron load and insulin resistance, that predispose them to the development of type 2 diabetes. (author)

  11. Consuming Iron Biofortified Beans Increases Iron Status in Rwandan Women after 128 Days in a Randomized Controlled Feeding Trial.

    Science.gov (United States)

    Haas, Jere D; Luna, Sarah V; Lung'aho, Mercy G; Wenger, Michael J; Murray-Kolb, Laura E; Beebe, Stephen; Gahutu, Jean-Bosco; Egli, Ines M

    2016-08-01

    Food-based strategies to reduce nutritional iron deficiency have not been universally successful. Biofortification has the potential to become a sustainable, inexpensive, and effective solution. This randomized controlled trial was conducted to determine the efficacy of iron-biofortified beans (Fe-Beans) to improve iron status in Rwandan women. A total of 195 women (aged 18-27 y) with serum ferritin Beans, with 86 mg Fe/kg, or standard unfortified beans (Control-Beans), with 50 mg Fe/kg, 2 times/d for 128 d in Huye, Rwanda. Iron status was assessed by hemoglobin, serum ferritin, soluble transferrin receptor (sTfR), and body iron (BI); inflammation was assessed by serum C-reactive protein (CRP) and serum α1-acid glycoprotein (AGP). Anthropometric measurements were performed at baseline and at end line. Random weekly serial sampling was used to collect blood during the middle 8 wk of the feeding trial. Mixed-effects regression analysis with repeated measurements was used to evaluate the effect of Fe-Beans compared with Control-Beans on iron biomarkers throughout the course of the study. At baseline, 86% of subjects were iron-deficient (serum ferritin beans/d. The Fe-Beans group consumed 14.5 ± 1.6 mg Fe/d from biofortified beans, whereas the Control-Beans group consumed 8.6 ± 0.8 mg Fe/d from standard beans (P Beans group had significantly greater increases in hemoglobin (3.8 g/L), log serum ferritin (0.1 log μg/L), and BI (0.5 mg/kg) than did controls after 128 d. For every 1 g Fe consumed from beans over the 128 study days, there was a significant 4.2-g/L increase in hemoglobin (P beans significantly improved iron status in Rwandan women. This trial was registered at clinicaltrials.gov as NCT01594359. © 2016 American Society for Nutrition.

  12. Rice and Bean Targets for Biofortification Combined with High Carotenoid Content Crops Regulate Transcriptional Mechanisms Increasing Iron Bioavailability

    Science.gov (United States)

    Dias, Desirrê Morais; de Castro Moreira, Maria Eliza; Gomes, Mariana Juste Contin; Lopes Toledo, Renata Celi; Nutti, Marilia Regini; Pinheiro Sant’Ana, Helena Maria; Martino, Hércia Stampini Duarte

    2015-01-01

    Iron deficiency affects thousands of people worldwide. Biofortification of staple food crops aims to support the reduction of this deficiency. This study evaluates the effect of combinations of common beans and rice, targets for biofortification, with high carotenoid content crops on the iron bioavailability, protein gene expression, and antioxidant effect. Iron bioavailability was measured by the depletion/repletion method. Seven groups were tested (n = 7): Pontal bean (PB); rice + Pontal bean (R + BP); Pontal bean + sweet potato (PB + SP); Pontal bean + pumpkin (PB + P); Pontal bean + rice + sweet potato (PB + R + P); Pontal bean + rice + sweet potato (PB + R + SP); positive control (Ferrous Sulfate). The evaluations included: hemoglobin gain, hemoglobin regeneration efficiency (HRE), gene expression of divalente metal transporter 1 (DMT-1), duodenal citocromo B (DcytB), ferroportin, hephaestin, transferrin and ferritin and total plasma antioxidant capacity (TAC). The test groups, except the PB, showed higher HRE (p bioavailability and antioxidant capacity. PMID:26610564

  13. Relationship Between Dietary Factors and Bodily Iron Status Among Japanese Collegiate Elite Female Rhythmic Gymnasts.

    Science.gov (United States)

    Kokubo, Yuki; Yokoyama, Yuri; Kisara, Kumiko; Ohira, Yoshiko; Sunami, Ayaka; Yoshizaki, Takahiro; Tada, Yuki; Ishizaki, Sakuko; Hida, Azumi; Kawano, Yukari

    2016-04-01

    This cross-sectional study explored the prevalence of iron deficiency (ID) and associations between dietary factors and incidence of ID in female rhythmic gymnasts during preseason periods. Participants were 60 elite collegiate rhythmic gymnasts (18.1 ± 0.3 years [M ± SD]) who were recruited every August over the course of 8 years. Participants were divided into 2 groups according to the presence or absence of ID. Presence of ID was defined either by ferritin less than 12 μg/L or percentage of transferrin saturation less than 16%. Anthropometric and hematologic data, as well as dietary intake, which was estimated via a semiquantitative food frequency questionnaire, were compared. ID was noted in 48.3% of participants. No significant group-dependent differences were observed in physical characteristics, red blood cell counts, hemoglobin, hematocrit, haptoglobin, or erythropoietin concentrations. The ID group had a significantly lower total iron-binding capacity; serum-free iron; percentage of transferrin saturation; ferritin; and intake of protein, fat, zinc, vitamin B2, vitamin B6, beans, and eggs but not iron or vitamin C. The recommended dietary allowance for intake of protein, iron, zinc, and various vitamins was not met by 30%, 90%, 70%, and 22%-87% of all participants, respectively. Multiple logistic analysis showed that protein intake was significantly associated with the incidence of ID (odds ratio = 0.814, 95% confidence interval [0.669, 0.990], p = .039). Participants in the preseason's weight-loss periods showed a tendency toward insufficient nutrient intake and were at a high risk for ID, particularly because of lower protein intake.

  14. Genome-wide association study identifies TF as a significant modifier gene of iron metabolism in HFE hemochromatosis.

    Science.gov (United States)

    de Tayrac, Marie; Roth, Marie-Paule; Jouanolle, Anne-Marie; Coppin, Hélène; le Gac, Gérald; Piperno, Alberto; Férec, Claude; Pelucchi, Sara; Scotet, Virginie; Bardou-Jacquet, Edouard; Ropert, Martine; Bouvet, Régis; Génin, Emmanuelle; Mosser, Jean; Deugnier, Yves

    2015-03-01

    Hereditary hemochromatosis (HH) is the most common form of genetic iron loading disease. It is mainly related to the homozygous C282Y/C282Y mutation in the HFE gene that is, however, a necessary but not a sufficient condition to develop clinical and even biochemical HH. This suggests that modifier genes are likely involved in the expressivity of the disease. Our aim was to identify such modifier genes. We performed a genome-wide association study (GWAS) using DNA collected from 474 unrelated C282Y homozygotes. Associations were examined for both quantitative iron burden indices and clinical outcomes with 534,213 single nucleotide polymorphisms (SNP) genotypes, with replication analyses in an independent sample of 748 C282Y homozygotes from four different European centres. One SNP met genome-wide statistical significance for association with transferrin concentration (rs3811647, GWAS p value of 7×10(-9) and replication p value of 5×10(-13)). This SNP, located within intron 11 of the TF gene, had a pleiotropic effect on serum iron (GWAS p value of 4.9×10(-6) and replication p value of 3.2×10(-6)). Both serum transferrin and iron levels were associated with serum ferritin levels, amount of iron removed and global clinical stage (pHFE-associated HH (HFE-HH) patients, identified the rs3811647 polymorphism in the TF gene as the only SNP significantly associated with iron metabolism through serum transferrin and iron levels. Because these two outcomes were clearly associated with the biochemical and clinical expression of the disease, an indirect link between the rs3811647 polymorphism and the phenotypic presentation of HFE-HH is likely. Copyright © 2014 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

  15. Sustainability of the effects of medicinal iron and iron rich food supplementation on haemoglobin, intelligence quotient and growth of school aged girls

    Directory of Open Access Journals (Sweden)

    Monika Jain

    2014-12-01

    Full Text Available Anaemia in school aged girls is an important but neglected issue. Since iron supplementation programmes have had little reported success in reducing anaemia, interest is turning to food based approaches that have higher potential for achieving far reaching benefits. The purpose of the study was to observe sustainability of the effect of iron and food supplementation on haemoglobin (Hb, intelligence quotient (IQ and growth of the subjects. At baseline, estimation of haemoglobin (Hb, red cell indices, serum iron, total iron binding capacity, serum transferrin saturation and serum ferritin was done. IQ, weight and height were measured using standard procedures. Anaemic subjectswere divided into three groups, viz., (i twice weekly supplementation of iron folic acid syrup (53 mg iron/week; (ii daily supplementation of 4 niger seed and defatted soyaflour biscuits plus 2 lemons (45 mg iron/week and (iii control. Non anaemic group(NAC was not intervened. Endline data was collected after 120 days. Follow up for Hb, IQ, weight and height was done 4 months after cessation of supplementation. The prevalence of anaemia was 77% in the study population; 46% subjects had mild anaemia and 32% had moderate anaemia. Iron status was lower in anaemic subjects (p<0.001.Iron supplementation was more effective in raising Hb and building iron stores than iron rich food supplementation. Iron supplementation improved IQ but did not bring about catch up of anaemics to non anaemics. Iron rich food supplementation was better than medicinal iron in promoting growth in anaemic girls. The impact of iron rich food supplementation on Hb, IQ and growth sustained for 4 months while that of medicinal iron did not. Effects of food supplementation are sustainable for 4 months, therefore, this strategy holds more potential to control anaemia, in school aged girls.

  16. The Role of Eating Habits on the Iron Status of Pregnant Women.

    Science.gov (United States)

    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.

  17. Hepcidin Protects Neuron from Hemin-Mediated Injury by Reducing Iron

    Directory of Open Access Journals (Sweden)

    Yu-Fu Zhou

    2017-05-01

    Full Text Available Hemin plays a key role in mediating secondary neuronal injury after intracerebral hemorrhage (ICH and the cell toxicity of hemin is thought to be due to iron that is liberated when hemin is degraded. In a recent study, we demonstrated the iron regulatory hormone hepcidin reduces brain iron in iron-overloaded rats. Therefore, we hypothesized that hepcidin might be able to reduce iron and then protect neurons from hemin or iron-mediated neurotoxicity in hemin-treated neuronal cells. Here, we tested the hypothesis and demonstrated that ad-hepcidin and hepcidin peptide both have the ability to suppress the hemin-induced increase in LDH release and apoptotic cell numbers, to reduce cell iron and ferritin contents, and to inhibit expression of transferrin receptor 1, divalent metal transporter 1, and ferroportin 1 in hemin-treated neurons. We conclude that hepcidin protects neuron from hemin-mediated injury by reducing iron via inhibition of expression of iron transport proteins.

  18. Multilayer Ferritin Array for Bionanobattery

    Science.gov (United States)

    Chu, Sang-Hyon (Inventor); Choi, Sang H. (Inventor); Kim, Jae-Woo (Inventor); Lillehei, Peter T. (Inventor); Park, Yeonjoon (Inventor); King, Glen C. (Inventor); Elliott, James R., Jr. (Inventor)

    2009-01-01

    A thin-film electrode for a bio-nanobattery is produced by consecutively depositing arrays of a ferritin protein on a substrate, employing a spin self-assembly procedure. By this procedure, a first ferritin layer is first formed on the substrate, followed by building a second, oppositely-charged ferritin layer on the top of the first ferritin layer to form a bilayer structure. Oppositely-charged ferritin layers are subsequently deposited on top of each other until a desired number of bilayer structures is produced. An ordered, uniform, stable and robust, thin-film electrode material of enhanced packing density is presented, which provides optimal charge density for the bio-nanobattery.

  19. The influence of maternal smoking on transferrin sialylation and fetal biometric parameters.

    Science.gov (United States)

    Wrześniak, Marta; Królik, Małgorzata; Kepinska, Marta; Milnerowicz, Halina

    2016-10-01

    Transferrin is a glycosylated protein responsible for transporting iron, an essential metal responsible for proper fetal development. Tobacco is a heavily used xenobiotic having a negative impact on the human body and pregnancy outcomes. Aims of this study was to examine the influence of tobacco smoking on transferrin sialic acid residues and their connection with fetal biometric parameters in women with iron-deficiency. The study involved 173 samples from pregnant women, smokers and non-smokers, iron deficient and not. Transferrin sialylation was determined by capillary electrophoresis. The cadmium (Cd) level was measured by atomic absorption and the sialic acid concentration by the resorcinol method. Women with iron deficiencies who smoked gave birth earlier than non-smoking, non-iron-deficient women. The Cd level, but not the cotinine level, was positively correlated with transferrin sialylation in the blood of iron-deficient women who smoked; 3-, 4-, 5- and 6-sialoTf correlated negatively with fetal biometric parameters in the same group. It has been shown the relationship between Cd from tobacco smoking and fetal biometric parameters observed only in the iron deficient group suggests an additive effect of these two factors, and indicate that mothers with anemia may be more susceptible to Cd toxicity and disturbed fetal development. Copyright © 2016 Elsevier B.V. All rights reserved.

  20. A genetic risk factor for low serum ferritin levels in Danish blood donors

    DEFF Research Database (Denmark)

    Sørensen, Erik; Grau, Katrine; Berg, Trine

    2012-01-01

    BACKGROUND: Iron deficiency is a frequent side effect of blood donation. In recent years, several studies have described genetic variants associated with iron concentrations. However, the impact of these variants on iron levels is unknown in blood donors. Knowledge of genetic variants....../or restless leg syndrome (RLS) were investigated in two groups of female blood donors. The first group had low iron stores (serum ferritin ≤ 12 µg/L, n = 657), and the second group had normal to high iron stores (serum ferritin > 30 µg/L, n = 645). Genotype distribution for each of the SNPs was compared......: A frequent polymorphism in BTBD9 was significantly associated with serum ferritin. This polymorphism has previously been associated with RLS, but not low iron stores in blood donors....

  1. Ferritin levels and risk of heart failure-the Atherosclerosis Risk in Communities Study.

    Science.gov (United States)

    Silvestre, Odilson M; Gonçalves, Alexandra; Nadruz, Wilson; Claggett, Brian; Couper, David; Eckfeldt, John H; Pankow, James S; Anker, Stefan D; Solomon, Scott D

    2017-03-01

    Severe iron overload is associated with cardiac damage, while iron deficiency has been related to worse outcomes in subjects with heart failure (HF). This study investigated the relationship between ferritin, a marker of iron status, and the incidence of HF in a community-based cohort. We examined 1063 participants who were free of heart failure from the Atherosclerosis Risk in Communities (ARIC) Study in whom ferritin serum levels were measured at baseline (1987-1989). The participants (mean age 52.7 ± 5.5 years, 62% women), were categorized in low (200 ng/mL in women and >300 ng/mL in men; n = 247) ferritin levels. Multivariable Cox proportional hazards models were used to evaluate the relationship between ferritin and incident HF. After 21 ± 4.6 years of follow-up, HF occurred in 144 (13.5%) participants. When compared with participants with normal ferritin levels, participants with low ferritin levels had a higher risk of HF [hazard ratio (HR) = 2.24, 95% confidence interval (CI) 1.15-4.35; P = 0.02] as did those with high ferritin levels (HR = 1.81, 95% CI 1.01-3.25; P = 0.04), after adjusting for potential confounders. Notably, low ferritin levels remained associated with incident HF even after excluding subjects with anaemia (HR = 2.28, 95% CI 1.11-4.68; P = 0.03). Derangements in iron metabolism, either low or high ferritin serum levels, were associated with higher risk of incident HF in a general population, even without concurrent anaemia. These findings suggest that iron imbalance might play a role in the development of HF. © 2016 The Authors. European Journal of Heart Failure © 2016 European Society of Cardiology.

  2. A mutation in the HFE gene is associated with altered brain iron profiles and increased oxidative stress in mice.

    Science.gov (United States)

    Nandar, Wint; Neely, Elizabeth B; Unger, Erica; Connor, James R

    2013-06-01

    Because of the increasing evidence that H63D HFE polymorphism appears in higher frequency in neurodegenerative diseases, we evaluated the neurological consequences of H63D HFE in vivo using mice that carry H67D HFE (homologous to human H63D). Although total brain iron concentration did not change significantly in the H67D mice, brain iron management proteins expressions were altered significantly. The 6-month-old H67D mice had increased HFE and H-ferritin expression. At 12 months, H67D mice had increased H- and L-ferritin but decreased transferrin expression suggesting increased iron storage and decreased iron mobilization. Increased L-ferritin positive microglia in H67D mice suggests that microglia increase iron storage to maintain brain iron homeostasis. The 6-month-old H67D mice had increased levels of GFAP, increased oxidatively modified protein levels, and increased cystine/glutamate antiporter (xCT) and hemeoxygenase-1 (HO-1) expression indicating increased metabolic and oxidative stress. By 12 months, there was no longer increased astrogliosis or oxidative stress. The decrease in oxidative stress at 12 months could be related to an adaptive response by nuclear factor E2-related factor 2 (Nrf2) that regulates antioxidant enzymes expression and is increased in the H67D mice. These findings demonstrate that the H63D HFE impacts brain iron homeostasis, and promotes an environment of oxidative stress and induction of adaptive mechanisms. These data, along with literature reports on humans with HFE mutations provide the evidence to overturn the traditional paradigm that the brain is protected from HFE mutations. The H67D knock-in mouse can be used as a model to evaluate how the H63D HFE mutation contributes to neurodegenerative diseases. Copyright © 2013 Elsevier B.V. All rights reserved.

  3. Increased levels of advanced glycation end products positively correlate with iron overload and oxidative stress markers in patients with β-thalassemia major.

    Science.gov (United States)

    Mirlohi, Maryam Sadat; Yaghooti, Hamid; Shirali, Saeed; Aminasnafi, Ali; Olapour, Samaneh

    2018-04-01

    The impaired biosynthesis of the β-globin chain in β-thalassemia leads to the accumulation of unpaired alpha globin chains, failure in hemoglobin formation, and iron overload due to frequent blood transfusion. Iron excess causes oxidative stress and massive tissue injuries. Advanced glycation end products (AGEs) are harmful agents, and their production accelerates in oxidative conditions. This study was conducted on 45 patients with major β-thalassemia who received frequent blood transfusions and chelation therapy and were compared to 40 healthy subjects. Metabolic parameters including glycemic and iron indices, hepatic and renal functions tests, oxidative stress markers, and AGEs (carboxymethyl-lysine and pentosidine) levels were measured. All parameters were significantly increased in β-thalassemia compared to the control except for glutathione levels. Blood glucose, iron, serum ferritin, non-transferrin-bound iron (NTBI), MDA, soluble form of low-density lipoprotein receptor, glutathione peroxidase, total reactive oxygen species (ROS), and AGE levels were significantly higher in the β-thalassemia patients. Iron and ferritin showed a significant positive correlation with pentosidine (P overload in β-thalassemia major patients and highlight the enhanced formation of AGEs, which may play an important role in the pathogenesis of β-thalassemia major.

