Structural and Functional Models of Non-Heme Iron Enzymes : A Study of the 2-His-1-Carboxylate Facial Triad Structural Motif

NARCIS (Netherlands)

Bruijnincx, P.C.A.

2007-01-01

The structural and functional modeling of a specific group of non-heme iron enzymes by the synthesis of small synthetic analogues is the topic of this thesis. The group of non-heme iron enzymes with the 2-His-1-carboxylate facial triad has recently been established as a common platform for the

BIOINSPIRED DESIGN AND DIRECTED EVOLUTION OF IRON CONTAINING ENZYMES FOR GREENSYNTHETIC PROCESSES AND BIOREMEDIATION

Science.gov (United States)

SU833912Title: Bioinspired Design and Directed Evolution of Iron Containing Enzymes for Green Synthetic Processes and BioremediationEdward I. Solomon, Shaun D. Wong, Lei Liu, Caleb B. Bell, IIICynthia Nolt-HelmsProject Period: August 15, 2008 - August 14,...

Electrochromic devices based on wide band-gap nanocrystalline semiconductors functionalized with mononuclear charge transfer compounds

DEFF Research Database (Denmark)

Biancardo, M.; Argazzi, R.; Bignozzi, C.A.

2006-01-01

A series of ruthenium and iron mononuclear complexes were prepared and their spectroeletrochemical behavior characterized oil Optically Transparent Thin Layer Electrodes (OTTLE) and on Fluorine Doped SnO2 (FTO) conductive glasses coated with Sb-doped nanocrystalline SnO2. These systems display a ...

Antioxidant Enzyme Activity, Iron Content and Lipid Oxidation of Raw and Cooked Meat of Korean Native Chickens and Other Poultry

Directory of Open Access Journals (Sweden)

Muhlisin

2016-05-01

Full Text Available This study was conducted to observe antioxidant enzyme activity, iron content and lipid oxidation of Korean native chickens and other poultry. The breast and thigh meat of three Korean native chicken breeds including Woorimatdak, Hyunin black and Yeonsan ogye, and three commercial poultry breeds including the broiler, White Leghorn and Pekin duck (Anasplatyrhyncos domesticus were studied. The analyses of the antioxidant enzymes activity, iron content and lipid oxidation were performed in raw and cooked samples. The activity of catalase (CAT in the thigh meat was higher than that of the breast meat of three Korean native chickens and the broiler, respectively. The activity of glutathione peroxidase (GPx in the uncooked thigh meat of three Korean native chickens was higher than that of the breasts. The breast meat of Woorimatdak and Pekin duck had higher superoxide dismutase (SOD activity than the others, while only the thigh meat of Pekin duck had the highest activity. Cooking inactivated CAT and decreased the activity of GPx and SOD. The thigh meat of Woorimatdak, White Leghorn, Yeonsan ogye and Hyunin black contained more total iron than the breast meat of those breeds. The heme-iron lost during cooking ranged from 3.2% to 14.8%. It is noted that the thigh meat had higher thiobarbituric acid reactive substances values than the breast in all chicken breeds. Though Woorimatdak showed higher antioxidant enzyme activity and lower released-iron percentage among Korean native chickens, no differences were found on lipid oxidation. We confirm that the dark meat of poultry exhibited higher antioxidant enzyme activity and contained more iron than the white meat.

Peroxide Activation for Electrophilic Reactivity by the Binuclear Non-heme Iron Enzyme AurF

International Nuclear Information System (INIS)

Park, Kiyoung; Li, Ning; Kwak, Yeonju; Srnec, Martin

2017-01-01

Binuclear non-heme iron enzymes activate O 2 for diverse chemistries that include oxygenation of organic substrates and hydrogen atom abstraction. This process often involves the formation of peroxo-bridged biferric intermediates, only some of which can perform electrophilic reactions. To elucidate the geometric and electronic structural requirements to activate peroxo reactivity, the active peroxo intermediate in 4-aminobenzoate N-oxygenase (AurF) has been characterized spectroscopically and computationally. A magnetic circular dichroism study of reduced AurF shows that its electronic and geometric structures are poised to react rapidly with O 2 . Nuclear resonance vibrational spectroscopic definition of the peroxo intermediate formed in this reaction shows that the active intermediate has a protonated peroxo bridge. Density functional theory computations on the structure established here show that the protonation activates peroxide for electrophilic/single-electron-transfer reactivity. As a result, this activation of peroxide by protonation is likely also relevant to the reactive peroxo intermediates in other binuclear non-heme iron enzymes.

Peroxo-Type Intermediates in Class I Ribonucleotide Reductase and Related Binuclear Non-Heme Iron Enzymes

DEFF Research Database (Denmark)

Kepp, Kasper Planeta; Bell, Caleb B.; Clay, MIchael D.

2009-01-01

We have performed a systematic study of chemically possible peroxo-type intermediates occurring in the non-heme di-iron enzyme class la ribonucleotide reductase, using spectroscopically calibrated computational chemistry. Density functional computations of equilibrium structures, Fe-O and O-O str...

Effect of molybdenum and iron supply on molybdenum (99Mo) and iron (59Fe) uptake and activity of certain enzymes in tomato plants grown in sand culture

International Nuclear Information System (INIS)

Chatterjee, C.; Agarwala, S.C.

1979-01-01

Tomato (Lycopersicon esculentum Mill. var. Marglobe) plants were raised under controlled sand culture to study the interaction of molybdenum and iron supply on the uptake of molybdenum and iron and activity of certain enzymes affected by iron and/or molybdenum supply. Iron deficiency caused a decrease in the molybdenum uptake and accentuated the effect of molybdenum deficiency in reducing the uptake and more so the translocation of molybdenum from roots to shoots, thus inducing more severe molybdenum deficiency. The deficiency of iron and molybdenum decreased the activity of catalase, succinate dehydrogenase and nitrate reductase, the most marked decrease being found in plants supplied with both iron and molybdenum at low levels. Changes in the activities of nitrate reductase and catalase can be attributed to the interaction of iron and molybdenum supply in their absorption and translocation. (auth.)

Assessment of Dextran Antigenicity of Intravenous Iron Preparations with Enzyme-Linked Immunosorbent Assay (ELISA).

Science.gov (United States)

Neiser, Susann; Koskenkorva, Taija S; Schwarz, Katrin; Wilhelm, Maria; Burckhardt, Susanna

2016-07-21

Intravenous iron preparations are typically classified as non-dextran-based or dextran/dextran-based complexes. The carbohydrate shell for each of these preparations is unique and is key in determining the various physicochemical properties, the metabolic pathway, and the immunogenicity of the iron-carbohydrate complex. As intravenous dextran can cause severe, antibody-mediated dextran-induced anaphylactic reactions (DIAR), the purpose of this study was to explore the potential of various intravenous iron preparations, non-dextran-based or dextran/dextran-based, to induce these reactions. An IgG-isotype mouse monoclonal anti-dextran antibody (5E7H3) and an enzyme-linked immunosorbent assay (ELISA) were developed to investigate the dextran antigenicity of low molecular weight iron dextran, ferumoxytol, iron isomaltoside 1000, ferric gluconate, iron sucrose and ferric carboxymaltose, as well as isomaltoside 1000, the isolated carbohydrate component of iron isomaltoside 1000. Low molecular weight iron dextran, as well as dextran-based ferumoxytol and iron isomaltoside 1000, reacted with 5E7H3, whereas ferric carboxymaltose, iron sucrose, sodium ferric gluconate, and isolated isomaltoside 1000 did not. Consistent results were obtained with reverse single radial immunodiffusion assay. The results strongly support the hypothesis that, while the carbohydrate alone (isomaltoside 1000) does not form immune complexes with anti-dextran antibodies, iron isomaltoside 1000 complex reacts with anti-dextran antibodies by forming multivalent immune complexes. Moreover, non-dextran based preparations, such as iron sucrose and ferric carboxymaltose, do not react with anti-dextran antibodies. This assay allows to assess the theoretical possibility of a substance to induce antibody-mediated DIARs. Nevertheless, as this is only one possible mechanism that may cause a hypersensitivity reaction, a broader set of assays will be required to get an understanding of the mechanisms that may

Preparation, Crystallization and X-ray Diffraction Analysis to 1.5 A Resolution of Rat Cysteine Dioxygenase, a Mononuclear Iron Enzyme Responsible for Cysteine Thiol Oxidation

Energy Technology Data Exchange (ETDEWEB)

Simmons,C.; Hao, Q.; Stipanuk, M.

2005-01-01

Cysteine dioxygenase (CDO; EC 1.13.11.20) is an {approx}23 kDa non-heme iron metalloenzyme that is responsible for the oxidation of cysteine by O2, yielding cysteinesulfinate. CDO catalyzes the first step in the conversion of cysteine to taurine, as well as the first step in the catabolism of cysteine to pyruvate plus sulfate. Recombinant rat CDO was heterologously expressed, purified and crystallized. The protein was expressed as a fusion protein bearing a polyhistidine tag to facilitate purification, a thioredoxin tag to improve solubility and a factor Xa cleavage site to permit removal of the entire N-terminus, leaving only the 200 amino acids inherent to the native protein. A multi-step purification scheme was used to achieve >95% purity of CDO. The optimal CDO crystals diffracted to 1.5 Angstroms resolution and belonged to space group P4{sub 3}2{sub 1}2 or P4{sub 1}2{sub 1}2, with unit-cell parameters a = b = 57.55, c = 123.06 Angstrom, {alpha} = {beta} = {gamma} = 90. CDO shows little homology to any other proteins; therefore, the structure of the enzyme will be determined by ab initio phasing using a selenomethionyl derivative.

Biochemical, Kinetic, and Spectroscopic Characterization of Ruegeria pomeroyi DddW--A Mononuclear Iron-Dependent DMSP Lyase.

Directory of Open Access Journals (Sweden)

Adam E Brummett

Full Text Available The osmolyte dimethylsulfoniopropionate (DMSP is a key nutrient in marine environments and its catabolism by bacteria through enzymes known as DMSP lyases generates dimethylsulfide (DMS, a gas of importance in climate regulation, the sulfur cycle, and signaling to higher organisms. Despite the environmental significance of DMSP lyases, little is known about how they function at the mechanistic level. In this study we biochemically characterize DddW, a DMSP lyase from the model roseobacter Ruegeria pomeroyi DSS-3. DddW is a 16.9 kDa enzyme that contains a C-terminal cupin domain and liberates acrylate, a proton, and DMS from the DMSP substrate. Our studies show that as-purified DddW is a metalloenzyme, like the DddQ and DddP DMSP lyases, but contains an iron cofactor. The metal cofactor is essential for DddW DMSP lyase activity since addition of the metal chelator EDTA abolishes its enzymatic activity, as do substitution mutations of key metal-binding residues in the cupin motif (His81, His83, Glu87, and His121. Measurements of metal binding affinity and catalytic activity indicate that Fe(II is most likely the preferred catalytic metal ion with a nanomolar binding affinity. Stoichiometry studies suggest DddW requires one Fe(II per monomer. Electronic absorption and electron paramagnetic resonance (EPR studies show an interaction between NO and Fe(II-DddW, with NO binding to the EPR silent Fe(II site giving rise to an EPR active species (g = 4.29, 3.95, 2.00. The change in the rhombicity of the EPR signal is observed in the presence of DMSP, indicating that substrate binds to the iron site without displacing bound NO. This work provides insight into the mechanism of DMSP cleavage catalyzed by DddW.

Leishmania mexicana amazonensis: heterogeneity in 5-nucleotidase and peroxidase activities of mononuclear phagocytes during in vivo and in vitro infection

OpenAIRE

Côrte-Real, Suzana; Grimaldi Junior, Gabriel; Meirelles, Maria de Nazareth Leal de

1988-01-01

The degree of maturation of cells of the Mononuclear Phagocyte System (MPS), during in vivo and in vitro infection by Leishmania mexicana amazonenesis, was evaluated in this study. The macrophages' differentiation was assayed by cytochemical characterization at the ultrastrctural level, using two well-established markers: 5'-nucleotidase enzyme activity, for revealing the mature cells, and the peroxidase activity present in the cell granules to demonstrate immature mononuclear phagocytes. onl...

The crystal structure of tryptophan hydroxylase with bound amino acid substrate

DEFF Research Database (Denmark)

Windahl, Michael Skovbo; Petersen, Charlotte Rode; Christensen, Hans Erik Mølager

2008-01-01

Tryptophan hydroxylase (TPH) is a mononuclear non-heme iron enzyme, which catalyzes the reaction between tryptophan, O2, and tetrahydrobiopterin (BH4) to produce 5-hydroxytryptophan and 4a-hydroxytetrahydrobiopterin. This is the first and rate-limiting step in the biosynthesis of the neurotransmi......Tryptophan hydroxylase (TPH) is a mononuclear non-heme iron enzyme, which catalyzes the reaction between tryptophan, O2, and tetrahydrobiopterin (BH4) to produce 5-hydroxytryptophan and 4a-hydroxytetrahydrobiopterin. This is the first and rate-limiting step in the biosynthesis...... acid hydroxylase with bound natural amino acid substrate. The iron coordination can be described as distorted trigonal bipyramidal coordination with His273, His278, and Glu318 (partially bidentate) and one imidazole as ligands. The tryptophan stacks against Pro269 with a distance of 3.9 Å between...

Catalytic properties of extraframework iron-containing species in ZSM-5 for N2O decomposition

NARCIS (Netherlands)

Li, G.; Pidko, E.A.; Filot, I.A.W.; Santen, van R.A.; Li, Can; Hensen, E.J.M.

2013-01-01

The reactivity of mononuclear and binuclear iron-containing complexes in ZSM-5 zeolite for catalytic N2O decomposition has been investigated by periodic DFT calculations and microkinetic modeling. On mononuclear sites, the activation of a first N2O molecule is favorable. The rate of catalytic N2O

Leishmania mexicana amazonensis: heterogeneity in 5-nucleotidase and peroxidase activities of mononuclear phagocytes during in vivo and in vitro infection Leishmania mexicana amazonensis: heterogeneidade da 5’-Nucleotidase e da peroxidase em fagócitos mononucleares durante infecção in vivo e in vitro

OpenAIRE

Suzana Côrte-Real; Gabriel Grimaldi Junior; Maria de Nazareth Leal de Meirelles

1988-01-01

The degree of maturation of cells of the Mononuclear Phagocyte System (MPS), during in vivo and in vitro infection by Leishmania mexicana amazonenesis, was evaluated in this study. The macrophages' differentiation was assayed by cytochemical characterization at the ultrastrctural level, using two well-established markers: 5'-nucleotidase enzyme activity, for revealing the mature cells, and the peroxidase activity present in the cell granules to demonstrate immature mononuclear phagocytes. onl...

Diphthamide biosynthesis requires an organic radical generated by an iron-sulphur enzyme

Energy Technology Data Exchange (ETDEWEB)

Zhang, Yang; Zhu, Xuling; Torelli, Andrew T; Lee, Michael; Dzikovski, Boris; Koralewski, Rachel M; Wang, Eileen; Freed, Jack; Krebs, Carsten; Ealick, Steve E; Lin, Hening [Cornell; (Penn)

2010-08-30

Archaeal and eukaryotic translation elongation factor 2 contain a unique post-translationally modified histidine residue called diphthamide, which is the target of diphtheria toxin. The biosynthesis of diphthamide was proposed to involve three steps, with the first being the formation of a C-C bond between the histidine residue and the 3-amino-3-carboxypropyl group of S-adenosyl-l-methionine (SAM). However, further details of the biosynthesis remain unknown. Here we present structural and biochemical evidence showing that the first step of diphthamide biosynthesis in the archaeon Pyrococcus horikoshii uses a novel iron-sulphur-cluster enzyme, Dph2. Dph2 is a homodimer and each of its monomers can bind a [4Fe-4S] cluster. Biochemical data suggest that unlike the enzymes in the radical SAM superfamily, Dph2 does not form the canonical 5'-deoxyadenosyl radical. Instead, it breaks the C_γ,Met-S bond of SAM and generates a 3-amino-3-carboxypropyl radical. Our results suggest that P. horikoshii Dph2 represents a previously unknown, SAM-dependent, [4Fe-4S]-containing enzyme that catalyses unprecedented chemistry.

Magnetically responsive enzyme powders

Energy Technology Data Exchange (ETDEWEB)

Pospiskova, Kristyna, E-mail: kristyna.pospiskova@upol.cz [Regional Centre of Advanced Technologies and Materials, Palacky University, Slechtitelu 11, 783 71 Olomouc (Czech Republic); Safarik, Ivo, E-mail: ivosaf@yahoo.com [Regional Centre of Advanced Technologies and Materials, Palacky University, Slechtitelu 11, 783 71 Olomouc (Czech Republic); Department of Nanobiotechnology, Institute of Nanobiology and Structural Biology of GCRC, Na Sadkach 7, 370 05 Ceske Budejovice (Czech Republic)

2015-04-15

Powdered enzymes were transformed into their insoluble magnetic derivatives retaining their catalytic activity. Enzyme powders (e.g., trypsin and lipase) were suspended in various liquid media not allowing their solubilization (e.g., saturated ammonium sulfate and highly concentrated polyethylene glycol solutions, ethanol, methanol, 2-propanol) and subsequently cross-linked with glutaraldehyde. Magnetic modification was successfully performed at low temperature in a freezer (−20 °C) using magnetic iron oxides nano- and microparticles prepared by microwave-assisted synthesis from ferrous sulfate. Magnetized cross-linked enzyme powders were stable at least for two months in water suspension without leakage of fixed magnetic particles. Operational stability of magnetically responsive enzymes during eight repeated reaction cycles was generally without loss of enzyme activity. Separation of magnetically modified cross-linked powdered enzymes from reaction mixtures was significantly simplified due to their magnetic properties. - Highlights: • Cross-linked enzyme powders were prepared in various liquid media. • Insoluble enzymes were magnetized using iron oxides particles. • Magnetic iron oxides particles were prepared by microwave-assisted synthesis. • Magnetic modification was performed under low (freezing) temperature. • Cross-linked powdered trypsin and lipase can be used repeatedly for reaction.

Preparation, crystallization and X-ray diffraction analysis to 1.5 Å resolution of rat cysteine dioxygenase, a mononuclear iron enzyme responsible for cysteine thiol oxidation

Energy Technology Data Exchange (ETDEWEB)

Simmons, Chad R. [Division of Nutritional Sciences, Cornell University, Ithaca, NY 14853-8001 (United States); Hao, Quan [MacCHESS at the Cornell High Energy Synchrotron Source, Cornell University, Ithaca, NY 14853-8001 (United States); Stipanuk, Martha H., E-mail: mhs6@cornell.edu [Division of Nutritional Sciences, Cornell University, Ithaca, NY 14853-8001 (United States)

2005-11-01

Recombinant rat cysteine dioxygenase (CDO) has been expressed, purified and crystallized and X-ray diffraction data have been collected to 1.5 Å resolution. Cysteine dioxygenase (CDO; EC 1.13.11.20) is an ∼23 kDa non-heme iron metalloenzyme that is responsible for the oxidation of cysteine by O{sub 2}, yielding cysteinesulfinate. CDO catalyzes the first step in the conversion of cysteine to taurine, as well as the first step in the catabolism of cysteine to pyruvate plus sulfate. Recombinant rat CDO was heterologously expressed, purified and crystallized. The protein was expressed as a fusion protein bearing a polyhistidine tag to facilitate purification, a thioredoxin tag to improve solubility and a factor Xa cleavage site to permit removal of the entire N-terminus, leaving only the 200 amino acids inherent to the native protein. A multi-step purification scheme was used to achieve >95% purity of CDO. The optimal CDO crystals diffracted to 1.5 Å resolution and belonged to space group P4{sub 3}2{sub 1}2 or P4{sub 1}2{sub 1}2, with unit-cell parameters a = b = 57.55, c = 123.06 Å, α = β = γ = 90°. CDO shows little homology to any other proteins; therefore, the structure of the enzyme will be determined by ab initio phasing using a selenomethionyl derivative.

2010 IRON-SULFUR ENZYMES GORDON RESEARCH CONFERENCE, JUNE 6-11, 2010

Energy Technology Data Exchange (ETDEWEB)

Nancy Ryan Gray

2010-06-11

Iron-sulfur (FeS) centers are essential for biology and inspirational in chemistry. These protein cofactors are broadly defined as active sites in which Fe is coordinated by S-donor ligands, often in combination with extra non-protein components, for example, additional metal atoms such as Mo and Ni, and soft ligands such as CN{sup -} and CO. Iron-sulfur centers are inherently air sensitive: they are found in essentially all organisms and it is possible that they were integral components of the earliest forms of life, well before oxygen (O{sub 2}) appeared. Proteins containing FeS cofactors perform a variety of biological functions ranging across electron transfer, acid-base catalysis, and sensing where they are agents for cell regulation through transcription (DNA) or translation (RNA). They are redox catalysts for radical-based reactions and the activation of H{sub 2}, N{sub 2} and CO{sub 2}, processes that offer scientific and economic challenges for industry. Iron-sulfur centers provide the focus for fundamental investigations of chemical bonding, spectroscopy and paramagnetism, and their functions have numerous implications for health and medicine and applications for technology, including renewable energy. The 2010 Iron-Sulfur Enzymes GRC will bring together researchers from different disciplines for in-depth discussions and presentations of the latest developments. There will be sessions on structural and functional analogues of FeS centers, advances in physical methods, roles of FeS centers in energy and technology, catalysis (including radical-based rearrangements and the activation of nitrogen, hydrogen and carbon), long-range electron transfer, FeS centers in health and disease, cellular regulation, cofactor assembly, their relevance in industry, and experiments and hypotheses relating to the origins of life.

A Mononuclear Iron-Dependent Methyltransferase Catalyzes Initial Steps in Assembly of the Apratoxin A Polyketide Starter Unit.

Science.gov (United States)

Skiba, Meredith A; Sikkema, Andrew P; Moss, Nathan A; Tran, Collin L; Sturgis, Rebecca M; Gerwick, Lena; Gerwick, William H; Sherman, David H; Smith, Janet L

2017-12-15

Natural product biosynthetic pathways contain a plethora of enzymatic tools to carry out difficult biosynthetic transformations. Here, we discover an unusual mononuclear iron-dependent methyltransferase that acts in the initiation steps of apratoxin A biosynthesis (AprA MT1). Fe 3+ -replete AprA MT1 catalyzes one or two methyl transfer reactions on the substrate malonyl-ACP (acyl carrier protein), whereas Co 2+ , Fe 2+ , Mn 2+ , and Ni 2+ support only a single methyl transfer. MT1 homologues exist within the "GNAT" (GCN5-related N-acetyltransferase) loading modules of several modular biosynthetic pathways with propionyl, isobutyryl, or pivaloyl starter units. GNAT domains are thought to catalyze decarboxylation of malonyl-CoA and acetyl transfer to a carrier protein. In AprA, the GNAT domain lacks both decarboxylation and acyl transfer activity. A crystal structure of the AprA MT1-GNAT di-domain with bound Mn 2+ , malonate, and the methyl donor S-adenosylmethionine (SAM) reveals that the malonyl substrate is a bidentate metal ligand, indicating that the metal acts as a Lewis acid to promote methylation of the malonyl α-carbon. The GNAT domain is truncated relative to functional homologues. These results afford an expanded understanding of MT1-GNAT structure and activity and permit the functional annotation of homologous GNAT loading modules both with and without methyltransferases, additionally revealing their rapid evolutionary adaptation in different biosynthetic contexts.

Neelaredoxin, an iron-binding protein from the syphilis spirochete, Treponema pallidum, is a superoxide reductase.

Science.gov (United States)

Jovanović, T; Ascenso, C; Hazlett, K R; Sikkink, R; Krebs, C; Litwiller, R; Benson, L M; Moura, I; Moura, J J; Radolf, J D; Huynh, B H; Naylor, S; Rusnak, F

2000-09-15

Treponema pallidum, the causative agent of venereal syphilis, is a microaerophilic obligate pathogen of humans. As it disseminates hematogenously and invades a wide range of tissues, T. pallidum presumably must tolerate substantial oxidative stress. Analysis of the T. pallidum genome indicates that the syphilis spirochete lacks most of the iron-binding proteins present in many other bacterial pathogens, including the oxidative defense enzymes superoxide dismutase, catalase, and peroxidase, but does possess an orthologue (TP0823) for neelaredoxin, an enzyme of hyperthermophilic and sulfate-reducing anaerobes shown to possess superoxide reductase activity. To analyze the potential role of neelaredoxin in treponemal oxidative defense, we examined the biochemical, spectroscopic, and antioxidant properties of recombinant T. pallidum neelaredoxin. Neelaredoxin was shown to be expressed in T. pallidum by reverse transcriptase-polymerase chain reaction and Western blot analysis. Recombinant neelaredoxin is a 26-kDa alpha(2) homodimer containing, on average, 0.7 iron atoms/subunit. Mössbauer and EPR analysis of the purified protein indicates that the iron atom exists as a mononuclear center in a mixture of high spin ferrous and ferric oxidation states. The fully oxidized form, obtained by the addition of K(3)(Fe(CN)(6)), exhibits an optical spectrum with absorbances at 280, 320, and 656 nm; the last feature is responsible for the protein's blue color, which disappears upon ascorbate reduction. The fully oxidized protein has a A(280)/A(656) ratio of 10.3. Enzymatic studies revealed that T. pallidum neelaredoxin is able to catalyze a redox equilibrium between superoxide and hydrogen peroxide, a result consistent with it being a superoxide reductase. This finding, the first description of a T. pallidum iron-binding protein, indicates that the syphilis spirochete copes with oxidative stress via a primitive mechanism, which, thus far, has not been described in pathogenic

Iron deficiency or anemia of inflammation? : Differential diagnosis and mechanisms of anemia of inflammation.

Science.gov (United States)

Nairz, Manfred; Theurl, Igor; Wolf, Dominik; Weiss, Günter

2016-10-01

Iron deficiency and immune activation are the two most frequent causes of anemia, both of which are based on disturbances of iron homeostasis. Iron deficiency anemia results from a reduction of the body's iron content due to blood loss, inadequate dietary iron intake, its malabsorption, or increased iron demand. Immune activation drives a diversion of iron fluxes from the erythropoietic bone marrow, where hemoglobinization takes place, to storage sites, particularly the mononuclear phagocytes system in liver and spleen. This results in iron-limited erythropoiesis and anemia. This review summarizes current diagnostic and pathophysiological concepts of iron deficiency anemia and anemia of inflammation, as well as combined conditions, and provides a brief outlook on novel therapeutic options.

DNA binding and cleavage activity by a mononuclear iron(II)Schiff ...

Indian Academy of Sciences (India)

e-mail: rajarshi_chem@yahoo.co.in; bunair@clri.res.in. MS received 21 January ..... thesis, single crystal X-ray structural characterization of an iron(II) complex (1) ... of Burdwan and Council for Scientific and Industrial. Research (CSIR), New ...

NRVS Studies of the Peroxide Shunt Intermediate in a Rieske Dioxygenase and Its Relation to the Native FesupII/supOinf2/infReaction

Czech Academy of Sciences Publication Activity Database

Sutherlin, K. D.; Rivard, B. S.; Böttger, L. H.; Liu, L. V.; Rogers, M. S.; Srnec, Martin; Park, K.; Yoda, Y.; Kitao, S.; Kobayashi, Y.; Saito, M.; Seto, M.; Hu, M.; Zhao, J.; Lipscomb, J. D.; Solomon, E. I.

2018-01-01

Roč. 140, č. 16 (2018), s. 5544-5559 ISSN 0002-7863 Institutional support: RVO:61388955 Keywords : NRVS studies * Rieske dioxygenase * mononuclear nonheme iron enzymes Subject RIV: CF - Physical ; The oretical Chemistry OBOR OECD: Physical chemistry Impact factor: 13.858, year: 2016

Iron-Dependent Enzyme Catalyzes the Initial Step in Biodegradation of N-Nitroglycine by Variovorax sp. Strain JS1663.

Science.gov (United States)

Mahan, Kristina M; Zheng, Hangping; Fida, Tekle T; Parry, Ronald J; Graham, David E; Spain, Jim C

2017-08-01

Nitramines are key constituents of most of the explosives currently in use and consequently contaminate soil and groundwater at many military facilities around the world. Toxicity from nitramine contamination poses a health risk to plants and animals. Thus, understanding how nitramines are biodegraded is critical to environmental remediation. The biodegradation of synthetic nitramine compounds such as hexahydro-1,3,5-trinitro-1,3,5-triazine (RDX) has been studied for decades, but little is known about the catabolism of naturally produced nitramine compounds. In this study, we report the isolation of a soil bacterium, Variovorax sp. strain JS1663, that degrades N -nitroglycine (NNG), a naturally produced nitramine, and the key enzyme involved in its catabolism. Variovorax sp. JS1663 is a Gram-negative, non-spore-forming motile bacterium isolated from activated sludge based on its ability to use NNG as a sole growth substrate under aerobic conditions. A single gene ( nnlA ) encodes an iron-dependent enzyme that releases nitrite from NNG through a proposed β-elimination reaction. Bioinformatics analysis of the amino acid sequence of NNG lyase identified a PAS (Per-Arnt-Sim) domain. PAS domains can be associated with heme cofactors and function as signal sensors in signaling proteins. This is the first instance of a PAS domain present in a denitration enzyme. The NNG biodegradation pathway should provide the basis for the identification of other enzymes that cleave the N-N bond and facilitate the development of enzymes to cleave similar bonds in RDX, nitroguanidine, and other nitramine explosives. IMPORTANCE The production of antibiotics and other allelopathic chemicals is a major aspect of chemical ecology. The biodegradation of such chemicals can play an important ecological role in mitigating or eliminating the effects of such compounds. N -Nitroglycine (NNG) is produced by the Gram-positive filamentous soil bacterium Streptomyces noursei This study reports the

Selective and reusable iron(II)-based molecular sensor for the vapor-phase detection of alcohols.

Science.gov (United States)

Naik, Anil D; Robeyns, Koen; Meunier, Christophe F; Léonard, Alexandre F; Rotaru, Aurelian; Tinant, Bernard; Filinchuk, Yaroslav; Su, Bao Lian; Garcia, Yann

2014-02-03

A mononuclear iron(II) neutral complex (1) is screened for sensing abilities for a wide spectrum of chemicals and to evaluate the response function toward physical perturbation like temperature and mechanical stress. Interestingly, 1 precisely detects methanol among an alcohol series. The sensing process is visually detectable, fatigue-resistant, highly selective, and reusable. The sensing ability is attributed to molecular sieving and subsequent spin-state change of iron centers, after a crystal-to-crystal transformation.

Mononuclear phagocytes as a target, not a barrier, for drug delivery.

Science.gov (United States)

Yong, Seok-Beom; Song, Yoonsung; Kim, Hyung Jin; Ain, Qurrat Ul; Kim, Yong-Hee

2017-08-10

Mononuclear phagocytes have been generally recognized as a barrier to drug delivery. Recently, a new understanding of mononuclear phagocytes (MPS) ontogeny has surfaced and their functions in disease have been unveiled, demonstrating the need for re-evaluation of perspectives on mononuclear phagocytes in drug delivery. In this review, we described mononuclear phagocyte biology and focus on their accumulation mechanisms in disease sites with explanations of monocyte heterogeneity. In the 'MPS as a barrier' section, we summarized recent studies on mechanisms to avoid phagocytosis based on two different biological principles: protein adsorption and self-recognition. In the 'MPS as a target' section, more detailed descriptions were given on mononuclear phagocyte-targeted drug delivery systems and their applications to various diseases. Collectively, we emphasize in this review that mononuclear phagocytes are potent targets for future drug delivery systems. Mononuclear phagocyte-targeted delivery systems should be created with an understanding of mononuclear phagocyte ontogeny and pathology. Each specific subset of phagocytes should be targeted differently by location and function for improved disease-drug delivery while avoiding RES clearance such as Kupffer cells and splenic macrophages. Copyright © 2017 Elsevier B.V. All rights reserved.

Iron overload impact on P-ATPases.

Science.gov (United States)

Sousa, Leilismara; Pessoa, Marco Tulio C; Costa, Tamara G F; Cortes, Vanessa F; Santos, Herica L; Barbosa, Leandro Augusto

2018-03-01

Iron is a chemical element that is active in the fundamental physiological processes for human life, but its burden can be toxic to the body, mainly because of the stimulation of membrane lipid peroxidation. For this reason, the action of iron on many ATPases has been studied, especially on P-ATPases, such as the Na + ,K + -ATPase and the Ca 2+ -ATPase. On the Fe 2+ -ATPase activity, the free iron acts as an activator, decreasing the intracellular Fe 2+ and playing a protection role for the cell. On the Ca 2+ -ATPase activity, the iron overload decreases the enzyme activity, raising the cytoplasmic Ca 2+ and decreasing the sarco/endoplasmic reticulum and the Golgi apparatus Ca 2+ concentrations, which could promote an enzyme oxidation, nitration, and fragmentation. However, the iron overload effect on the Na + ,K + -ATPase may change according to the tissue expressions. On the renal cells, as well as on the brain and the heart, iron promotes an enzyme inactivation, whereas its effect on the erythrocytes seems to be the opposite, directly stimulating the ATPase activity, or stimulating it by signaling pathways involving ROS and PKC. Modulations in the ATPase activity may impair the ionic transportation, which is essential for cell viability maintenance, inducing irreversible damage to the cell homeostasis. Here, we will discuss about the iron overload effect on the P-ATPases, such as the Na + ,K + -ATPase, the Ca 2+ -ATPase, and the Fe 2+ -ATPase.

Cytosolic iron chaperones: Proteins delivering iron cofactors in the cytosol of mammalian cells.

Science.gov (United States)

Philpott, Caroline C; Ryu, Moon-Suhn; Frey, Avery; Patel, Sarju

2017-08-04

Eukaryotic cells contain hundreds of metalloproteins that are supported by intracellular systems coordinating the uptake and distribution of metal cofactors. Iron cofactors include heme, iron-sulfur clusters, and simple iron ions. Poly(rC)-binding proteins are multifunctional adaptors that serve as iron ion chaperones in the cytosolic/nuclear compartment, binding iron at import and delivering it to enzymes, for storage (ferritin) and export (ferroportin). Ferritin iron is mobilized by autophagy through the cargo receptor, nuclear co-activator 4. The monothiol glutaredoxin Glrx3 and BolA2 function as a [2Fe-2S] chaperone complex. These proteins form a core system of cytosolic iron cofactor chaperones in mammalian cells. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

Multi-Copper Oxidases and Human Iron Metabolism

Science.gov (United States)

Vashchenko, Ganna; MacGillivray, Ross T. A.

2013-01-01

Multi-copper oxidases (MCOs) are a small group of enzymes that oxidize their substrate with the concomitant reduction of dioxygen to two water molecules. Generally, multi-copper oxidases are promiscuous with regards to their reducing substrates and are capable of performing various functions in different species. To date, three multi-copper oxidases have been detected in humans—ceruloplasmin, hephaestin and zyklopen. Each of these enzymes has a high specificity towards iron with the resulting ferroxidase activity being associated with ferroportin, the only known iron exporter protein in humans. Ferroportin exports iron as Fe2+, but transferrin, the major iron transporter protein of blood, can bind only Fe3+ effectively. Iron oxidation in enterocytes is mediated mainly by hephaestin thus allowing dietary iron to enter the bloodstream. Zyklopen is involved in iron efflux from placental trophoblasts during iron transfer from mother to fetus. Release of iron from the liver relies on ferroportin and the ferroxidase activity of ceruloplasmin which is found in blood in a soluble form. Ceruloplasmin, hephaestin and zyklopen show distinctive expression patterns and have unique mechanisms for regulating their expression. These features of human multi-copper ferroxidases can serve as a basis for the precise control of iron efflux in different tissues. In this manuscript, we review the biochemical and biological properties of the three human MCOs and discuss their potential roles in human iron homeostasis. PMID:23807651

Iron from haemoglobin and haemin modulates nucleotide hydrolysis in Trichomonas vaginalis.

Science.gov (United States)

Vieira, Patrícia de Brum; Silva, Nícolas Luiz Feijó; Kist, Luiza Wilges; Oliveira, Giovanna Medeiros Tavares de; Bogo, Maurício Reis; Carli, Geraldo Atillio de; Macedo, Alexandre José; Tasca, Tiana

2015-04-01

Extracellular ATP may act as a danger signalling molecule, inducing inflammation and immune responses in infection sites. The ectonucleotidases NTPDase and ecto-5'-nucleotidase are enzymes that modulate extracellular nucleotide levels; these enzymes have been previously characterised in Trichomonas vaginalis. Iron plays an important role in the complex trichomonal pathogenesis. Herein, the effects of iron on growth, nucleotide hydrolysis and NTPDase gene expression in T. vaginalis isolates from female and male patients were evaluated. Iron from different sources sustained T. vaginalis growth. Importantly, iron from haemoglobin (HB) and haemin (HM) enhanced NTPDase activity in isolates from female patients and conversely reduced the enzyme activity in isolates from male patients. Iron treatments could not alter the NTPDase transcript levels in T. vaginalis. Furthermore, our results reveal a distinct ATP, ADP and AMP hydrolysis profile between isolates from female and male patients influenced by iron from HB and HM. Our data indicate the participation of NTPDase and ecto-5'-nucleotidase in the establishment of trichomonas infection through ATP degradation and adenosine production influenced by iron.

Iron from haemoglobin and haemin modulates nucleotide hydrolysis in Trichomonas vaginalis

Directory of Open Access Journals (Sweden)

Patrícia de Brum Vieira

2015-04-01

Full Text Available Extracellular ATP may act as a danger signalling molecule, inducing inflammation and immune responses in infection sites. The ectonucleotidases NTPDase and ecto-5’-nucleotidase are enzymes that modulate extracellular nucleotide levels; these enzymes have been previously characterised in Trichomonas vaginalis. Iron plays an important role in the complex trichomonal pathogenesis. Herein, the effects of iron on growth, nucleotide hydrolysis and NTPDase gene expression in T. vaginalis isolates from female and male patients were evaluated. Iron from different sources sustained T. vaginalis growth. Importantly, iron from haemoglobin (HB and haemin (HM enhanced NTPDase activity in isolates from female patients and conversely reduced the enzyme activity in isolates from male patients. Iron treatments could not alter the NTPDase transcript levels in T. vaginalis. Furthermore, our results reveal a distinct ATP, ADP and AMP hydrolysis profile between isolates from female and male patients influenced by iron from HB and HM. Our data indicate the participation of NTPDase and ecto-5’-nucleotidase in the establishment of trichomonas infection through ATP degradation and adenosine production influenced by iron.

Iron nutrition and premenopausal women: effects of poor iron status on physical and neuropsychological performance.

Science.gov (United States)

McClung, James P; Murray-Kolb, Laura E

2013-01-01

Iron is a nutritionally essential trace element that functions through incorporation into proteins and enzymes, many of which contribute to physical and neuropsychological performance. Poor iron status, including iron deficiency (ID; diminished iron stores) and iron deficiency anemia (IDA; poor iron stores and diminished hemoglobin), affects billions of people worldwide. This review focuses on physical and neuropsychological outcomes associated with ID and IDA in premenopausal women, as the prevalence of ID and IDA is often greater in premenopausal women than other population demographics. Recent studies addressing the physiological effects of poor iron status on physical performance, including work productivity, voluntary activity, and athletic performance, are addressed. Similarly, the effects of iron status on neurological performance, including cognition, affect, and behavior, are summarized. Nutritional countermeasures for the prevention of poor iron status and the restoration of decrements in performance outcomes are described.

Effects of trace element concentration on enzyme controlled stable isotope fractionation during aerobic biodegradation of toluene.

Science.gov (United States)

Mancini, Silvia A; Hirschorn, Sarah K; Elsner, Martin; Lacrampe-Couloume, Georges; Sleep, Brent E; Edwards, Elizabeth A; Lollar, Barbara Sherwood

2006-12-15

The effects of iron concentration on carbon and hydrogen isotopic fractionation during aerobic biodegradation of toluene by Pseudomonas putida mt-2 were investigated using a low iron medium and two different high iron media. Mean carbon enrichment factors (epsilonc) determined using a Rayleigh isotopic model were smaller in culture grown under high iron conditions (epsilonc = -1.7+/-0.1%) compared to low iron conditions (epsilonc = -2.5+/-0.3%). Mean hydrogen enrichment factors (epsilonH) were also significantly smaller for culture grown under high iron conditions (epsilonH = -77 +/-4%) versus low iron conditions (EpsilonH = -159+/-11%). A mechanistic model for enzyme kinetics was used to relate differences in the magnitude of isotopic fractionation for low iron versus high iron cultures to the efficiency of the enzymatic transformation. The increase of carbon and hydrogen enrichment factors at low iron concentrations suggests a slower enzyme-catalyzed substrate conversion step (k2) relative to the enzyme-substrate binding step (k-l) at low iron concentration. While the observed differences were subtle and, hence, do not significantly impact the ability to use stable isotope analysis in the field, these results demonstrated that resolvable differences in carbon and hydrogen isotopic fractionation were related to low and high iron conditions. This novel result highlights the need to further investigate the effects of other trace elements known to be key components of biodegradative enzymes.

Role of peripheral blood mononuclear cell transportation from mother to baby in HBV intrauterine infection.

Science.gov (United States)

Shao, Qingliang; Zhao, Xiaxia; Yao Li, M D

2013-12-01

We aimed to investigate the role of peripheral blood mononuclear cell transportation from mother to baby in hepatitis B virus (HBV) intrauterine infection. Thirty HBsAg-positive pregnant women in the second trimester and their aborted fetuses were included in this study. Enzyme-linked-immunosorbent-assay was utilized to detect HBsAg in the peripheral blood of pregnant women and the femoral vein blood of their aborted fetuses. HBV-DNA in serum and peripheral blood mononuclear cells (PBMC) and GSTM1 alleles of pregnant women and their aborted fetuses were detected by nested polymerase chain reaction (PCR) and seminested PCR, respectively. We also examined the location of placenta HBsAg and HBcAb using immunohistochemical staining. The expression of placenta HBV-DNA was detected by in situ hybridization. For the 30 aborted fetuses, the HBV intrauterine infection rate was 43.33%. The HBV-positive rates of HBsAg in peripheral blood, serum, and PBMC were 10% (3/30), 23.33% (7/30), and 33.33% (10/30), respectively. Maternal-fetal PBMC transport was significantly positively correlated with fetal PBMC HBV-DNA (P = 0.004). Meanwhile, the rates of HBV infection gradually decreased from the maternal side to the fetus side of placenta (decidual cells > trophoblastic cells > villous mesenchymal cells > villous capillary endothelial cells). However, no significant correlation between placenta HBV infection and HBV intrauterine infection was observed (P = 0.410). HBV intrauterine infection was primarily due to peripheral blood mononuclear cell maternal-fetal transportation in the second trimester in pregnant women.

Minerals Masquerading As Enzymes: Abiotic Oxidation Of Soil Organic Matter In An Iron-Rich Humid Tropical Forest Soil

Science.gov (United States)

Hall, S. J.; Silver, W. L.

2010-12-01

Oxidative reactions play an important role in decomposing soil organic matter fractions that resist hydrolytic degradation, and fundamentally affect the cycling of recalcitrant soil carbon across ecosystems. Microbial extracellular oxidative enzymes (e.g. lignin peroxidases and laccases) have been assumed to provide a dominant role in catalyzing soil organic matter oxidation, while other potential oxidative mechanisms remain poorly explored. Here, we show that abiotic reactions mediated by the oxidation of ferrous iron (Fe(II)) could explain high potential oxidation rates in humid tropical forest soils, which often contain high concentrations of Fe(II) and experience rapid redox fluctuations between anaerobic and aerobic conditions. These abiotic reactions could provide an additional mechanism to explain high rates of decomposition in these ecosystems, despite frequent oxygen deficits. We sampled humid tropical forest soils in Puerto Rico, USA from various topographic positions, ranging from well-drained ridges to riparian valleys that experience broad fluctuations in redox potential. We measured oxidative activity by adding the model humic compound L-DOPA to soil slurries, followed by colorimetric measurements of the supernatant solution over time. Dilute hydrogen peroxide was added to a subset of slurries to measure peroxidative activity. We found that oxidative and peroxidative activity correlated positively with soil Fe(II) concentrations, counter to prevailing theory that low redox potential should suppress oxidative enzymes. Boiling or autoclaving sub-samples of soil slurries to denature any enzymes present typically increased peroxidative activity and did not eliminate oxidative activity, further suggesting the importance of an abiotic mechanism. We found substantial differences in the oxidation products of the L-DOPA substrate generated by our soil slurries in comparison with oxidation products generated by a purified enzyme (mushroom tyrosinase

Adsorption of antimony onto iron oxyhydroxides: Adsorption behavior and surface structure

Energy Technology Data Exchange (ETDEWEB)

Guo, Xuejun; Wu, Zhijun [State Key Laboratory of Water Environment Simulation, School of Environment, Beijing Normal University, No. 19 Xinjiekouwai Street, Beijing 100875 (China); He, Mengchang, E-mail: hemc@bnu.edu.cn [State Key Laboratory of Water Environment Simulation, School of Environment, Beijing Normal University, No. 19 Xinjiekouwai Street, Beijing 100875 (China); Meng, Xiaoguang [Center for Environmental Systems, Stevens Institute of Technology, Hoboken, NJ 07030 (United States); Jin, Xin [State Key Laboratory of Water Environment Simulation, School of Environment, Beijing Normal University, No. 19 Xinjiekouwai Street, Beijing 100875 (China); Qiu, Nan; Zhang, Jing [Beijing Synchrotron Radiation Facility (BSRF), Institute of High Energy Physics, Chinese Academy of Sciences, Beijing 100049 (China)

2014-07-15

Graphical abstract: - Highlights: • Antimony adsorption depended on the Sb species, pH, and the type of iron oxides. • Sb(V) adsorption favored at acidic pH, Sb(III) adsorption optimized in wider pH. • Antimony was adsorbed onto the iron oxides by the inner-sphere surface complex. • Bidentate mononuclear ({sup 2}E) was the dominant form of Sb incorporated into HFO. • XAFS and XPS indicated Sb(III) adsorbed was slowly oxidized to Sb(V). - Abstract: Antimony is detected in soil and water with elevated concentration due to a variety of industrial applications and mining activities. Though antimony is classified as a pollutant of priority interest by the United States Environmental Protection Agency (USEPA) and Europe Union (EU), very little is known about its environmental behavior and adsorption mechanism. In this study, the adsorption behaviors and surface structure of antimony (III/V) on iron oxides were investigated using batch adsorption techniques, surface complexation modeling (SCM), X-ray photon spectroscopy (XPS) and extended X-ray absorption fine structure spectroscopy (EXAFS). The adsorption isotherms and edges indicated that the affinity of Sb(V) and Sb(III) toward the iron oxides depended on the Sb species, solution pH, and the characteristics of iron oxides. Sb(V) adsorption was favored at acidic pH and decreased dramatically with increasing pH, while Sb(III) adsorption was constant over a broad pH range. When pH is higher than 7, Sb(III) adsorption by goethite and hydrous ferric oxide (HFO) was greater than Sb(V). EXAFS analysis indicated that the majority of Sb(III), either adsorbed onto HFO or co-precipitated by FeCl{sub 3}, was oxidized into Sb(V) probably due to the involvement of O{sub 2} in the long duration of sample preservation. Only one Sb–Fe subshell was filtered in the EXAFS spectra of antimony adsorption onto HFO, with the coordination number of 1.0–1.9 attributed to bidentate mononuclear edge-sharing ({sup 2}E) between Sb and

Independent Evolution of Six Families of Halogenating Enzymes.

Science.gov (United States)

Xu, Gangming; Wang, Bin-Gui

2016-01-01

Halogenated natural products are widespread in the environment, and the halogen atoms are typically vital to their bioactivities. Thus far, six families of halogenating enzymes have been identified: cofactor-free haloperoxidases (HPO), vanadium-dependent haloperoxidases (V-HPO), heme iron-dependent haloperoxidases (HI-HPO), non-heme iron-dependent halogenases (NI-HG), flavin-dependent halogenases (F-HG), and S-adenosyl-L-methionine (SAM)-dependent halogenases (S-HG). However, these halogenating enzymes with similar biological functions but distinct structures might have evolved independently. Phylogenetic and structural analyses suggest that the HPO, V-HPO, HI-HPO, NI-HG, F-HG, and S-HG enzyme families may have evolutionary relationships to the α/β hydrolases, acid phosphatases, peroxidases, chemotaxis phosphatases, oxidoreductases, and SAM hydroxide adenosyltransferases, respectively. These halogenating enzymes have established sequence homology, structural conservation, and mechanistic features within each family. Understanding the distinct evolutionary history of these halogenating enzymes will provide further insights into the study of their catalytic mechanisms and halogenation specificity.

Iron uptake and increased intracellular enzyme activity follow host lactoferrin binding by Trichomonas vaginalis receptors

Energy Technology Data Exchange (ETDEWEB)

Peterson, K.M.; Alderete, J.F.