  4. Nickel decreases cellular iron level and converts cytosolic aconitase to iron-regulatory protein 1 in A549 cells

    International Nuclear Information System (INIS)

    Chen Haobin; Davidson, Todd; Singleton, Steven; Garrick, Michael D.; Costa, Max

    2005-01-01

    Nickel (Ni) compounds are well-established carcinogens and are known to initiate a hypoxic response in cells via the stabilization and transactivation of hypoxia-inducible factor-1 alpha (HIF-1α). This change may be the consequence of nickel's interference with the function of several Fe(II)-dependent enzymes. In this study, the effects of soluble nickel exposure on cellular iron homeostasis were investigated. Nickel treatment decreased both mitochondrial and cytosolic aconitase (c-aconitase) activity in A549 cells. Cytosolic aconitase was converted to iron-regulatory protein 1, a form critical for the regulation of cellular iron homeostasis. The increased activity of iron-regulatory protein 1 after nickel exposure stabilized and increased transferrin receptor (Tfr) mRNA and antagonized the iron-induced ferritin light chain protein synthesis. The decrease of aconitase activity after nickel treatment reflected neither direct interference with aconitase function nor obstruction of [4Fe-4S] cluster reconstitution by nickel. Exposure of A549 cells to soluble nickel decreased total cellular iron by about 40%, a decrease that likely caused the observed decrease in aconitase activity and the increase of iron-regulatory protein 1 activity. Iron treatment reversed the effect of nickel on cytosolic aconitase and iron-regulatory protein 1. To assess the mechanism for the observed effects, human embryonic kidney (HEK) cells over expressing divalent metal transporter-1 (DMT1) were compared to A549 cells expressing only endogenous transporters for inhibition of iron uptake by nickel. The inhibition data suggest that nickel can enter via DMT1 and compete with iron for entry into the cell. This disturbance of cellular iron homeostasis by nickel may have a great impact on the ability of the cell to regulate a variety of cell functions, as well as create a state of hypoxia in cells under normal oxygen tension. These effects may be very important in how nickel exerts phenotypic

  5. A 3-marker index improves the identification of iron disorders in CKD anaemia.

    Directory of Open Access Journals (Sweden)

    Lucile Mercadal

    Full Text Available BACKGROUND: Iron disorders are common and complex in chronic kidney disease (CKD. We sought to determine whether a 3-marker index would improve the classification of iron disorders in CKD anaemia. METHODS: We studied the association between Hb level and iron indexes combining 2 or 3 of the following markers: serum ferritin (<40 ng/mL, transferrin saturation (TSAT<20% and total iron binding capacity (TIBC<50 µmol/L in 1011 outpatients with non-dialysis CKD participating in the Nephrotest study. All had glomerular filtration rates measured (mGFR by (51Cr-EDTA renal clearance; 199 also had hepcidin measures. RESULTS: The TSAT-TIBC-ferritin index explained Hb variation better than indexes combining TSAT-TIBC or ferritin-TSAT. It showed hypotransferrinaemia and non-inflammatory functional iron deficiency (ID to be more common than either absolute or inflammatory ID: 20%, 19%, 6%, and 2%, respectively. Hb was lower in all abnormal, compared with normal, iron profiles, and decreased more when mGFR was below 30 mL/min/1.73 m(2 (interaction p<0.0001. In patients with mGFR<30 mL/min/1.73 m(2, the Hb decreases associated with hypotransferrinaemia, non-inflammatory functional ID, and absolute ID were 0.83±0.16 g/dL, 0.51±0.18 and 0.89±0.29, respectively. Compared with normal iron profiles, hepcidin was severely depressed in absolute ID but higher in hypotransferrinaemia. CONCLUSIONS: The combined TSAT-TIBC-ferritin index identifies hypotransferrinaemia and non-inflammatory functional ID as the major mechanisms of iron disorders in CKD anaemia. Both disorders were associated with a greater decrease in Hb when mGFR was <30 mL/min/1.73 m(2. Taking these iron profiles into account may be useful in stratifying patients in clinical trials of CKD anaemia and might improve the management of iron therapy.

  6. Cellular location of rat muscle ferritins and their preferential loss during cell isolation.

    Science.gov (United States)

    Linder, M C; Roboz, M; McKown, M J; Pardridge, W M; Zak, R

    1984-04-10

    Heart and other muscles of the rat contain two forms of ferritin separable in polyacrylamide gel electrophoresis. The cellular location of the fast- and slow-migrating ferritins was investigated using primary cultures of hindlimb skeletal muscle, and isolated myocardial cell populations. Muscle and non-muscle cells were isolated in good yield from hearts of adult rats pretreated with large doses of iron to increase their ferritin content. In virtually all cases, the isolated muscle cells contained traces only of the fast-migrating species and the non-muscle cells contained small amounts of the slow-migrating ferritin. During cell isolation, 90-100% of both ferritins was lost and could be recovered in the perfusates and solutions employed, while one third of the total tissue protein, and a larger percentage of creatine phosphokinase, was recovered in the isolated cells. Primary cultures of thigh muscle from adult rats which had differentiated into multi-nucleated myotubes, were incubated for 1-3 days with chelated iron. These cells contained substantial amounts of the electrophoretically fast migrating ferritin, with its characteristic larger Stokes' radius (determined by quantitative polyacrylamide gel electrophoresis). None of the slow-migrating ferritin species was detected, although hindlimb muscle from iron-treated rats contained both forms. It is concluded that the fast-migrating ferritin of muscle, which is much larger and more asymmetric than other ferritins, is confined to the muscle cell population, while the other form is predominantly or exclusively in the non-muscle cells. Both ferritins are lost preferentially over other proteins during procedures which injure muscle tissue.

  7. The effect of gold kiwifruit consumed with an iron fortified breakfast cereal meal on iron status in women with low iron stores: A 16 week randomised controlled intervention study

    Directory of Open Access Journals (Sweden)

    Coad Jane

    2010-01-01

    Full Text Available Abstract Background Dietary treatment is often recommended as the first line of treatment for women with mild iron deficiency. Although it is well established that ascorbic acid enhances iron absorption, it is less clear whether the consumption of ascorbic acid rich foods (such as kiwifruit with meals fortified with iron improves iron status. The aim of this study is to investigate whether the consumption of ZESPRI® GOLD kiwifruit (a fruit high in ascorbic acid and carotenoids with an iron fortified breakfast cereal meal increases iron status in women with low iron stores. Methods/Design Eighty nine healthy women aged 18-44 years with low iron stores (serum ferritin (SF ≤ 25 μg/L, haemoglobin (Hb ≥ 115 g/L living in Auckland, New Zealand were randomised to receive an iron fortified breakfast cereal (16 mg iron per serve and either two ZESPRI® GOLD kiwifruit or a banana (low ascorbic acid and carotenoid content to eat at breakfast time every day for 16 weeks. Iron status (SF, Hb, C-reactive protein (CRP and soluble transferrin receptor (sTfR, ascorbic acid and carotenoid status were measured at baseline and after 16 weeks. Anthropometric measures, dietary intake, physical activity and blood loss were measured before and after the 16 week intervention. Discussion This randomised controlled intervention study will be the first study to investigate the effect of a dietary based intervention of an iron fortified breakfast cereal meal combined with an ascorbic acid and carotenoid rich fruit on improving iron status in women with low iron stores. Trial registration ACTRN12608000360314

  8. Effect of oxidative stress induced by intracranial iron overload on central pain after spinal cord injury.

    Science.gov (United States)

    Meng, Fan Xing; Hou, Jing Ming; Sun, Tian Sheng

    2017-02-08

    Central pain (CP) is a common clinical problem in patients with spinal cord injury (SCI). Recent studies found the pathogenesis of CP was related to the remodeling of the brain. We investigate the roles of iron overload and subsequent oxidative stress in the remodeling of the brain after SCI. We established a rat model of central pain after SCI. Rats were divided randomly into four groups: SCI, sham operation, SCI plus deferoxamine (DFX) intervention, and SCI plus nitric oxide synthase (NOS) inhibitor treatment. Pain behavior was observed and thermal pain threshold was measured regularly, and brain levels of iron, transferrin receptor 1 (TfR1), ferritin (Fn), and lactoferrin (Lf), were detected in the different groups 12 weeks after establishment of the model. Rats demonstrated self-biting behavior after SCI. Furthermore, the latent period of thermal pain was reduced and iron levels in the hind limb sensory area, hippocampus, and thalamus increased after SCI. Iron-regulatory protein (IRP) 1 levels increased in the hind limb sensory area, while Fn levels decreased. TfR1 mRNA levels were also increased and oxidative stress was activated. Oxidative stress could be inhibited by ferric iron chelators and NOS inhibitors. SCI may cause intracranial iron overload through the NOS-iron-responsive element/IRP pathway, resulting in central pain mediated by the oxidative stress response. Iron chelators and oxidative stress inhibitors can effectively relieve SCI-associated central pain.

  9. Relationship of Baseline Hemoglobin Level with Serum Ferritin, Postphlebotomy Hemoglobin Changes, and Phlebotomy Requirements among HFE C282Y Homozygotes

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    Seyed Ali Mousavi

    2015-01-01

    Full Text Available Objectives. We aimed to examine whether baseline hemoglobin levels in C282Y-homozygous patients are related to the degree of serum ferritin (SF elevation and whether patients with different baseline hemoglobin have different phlebotomy requirements. Methods. A total of 196 patients (124 males and 72 females who had undergone therapeutic phlebotomy and had SF and both pre- and posttreatment hemoglobin values were included in the study. Results. Bivariate correlation analysis suggested that baseline SF explains approximately 6 to 7% of the variation in baseline hemoglobin. The results also showed that males who had higher (≥150 g/L baseline hemoglobin levels had a significantly greater reduction in their posttreatment hemoglobin despite requiring fewer phlebotomies to achieve iron depletion than those who had lower (<150 g/L baseline hemoglobin, regardless of whether baseline SF was below or above 1000 µg/L. There were no significant differences between hemoglobin subgroups regarding baseline and treatment characteristics, except for transferrin saturation between male subgroups with SF above 1000 µg/L. Similar differences were observed when females with higher (≥138 g/L baseline hemoglobin were compared with those with lower (<138 g/L baseline hemoglobin. Conclusion. Dividing C282Y-homozygous patients into just two subgroups according to the degree of baseline SF elevation may obscure important subgroup variations.

  10. Relationship of Baseline Hemoglobin Level with Serum Ferritin, Postphlebotomy Hemoglobin Changes, and Phlebotomy Requirements among HFE C282Y Homozygotes

    Science.gov (United States)

    Mousavi, Seyed Ali; Mahmood, Faiza; Aandahl, Astrid; Knutsen, Teresa Risopatron; Llohn, Abid Hussain

    2015-01-01

    Objectives. We aimed to examine whether baseline hemoglobin levels in C282Y-homozygous patients are related to the degree of serum ferritin (SF) elevation and whether patients with different baseline hemoglobin have different phlebotomy requirements. Methods. A total of 196 patients (124 males and 72 females) who had undergone therapeutic phlebotomy and had SF and both pre- and posttreatment hemoglobin values were included in the study. Results. Bivariate correlation analysis suggested that baseline SF explains approximately 6 to 7% of the variation in baseline hemoglobin. The results also showed that males who had higher (≥150 g/L) baseline hemoglobin levels had a significantly greater reduction in their posttreatment hemoglobin despite requiring fewer phlebotomies to achieve iron depletion than those who had lower (baseline hemoglobin, regardless of whether baseline SF was below or above 1000 µg/L. There were no significant differences between hemoglobin subgroups regarding baseline and treatment characteristics, except for transferrin saturation between male subgroups with SF above 1000 µg/L. Similar differences were observed when females with higher (≥138 g/L) baseline hemoglobin were compared with those with lower (baseline hemoglobin. Conclusion. Dividing C282Y-homozygous patients into just two subgroups according to the degree of baseline SF elevation may obscure important subgroup variations. PMID:26380265

  11. Iron deficiency and anemia are prevalent in women with multiple gestations.

    Science.gov (United States)

    Ru, Yuan; Pressman, Eva K; Cooper, Elizabeth M; Guillet, Ronnie; Katzman, Philip J; Kent, Tera R; Bacak, Stephen J; O'Brien, Kimberly O

    2016-10-01

    Little attention has been placed on the unique iron demands that may exist in women with multiple gestations. This merits attention because iron deficiency (ID) during pregnancy is associated with adverse pregnancy outcomes that are known to be more prevalent in multiple births. We characterized longitudinal changes in iron status across pregnancy in a cohort of healthy women with multiple gestations and identified determinants of maternal ID and anemia. A group of 83 women carrying twins, triplets, or quadruplets (aged 20-46 y) was recruited from 2011 to 2014. Blood samples obtained during pregnancy (∼24 wk; n = 73) and at delivery (∼35 wk; n = 61) were used to assess hemoglobin, serum ferritin (SF), soluble transferrin receptor (sTfR), hepcidin, serum iron, erythropoietin, serum folate, vitamin B-12, C-reactive protein, and interleukin-6. The prevalence of tissue ID (sTfR >8.5 mg/L) increased significantly from pregnancy to delivery (9.6% compared with 23%, P = 0.03). Women with depleted iron stores (SF anemia at delivery, and 25% (n = 5) developed iron deficiency anemia (IDA). Overall, 44.6% of women studied (n = 37/83) were anemic at delivery, and 18% of women (n = 11/61) had IDA. Erythropoietin during pregnancy was significantly negatively associated with hemoglobin at delivery. Women with erythropoietin >75th percentile during pregnancy exhibited a 3-fold greater risk of anemia, suggesting that erythropoietin is a sensitive predictor of anemia at delivery. Inflammation was present at delivery, which limited the utility of ferritin or hepcidin as iron-status indicators at delivery. ID and anemia are highly prevalent in women with multiple gestations. Additional screening and iron supplementation may be warranted in this high-risk population given the known associations between ID anemia and adverse maternal and neonatal outcomes. This trial was registered at clinicaltrials.gov as NCT01582802. © 2016 American Society for Nutrition.

  12. Cardiac iron overload in chronically transfused patients with thalassemia, sickle cell anemia, or myelodysplastic syndrome.

    Directory of Open Access Journals (Sweden)

    Mariane de Montalembert

    Full Text Available The risk and clinical significance of cardiac iron overload due to chronic transfusion varies with the underlying disease. Cardiac iron overload shortens the life expectancy of patients with thalassemia, whereas its effect is unclear in those with myelodysplastic syndromes (MDS. In patients with sickle cell anemia (SCA, iron does not seem to deposit quickly in the heart. Our primary objective was to assess through a multicentric study the prevalence of cardiac iron overload, defined as a cardiovascular magnetic resonance T2*8 ECs in the past year, and age older than 6 years. We included from 9 centers 20 patients with thalassemia, 41 with SCA, and 25 with MDS in 2012-2014. Erythrocytapharesis did not consistently prevent iron overload in patients with SCA. Cardiac iron overload was found in 3 (15% patients with thalassemia, none with SCA, and 4 (16% with MDS. The liver iron content (LIC ranged from 10.4 to 15.2 mg/g dry weight, with no significant differences across groups (P = 0.29. Abnormal T2* was not significantly associated with any of the measures of transfusion or chelation. Ferritin levels showed a strong association with LIC. Non-transferrin-bound iron was high in the thalassemia and MDS groups but low in the SCA group (P<0.001. Hepcidin was low in thalassemia, normal in SCA, and markedly elevated in MDS (P<0.001. Two mechanisms may explain that iron deposition largely spares the heart in SCA: the high level of erythropoiesis recycles the iron and the chronic inflammation retains iron within the macrophages. Thalassemia, in contrast, is characterized by inefficient erythropoiesis, unable to handle free iron. Iron accumulation varies widely in MDS syndromes due to the competing influences of abnormal erythropoiesis, excess iron supply, and inflammation.

  13. Role of nitric oxide in cellular iron metabolism.

    Science.gov (United States)

    Kim, Sangwon; Ponka, Prem

    2003-03-01

    Iron regulatory proteins (IRP1 and IRP2) control the synthesis of transferrin receptors (TfR) and ferritin by binding to iron-responsive elements (IREs) which are located in the 3' untranslated region (UTR) and the 5' UTR of their respective mRNAs. Cellular iron levels affect binding of IRPs to IREs and consequently expression of TfR and ferritin. Moreover, NO*, a redox species of nitric oxide that interacts primarily with iron, can activate IRP1 RNA-binding activity resulting in an increase in TfR mRNA levels. We have shown that treatment of RAW 264.7 cells (a murine macrophage cell line) with NO+ (nitrosonium ion, which causes S-nitrosylation of thiol groups) resulted in a rapid decrease in RNA-binding of IRP2, followed by IRP2 degradation, and these changes were associated with a decrease in TfR mRNA levels. Moreover, we demonstrated that stimulation of RAW 264.7 cells with lipopolysaccharide (LPS) and interferon-gamma (IFN-gamma) increased IRP1 binding activity, whereas RNA-binding of IRP2 decreased and was followed by a degradation of this protein. Furthermore, the decrease of IRP2 binding/protein levels was associated with a decrease in TfR mRNA levels in LPS/IFN-gamma-treated cells, and these changes were prevented by inhibitors of inducible nitric oxide synthase. These results suggest that NO+-mediated degradation of IRP2 plays a major role in iron metabolism during inflammation.

  14. Iron, zinc, copper and magnesium nutritional status in Mexican children aged 1 to 11 years.

    Science.gov (United States)

    Morales-Ruán, Ma del Carmen; Villalpando, Salvador; García-Guerra, Armando; Shamah-Levy, Teresa; Robledo-Pérez, Ricardo; Avila-Arcos, Marco Antonio; Rivera, Juan A

    2012-01-01

    To describe the micronutrient nutritional status of a national sample of 1-11 year old Mexican children surveyed in 2006 in National Health and Nutrition Survey (ENSANUT 2006) and their association with dietary and sociodemographic factors. Serum samples were used (n=5 060) to measure the concentrations of ferritin, transferrin receptor, zinc, copper and magnesium. Prevalence of deficiencies in 1-4 and 5-11y old children were for iron (using low ferritin) 26.0 and 13.0%; zinc, 28.1 and 25.8%, respectively; and copper, ≈30% in both age groups. Magnesium low serum concentrations (MLSC), were found in 12.0% and 28.4% of the children, respectively. Being beneficiary of Liconsa (OR=0.32; C.I.95%, 0.17-0.61) or belonging to higher socioeconomic status (OR=0.63; C.I.95%, 0.41-0.97) were protective against iron deficiency. Increasing age (OR=0.59; C.I.95%, 1.19-1.32) and living in the Central Region (OR=0.59; C.I.95%, 0.36-0.97) were protective against MLSC. Deficiencies of iron and zinc are serious public health problems in Mexican children.

  15. Biomarkers of Hypochromia: The Contemporary Assessment of Iron Status and Erythropoiesis

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    Eloísa Urrechaga

    2013-01-01

    Full Text Available Iron status is the result of the balance between the rate of erythropoiesis and the amount of the iron stores. Direct consequence of an imbalance between the erythroid marrow iron requirements and the actual supply is a reduction of red cell hemoglobin content, which causes hypochromic mature red cells and reticulocytes. The diagnosis of iron deficiency is particularly challenging in patients with acute or chronic inflammatory conditions because most of the biochemical markers for iron metabolism (serum ferritin and transferrin are affected by acute phase reaction. For these reasons, interest has been generated in the use of erythrocyte and reticulocyte parameters, available on the modern hematology analyzers. Reported during blood analysis routinely performed on the instrument, these parameters can assist in early detection of clinical conditions (iron deficiency, absolute, or functional; ineffective erythropoiesis, including iron restricted or thalassemia, without additional cost. Technological progress has meant that in recent years modern analyzers report new parameters that provide further information from the traditional count. Nevertheless these new parameters are exclusive of each manufacturer, and they are patented. This is an update of these new laboratory test biomarkers of hypochromia reported by different manufactures, their meaning, and clinical utility on daily practice.