1984-08-01

Lactoferrin acquisition and iron uptake by pathogenic Trichomonas vaginalis was examined. Saturation binding kinetics were obtained for trichomonads using increasing amounts of radioiodinated lactoferrin, while no significant binding by transferrin under similar conditions was achieved. Only unlabeled lactoferrin successfully and stoichiometrically competed with 125I-labeled lactoferrin binding. Time course studies showed maximal lactoferrin binding by 30 min at 37 degrees C. Data suggest no internalization of bound lactoferrin. The accumulation of radioactivity in supernatants after incubation of T. vaginalis with 125I-labeled lactoferrin and washing in PBS suggested the presence of low affinity sites for this host macromolecule. Scatchard analysis indicated the presence of 90,000 receptors per trichomonad with an apparent Kd of 1.0 microM. Two trichomonad lactoferrin binding proteins were identified by affinity chromatography and immunoprecipitation of receptor-ligand complexes. A 30-fold accumulation of iron was achieved using 59Fe-lactoferrin when compared to the steady state concentration of bound lactoferrin. The activity of pyruvate/ferrodoxin oxidoreductase, an enzyme involved in trichomonal energy metabolism, increased more than sixfold following exposure of the parasites to lactoferrin, demonstrating a biologic response to the receptor-mediated binding of lactoferrin. These data suggest that T. vaginalis possesses specific receptors for biologically relevant host proteins and that these receptors contribute to the metabolic processes of the parasites.

Iron uptake and increased intracellular enzyme activity follow host lactoferrin binding by Trichomonas vaginalis receptors

International Nuclear Information System (INIS)

Peterson, K.M.; Alderete, J.F.

1984-01-01

Lactoferrin acquisition and iron uptake by pathogenic Trichomonas vaginalis was examined. Saturation binding kinetics were obtained for trichomonads using increasing amounts of radioiodinated lactoferrin, while no significant binding by transferrin under similar conditions was achieved. Only unlabeled lactoferrin successfully and stoichiometrically competed with 125I-labeled lactoferrin binding. Time course studies showed maximal lactoferrin binding by 30 min at 37 degrees C. Data suggest no internalization of bound lactoferrin. The accumulation of radioactivity in supernatants after incubation of T. vaginalis with 125I-labeled lactoferrin and washing in PBS suggested the presence of low affinity sites for this host macromolecule. Scatchard analysis indicated the presence of 90,000 receptors per trichomonad with an apparent Kd of 1.0 microM. Two trichomonad lactoferrin binding proteins were identified by affinity chromatography and immunoprecipitation of receptor-ligand complexes. A 30-fold accumulation of iron was achieved using 59Fe-lactoferrin when compared to the steady state concentration of bound lactoferrin. The activity of pyruvate/ferrodoxin oxidoreductase, an enzyme involved in trichomonal energy metabolism, increased more than sixfold following exposure of the parasites to lactoferrin, demonstrating a biologic response to the receptor-mediated binding of lactoferrin. These data suggest that T. vaginalis possesses specific receptors for biologically relevant host proteins and that these receptors contribute to the metabolic processes of the parasites

Impaired T-lymphocyte colony formation by cord blood mononuclear cells

International Nuclear Information System (INIS)

Herrod, H.G.; Valenski, W.R.

1982-01-01

When compared to adult mononuclear cells, cord blood mononuclear cells demonstrated significantly decreased T-lymphocyte colony formation (1351 +/- 643 vs 592 +/- 862, P less than 0.01). This diminished colony-forming activity did not appear to be associated with impaired responsiveness to the stimulant phytohemagglutinin or with excessive suppressor-cell activity. Irradiation reduced the colony-forming capacity of cord blood mononuclear cells more than it did that of adult mononuclear cells. Depletion of adherent cells reduced cord blood mononuclear-cell colony-forming capacity by 40%, while similar treatment reduced adult colony formation by 10%. Lymphocyte proliferation in liquid culture of cord and adult cells was minimally affected by these procedures. The colony-forming capacity of cord blood could be enhanced by the addition of irradiated adult cells (284 +/- 72 vs 752 +/- 78, P less than 0.01). This enhancement was demonstrated to be due to a soluble factor produced by a population of irradiated adult cells depleted of the OKT8+ subpopulation of lymphocytes. These results indicate that the progenitor cells of T-lymphocyte colonies in cord blood have distinct biologic characteristics when compared to colony progenitors present in adult blood. This assay may prove to be useful in our efforts to understand the differentiation of T-cell function in man

Human and mouse mononuclear phagocyte networks: a tale of two species?

Directory of Open Access Journals (Sweden)

Gary eReynolds

2015-06-01

Full Text Available Dendritic cells (DCs, monocytes and macrophages are a heterogeneous population of mononuclear phagocytes that are involved in antigen processing and presentation to initiate and regulate immune responses to pathogens, vaccines, tumour and tolerance to self. In addition to their afferent sentinel function, DCs and macrophages are also critical as effectors and coordinators of inflammation and homeostasis in peripheral tissues. Harnessing DCs and macrophages for therapeutic purposes has major implications for infectious disease, vaccination, transplantation, tolerance induction, inflammation and cancer immunotherapy. There has been a paradigm shift in our understanding of the developmental origin and function of the cellular constituents of the mononuclear phagocyte system. Significant progress has been made in tandem in both human and mouse mononuclear phagocyte biology. This progress has been accelerated by comparative biology analysis between mouse and human, which has proved to be an exceptionally fruitful strategy to harmonise findings across species. Such analyses have provided unexpected insights and facilitated productive reciprocal and iterative processes to inform our understanding of human and mouse mononuclear phagocytes. In this review, we discuss the strategies, power and utility of comparative biology approaches to integrate recent advances in human and mouse mononuclear phagocyte biology and its potential to drive forward clinical translation of this knowledge. We also present a functional framework on the parallel organisation of human and mouse mononuclear phagocyte networks.

Anemia in chronic renal failure. Ferrokinetic, erythrocytes-survival time and enzymes of erythrocytes on chronic dialysed patients

Energy Technology Data Exchange (ETDEWEB)

Junkers, K; Jontofson, R; Meuret, G; Blume, K G; Heinze, V [Freie Univ. Berlin (F.R. Germany). Nuklearmedizinische Abt.; Freiburg Univ. (F.R. Germany). Nuklearmedizinische Abt.; Freiburg Univ. (F.R. Germany). Medizinische Poliklinik)

1975-12-01

Radio-iron utilization was nearly normal in these patients, only bilateral nephrectomized patients showed a reduced radio-iron utilization. Red blood half-life span was shortened in all patients, well corresponding to the degree of anemia. Parameters of erythropoesis like plasma iron clearance, bone marrow transit time, erythron iron turnover, non-erythron iron turnover and hemolysis iron turnover failed to quantitate disorders of red blood cell regeneration in these patients. No defect in red blood cell enzyme activity could be demonstrated. Enzymes of glycolysis were increased corresponding to the reduced erythrocyte half-life span.

Applications of biocatalysis in fragrance chemistry: the enantiomers of alpha-, beta-, and gamma-irones.

Science.gov (United States)

Brenna, Elisabetta; Fuganti, Claudio; Serra, Stefano

2008-11-01

The history of iris extracts, and of the isolation and enzyme-mediated synthesis of their odoriferous principle, the "irones", will be used to describe the improvement brought about by chemistry and biocatalysis in the development of natural fragrances. In particular, this tutorial review will discuss how the progress in the field of enzyme chemistry allowed the optimisation of accelerated procedures for the preparation of natural irone extracts, and the synthesis of all the ten isomers of irone, starting from commercial irone alpha.

Dinitrosyl iron complexes with glutathione as NO and NO⁺ donors.

Science.gov (United States)

Borodulin, Rostislav R; Kubrina, Lyudmila N; Mikoyan, Vasak D; Poltorakov, Alexander P; Shvydkiy, Vyacheslav О; Burbaev, Dosymzhan Sh; Serezhenkov, Vladimir A; Yakhontova, Elena R; Vanin, Anatoly F

2013-02-28

It has been found that heating of solutions of the binuclear form of dinitrosyl iron complexes (B-DNIC) with glutathione in a degassed Thunberg apparatus (рН 1.0, 70°С, 6 h) results in their decomposition with a concomitant release of four gaseous NO molecules per one B-DNIC. Further injection of air into the Thunberg apparatus initiates fast oxidation of NO to NO₂ and formation of two GS-NO molecules per one B-DNIC. Under similar conditions, the decomposition of B-DNIC solutions in the Thunberg apparatus in the presence of air is complete within 30-40 min and is accompanied by formation of four GS-NO molecules per one B-DNIC. It is suggested that the latter events are determined by oxidation of B-DNIC iron and concominant release of four nitrosonium ions (NO⁺) from each complex. Binding of NO⁺ to thiol groups of glutathione provokes GS-NO synthesis. At neutral рН, decomposition of B-DNIC is initiated by strong iron chelators, viz., о-phenanthroline and N-methyl-d-glucamine dithiocarbamate (MGD). In the former case, the reaction occurs under anaerobic conditions (degassed Thunberg apparatus) and is accompanied by a release of four NO molecules from B-DNIC. Under identical conditions, MGD-induced decomposition of B-DNIC gives two EPR-active mononuclear mononitrosyl iron complexes with MGD (MNIC-MGD) able to incorporate two iron molecules and two NO molecules from each B-DNIC. The other two NO molecules released from B-DNIC (most probably, in the form of nitrosonium ions) bind to thiol groups of MGD to give corresponding S-nitrosothiols. Acidification of test solutions to рН 1.0 initiates hydrolysis of MGD and, as a consequence, decomposition of MNIC-MGD and the S-nitrosated form of MGD; the gaseous phase contains four NO molecules (as calculated per each B-DNIC). The data obtained testify to the ability of B-DNIC with glutathione (and, probably, of B-DNIC with other thiol-containing ligands) to release both NO molecules and nitrosonium ions upon their

Iron-induced changes in the proteome of Trichomonas vaginalis hydrogenosomes.

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Neritza Campo Beltrán

Full Text Available Iron plays a crucial role in metabolism as a key component of catalytic and redox cofactors, such as heme or iron-sulfur clusters in enzymes and electron-transporting or regulatory proteins. Limitation of iron availability by the host is also one of the mechanisms involved in immunity. Pathogens must regulate their protein expression according to the iron concentration in their environment and optimize their metabolic pathways in cases of limitation through the availability of respective cofactors. Trichomonas vaginalis, a sexually transmitted pathogen of humans, requires high iron levels for optimal growth. It is an anaerobe that possesses hydrogenosomes, mitochondrion-related organelles that harbor pathways of energy metabolism and iron-sulfur cluster assembly. We analyzed the proteomes of hydrogenosomes obtained from cells cultivated under iron-rich and iron-deficient conditions employing two-dimensional peptide separation combining IEF and nano-HPLC with quantitative MALDI-MS/MS. We identified 179 proteins, of which 58 were differentially expressed. Iron deficiency led to the upregulation of proteins involved in iron-sulfur cluster assembly and the downregulation of enzymes involved in carbohydrate metabolism. Interestingly, iron affected the expression of only some of multiple protein paralogues, whereas the expression of others was iron independent. This finding indicates a stringent regulation of differentially expressed multiple gene copies in response to changes in the availability of exogenous iron.

Monovalent Cation Activation of the Radical SAM Enzyme Pyruvate Formate-Lyase Activating Enzyme.

Science.gov (United States)

Shisler, Krista A; Hutcheson, Rachel U; Horitani, Masaki; Duschene, Kaitlin S; Crain, Adam V; Byer, Amanda S; Shepard, Eric M; Rasmussen, Ashley; Yang, Jian; Broderick, William E; Vey, Jessica L; Drennan, Catherine L; Hoffman, Brian M; Broderick, Joan B

2017-08-30

Pyruvate formate-lyase activating enzyme (PFL-AE) is a radical S-adenosyl-l-methionine (SAM) enzyme that installs a catalytically essential glycyl radical on pyruvate formate-lyase. We show that PFL-AE binds a catalytically essential monovalent cation at its active site, yet another parallel with B 12 enzymes, and we characterize this cation site by a combination of structural, biochemical, and spectroscopic approaches. Refinement of the PFL-AE crystal structure reveals Na + as the most likely ion present in the solved structures, and pulsed electron nuclear double resonance (ENDOR) demonstrates that the same cation site is occupied by 23 Na in the solution state of the as-isolated enzyme. A SAM carboxylate-oxygen is an M + ligand, and EPR and circular dichroism spectroscopies reveal that both the site occupancy and the identity of the cation perturb the electronic properties of the SAM-chelated iron-sulfur cluster. ENDOR studies of the PFL-AE/[ 13 C-methyl]-SAM complex show that the target sulfonium positioning varies with the cation, while the observation of an isotropic hyperfine coupling to the cation by ENDOR measurements establishes its intimate, SAM-mediated interaction with the cluster. This monovalent cation site controls enzyme activity: (i) PFL-AE in the absence of any simple monovalent cations has little-no activity; and (ii) among monocations, going down Group 1 of the periodic table from Li + to Cs + , PFL-AE activity sharply maximizes at K + , with NH 4 + closely matching the efficacy of K + . PFL-AE is thus a type I M + -activated enzyme whose M + controls reactivity by interactions with the cosubstrate, SAM, which is bound to the catalytic iron-sulfur cluster.

Sensitization to epithelial antigens in chronic mucosal inflammatory disease. Characterization of human intestinal mucosa-derived mononuclear cells reactive with purified epithelial cell-associated components in vitro.

OpenAIRE

Roche, J K; Fiocchi, C; Youngman, K

1985-01-01

To explore the auto-reactive potential of cells infiltrating the gut mucosa in idiopathic chronic inflammatory bowel disease, intestinal lamina propria mononuclear cells (LPMC) were isolated, characterized morphologically and phenotypically, and evaluated for antigen-specific reactivity. The last was assessed by quantitating LPMC cytotoxic capabilities against purified, aqueous-soluble, organ-specific epithelial cell-associated components (ECAC) characterized previously. Enzyme-isolated infla...

Bio-inspired Iron Catalysts for Hydrocarbon Oxidations

Energy Technology Data Exchange (ETDEWEB)

Que, Jr., Lawrence [Univ. of Minnesota, Minneapolis, MN (United States)

2016-03-22

Stereoselective oxidation of C–H and C=C bonds are catalyzed by nonheme iron enzymes. Inspired by these bioinorganic systems, our group has been exploring the use of nonheme iron complexes as catalysts for the oxidation of hydrocarbons using H2O2 as an environmentally friendly and atom-efficient oxidant in order to gain mechanistic insights into these novel transformations. In particular, we have focused on clarifying the nature of the high-valent iron oxidants likely to be involved in these transformations.

Magnetically responsive enzyme powders

Czech Academy of Sciences Publication Activity Database

Pospišková, K.; Šafařík, Ivo

2015-01-01

Roč. 380, APR 2015 (2015), s. 197-200 ISSN 0304-8853 R&D Projects: GA MŠk(CZ) LD13021 Institutional support: RVO:67179843 Keywords : enzyme powders * cross-linking * magnetic modification * magnetic separation * magnetic iron oxides particles * microwave-assisted synthesis Subject RIV: CE - Biochemistry Impact factor: 2.357, year: 2015

Electrochemistry of Simple Organometallic Models of Iron-Iron Hydrogenases in Organic Solvent and Water.

Science.gov (United States)

Gloaguen, Frederic

2016-01-19

Synthetic models of the active site of iron-iron hydrogenases are currently the subjects of numerous studies aimed at developing H2-production catalysts based on cheap and abundant materials. In this context, the present report offers an electrochemist's view of the catalysis of proton reduction by simple binuclear iron(I) thiolate complexes. Although these complexes probably do not follow a biocatalytic pathway, we analyze and discuss the interplay between the reduction potential and basicity and how these antagonist properties impact the mechanisms of proton-coupled electron transfer to the metal centers. This question is central to any consideration of the activity at the molecular level of hydrogenases and related enzymes. In a second part, special attention is paid to iron thiolate complexes holding rigid and unsaturated bridging ligands. The complexes that enjoy mild reduction potentials and stabilized reduced forms are promising iron-based catalysts for the photodriven evolution of H2 in organic solvents and, more importantly, in water.

Sumatriptan increases the proliferation of peripheral blood mononuclear cells from HIV-infected individuals and healthy blood donors in vitro

DEFF Research Database (Denmark)

Afzelius, P; Nielsen, Jens Ole

2000-01-01

responsible for regulation of the intracellular levels of cAMP. In a preliminary study sumatriptan increased the proliferative responses of PBMC to a polyclonal activator in vitro in 9 of 10 HIV-seropositive individuals (p=0.007), and in 7 of 9 healthy blood donors (p=0.05). This was probably due...... of the intracellular second messenger adenosine 3',5'-cyclic monophosphate (cAMP) has been shown to cause impaired proliferative capacity of peripheral blood mononuclear cells (PBMC) from HIV-infected individuals in vitro. Sumatriptan, a 5HT1d receptor agonist, inhibits the activity of adenylyl cyclases, the enzymes...

Diversity and functions of intestinal mononuclear phagocytes

DEFF Research Database (Denmark)

Joeris, Thorsten; Müller-Luda, K; Agace, William Winston

2017-01-01

The intestinal lamina propria (LP) contains a diverse array of mononuclear phagocyte (MNP) subsets, including conventional dendritic cells (cDC), monocytes and tissue-resident macrophages (mφ) that collectively play an essential role in mucosal homeostasis, infection and inflammation. In the curr......The intestinal lamina propria (LP) contains a diverse array of mononuclear phagocyte (MNP) subsets, including conventional dendritic cells (cDC), monocytes and tissue-resident macrophages (mφ) that collectively play an essential role in mucosal homeostasis, infection and inflammation....... In the current review we discuss the function of intestinal cDC and monocyte-derived MNP, highlighting how these subsets play several non-redundant roles in the regulation of intestinal immune responses. While much remains to be learnt, recent findings also underline how the various populations of MNP adapt...

Phytases for improved iron absorption

DEFF Research Database (Denmark)

Nielsen, Anne Veller Friis; Meyer, Anne S.

2016-01-01

Phytase enzymes present an alternative to iron supplements, because they have been shown to improve iron absorption by means of catalysing the degradation of a potent iron absorption inhibitor: phytic acid. Phytic acid is a hexaphosphate of inositol and is particularly prevalent in cereal grains......, where it serves as a storage molecule for phosphorous. Phytic acid is also associated with minerals. The minerals are bound by chelation to the negatively charged phosphate groups in phytic acid. Phytases catalyse the dephosphorylation of phytic acid, thus releasing bound minerals to make them available...... for absorption. This article presents research on phytase catalysis in gastric conditions and considers potential benefits and drawbacks for using phytases as a food supplement....

Iron-mediated soil carbon response to water-table decline in an alpine wetland

Science.gov (United States)

Wang, Yiyun; Wang, Hao; He, Jin-Sheng; Feng, Xiaojuan

2017-06-01

The tremendous reservoir of soil organic carbon (SOC) in wetlands is being threatened by water-table decline (WTD) globally. However, the SOC response to WTD remains highly uncertain. Here we examine the under-investigated role of iron (Fe) in mediating soil enzyme activity and lignin stabilization in a mesocosm WTD experiment in an alpine wetland. In contrast to the classic `enzyme latch' theory, phenol oxidative activity is mainly controlled by ferrous iron [Fe(II)] and declines with WTD, leading to an accumulation of dissolvable aromatics and a reduced activity of hydrolytic enzyme. Furthermore, using dithionite to remove Fe oxides, we observe a significant increase of Fe-protected lignin phenols in the air-exposed soils. Fe oxidation hence acts as an `iron gate' against the `enzyme latch' in regulating wetland SOC dynamics under oxygen exposure. This newly recognized mechanism may be key to predicting wetland soil carbon storage with intensified WTD in a changing climate.

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

Sorptive Uptake Studies of an Aryl-Arsenical with Iron Oxide Composites on an Activated Carbon Support

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Jae H. Kwon

2014-03-01

Full Text Available Sorption uptake kinetics and equilibrium studies for 4-hydroxy-3-nitrobenzene arsonic acid (roxarsone was evaluated with synthetic magnetite (Mag-P, commercial magnetite (Mag-C, magnetite 10%, 19%, and 32% composite material (CM-10, -19, -32 that contains granular activated carbon (GAC, and synthetic goethite at pH 7.00 in water at 21 °C for 24 h. GAC showed the highest sorptive removal of roxarsone and the relative uptake for each sorbent material with roxarsone are listed in descending order as follows: GAC (471 mg/g > goethite (418 mg/g > CM-10 (377 mg/g CM-19 (254 mg/g > CM-32 (227 mg/g > Mag-P (132 mg/g > Mag-C (29.5 mg/g. The As (V moiety of roxarsone is adsorbed onto the surface of the iron oxide/oxyhydrate and is inferred as inner-sphere surface complexes; monodentate-mononuclear, bidentate-mononuclear, and bidentate-binuclear depending on the protolytic speciation of roxarsone. The phenyl ring of roxarsone provides the primary driving force for the sorptive interaction with the graphene surface of GAC and its composites. Thus, magnetite composites are proposed as multi-purpose adsorbents for the co-removal of inorganic and organic arsenicals due to the presence of graphenic and iron oxide active adsorption sites.

Freeze-quench (57)Fe-Mössbauer spectroscopy: trapping reactive intermediates.

Science.gov (United States)

Krebs, Carsten; Bollinger, J Martin

2009-01-01

(57)Fe-Mössbauer spectroscopy is a method that probes transitions between the nuclear ground state (I=1/2) and the first nuclear excited state (I=3/2). This technique provides detailed information about the chemical environment and electronic structure of iron. Therefore, it has played an important role in studies of the numerous iron-containing proteins and enzymes. In conjunction with the freeze-quench method, (57)Fe-Mössbauer spectroscopy allows for monitoring changes of the iron site(s) during a biochemical reaction. This approach is particularly powerful for detection and characterization of reactive intermediates. Comparison of experimentally determined Mössbauer parameters to those predicted by density functional theory for hypothetical model structures can then provide detailed insight into the structures of reactive intermediates. We have recently used this methodology to study the reactions of various mononuclear non-heme-iron enzymes by trapping and characterizing several Fe(IV)-oxo reaction intermediates. In this article, we summarize these findings and demonstrate the potential of the method. © Springer Science+Business Media B.V. 2009

Autologous bone marrow mononuclear cell delivery to dilated ...

African Journals Online (AJOL)

Autologous bone marrow mononuclear cell delivery to dilated cardiomyopathy patients: A clinical trial. PLN Kaparthi, G Namita, LK Chelluri, VSP Rao, PK Shah, A Vasantha, SK Ratnakar, K Ravindhranath ...

A Model Study on the Possible Effects of an External Electrical Field on Enzymes Having Dinuclear Iron Cluster [2Fe-2S

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Lemi Türker

2012-01-01

Full Text Available Hydrogenases which catalyze the H2 ↔ 2H+ + 2e− reaction are metalloenzymes that can be divided into two classes, the NiFe and Fe enzymes, on the basis of their metal content. Iron-sulfur clusters [2Fe-2S] and [4Fe-4S] are common in ironhydrogenases. In the present model study, [2Fe-2S] cluster has been considered to visualize the effect of external electric field on various quantum chemical properties of it. In the model, all the cysteinyl residues are in the amide form. The PM3 type semiempirical calculations have been performed for the geometry optimization of the model structure in the absence and presence of the external field. Then, single point DFT calculations (B3LYP/6-31+G(d have been carried out. Depending on the direction of the field, the chemical reactivity of the model enzyme varies which suggests that an external electric field could, under proper conditions, improve the enzymatic hydrogen production.

EPR Characterization of Dinitrosyl Iron Complexes with Thiol-Containing Ligands as an Approach to Their Identification in Biological Objects: An Overview.

Science.gov (United States)

Vanin, Anatoly F

2018-06-01

The overview demonstrates how the use of only one physico-chemical approach, viz., the electron paramagnetic resonance method, allowed detection and identification of dinitrosyl iron complexes with thiol-containing ligands in various animal and bacterial cells. These complexes are formed in biological objects in the paramagnetic (electron paramagnetic resonance-active) mononuclear and diamagnetic (electron paramagnetic resonance-silent) binuclear forms and control the activity of nitrogen monoxide, one of the most universal regulators of metabolic processes in the organism. The analysis of electronic and spatial structures of dinitrosyl iron complex sheds additional light on the mechanism whereby dinitrosyl iron complex with thiol-containing ligands function in human and animal cells as donors of nitrogen monoxide and its ionized form, viz., nitrosonium ions (NO + ).

Iron content and acid phosphatase activity in hepatic parenchymal lysosomes of patients with hemochromatosis before and after phlebotomy treatment

International Nuclear Information System (INIS)

Cleton, M.I.; de Bruijn, W.C.; van Blokland, W.T.; Marx, J.J.; Roelofs, J.M.; Rademakers, L.H.