  16. Magnetic model for a horse-spleen ferritin with a three-phase core structure

    Energy Technology Data Exchange (ETDEWEB)

    Jung, J.H.; Eom, T.W. [Quantum Photonic Science Research Center, Department of Physics and Research Institute for Natural Sciences, Hanyang University, Seoul 133-791 (Korea, Republic of); Lee, Y.P., E-mail: yplee@hanyang.ac.kr [Quantum Photonic Science Research Center, Department of Physics and Research Institute for Natural Sciences, Hanyang University, Seoul 133-791 (Korea, Republic of); Rhee, J.Y. [Department of Physics, Sungkyunkwan University, Suwon (Korea, Republic of); Choi, E.H. [Kwangwoon University, Seoul (Korea, Republic of)

    2011-12-15

    The increasing interests in magnetic nanoparticles has prompted research on ferritin, which is naturally a well-defined iron-storage protein in most living organisms. However, the exact magnetic behavior of ferritin is not well understood, because the crystal structures of ferritin and ferrihydrite, its major component, are not fully understood. Briefly, we discuss the previous magnetization models of ferritin and ferrihydrite and we present a new model ({Sigma}3L) of the initial magnetization of ferritin, considering its different phases. The new model includes three Langevin-function terms, which represent three different magnetic moments provided by the likely hydroxide and oxide mineral phases in ferritin. Compared to previous models, our simple model fits the experimental data 12 times better in terms of the sum of least squares. The magnetic independence of each component supports the multi-phase compositional model of the mineral core of horse-spleen ferritin. This {Sigma}3L model gives a quantization of the amounts of the different phases within horse-spleen ferritins that matches other published experimental data: 60-80% ferrihydrite, 15-25% maghemite/magnetite, and 1-10% hematite. - Highlights: > We present a new model ({Sigma}3L) of the initial magnetization of ferritin, considering its different phases. > New model includes three Langevin-function terms, which represent three different magnetic moments provided by ferritin phases. > Compared to previous models, our simple model fits the experimental data 12 times better in terms of the sum of least square. > The magnetic independence of each component supports that ferritin and ferrihydrite are composed of different phases.

  17. Transferrin-bearing polypropylenimine dendrimer for targeted gene delivery to the brain.

    Science.gov (United States)

    Somani, Sukrut; Blatchford, David R; Millington, Owain; Stevenson, M Lynn; Dufès, Christine

    2014-08-28

    The possibility of using genes as medicines to treat brain diseases is currently limited by the lack of safe and efficacious delivery systems able to cross the blood-brain barrier, thus resulting in a failure to reach the brain after intravenous administration. On the basis that iron can effectively reach the brain by using transferrin receptors for crossing the blood-brain barrier, we propose to investigate if a transferrin-bearing generation 3-polypropylenimine dendrimer would allow the transport of plasmid DNA to the brain after intravenous administration. In vitro, the conjugation of transferrin to the polypropylenimine dendrimer increased the DNA uptake by bEnd.3 murine brain endothelioma cells overexpressing transferrin receptors, by about 1.4-fold and 2.3-fold compared to that observed with the non-targeted dendriplex and naked DNA. This DNA uptake appeared to be optimal following 2h incubation with the treatment. In vivo, the intravenous injection of transferrin-bearing dendriplex more than doubled the gene expression in the brain compared to the unmodified dendriplex, while decreasing the non-specific gene expression in the lung. Gene expression was at least 3-fold higher in the brain than in any tested peripheral organs and was at its highest 24h following the injection of the treatments. These results suggest that transferrin-bearing polypropylenimine dendrimer is a highly promising gene delivery system to the brain. Copyright © 2014 Elsevier B.V. All rights reserved.

  18. Complex formation of transferrin with tetravalent plutonium and cerium

    International Nuclear Information System (INIS)

    Subramanian, M.S.; Oomen, I.K.

    1981-01-01

    Gel filtration experiments with 239 Pu labelled In Vitro bovine serum showed that the metal ion is bound to the transferrin of the serum proteins as in the case of iron labelled serum. This was confirmed by polyacrylamide gel electrophoresis. The ovotransferrin prepared from chicken egg white which was devoid of hemopexin contaminant was found to complex both tetravalent plutonium and cerium giving visible absorption peak at 365 and 435 nm respectively. The binding capacity of ovotransferrin with tetravalent plutonium and cerium, determined by spectrophotometric titration indicates that two metal ions are bound to each protein molecule as in the case of iron. The average molecular weight computed from this binding capacity measurements was found to be 71,000-75,000. The number of protons liberated for each metal ion bound was found to be three as in the case of iron. (author)

  19. Radioisotope binding capacity of serum for folic acid, vitamin B12 and ferritin in hematologic and rheumatologic patients

    International Nuclear Information System (INIS)

    Ringelhann, B.; Revicky, A.; Arvai, I.; Megyeri, A.; Goemoer, B.; Josfay, L.; Csak, E.

    1980-01-01

    Folic acid, vitamin B 12 and ferritin levels were determined by radioimmunoassay in patients suffering from hemic and rheumatic diseases, resp. Compared to the controls the folic acid levels were lower in some cases, the deficiency of folic acid absorption and distribution possibly being caused by the disease. Vitamin B 12 was only slightly decreased. In ankylosing spondylitis the transferrin level was similar to that of the controls, but in rheumatoid arthritis and in patients suffering from various diseases it was increased

  20. Ferritin Elevation and Improved Responsiveness to Erythropoiesis-Stimulating Agents in Patients on Ferric Citrate Hydrate

    Directory of Open Access Journals (Sweden)

    Keitaro Yokoyama

    2017-05-01

    Discussion: It is suggested that not only iron load but also the erythropoiesis-stimulating agent dose reduction may be involved in ferritin elevation during ferric citrate hydrate treatment, resulting in a decrease of erythropoietin resistance index.

  1. Iron and Your Child

    Science.gov (United States)

    ... deficiency isn't corrected, it can lead to iron-deficiency anemia (a decrease in the number of red blood ... Parents Kids Teens Anemia Blood Test: Ferritin (Iron) Iron-Deficiency Anemia Vegetarianism Menstrual Problems Pregnant or Breastfeeding? Nutrients You ...

  2. Proteomic analysis of human bladder epithelial cells by 2D blue native SDS-PAGE reveals TCDD-induced alterations of calcium and iron homeostasis possibly mediated by nitric oxide.

    Science.gov (United States)

    Verma, Nisha; Pink, Mario; Petrat, Frank; Rettenmeier, Albert W; Schmitz-Spanke, Simone

    2015-01-02

    A proteomic analysis of the interaction among multiprotein complexes involved in 2,3,7,8-dibenzo-p-dioxin (TCDD)-mediated toxicity in urinary bladder epithelial RT4 cells was performed using two-dimensional blue native SDS-PAGE (2D BN/SDS-PAGE). To enrich the protein complexes, unexposed and TCDD-exposed cells were fractionated. BN/SDS-PAGE of the resulting fractions led to an effective separation of proteins and protein complexes of various origins, including cell membrane, mitochondria, and other intracellular compartments. Major differences between the proteome of control and exposed cells involved the alteration of many calcium-regulated proteins (calmodulin, protein S100-A2, annexin A5, annexin A10, gelsolin isoform b) and iron-regulated proteins (ferritin, heme-binding protein 2, transferrin). On the basis of these findings, the intracellular calcium concentration was determined, revealing a significant increase after 24 h of exposure to TCDD. Moreover, the concentration of the labile iron pool (LIP) was also significantly elevated in TCDD-exposed cells. This increase was strongly inhibited by the calmodulin (CaM) antagonist W-7, which pointed toward a possible interaction between iron and calcium signaling. Because nitric oxide (NO) production was significantly enhanced in TCDD-exposed cells and was also inhibited by W-7, we hypothesize that alterations in calcium and iron homeostasis upon exposure to TCDD may be linked through NO generated by CaM-activated nitric oxide synthase. In our model, we propose that NO produced upon TCDD exposure interacts with the iron centers of iron-regulatory proteins (IRPs) that modulate the alteration of ferritin and transferrin, resulting in an augmented cellular LIP and, hence, increased toxicity.

  3. Expression and structural and functional properties of human ferritin L-chain from Escherichia coli

    International Nuclear Information System (INIS)

    Levi, S.; Salfeld, J.; Franceschinelli, F.; Cozzi, A.; Dorner, M.H.; Arosio, P.

    1989-01-01

    The human ferritin L-chain cDNA was cloned into a vector for overproduction in Escherichia coli, under the regulation of a λ promoter. The plasmid obtained contains the full L-chain coding region modified at the first two codons. It is able to direct the synthesis of the L-chain which can constitute up to 15% of the total soluble protein of bacterial extract. The L-chains assemble to form a ferritin homopolymer with electrophoretic mobility, molecular weight, thermal stability, spectroscopic, and immunological properties analogous to natural ferritin from human liver (95% L-chain). This recombinant L-ferritin is able to incorporate and retain iron in solution at physiological pH values. At variance with the H-ferritin, the L form does not uptake iron at acidic pH values and does not show detectable ferroxidase activity. It is concluded that ferritin L-chain lacks the ferroxidase site present in the H-chain and that the two chains may have specialized functions in intracellular iron metabolism

  4. A rare case of iron-pill induced gastritis in a female teenager: A case report and a review of the literature.

    Science.gov (United States)

    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.

  5. Local iron homeostasis in the breast ductal carcinoma microenvironment

    International Nuclear Information System (INIS)

    Marques, Oriana; Porto, Graça; Rêma, Alexandra; Faria, Fátima; Cruz Paula, Arnaud; Gomez-Lazaro, Maria; Silva, Paula; Martins da Silva, Berta; Lopes, Carlos

    2016-01-01

    While the deregulation of iron homeostasis in breast epithelial cells is acknowledged, iron-related alterations in stromal inflammatory cells from the tumor microenvironment have not been explored. Immunohistochemistry for hepcidin, ferroportin 1 (FPN1), transferrin receptor 1 (TFR1) and ferritin (FT) was performed in primary breast tissues and axillary lymph nodes in order to dissect the iron-profiles of epithelial cells, lymphocytes and macrophages. Furthermore, breast carcinoma core biopsies frozen in optimum cutting temperature (OCT) compound were subjected to imaging flow cytometry to confirm FPN1 expression in the cell types previously evaluated and determine its cellular localization. We confirm previous results by showing that breast cancer epithelial cells present an ‘iron-utilization phenotype’ with an increased expression of hepcidin and TFR1, and decreased expression of FT. On the other hand, lymphocytes and macrophages infiltrating primary tumors and from metastized lymph nodes display an ‘iron-donor’ phenotype, with increased expression of FPN1 and FT, concomitant with an activation profile reflected by a higher expression of TFR1 and hepcidin. A higher percentage of breast carcinomas, compared to control mastectomy samples, present iron accumulation in stromal inflammatory cells, suggesting that these cells may constitute an effective tissue iron reservoir. Additionally, not only the deregulated expression of iron-related proteins in epithelial cells, but also on lymphocytes and macrophages, are associated with clinicopathological markers of breast cancer poor prognosis, such as negative hormone receptor status and tumor size. The present results reinforce the importance of analyzing the tumor microenvironment in breast cancer, extending the contribution of immune cells to local iron homeostasis in the tumor microenvironment context

  6. Iron

    Science.gov (United States)

    Iron is a mineral that our bodies need for many functions. For example, iron is part of hemoglobin, a protein which carries ... It helps our muscles store and use oxygen. Iron is also part of many other proteins and ...

  7. Randomized controlled trial assessing the efficacy of a reusable fish-shaped iron ingot to increase hemoglobin concentration in anemic, rural Cambodian women.

    Science.gov (United States)

    Rappaport, Aviva I; Whitfield, Kyly C; Chapman, Gwen E; Yada, Rickey Y; Kheang, Khin Meng; Louise, Jennie; Summerlee, Alastair J; Armstrong, Gavin R; Green, Timothy J

    2017-08-01

    Background: Anemia affects 45% of women of childbearing age in Cambodia. Iron supplementation is recommended in populations in which anemia prevalence is high. However, there are issues of cost, distribution, and adherence. A potential alternative is a reusable fish-shaped iron ingot, which, when added to the cooking pot, leaches iron into the fluid in which it is prepared. Objective: We sought to determine whether there was a difference in hemoglobin concentrations in rural Cambodian anemic women (aged 18-49 y) who cooked with the iron ingot or consumed a daily iron supplement compared with a control after 1 y. Design: In Preah Vihear, 340 women with mild or moderate anemia were randomly assigned to 1 ) an iron-ingot group, 2 ) an iron-supplement (18 mg/d) group, or 3 ) a nonplacebo control group. A venous blood sample was taken at baseline and at 6 and 12 mo. Blood was analyzed for hemoglobin, serum ferritin, and serum transferrin receptor. Hemoglobin electrophoresis was used to detect structural hemoglobin variants. Results: Anemia prevalence was 44% with the use of a portable hemoglobinometer during screening. At baseline, prevalence of iron deficiency was 9% on the basis of a low serum ferritin concentration. There was no significant difference in mean hemoglobin concentrations between the iron-ingot group (115 g/L; 95% CI: 113, 118 g/L; P = 0.850) or iron-supplement group (115 g/L; 95% CI: 113, 117 g/L; P = 0.998) compared with the control group (115 g/L; 95% CI: 113, 117 g/L) at 12 mo. Serum ferritin was significantly higher in the iron-supplement group (73 μg/L; 95% CI: 64, 82 μg/L; P = 0.002) than in the control group at 6 mo; however, this significance was not maintained at 12 mo (73 μg/L; 95% CI: 58, 91 μg/L; P = 0.176). Conclusions: Neither the iron ingot nor iron supplements increased hemoglobin concentrations in this population at 6 or 12 mo. We do not recommend the use of the fish-shaped iron ingot in Cambodia or in countries where the prevalence

  8. Efficacy of iron supplementation may be misinterpreted using conventional measures of iron status in iron-depleted, nonanemic women undergoing aerobic exercise training.

    Science.gov (United States)

    Pompano, Laura M; Haas, Jere D

    2017-12-01

    Background: Despite its known detrimental effects, iron deficiency remains the most common micronutrient deficiency in the world. Many interventions that aim to improve iron status involve physically active populations. Intense aerobic exercise training negatively affects iron status; however, the impact of regular moderate aerobic exercise on the effectiveness of iron supplementation remains unclear. Objective: This study aimed to determine whether aerobic training modifies the assessment of the effectiveness of iron supplementation in improving conventional iron status measures. Design: Seventy-two iron-depleted, nonanemic Chinese women [serum ferritin (sFer) 110 g/L] were included in an 8-wk, partially blinded, randomized controlled trial with a 2 × 2 factorial design including iron supplements (42 mg elemental Fe/d) or placebo and aerobic training (five 25-min sessions/wk at 75-85% of maximum heart rate) or no training. Linear mixed models were used to evaluate the relation between supplement type, training, and changes in iron status over time, measured by sFer, hemoglobin, soluble transferrin receptor (sTfR), and estimated total body iron. Results: After treatment, both the iron-supplemented trained and untrained groups showed significantly improved sFer, sTfR, and body iron values compared with either of the placebo groups. Similarly, trained participants had significantly higher aerobic fitness measures than untrained participants. Training modified the sFer response to supplementation (training by supplement interaction, P = 0.07), with the iron-supplemented trained group having significantly lower sFer than the iron-supplemented untrained group at week 8 (mean ± SD: 31.8 ± 13.5 and 47.6 ± 15.7 μg/L, respectively; P = 0.042), whereas there was no significant difference between the placebo trained and untrained groups (21.3 ± 12.2 and 20.3 ± 7.0 μg/L, respectively; P = 1.00). Conclusions: Regular aerobic training reduces the apparent effectiveness

  9. Phorbol diesters and transferrin modulate lymphoblastoid cell transferrin receptor expression by two different mechanisms

    International Nuclear Information System (INIS)

    Alcantara, O.; Phillips, J.L.; Boldt, D.H.

    1986-01-01

    Expression of transferrin receptors (TfR) by activated lymphocytes is necessary for lymphocyte DNA synthesis and proliferation. Regulation of TfR expression, therefore, is a mechanism by which the lymphocyte's proliferative potential may be directed and controlled. The authors studied mechanisms by which lymphoblastoid cells modulate TfR expression during treatment with phorbol diesters or iron transferrin (FeTf), agents which cause downregulation of cell surface TfR. Phorbol diester-induced TfR downregulation occurred rapidly, being detectable at 2 min and reaching maximal decreases of 50% by 15 min. It was inhibited by cold but not by agents that destabilize cytoskeletal elements. Furthermore, this downregulation was reversed rapidly by washing or by treatment with the membrane interactive agent, chlorpromazine. In contrast, FeTf-induced TfR downregulation occurred slowly. Decreased expression of TfR was detectable only after 15 min and maximal downregulation was achieved after 60 min. Although FeTf-induced downregulation also was inhibited by cold, it was inhibited in addition by a group of microtubule destabilizing agents (colchicine, vinblastine, podophyllotoxin) or cytochalasin B, a microfilament inhibitor. Furthermore, FeTf-induced downregulation was not reversed readily by washing or by treatment with chlorpromazine. Phorbol diesters cause TfR downregulation by a cytoskeleton-independent mechanism. These data indicate that TfR expression is regulated by two independent mechanisms in lymphoblastoid cells, and they provide the possibility that downregulation of TfR by different mechanisms may result in different effects in these cells

  10. Iron deficiency anemia and cognitive function in infancy.

    Science.gov (United States)

    Carter, R Colin; Jacobson, Joseph L; Burden, Matthew J; Armony-Sivan, Rinat; Dodge, Neil C; Angelilli, Mary Lu; Lozoff, Betsy; Jacobson, Sandra W

    2010-08-01

    This study examined effects of iron deficiency anemia (IDA) on specific domains of infant cognitive function and the role of IDA-related socioemotional deficits in mediating and/or moderating these effects. Infants were recruited during routine 9-month visits to an inner-city clinic. IDA was defined as hemoglobin level or =2 abnormal iron deficiency indicators (mean corpuscular volume, red cell distribution width, zinc protoporphyrin, transferrin saturation, and ferritin). At 9 and 12 months, the Fagan Test of Infant Intelligence (FTII); A-not-B task; Emotionality, Activity, and Sociability Temperament Survey; and Behavior Rating Scale were administered. Analyses were adjusted for potential confounders, including age and sociodemographic variables. Twenty-eight infants met criteria for IDA, 28 had nonanemic iron deficiency (NA ID) and 21 had iron sufficiency (IS). There was a linear effect for object permanence at 9 months: infants with IDA were least likely to exhibit object permanence, IS most likely, and NA ID intermediate. Infants with IDA and those with hemoglobin level object permanence and short-term memory encoding and/or retrieval in infants with IDA at 9 months. These cognitive effects were attributable, in part, to IDA-related deficits in socioemotional function. Children with poor socioemotional performance seem to be more vulnerable to the effects of IDA on cognitive function.

  11. Redox, iron, and nutritional status of children during swimming training.

    Science.gov (United States)

    Kabasakalis, Athanasios; Kalitsis, Konstantinos; Nikolaidis, Michalis G; Tsalis, George; Kouretas, Dimitris; Loupos, Dimitris; Mougios, Vassilis

    2009-11-01

    Effects of exercise training on important determinants of children's long-term health, such as redox and iron status, have not been adequately investigated. The aim of the present study was to examine changes in markers of the redox, iron and nutritional status of boy and girl swimmers during a prolonged period of training. 11 boys and 13 girls, aged 10-11 years, were members of a swimming club. They were assessed at the beginning of the training season, at 13 weeks and at 23 weeks through blood sampling and recording of the diet. Reduced glutathione increased at 13 and 23 weeks, whereas oxidised glutathione decreased at 13 weeks, resulting in an increase of the reduced/oxidised glutathione ratio at 13 and 23 weeks. Total antioxidant capacity, catalase, thiobarbituric acid-reactive substances, hemoglobin, transferrin saturation and ferritin did not change significantly. Carbohydrate intake was below 50% of energy and fat intake was above 40% of energy. Intakes of saturated fatty acids and cholesterol were excessive. Iron intake was adequate but intakes of folate, vitamin E, calcium and magnesium did not meet the recommended daily allowances. No significant differences were found between sexes in any of the parameters measured. In conclusion, child swimmers improved the redox status of glutathione during training, although the intake of antioxidant nutrients did not change. The iron status was not impaired by training. Suboptimal intake of several nutrients suggests the need for nutritional monitoring and education of children athletes.