1988-01-01

Lysosomal structures in liver parenchymal cells of 3 patients with iron overload and of 3 subjects without iron-storage disorders were investigated. A combination of enzyme cytochemistry--with cerium as a captive ion to demonstrate lysosomal acid phosphatase activity--and electron probe X-ray microanalysis (EPMA) was used. We were able (1) to define and quantify lysosomal structures as lysosomes, siderosomes, or residual bodies, (2) to quantify the amount of iron and cerium simultaneously in these structures, and (3) to evaluate a possible relation between iron storage and enzyme activity. With histopathologically increased iron storage, the number of siderosomes had increased at the cost of lysosomes, with a corresponding increase in acid phosphatase activity in both organelles. In histopahtologically severe iron overload, however, acid phosphatase activity was low or not detectable and most of the iron was stored in residual bodies. After phlebotomy treatment, the number of siderosomes had decreased in favor of the lysosomes, approaching values obtained in control subjects, and acid phosphatase activity was present in all iron-containing structures. In this way a relationship between iron storage and enzyme activity was established. The iron content of the individual lysosomal structures per unit area had increased with histopathologically increased iron storage and had decreased after phlebotomy treatment. From this observation, it is concluded that the iron status of the patient is not only reflected by the amount of iron-containing hepatocytes but, as well, by the iron content lysosomal unit area

Thiol dioxygenase turnover yields benzothiazole products from 2-mercaptoaniline and O2-dependent oxidation of primary alcohols.

Science.gov (United States)

Morrow, William P; Sardar, Sinjinee; Thapa, Pawan; Hossain, Mohammad S; Foss, Frank W; Pierce, Brad S

2017-10-01

Thiol dioxygenases are non-heme mononuclear iron enzymes that catalyze the O 2 -dependent oxidation of free thiols (-SH) to produce the corresponding sulfinic acid (-SO 2 - ). Previous chemical rescue studies identified a putative Fe III -O 2 - intermediate that precedes substrate oxidation in Mus musculus cysteine dioxygenase (Mm CDO). Given that a similar reactive intermediate has been identified in the extradiol dioxygenase 2, 3-HCPD, it is conceivable that these enzymes share other mechanistic features with regard to substrate oxidation. To explore this possibility, enzymatic reactions with Mm CDO (as well as the bacterial 3-mercaptopropionic acid dioxygenase, Av MDO) were performed using a substrate analogue (2-mercaptoaniline, 2ma). This aromatic thiol closely approximates the catecholic substrate of homoprotocatechuate of 2, 3-HPCD while maintaining the 2-carbon thiol-amine separation preferred by Mm CDO. Remarkably, both enzymes exhibit 2ma-gated O 2 -consumption; however, none of the expected products for thiol dioxygenase or intra/extradiol dioxygenase reactions were observed. Instead, benzothiazoles are produced by the condensation of 2ma with aldehydes formed by an off-pathway oxidation of primary alcohols added to aqueous reactions to solubilize the substrate. The observed oxidation of 1º-alcohols in 2ma-reactions is consistent with the formation of a high-valent intermediate similar to what has been reported for cytochrome P450 and mononuclear iron model complexes. Copyright © 2017 Elsevier Inc. All rights reserved.

Proteomic analysis of iron acquisition, metabolic and regulatory responses of Yersinia pestis to iron starvation

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Fleischmann Robert D

2010-01-01

Full Text Available Abstract Background The Gram-negative bacterium Yersinia pestis is the causative agent of the bubonic plague. Efficient iron acquisition systems are critical to the ability of Y. pestis to infect, spread and grow in mammalian hosts, because iron is sequestered and is considered part of the innate host immune defence against invading pathogens. We used a proteomic approach to determine expression changes of iron uptake systems and intracellular consequences of iron deficiency in the Y. pestis strain KIM6+ at two physiologically relevant temperatures (26°C and 37°C. Results Differential protein display was performed for three Y. pestis subcellular fractions. Five characterized Y. pestis iron/siderophore acquisition systems (Ybt, Yfe, Yfu, Yiu and Hmu and a putative iron/chelate outer membrane receptor (Y0850 were increased in abundance in iron-starved cells. The iron-sulfur (Fe-S cluster assembly system Suf, adapted to oxidative stress and iron starvation in E. coli, was also more abundant, suggesting functional activity of Suf in Y. pestis under iron-limiting conditions. Metabolic and reactive oxygen-deactivating enzymes dependent on Fe-S clusters or other iron cofactors were decreased in abundance in iron-depleted cells. This data was consistent with lower activities of aconitase and catalase in iron-starved vs. iron-rich cells. In contrast, pyruvate oxidase B which metabolizes pyruvate via electron transfer to ubiquinone-8 for direct utilization in the respiratory chain was strongly increased in abundance and activity in iron-depleted cells. Conclusions Many protein abundance differences were indicative of the important regulatory role of the ferric uptake regulator Fur. Iron deficiency seems to result in a coordinated shift from iron-utilizing to iron-independent biochemical pathways in the cytoplasm of Y. pestis. With growth temperature as an additional variable in proteomic comparisons of the Y. pestis fractions (26°C and 37°C, there was

Superoxide scavenging activity of pirfenidone-iron complex

International Nuclear Information System (INIS)

Mitani, Yoshihiro; Sato, Keizo; Muramoto, Yosuke; Karakawa, Tomohiro; Kitamado, Masataka; Iwanaga, Tatsuya; Nabeshima, Tetsuji; Maruyama, Kumiko; Nakagawa, Kazuko; Ishida, Kazuhiko; Sasamoto, Kazumi

2008-01-01

Pirfenidone (PFD) is focused on a new anti-fibrotic drug, which can minimize lung fibrosis etc. We evaluated the superoxide (O 2 ·- ) scavenging activities of PFD and the PFD-iron complex by electron spin resonance (ESR) spectroscopy, luminol-dependent chemiluminescence assay, and cytochrome c reduction assay. Firstly, we confirmed that the PFD-iron complex was formed by mixing iron chloride with threefold molar PFD, and the complex was stable in distillated water and ethanol. Secondary, the PFD-iron complex reduced the amount of O 2 ·- produced by xanthine oxidase/hypoxanthine without inhibiting the enzyme activity. Thirdly, it also reduced the amount of O 2 ·- released from phorbor ester-stimulated human neutrophils. PFD alone showed few such effects. These results suggest the possibility that the O 2 ·- scavenging effect of the PFD-iron complex contributes to the anti-fibrotic action of PFD used for treating idiopathic pulmonary fibrosis

Ceruloplasmin-ferroportin system of iron traffic in vertebrates

Institute of Scientific and Technical Information of China (English)

Giovanni; Musci; Fabio; Polticelli; Maria; Carmela; Bonaccorsi; di; Patti

2014-01-01

Safe trafficking of iron across the cell membrane is a delicate process that requires specific protein carriers. While many proteins involved in iron uptake by cells are known, only one cellular iron export protein has been identified in mammals: ferroportin(SLC40A1). Ceruloplasmin is a multicopper enzyme endowed with ferroxidase activity that is found as a soluble isoform in plasma or as a membrane-associated isoform in specific cell types. According to the currently accepted view, ferrous iron transported out of the cell by ferroportin would be safely oxidized by ceruloplasmin to facilitate loading on transferrin. Therefore, the ceruloplasminferroportin system represents the main pathway for cellular iron egress and it is responsible for physiological regulation of cellular iron levels. The most recent findings regarding the structural and functional features of ceruloplasmin and ferroportin and their relationship will be described in this review.

Electronic and Spatial Structures of Water-Soluble Dinitrosyl Iron Complexes with Thiol-Containing Ligands Underlying Their Ability to Act as Nitric Oxide and Nitrosonium Ion Donors

OpenAIRE

Vanin, Anatoly F.; Burbaev, Dosymzhan Sh.

2011-01-01

The ability of mononuclear dinitrosyl iron commplexes (M-DNICs) with thiolate ligands to act as NO donors and to trigger S-nitrosation of thiols can be explain only in the paradigm of the model of the [Fe+(NO+)2] core ({Fe(NO)2}7 according to the Enemark-Feltham classification). Similarly, the {(RS−)2Fe+(NO+)2}+ structure describing the distribution of unpaired electron density in M-DNIC corresponds to the low-spin (S = 1/2) state with a d7 electron configuration of the iron atom and predomin...

Relationship between elevated liver enzyme with iron overload and viralhepatitis in thalassemia major patients in Northern Iran

International Nuclear Information System (INIS)

Ameli, M.; Besharati, S.; Nemati, K.; Zamani, F.

2008-01-01

Objective was to determine the relationship between elevated liverenzymes with iron overload and viral hepatitis in thalassemia patients. Thisdescriptive cross-sectional study was carried out in the thalassemic ward ofTonekabon Hospital, Mazandaran, Northern Iran from 20 April to 20 Septemberof 2006. Patients were studied with respect to age, liver enzymes,anti-hepatitis C virus (anti-HCV) antibody and hepatitis B surface antigen(HBsAg), transferring saturation (TSAT)and blood transfusion index(multiplication of frequency and units of transfusion). Alanineaminotransferase (ALT) >=40 U/L was considered elevated. Sixty-five patientswere evaluated (median age 19.51+-8.9 years, range 4-54). Eleven patientswere anti-HCV positive (16.9%). The mean serum ferritin was significantlyhigher in patients with ALT>=40 (2553.08 ug/L versus 1783.7750 ug/L)(p=0.012). The mean ALT was significantly higher in patients with TSAT >=60%(41.26 U/L versus 28.82 U/L) (p=0.021). The relationship between ALT>=40 andanti-HCV positively was statistically significant. The mean ALT was 60.91 U/Lin anti-HCV positive patients and 39.29 U/L in the negative group (p=0.001).The mean serum iron and transfusion index were significantly higher inanti-HCV positive versus negative patients (234.0 versus 195.4815; p=0.02),(1693.6 versus 1036.29, p=0.014). Close association between elevated ALT withiron overload, transfusion index, age and anti-HCV positivity in thalassemiapatients of Tonekabon is recommended to re-evaluate transfusion and Desferaldoses and therapies other than blood transfusion. (author)

Effect of zero-valent iron and trivalent iron on UASB rapid start-up.

Science.gov (United States)

Wang, Jie; Fang, Hongyan; Jia, Hui; Yang, Guang; Gao, Fei; Liu, Wenbin

2018-01-01

In order to realize the rapid start-up of upflow anaerobic sludge blanket (UASB) reactor, the iron ion in different valence state was added to UASB. The results indicated that the start-up time of R3 (FeCl 3 ) was 48 h faster than that of R2 (zero-valent iron (ZVI)). It was because the FeCl 3 could rapidly promote granulation of sludge as a flocculant. However, ZVI released Fe 2+ through corrosion slowly, and then the Fe 2+ increased start-up speed by enhancing enzyme activity and enriching methanogens. In addition, the ZVI and FeCl 3 could promote hydrolysis acidification and strengthen the decomposition of long-chain fatty acids. The detection of iron ions showed that iron ions mainly existed in the sludge. Because the high concentration of Fe 2+ could inhibit anaerobic bacteria activity, excess Fe 3+ could be changed into iron hydroxide precipitation to hinder the mass transfer process of anaerobic bacteria under the alkaline condition. The FeCl 3 was suitable to be added at the initial stage of UASB start-up, and the ZVI was more fitted to be used in the middle stage of reactor start-up to improve the redox ability.

Identification of the iron-sulfur center of spinach ferredoxin-nitrite reductase as a tetranuclear center, and preliminary EPR studies of mechanism.

Science.gov (United States)

Lancaster, J R; Vega, J M; Kamin, H; Orme-Johnson, N R; Orme-Johnson, W H; Krueger, R J; Siegel, L M

1979-02-25

EPR spectroscopic and chemical analyses of spinach nitrite reductase show that the enzyme contains one reducible iron-sulfur center, and one site for binding either cyanide or nitrite, per siroheme. The heme is nearly all in the high spin ferric state in the enzyme as isolated. The extinction coefficient of the enzyme has been revised to E386 = 7.6 X 10(4) cm-1 (M heme)-1. The iron-sulfur center is reduced with difficulty by agents such as reduced methyl viologen (equilibrated with 1 atm of H2 at pH 7.7 in the presence of hydrogenase) or dithionite. Complexation of the enzyme with CO (a known ligand for nitrite reductase heme) markedly increases the reducibility of the iron-sulfur center. New chemical analyses and reinterpretation of previous data show that the enzyme contains 6 mol of iron and 4 mol of acid-labile S2-/mol of siroheme. The EPR spectrum of reduced nitrite reductase in 80% dimethyl sulfoxide establishes clearly that the enzyme contains a tetranuclear iron-sulfur (Fe4S4) center. The ferriheme and Fe4S4 centers are reduced at similar rates (k = 3 to 4 s-1) by dithionite. The dithionite-reduced Fe4S4 center is rapidly (k = 100 s-1) reoxidized by nitrite. These results indicate a role for the Fe4S4 center in catalysis.

Clinical study on insulin receptors of mononuclear cells in diabetes

Energy Technology Data Exchange (ETDEWEB)

Dalimunthe, D [Hiroshima Univ. (Japan). School of Medicine

1980-12-01

/sup 125/I-insulin binding activity to mononuclear cells was studied in 75 noninsulin-dependent diabetic subjects and 31 normal subjects and the following results were obtained. 1. /sup 125/I-insulin binding is directly proportional to the mononuclear cell concentrations. There is a linear increase of specific /sup 125/I-insulin binding. 2. The binding of /sup 125/I-insulin to mononuclear cells is displaced by the increasing concentration of native insulin. 3. The /sup 125/I-insulin degradation in the incubation medium after incubation of mononuclear cells for 24 hours at 4/sup 0/C was almost 5% in this study. 4. The insulin binding activity in diabetic subjects was lower than that in normal subjects (P < 0.001) without any significant difference in affinity constant. 5. The relationship of binding activity to age of diabetics (r = 0.06, N.S), relative body weitht (r = 0.06, N.S) and duration of diabetes from onset was not significant. 6. In untreated noninsulin-dependent diabetics the insulin binding activity was inversely correlated to fasting blood glucose level (r = 0.78, P < 0.001) and slightly inversely correlated to serum insulin level (r = 0.47, P < 0.01). A slight inverse correlation was also observed in serum triglyceride level (r = 0.53, P < 0.01) and in total cholesterol level (r = 0.29, P < 0.05). 7. No significant difference between the binding activity was observed by grade of diabetic retinopathy. 8. After treatment with diet and/or sulfonylurea, the diabetics exhibited a significant increase in insulin binding activity (P < 0.005) but no significant difference in plasma insulin level, body weight and plasma lipid levels was observed.

Plasmodium and mononuclear phagocytes.

Science.gov (United States)

Mac-Daniel, Laura; Ménard, Robert

2015-01-01

Plasmodium, the causative agent of malaria, initially multiplies inside liver cells and then in successive cycles inside erythrocytes, causing the symptoms of the disease. In this review, we discuss interactions between the extracellular and intracellular forms of the Plasmodium parasite and innate immune cells in the mammalian host, with a special emphasis on mononuclear phagocytes. We overview here what is known about the innate immune cells that interact with parasites, mechanisms used by the parasite to evade them, and the protective or detrimental contribution of these interactions on parasite progression through its life cycle and pathology in the host. Copyright © 2014 Elsevier Ltd. All rights reserved.

Regeneration of the liver at different periods of mononuclear infiltration induced by zymosan granules

International Nuclear Information System (INIS)

Shcherbakov, V.I.; Komlyagina, T.G.; Mayanskii, D.N.

1985-01-01

The aim of this investigation was to discover how the liver,with areas of mononuclear infiltration, developing in response to activation of Kupffer cells (KC) by zymosan granules (ZG), regenerates. In the experiments, an intraperitoneal injection of 1 microCi of 3 H-thymidine/g body weight was given to the mice 1 h before sacrifice. Proliferation of hepatocytes and regeneration of the liver were intensified most when partial resection of the liver (PRL) was performed at the peak of mononuclear infiltration of the liver, namely five days after injection of ZG. The data indicate that not only activated KC, but also areas of mononuclear infiltration potentiate hepatocyte regeneration

Oxidation of ethane to ethanol by N2O in a metal-organic framework with coordinatively unsaturated iron(II) sites.

Science.gov (United States)

Xiao, Dianne J; Bloch, Eric D; Mason, Jarad A; Queen, Wendy L; Hudson, Matthew R; Planas, Nora; Borycz, Joshua; Dzubak, Allison L; Verma, Pragya; Lee, Kyuho; Bonino, Francesca; Crocellà, Valentina; Yano, Junko; Bordiga, Silvia; Truhlar, Donald G; Gagliardi, Laura; Brown, Craig M; Long, Jeffrey R

2014-07-01

Enzymatic haem and non-haem high-valent iron-oxo species are known to activate strong C-H bonds, yet duplicating this reactivity in a synthetic system remains a formidable challenge. Although instability of the terminal iron-oxo moiety is perhaps the foremost obstacle, steric and electronic factors also limit the activity of previously reported mononuclear iron(IV)-oxo compounds. In particular, although nature's non-haem iron(IV)-oxo compounds possess high-spin S = 2 ground states, this electronic configuration has proved difficult to achieve in a molecular species. These challenges may be mitigated within metal-organic frameworks that feature site-isolated iron centres in a constrained, weak-field ligand environment. Here, we show that the metal-organic framework Fe2(dobdc) (dobdc(4-) = 2,5-dioxido-1,4-benzenedicarboxylate) and its magnesium-diluted analogue, Fe0.1Mg1.9(dobdc), are able to activate the C-H bonds of ethane and convert it into ethanol and acetaldehyde using nitrous oxide as the terminal oxidant. Electronic structure calculations indicate that the active oxidant is likely to be a high-spin S = 2 iron(IV)-oxo species.

CHRONIC HEART FAILURE AND IRON-DEFICIENT ANEMIA

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M. V. Melnik

2015-12-01

Full Text Available 62 chronic heart failure (CHF patients with iron-deficient anemia (IDA were studied. Standard CHF therapy (angiotensin converting enzyme inhibitors, β-blockers, diuretics, cardiac glycosides was accompanied with the correction of iron deficiency by intravenous injection of Venofer and subsequent Ferro-Folgamma prescription (average daily dose of iron 137,75±5mg. After treatment serum iron level increased by 95,5% and hemoglobin level – by 9,8%. Left ventricular ejection fraction increased by 32,2% and physical activity tolerance – by 47,6%. Before treatment 32 CHF patients with IDA (51,6% had III functional class (FC of CHF according to NYHA and 16 patients (25,8% – IV FC. After treatment I FC was observed in 18 CHF patients (29%, II FC – in 26 patients and only 18 patients demonstrated III FC of CHF.

CHRONIC HEART FAILURE AND IRON-DEFICIENT ANEMIA

Directory of Open Access Journals (Sweden)

M. V. Melnik

2007-01-01

Full Text Available 62 chronic heart failure (CHF patients with iron-deficient anemia (IDA were studied. Standard CHF therapy (angiotensin converting enzyme inhibitors, β-blockers, diuretics, cardiac glycosides was accompanied with the correction of iron deficiency by intravenous injection of Venofer and subsequent Ferro-Folgamma prescription (average daily dose of iron 137,75±5mg. After treatment serum iron level increased by 95,5% and hemoglobin level – by 9,8%. Left ventricular ejection fraction increased by 32,2% and physical activity tolerance – by 47,6%. Before treatment 32 CHF patients with IDA (51,6% had III functional class (FC of CHF according to NYHA and 16 patients (25,8% – IV FC. After treatment I FC was observed in 18 CHF patients (29%, II FC – in 26 patients and only 18 patients demonstrated III FC of CHF.

Influence and interaction of iron and cadmium on photosynthesis and antioxidative enzymes in two rice cultivars.

Science.gov (United States)

Liu, Houjun; Zhang, Chengxin; Wang, Junmei; Zhou, Chongjun; Feng, Huan; Mahajan, Manoj D; Han, Xiaori

2017-03-01

In this study, a soil pot experiment was conducted to investigate the changes in photosynthesis and antioxidative enzymes in two rice varieties (Shendao 6 and Shennong 265) supplied with iron (Fe), cadmium (Cd), and Fe and Cd together. The concentrations of Fe and Cd in the soil were 0, 1.0 g Fe·kg -1 and 0, 2.0 mg Cd·kg -1 , respectively. Photosynthetic indices and antioxidative enzyme activities were recorded at different rice growth stages. At the early stage, Cd showed a transient stimulatory effect on the photosynthetic rate of Shennong 265. For Shendao 6, however, Cd showed a transient stimulatory effect on photosynthetic rate, intercellular CO 2 concentration, stomatal conductance and transpiration efficiency. In addition, the results show that Cd can also enhance the superoxide dismutase (SOD) and peroxidase (POD) activities, but reduce the malondialdehyde (MDA) and soluble protein contents in the two rice cultivars. Subsequently, Cd starts to inhibit photosynthesis and SOD activity until the ripening stage, causing the lowest photosynthetic rate and SOD activity at this stage. In contrast, Fe alleviates the Cd-induced changes at earlier or later growth stage. Notably at the later growth stage, the results show that the interaction between Fe and Cd increases the SOD and catalase (CAT) activities, while decreasing the lipid peroxidation and promoting photosynthesis. As a result, it ultimately increases the biomass. The results from this study suggest that Fe (as Fe fertilizer) is a promising alternative for agricultural use to enhance the plant development and, simultaneously, to reduce Cd toxicity in extensively polluted soils. Copyright © 2016 Elsevier Ltd. All rights reserved.

Lactam hydrolysis catalyzed by mononuclear metallo-ß-bactamases

DEFF Research Database (Denmark)

Olsen, Lars; Antony, J; Ryde, U

2003-01-01

Two central steps in the hydrolysis of lactam antibiotics catalyzed by mononuclear metallo-beta-lactamases, formation of the tetrahedral intermediate and its breakdown by proton transfer, are studied for model systems using the density functional B3LYP method. Metallo-beta-lactamases have two metal...

Effect of human polymorphonuclear and mononuclear leukocytes on chromosomal and plasmid DNA of Escherichia coli. Role of acid DNase

International Nuclear Information System (INIS)

Rozenberg-Arska, M.; van Strijp, J.A.; Hoekstra, W.P.; Verhoef, J.

1984-01-01

Phagocytosis and killing by polymorphonuclear and mononuclear leukocytes are important host resistance factors against invading microorganisms. Evidence showing that killing is rapidly followed by degradation of bacterial components is limited. Therefore, we studied the fate of Escherichia coli DNA following phagocytosis of E. coli by polymorphonuclear and mononuclear leukocytes. [ 3 H]Thymidine-labeled, unencapsulated E. coli PC2166 and E. coli 048K1 were incubated in serum, washed, and added to leukocytes. Uptake and killing of the bacteria and degradation of DNA were measured. Although phagocytosis and killing by mononuclear leukocytes was less efficient than that by polymorphonuclear leukocytes, only mononuclear leukocytes were able to degrade E. coli PC2166 DNA. Within 2 h, 60% of the radioactivity added to mononuclear leukocytes was released into the supernate, of which 40% was acid soluble. DNA of E. coli 048K1 was not degraded. To further analyze the capacity of mononuclear leukocytes to degrade E. coli DNA, chromosomal and plasmid DNA was isolated from ingested bacteria and subjected to agarose gel-electrophoresis. Only chromosomal DNA was degraded after phagocytosis. Plasmid DNA of E. coli carrying a gene coding for ampicillin resistance remained intact for a 2-h period after ingestion, and was still able to transform recipient E. coli cells after this period. Although we observed no DNA degradation during phagocytosis by polymorphonuclear leukocytes, lysates of both polymorphonuclear and mononuclear leukocytes contained acid-DNase activity with a pH optimum of 4.9. However, the DNase activity of mononuclear leukocytes was 20 times higher than that of polymorphonuclear leukocytes. No difference was observed between DNase activity from polymorphonuclear and mononuclear leukocytes from a chronic granulomatous disease patient with DNase activity from control polymorphonuclear and mononuclear leukocytes

Dietary iron controls circadian hepatic glucose metabolism through heme synthesis.

Science.gov (United States)

Simcox, Judith A; Mitchell, Thomas Creighton; Gao, Yan; Just, Steven F; Cooksey, Robert; Cox, James; Ajioka, Richard; Jones, Deborah; Lee, Soh-Hyun; King, Daniel; Huang, Jingyu; McClain, Donald A

2015-04-01

The circadian rhythm of the liver maintains glucose homeostasis, and disruption of this rhythm is associated with type 2 diabetes. Feeding is one factor that sets the circadian clock in peripheral tissues, but relatively little is known about the role of specific dietary components in that regard. We assessed the effects of dietary iron on circadian gluconeogenesis. Dietary iron affects circadian glucose metabolism through heme-mediated regulation of the interaction of nuclear receptor subfamily 1 group d member 1 (Rev-Erbα) with its cosuppressor nuclear receptor corepressor 1 (NCOR). Loss of regulated heme synthesis was achieved by aminolevulinic acid (ALA) treatment of mice or cultured cells to bypass the rate-limiting enzyme in hepatic heme synthesis, ALA synthase 1 (ALAS1). ALA treatment abolishes differences in hepatic glucose production and in the expression of gluconeogenic enzymes seen with variation of dietary iron. The differences among diets are also lost with inhibition of heme synthesis with isonicotinylhydrazine. Dietary iron modulates levels of peroxisome proliferator-activated receptor γ coactivator 1α (PGC-1α), a transcriptional activator of ALAS1, to affect hepatic heme. Treatment of mice with the antioxidant N-acetylcysteine diminishes PGC-1α variation observed among the iron diets, suggesting that iron is acting through reactive oxygen species signaling. © 2015 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.