  12. Anaemia and Iron Homeostasis in a Cohort of HIV-Infected Patients: A Cross-Sectional Study in Ghana

    Directory of Open Access Journals (Sweden)

    Christian Obirikorang

    2016-01-01

    Full Text Available Aim. We determined the prevalence of anaemia and evaluated markers of iron homeostasis in a cohort of HIV patients. Methods. A comparative cross-sectional study on 319 participants was carried out at the Tamale Teaching Hospital from July 2013 to December 2013, 219 patients on HAART (designated On-HAART and 100 HAART-naive patients. Data gathered include sociodemography, clinical history, and selected laboratory assays. Results. Prevalence of anaemia was 23.8%. On-HAART participants had higher CD4/CD3 lymphocyte counts, Hb, HCT/PCV, MCV, MCH, iron, ferritin, and TSAT (P<0.05. Hb, iron, ferritin, and TSAT decreased from grade 1 to grade 3 anaemia and CD4/CD3 lymphocyte count was lowest in grade 3 anaemia (P<0.05. Iron (P=0.0072 decreased with disease severity whilst transferrin (P=0.0143 and TIBC (P=0.0143 increased with disease severity. Seventy-six (23.8% participants fulfilled the criteria for anaemia, 86 (26.9% for iron deficiency, 41 (12.8% for iron deficiency anaemia, and 17 (5.3% for iron overload. The frequency of anaemia was higher amongst participants not on HAART (OR 2.6 for grade 1 anaemia; OR 3.0 for grade 3 anaemia. Conclusion. In this study population, HIV-associated anaemia is common and is related to HAART status and disease progression. HIV itself is the most important cause of anaemia and treatment of HIV should be a priority compared to iron supplementation.

  13. Assessment of regression models for adjustment of iron status biomarkers for inflammation in children with moderate acute malnutrition in Burkina Faso

    DEFF Research Database (Denmark)

    Cichon, Bernardette; Ritz, Christian; Fabiansen, Christian

    2017-01-01

    BACKGROUND: Biomarkers of iron status are affected by inflammation. In order to interpret them in individuals with inflammation, the use of correction factors (CFs) has been proposed. OBJECTIVE: The objective of this study was to investigate the use of regression models as an alternative to the CF...... approach. METHODS: Morbidity data were collected during clinical examinations with morbidity recalls in a cross-sectional study in children aged 6-23 mo with moderate acute malnutrition. C-reactive protein (CRP), α1-acid glycoprotein (AGP), serum ferritin (SF), and soluble transferrin receptor (sTfR) were......TfR with the use of the best-performing model led to a 17% point increase and iron deficiency. CONCLUSION: Regression analysis is an alternative to adjust SF and may be preferable in research settings, because it can take morbidity and severity...

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

    Science.gov (United States)

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

    2016-10-01

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

  15. Targeting, Monitoring and Effect of Oral Iron Therapy on Haemoglobin Levels in Older Patients Discharged to Primary Care from Inpatient Rehabilitation: A Cohort Study Using Routinely Collected Data.

    Science.gov (United States)

    Thomson, Zach; Hands, Katherine J; Witham, Miles D

    2016-08-01

    Oral iron is commonly prescribed to older patients with suspected or confirmed iron-deficiency anaemia; however, few studies have examined the effectiveness of oral iron therapy in the real world in this population. We therefore determined the prevalence of iron deficiency in older people prescribed oral iron, examined the response mounted to therapy and ascertained predictors of response to oral iron. We analysed a routinely collected, linked dataset from older patients who had undergone inpatient rehabilitation between 1999 and 2011. An initial analysis examined patients within this cohort who were prescribed iron after rehabilitation and derived three groups based upon their ferritin and transferrin indices: probably, possibly and not iron deficient. A second analysis compared pre- and post-treatment haemoglobin to determine the degree of response to iron therapy across each category of deficiency. Finally, patient demographics, linked biochemistry data and comorbid disease based on International Classification of Disease (ICD-10) codes from previous hospital admissions were used in regression modelling to evaluate factors affecting response to therapy. A total of 490 patients were prescribed oral iron within 90 days of rehabilitation discharge. Of these, 413 (84 %) had iron indices performed; 94 (23 %) were possibly deficient, 224 (54 %) were probably deficient, and 95 (23 %) were not deficient. Of the 490 patients, 360 had both pre- and post-treatment haemoglobin data and iron indices; probably deficient patients mounted a slightly greater response to oral iron (17 vs. 12 g/L for not deficient; p < 0.05). Only pre-treatment haemoglobin, mean cell volume and lower gastrointestinal pathology were significant predictors of a response to oral iron therapy. Notably, acid-suppressant use was not a predictor of response. We conclude that many older patients are exposed to oral iron without good evidence of either iron deficiency or a significant response to

  16. Effect of nutrition education and diet modification in iron depleted preschool children in nurseries in Tehran: a pilot study.

    Science.gov (United States)

    Khoshnevisan, Farnaz; Kimiagar, Masood; Kalantaree, Nasser; Valaee, Nasser; Shaheedee, Nooshin

    2004-07-01

    In view of the high prevalence of iron deficiency in preschool children and its consequences, this study was carried out to examine the effect of nutrition education and dietary modification on 438 two- to six-year-old nursery school children in Tehran in 1999. Sixty-two children who were judged anemic, iron-depleted, or having low iron stores were randomly allocated to "control," "dietary modification" (consuming one additional citrus fruit after lunch), and "nutrition education" (teaching the mothers proper eating patterns based on the food pyramid) groups. Food habits were surveyed, including 24-hour dietary recall and food frequency, as well as timing of consumption of special items; this survey was carried out for each child before and after intervention. After three months, blood samples were taken from the subjects. The prevalence of anemia, iron depletion, and low iron stores was 11.4, 62.8, and 15.1% respectively, with no significant differences observed in hemoglobin and percent transferrin saturation (%TS) between the groups. Mean+/-SD serum ferritin concentrations in "control," "diet modification," and "nutrition education" groups were 8.9+/-3.1, 9.5+/-3.7, and 6.9+/-2.3 microg/dL. The same figures at the end of intervention were 6.9+/-3.5, 11.2+/-5, and 10.7+/-5.9 microg/dL, respectively. Analysis of variance showed ferritin concentrations to be significantly different, in that there was a reduction in the control and elevation in the nutrition education groups. There was no significant difference in %TS before and after the intervention. During three months of intervention, changes in frequency of fruit and fruit juice intake after the meals in nutrition education and diet modification groups were significantly correlated to serum ferritin alteration. Frequency of fruit juice intake (rich in vitamin C) after meals (at least five times a week) can significantly increase serum ferritin within three months. Therefore, educating mothers of iron

  17. Brain iron accumulation affects myelin-related molecular systems implicated in a rare neurogenetic disease family with neuropsychiatric features.

    Science.gov (United States)

    Heidari, M; Johnstone, D M; Bassett, B; Graham, R M; Chua, A C G; House, M J; Collingwood, J F; Bettencourt, C; Houlden, H; Ryten, M; Olynyk, J K; Trinder, D; Milward, E A

    2016-11-01

    The 'neurodegeneration with brain iron accumulation' (NBIA) disease family entails movement or cognitive impairment, often with psychiatric features. To understand how iron loading affects the brain, we studied mice with disruption of two iron regulatory genes, hemochromatosis (Hfe) and transferrin receptor 2 (Tfr2). Inductively coupled plasma atomic emission spectroscopy demonstrated increased iron in the Hfe -/- × Tfr2 mut brain (P=0.002, n ≥5/group), primarily localized by Perls' staining to myelinated structures. Western immunoblotting showed increases of the iron storage protein ferritin light polypeptide and microarray and real-time reverse transcription-PCR revealed decreased transcript levels (Pgross myelin structure and integrity appear unaffected (P>0.05). Overlap (P0.05). These results implicate myelin-related systems involved in NBIA neuropathogenesis in early responses to iron loading. This may contribute to behavioral symptoms in NBIA and hemochromatosis and is relevant to patients with abnormal iron status and psychiatric disorders involving myelin abnormalities or resistant to conventional treatments.

  18. Iron deficiency is associated with food insecurity in pregnant females in the United States: National Health and Nutrition Examination Survey 1999-2010.

    Science.gov (United States)

    Park, Clara Y; Eicher-Miller, Heather A

    2014-12-01

    Food-insecure pregnant females may be at greater risk of iron deficiency (ID) because nutrition needs increase and more resources are needed to secure food during pregnancy. This may result in a higher risk of infant low birth weight and possibly cognitive impairment in the neonate. The relationships of food insecurity and poverty income ratio (PIR) with iron intake and ID among pregnant females in the United States were investigated using National Health and Nutrition Examination Survey 1999-2010 data (n=1,045). Food security status was classified using the US Food Security Survey Module. One 24-hour dietary recall and a 30-day supplement recall were used to assess iron intake. Ferritin, soluble transferrin receptor, or total body iron classified ID. Difference of supplement intake prevalence, difference in mean iron intake, and association of ID and food security status or PIR were assessed using χ(2) analysis, Student t test, and logistic regression analysis (adjusted for age, race, survey year, PIR/food security status, education, parity, trimester, smoking, C-reactive protein level, and health insurance coverage), respectively. Mean dietary iron intake was similar among groups. Mean supplemental and total iron intake were lower, whereas odds of ID, classified by ferritin status, were 2.90 times higher for food-insecure pregnant females compared with food-secure pregnant females. Other indicators of ID were not associated with food security status. PIR was not associated with iron intake or ID. Food insecurity status may be a better indicator compared with income status to identify populations at whom to direct interventions aimed at improving access and education regarding iron-rich foods and supplements. Copyright © 2014 Academy of Nutrition and Dietetics. Published by Elsevier Inc. All rights reserved.

  19. Estrogen-induced disruption of intracellular iron metabolism leads to oxidative stress, membrane damage, and cell cycle arrest in MCF-7 cells.

    Science.gov (United States)

    Bajbouj, Khuloud; Shafarin, Jasmin; Abdalla, Maher Y; Ahmad, Iman M; Hamad, Mawieh

    2017-10-01

    It is well established that several forms of cancer associate with significant iron overload. Recent studies have suggested that estrogen (E2) disrupts intracellular iron homeostasis by reducing hepcidin synthesis and maintaining ferroportin integrity. Here, the ability of E2 to alter intracellular iron status and cell growth potential was investigated in MCF-7 cells treated with increasing concentrations of E2. Treated cells were assessed for intracellular iron status, the expression of key proteins involved in iron metabolism, oxidative stress, cell survival, growth, and apoptosis. E2 treatment resulted in a significant reduction in hepcidin expression and a significant increase in hypoxia-inducible factor 1 alpha, ferroportin, transferrin receptor, and ferritin expression; a transient decrease in labile iron pool; and a significant increase in total intracellular iron content mainly at 20 nM/48 h E2 dose. Treated cells also showed increased total glutathione and oxidized glutathione levels, increased superoxide dismutase activity, and increased hemoxygenase 1 expression. Treatment with E2 at 20 nM for 48 h resulted in a significant reduction in cell growth (0.35/1 migration rate) and decreased cell survival (iron metabolism and precipitates adverse effects concerning cell viability, membrane integrity, and growth potential.

  20. Isotope-aided studies of the bioavailability of iron and zinc from human diets consumed in Poland

    International Nuclear Information System (INIS)

    Rafalski, H.; Switoniak, T.

    1994-01-01

    The bioavailability of food iron is affected by a number of physiological and dietary variables and it should be checked for the population living in natural conditions. The primary purpose of this study was to measure in volunteers iron absorption after oral administration of a wheat roll enriched with 15 mg of Fe as FeSO 4· 7H 2 O and 20 μCi of 59 Fe. For assessment of iron absorption whole body counting was used. The secondary purpose was to relate the available iron to iron stores, anthropometric indices, bleeding days and dietary variables. Thirteen female and 7 male healthy subjects aged between 19 and 47 years were observed. Hematological measurements on blood: serum ferritin (SF), serum iron (SI), total iron binding capacity (TIBC), transferrin (ST), transferrin saturation (TS), hemoglobin (Hb), hematocrit (Hct), red blood cell (RBC), mean corpuscular volume (MCV) were made. The subjects were examined by a specialist in internal medicine. Their 24-hour recall food intake was performed by questionnaire. The findings concerning the purposes of the study may be summarized as follows: 1) mean absorbed iron was 1.6 ± 1.2 mg for women, and 0.5±0.2 mg for men; 2) iron stores evaluated from SF were in women 2.6± 1.7 mg/kg body weight and in men 10.4±5.4 mg/kg; 3) blood indices proved iron deficiency anemia in 1 woman, Hb = 9.2 g/dL, SF = 1.8 μg/L, TS = 6%; in 4 women deficient iron stores were observed, Hb > 12g/dL, SF < 12 mg/L; 8 women and 7 men were normal; 4) in women the absorbed iron related inversely to SF (-0.61) and iron stores (-0.61); 5) the iron stores related to the sum of four skinfolds in women (0.55) and in men (0.80), in women it related to body weight (0.77) too; 6) in women the absorbed iron related to bleeding days (0.69); 7) in women ascorbic acid consumption related to iron store indices; SF, SI and TS. (author). 2 figs, 3 tabs

  1. Relationship of serum ferritin level and tic severity in children with Tourette syndrome.

    Science.gov (United States)

    Ghosh, Debabrata; Burkman, Elizabeth

    2017-08-01

    Tics can be considered hyperkinetic movements akin to restless leg syndrome (RLS). Drawing the analogy of iron deficiency as an etiology of RLS, it is conceivable that iron deficiency may underlie or worsen tics in Tourette syndrome (TS). The purpose of this study was to evaluate the relationship between serum ferritin levels and tic severity, as well as consequent impact on life, in children with TS. Children tic severity, impact on life, medication, comorbidities, blood count, and serum ferritin at diagnosis and follow-up. In fifty-seven patients, M:F = 2:1, serum ferritin was 48.0 ± 33.28 ng/mL, tic severity score 2.3 ± 0.80, impact on life score 2.2 ± 0.93, and composite score 4.57 ± 1.6. Serum ferritin was not influenced by comorbid obsessive compulsive disorder (OCD), attention deficit hyperactive disorder (ADHD), or anxiety (P > 0.16). Thirty-eight percent with low serum ferritin (≤50 ng/mL) (n = 37) had severe tics (>5 composite score), compared with 25% in normal ferritin group (n = 20). Over 6-12 months, tic severity score improved in both iron treated groups, deficient (2.70 to 1.90) and sufficient (2.40 to 1.95), whereas tics worsened or remained the same when not treated with iron. Our data suggest iron deficiency may be associated with more severe tics with higher impact on TS children, independent of the presence of OCD, ADHD, or anxiety. Iron supplementation showed a trend towards improvement of tic severity upon follow-up. We suggest a double-blind, placebo-controlled prospective study to reach a definite conclusion.

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

    Science.gov (United States)

    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

  3. Effect of RBC concentrate transfusions on serum ferritin content in children with acute leukaemia.

    Science.gov (United States)

    Bebeshko, V G; Bruslova, E M; Tsvietkova, N M; Iatsemirskii, S M; Puchkareva, T I; Gonchar, L A; Krukovska, V V; Zelinska, A V; Mishchenko, L P

    2013-01-01

    To study the serum ferritin levels in children with acute leukemia, depending on the number of transfusions of RBC concentrate and period of disease. We studied the red blood count, serum iron and ferritin levels in 54 patients with acute leukemia before chemotherapy, at the time of a standardized treatment protocol, and after transfusions of RBC concentrates. In the debute of acute leukemia just before treatment lauch the serum ferritin in 81.5% of children was 2.3-2.5 higher than normal. The need for transfusion of RBC concentrates was higher under serum ferritin level exceeding 500 ng/mL. The association was established between ferritin content and age of the children, variant of acute leukemia and period of the disease. The level of serum ferritin can be used as a marker of ferrokinetic status for timely diagnosis of iron overload in children with acute leukemias and for application of treatment-and-prophylactic actions. Bebeshko V. G., Bruslova K. M., Cvjetkova N. M., Jacemyrskyj S. M., Pushkarova T. I., Gonchar L. O., Krukovska V. V., Zelinska A. V., Mishhenko L. P., 2013.

  4. Association of Serum Ferritin Levels with Metabolic Syndrome and Insulin Resistance.

    Science.gov (United States)

    Padwal, Meghana K; Murshid, Mohsin; Nirmale, Prachee; Melinkeri, R R

    2015-09-01

    The impact of CVDs and Type II DM is increasing over the last decade. It has been estimated that by 2025 their incidence will double. Ferritin is one of the key proteins regulating iron homeostasis and is a widely available clinical biomarker of iron status. Some studies suggest that prevalence of atherosclerosis and insulin resistance increases significantly with increasing serum ferritin. Metabolic syndrome is known to be associated with increased risk of atherosclerosis as well as insulin resistance. The present study was designed to explore the association of serum ferritin levels with metabolic syndrome and insulin resistance. The present study was prospective, cross sectional. The study protocol was approved by IEC. The study group consisted of 90 participants (50 cases of metabolic syndrome and 40 age and sex matched controls). Diagnosis of metabolic syndrome was done as per NCEP ATP III criteria. Estimation of serum Ferritin and Insulin was done by Chemiluminescence Immunoassay (CLIA) while Glucose by Glucose Oxidase and Peroxidase (GOD-POD) method. Insulin Resistance was calculated by HOMA IR score. Data obtained was statistically analysed by using student t-test. We found statistically significant rise in the levels of serum ferritin (p=syndrome as compared with controls. High serum ferritin levels though within normal range are significantly associated with both metabolic syndrome and insulin resistance.

  5. The Crystal Structure of a Maxi/Mini-Ferritin Chimera Reveals Guiding Principles for the Assembly of Protein Cages

    Energy Technology Data Exchange (ETDEWEB)

    Cornell, Thomas A. [Department; Division; Srivastava, Yogesh [Genome; Jauch, Ralf [Genome Institute of Singapore, Singapore; Genome; Fan, Rongli [Division; Orner, Brendan P. [Department; Division

    2017-07-19

    Cage proteins assemble into nanoscale structures with large central cavities. They play roles, including those as virus capsids and chaperones, and have been applied to drug delivery and nanomaterials. Furthermore, protein cages have been used as model systems to understand and design protein quaternary structure. Ferritins are ubiquitous protein cages that manage iron homeostasis and oxidative damage. Two ferritin subfamilies have strongly similar tertiary structure yet distinct quaternary structure: maxi-ferritins normally assemble into 24-meric, octahedral cages with C-terminal E-helices centered around 4-fold symmetry axes, and mini-ferritins are 12-meric, tetrahedral cages with 3-fold axes defined by C-termini lacking E-domains. To understand the role E-domains play in ferritin quaternary structure, we previously designed a chimera of a maxi-ferritin E-domain fused to the C-terminus of a mini-ferritin. The chimera is a 12-mer cage midway in size between those of the maxi- and mini-ferritin. The research described herein sets out to understand (a) whether the increase in size over a typical mini-ferritin is due to a frozen state where the E-domain is flipped out of the cage and (b) whether the symmetrical preference of the E-domain in the maxi-ferritin (4-fold axis) overrules the C-terminal preference in the mini-ferritin (3-fold axis). With a 1.99 Å resolution crystal structure, we determined that the chimera assembles into a tetrahedral cage that can be nearly superimposed with the parent mini-ferritin, and that the E-domains are flipped external to the cage at the 3-fold symmetry axes.

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

    Directory of Open Access Journals (Sweden)

    Andreia Silva Evangelista

    2015-01-01

    Full Text Available 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.

  7. Relationship between Plasma Ferritin Level and Siderocyte Number in Splenectomized β-Thalassemia/HbE Patients

    Directory of Open Access Journals (Sweden)

    A. Tripatara

    2012-01-01

    Full Text Available Introduction. In iron overload status, excess iron deposits in reticuloendothelial cells and tissues and can be detected using Prussian blue staining. The aim of this paper was to investigate the relationship between siderocyte numbers and plasma ferritin levels (a practically standard marker of iron overload in the blood of the splenectomized and nonsplenectomized β-thalassemia/HbE patients, who are at risk of iron overload. Methods. EDTA blood samples from 64 patients with 35 splenectomized and 29 nonsplenectomized β-thalassemia/HbE patients, who received regular blood transfusions, and 20 normal individuals were investigated for siderocyte numbers, plasma ferritin levels, and complete blood counts. Results. The average percent siderocytes in splenectomized and nonsplenectomized β-thalassemia/HbE patients were 11.5% and 0.08%, respectively, and plasma ferritin levels of 2,332 μg/L and 1,279 μg/L, respectively. Percent siderocytes showed a good correlation with plasma ferritin levels only in splenectomized patients (r=0.69, P<0.001. A receiver operating curve analysis from splenectomized patients’ data indicated that siderocytes at 3% cut-off are the best predictor for plasma ferritin level ≥1,000 μg/L with 92.9% sensitivity and 42.9% specificity. Conclusion. Circulating siderocyte numbers can be used as a screening test for the assessment of the iron overload in splenectomized β-thalassemia/HbE patients in the place where serum ferritin is not available.