Use of 99mTc-Mononuclear Leukocyte Scintigraphy in Nosocomial Fever

International Nuclear Information System (INIS)

Gutfilen, B.; Lopes de Souza, S.A.; Martins, F.P.P.; Cardoso, L.R.; Pinheiro Pessoa, M.C.; Fonseca, L.M.B.

2006-01-01

Purpose: To determine the overall diagnostic accuracy of mononuclear leukocyte- 99m Tc scintigraphy in the routine detection of infectious lesions and fever of unknown origin (FUO) in inpatients. Material and Methods: The use of mononuclear leukocyte 99m Tc scintigraphy is presented in 87 patients who fulfilled the Durack and Street diagnostic criteria of nosocomial FUO; 66 patients were suspected of having infectious lesions (myocarditis, endocarditis, infected catheters, diabetic foot, and osteomyelitis) and 21 patients presented with unknown causes of FUO. Scans were carried out 1, 3, and 24 h after injection of labeled leukocytes. Results: In three cases (3/27) where scintigraphs were negative, biopsies were positive. There were two (2/87) false-positive scintigrams. We found a 95.8% sensitivity and 92.3% specificity. PPV was 93.8%, PPN 94.7%, and accuracy 94.2%. Conclusion: Mononuclear leukocyte 99m Tc scintigraphy showed high sensitivity, specificity, positive and negative predictive values in patients with nosocomial FUO. These results suggest an important role for nuclear medicine in the management of patients with infection/inflammation

Ethylene biosynthesis by 1-aminocyclopropane-1-carboxylic acid oxidase: a DFT study.

Science.gov (United States)

Bassan, Arianna; Borowski, Tomasz; Schofield, Christopher J; Siegbahn, Per E M

2006-11-24

The reaction catalyzed by the plant enzyme 1-aminocyclopropane-1-carboxylic acid oxidase (ACCO) was investigated by using hybrid density functional theory. ACCO belongs to the non-heme iron(II) enzyme superfamily and carries out the bicarbonate-dependent two-electron oxidation of its substrate ACC (1-aminocyclopropane-1-carboxylic acid) concomitant with the reduction of dioxygen and oxidation of a reducing agent probably ascorbate. The reaction gives ethylene, CO(2), cyanide and two water molecules. A model including the mononuclear iron complex with ACC in the first coordination sphere was used to study the details of O-O bond cleavage and cyclopropane ring opening. Calculations imply that this unusual and complex reaction is triggered by a hydrogen atom abstraction step generating a radical on the amino nitrogen of ACC. Subsequently, cyclopropane ring opening followed by O-O bond heterolysis leads to a very reactive iron(IV)-oxo intermediate, which decomposes to ethylene and cyanoformate with very low energy barriers. The reaction is assisted by bicarbonate located in the second coordination sphere of the metal.

The production of collagenase by adherent mononuclear cells cultured from human peripheral blood.

Science.gov (United States)

Louie, J S; Weiss, J; Ryhänen, L; Nies, K M; Rantala-Ryhänen, S; Uitto, J

1984-12-01

Mononuclear cells were isolated from human peripheral blood by Ficoll-Hypaque centrifugation, and the cells adherent to plastic substrata were cultured in serum-free media supplemented with lactalbumin hydrolysate. These cell cultures, which consisted predominantly of monocyte-macrophages as judged by nonspecific esterase staining, accumulated collagenase in the medium. This collagenase resembled other vertebrate collagenases in that it cleaved native triple-helical type I collagen at a locus 3/4-length away from the amino-terminal end of the molecule. The collagenase activity was inhibited by Na2EDTA, dithiothreitol, and fetal calf serum, while the addition of Ca++ or N-ethylmaleimide enhanced the enzyme activity. The accumulation of collagenase in the culture media was markedly enhanced by the incubation of cells with concanavalin A or phorbol myristic acetate. In the presence of cycloheximide, the levels of collagenase activity were markedly reduced, suggesting that active protein synthesis was required to express the enzyme activity. In additional experiments, monocytes were further purified by counterflow centrifugation-elutriation. The collagenase production was markedly increased in cultures enriched in monocyte-macrophages and devoid of polymorphonuclear leukocytes. The accumulation of collagenase in monocyte cultures incubated for 48 hours in the presence of concanavalin A or phorbol myristic acetate was of the same order of magnitude as in parallel cultures containing the same number of polymorphonuclear leukocytes purified by Ficoll-Hypaque centrifugation and Plasmagel sedimentation.(ABSTRACT TRUNCATED AT 250 WORDS)

Magnetic tumor targeting of β-glucosidase immobilized iron oxide nanoparticles

Science.gov (United States)

Zhou, Jie; Zhang, Jian; David, Allan E.; Yang, Victor C.

2013-09-01

Directed enzyme/prodrug therapy (DEPT) has promising application for cancer therapy. However, most current DEPT strategies face shortcomings such as the loss of enzyme activity during preparation, low delivery and transduction efficiency in vivo and difficultly of monitoring. In this study, a novel magnetic directed enzyme/prodrug therapy (MDEPT) was set up by conjugating β-glucosidase (β-Glu) to aminated, starch-coated, iron oxide magnetic iron oxide nanoparticles (MNPs), abbreviated as β-Glu-MNP, using glutaraldehyde as the crosslinker. This β-Glu-MNP was then characterized in detail by size distribution, zeta potential, FTIR spectra, TEM, SQUID and magnetophoretic mobility analysis. Compared to free enzyme, the conjugated β-Glu on MNPs retained 85.54% ± 6.9% relative activity and showed much better temperature stability. The animal study results showed that β-Glu-MNP displays preferable pharmacokinetics characteristics in relation to MNPs. With an adscititious magnetic field on the surface of a tumor, a significant quantity of β-Glu-MNP was selectively delivered into a subcutaneous tumor of a glioma-bearing mouse. Remarkably, the enzyme activity of the delivered β-Glu in tumor lesions showed as high as 20.123±5.022 mU g-1 tissue with 2.14 of tumor/non-tumor β-Glu activity.

Nonheme oxoiron(IV) complexes of pentadentate N5 ligands: spectroscopy, electrochemistry, and oxidative reactivity

OpenAIRE

Wang, Dong; Ray, Kallol; Collins, Michael J.; Farquhar, Erik R.; Frisch, Jonathan R.; Gomez, Laura; Jackson, Timothy A.; Kerscher, Marion; Waleska, Arkadius; Comba, Peter; Costas, Miquel; Que, Lawrence, Jr.

2013-01-01

Oxoiron(IV) species have been found to act as the oxidants in the catalytic cycles of several mononuclear nonheme iron enzymes that activate dioxygen. To gain insight into the factors that govern the oxidative reactivity of such complexes, a series of five synthetic S = 1 [FeIV(O)(LN5)]2+ complexes has been characterized with respect to their spectroscopic and electrochemical properties as well as their relative abilities to carry out oxo transfer and hydrogen atom abstraction. The Fe=O units...

Iron Homeostasis in Peripheral Nervous System, Still a Black Box?

Science.gov (United States)

Taveggia, Carla

2014-01-01

Abstract Significance: Iron is the most abundant transition metal in biology and an essential cofactor for many cellular enzymes. Iron homeostasis impairment is also a component of peripheral neuropathies. Recent Advances: During the past years, much effort has been paid to understand the molecular mechanism involved in maintaining systemic iron homeostasis in mammals. This has been stimulated by the evidence that iron dyshomeostasis is an initial cause of several disorders, including genetic and sporadic neurodegenerative disorders. Critical Issues: However, very little has been done to investigate the physiological role of iron in peripheral nervous system (PNS), despite the development of suitable cellular and animal models. Future Directions: To stimulate research on iron metabolism and peripheral neuropathy, we provide a summary of the knowledge on iron homeostasis in the PNS, on its transport across the blood–nerve barrier, its involvement in myelination, and we identify unresolved questions. Furthermore, we comment on the role of iron in iron-related disorder with peripheral component, in demyelinating and metabolic peripheral neuropathies. Antioxid. Redox Signal. 21, 634–648. PMID:24409826

Equine peripheral blood mononuclear cells proliferate in response to tetanus toxoid antigen.

Science.gov (United States)

McKelvie, J; Little, S; Foster, A P; Cunningham, F M; Hamblin, A

1998-01-01

It has been reported that equine peripheral blood mononuclear cells (PBMNs) do not proliferate in response to tetanus toxoid (TT) (Frayne and Stokes 1995, Research in Veterinary Science 59, 79-81). Here we demonstrate that lymphocyte proliferation responses to TT, which are characteristic of a recall antigen, may be achieved under certain culture conditions. Given that TT vaccination is routinely applied to many horses, TT is a suitable antigen for the investigation of cellular immune responses by peripheral blood mononuclear cells in the horse.

Leishmania mexicana amazonensis: heterogeneity in 5-nucleotidase and peroxidase activities of mononuclear phagocytes during in vivo and in vitro infection Leishmania mexicana amazonensis: heterogeneidade da 5’-Nucleotidase e da peroxidase em fagócitos mononucleares durante infecção in vivo e in vitro

Directory of Open Access Journals (Sweden)

Suzana Côrte-Real

1988-03-01

Full Text Available The degree of maturation of cells of the Mononuclear Phagocyte System (MPS, during in vivo and in vitro infection by Leishmania mexicana amazonenesis, was evaluated in this study. The macrophages' differentiation was assayed by cytochemical characterization at the ultrastrctural level, using two well-established markers: 5'-nucleotidase enzyme activity, for revealing the mature cells, and the peroxidase activity present in the cell granules to demonstrate immature mononuclear phagocytes. only a few mcrophages, demonstrating 5'-nucleotidase positive reaction in both the plasma membrane and within their cytoplasmic vesicles, were found scattered in the chronic inflammation at the L. m. amazonensis lesions in albino mice. However, by the peroxidase activity analysis, we were also able to demonstrate the presence of immature MPS cells, which predominate, together with parasitized vacuolated macrophages, in chronic lesions induced in this systemby L. m. amazonensis. The implications of these results on the pathogenesis of murine cutaneous leishmaniasis are discussed.Um estudo sobre o grau de maturação das células do Sistema Fagocítico Mononuclear foi realizado durante a infecção in vivo e in vitro com a Leishmania mexicana amazonensis. A caracterização da diferenciação das células fagocíticas foi obtida com a localização ultraestrutural de dois marcadores enzimáticos bam conhecidos: a enzima 5'-Nucleotidase marcadora de membrana plasmática de células maduras e a enzima peroxidase, presente em grânulos, marcadora de células imaturas. A atividade da enzima 5'-Nucleotidase foi encontrada apenas em alguns macrófagos, presentes no foco inflamatório, em projeções da membrana plasmática e em algumas vesículas citoplasmáticas. Macrófagos peritoneais de camundongo apresentaram a mesma reatividade para este marcador. Contudo a análise da atividade peroxidásica demonstrou a predominância da presença de fagócitos mononucleares

Sodium nitroprusside may modulate Escherichia coli antioxidant enzyme expression by interacting with the ferric uptake regulator.

Science.gov (United States)

Bertrand, R; Danielson, D; Gong, V; Olynik, B; Eze, M O

2012-01-01

Efforts to explore possible relationships between nitric oxide (NO) and antioxidant enzymes in an Escherichia coli model have uncovered a possible interaction between sodium nitroprusside (SNP), a potent, NO-donating drug, and the ferric uptake regulator (Fur), an iron(II)--dependent regulator of antioxidant and iron acquisition proteins present in Gram-negative bacteria. The enzymatic profiles of superoxide dismutase and hydroperoxidase during logarithmic phase of growth were studied via non-denaturing polyacrylamide gel electrophoresis and activity staining specific to each enzyme. Though NO is known to induce transcription of the manganese-bearing isozyme of SOD (MnSOD), treatment with SNP paradoxically suppressed MnSOD expression and greatly enhanced the activity of the iron-containing equivalent (FeSOD). Fur, one of six global regulators of MnSOD transcription, is uniquely capable of suppressing MnSOD while enhancing FeSOD expression through distinct mechanisms. We thus hypothesize that Fur is complacent in causing this behaviour and that the iron(II) component of SNP is activating Fur. E. coli was also treated with the SNP structural analogues, potassium ferricyanide (PFi) and potassium ferrocyanide (PFo). Remarkably, the ferrous PFo was capable of mimicking the SNP-related pattern, whereas the ferric PFi was not. As Fur depends upon ferrous iron for activation, we submit this observation of redox-specificity as preliminary supporting evidence for the hypothesized Fur-SNP interaction. Iron is an essential metal that the human innate immune system sequesters to prevent its use by invading pathogens. As NO is known to inhibit iron-bound Fur, and as activated Fur regulates iron uptake through feedback inhibition, we speculate that the administration of this drug may disrupt this strategic management of iron in favour of residing Gram-negative species by providing a source of iron in an otherwise iron-scarce environment capable of encouraging its own uptake

A clinical study on insulin receptors of mononuclear cells in diabetes

International Nuclear Information System (INIS)

Dalimunthe, D.

1980-01-01

125 I-insulin binding activity to mononuclear cells was studied in 75 noninsulin-dependent diabetic subjects and 31 normal subjects and the following results were obtained. 1. 125 I-insulin binding is directly proportional to the mononuclear cell concentrations. There is a linear increase of specific 125 I-insulin binding. 2. The binding of 125 I-insulin to mononuclear cells is displaced by the increasing concentration of native insulin. 3. The 125 I-insulin degradation in the incubation medium after incubation of mononuclear cells for 24 hours at 4 0 C was almost 5% in this study. 4. The insulin binding activity in diabetic subjects was lower than that in normal subjects (P < 0.001) without any significant difference in affinity constant. 5. The relationship of binding activity to age of diabetics (r = 0.06, N.S), relative body weitht (r = 0.06, N.S) and duration of diabetes from onset was not significant. 6. In untreated noninsulin-dependent diabetics the insulin binding activity was inversely correlated to fasting blood glucose level (r = 0.78, P < 0.001) and slightly inversely correlated to serum insulin level (r = 0.47, P < 0.01). A slight inverse correlation was also observed in serum triglyceride level (r = 0.53, P < 0.01) and in total cholesterol level (r = 0.29, P < 0.05). 7. No significant difference between the binding activity was observed by grade of diabetic retinopathy. 8. After treatment with diet and/or sulfonylurea, the diabetics exhibited a significant increase in insulin binding activity (P < 0.005) but no significant difference in plasma insulin level, body weight and plasma lipid levels was observed. (author)

Cell therapy with bone marrow mononuclear cells in elastase-induced pulmonary emphysema.

Science.gov (United States)

Longhini-Dos-Santos, Nathalia; Barbosa-de-Oliveira, Valter Abraão; Kozma, Rodrigo Heras; Faria, Carolina Arruda de; Stessuk, Talita; Frei, Fernando; Ribeiro-Paes, João Tadeu

2013-04-01

Emphysema is characterized by destruction of alveolar walls with loss of gas exchange surface and consequent progressive dyspnea. This study aimed to evaluate the efficiency of cell therapy with bone marrow mononuclear cells (BMMC) in an animal model of elastase-induced pulmonary emphysema. Emphysema was induced in C57Bl/J6 female mice by intranasal instillation of elastase. After 21 days, the mice received bone marrow mononuclear cells from EGFP male mice with C57Bl/J6 background. The groups were assessed by comparison and statistically significant differences (p pulmonary emphysema.

Leishmania and its quest for iron: An update and overview.

Science.gov (United States)

Zaidi, Amir; Singh, Krishn Pratap; Ali, Vahab

2017-01-01

Parasites of genus Leishmania are the causative agents of complex neglected diseases called leishmaniasis and continue to be a significant health concern globally. Iron is a vital nutritional requirement for virtually all organisms, including pathogenic trypanosomatid parasites, and plays a crucial role in many facets of cellular metabolism as a cofactor of several enzymes. Iron acquisition is essential for the survival of parasites. Yet parasites are also vulnerable to the toxicity of iron and reactive oxygen species. The aim of this review is to provide an update on the current knowledge about iron acquisition and usage by Leishmania species. We have also discussed about host strategy to modulate iron availability and the strategies deployed by Leishmania parasites to overcome iron withholding defences and thus favour parasite growth within host macrophages. Since iron plays central roles in the host's response and parasite metabolism, a comprehensive understanding of the iron metabolism is beneficial to identify potential viable therapeutic opportunities against leishmaniasis. Copyright © 2016 Elsevier B.V. All rights reserved.

Interaction of Carthamus tinctorius lignan arctigenin with the binding site of tryptophan-degrading enzyme indoleamine 2,3-dioxygenase☆

Science.gov (United States)

Temml, Veronika; Kuehnl, Susanne; Schuster, Daniela; Schwaiger, Stefan; Stuppner, Hermann; Fuchs, Dietmar

2013-01-01

Mediterranean Carthamus tinctorius (Safflower) is used for treatment of inflammatory conditions and neuropsychiatric disorders. Recently C. tinctorius lignans arctigenin and trachelogenin but not matairesinol were described to interfere with the activity of tryptophan-degrading enzyme indoleamine 2,3-dioxygenase (IDO) in peripheral blood mononuclear cells in vitro. We examined a potential direct influence of compounds on IDO enzyme activity applying computational calculations based on 3D geometry of the compounds. The interaction pattern analysis and force field-based minimization was performed within LigandScout 3.03, the docking simulation with MOE 2011.10 using the X-ray crystal structure of IDO. Results confirm the possibility of an intense interaction of arctigenin and trachelogenin with the binding site of the enzyme, while matairesinol had no such effect. PMID:24251110

Use of {sup 99m}Tc-Mononuclear Leukocyte Scintigraphy in Nosocomial Fever

Energy Technology Data Exchange (ETDEWEB)

Gutfilen, B.; Lopes de Souza, S.A.; Martins, F.P.P.; Cardoso, L.R.; Pinheiro Pessoa, M.C.; Fonseca, L.M.B. [Univ. Federal do Rio de Janeiro (Brazil). Dept. de Radiologia

2006-09-15

Purpose: To determine the overall diagnostic accuracy of mononuclear leukocyte-{sup 99m}Tc scintigraphy in the routine detection of infectious lesions and fever of unknown origin (FUO) in inpatients. Material and Methods: The use of mononuclear leukocyte {sup 99m}Tc scintigraphy is presented in 87 patients who fulfilled the Durack and Street diagnostic criteria of nosocomial FUO; 66 patients were suspected of having infectious lesions (myocarditis, endocarditis, infected catheters, diabetic foot, and osteomyelitis) and 21 patients presented with unknown causes of FUO. Scans were carried out 1, 3, and 24 h after injection of labeled leukocytes. Results: In three cases (3/27) where scintigraphs were negative, biopsies were positive. There were two (2/87) false-positive scintigrams. We found a 95.8% sensitivity and 92.3% specificity. PPV was 93.8%, PPN 94.7%, and accuracy 94.2%. Conclusion: Mononuclear leukocyte {sup 99m}Tc scintigraphy showed high sensitivity, specificity, positive and negative predictive values in patients with nosocomial FUO. These results suggest an important role for nuclear medicine in the management of patients with infection/inflammation.

A novel nanostructured iron oxide-gold bioelectrode for hydrogen peroxide sensing

Energy Technology Data Exchange (ETDEWEB)

Thandavan, Kavitha; Gandhi, Sakthivel; Sethuraman, Swaminathan; Krishnan, Uma Maheswari [Centre for Nanotechnology and Advanced Biomaterials, School of Chemical and Biotechnology, SASTRA University, Thanjavur 613 401 (India); Rayappan, John Bosco Balaguru, E-mail: umakrishnan@sastra.edu [Centre for Nanotechnology and Advanced Biomaterials, School of Electrical and Electronics Engineering, SASTRA University, Thanjavur 613 401 (India)

2011-07-01

Fe{sub 3}O{sub 4} nanoparticles covalently linked to a gold electrode have been used for immobilizing catalase (CAT) enzyme to sense the presence of various concentrations of H{sub 2}O{sub 2}. These nanoparticles ranging from 20 to 30 nm were synthesized by thermal co-precipitation of ferric and ferrous chlorides. SEM and XRD have been used for morphological and structural characterization of Fe{sub 3}O{sub 4} nanoparticles. CAT enzyme was linked covalently to the surface of iron oxide using carbodiimide in phosphate buffer (pH 7.4) at 4 deg. C. The enzyme-iron oxide link was confirmed by FT-IR spectroscopy. Sensing studies carried out using cyclic voltammetry showed a linear response of the CAT/nano Fe{sub 3}O{sub 4}/Au bioelectrode towards H{sub 2}O{sub 2} between 1.5 and 13.5 {mu}M with a very sharp response time of 2 s.

Reduction of ferric iron by acidophilic heterotrophic bacteria: evidence for constitutive and inducible enzyme systems in Acidiphilium spp.

Science.gov (United States)

Johnson, D B; Bridge, T A M

2002-01-01

To compare the abilities of two obligately acidophilic heterotrophic bacteria, Acidiphilium acidophilum and Acidiphilium SJH, to reduce ferric iron to ferrous when grown under different culture conditions. Bacteria were grown in batch culture, under different aeration status, and in the presence of either ferrous or ferric iron. The specific rates of ferric iron reduction by fermenter-grown Acidiphilium SJH were unaffected by dissolved oxygen (DO) concentrations, while iron reduction by A. acidophilum was highly dependent on DO concentrations in the growth media. The ionic form of iron present (ferrous or ferric) had a minimal effect on the abilities of harvested cells to reduce ferric iron. Whole cell protein profiles of Acidiphilium SJH were very similar, regardless of the DO status of the growth medium, while additional proteins were present in A. acidophilum grown microaerobically compared with aerobically-grown cells. The dissimilatory reduction of ferric iron is constitutive in Acidiphilium SJH while it is inducible in A. acidophilum. Ferric iron reduction by Acidiphilium spp. may occur in oxygen-containing as well as anoxic acidic environments. This will detract from the effectiveness of bioremediation systems where removal of iron from polluted waters is mediated via oxidation and precipitation of the metal.

Iron inhibits hydroxyapatite crystal growth in vitro.

Science.gov (United States)

Guggenbuhl, Pascal; Filmon, Robert; Mabilleau, Guillaume; Baslé, Michel F; Chappard, Daniel

2008-07-01

Hemochromatosis is a known cause of osteoporosis in which the pathophysiology of bone loss is largely unknown and the role of iron remains questionable. We have investigated the effects of iron on the growth of hydroxyapatite crystals in vitro on carboxymethylated poly(2-hydroxyethyl methacrylate) pellets. This noncellular and enzyme-independent model mimics the calcification of woven bone (composed of calcospherites made of hydroxyapatite crystals). Polymer pellets were incubated with body fluid containing iron at increasing concentrations (20, 40, 60 micromol/L). Hydroxyapatite growth was studied by chemical analysis, scanning electron microscopy, and Raman microscopy. When incubated in body fluid containing iron, significant differences were observed with control pellets. Iron was detected at a concentration of 5.41- to 7.16-fold that of controls. In pellets incubated with iron, there was a approximately 3- to 4-fold decrease of Ca and P and a approximately 1.3- to 1.4-fold increase in the Ca/P ratio. There was no significant difference among the iron groups of pellets, but a trend to a decrease of Ca with the increase of iron concentration was noted. Calcospherite diameters were significantly lower on pellets incubated with iron. Raman microspectroscopy showed a decrease in crystallinity (measured by the full width of the half height of the 960 Deltacm(-1) band) with a significant increase in carbonate substitution (measured by the intensity ratio of 1071 to 960 Deltacm(-1) band). Energy dispersive x-ray analysis identified iron in the calcospherites. In vitro, iron is capable to inhibit bone crystal growth with significant changes in crystallinity and carbonate substitution.