  8. Iron absorption in relation to iron status

    International Nuclear Information System (INIS)

    Magnusson, B.; Bjoern-Rasmussen, E.; Hallberg, L.; Rossander, L.

    1981-01-01

    The absorption from a 3 mg dose of ferrous iron was measured in 250 male subjects. The absorption was related to the log concentration of serum ferritin in 186 subjects of whom 99 were regular blood donors (r= -0.76), and to bone marrow haemosiderin grading in 52 subjects with varying iron status. The purpose was to try and establish a percentage absorption from such a dose that is representative of subjects who are borderline iron deficient. This information is necessary for food iron absorption studies in order (1) to calculate the absorption of iron from the diet at a given iron status and (2) compare the absorption of iron from different meals studied in different groups of subjects by different investigarors. The results suggest that an absorption of about 40% of a 3 mg reference dose of ferrous iron is given in a fasting state, roughly corresponds to the absorption in borderline-iron-deficient subjects. The results indicate that this 40% absorption value corresponds to a serum ferritin level of 30 μg/l and that food iron absorption in a group of subjects should be expressed preferably as the absorption corresponding to a reference-dose absorption of 45%, or possibly a serum ferritin level of 30 μg/l. (author)

  9. Deletion of Iron Regulatory Protein 1 Causes Polycythemia and Pulmonary Hypertension in Mice through Translational De-repression of HIF2α

    Science.gov (United States)

    Ghosh, Manik C.; Zhang, De-Liang; Jeong, Suh Young; Kovtunovych, Gennadiy; Ollivierre-Wilson, Hayden; Noguchi, Audrey; Tu, Tiffany; Senecal, Thomas; Robinson, Gabrielle; Crooks, Daniel R.; Tong, Wing-Hang; Ramaswamy, Kavitha; Singh, Anamika; Graham, Brian B.; Tuder, Rubin M.; Yu, Zu-Xi; Eckhaus, Michael; Lee, Jaekwon; Springer, Danielle A.; Rouault, Tracey A.

    2013-01-01

    SUMMARY Iron regulatory proteins 1 and 2 (Irps) post-transcriptionally control the expression of transcripts that contain iron responsive element (IRE) sequences, including ferritin, ferroportin, transferrin receptor and hypoxia inducible factor 2α (HIF2α). We report here that mice with targeted deletion of Irp1 developed pulmonary hypertension and polycythemia that was exacerbated by a low iron diet. Hematocrits increased to 65% in iron-starved mice, and many polycythemic mice died of abdominal hemorrhages. Irp1 deletion enhanced HIF2α protein expression in kidneys of Irp1−/− mice, which led to increased erythropoietin (EPO) expression, polycythemia and concomitant tissue iron deficiency. Increased HIF2α expression in pulmonary endothelial cells induced high expression of endothelin-1, likely contributing to the pulmonary hypertension of Irp1−/− mice. Our results reveal why anemia is an early physiological consequence of iron deficiency, highlight the physiological significance of Irp1 in regulating erythropoiesis and iron distribution, and provide important insights into the molecular pathogenesis of pulmonary hypertension. PMID:23395173

  10. 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.

    Science.gov (United States)

    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.

  11. Consumption of Iron-Biofortified Beans Positively Affects Cognitive Performance in 18- to 27-Year-Old Rwandan Female College Students in an 18-Week Randomized Controlled Efficacy Trial.

    Science.gov (United States)

    Murray-Kolb, Laura E; Wenger, Michael J; Scott, Samuel P; Rhoten, Stephanie E; Lung'aho, Mercy G; Haas, Jere D

    2017-11-01

    Background: Evidence shows that iron deficiency in adulthood may affect cognitive performance, possibly by disrupting neurotransmitter regulation or brain energy metabolism. Women of reproductive age (WRA) are among those who are most vulnerable to iron deficiency; however, they have been largely ignored in the literature relating iron status to cognition. Objective: Our aim was to determine the efficacy of iron-biofortified beans in improving cognition in WRA compared with control beans. Methods: A double-blind, randomized intervention study was conducted in 150 women aged 18-27 y with low iron status (ferritin beans (86.1 ppm iron) or control beans (50.1 ppm iron) daily for 18 wk. Iron status was assessed based on hemoglobin, ferritin, transferrin receptor, and body iron values and on cognitive performance on 5 computerized tasks at baseline and endline. Results: Groups did not differ on any variables at baseline. Per protocol analyses revealed that consumption of the biofortified beans resulted in a 17% larger improvement in the speed of spatial selective attention; a nearly 7-fold larger improvement in the speed, a 68% greater improvement in the efficiency, and a >2-fold greater improvement in the specificity of memory retrieval; and a >2-fold larger improvement in the speed and a >3-fold larger improvement in the efficiency of memory search-all of which are relative to consumption of the control beans ( P beans for 18 wk improved cognitive performance, especially the efficiency of search and the speed of retrieval on memory tasks, in young adult women. This trial was registered at clinicaltrials.gov as NCT01594359.

  12. Prevalencia de anemia y deficiencia de hierro en escolares jujeños de 12 años Prevalence of anemia and iron deficiency in 12 year old school children from Jujuy

    Directory of Open Access Journals (Sweden)

    María C. Buys

    2005-04-01

    Full Text Available La deficiencia de hierro es una de las deficiencias de micronutrientes más comunes. Los adolescentes son un grupo vulnerable. Un reconocimiento oportuno puede prevenir una anemia ferropénica, etapa final y grave de dicha deficiencia, insuficientemente conocida en nuestro país. El objetivo de este estudio fue determinar los valores hematológicos en adolescentes y conocer las prevalencias de anemia y deficiencia de hierro. Definidas como a anemia: hematocrito (Hto Iron deficiency is highly frequent among adolescents. Its early detection can prevent the development of a ferropenic anemia, a serious condition. The problem has not been well studied in our country. The purpose of this work was to determine the frequency of iron deficiency and anemia in adolescents. The criteria considered were: hematocrit below 38%, b saturation transferrin below 16%, c ferritin below 15 ng/ml. The study was carried out in 2.265 schoolchildren, 12 years old, of both sexes, in urban and periurban areas in the city of San Salvador de Jujuy (1.250 a.s.l.. The following parameters were measured: hematocrit as well as serum iron and total iron binding capacity, both by colorimetric method. Ferritin was measured by ELISA. Anemia was not found. Iron deficiency as estimated by the iron functional component, was found in 25% of girls and 21% of boys and, through iron stores, in 28% of girls and 18% of boys. Iron deficiency stores in both sexes is the more relevant alteration, indicating that the population sample here studied constitutes a highly vulnerable group. The early detection of iron deficiency will help physical and intellectual development so that adequate sanitary policies are necessary for its prevention.

  13. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... have less hemoglobin than normal. Hemoglobin is a protein inside red blood cells that carries oxygen from the lungs to tissues ... stored iron has been used. Ferritin is a protein that helps store iron in your ... very young red blood cells. Peripheral smear to see if your red blood ...

  14. Iron deficiency in children

    African Journals Online (AJOL)

    cell and excess iron is stored as ferritin to protect the cell from oxidative ... iron deficiency has negative effects during pregnancy and in the postpartum period, which affects maternal health ... use of undiluted cow's milk and a predominant cow's milk intake in .... on bone marrow smear or biopsy for the definitive diagnosis of.

  15. Gender differences in associations of serum ferritin and diabetes, metabolic syndrome, and obesity in the China Health and Nutrition Survey.

    Science.gov (United States)

    Han, Ling-ling; Wang, Yu-xia; Li, Jia; Zhang, Xiao-lei; Bian, Che; Wang, He; Du, Shufa; Suo, Lin-na

    2014-11-01

    This study examines gender differences in associations of serum ferritin and diabetes, metabolic syndrome (MetS), and obesity in Chinese. Based on a nationwide, population-based China Health and Nutrition survey this study included 8564 men and women aged 18 years or older. Anthropometric and fasting blood glucose, insulin, lipids, ferritin, and transferrin data were collected. Ferritin concentrations were higher in men than women (201.55 ± 3.6 versus 80.46 ± 1.64 ng/mL, p obesity, and overweight were 8.05, 8.97, 4.67, 25.88% among men and 14.23, 6.58, 5.81, 26.82% among women, respectively. Elevated ferritin concentrations were associated with higher body mass index, waist circumference, lipids, insulin, glucose (all p obesity (p = 0.010), overweight (p gender difference in associations between ferritin and MetS, obesity, and diabetes in Chinese adults. Further evaluations of the variation in gender on these associations are warranted to understand the mechanisms behind gender differences. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  16. H Ferritin Gene Silencing in a Human Metastatic Melanoma Cell Line: A Proteomic Analysis

    DEFF Research Database (Denmark)

    Di Sanzo, Maddalena; Gaspari, Marco; Misaggi, Roberta

    2011-01-01

    Ferritin, the major intracellular iron-storage protein, is made of 24 subunits of two types, H and L. Besides regulating intracellular iron homeostasis, it has been found that ferritin, in particular the H subunit (FHC), is involved in different biological events such as cell differentiation...... and pathologic states (i.e., neurodegeneration and cancer). This study is aimed at investigating the whole-cell proteome of FHC-expressing and sh-RNA-silenced human metastatic melanoma cells (MM07(m)) in the attempt to identify and classify the highest number of proteins directly or indirectly controlled...... of H ferritin signaling pathways and lend support to the hypothesis that specific targeting of this gene might be an attractive and potentially effective strategy for the management of metastatic melanoma....

  17. Iron supplementation prevents a decline in iron stores and enhances strength performance in elite female volleyball players during the competitive season.

    Science.gov (United States)

    Mielgo-Ayuso, Juan; Zourdos, Michael C; Calleja-González, Julio; Urdampilleta, Aritz; Ostojic, Sergej

    2015-06-01

    The primary aim of this study was to examine the effects of 11 weeks of iron supplementation on hematological and strength markers in elite female volleyball players. Twenty-two volleyball players (aged 27.0 ± 5.6 years) from 2 Spanish First National League teams participated and were counterbalanced into 1 of 2 groups based upon iron status: (i) control group (CG, n = 11); or (ii) iron treatment group (ITG, n = 11), which received 325 mg/day of ferrous sulphate daily. Subjects performed their team's regimen of training or match play every day. Both groups were tested for hematological and strength levels at 2 points: (i) baseline (T0, before preseason) and (ii) 11 weeks later (T11, post-testing). Hematological parameters were serum iron (sFe), serum ferritin (FER), transferrin saturation index (TSI), and hemoglobin (Hb); strength assessments were bench press, military press, half-squat, power clean, clean and jerk, and pull-over. CG experienced a significant decrease (p 0.05). Consequently, in ITG all hematological parameters were significantly greater (p volleyball players during the competitive season.

  18. Specificity of chicken and mammalian transferrins in myogenesis

    International Nuclear Information System (INIS)

    Beach, R.L.; Popiela, Heinz; Festoff, B.W.

    1985-01-01

    Chicken transferrins isolated from eggs, embryo extract, serum or ischiatic-peroneal nerves are able to stimulate incorporation of ( 3 H)thymidine, and promote myogenesis by primary chicken muscles cells in vitro. Mammalian transferrins (bovine, rat, mouse, horse, rabbit, and human) do not promote ( 3 H)thymidine incorporation or myotube development. Comparison of the peptide fragments obtained after chemical or limited proteolytic cleavage demonstrates that the four chicken transferrins are all indistinguishable, but they differ considerably from the mammalian transferrins. The structural differences between chicken and mammalian transferrins probably account for the inability of mammalian transferrins to act as mitogens for, and to support myogenesis of, primary chicken muscle cells. (author)

  19. Iron status in Danish women, 1984-1994: a cohort comparison of changes in iron stores and the prevalence of iron deficiency and iron overload

    DEFF Research Database (Denmark)

    Milman, N.; Byg, K.E.; Ovesen, Lars

    2003-01-01

    Background and objectives: From 1954 to 1986, flour in Denmark was fortified with 30 mg carbonyl iron per kilogram. This mandatory enrichment of cereal products was abolished in 1987. The aim was to evaluate iron status in the Danish female population before and after abolishment of iron...... fortification. Methods: Iron status, serum ferritin and haemoglobin, was assessed in population surveys in 1983-1984 comprising 1221 Caucasian women (1089 non-blood-donors, 130 donors) and in 1993-1994 comprising 1261 women (1155 non-blood-donors, 104 donors) equally distributed in age cohorts of 40, 50, 60......, postmenopausal women had median ferritin of 75 mug/L and in 1994 of 93 mug/L (P iron stores (ferritin iron stores (ferritin less...

  20. Elevated levels of ferritin in the cerebrospinal fluid of amyotrophic lateral sclerosis patients.

    Science.gov (United States)

    Zheng, Y; Gao, L; Wang, D; Zang, D

    2017-08-01

    The aim of the study was to detect changes in the levels of ferritin heavy chain (FHC), ferritin light chain (FLC), and transferrin in the cerebrospinal fluid (CSF) and serum of amyotrophic lateral sclerosis (ALS) patients and to analyze the correlations between the levels of these proteins and various clinical parameters. Cerebrospinal fluid and serum samples were obtained from 54 ALS patients and 46 non-inflammatory neurological disease control (non-INDC) patients. CSF and serum FHC, FLC, and transferring levels were measured via the enzyme-linked immunosorbent method using a commercial ELISA kit, and the times from onset (durations), ALS functional rating scale-revised (ALSFRS-r) scores, and disease progression rates (DPRs) were analyzed by registered neurologists. Statistical analysis was performed via Prism software. Compared with controls, ALS patients exhibited significantly increased FHC and FLC levels in CSF, which were positively correlated with DPR and negatively correlated with duration. Serum transferrin levels were significantly increased in ALS patients but were not correlated with disease progression. FHC and FLC in CSF rapidly increased as the disease worsened. This study demonstrated that the clinical measurement of FHC and FLC in CSF may be beneficial for disease differentiation and evaluating progression in patients with ALS. Compared with levels in serum, the levels of FHC and FLC in CSF might be more reliable for diagnosing and assessing the progression of ALS. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  1. Microglial dystrophy in the aged and Alzheimer's disease brain is associated with ferritin immunoreactivity.

    Science.gov (United States)

    Lopes, Kryslaine O; Sparks, D Larry; Streit, Wolfgang J

    2008-08-01

    Degeneration of microglial cells may be important for understanding the pathogenesis of aging-related neurodegeneration and neurodegenerative diseases. In this study, we analyzed the morphological characteristics of microglial cells in the nondemented and Alzheimer's disease (AD) human brain using ferritin immunohistochemistry. The central hypothesis was that expression of the iron storage protein ferritin increases the susceptibility of microglia to degeneration, particularly in the aged brain since senescent microglia might become less efficient in maintaining iron homeostasis and free iron can promote oxidative damage. In a primary set of 24 subjects (age range 34-97 years) examined, microglial cells immunoreactive for ferritin were found to constitute a subpopulation of the larger microglial pool labeled with an antibody for HLA-DR antigens. The majority of these ferritin-positive microglia exhibited aberrant morphological (dystrophic) changes in the aged and particularly in the AD brain. No spatial correlation was found between ferritin-positive dystrophic microglia and senile plaques in AD tissues. Analysis of a secondary set of human postmortem brain tissues with a wide range of postmortem intervals (PMI, average 10.94 +/- 5.69 h) showed that the occurrence of microglial dystrophy was independent of PMI and consequently not a product of tissue autolysis. Collectively, these results suggest that microglial involvement in iron storage and metabolism contributes to their degeneration, possibly through increased exposure of the cells to oxidative stress. We conclude that ferritin immunohistochemistry may be a useful method for detecting degenerating microglia in the human brain. (c) 2008 Wiley-Liss, Inc.

  2. Abnormal brain iron metabolism in Irp2 deficient mice is associated with mild neurological and behavioral impairments.

    Directory of Open Access Journals (Sweden)

    Kimberly B Zumbrennen-Bullough

    Full Text Available Iron Regulatory Protein 2 (Irp2, Ireb2 is a central regulator of cellular iron homeostasis in vertebrates. Two global knockout mouse models have been generated to explore the role of Irp2 in regulating iron metabolism. While both mouse models show that loss of Irp2 results in microcytic anemia and altered body iron distribution, discrepant results have drawn into question the role of Irp2 in regulating brain iron metabolism. One model shows that aged Irp2 deficient mice develop adult-onset progressive neurodegeneration that is associated with axonal degeneration and loss of Purkinje cells in the central nervous system. These mice show iron deposition in white matter tracts and oligodendrocyte soma throughout the brain. A contrasting model of global Irp2 deficiency shows no overt or pathological signs of neurodegeneration or brain iron accumulation, and display only mild motor coordination and balance deficits when challenged by specific tests. Explanations for conflicting findings in the severity of the clinical phenotype, brain iron accumulation and neuronal degeneration remain unclear. Here, we describe an additional mouse model of global Irp2 deficiency. Our aged Irp2-/- mice show marked iron deposition in white matter and in oligodendrocytes while iron content is significantly reduced in neurons. Ferritin and transferrin receptor 1 (TfR1, Tfrc, expression are increased and decreased, respectively, in the brain from Irp2-/- mice. These mice show impairments in locomotion, exploration, motor coordination/balance and nociception when assessed by neurological and behavioral tests, but lack overt signs of neurodegenerative disease. Ultrastructural studies of specific brain regions show no evidence of neurodegeneration. Our data suggest that Irp2 deficiency dysregulates brain iron metabolism causing cellular dysfunction that ultimately leads to mild neurological, behavioral and nociceptive impairments.

  3. Revelation of endogenously bound Fe{sup 2+} ions in the crystal structure of ferritin from Escherichia coli

    Energy Technology Data Exchange (ETDEWEB)

    Thiruselvam, Viswanathan [Centre of Advanced Study in Crystallography and Biophysics, University of Madras, Guindy Campus, Chennai 600 025 (India); Sivaraman, Padavattan [RIKEN SPring-8 Center, Harima Institute, 1-1-1 Kouto, Sayo, Hyogo 679-5148 (Japan); Kumarevel, Thirumananseri, E-mail: kumarevel.thirumananseri@riken.jp [RIKEN SPring-8 Center, Harima Institute, 1-1-1 Kouto, Sayo, Hyogo 679-5148 (Japan); Structural Biology Laboratory, RIKEN Yokohama Institute, RIKEN, 1-7-22 Suehiro-cho, Tsurumi, Yokohama 230-0045 (Japan); Ponnuswamy, Mondikalipudur Nanjappagounder, E-mail: mnpsy2004@yahoo.com [Centre of Advanced Study in Crystallography and Biophysics, University of Madras, Guindy Campus, Chennai 600 025 (India)

    2014-10-24

    Highlights: • Crystal structure of ferritin was determined. • Endogenously expressed iron’s were identified. • Binuclear iron sites were observed at A and B active sites. - Abstract: Ferritin is an iron regulatory protein. It is responsible for storage and detoxification of excess iron thereby it regulates iron level in the body. Here we report the crystal structure of ferritin with two endogenously expressed Fe atoms binding in both the sites. The protein was purified and characterized by MALDI-TOF and N-terminal amino acid sequencing. The crystal belongs to I4 space group and it diffracted up to 2.5 Å. The structural analysis suggested that it crystallizes as hexamer and confirmed that it happened to be the first report of endogenously expressed Fe ions incorporated in both the A and B sites, situated in between the helices.