Impairment of Interrelated Iron- and Copper Homeostatic Mechanisms in Brain Contributes to the Pathogenesis of Neurodegenerative Disorders

Science.gov (United States)

Skjørringe, Tina; Møller, Lisbeth Birk; Moos, Torben

2012-01-01

Iron and copper are important co-factors for a number of enzymes in the brain, including enzymes involved in neurotransmitter synthesis and myelin formation. Both shortage and an excess of iron or copper will affect the brain. The transport of iron and copper into the brain from the circulation is strictly regulated, and concordantly protective barriers, i.e., the blood-brain barrier (BBB) and the blood-cerebrospinal fluid (CSF) barrier (BCB) have evolved to separate the brain environment from the circulation. The uptake mechanisms of the two metals interact. Both iron deficiency and overload lead to altered copper homeostasis in the brain. Similarly, changes in dietary copper affect the brain iron homeostasis. Moreover, the uptake routes of iron and copper overlap each other which affect the interplay between the concentrations of the two metals in the brain. The divalent metal transporter-1 (DMT1) is involved in the uptake of both iron and copper. Furthermore, copper is an essential co-factor in numerous proteins that are vital for iron homeostasis and affects the binding of iron-response proteins to iron-response elements in the mRNA of the transferrin receptor, DMT1, and ferroportin, all highly involved in iron transport. Iron and copper are mainly taken up at the BBB, but the BCB also plays a vital role in the homeostasis of the two metals, in terms of sequestering, uptake, and efflux of iron and copper from the brain. Inside the brain, iron and copper are taken up by neurons and glia cells that express various transporters. PMID:23055972

CCR1+/CCR5+ mononuclear phagocytes accumulate in the central nervous system of patients with multiple sclerosis

DEFF Research Database (Denmark)

Trebst, C; Sørensen, Torben Lykke; Kivisäkk, P

2001-01-01

Mononuclear phagocytes (monocytes, macrophages, and microglia) are considered central to multiple sclerosis (MS) pathogenesis. Molecular cues that mediate mononuclear phagocyte accumulation and activation in the central nervous system (CNS) of MS patients may include chemokines RANTES/CCL5...

HIV-1 isolation from infected peripheral blood mononuclear cells

NARCIS (Netherlands)

Dispinseri, Stefania; Saba, Elisa; Vicenzi, Elisa; Kootstra, Neeltje A.; Schuitemaker, Hanneke; Scarlatti, Gabriella

2014-01-01

Human immunodeficiency virus 1 (HIV-1) isolation from peripheral blood mononuclear cells (PBMCs) allows retrieval of replication-competent viral variants. In order to impose the smallest possible selective pressure on the viral isolates, isolation must be carried out in primary cultures of cells and

Release of an endogenous pyrogen in vitro from rabbit mononuclear cells.

Science.gov (United States)

Atkins, E; Bodel, P; Francis, L

1967-08-01

The capacity of rabbit mononuclear cells to release an endogenous pyrogen (EP) in vitro has been studied. After incubation with tuberculin, preparations of predominantly monocytic cells, derived from the respiratory passages of the lungs of rabbits sensitized with BCG, were activated to release EP. Pyrogen production occurred more slowly with lung monocytes than with blood leukocytes of similarly sensitized rabbits and 9 to 10 hr incubation in a fully supportive medium was required to produce clear-cut results. As previously reported with blood leukocytes, mononuclear cells from the lungs of normal animals were also activated by tuberculin but to a lesser degree than were those from specifically sensitized rabbits. Under a variety of conditions, mononuclear cells from either spleen or lymph nodes of the same sensitized rabbits failed to release detectable amounts of pyrogen when incubated with tuberculin in vitro but were activated in a majority of instances when phagocytosis of heat-killed staphylococci was used as the stimulus. Release of pyrogen from lung monocytes appears to be an active process that is both temperature-dependent and requires protein synthesis. Neither serum antibody nor complement appears to play a role in this process. Evidence is presented that the granulocyte is the main source of pyrogen evolved by blood leukocytes incubated in vitro with OT or heat-killed staphylococci, whereas the lung macrophage and/or monocyte is responsible for most of the pyrogen released from the lung cell preparations. From these studies, it is concluded that mononuclear cells can be activated in vitro by several microbial stimuli and must be considered an additional cellular source of EP. The clinical implications of these findings for the pathogenesis of fever in granulomatous diseases where the monocyte is the predominant cell are discussed.

A study of light scattering of mononuclear blood cells with scanning flow cytometry

International Nuclear Information System (INIS)

Zharinov, Alexey; Tarasov, Peter; Shvalov, Alexander; Semyanov, Konstantin; Bockstaele, Dirk R. van; Maltsev, Valeri

2006-01-01

This study describes the measurement of light scattering of human mononuclear blood cells, the development of an appropriate optical model for those cells, and solution of the inverse light-scattering problem. The angular dependency of light-scattering intensity of mononuclear blood cells was experimentally measured by means of scanning flow cytometry. A sphere consisting of several concentric homogeneous layers with different refractive indices was tested as an optical model for mononuclear blood cells. A five-layer model has given the best agreement between experimental and theoretical light-scattering profiles. The inverse light-scattering problem was solved for a five-layer model with an optimization procedure that allows one to retrieve cell parameters: cell size relates to the outer diameter of the fifth layer; size of the nucleus relates to the outer diameter of the third layer. Mean values of cell size, nuclear size, refractive indices of nucleus and cellular cytoplasm were determined for blood monocytes and lymphocytes

Iron chelation excludes protein synthesis inhibition in the ...

African Journals Online (AJOL)

Ribonucleotide reductase, an iron requiring enzyme necessary in the production of deoxyribonucleotides required for replication in cell division and proliferation is induced during the S phase of the cell cycle. We have compared the trypanocidal properties of four antibiotics that show bactericidal activities by destabilizing ...

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.

Experimental and Computational Evidence for the Mechanism of Intradiol Catechol Dioxygenation by Non- Heme Iron(III) Complexes

NARCIS (Netherlands)

Jastrzebski, Robin; Quesne, Matthew G.; Weckhuysen, Bert M.; de Visser, Sam P.; Bruijnincx, Pieter C. A.

2014-01-01

Catechol intradiol dioxygenation is a unique reaction catalyzed by iron-dependent enzymes and nonheme iron(III) complexes. The mechanism by which these systems activate dioxygen in this important metabolic process remains controversial. Using a combination of kinetic measurements and computational

Beyond Iron: Iridium-Containing P450 Enzymes for Selective Cyclopropanations of Structurally Diverse Alkenes

International Nuclear Information System (INIS)

Key, Hanna M.; Dydio, Paweł; Liu, Zhennan

2017-01-01

Enzymes catalyze organic transformations with exquisite levels of selectivity, including chemoselectivity, stereoselectivity, and substrate selectivity, but the types of reactions catalyzed by enzymes are more limited than those of chemical catalysts. Thus, the convergence of chemical catalysis and biocatalysis can enable enzymatic systems to catalyze abiological reactions with high selectivity. Recently, we disclosed artificial enzymes constructed from the apo form of heme proteins and iridium porphyrins that catalyze the insertion of carbenes into a C-H bond. Here, we postulated that the same type of Ir(Me)-PIX enzymes could catalyze the cyclopropanation of a broad range of alkenes with control of multiple modes of selectivity. Here, we report the evolution of artificial enzymes that are highly active and highly stereoselective for the addition of carbenes to a wide range of alkenes. These enzymes catalyze the cyclopropanation of terminal and internal, activated and unactivated, electron-rich and electron-deficient, conjugated and nonconjugated alkenes. In particular, Ir(Me)-PIX enzymes derived from CYP119 catalyze highly enantio- and diastereoselective cyclopropanations of styrene with ±98% ee, > 70:1 dr, > 75% yield, and ~10,000 turnovers (TON), as well as 1,2-disubstituted styrenes with up to 99% ee, 35:1 dr, and 54% yield. Moreover, Ir(Me)-PIX enzymes catalyze cyclopropanation of internal, unactivated alkenes with up to 99% stereoselectivity, 76% yield, and 1300 TON. They also catalyze cyclopropanation of natural products with diastereoselectivities that are complementary to those attained with standard transition metal catalysts. Finally, Ir(Me)-PIX P450 variants react with substrate selectivity that is reminiscent of natural enzymes; they react preferentially with less reactive internal alkenes in the presence of more reactive terminal alkenes. Altogether, the studies reveal the suitability of Ir-containing P450s to combine the broad reactivity and

Microbial Community Composition Impacts Pathogen Iron Availability during Polymicrobial Infection.

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Apollo Stacy

2016-12-01

Full Text Available Iron is an essential nutrient for bacterial pathogenesis, but in the host, iron is tightly sequestered, limiting its availability for bacterial growth. Although this is an important arm of host immunity, most studies examine how bacteria respond to iron restriction in laboratory rather than host settings, where the microbiome can potentially alter pathogen strategies for acquiring iron. One of the most important transcriptional regulators controlling bacterial iron homeostasis is Fur. Here we used a combination of RNA-seq and chromatin immunoprecipitation (ChIP-seq to characterize the iron-restricted and Fur regulons of the biofilm-forming opportunistic pathogen Aggregatibacter actinomycetemcomitans. We discovered that iron restriction and Fur regulate 4% and 3.5% of the genome, respectively. While most genes in these regulons were related to iron uptake and metabolism, we found that Fur also directly regulates the biofilm-dispersing enzyme Dispersin B, allowing A. actinomycetemcomitans to escape from iron-scarce environments. We then leveraged these datasets to assess the availability of iron to A. actinomycetemcomitans in its primary infection sites, abscesses and the oral cavity. We found that A. actinomycetemcomitans is not restricted for iron in a murine abscess mono-infection, but becomes restricted for iron upon co-infection with the oral commensal Streptococcus gordonii. Furthermore, in the transition from health to disease in human gum infection, A. actinomycetemcomitans also becomes restricted for iron. These results suggest that host iron availability is heterogeneous and dependent on the infecting bacterial community.

Global transcriptional response to Hfe deficiency and dietary iron overload in mouse liver and duodenum.

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Alejandra Rodriguez

2009-09-01

Full Text Available Iron is an essential trace element whose absorption is usually tightly regulated in the duodenum. HFE-related hereditary hemochromatosis (HH is characterized by abnormally low expression of the iron-regulatory hormone, hepcidin, which results in increased iron absorption. The liver is crucial for iron homeostasis as it is the main production site of hepcidin. The aim of this study was to explore and compare the genome-wide transcriptome response to Hfe deficiency and dietary iron overload in murine liver and duodenum. Illumina arrays containing over 47,000 probes were used to study global transcriptional changes. Quantitative RT-PCR (Q-RT-PCR was used to validate the microarray results. In the liver, the expression of 151 genes was altered in Hfe(-/- mice while dietary iron overload changed the expression of 218 genes. There were 173 and 108 differentially expressed genes in the duodenum of Hfe(-/- mice and mice with dietary iron overload, respectively. There was 93.5% concordance between the results obtained by microarray analysis and Q-RT-PCR. Overexpression of genes for acute phase reactants in the liver and a strong induction of digestive enzyme genes in the duodenum were characteristic of the Hfe-deficient genotype. In contrast, dietary iron overload caused a more pronounced change of gene expression responsive to oxidative stress. In conclusion, Hfe deficiency caused a previously unrecognized increase in gene expression of hepatic acute phase proteins and duodenal digestive enzymes.

The Role of Serum Copper and Iron in Oral Submucous Fibrosis

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Master Luquman

2004-01-01

Full Text Available Oral submucous fibrosis (OSMF is a chronic insidious disease of multifactorial etiology. The habit of chewing arecanut is thought to be one of the most important etiologic factors. Copper and iron are elements in the human body that form part of important enzymes. We estimated the serum copper and iron in patients with OSMF as well as normal controls and discuss the role of these elements in the etiology of OSMF.

Experimental and Computational Evidence for the Mechanism of Intradiol Catechol Dioxygenation by Non-Heme Iron(III) Complexes

Science.gov (United States)

Jastrzebski, Robin; Quesne, Matthew G; Weckhuysen, Bert M; de Visser, Sam P; Bruijnincx, Pieter C A

2014-01-01

Catechol intradiol dioxygenation is a unique reaction catalyzed by iron-dependent enzymes and non-heme iron(III) complexes. The mechanism by which these systems activate dioxygen in this important metabolic process remains controversial. Using a combination of kinetic measurements and computational modelling of multiple iron(III) catecholato complexes, we have elucidated the catechol cleavage mechanism and show that oxygen binds the iron center by partial dissociation of the substrate from the iron complex. The iron(III) superoxide complex that is formed subsequently attacks the carbon atom of the substrate by a rate-determining C=O bond formation step. PMID:25322920

Microbial siderophore-based iron assimilation and therapeutic applications.

Science.gov (United States)

Li, Kunhua; Chen, Wei-Hung; Bruner, Steven D

2016-06-01

Siderophores are structurally diverse, complex natural products that bind metals with extraordinary specificity and affinity. The acquisition of iron is critical for the survival and virulence of many pathogenic microbes and diverse strategies have evolved to synthesize, import and utilize iron. There has been a substantial increase of known siderophore scaffolds isolated and characterized in the past decade and the corresponding biosynthetic gene clusters have provided insight into the varied pathways involved in siderophore biosynthesis, delivery and utilization. Additionally, therapeutic applications of siderophores and related compounds are actively being developed. The study of biosynthetic pathways to natural siderophores augments the understanding of the complex mechanisms of bacterial iron acquisition, and enables a complimentary approach to address virulence through the interruption of siderophore biosynthesis or utilization by targeting the key enzymes to the siderophore pathways.

Combined in situ zymography, immunofluorescence, and staining of iron oxide particles in paraffin-embedded, zinc-fixed tissue sections.

Science.gov (United States)

Haeckel, Akvile; Schoenzart, Lena; Appler, Franziska; Schnorr, Joerg; Taupitz, Matthias; Hamm, Bernd; Schellenberger, Eyk

2012-01-01

Superparamagnetic iron oxide particles are used as potent contrast agents in magnetic resonance imaging. In histology, these particles are frequently visualized by Prussian blue iron staining of aldehyde-fixed, paraffin-embedded tissues. Recently, zinc salt-based fixative was shown to preserve enzyme activity in paraffin-embedded tissues. In this study, we demonstrate that zinc fixation allows combining in situ zymography with fluorescence immunohistochemistry (IHC) and iron staining for advanced biologic investigation of iron oxide particle accumulation. Very small iron oxide particles, developed for magnetic resonance angiography, were applied intravenously to BALB/c nude mice. After 3 hours, spleens were explanted and subjected to zinc fixation and paraffin embedding. Cut tissue sections were further processed to in situ zymography, IHC, and Prussian blue staining procedures. The combination of in situ zymography as well as IHC with subsequent Prussian blue iron staining on zinc-fixed paraffin-embedded tissues resulted in excellent histologic images of enzyme activity, protease distribution, and iron oxide particle accumulation. The combination of all three stains on a single section allowed direct comparison with only moderate degradation of fluorescein isothiocyanate-labeled substrate. This protocol is useful for investigating the biologic environment of accumulating iron oxide particles, with excellent preservation of morphology.

Beta-Thalassemia Major and Female Fertility: The Role of Iron and Iron-Induced Oxidative Stress

Science.gov (United States)

Roussou, Paraskevi; Tsagarakis, Nikolaos J.; Diamanti-Kandarakis, Evanthia

2013-01-01

Endocrine complications due to haemosiderosis are present in a significant number of patients with beta-thalassemia major (BTM) worldwide and often become barriers in their desire for parenthood. Thus, although spontaneous fertility can occur, the majority of females with BTM is infertile due to hypogonadotropic hypogonadism (HH) and need assisted reproductive techniques. Infertility in these women seems to be attributed to iron deposition and iron-induced oxidative stress (OS) in various endocrine organs, such as hypothalamus, pituitary, and female reproductive system, but also through the iron effect on other organs, such as liver and pancreas, contributing to the impaired metabolism of hormones and serum antioxidants. Nevertheless, the gonadal function of these patients is usually intact and fertility is usually retrievable. Meanwhile, a significant prooxidants/antioxidants imbalance with subsequent increased (OS) exists in patients with BTM, which is mainly caused by tissue injury due to overproduction of free radicals by secondary iron overload, but also due to alteration in serum trace elements and antioxidant enzymes. Not only using the appropriate antioxidants, essential trace elements, and minerals, but also regulating the advanced glycation end products, could probably reduce the extent of oxidative damage and related complications and retrieve BTM women's infertility. PMID:24396593

Mycobacterial antigens stimulate rheumatoid mononuclear cells to cartilage proteoglycan depletion

NARCIS (Netherlands)

Wilbrink, B.; Bijlsma, J. W.; Huber-Bruning, O.; van Roy, J. L.; den Otter, W.; van Eden, W.

1990-01-01

In a coculture with porcine articular cartilage explants unstimulated blood mononuclear cells (BMC) from patients with rheumatoid arthritis (RA), but not from healthy controls, induced proteoglycan depletion of dead cartilage. Specific stimulation of the RA BMC with Mycobacterium tuberculosis (MT),

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

The effect of haem biosynthesis inhibitors and inducers on intestinal iron absorption and liver haem biosynthetic enzyme activities

International Nuclear Information System (INIS)

Laftah, A.H.; Simpson, R.J.; Peters, T.J.; Raja, K.B.

2008-01-01

The relation between haem biosynthesis and intestinal iron absorption is not well understood, we therefore investigated the effect of compounds that alter haem metabolism on duodenal iron absorption. CD1 mice were treated with either an inhibitor (succinyl acetone (SA)) or stimulator (2-allyl-2-isopropylacetamide (AIA)) of haem biosynthesis. 5-Aminolaevulinic acid (ALA) dehydratase and urinary ALA and porphobilinogen (PBG) levels, were determined. Intestinal iron absorption was assayed with in vivo and in vitro techniques. Liver hepcidin (Hamp1) and duodenal iron transporter mRNA levels were measured using RT-PCR. AIA caused increased hepatic ALA synthase (1.6-fold) and ALA dehydratase (1.4-fold, both p < 0.005) activities and increased urinary ALA and PBG excretion (2.1- and 1.4-fold, p < 0.005, p < 0.05, respectively). In vivo intestinal iron absorption was reduced to 49% of control (p < 0.005). Mice treated with SA showed decreased urinary ALA and PBG levels (75 and 55% control, both p < 0.005) and reductions in both ALA synthase and ALA dehydratase activities (77 and 56% control, p < 0.05, p < 0.005, respectively) in the liver. Liver and duodenal haem and cytochrome oxidase levels were not significantly decreased. Iron absorption was enhanced (1.26-fold, p < 0.05) and hepatic Hamp1 mRNA was reduced (53% of control, p < 0.05). In vitro duodenal iron uptake after mice were injected with SA also demonstrated an increase in Fe(III) reduction and uptake (1.27- and 1.41-fold, p < 0.01 respectively). Simultaneous injections of SA and ALA blocked the enhancing effect on iron absorption seen with SA alone. We conclude that alterations in haem biosynthesis can influence iron absorption and in particular, the intermediate ALA seems to be an inhibitor of iron absorption

Monomeric Yeast Frataxin is an Iron-Binding Protein

International Nuclear Information System (INIS)

Cook, J.; Bencze, K.; Jankovic, A.; Crater, A.; Busch, C.; Bradley, P.; Stemmler, A.; Spaller, M.; Stemmler, T.

2006-01-01

Friedreich's ataxia, an autosomal cardio- and neurodegenerative disorder that affects 1 in 50 000 humans, is caused by decreased levels of the protein frataxin. Although frataxin is nuclear-encoded, it is targeted to the mitochondrial matrix and necessary for proper regulation of cellular iron homeostasis. Frataxin is required for the cellular production of both heme and iron-sulfur (Fe-S) clusters. Monomeric frataxin binds with high affinity to ferrochelatase, the enzyme involved in iron insertion into porphyrin during heme production. Monomeric frataxin also binds to Isu, the scaffold protein required for assembly of Fe-S cluster intermediates. These processes (heme and Fe-S cluster assembly) share requirements for iron, suggesting that monomeric frataxin might function as the common iron donor. To provide a molecular basis to better understand frataxin's function, we have characterized the binding properties and metal-site structure of ferrous iron bound to monomeric yeast frataxin. Yeast frataxin is stable as an iron-loaded monomer, and the protein can bind two ferrous iron atoms with micromolar binding affinity. Frataxin amino acids affected by the presence of iron are localized within conserved acidic patches located on the surfaces of both helix-1 and strand-1. Under anaerobic conditions, bound metal is stable in the high-spin ferrous state. The metal-ligand coordination geometry of both metal-binding sites is consistent with a six-coordinate iron-(oxygen/nitrogen) based ligand geometry, surely constructed in part from carboxylate and possibly imidazole side chains coming from residues within these conserved acidic patches on the protein. On the basis of our results, we have developed a model for how we believe yeast frataxin interacts with iron

Blood Mononuclear Cell Mitochondrial Respiratory Chain Complex IV Activity is Decreased in Multiple Sclerosis Patients: Effects of β-Interferon Treatment

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Iain Hargreaves

2018-02-01

Full Text Available Objectives: Evidence of mitochondrial respiratory chain (MRC dysfunction and oxidative stress has been implicated in the pathophysiology of multiple sclerosis (MS. However, at present, there is no reliable low invasive surrogate available to evaluate mitochondrial function in these patients. In view of the particular sensitivity of MRC complex IV to oxidative stress, the aim of this study was to assess blood mononuclear cell (BMNC MRC complex IV activity in MS patients and compare these results to age matched controls and MS patients on β-interferon treatment. Methods: Spectrophotometric enzyme assay was employed to measure MRC complex IV activity in blood mononuclear cell obtained multiple sclerosis patients and aged matched controls. Results: MRC Complex IV activity was found to be significantly decreased (p < 0.05 in MS patients (2.1 ± 0.8 k/nmol × 10−3; mean ± SD] when compared to the controls (7.2 ± 2.3 k/nmol × 10−3. Complex IV activity in MS patients on β-interferon (4.9 ± 1.5 k/nmol × 10−3 was not found to be significantly different from that of the controls. Conclusions: This study has indicated evidence of peripheral MRC complex IV deficiency in MS patients and has highlighted the potential utility of BMNCs as a potential means to evaluate mitochondrial function in this disorder. Furthermore, the reported improvement of complex IV activity may provide novel insights into the mode(s of action of β-interferon.

Aspergillus niger Secretes Citrate to Increase Iron Bioavailability

Science.gov (United States)

Odoni, Dorett I.; van Gaal, Merlijn P.; Schonewille, Tom; Tamayo-Ramos, Juan A.; Martins dos Santos, Vitor A. P.; Suarez-Diez, Maria; Schaap, Peter J.

2017-01-01

Aspergillus niger has an innate ability to secrete various organic acids, including citrate. The conditions required for A. niger citrate overproduction are well described, but the physiological reasons underlying extracellular citrate accumulation are not yet fully understood. One of the less understood culture conditions is the requirement of growth-limiting iron concentrations. While this has been attributed to iron-dependent citrate metabolizing enzymes, this straightforward relationship does not always hold true. Here, we show that an increase in citrate secretion under iron limited conditions is a physiological response consistent with a role of citrate as A. niger iron siderophore. We found that A. niger citrate secretion increases with decreasing amounts of iron added to the culture medium and, in contrast to previous findings, this response is independent of the nitrogen source. Differential transcriptomics analyses of the two A. niger mutants NW305 (gluconate non-producer) and NW186 (gluconate and oxalate non-producer) revealed up-regulation of the citrate biosynthesis gene citA under iron limited conditions compared to iron replete conditions. In addition, we show that A. niger can utilize Fe(III) citrate as iron source. Finally, we discuss our findings in the general context of the pH-dependency of A. niger organic acid production, offering an explanation, besides competition, for why A. niger organic acid production is a sequential process influenced by the external pH of the culture medium. PMID:28824560

Synthesis, characterization, applications, and challenges of iron oxide nanoparticles

Science.gov (United States)

Ali, Attarad; Zafar, Hira; Zia, Muhammad; ul Haq, Ihsan; Phull, Abdul Rehman; Ali, Joham Sarfraz; Hussain, Altaf

2016-01-01

Recently, iron oxide nanoparticles (NPs) have attracted much consideration due to their unique properties, such as superparamagnetism, surface-to-volume ratio, greater surface area, and easy separation methodology. Various physical, chemical, and biological methods have been adopted to synthesize magnetic NPs with suitable surface chemistry. This review summarizes the methods for the preparation of iron oxide NPs, size and morphology control, and magnetic properties with recent bioengineering, commercial, and industrial applications. Iron oxides exhibit great potential in the fields of life sciences such as biomedicine, agriculture, and environment. Nontoxic conduct and biocompatible applications of magnetic NPs can be enriched further by special surface coating with organic or inorganic molecules, including surfactants, drugs, proteins, starches, enzymes, antibodies, nucleotides, nonionic detergents, and polyelectrolytes. Magnetic NPs can also be directed to an organ, tissue, or tumor using an external magnetic field for hyperthermic treatment of patients. Keeping in mind the current interest in iron NPs, this review is designed to report recent information from synthesis to characterization, and applications of iron NPs. PMID:27578966

Chemistry of Iron N -heterocyclic carbene complexes: Syntheses, structures, reactivities, and catalytic applications

KAUST Repository

Riener, Korbinian

2014-05-28

Iron is the most abundant transition metal in Earth\\'s crust. It is relatively inexpensive, not very toxic, and environmentally benign. Undoubtedly, due to the involvement in a multitude of biological processes, which heavily rely on the rich functionalities of iron-containing enzymes, iron is one of the most important elements in nature. Additionally, three-coordinate iron complexes have been reported during the past several years. In this review, the mentioned iron NHC complexes are categorized by their main structure and reactivity attributes. Thus, monocarbene and bis-monocarbene complexes are presented first. This class is subdivided into carbonyl, nitrosyl, and halide compounds followed by a brief section on other, more unconventional iron NHC motifs. Subsequently, donor-substituted complexes bearing bi-, tri-, tetra-, or even pentadentate ligands and further pincer as well as scorpionato motifs are described.

Synthesis of the iron phthalocyaninate radical cation μ-nitrido dimer and its interaction with hydrogen peroxide

Science.gov (United States)

Grishina, E. S.; Makarova, A. S.; Kudrik, E. V.; Makarov, S. V.; Koifman, O. I.

2016-03-01

The iron phthalocyaninate μ-nitrido dimer radical cation, as well as the μ-nitrido dimer complexes of iron phthalocyaninate, was found to have high catalytic activity in the oxidation of organic compounds. It was concluded that this compound is of interest as a model of active intermediates—catalase and oxidase enzymes.

Iron transport and storage in the coccolithophore: Emiliania huxleyi.

Science.gov (United States)

Hartnett, Andrej; Böttger, Lars H; Matzanke, Berthold F; Carrano, Carl J

2012-11-01

Iron is an essential element for all living organisms due to its ubiquitous role in redox and other enzymes, especially in the context of respiration and photosynthesis. The iron uptake and storage systems of terrestrial/higher plants are now reasonably well understood with two basic strategies for iron uptake being distinguished: strategy I plants use a mechanism involving soil acidification and induction of Fe(III)-chelate reductase (ferrireductase) and Fe(II) transporter proteins while strategy II plants have evolved sophisticated systems based on high-affinity, iron specific, binding compounds called phytosiderophores. In contrast, there is little knowledge about the corresponding systems in marine plant-like lineages. Herein we report a study of the iron uptake and storage mechanisms in the coccolithophore Emiliania huxleyi. Short term radio-iron uptake studies indicate that iron is taken up by Emiliania in a time and concentration dependent manner consistent with an active transport process. Based on inhibitor studies it appears that iron is taken up directly as Fe(iii). However if a reductive step is involved the Fe(II) must not be accessible to the external environment. Upon long term exposure to (57)Fe we have been able, using a combination of Mössbauer and XAS spectroscopies, to identify a single metabolite which displays spectral features similar to the phosphorus-rich mineral core of bacterial and plant ferritins.

Alleviation of iron toxicity in Schinus terebinthifolius Raddi (Anacardiaceae) by humic substances.

Science.gov (United States)

Dobbss, Leonardo Barros; Dos Santos, Tamires Cruz; Pittarello, Marco; de Souza, Sávio Bastos; Ramos, Alessandro Coutinho; Busato, Jader Galba

2018-04-01

One of the industrial pillars of Espírito Santo state, South East of Brazil, is iron-mining products processing. This activity brings to a high level of coastal pollution due to deposition of iron particulate on fragile ecosystems as mangroves and restinga. Schinus therebinthifolius (aroeira) is a widespread restinga species. This work tested iron toxicity alleviation by vermicompost humic substances (HS) added to aroeira seedlings in hydroponic conditions. Catalase, peroxidase, and ascorbate peroxidase are antioxidant enzymes that work as reactive oxygen species (ROS) scavengers: they increase their activity as an answer to ROS concentration rise that is the consequence of metal accumulation or humic substance stimulation. S. terebinthifolius seedlings treated with HS and Fe augmented their antioxidant enzyme activities significantly less than seedlings treated separately with HS and Fe; their significantly lower Fe accumulation and the slight increase of root and leaf area confirm the biostimulating effect of HS and their role in blocking Fe excess outside the roots. The use of HS can be useful for the recovery of areas contaminated by heavy metals.

The NAD+ precursor nicotinic acid improves genomic integrity in human peripheral blood mononuclear cells after X-irradiation.

Science.gov (United States)

Weidele, Kathrin; Beneke, Sascha; Bürkle, Alexander

2017-04-01

NAD + is an essential cofactor for enzymes catalyzing redox-reactions as well as an electron carrier in energy metabolism. Aside from this, NAD + consuming enzymes like poly(ADP-ribose) polymerases and sirtuins are important regulators involved in chromatin-restructuring processes during repair and epigenetics/transcriptional adaption. In order to replenish cellular NAD + levels after cleavage, synthesis starts from precursors such as nicotinamide, nicotinamide riboside or nicotinic acid to match the need for this essential molecule. In the present study, we investigated the impact of supplementation with nicotinic acid on resting and proliferating human mononuclear blood cells with a focus on DNA damage and repair processes. We observed that nicotinic acid supplementation increased NAD + levels as well as DNA repair efficiency and enhanced genomic stability evaluated by micronucleus test after x-ray treatment. Interestingly, resting cells displayed lower basal levels of DNA breaks compared to proliferating cells, but break-induction rates were identical. Despite similar levels of p53 protein upregulation after irradiation, higher NAD + concentrations led to reduced acetylation of this protein, suggesting enhanced SIRT1 activity. Our data reveal that even in normal primary human cells cellular NAD + levels may be limiting under conditions of genotoxic stress and that boosting the NAD + system with nicotinic acid can improve genomic stability. Copyright © 2017 Elsevier B.V. All rights reserved.

Generation of Human Induced Pluripotent Stem Cells from Peripheral Blood Mononuclear Cells Using Sendai Virus.

Science.gov (United States)

Soares, Filipa A C; Pedersen, Roger A; Vallier, Ludovic

2016-01-01

This protocol describes the efficient isolation of peripheral blood mononuclear cells from circulating blood via density gradient centrifugation and subsequent generation of integration-free human induced pluripotent stem cells. Peripheral blood mononuclear cells are cultured for 9 days to allow expansion of the erythroblast population. The erythroblasts are then used to derive human induced pluripotent stem cells using Sendai viral vectors, each expressing one of the four reprogramming factors Oct4, Sox2, Klf4, and c-Myc.

Two Zn coordination polymers with meso-helical chains based on mononuclear or dinuclear cluster units

Energy Technology Data Exchange (ETDEWEB)

Qin, Ling, E-mail: qinling@hfut.edu.cn [Department of Chemical Engineering and Food Processing, Xuancheng Campus, Hefei University of Technology, Xuancheng 242000, Anhui (China); Jiangsu Engineering Technology Research Center of Environmental Cleaning Materials (CEM), School of Environmental Sciences and Engineering, Nanjing University of Information Science and Technology (China); State Key Laboratory of Coordination Chemistry, School of Chemistry and Chemical Engineering, Nanjing National Laboratory of Microstructures, Nanjing University, Nanjing 210093 (China); Qiao, Wen-Cheng; Zuo, Wei-Juan; Zeng, Si-Ying; Mei, Cao; Liu, Chang-Jiang [Department of Chemical Engineering and Food Processing, Xuancheng Campus, Hefei University of Technology, Xuancheng 242000, Anhui (China)

2016-07-15

Two zinc coordination polymers {[Zn_2(TPPBDA)(oba)_2]·DMF·1.5H_2O}{sub n} (1), {[Zn(TPPBDA)_1_/_2(tpdc)]·DMF}{sub n} (2) have been synthesized by zinc metal salt, nanosized tetradentate pyridine ligand with flexible or rigid V-shaped carboxylate co-ligands. These complexes were characterized by elemental analyses and X-ray single-crystal diffraction analyses. Compound 1 is a 2-fold interpenetrated 3D framework with [Zn{sub 2}(CO{sub 2}){sub 4}] clusters. Compound 2 can be defined as a five folded interpenetrating bbf topology with mononuclear Zn{sup 2+}. These mononuclear or dinuclear cluster units are linked by mix-ligands, resulting in various degrees of interpenetration. In addition, the photoluminescent properties for TPPBDA ligand under different state and coordination polymers have been investigated in detail. - Graphical abstract: Two zinc coordination polymers have been synthesized by zinc metal salt, nanosized tetradentate pyridine ligand with flexible or rigid V-shaped carboxylate co-ligands. Compound 1 is a 2-fold interpenetrated 3D framework with [Zn{sub 2}(CO{sub 2}){sub 4}] clusters. Compound 2 can be defined as a five folded interpenetrating bbf topology with mononuclear Zn{sup 2+}. In addition, the photoluminescent properties for TPPBDA ligand under different status and coordination polymers have been investigated in detail. Display Omitted - Highlights: • Two Zn coordination polymers based on mononuclear or dinuclear cluster units have been synthesized. • Compound 1 is a 2-fold interpenetrated 3D framework with [Zn{sub 2}(CO{sub 2}){sub 4}] clusters. • Compound 2 is a five folded interpenetrating bbf topology with mononuclear Zn{sup 2+}. • The photoluminescent properties for TPPBDA with different state and two coordination polymers have been investigated.

The comparison of knee osteoarthritis treatment with single-dose bone marrow-derived mononuclear cells vs. hyaluronic acid injections.

Science.gov (United States)

Goncars, Valdis; Jakobsons, Eriks; Blums, Kristaps; Briede, Ieva; Patetko, Liene; Erglis, Kristaps; Erglis, Martins; Kalnberzs, Konstantins; Muiznieks, Indrikis; Erglis, Andrejs

2017-01-01

The aim of this study was to compare treatment methods of the knee joint degenerative osteoarthritis, using autologous bone marrow-derived mononuclear cells and hyaluronic acid injections and observe prevalence of adverse effects in both groups. A prospective randomized controlled clinical trial was carried out. The analysis of pain and changes in osteoarthritis symptoms after a single intra-articular bone marrow-derived mononuclear cell injection into the knee joint in the Kellgren-Lawrence stage II-III osteoarthritis during the 12-month period were performed. The results were compared with the control group treated routinely by hyaluronic acid injections therapy. A therapy group of patients (n=28) received single bone marrow-derived mononuclear cell intra-articular injections. A control group of patients (n=28) was treated with a total of three sodium hyaluronate intra-articular injections each one performed a week apart. The clinical results were obtained using the Knee Osteoarthritis Outcome Score (KOOS) and the Knee Society Score (KSS) before and 3, 6, and 12 months after injection. A statistically significant improvement was observed in the mononuclear cell group over the starting point in all scores. At the endpoint at month 12, the KOOS score improved significantly (Phyaluronic acid versus the bone marrow-derived mononuclear cells group at time points 6 and 12 months demonstrated a statistically significant (Phyaluronic acid group. In both groups serious adverse effects were not observed. The intra-articular injection of bone marrow-derived mononuclear cells is a safe manipulation with no side effects during the 12-month period. This treatment provides statistically significant clinical improvement between the starting point and 1, 3, 6, and 12 months after. When compared to hyaluronic acid treatment, better pain relief in the long-term period of mononuclear cell group was observed. Copyright © 2017 The Lithuanian University of Health Sciences. Production

Evaluation of Application Methods Efficiency of Zinc and Iron for Canola(Brassica napus L.

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Ahmad BYBORDI

2010-03-01

Full Text Available In order to evaluation of application method efficiency of zinc and iron microelements in canola, an experiment was conducted in the Agricultural Research Station of Eastern Azerbaijan province in 2008. The experimental design was a RCBD with eight treatments (F1: control, F2: iron, F3: zinc, F4: iron + zinc in the form of soil utility, F5: iron, F6: zinc, F7: iron+ zinc in the form of solution foliar application, and F8: iron + zinc in the form of soil utility and foliar application. Analysis of variance showed that there were significant differences among treatments on given traits, antioxidant enzymes activity, fatty acids percentage, plant height, seed weight to capitulum weight ratio, protein percentage, oil percentage, oil yield, 1000 seed weight, seed yield, nitrogen, phosphorous and potassium percentage of leaves, zinc and iron content of leaves and capitulum diameters. The highest seed yield, oil yield, oil percentage, 1000 seed weight, seed weight to capitulum weight ratio and protein percentage were obtained from the soil and foliar application of iron + zinc treatments (F8. Also, the highest amounts of nitrogen, phosphorous and potassium concentration in leaves were achieved from control treatment which was an indication of non-efficiency of iron and zinc on the absorption rate of these substances in the leaves. The correlation between effective traits on the seed yield, such as, capitalism diameter, number of seed rows in capitulum, seed weight to capitulum weight ratio and 1000 seed weight were positively significant. In general, foliar and soil application of zinc and iron had the highest efficiency in aspect of seed production. The comparison of the various methods of fertilization showed that foliar application was more effective than soil application. Also, micronutrient foliar application increased concentration of elements, especially zinc and iron. Antioxidant enzymes activity was different in response to treatments also the

86Rubidium uptake in mononuclear leucocytes from young subjects at increased risk of developing essential hypertension

DEFF Research Database (Denmark)

Nielsen, J R; Johansen, Torben; Pedersen, K E

1988-01-01

This study was designed to assess any changes in mononuclear leucocytes from young men at increased risk of developing essential hypertension and to determine whether any changes found were associated with borderline hypertension and/or heredity. To this end we used mononuclear leucocytes......, and especially in those borderline hypertensives with at least one hypertensive parent. The latter group was also the group at greatest risk of developing essential hypertension....

INFLUENCE OF ALPHA-1-ACID GLYCOPROTEIN UPON PRODUCTION OF CYTOKINES BY PERIPHERAL BLOOD MONONUCLEARS

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М. V. Osikov

2007-01-01

Full Text Available Abstract. Alpha-1-acid glycoprotein (orosomucoid is a multifunctional acute phase reactant belonging to the family of lipocalines from plasma alpha-2 globulin fraction. In present study, we investigated dosedependent effects of orosomucoid upon secretion of IL-1â, IL-2, IL-3, IL-4 by mononuclear cells from venous blood of healthy volunteers. Mononuclear cells were separated by means of gradient centrifugation, followed by incubation for 24 hours with 250, 500, or 1000 mcg of orosomucoid per ml RPMI-1640 medium (resp., low, medium and high dose. The levels of cytokine production were assayed by ELISA technique. Orosomucoid-induced secretion of IL-1â and IL-4 was increased, whereas IL-3 secretion was inhibited. IL-2 production was suppressed at low doses of orosomucoid, and stimulated at medium and high doses. The effect of alpha-1-acid glycoprotein upon production of IL-2, IL-3 and IL-4 was dose-dependent. Hence, these data indicate that orosomucoid is capable of modifying IL-1â, IL-2, IL-3, and IL-4 secretion by blood mononuclear cells.

Heme metabolism as an integral part of iron homeostasis

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Paweł Lipiński

2014-01-01

Full Text Available Heme, a ferrous iron protoporphyrin IX complex, is employed as a prosthetic group in a number of diverse heme proteins that participate in important cellular and systemic physiological processes. Provision of an adequate amount of iron for heme biosynthesis is one of the elemental hallmarks of intracellular iron homeostasis. In the cell the bioavailability of iron for the two main iron biological pathways – heme synthesis and the biogenesis of iron-sulfur clusters ([Fe-S] – is mainly regulated by the IRP/IRE posttranscriptional system. The biogenesis of [Fe-S] centers is crucial for heme synthesis because these co-factors determine the activity of IRP1 and that of ferrochelatase, an enzyme responsible for the insertion of an iron into protoporphyrin IX to produce heme. On the other hand, delivery of iron for heme and hemoglobin synthesis in erythroblasts, precursors of erythrocytes in bone marrow, is an indispensable element of body iron homeostasis. This process relies on the recovery of iron from senescent red blood cells through the enzymatic degradation of heme molecules and recycling of iron to the circulation. Molecular coordination of these processes involves the activity of heme oxygenase 1, IRP1 and IRP2 as well as the functioning of the hepcidin-ferroportin regulatory axis. Recent studies show in mammals the existence of an expanded system of proteins involved in the transport of intact heme molecules at the cellular and systemic levels. The biological role of this system is of particular importance when the concentration of free heme reaches a toxic level in the body (intravascular hemolysis as well as locally in cells having intensive heme metabolism such as erythroblasts and macrophages.

[Heme metabolism as an integral part of iron homeostasis].

Science.gov (United States)

Lipiński, Paweł; Starzyński, Rafał R; Styś, Agnieszka; Gajowiak, Anna; Staroń, Robert

2014-01-02

Heme, a ferrous iron protoporphyrin IX complex, is employed as a prosthetic group in a number of diverse heme proteins that participate in important cellular and systemic physiological processes. Provision of an adequate amount of iron for heme biosynthesis is one of the elemental hallmarks of intracellular iron homeostasis. In the cell the bioavailability of iron for the two main iron biological pathways--heme synthesis and the biogenesis of iron-sulfur clusters ([Fe-S])--is mainly regulated by the IRP/IRE posttranscriptional system. The biogenesis of [Fe-S] centers is crucial for heme synthesis because these co-factors determine the activity of IRP1 and that of ferrochelatase, an enzyme responsible for the insertion of an iron into protoporphyrin IX to produce heme. On the other hand, delivery of iron for heme and hemoglobin synthesis in erythroblasts, precursors of erythrocytes in bone marrow, is an indispensable element of body iron homeostasis. This process relies on the recovery of iron from senescent red blood cells through the enzymatic degradation of heme molecules and recycling of iron to the circulation. Molecular coordination of these processes involves the activity of heme oxygenase 1, IRP1 and IRP2 as well as the functioning of the hepcidin-ferroportin regulatory axis. Recent studies show in mammals the existence of an expanded system of proteins involved in the transport of intact heme molecules at the cellular and systemic levels. The biological role of this system is of particular importance when the concentration of free heme reaches a toxic level in the body (intravascular hemolysis) as well as locally in cells having intensive heme metabolism such as erythroblasts and macrophages.

Iron and stony-iron meteorites

DEFF Research Database (Denmark)

Ruzicka, Alex M.; Haack, Henning; Chabot, Nancy L.

2017-01-01

By far most of the melted and differentiated planetesimals that have been sampled as meteorites are metal-rich iron meteorites or stony iron meteorites. The parent asteroids of these meteorites accreted early and differentiated shortly after the solar system formed, producing some of the oldest...... and interpretations for iron and stony iron meteorites (Plate 13.1). Such meteorites provide important constraints on the nature of metal-silicate separation and mixing in planetesimals undergoing partial to complete differentiation. They include iron meteorites that formed by the solidification of cores...... (fractionally crystallized irons), irons in which partly molten metal and silicates of diverse types were mixed together (silicate-bearing irons), stony irons in which partly molten metal and olivine from cores and mantles were mixed together (pallasites), and stony irons in which partly molten metal...

Iron(III) complexes of certain tetradentate phenolate ligands as ...

Indian Academy of Sciences (India)

non-heme iron enzymes, which catalyse the oxidative cleavage of catechols to cis, cis-muconic acids with the incorporation of ... nature of heterocyclic rings of the ligands and the methyl substituents on them regulate the electronic spectral features .... and simple substitution reactions.19,21 The complexes of [H2(L5)] and ...

The induction of two biosynthetic enzymes helps Escherichia coli sustain heme synthesis and activate catalase during hydrogen peroxide stress.

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Mancini, Stefano; Imlay, James A

2015-05-01

Hydrogen peroxide pervades many natural environments, including the phagosomes that mediate cell-based immunity. Transcriptomic analysis showed that during protracted low-grade H(2)O(2) stress, Escherichia coli responds by activating both the OxyR defensive regulon and the Fur iron-starvation response. OxyR induced synthesis of two members of the nine-step heme biosynthetic pathway: ferrochelatase (HemH) and an isozyme of coproporphyrinogen III oxidase (HemF). Mutations that blocked either adaptation caused the accumulation of porphyrin intermediates, inadequate activation of heme enzymes, low catalase activity, defective clearance of H(2)O(2) and a failure to grow. Genetic analysis indicated that HemH induction is needed to compensate for iron sequestration by the mini-ferritin Dps. Dps activity protects DNA and proteins by limiting Fenton chemistry, but it interferes with the ability of HemH to acquire the iron that it needs to complete heme synthesis. HemF is a manganoprotein that displaces HemN, an iron-sulfur enzyme whose synthesis and/or stability is apparently problematic during H(2)O(2) stress. Thus, the primary responses to H(2)O(2), including the sequestration of iron, require compensatory adjustments in the mechanisms of iron-cofactor synthesis. The results support the growing evidence that oxidative stress is primarily an iron pathology. © 2015 John Wiley & Sons Ltd.

The effects of compound danshen dripping pills and human umbilical cord blood mononuclear cell transplant after acute myocardial infarction.

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Jun, Yi; Chunju, Yuan; Qi, Ai; Liuxia, Deng; Guolong, Yu

2014-04-01

The low frequency of survival of stem cells implanted in the myocardium after acute myocardial infarction may be caused by inflammation and oxidative stress in the myocardial microenvironment. We evaluated the effects of a traditional Chinese medicine, Compound Danshen Dripping Pills, on the cardiac microenvironment and cardiac function when used alone or in combination with human umbilical cord blood mononuclear cell transplant after acute myocardial infarction. After surgically induced acute myocardial infarction, rabbits were treated with Compound Danshen Dripping Pills alone or in combination with human umbilical cord blood mononuclear cell transplant. Evaluation included histology, measurement of left ventricular ejection fraction and fractional shortening, leukocyte count, count of green fluorescent protein positive cells, superoxide dismutase activity, and malondialdehyde content. Combination treatment with Compound Danshen Dripping Pills and human umbilical cord blood mononuclear cell transplant significantly increased the survival of implanted cells, inhibited cardiac cell apoptosis, decreased oxidative stress, decreased the inflammatory response, and improved cardiac function. Rabbits treated with either Compound Danshen Dripping Pills or human umbilical cord blood mononuclear cells alone had improvement in these effects compared with untreated control rabbits. Combination therapy with Compound Danshen Dripping Pills and human umbilical cord blood mononuclear cells may improve cardiac function and morphology after acute myocardial infarction.

Potential of Phytase-Mediated Iron Release from Cereal-Based Foods: A Quantitative View

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Nielsen, Anne V. F.; Tetens, Inge; Meyer, Anne S.

2013-01-01

The major part of iron present in plant foods such as cereals is largely unavailable for direct absorption in humans due to complexation with the negatively charged phosphate groups of phytate (myo-inositol (1,2,3,4,5,6)-hexakisphosphate). Human biology has not evolved an efficient mechanism to naturally release iron from iron phytate complexes. This narrative review will evaluate the quantitative significance of phytase-catalysed iron release from cereal foods. In vivo studies have shown how addition of microbially derived phytases to cereal-based foods has produced increased iron absorption via enzyme-catalysed dephosphorylation of phytate, indicating the potential of this strategy for preventing and treating iron deficiency anaemia. Despite the immense promise of this strategy and the prevalence of iron deficiency worldwide, the number of human studies elucidating the significance of phytase-mediated improvements in iron absorption and ultimately in iron status in particularly vulnerable groups is still low. A more detailed understanding of (1) the uptake mechanism for iron released from partially dephosphorylated phytate chelates, (2) the affinity of microbially derived phytases towards insoluble iron phytate complexes, and (3) the extent of phytate dephosphorylation required for iron release from inositol phosphates is warranted. Phytase-mediated iron release can improve iron absorption from plant foods. There is a need for development of innovative strategies to obtain better effects. PMID:23917170

Role of Serum Iron in the Activation of Lipid Peroxidation in Critical Conditions

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Yu. P. Orlov

2006-01-01

Full Text Available Twenty-four critically ill patients due to generalized purulent peritonitis, pancreatonecrosis, thermal skin injuries, and severe poisoning by acetic acid were examined. The general regularities of the effect of high serum iron concentrations on the health status of patients, on the activity of antioxidative enzymes, and on the initiation of lipid peroxidation (LPO processes, as supported by the values of Fe2+-induced chemiluminescence, were revealed. In critically ill patients, iron metabolism occurs with the overload of a transport protein, such as transferrin, which is caused by intravascular hemolysis and hemoglobin metabolism to ionized iron. The overload of proteins responsible for iron transport leads to the tissue accumulation of free (ferrous and ferric iron that is actively involved in the processes of LPO initiation with excess synthesis of cytotoxic radicals, which in turn accounts for the severity of endotoxicosis.

Automated processing of human bone marrow can result in a population of mononuclear cells capable of achieving engraftment following transplantation.