  4. Helicobacter pylori seropositivity's association with markers of iron, 1-carbon metabolism, and antioxidant status among US adults: a structural equations modeling approach.

    Directory of Open Access Journals (Sweden)

    May A Beydoun

    Full Text Available We tested a model in which Helicobacter pylori seropositivity (Hps predicted iron status, which in turn acted as a predictor for markers of 1-C metabolism that were then allowed to predict antioxidant status.National Health and Nutrition Examination Surveys (NHANES 1999-2000 cross-sectional data among adults aged 20-85 y were analyzed (n = 3,055. Markers of Hps, iron status (serum ferritin and transferrin saturation (TS; 1-C metabolism (serum folate (FOLserum, B-12, total homocysteine (tHcy, methylmalonic acid (MMA and antioxidant status (vitamins A and E were entered into a structural equations model (SEM.Predictors of Hps included older age, lower education and income, racial/ethnic groups (lowest among Non-Hispanic Whites, and lifetime cigarette smoking. SEM modeling indicated that Hps had a direct inverse relationship with iron status (combining serum ferritin and TS which in turn was positively related to 1-C metabolites (higher serum folate, B-12 or lower tHcy/MMA that were positively associated with antioxidant status (combining serum vitamins A and E. Another pathway that was found bypassed 1-C metabolites (Hps → Iron_st → Antiox. The sum of all indirect effects from Hps combining both pathways and the other indirect pathways in the model (Hps → Iron_st → OneCarbon; Hps →OneCarbon →Antiox was estimated at β = -0.006±0.003, p<0.05.In sum, of the total effect of H. pylori seropositivity on antioxidant status, two significant indirect pathways through Iron status and 1-Carbon metabolites were found. Randomized controlled trials should be conducted to uncover the concomitant causal effect of H. pylori eradication on improving iron status, folate, B-12 and antioxidant status among H. pylori seropositive individuals.

  5. Ferritin nanoparticles for improved self-renewal and differentiation of human neural stem cells.

    Science.gov (United States)

    Lee, Jung Seung; Yang, Kisuk; Cho, Ann-Na; Cho, Seung-Woo

    2018-01-01

    Biomaterials that promote the self-renewal ability and differentiation capacity of neural stem cells (NSCs) are desirable for improving stem cell therapy to treat neurodegenerative diseases. Incorporation of micro- and nanoparticles into stem cell culture has gained great attention for the control of stem cell behaviors, including proliferation and differentiation. In this study, ferritin, an iron-containing natural protein nanoparticle, was applied as a biomaterial to improve the self-renewal and differentiation of NSCs and neural progenitor cells (NPCs). Ferritin nanoparticles were added to NSC or NPC culture during cell growth, allowing for incorporation of ferritin nanoparticles during neurosphere formation. Compared to neurospheres without ferritin treatment, neurospheres with ferritin nanoparticles showed significantly promoted self-renewal and cell-cell interactions. When spontaneous differentiation of neurospheres was induced during culture without mitogenic factors, neuronal differentiation was enhanced in the ferritin-treated neurospheres. In conclusion, we found that natural nanoparticles can be used to improve the self-renewal ability and differentiation potential of NSCs and NPCs, which can be applied in neural tissue engineering and cell therapy for neurodegenerative diseases.

  6. Mechanism and developmental changes in iron transport across the blood-brain barrier.

    Science.gov (United States)

    Morgan, Evan H; Moos, Torben

    2002-01-01

    Transferrin and iron uptake by the brain were measured using [(59)Fe-(125)I]transferrin injected intravenously in rats aged from 15 days to 22 weeks. The values for both decreased with age. In rats aged 18 and 70 days the uptake was measured at short time intervals after the injection. When expressed as the volume of distribution (Vd), which represents the volume of plasma from which the transferrin and iron were derived, the results for iron were greater than those of transferrin as early as 7 min after injection and the difference increased rapidly with time, especially in the younger animals. A very similar time course was found for uptake by bone marrow (femurs) where iron uptake involves receptor-mediated endocytosis of Fe-transferrin, release of iron in the cell and recycling of apo-transferrin to the blood. It is concluded that, during transport of transferrin-bound plasma iron into the brain, a similar process occurs in brain capillary endothelial cells (BCECs) and that transcytosis of transferrin into the brain interstitium is only a minor pathway. Also, the high rate of iron transport into the brain in young animals, when iron requirements are high due to rapid growth of the brain, is a consequence of the level of expression and rate of recycling of transferrin receptors on BCECs. As the animal and brain mature both decrease. Copyright 2002 S. Karger AG, Basel

  7. Molecular cloning, expression and isolation of ferritins from two tick species - Ornithodoros moubata and Ixodes ricinus

    Czech Academy of Sciences Publication Activity Database

    Kopáček, Petr; Ždychová, J.; Yoshiga, T.; Weise, C.; Rudenko, Natalia; Law, J. H.

    2003-01-01

    Roč. 33, č. 1 (2003), s. 103-113 ISSN 0965-1748 R&D Projects: GA ČR GA206/00/0266 Institutional research plan: CEZ:AV0Z6022909; CEZ:MSM 123100003 Keywords : ferritin * iron metabolism * tick Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 2.358, year: 2003

  8. HIV and other predictors of serum folate, serum ferritin, and hemoglobin in pregnancy

    DEFF Research Database (Denmark)

    Friis, Henrik; Gomo, E; Kæstel, Pernille

    2001-01-01

    BACKGROUND: Folate and iron status and hemoglobin concentrations are important to maternal and infant health. OBJECTIVE: Our goal was to identify predictors of serum folate, serum ferritin, and hemoglobin. DESIGN: This was a cross-sectional study of 1669 pregnant women (22-35 wk of gestation) in ...

  9. Minimal impact of an iron-fortified lipid-based nutrient supplement on Hb and iron status

    DEFF Research Database (Denmark)

    James, Philip; Friis, Henrik; Woodd, Susannah

    2015-01-01

    in the intervention arm during the second stage, given from 2 to 6 weeks post-ART. Hb, serum C-reactive protein (CRP), serum ferritin and soluble transferrin receptor (sTfR) were measured at recruitment and 6 weeks post-ART. Multivariable linear regression models were used to assess the impact of the intervention...

  10. Transferrin-polycation-mediated introduction of DNA into human leukemic cells: Stimulation by agents that affect the survival of transfected DNA or modulate transferrin receptor levels

    International Nuclear Information System (INIS)

    Cotten, M.; Laengle-Rouault, F.; Kirlappos, H.; Wagner, E.; Mechtler, K.; Zenke, M.; Beug, H.; Birnstiel, M.L.

    1990-01-01

    The authors have subverted a receptor-mediated endocytosis event to transport genes into human leukemic cells. By coupling the natural iron-delivery protein transferrin to the DNA-binding polycations polylysine or protamine, they have created protein conjugates that bind nucleic acids and carry them into the cell during the normal transferrin cycle. They demonstrate here that this procedure is useful for a human leukemic cell line. They enhanced the rate of gene delivery by (i) increasing the transferrin receptor density through treatment of the cells with the cell permeable iron chelator desferrioxamine, (ii) interfering with the synthesis of heme with succinyl acetone treatment, or (iii) stimulating the degradation of heme with cobalt chloride treatment. Consistent with gene delivery as an endocytosis event, they show that the subsequent expression in K-562 cells of a gene included in the transported DNA depends upon the cellular presence of the lysosomotropic agent chloroquine. By contrast, monensin blocks transferrinfection, as does incubation of the cells at 18 degree C

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

    Science.gov (United States)

    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.

  12. Anemia of Chronic Disease and Iron Deficiency Anemia in Inflammatory Bowel Diseases: Pathophysiology, Diagnosis, and Treatment.

    Science.gov (United States)

    Murawska, Natalia; Fabisiak, Adam; Fichna, Jakub

    2016-05-01

    Anemia coexists with inflammatory bowel disease (IBD) in up to two-thirds of patients, significantly impairing quality of life. The most common types of anemia in patients with IBD are iron deficiency anemia and anemia of chronic disease, which often overlap. In most cases, available laboratory tests allow successful diagnosis of iron deficiency, where difficulties appear, recently established indices such as soluble transferrin-ferritin ratio or percentage of hypochromic red cells are used. In this review, we discuss the management of the most common types of anemia in respect of the latest available data. Thus, we provide the mechanisms underlying pathophysiology of these entities; furthermore, we discuss the role of hepcidin in developing anemia in IBD. Next, we present the treatment options for each type of anemia and highlight the importance of individual choice of action. We also focus on newly developed intravenous iron preparations and novel, promising drug candidates targeting hepcidin. Concurrently, we talk about difficulties in differentiating between the true and functional iron deficiency, and discuss tools facilitating the process. Finally, we emphasize the importance of proper diagnosis and treatment of anemia in IBD. We conclude that management of anemia in patients with IBD is tricky, and appropriate screening of patients regarding anemia is substantial.

  13. Nitric oxide induces hypoxia ischemic injury in the neonatal brain via the disruption of neuronal iron metabolism.

    Science.gov (United States)

    Lu, Qing; Harris, Valerie A; Rafikov, Ruslan; Sun, Xutong; Kumar, Sanjiv; Black, Stephen M

    2015-12-01

    We have recently shown that increased hydrogen peroxide (H2O2) generation is involved in hypoxia-ischemia (HI)-mediated neonatal brain injury. H2O2 can react with free iron to form the hydroxyl radical, through Fenton Chemistry. Thus, the objective of this study was to determine if there was a role for the hydroxyl radical in neonatal HI brain injury and to elucidate the underlying mechanisms. Our data demonstrate that HI increases the deposition of free iron and hydroxyl radical formation, in both P7 hippocampal slice cultures exposed to oxygen-glucose deprivation (OGD), and the neonatal rat exposed to HI. Both these processes were found to be nitric oxide (NO) dependent. Further analysis demonstrated that the NO-dependent increase in iron deposition was mediated through increased transferrin receptor expression and a decrease in ferritin expression. This was correlated with a reduction in aconitase activity. Both NO inhibition and iron scavenging, using deferoxamine administration, reduced hydroxyl radical levels and neuronal cell death. In conclusion, our results suggest that increased NO generation leads to neuronal cell death during neonatal HI, at least in part, by altering iron homeostasis and hydroxyl radical generation. Copyright © 2015 The Authors. Published by Elsevier B.V. All rights reserved.

  14. Serum Ferritin Is Associated with Metabolic Syndrome and Red Meat Consumption

    Directory of Open Access Journals (Sweden)

    Avila Felipe

    2015-01-01

    Full Text Available Background and Aims. Hyperferritinemia has been related with a wide spectrum of pathologies, including diabetes, cardiovascular disease, neurodegenerative disorders, and metabolic syndrome. The aim of this study was to investigate the association between hyperferritinemia and iron consumption. Methods and Results. Serum ferritin concentration was evaluated in 66 presumed healthy men, along with other clinical and biochemical markers of chronic diseases. A three-day food questionnaire was applied for nutrition information. Hyperferritinemia was a condition found in 13.4% of the volunteers analyzed. Significant correlations were found between serum ferritin concentration and metabolic syndrome parameters (HDL cholesterol, triglycerides, and fasting glucose as well as an increase of the serum ferritin mean value with the number of risk factors of metabolic syndrome. Also, oxidative stress markers (carbonyl groups, AOPP, and glycated hemoglobin, hepatic damage markers (GGT, SGOT, and parameters related to insulin resistance (HOMA, blood insulin, and blood glucose correlate significantly with serum ferritin. Volunteers had an excessive iron intake, principally by bread consumption. Analyses of food intake showed that red meat consumption correlates significantly with serum ferritin. Conclusion. Red meat consumption, metabolic syndrome, and chronic disease markers are associated with hyperferritinemia in a population of Chilean men.

  15. Association Studies of HFE C282Y and H63D Variants with Oral Cancer Risk and Iron Homeostasis Among Whites and Blacks

    Directory of Open Access Journals (Sweden)

    Nathan R. Jones

    2015-12-01

    Full Text Available Background: Polymorphisms in the hemochromatosis (HFE gene are associated with excessive iron absorption from the diet, and pro-oxidant effects of iron accumulation are thought to be a risk factor for several types of cancer. Methods: The C282Y (rs1800562 and H63D (rs1799945 polymorphisms were genotyped in 301 oral cancer cases and 437 controls and analyzed in relation to oral cancer risk, and serum iron biomarker levels from a subset of 130 subjects. Results: Individuals with the C282Y allele had lower total iron binding capacity (TIBC (321.2 ± 37.2 µg/dL vs. 397.7 ± 89.0 µg/dL, p = 0.007 and higher percent transferrin saturation (22.0 ± 8.7 vs. 35.6 ± 22.9, p = 0.023 than wild type individuals. Iron and ferritin levels approached significantly higher levels for the C282Y allele (p = 0.0632 and p = 0.0588, respectively. Conclusions: Iron biomarker levels were elevated by the C282Y allele, but neither (rs1800562 nor (rs1799945 was associated with oral cancer risk in blacks and whites.

  16. Heme-coordinated histidine residues form non-specific functional "ferritin-heme" peroxidase system: Possible and partial mechanistic relevance to oxidative stress-mediated pathology in neurodegenerative diseases.

    Science.gov (United States)

    Esmaeili, Sajjad; Kooshk, Mohammad Reza Ashrafi; Asghari, Seyyed Mohsen; Khodarahmi, Reza

    2016-10-01

    Ferritin is a giant protein composed of 24 subunits which is able to sequester up to 4500 atoms of iron. We proposed two kinds of heme binding sites in mammalian ferritins and provided direct evidence for peroxidase activity of heme-ferritin, since there is the possibility that "ferritin-heme" systems display unexpected catalytic behavior like heme-containing enzymes. In the current study, peroxidase activity of heme-bound ferritin was studied using TMB(1), l-DOPA, serotonin, and dopamine, in the presence of H2O2, as oxidant substrate. The catalytic oxidation of TMB was consistent with first-order kinetics with respect to ferritin concentration. Perturbation of the binding affinity and catalytic behavior of heme-bound His-modified ferritin were also documented. We also discuss the importance of the peroxidase-/nitrative-mediated oxidation of vital molecules as well as ferritin-induced catalase inhibition using in vitro experimental system. Uncontrollable "heme-ferritin"-based enzyme activity as well as up-regulation of heme and ferritin may inspire that some oxidative stress-mediated cytotoxic effects in AD-affected cells could be correlated to ferritin-heme interaction and/or ferritin-induced catalase inhibition and describe its contribution as an important causative pathogenesis mechanism in some neurodegenerative disorders. Copyright © 2016 Elsevier B.V. All rights reserved.

  17. Expression of Duodenal Iron Transporter Proteins in Diabetic Patients with and without Iron Deficiency Anemia

    Directory of Open Access Journals (Sweden)

    Efrat Broide

    2018-01-01

    Full Text Available The role of iron transport proteins in the pathogenesis of anemia in patients with diabetes mellitus (T2DM is still unclear. We investigated the expression of duodenal transporter proteins in diabetic patients with and without iron deficiency anemia (IDA. Methods. Overall, 39 patients were included: 16 with T2DM and IDA (group A, 11 with T2DM without IDA (group B, and 12 controls (group C. Duodenal mucosal expression of divalent metal transporter 1 (DMT1, ferroportin 1 (FPN, hephaestin (HEPH, and transferrin receptor 1 (TfR was evaluated by Western blotting. Chronic disease activity markers were measured as well. Results. FPN expression was increased in group A compared to group B and controls: 1.17 (0.72–1.46, 0.76 (0.53–1.04, and 0.71 (0.64–0.86, respectively (p=0.011. TfR levels were over expressed in groups A and B compared to controls: 0.39 (0.26–0.61, 0.36 (0.24–0.43, and 0.18 (0.16–0.24, respectively, (p=0.004. The three groups did not differ significantly with regard to cellular HEPH and DMT1 expression. The normal CRP and serum ferritin levels, accompanied with normal FPN among diabetic patients without IDA, do not support the association of IDA with chronic inflammatory state. Conclusion. In patients with T2DM and IDA, duodenal iron transport protein expression might be dependent on body iron stores rather than by chronic inflammation or diabetes per se.

  18. Why should neuroscientists worry about iron? The emerging role of ferroptosis in the pathophysiology of neuroprogressive diseases.

    Science.gov (United States)

    Morris, Gerwyn; Berk, Michael; Carvalho, André F; Maes, Michael; Walker, Adam J; Puri, Basant K

    2018-04-02

    Ferroptosis is a unique form of programmed death, characterised by cytosolic accumulation of iron, lipid hydroperoxides and their metabolites, and effected by the fatal peroxidation of polyunsaturated fatty acids in the plasma membrane. It is a major driver of cell death in neurodegenerative neurological diseases. Moreover, cascades underpinning ferroptosis could be active drivers of neuropathology in major psychiatric disorders. Oxidative and nitrosative stress can adversely affect mechanisms and proteins governing cellular iron homeostasis, such as the iron regulatory protein/iron response element system, and can ultimately be a source of abnormally high levels of iron and a source of lethal levels of lipid membrane peroxidation. Furthermore, neuroinflammation leads to the upregulation of divalent metal transporter1 on the surface of astrocytes, microglia and neurones, making them highly sensitive to iron overload in the presence of high levels of non-transferrin-bound iron, thereby affording such levels a dominant role in respect of the induction of iron-mediated neuropathology. Mechanisms governing systemic and cellular iron homeostasis, and the related roles of ferritin and mitochondria are detailed, as are mechanisms explaining the negative regulation of ferroptosis by glutathione, glutathione peroxidase 4, the cysteine/glutamate antiporter system, heat shock protein 27 and nuclear factor erythroid 2-related factor 2. The potential role of DJ-1 inactivation in the precipitation of ferroptosis and the assessment of lipid peroxidation are described. Finally, a rational approach to therapy is considered, with a discussion on the roles of coenzyme Q 10 , iron chelation therapy, in the form of deferiprone, deferoxamine (desferrioxamine) and deferasirox, and N-acetylcysteine. Copyright © 2017 Elsevier B.V. All rights reserved.

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

    Science.gov (United States)

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

    2017-12-01

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

  20. Purification and characterisation of ferritin from the Baltic blue mussel Mytilus trossulus

    Directory of Open Access Journals (Sweden)

    Potrykus Joanna

    2009-12-01

    Full Text Available Baltic blue mussels Mytilus trossulus were collected from the Gulf of Gdańsk (southern Baltic Sea in order to isolate ferritin from its soft tissues, as well as to purify and characterise this protein.     Proteins were isolated from the inner organs of M. trossulus (hepatopancreas, gills and soft tissue residue by thermal denaturation(70°C and acidification (pH 4.5 of the homogenates, followed by ammonium sulphate ((NH42SO4 fractionation.The ferritin was then separated by ultracentrifugation (100 000 × g, 120 min.. The protein content in thepurified homogenates was determined by the Lowry method using bovine serum albumin(BSA and horse spleen ferritin (HSF as standards. PAGE-SDS and Western blotting analysis permitted identification of ferritinin the purified preparations. Additionally, the purified homogenates and mussel soft tissue were analysed for their heavy metal contents(especially cadmium and iron in a Video 11 E atomic absorption spectrophotometer, following wet digestion of the samples (HNO3/HClO4.     The electrophoregrams showed that the inner organs of M. trossulus contained ferritin, which, like plant ferritin, is characterised by thepresence of subunits in the electrophoregram in the 26.6-28.0 kDa range. The highest ferritin content was recorded in the hepatopancreas,followed by the gills and the soft tissue residue. With regard to the sampling stations, the highest content of ferritin wasnoted in the animals sampled off Sopot (station D3, and in those collected by a diver off Jastarnia (W1 and Gdynia (W4. Ferritinisolated from the inner organs of mussels collected from these stations also contained the largest quantities of heavy metals(Cd and Fe. Ferritin isolated from the inner organs of mussels collected by a diver from wrecks - sites where the concentrationsof iron and other trace metals in the sea water are high - contained higher quantities of heavy metals (Cd and Fe than the ferritinisolated from the inner organs

  1. Iron

    DEFF Research Database (Denmark)

    Hansen, Jakob Bondo; Moen, I W; Mandrup-Poulsen, T

    2014-01-01

    and discuss recent evidence, suggesting that iron is a key pathogenic factor in both type 1 and type 2 diabetes with a focus on inflammatory pathways. Pro-inflammatory cytokine-induced β-cell death is not fully understood, but may include iron-induced ROS formation resulting in dedifferentiation by activation...... of transcription factors, activation of the mitochondrial apoptotic machinery or of other cell death mechanisms. The pro-inflammatory cytokine IL-1β facilitates divalent metal transporter 1 (DMT1)-induced β-cell iron uptake and consequently ROS formation and apoptosis, and we propose that this mechanism provides...

  2. H ferritin silencing induces protein misfolding in K562 cells: A Raman analysis

    KAUST Repository

    Zolea, Fabiana

    2015-10-09

    The redox state of the cell is involved in the regulation of many physiological functions as well as in the pathogenesis of several diseases, and is strictly dependent on the amount of iron in its catalytically active state. Alterations of iron homeostasis determine increased steady-state concentrations of Reactive Oxygen Species (ROS) that cause lipid peroxidation, DNA damage and altered protein folding. Ferritin keeps the intracellular iron in a non-toxic and readily available form and consequently plays a central role in iron and redox homeostasis. The protein is composed by 24 subunits of the H- and L-type, coded by two different genes, with structural and functional differences. The aim of this study was to shed light on the role of the single H ferritin subunit (FHC) in keeping the native correct protein three-dimensional structure. To this, we performed Raman spectroscopy on protein extracts from K562 cells subjected to FHC silencing. The results show a significant increase in the percentage of disordered structures content at a level comparable to that induced by H2O2 treatment in control cells. ROS inhibitor and iron chelator were able to revert protein misfolding. This integrated approach, involving Raman spectroscopy and targeted-gene silencing, indicates that an imbalance of the heavy-to-light chain ratio in the ferritin composition is able to induce severe but still reversible modifications in protein folding and uncovers new potential pathogenetic mechanisms associated to intracellular iron perturbation.

  3. H ferritin silencing induces protein misfolding in K562 cells: A Raman analysis

    KAUST Repository

    Zolea, Fabiana; Biamonte, Flavia; Candeloro, Patrizio; Di Sanzo, Maddalena; Cozzi, Anna; Di Vito, Anna; Quaresima, Barbara; Lobello, Nadia; Trecroci, Francesca; Di Fabrizio, Enzo M.; Levi, Sonia; Cuda, Giovanni; Costanzo, Francesco

    2015-01-01

    The redox state of the cell is involved in the regulation of many physiological functions as well as in the pathogenesis of several diseases, and is strictly dependent on the amount of iron in its catalytically active state. Alterations of iron homeostasis determine increased steady-state concentrations of Reactive Oxygen Species (ROS) that cause lipid peroxidation, DNA damage and altered protein folding. Ferritin keeps the intracellular iron in a non-toxic and readily available form and consequently plays a central role in iron and redox homeostasis. The protein is composed by 24 subunits of the H- and L-type, coded by two different genes, with structural and functional differences. The aim of this study was to shed light on the role of the single H ferritin subunit (FHC) in keeping the native correct protein three-dimensional structure. To this, we performed Raman spectroscopy on protein extracts from K562 cells subjected to FHC silencing. The results show a significant increase in the percentage of disordered structures content at a level comparable to that induced by H2O2 treatment in control cells. ROS inhibitor and iron chelator were able to revert protein misfolding. This integrated approach, involving Raman spectroscopy and targeted-gene silencing, indicates that an imbalance of the heavy-to-light chain ratio in the ferritin composition is able to induce severe but still reversible modifications in protein folding and uncovers new potential pathogenetic mechanisms associated to intracellular iron perturbation.

  4. Iron

    Science.gov (United States)

    ... Share: Search the ODS website Submit Search NIH Office of Dietary Supplements Consumer Datos en español Health ... eating a variety of foods, including the following: Lean meat, seafood, and poultry. Iron-fortified breakfast cereals ...

  5. Transferrin Family Genes in the Brown Planthopper, Nilaparvata lugens (Hemiptera: Delphacidae) in Response to Three Insecticides.

    Science.gov (United States)

    Wu, Shun-Fan; Li, Jian; Zhang, Yong; Gao, Cong-Fen

    2018-02-09

    Transferrins are involved in iron metabolism, immunity, xenobiotics tolerance, and development in eukaryotic organisms including insects. However, little is known about the relationship between transferrins and insecticide toxicology and resistance. Three transferrin family genes, NlTsf1, NlTsf2, and NlTsf3, of the brown planthopper, Nilaparvata lugens (Stål) (Hemiptera: Delphacidae)a major insect pest of rice field in Asia, had been identified and characterized in this study. Quantitative polymerase chain reaction results demonstrated that NlTsf1 was significantly higher than the other two genes in different tissues. All of them were expressed at higher levels in abdomen and head than in antenna, leg, stylet, and thorax. Compared with the control, the expression of three N. lugens transferrin family genes decreased dramatically 24 h after treatment with buprofezin, pymetrozine and imidacloprid. Published by Oxford University Press on behalf of Entomological Society of America 2017. This work is written by (a) US Government employee(s) and is in the public domain in the US.

  6. Iron status and its determinants in a nationally representative sample of pregnant women.

    Science.gov (United States)

    Vandevijvere, Stefanie; Amsalkhir, Sihame; Van Oyen, Herman; Egli, Ines; Ines, Egli; Moreno-Reyes, Rodrigo

    2013-05-01

    Iron-deficiency anemia is associated with adverse neonatal health outcomes. Iron status and its determinants were assessed in a representative sample of Belgian pregnant women. Blood samples were collected and a questionnaire was completed face-to-face. Hemoglobin (Hb) and mean cell volume were measured using a Beckman Coulter Hematology Analyzer and serum ferritin (SF) and transferrin receptor (sTfr) concentrations by immunoassay. In total, 55 obstetric clinics and 1,311 pregnant women were included. Approximately 40% of third-trimester and 6% of first-trimester women had SF levels less than 15 μg/L. Approximately 21% of third-trimester and 4% of first-trimester women had anemia (Hb 8.5 mg/L). The median body iron stores were 8.1 mg/kg among first-trimester women, but only 3.6 mg/kg among third-trimester women. SF levels were significantly positively associated with age and education level, and were higher among nulliparous women and lower among North-African women. sTfr concentrations were significantly negatively associated with age and were lower among smokers, nulliparous women, and women who planned their pregnancy. Despite the fact that two thirds of Belgian pregnant women took iron-containing supplements, iron deficiency and iron-deficiency anemia were frequent in third-trimester women. The World Health Organization regards this as a moderate public health problem. National iron supplementation guidelines are needed in Belgium to optimize iron status during pregnancy. Copyright © 2013 Academy of Nutrition and Dietetics. Published by Elsevier Inc. All rights reserved.

  7. Iron-induced neuronal damage in a rat model of post-traumatic stress disorder.

    Science.gov (United States)

    Zhao, Ming; Yu, Zhibo; Zhang, Yang; Huang, Xueling; Hou, Jingming; Zhao, YanGang; Luo, Wei; Chen, Lin; Ou, Lan; Li, Haitao; Zhang, Jiqiang

    2016-08-25

    Previous studies have shown that iron redistribution and deposition in the brain occurs in some neurodegenerative diseases, and oxidative damage due to abnormal iron level is a primary cause of neuronal death. In the present study, we used the single prolonged stress (SPS) model to mimic post-traumatic stress disorder (PTSD), and examined whether iron was involved in the progression of PTSD. The anxiety-like behaviors of the SPS group were assessed by the elevated plus maze (EPM) and open field tests, and iron levels were measured by inductively coupled plasma optical emission spectrometer (ICP-OES). Expression of glucocorticoid receptors and transferrin receptor 1 (TfR1) and ferritin (Fn) was detected by Western blot and immunohistochemistry in selected brain areas; TfR1 and Fn mRNA expression were detected by quantitative-polymerase chain reaction (Q-PCR). Ultrastructures of the hippocampus were observed under a transmission electron microscope. Our results showed that SPS exposure induced anxiety-like symptoms and increased the level of serum cortisol and the concentration of iron in key brain areas such as the hippocampus, prefrontal cortex, and striatum. The stress induced region-specific changes in both protein and mRNA levels of TfR1 and Fn. Moreover, swelling mitochondria and cell apoptosis were observed in neurons in brain regions with iron accumulation. We concluded that SPS stress increased iron in some cognition-related brain regions and subsequently cause neuronal injury, indicating that the iron may function in the pathology of PTSD. Copyright © 2016 IBRO. Published by Elsevier Ltd. All rights reserved.

  8. Ferritin cage for encapsulation and delivery of bioactive nutrients: From structure, property to applications.

    Science.gov (United States)

    Zang, Jiachen; Chen, Hai; Zhao, Guanghua; Wang, Fudi; Ren, Fazheng

    2017-11-22

    Ferritin is a class of naturally occurring iron storage proteins, which is distributed widely in animal, plant, and bacteria. It usually consists of 24 subunits that form a hollow protein shell with high symmetry. One holoferritin molecule can store up to 4500 iron atom within its inner cavity, and it becomes apoferritin upon removal of iron from the cavity. Recently, scientists have subverted these nature functions and used reversibly self-assembled property of apoferritin cage controlled by pH for the encapsulation and delivery of bioactive nutrients or anticancer drug. In all these cases, the ferritin cages shield their cargo from the influence of external conditions and provide a controlled microenvironment. More importantly, upon encapsulation, ferritin shell greatly improved the water solubility, thermal stability, photostability, and cellular uptake activity of these small bioactive compounds. This review aims to highlight recent advances in applications of ferritin cage as a novel vehicle in the field of food science and nutrition. Future outlooks are highlighted with the aim to suggest a research line to follow for further studies.

  9. Coating Nanoparticles with Plant-Produced Transferrin-Hydrophobin Fusion Protein Enhances Their Uptake in Cancer Cells

    DEFF Research Database (Denmark)

    Reuter, Lauri J.; Shahbazi, Mohammad-Ali; Makila, Ermei M.

    2017-01-01

    can be expressed in Nicotiana benthamiana plants as a fusion with Trichoderma reesei hydrophobins HFBI, HFBII, or HFBIV. Transferrin-HFBIV was further expressed in tobacco BY-2 suspension cells. Both partners of the fusion protein retained their functionality; the hydrophobin moiety enabled migration...... to a surfactant phase in an aqueous two-phase system, and the transferrin moiety was able to reversibly bind iron. Coating porous silicon nanoparticles with the fusion protein resulted in uptake of the nanoparticles in human cancer cells. This study provides a proof-of concept for the functionalization...

  10. Lactoferrin Efficiently Counteracts the Inflammation-Induced Changes of the Iron Homeostasis System in Macrophages.

    Science.gov (United States)

    Cutone, Antimo; Rosa, Luigi; Lepanto, Maria Stefania; Scotti, Mellani Jinnett; Berlutti, Francesca; Bonaccorsi di Patti, Maria Carmela; Musci, Giovanni; Valenti, Piera

    2017-01-01

    Human lactoferrin (hLf), an 80-kDa multifunctional iron-binding cationic glycoprotein, is constitutively secreted by exocrine glands and by neutrophils during inflammation. hLf is recognized as a key element in the host immune defense system. The in vitro and in vivo experiments are carried out with bovine Lf (bLf), which shares high sequence homology and identical functions with hLf, including anti-inflammatory activity. Here, in "pure" M1 human macrophages, obtained by stimulation with a mixture of 10 pg/ml LPS and 20 ng/ml IFN-γ, as well as in a more heterogeneous macrophage population, challenged with high-dose of LPS (1 µg/ml), the effect of bLf on the expression of the main proteins involved in iron and inflammatory homeostasis, namely ferroportin (Fpn), membrane-bound ceruloplasmin (Cp), cytosolic ferritin (Ftn), transferrin receptor 1, and cytokines has been investigated. The increase of IL-6 and IL-1β cytokines, following the inflammatory treatments, is associated with both upregulation of cytosolic Ftn and downregulation of Fpn, membrane-bound Cp, and transferrin receptor 1. All these changes take part into intracellular iron overload, a very unsafe condition leading in vivo to higher host susceptibility to infections as well as iron deficiency in the blood and anemia of inflammation. It is, therefore, of utmost importance to counteract the persistence of the inflammatory status to rebalance iron levels between tissues/secretions and blood. Moreover, levels of the antiinflammatory cytokine IL-10 were increased in cells treated with high doses of LPS. Conversely, IL-10 decreased when the LPS/IFN-γ mix was used, suggesting that only the inflammation triggered by LPS high doses can switch on an anti-inflammatory response in our macrophagic model. Here, we demonstrate that bLf, when included in the culture medium, significantly reduced IL-6 and IL-1β production and efficiently prevented the changes of Fpn, membrane-bound Cp, cytosolic Ftn, and

  11. Lactoferrin Efficiently Counteracts the Inflammation-Induced Changes of the Iron Homeostasis System in Macrophages

    Directory of Open Access Journals (Sweden)

    Antimo Cutone

    2017-06-01

    Full Text Available Human lactoferrin (hLf, an 80-kDa multifunctional iron-binding cationic glycoprotein, is constitutively secreted by exocrine glands and by neutrophils during inflammation. hLf is recognized as a key element in the host immune defense system. The in vitro and in vivo experiments are carried out with bovine Lf (bLf, which shares high sequence homology and identical functions with hLf, including anti-inflammatory activity. Here, in “pure” M1 human macrophages, obtained by stimulation with a mixture of 10 pg/ml LPS and 20 ng/ml IFN-γ, as well as in a more heterogeneous macrophage population, challenged with high-dose of LPS (1 µg/ml, the effect of bLf on the expression of the main proteins involved in iron and inflammatory homeostasis, namely ferroportin (Fpn, membrane-bound ceruloplasmin (Cp, cytosolic ferritin (Ftn, transferrin receptor 1, and cytokines has been investigated. The increase of IL-6 and IL-1β cytokines, following the inflammatory treatments, is associated with both upregulation of cytosolic Ftn and downregulation of Fpn, membrane-bound Cp, and transferrin receptor 1. All these changes take part into intracellular iron overload, a very unsafe condition leading in vivo to higher host susceptibility to infections as well as iron deficiency in the blood and anemia of inflammation. It is, therefore, of utmost importance to counteract the persistence of the inflammatory status to rebalance iron levels between tissues/secretions and blood. Moreover, levels of the antiinflammatory cytokine IL-10 were increased in cells treated with high doses of LPS. Conversely, IL-10 decreased when the LPS/IFN-γ mix was used, suggesting that only the inflammation triggered by LPS high doses can switch on an anti-inflammatory response in our macrophagic model. Here, we demonstrate that bLf, when included in the culture medium, significantly reduced IL-6 and IL-1β production and efficiently prevented the changes of Fpn, membrane-bound Cp

  12. Using iron studies to predict HFE mutations in New Zealand: implications for laboratory testing.

    Science.gov (United States)

    O'Toole, Rebecca; Romeril, Kenneth; Bromhead, Collette

    2017-04-01

    The diagnosis of hereditary haemochromatosis (HH) is not straightforward because symptoms are often absent or non-specific. Biochemical markers of iron-overloading may be affected by other conditions. To measure the correlation between iron studies and HFE genotype to inform evidence-based recommendations for laboratory testing in New Zealand. Results from 2388 patients genotyped for C282Y, H63D and S65C in Wellington, New Zealand from 2007 to 2013 were compared with their biochemical phenotype as quantified by serum ferritin (SF), transferrin saturation (TS), serum iron (SI) and serum transferrin (ST). The predictive power of these markers was evaluated by receiver operator characteristic (ROC) curve analysis, and if a statistically significant association for a variable was seen, sensitivity, specificity and predictive values were calculated. Test ordering patterns showed that 62% of HFE genotyping tests were ordered because of an elevated SF alone and only 11% of these had a C-reactive protein test to rule out an acute phase reaction. The association between SF and significant HFE genotypes SF was low. However, TS values ≥45% predicted HH mutations with the highest sensitivity and specificity. A SF of >1000 µg/L was found in one at-risk patient (C282Y homozygote) who had a TS <45%. Our analysis highlights the need for clear guidelines for investigation of hyperferritinaemia and HH in New Zealand. Using our findings, we developed an evidence-based laboratory testing algorithm based on a TS ≥45%, a SF ≥1000 µg/L and/or a family history of HH which identified all C282Y homozygotes in this study. © 2016 Royal Australasian College of Physicians.

  13. Accuracy of various iron parameters in the prediction of iron deficiency in an acute care hospital

    NARCIS (Netherlands)

    Ong, K. H.; Tan, H. L.; Lai, H. C.; Kuperan, P.

    2005-01-01

    INTRODUCTION: Iron parameters like serum ferritin and iron saturation are routinely used in diagnosing iron deficiency. However, these tests are influenced by many factors. We aimed to review the accuracy of iron parameters among inpatients in an acute care hospital. MATERIALS AND METHODS: From

  14. Genetic factors influencing ferritin levels in 14,126 blood donors

    DEFF Research Database (Denmark)

    Sørensen, Erik; Rigas, Andreas S; Thørner, Lise W

    2015-01-01

    BACKGROUND: Many biologic functions depend on sufficient iron levels, and iron deficiency is especially common among blood donors. Genetic variants associated with iron levels have been identified, but the impact of genetic variation on iron levels among blood donors remains unclear. STUDY DESIGN...... AND METHODS: The effect of six single-nucleotide polymorphisms (SNPs) on ferritin levels in 14,126 blood donors were investigated in four genes: in Human Hemochromatosis Protein gene (HFE; rs1800562 and rs179945); in Transmembrane Protease gene, Serine 6 (TMPRSS6-regulating hepcidin; rs855791); in BTB domain...... with iron deficiency in women. Results for all other genetic variants were insignificant. CONCLUSION: Genetic variants associated with hemochromatosis may protect donors against depleted iron stores. In addition, we showed that presence of the T-allele at rs855791 in TMPRSS6 was associated with lower iron...

  15. Rice and Bean Targets for Biofortification Combined with High Carotenoid Content Crops Regulate Transcriptional Mechanisms Increasing Iron Bioavailability

    Directory of Open Access Journals (Sweden)

    Desirrê Morais Dias

    2015-11-01

    Full Text Available Iron deficiency affects thousands of people worldwide. Biofortification of staple food crops aims to support the reduction of this deficiency. This study evaluates the effect of combinations of common beans and rice, targets for biofortification, with high carotenoid content crops on the iron bioavailability, protein gene expression, and antioxidant effect. Iron bioavailability was measured by the depletion/repletion method. Seven groups were tested (n = 7: Pontal bean (PB; rice + Pontal bean (R + BP; Pontal bean + sweet potato (PB + SP; Pontal bean + pumpkin (PB + P; Pontal bean + rice + sweet potato (PB + R + P; Pontal bean + rice + sweet potato (PB + R + SP; positive control (Ferrous Sulfate. The evaluations included: hemoglobin gain, hemoglobin regeneration efficiency (HRE, gene expression of divalente metal transporter 1 (DMT-1, duodenal citocromo B (DcytB, ferroportin, hephaestin, transferrin and ferritin and total plasma antioxidant capacity (TAC. The test groups, except the PB, showed higher HRE (p < 0.05 than the control. Gene expression of DMT-1, DcytB and ferroportin increased (p < 0.05 in the groups fed with high content carotenoid crops (sweet potato or pumpkin. The PB group presented lower (p < 0.05 TAC than the other groups. The combination of rice and common beans, and those with high carotenoid content crops increased protein gene expression, increasing the iron bioavailability and antioxidant capacity.

  16. ESR spectroscopy of blood serum in thalassemia: discrimination of iron overload severity in deferoxamine-cured patients

    International Nuclear Information System (INIS)

    Preoteasa, E.A.; Schianchi, G.; Giori, D.C.; Pedrazzi, G.

    1997-01-01

    Iron impairments in homozygous β-thalassemia include iron overload syndrome, partially prevented by deferoxamine (DF) and methemalbumin (MHA) in serum. The latter has been studied by electron spin resonance ESR before the clinical use of DF and recently in DF cured subjects. We monitored by X-band ESR at 163 K, the Fe (III) bound in MHA and transferrin (Tf) in serum from transfused, DF-cured patients. Plotting MHA/Tf versus individual DF dose divided the patients into two subgroups, A and B; A with the two variables correlated linearly and B presenting no correlation. The patients in B presented a higher incidence and severity of clinical complications and lower therapy responsiveness as compared to subjects in A. The ratio MHA/Tf evidenced a quadratic dependence on the mass of transfused erythrocytes (TE) in A, and no regularity in B. Similar patterns appeared in plots of ferritin (FT) and hemoglobin (Hb) vs. DF and TE, but all correlation become visible only after A vs. B discrimination by ESR. The results point to a heavier iron overload in B than in A patients, suggesting different Hb degradation pathways in the two subgroups with more toxic 'free' iron produced in B than in A. Therefore, ESR of serum might serve for improving the precision of diagnosis, for prognosis of dissimilar therapeutic efficiency of DF in patients and for monitoring the long-term efficiency of therapy in homozygous β-thalassemia. (authors)

  17. Relative iron "overload" in offspring of patients with type 2 diabetes mellitus: a new component in the conundrum of insulin resistance syndrome?

    Science.gov (United States)

    Psyrogiannis, Agathoklis; Kyriazopoulou, Venetsana; Symeonidis, Argiris; Leotsinidis, Michalis; Vagenakis, Apostolos G

    2003-01-01

    There are a few reports suggesting that subtle disturbances of iron metabolism are frequently found in patients with type 2 diabetes (DM2), but it is not known if these disturbances precede or accompany the diabetic state. We investigated the serum iron indices in 41 offspring of DM2 parents (group I) with normal glucose tolerance, and in 49 offspring whose parents had no history of DM2 and were matched for sex, age, body mass index (BMI), waist to hip ratio (WHR) and blood pressure (group II). Serum iron, ferritin, total iron binding capacity (TIBC), transferrin saturation, serum triglycerides, cholesterol, Apo-B, high density lipoprotein (HDL) and glucose and insulin values during an oral glucose tolerance test were measured. Insulin resistance was assessed using the homeostasis model assessment (HOMA - Insuline resistence index-IRI). In comparison to controls (group II), the offspring of DM2 subjects (group I) had higher fasting serum triglycerides (mean +/- SD 2.25+/-2.08 vs. 1.6+/-0.8 mmol/L, pinsulin in the Area Under the Curve (204.7+/-140.8 v. 153.1 +/- 63.0 microU/ml, pinsulin resistance. Hence, the relative iron "overload" in offspring of type 2 diabetics is present along with insulin resistance and might worsen the hepatic insulin insensitivity already present in these patients.

  18. HFE MUTATIONS AND IRON OVERLOAD IN PATIENTS WITH ALCOHOLIC LIVER DISEASE

    Directory of Open Access Journals (Sweden)

    Luis COSTA-MATOS

    2013-03-01

    Full Text Available Context Alcoholic liver disease (ALD is generally associated with iron overload, which may contribute to its pathogenesis, through increased oxidative stress and cellular damage. There are conflicting reports in literature about hemochromatosis (HFE gene mutations and the severity of liver disease in alcoholic patients. Objectives To compare the prevalence of mutations in the hemochromatosis (HFE gene between patients with ALD and healthy controls; to assess the relation of HFE mutations with liver iron stores and liver disease severity. Methods Liver biopsy specimens were obtained from 63 ALD patients (during routine treatment and 52 healthy controls (during elective cholecystectomy. All individuals underwent routine liver function tests and HFE genotyping (to detect wild-type sequences and C282Y, H63D, S65C, E168Q, E168X, V59M, H63H, P160delC, Q127H, Q283P, V53M and W164X mutations. Associations between HFE mutations and risk of excessive liver iron stores, abnormal serum ferritin, liver fibrosis, or necroinflammatory activity were assessed by multivariate logistic regression analysis. Results ALD patients had significantly higher serum ferritin and transferrin saturation than controls (both P<0.05, but the distribution of HFE mutations was similar between the two groups. For ALD patients, the odds ratio for having at least one HFE mutation and excessive liver iron stores was 17.23 (95% confidence interval (CI: 2.09-142.34, P = 0.008. However, the presence of at least one HFE mutation was not associated with an increased risk of liver fibrosis or necroinflammatory activity. Active alcohol ingestion showed the strongest association to increased serum ferritin (OR = 8.87, 95% CI: 2.11-34.78, P = 0.003. Conclusions ALD patients do not present with a differential profile of HFE mutations from healthy controls. In ALD patients, however, the presence of at least one HFE mutation increases the risk of having excessive liver iron stores but has no

  19. New parameters and reference values for monitoring iron status in Middle Eastern adolescent male athletes.

    Science.gov (United States)

    Voss, S C; Varamenti, E; Elzain Elgingo, M; Bourdon, P C

    2014-04-01

    Hematological and biochemical parameters of 160 Middle Eastern adolescent male athletes (aged from 12-18 years) were tested in order to investigate their iron status and to establish reference values for this population. A focus of this study was also the investigation of Reticulocyte hemoglobin (RetHe) and soluble transferrin receptor (sTfR). Complete blood count, reticulocyte and sera parameters were analyzed at the beginning of the training season for these adolescent athletes. As the diagnosis of iron deficiency in adolescents is extremely difficult subjects were subdivided in three age groups (12-13, 14-15, 16-18). For most of the parameters our results confirmed the existing reference values reported in young athletes. Exceptions were however found with lower Mean Cell Volumes (79.9±4.3 fl) in this group when compared to other age matched data. RetHe, ferritin and sTfR levels were monitored for the interpretation of the iron status in this population and reference values for these parameters were also established. Information to help evidence based decision making about the need for supplementation or further investigations is provided to physicians and nutritionists. RetHe with a proposed threshold value of 25 pg expands the list of parameters which can be used to monitor athletes.

  20. Zonulin, inflammation and iron status in patients with early stages of chronic kidney disease.

    Science.gov (United States)

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

    2018-01-01

    Zonulin is the only known regulator of intestinal permeability. It is also considered as a potential inflammatory marker in several conditions such as diabetes and inflammatory bowel syndrome. The aim of the study was to investigate zonulin levels in patients with early stages of CKD and its possible correlation with inflammation, anemia and iron status parameters. Eighty-eight patients with early stages of CKD and 23 healthy volunteers were enrolled in the study. Zonulin, hepcidin-25, soluble transferrin receptor, interleukin-6 and high-sensitivity C-reactive protein were measured using commercially available assays. Zonulin was significantly lower among patients with CKD in comparison with healthy volunteers. There were no statistically significant differences in zonulin concentration between patients with and without inflammation. Zonulin was significantly correlated with hepcidin only in patients with inflammation. Zonulin was neither related to iron nor related to ferritin. Zonulin cannot be considered as an inflammatory marker in CKD. It does not play a role in the disturbances of iron metabolism in CKD. Its physiological role remains to be elucidated.

  1. Ferritin associates with marginal band microtubules

    Czech Academy of Sciences Publication Activity Database

    Infante, A. A.; Infante, D.; Chan, M. C.; How, P.-Ch.; Kutschera, W.; Linhartová, Irena; Müllner, E. V.; Wiche, G.; Propst, F.

    2007-01-01

    Roč. 313, č. 8 (2007), s. 1602-1614 ISSN 0014-4827 Institutional research plan: CEZ:AV0Z50200510 Keywords : erythrocyte * platelet * ferritin Subject RIV: EE - Microbiology, Virology Impact factor: 3.695, year: 2007

  2. Octopus microvasculature: permeability to ferritin and carbon.

    Science.gov (United States)

    Browning, J

    1979-01-01

    The permeability of Octopus microvasculature was investigated by intravascular injection of carbon and ferritin. Vessels were tight to carbon while ferritin penetrated the pericyte junction, and was found extravascularly 1-2 min after its introduction. Vesicles occurred rarely in pericytes; fenestrae were absent. The discontinuous endothelial layer did not consitute a permeability barrier. The basement membrane, although retarding the movement of ferritin, was permeable to it; carbon did not penetrate the basement membrane. Evidence indicated that ferritin, and thus similarly sized and smaller water soluble materials, traverse the pericyte junction as a result of bulk fluid flow. Comparisons are made with the convective (or junctional) and slower, diffusive (or vesicular) passage of materials known to occur across the endothelium of continuous capillaries in mammals. Previous macrophysiological determinations concerning the permeability of Octopus vessels are questioned in view of these findings. Possible reasons for some major structural differences in the microcirculatory systems of cephalopods and vertebrates are briefly discussed.

  3. PCBP1 and NCOA4 regulate erythroid iron storage and heme biosynthesis.

    Science.gov (United States)

    Ryu, Moon-Suhn; Zhang, Deliang; Protchenko, Olga; Shakoury-Elizeh, Minoo; Philpott, Caroline C

    2017-05-01

    Developing erythrocytes take up exceptionally large amounts of iron, which must be transferred to mitochondria for incorporation into heme. This massive iron flux must be precisely controlled to permit the coordinated synthesis of heme and hemoglobin while avoiding the toxic effects of chemically reactive iron. In cultured animal cells, iron chaperones poly rC-binding protein 1 (PCBP1) and PCBP2 deliver iron to ferritin, the sole cytosolic iron storage protein, and nuclear receptor coactivator 4 (NCOA4) mediates the autophagic turnover of ferritin. The roles of PCBP, ferritin, and NCOA4 in erythroid development remain unclear. Here, we show that PCBP1, NCOA4, and ferritin are critical for murine red cell development. Using a cultured cell model of erythroid differentiation, depletion of PCBP1 or NCOA4 impaired iron trafficking through ferritin, which resulted in reduced heme synthesis, reduced hemoglobin formation, and perturbation of erythroid regulatory systems. Mice lacking Pcbp1 exhibited microcytic anemia and activation of compensatory erythropoiesis via the regulators erythropoietin and erythroferrone. Ex vivo differentiation of erythroid precursors from Pcbp1-deficient mice confirmed defects in ferritin iron flux and heme synthesis. These studies demonstrate the importance of ferritin for the vectorial transfer of imported iron to mitochondria in developing red cells and of PCBP1 and NCOA4 in mediating iron flux through ferritin.

  4. Iron and iron-related proteins in asbestosis.

    Science.gov (United States)

    ABSTRACT: We tested the postulate that iron homeostasis is altered among patients diagnosed to have asbestosis. Lung tissue from six individuals diagnosed to have had asbestosis at autopsy was stained for iron, ferritin, divalent metal transporter 1 (DMT1), and ferroportin 1 (FP...

  5. Binding of tryptophan and iron by reptilion plasnna proteins

    African Journals Online (AJOL)

    transport functions. Albumin of the alligator (Alligator mississippiensis) and other reptiles binds, amongst other ions, tryptophan (McMenamy & Watson 1968) and transferrin binds iron (Barber & Sheeler 1963). Multiple transferrins are present in the plasma of many reptiles. (Dessauer et af 1962) and the albumin region of the.

  6. Intracellular Delivery of a Planar DNA Origami Structure by the Transferrin-Receptor Internalization Pathway.

    Science.gov (United States)

    Schaffert, David H; Okholm, Anders H; Sørensen, Rasmus S; Nielsen, Jesper S; Tørring, Thomas; Rosen, Christian B; Kodal, Anne Louise B; Mortensen, Michael R; Gothelf, Kurt V; Kjems, Jørgen

    2016-05-01

    DNA origami provides rapid access to easily functionalized, nanometer-sized structures making it an intriguing platform for the development of defined drug delivery and sensor systems. Low cellular uptake of DNA nanostructures is a major obstacle in the development of DNA-based delivery platforms. Herein, significant strong increase in cellular uptake in an established cancer cell line by modifying a planar DNA origami structure with the iron transport protein transferrin (Tf) is demonstrated. A variable number of Tf molecules are coupled to the origami structure using a DNA-directed, site-selective labeling technique to retain ligand functionality. A combination of confocal fluorescence microscopy and quantitative (qPCR) techniques shows up to 22-fold increased cytoplasmic uptake compared to unmodified structures and with an efficiency that correlates to the number of transferrin molecules on the origami surface. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  7. Transferrin Sialylation in Smoking and Non-Smoking Pregnant Women with Intrauterine Growth Restriction.

    Science.gov (United States)

    Wrześniak, Marta; Kepinska, Marta; Bizoń, Anna; Milnerowicz-Nabzdyk, Ewa; Milnerowicz, Halina

    2015-01-01

    Transferrin (Tf) is a glycosylated protein responsible for transporting iron. Various sialylation levels of Tf are observed during physiological and pathological processes. We studied if the changes in iron stores as well as tobacco smoke may have an impact on foetal development and in consequence lead to intrauterine growth restriction (IUGR). In the third trimester of pregnancy, lower levels of 4-sialoTf isoform and higher levels of 5-sialoTf were observed in the serum of non-smoking women with IUGR in comparison to the control group. On the day of labour, level of 2-sialoTf was significantly lower and level of 3-sialo was Tf higher in the serum of non-smoking women. Level of 4-sialo was found lower in the serum of smoking women with IUGR than in the control group. The observed changes may suggest a connection between iron stores, transport of iron to the foetus and foetal development.

  8. Magnetic and quadrupolar studies of the iron storage overload in livers

    International Nuclear Information System (INIS)

    Rimbert, J.N.; Dumas, F.; Richardot, G.; Kellershohn, C.

    1986-01-01

    Absorption 57 Fe Moessbauer spectra, performed directly on tissues of liver with iron overload due to an excessive intestinal iron absorption or induced by hypertransfusional therapeutics, have pointed out a new high spin ferric storage iron besides the ferritin and hemosiderin. Moessbauer studies, carried out on ferritin and hemosiderin fractions isolated from normal and overloaded livers, show that this compound, only present in the secondary iron overload (transfusional pathway), seems characteristic of the physiological process which induces the iron overload. (Auth.)

  9. Clinical survey of blood dyscrasias among Hiroshima A-bomb survivors by periodical health examination, (6). Serum ferritin determination of anemic patients

    Energy Technology Data Exchange (ETDEWEB)

    Abe, T.; Dohy, H.; Okita, H. (Hiroshima Univ. (Japan). Research Inst. for Nuclear Medicine and Biology)

    1980-11-01

    Serum ferritin was determined in A-bomb survivors, and its significance was evaluated. A low-ferritin group included many of the females under the age of 50, who mostly had iron deficient anemia. A high-ferritin group included many older-aged A-bomb survivors who had secondary anemia due to hemochromatosis, paroxismal nocturnal hemoglobinuria (PNH), and multiple myeloma. Secondary anemia due to hemochromatosis, PNH, leukemia, and sideroblastic anemia was detected in those who were old and had underlying moderate or severe anemia with a high ferritin level. As the results of this investigation, blood examination combined with serum ferritin determination is valuable for diagnosis of anemia and detection of underlying diseases.

  10. Effects of Vitamin A Supplementation on Iron Status Indices and Iron Deficiency Anaemia: A Randomized Controlled Trial

    Directory of Open Access Journals (Sweden)

    Hesham M. Al-Mekhlafi

    2013-12-01

    Full Text Available Iron deficiency anaemia (IDA is the most common nutritional deficiency in the world including developed and developing countries. Despite intensive efforts to improve the quality of life of rural and aboriginal communities in Malaysia, anaemia and IDA are still major public health problems in these communities particularly among children. A randomized, double-blind, placebo-controlled trial was conducted on 250 Orang Asli (aboriginal schoolchildren in Malaysia to investigate the effects of a single high-dose of vitamin A supplementation (200,000 IU on iron status indices, anaemia and IDA status. The effect of the supplement was assessed after 3 months of receiving the supplements; after a complete 3-day deworming course of 400 mg/day of albendazole tablets. The prevalence of anaemia was found to be high: 48.5% (95% CI = 42.3, 54.8. Moreover, 34% (95% CI = 28.3, 40.2 of the children had IDA, which accounted for 70.1% of the anaemic cases. The findings showed that the reduction in serum ferritin level and the increments in haemoglobin, serum iron and transferrin saturation were found to be significant among children allocated to the vitamin A group compared to those allocated to the placebo group (p < 0.01. Moreover, a significant reduction in the prevalence of IDA by almost 22% than prevalence at baseline was reported among children in the vitamin A group compared with only 2.3% reduction among children in the placebo group. In conclusion, vitamin A supplementation showed a significant impact on iron status indices and IDA among Orang Asli children. Hence, providing vitamin A supplementation and imparting the knowledge related to nutritious food should be considered in the efforts to improve the nutritional and health status of these children as a part of efforts to improve the quality of life in rural and aboriginal communities.

  11. High Prevalence but Insufficient Treatment of Iron-Deficiency Anemia in Patients with Inflammatory Bowel Disease: Results of a Population-Based Cohort

    Science.gov (United States)

    Ott, Claudia; Liebold, Anne; Takses, Angela; Strauch, Ulrike G.; Obermeier, Florian

    2012-01-01

    Background. Iron-deficiency anemia is described to be a common problem in patients with inflammatory bowel disease (IBD), which is frequently associated with a reduced quality of life. Therefore, the aim of this study is to assess the prevalence of iron deficiency anemia in a population-based cohort at time of first diagnosis and during the early course of the disease. Methods. As far as available, lab values of patients registered in the population-based “Oberpfalz cohort” were screened. In anemic patients, we further investigated all laboratory results to differentiate between iron deficiency and other reasons for anemia. All patients with any kind of anemia were interviewed separately according to symptoms of iron-deficiency anemia and administration of iron. Results. In total, we evaluated hemoglobin values of 279 patients (183 Crohn's disease, 90 ulcerative colitis, and 6 indeterminate colitis). Lab data which allowed further differentiation of the type of anemia were available in 70% of anemic patients, in 34.4% values of iron, ferritin and transferrin saturation had been measured. At time of first diagnosis, an iron-deficiency anemia was diagnosed in 26 of 68 patients with anemia (38.2%, 20 CD, 4 UC, and 2 IC patients), but only 9 patients (34.6%) received subsequent iron therapy. After one year, 27 patients were identified to have an iron-deficiency anemia (19 CD, 8 UC), 20 of them were treated with iron (71.4%). Of 9 patients with proven iron-deficiency anemia at time of first diagnosis and subsequent administration of iron, 5 (55.5%) had iron-deficiency anemia despite permanent treatment after one year. In total, 38 patients (54.3%) did not receive any iron substitution at all despite of proven iron-deficiency anemia, and only 13 patients of 74 patients were treated with intravenous iron (17.6%). Conclusion. We found a high prevalence of iron-deficiency anemia at different points during the early course of disease in this population-based cohort of

  12. Carbohydrate deficient transferrin (CDT) in alcoholic cirrhosis: a kinetic study

    DEFF Research Database (Denmark)

    Henriksen, Jens Henrik; Grønbaek, M; Møller, Søren

    1997-01-01

    BACKGROUND/AIMS: Carbohydrate deficient transferrin has been introduced as a marker of excessive alcohol intake. The present study was undertaken in order to measure the circulating level of carbohydrate deficient transferrin in patients with alcoholic cirrhosis and to assess arteriovenous kinetics...... of carbohydrate deficient transferrin in liver and kidney. METHODS/RESULTS: The median value of serum carbohydrate deficient transferrin was 16.0 U/l in patients with alcoholic cirrhosis (n = 41), and this value was not significantly different from that of a normal control group (median 17.4 U/l, n = 55, ns......). Carbohydrate deficient transferrin was significantly higher in patients with cirrhosis and high current alcohol intake than in abstaining patients (20 vs. 14 U/l, p 50 g/day) had a significantly higher carbohydrate deficient transferrin...