Science.gov (United States)

Areman, E M; Cullis, H; Spitzer, T; Sacher, R A

1991-10-01

A concentrate of mononuclear bone marrow cells is often desired for ex vivo treatment with pharmacologic agents, monoclonal antibodies, cytokines, and other agents prior to transplantation. A method has been developed for automated separation of mononuclear cells from large volumes of harvested bone marrow. A programmable instrument originally designed for clinical ex vivo cell separation and the plasma-pheresis of patients and blood donors was adapted to permit rapid preparation, in a closed sterile system, of a bone marrow product enriched with mononuclear cells. A mean (+/- SEM) of 53 +/- 30 percent of the original mononuclear cells was recovered in a volume of 125 +/- 42 mL containing 82 +/- 12 percent mononuclear cells. This technique removed 95 +/- 9 percent of the red cells in the original marrow. No density gradient materials or sedimenting agents were employed in this process. Of 36 marrows processed by this technique, 19 autologous (6 of which were purged with 4-hydroperoxycyclophosphamide) and 7 allogeneic marrows have been transplanted, with all evaluable patients achieving a neutrophil count of 0.5 x 10(9) per L in a mean (+/- SEM) of 21 +/- 6 days.

El género Brucella y su interacción con el sistema mononuclear fagocítico

OpenAIRE

Arestegui, Mirta B.; Gualtieri S., Catalina; Domínguez, Javier; Scharovsky, O. Graciela

2001-01-01

Non-specific resistance is a fundamental component of the host immune response. The mononuclear phagocytic system (MPS) is part of innate resistance effector mechanisms, and is involved in several homeostatic, inflammatory and immunologic events. Mononuclear phagocytes (MNP), which are cells belonging to the MPS, play a central role in the main functions of multicellular organisms. Its early interaction with pathogens determines the evolution of the inf...

Iron plaque decreases cadmium accumulation in Oryza sativa L. and serves as a source of iron.

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Sebastian, A; Prasad, M N V

2016-11-01

Cadmium (Cd) contamination occurs in paddy soils; hence it is necessary to reduce Cd content of rice. Application and mode of action of ferrous sulphate in minimizing Cd in rice was monitored in the present study. Pot culture with Indian rice variety Swarna (MTU 7029) was maintained in Cd-spiked soil containing ferrous sulphates, which is expected to reduce Cd accumulation in rice. Responses in rhizosphere pH, root surface, metal accumulation in plant and molecular physiological processes were monitored. Iron plaque was induced on root surfaces after FeSO4 application and the amount of Fe in plaque reduced with increases in Cd in the soil. Rhizosphere pH decreased during plaque formation and became more acidic due to secretion of organic acids from the roots under Cd treatment. Moreover, iron chelate reductase activity increased with Cd treatment, but in the absence of Cd, activity of this enzyme increased in plaque-induced plants. Cd treatment caused expression of OsYSL18, whereas OsYSL15 was expressed only in roots without iron plaque. Fe content of plants increased during plaque formation, which protected plants from Cd-induced Fe deficiency and metal toxicity. This was corroborated with increased biomass, chlorophyll content and quantum efficiency of photo-synthesis among plaque-induced plants. We conclude that ferrous sulphate-induced iron plaque prevents Cd accumulation and Fe deficiency in rice. Iron released from plaque via organic acid mediated dissolution during Cd stress. © 2016 German Botanical Society and The Royal Botanical Society of the Netherlands.

Duodenal Cytochrome b (DCYTB in Iron Metabolism: An Update on Function and Regulation

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Darius J. R. Lane

2015-03-01

Full Text Available Iron and ascorbate are vital cellular constituents in mammalian systems. The bulk-requirement for iron is during erythropoiesis leading to the generation of hemoglobin-containing erythrocytes. Additionally; both iron and ascorbate are required as co-factors in numerous metabolic reactions. Iron homeostasis is controlled at the level of uptake; rather than excretion. Accumulating evidence strongly suggests that in addition to the known ability of dietary ascorbate to enhance non-heme iron absorption in the gut; ascorbate regulates iron homeostasis. The involvement of ascorbate in dietary iron absorption extends beyond the direct chemical reduction of non-heme iron by dietary ascorbate. Among other activities; intra-enterocyte ascorbate appears to be involved in the provision of electrons to a family of trans-membrane redox enzymes; namely those of the cytochrome b561 class. These hemoproteins oxidize a pool of ascorbate on one side of the membrane in order to reduce an electron acceptor (e.g., non-heme iron on the opposite side of the membrane. One member of this family; duodenal cytochrome b (DCYTB; may play an important role in ascorbate-dependent reduction of non-heme iron in the gut prior to uptake by ferrous-iron transporters. This review discusses the emerging relationship between cellular iron homeostasis; the emergent “IRP1-HIF2α axis”; DCYTB and ascorbate in relation to iron metabolism.

African Trypanosomiasis-Associated Anemia: The Contribution of the Interplay between Parasites and the Mononuclear Phagocyte System

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Benoit Stijlemans

2018-02-01

Full Text Available African trypanosomosis (AT is a chronically debilitating parasitic disease of medical and economic importance for the development of sub-Saharan Africa. The trypanosomes that cause this disease are extracellular protozoan parasites that have developed efficient immune escape mechanisms to manipulate the entire host immune response to allow parasite survival and transmission. During the early stage of infection, a profound pro-inflammatory type 1 activation of the mononuclear phagocyte system (MPS, involving classically activated macrophages (i.e., M1, is required for initial parasite control. Yet, the persistence of this M1-type MPS activation in trypanosusceptible animals causes immunopathology with anemia as the most prominent pathological feature. By contrast, in trypanotolerant animals, there is an induction of IL-10 that promotes the induction of alternatively activated macrophages (M2 and collectively dampens tissue damage. A comparative gene expression analysis between M1 and M2 cells identified galectin-3 (Gal-3 and macrophage migration inhibitory factor (MIF as novel M1-promoting factors, possibly acting synergistically and in concert with TNF-α during anemia development. While Gal-3 enhances erythrophagocytosis, MIF promotes both myeloid cell recruitment and iron retention within the MPS, thereby depriving iron for erythropoiesis. Hence, the enhanced erythrophagocytosis and suppressed erythropoiesis lead to anemia. Moreover, a thorough investigation using MIF-deficient mice revealed that the underlying mechanisms in AT-associated anemia development in trypanosusceptible and tolerant animals are quite distinct. In trypanosusceptible animals, anemia resembles anemia of inflammation, while in trypanotolerant animals’ hemodilution, mainly caused by hepatosplenomegaly, is an additional factor contributing to anemia. In this review, we give an overview of how trypanosome- and host-derived factors can contribute to trypanosomosis

The Effects of Dietary Fat and Iron Interaction on Brain Regional Iron Contents and Stereotypical Behaviors in Male C57BL/6J Mice

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Lumei Liu

2016-07-01

Full Text Available Adequate brain iron levels are essential for enzyme activities, myelination, and neurotransmitter synthesis in the brain. Although systemic iron deficiency has been found in genetically or dietary-induced obese subjects, the effects of obesity-associated iron dysregulation in brain regions have not been examined. The objective of this study was to examine the effect of dietary fat and iron interaction on brain regional iron contents and regional-associated behavior patterns in a mouse model. Thirty C57BL/6J male weanling mice were randomly assigned to six dietary treatment groups (n=5 with varying fat (control/high and iron (control/high/low contents. The stereotypical behaviors were measured during the 24th week. Blood, liver, and brain tissues were collected at the end of the 24th week. Brains were dissected into the hippocampus, midbrain, striatum, and thalamus regions. Iron contents and ferritin-H (FtH protein and mRNA expressions in these regions were measured. Correlations between stereotypical behaviors and brain regional iron contents were analyzed at the 5% significance level. Results showed that high-fat diet altered the stereotypical behaviors such as inactivity and total distance traveled (P<0.05. The high-fat diet altered brain iron contents and ferritin-H (FtH protein and mRNA expressions in a regional-specific manner: 1 high-fat diet significantly decreased the brain iron content in the striatum (P<0.05, but not other regions; and 2 thalamus has a more distinct change in FtH mRNA expression compared to other regions. Furthermore, high-fat diet resulted in a significant decreased total distance traveled and a significant correlation between iron content and sleeping in midbrain (P<0.05. Dietary iron also decreased brain iron content and FtH protein expression in a regionally specific manner. The effect of interaction between dietary fat and iron was observed in brain iron content and behaviors. All these findings will lay

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

International Nuclear Information System (INIS)

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

2016-01-01

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

Exquisite Enzyme-Fenton Biomimetic Catalysts for Hydroxyl Radical Production by Mimicking an Enzyme Cascade.

Science.gov (United States)

Zhang, Qi; Chen, Shuo; Wang, Hua; Yu, Hongtao

2018-03-14

Hydrogen peroxide (H 2 O 2 ) is a key reactant in the Fenton process. As a byproduct of enzymatic reaction, H 2 O 2 can be obtained via catalytical oxidation of glucose using glucose oxidase in the presence of O 2 . Another oxidation product (gluconic acid) can suitably adjust the microenvironmental pH contributing to the Fe 3+ /Fe 2+ cycle in the Fenton reaction. Enzymes are extremely efficient at catalyzing a variety of reactions with high catalytic activity, substrate specificity, and yields in living organisms. Inspired by the multiple functions of natural multienzyme systems, an exquisite nanozyme-modified α-FeOOH/porous carbon (PC) biomimetic catalyst constructed by in situ growth of glucose oxidase-mimicking Au nanoparticles and crystallization of adsorbed ferric ions within carboxyl into hierarchically PC is developed as an efficient enzyme-Fenton catalyst. The products (H 2 O 2 , ∼4.07 mmol·L -1 ) of the first enzymatic reaction are immediately used as substrates for the second Fenton-like reaction to generate the valuable • OH (∼96.84 μmol·L -1 ), thus mimicking an enzyme cascade pathway. α-FeOOH nanocrystals, attached by C-O-Fe bondings, are encapsulated into the mesoporous PC frameworks, facilitating the electron transfer between α-FeOOH and the PC support and greatly suppressing iron leaching. This study paves a new avenue for designing biomimetic enzyme-based Fenton catalysts mimicking a natural system for • OH production.

Genetic/metabolic effect of iron metabolism and rare anemias

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Clara Camaschella

2013-03-01

-linked sideroblastic anemia/ataxia, likely impairing the activity of ferrochelatase, which is an iron/sulfur-cluster- dependent enzyme. A recessive form affects GLRX5, a protein involved in the iron/sulfur cluster biogenesis. Aceruloplasminemia is a rare recessive syndrome characterized by anemia, diabetes, retinal degeneration, ataxia and other neurological symptoms, low serum iron but high serum ferritin, due to decreased iron recycling from macrophages and other cells. The study of these rare conditions has greatly contributed to our understanding of iron transport, utilization and recycling. Their distinction is clinically essential in order to plan the best treatment.

Iron in Alzheimer's and Control Hippocampi - Moessbauer, Atomic Absorption and ELISA Studies

International Nuclear Information System (INIS)

Galazka-Friedman, J.; Szlachta, K.; Bauminger, E.R.; Koziorowski, D.; Friedman, A.; Tomasiuk, R.; Jaklewicz, A.; Wszolek, Z.K.; Dickson, D.; Kaplinska, K.

2011-01-01

Alzheimer disease is a neurodegenerative process of unknown mechanism taking place in a part of the brain - hippocampus. Oxidative stress and the role of iron in it is one of the suggested mechanisms of cells death. In this study several methods were used to assess iron and iron binding compounds in human hippocampus tissues. Moessbauer spectroscopy was used for identification of the iron binding compound and determination of total iron concentration in 12 control and one Alzheimer disease sample of hippocampus. Moessbauer parameters obtained for all samples suggest that most of the iron is ferritin-like iron. The average concentration of iron determined by Moessbauer spectroscopy in control hippocampus was 45 ± 10 ng/mg wet tissue. The average concentration of iron in 10 Alzheimer disease samples determined by atomic absorption was 66 ± 13 ng/mg wet tissue. The concentration of H and L chains of ferritin in 20 control and 10 AD hippocampi was assessed with enzyme-linked immuno-absorbent assay. The concentration of H and L ferritin was higher in Alzheimer disease compared to control (19.36 ± 1.51 vs. 5.84 ± 0.55 ng/μg protein for H, and 1.39 ± 0.25 vs. 0.55 ± 0.10 for L). This 3-fold increase of the concentration of ferritin is accompanied by a small increase of the total iron concentration. (authors)

The comparison of knee osteoarthritis treatment with single-dose bone marrow-derived mononuclear cells vs. hyaluronic acid injections

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Valdis Goncars

2017-01-01

Conclusions: The intra-articular injection of bone marrow-derived mononuclear cells is a safe manipulation with no side effects during the 12-month period. This treatment provides statistically significant clinical improvement between the starting point and 1, 3, 6, and 12 months after. When compared to hyaluronic acid treatment, better pain relief in the long-term period of mononuclear cell group was observed.

Magnetic circular dichroism and computational study of mononuclear and dinuclear iron(iv) complexes† †Electronic supplementary information (ESI) available: VT MCD spectra, VT and VTVH MCD intensity analysis of complex 1, energies, S x, S z values and Boltzmann populations of S = 1 magnetic sublevels as a function of the applied magnetic field, derivation of the excited states arising from the 1b2 → 2b1 transition, determination of the C-term sign of band 1 and the E(2e → 2a1) transitions for complex 1, VTVH MCD spectra, VTVH simulations and the computed MCD spectrum of complex 2. See DOI: 10.1039/c4sc03268c Click here for additional data file.

Science.gov (United States)

Xue, Genqiang; Krivokapic, Itana; Petrenko, Taras

2015-01-01

High-valent iron(iv)-oxo species are key intermediates in the catalytic cycles of a range of O2-activating iron enzymes. This work presents a detailed study of the electronic structures of mononuclear ([FeIV(O)(L)(NCMe)]2+, 1, L = tris(3,5-dimethyl-4-methoxylpyridyl-2-methyl)amine) and dinuclear ([(L)FeIV(O)(μ-O)FeIV(OH)(L)]3+, 2) iron(iv) complexes using absorption (ABS), magnetic circular dichroism (MCD) spectroscopy and wave-function-based quantum chemical calculations. For complex 1, the experimental MCD spectra at 2–10 K are dominated by a broad positive band between 12 000 and 18 000 cm–1. As the temperature increases up to ∼20 K, this feature is gradually replaced by a derivative-shaped signal. The computed MCD spectra are in excellent agreement with experiment, which reproduce not only the excitation energies and the MCD signs of key transitions but also their temperature-dependent intensity variations. To further corroborate the assignments suggested by the calculations, the individual MCD sign for each transition is independently determined from the corresponding electron donating and accepting orbitals. Thus, unambiguous assignments can be made for the observed transitions in 1. The ABS/MCD data of complex 2 exhibit ten features that are assigned as ligand-field transitions or oxo- or hydroxo-to-metal charge transfer bands, based on MCD/ABS intensity ratios, calculated excitation energies, polarizations, and MCD signs. In comparison with complex 1, the electronic structure of the FeIV 0000000000000000000000000000000000 0000000000000000000000000000000000 0000000000000000000000000000000000 0000000000000000000000000000000000 0000000000000000000000000000000000 0000000000000000000000000000000000 0000000000000000000000000000000000 0000000000000000000000000000000000 0000000000000000000000000000000000 0000000000000000000000000000000000 0000000000000000000000000000000000 0000000000000000000000000000000000 0000000000000000000000000000000000

Frequency of mononuclear diploid cardiomyocytes underlies natural variation in heart regeneration.

Science.gov (United States)

Patterson, Michaela; Barske, Lindsey; Van Handel, Ben; Rau, Christoph D; Gan, Peiheng; Sharma, Avneesh; Parikh, Shan; Denholtz, Matt; Huang, Ying; Yamaguchi, Yukiko; Shen, Hua; Allayee, Hooman; Crump, J Gage; Force, Thomas I; Lien, Ching-Ling; Makita, Takako; Lusis, Aldons J; Kumar, S Ram; Sucov, Henry M

2017-09-01

Adult mammalian cardiomyocyte regeneration after injury is thought to be minimal. Mononuclear diploid cardiomyocytes (MNDCMs), a relatively small subpopulation in the adult heart, may account for the observed degree of regeneration, but this has not been tested. We surveyed 120 inbred mouse strains and found that the frequency of adult mononuclear cardiomyocytes was surprisingly variable (>7-fold). Cardiomyocyte proliferation and heart functional recovery after coronary artery ligation both correlated with pre-injury MNDCM content. Using genome-wide association, we identified Tnni3k as one gene that influences variation in this composition and demonstrated that Tnni3k knockout resulted in elevated MNDCM content and increased cardiomyocyte proliferation after injury. Reciprocally, overexpression of Tnni3k in zebrafish promoted cardiomyocyte polyploidization and compromised heart regeneration. Our results corroborate the relevance of MNDCMs in heart regeneration. Moreover, they imply that intrinsic heart regeneration is not limited nor uniform in all individuals, but rather is a variable trait influenced by multiple genes.

Relationship between plasma cholesterol levels and cholesterol esterification in isolated human mononuclear cells

International Nuclear Information System (INIS)

Dallongeville, J.; Davignon, J.; Lussier-Cacan, S.

1990-01-01

The authors studied the relationship between plasma lipoprotein concentrations and cholesterol esterification in freshly isolated human mononuclear cells from 27 normolipidemic and 32 hyperlipidemic individuals. Cells were either incubated for 5 hours with radiolabeled oleate immediately after isolation or were preincubated for 18 hours in the presence of exogenous cholesterol, and then incubated with [ 14 C]sodium-oleate-albumin complex. In the absence of exogenous cholesterol, control and hypercholesterolemic subjects had similarly low values of intracellular cholesterol esterification. In the presence of exogenous cholesterol, both hypertriglyceridemic and hypercholesterolemic subjects had higher cholesterol esterification than controls. There was a significant correlation between the rate of cholesterol esterification and plasma total cholesterol. These results suggest that plasma cholesterol levels may regulate mononuclear cell intra-cellular cholesterol esterification in humans

Rieske non-heme iron-dependent oxygenases catalyse diverse reactions in natural product biosynthesis.

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Perry, Christopher; de Los Santos, Emmanuel L C; Alkhalaf, Lona M; Challis, Gregory L

2018-04-13

Covering: up to the end of 2017The roles played by Rieske non-heme iron-dependent oxygenases in natural product biosynthesis are reviewed, with particular focus on experimentally characterised examples. Enzymes belonging to this class are known to catalyse a range of transformations, including oxidative carbocyclisation, N-oxygenation, C-hydroxylation and C-C desaturation. Examples of such enzymes that have yet to be experimentally investigated are also briefly described and their likely functions are discussed.

The Influence of Hepatitis C Virus Therapy on the DNA Base Excision Repair System of Peripheral Blood Mononuclear Cells.

Science.gov (United States)

Czarny, Piotr; Merecz-Sadowska, Anna; Majchrzak, Kinga; Jabłkowski, Maciej; Szemraj, Janusz; Śliwiński, Tomasz; Karwowski, Bolesław

2017-07-01

Hepatitis C virus (HCV) can infect extrahepatic tissues, including lymphocytes, creating reservoir of the virus. Moreover, HCV proteins can interact with DNA damage response proteins of infected cells. In this article we investigated the influence of the virus infection and a new ombitasvir/paritaprevir/ritonavir ± dasabuvir ± ribavirin (OBV/PTV/r ± DSV ± RBV) anti-HCV therapy on the PBMCs (peripheral blood mononuclear cells, mainly lymphocytes) DNA base excision repair (BER) system. BER protein activity was analyzed in the nuclear and mitochondrial extracts (NE and ME) of PBMC isolated from patients before and after therapy, and from subjects without HCV, using modeled double-strand DNA, with 2'-deoxyuridine substitution as the DNA damage. The NE and ME obtained from patients before therapy demonstrated lower efficacy of 2'-deoxyuridine removal and DNA repair polymerization than those of the control group or patients after therapy. Moreover, the extracts from the patients after therapy had similar activity to those from the control group. However, the efficacy of apurinic/apyrimidinic site excision in NE did not differ between the studied groups. We postulate that infection of lymphocytes by the HCV can lead to a decrease in the activity of BER enzymes. However, the use of novel therapy results in the improvement of glycosylase activity as well as the regeneration of endonuclease and other crucial repair enzymes.

Enhancement in irradiated mononuclear cells in culture of mitogen-induced incorporation of [3H]thymidine by homologous conditioned medium

International Nuclear Information System (INIS)

Sandru, G.; Greiner, R.

1994-01-01

Incorporation of [ 3 H]thymidine in irradiated peripheral blood mononuclear cell cultures irradiated in vitro was stimulated significantly by either concanavalin A or phytohemagglutinin only in the presence of homologous conditioned medium. Production of this activity by mononuclear cells was enhanced by irradiation and/or pulsed exposure to puromycin but was abolished by actinomycin D. Addition of anti-interleukin 1 or anti-interleukin 2 monoclonal antibodies to the conditioned medium before assay did not influence the stimulatory action. A similar significant stimulation of mononuclear cell cultures irradiated with 6 Gy by concanavalin A was obtained when purified preparations of homologous conditioned medium were used in the assay. Purification was done by ultrafiltration and concentration, heparin agarose chromatography, ammonium sulfate precipitation, concanavalin A agarose chromatography, DEAE-ion exchange chromatography and HPLC gel filtration chromatography. With SDS-PAGE and silver staining, the active HPLC fraction gave one band of 50 kDa, suggesting that this protein is responsible for the co-stimulatory effect of homologous conditioned medium for both mitogen-induced irradiated and nonirradiated mononuclear cell cultures. 42 refs., 9 figs., 3 tabs

Increased oxidative DNA damage in mononuclear leukocytes in vitiligo

Energy Technology Data Exchange (ETDEWEB)

Giovannelli, Lisa [Department of Preclinical and Clinical Pharmacology, University of Florence, Viale Pieraccini 6, 50139 Florence (Italy)]. E-mail: lisag@pharm.unifi.it; Bellandi, Serena [Department of Dermatological Sciences, University of Florence, Viale Pieraccini 6, 50139 Florence (Italy); Pitozzi, Vanessa [Department of Preclinical and Clinical Pharmacology, University of Florence, Viale Pieraccini 6, 50139 Florence (Italy); Fabbri, Paolo [Department of Dermatological Sciences, University of Florence, Viale Pieraccini 6, 50139 Florence (Italy); Dolara, Piero [Department of Preclinical and Clinical Pharmacology, University of Florence, Viale Pieraccini 6, 50139 Florence (Italy); Moretti, Silvia [Department of Dermatological Sciences, University of Florence, Viale Pieraccini 6, 50139 Florence (Italy)

2004-11-22

Vitiligo is an acquired pigmentary disorder of the skin of unknown aetiology. The autocytotoxic hypothesis suggests that melanocyte impairment could be related to increased oxidative stress. Evidences have been reported that in vitiligo oxidative stress might also be present systemically. We used the comet assay (single cell alkaline gel electrophoresis) to evaluate DNA strand breaks and DNA base oxidation, measured as formamidopyrimidine DNA glycosylase (FPG)-sensitive sites, in peripheral blood cells from patients with active vitiligo and healthy controls. The basal level of oxidative DNA damage in mononuclear leukocytes was increased in vitiligo compared to normal subjects, whereas DNA strand breaks (SBs) were not changed. This alteration was not accompanied by a different capability to respond to in vitro oxidative challenge. No differences in the basal levels of DNA damage in polymorphonuclear leukocytes were found between patients and healthy subjects. Thus, this study supports the hypothesis that in vitiligo a systemic oxidative stress exists, and demonstrates for the first time the presence of oxidative alterations at the nuclear level. The increase in oxidative DNA damage shown in the mononuclear component of peripheral blood leukocytes from vitiligo patients was not particularly severe. However, these findings support an adjuvant role of antioxidant treatment in vitiligo.

Increased oxidative DNA damage in mononuclear leukocytes in vitiligo

International Nuclear Information System (INIS)

Giovannelli, Lisa; Bellandi, Serena; Pitozzi, Vanessa; Fabbri, Paolo; Dolara, Piero; Moretti, Silvia

2004-01-01

Vitiligo is an acquired pigmentary disorder of the skin of unknown aetiology. The autocytotoxic hypothesis suggests that melanocyte impairment could be related to increased oxidative stress. Evidences have been reported that in vitiligo oxidative stress might also be present systemically. We used the comet assay (single cell alkaline gel electrophoresis) to evaluate DNA strand breaks and DNA base oxidation, measured as formamidopyrimidine DNA glycosylase (FPG)-sensitive sites, in peripheral blood cells from patients with active vitiligo and healthy controls. The basal level of oxidative DNA damage in mononuclear leukocytes was increased in vitiligo compared to normal subjects, whereas DNA strand breaks (SBs) were not changed. This alteration was not accompanied by a different capability to respond to in vitro oxidative challenge. No differences in the basal levels of DNA damage in polymorphonuclear leukocytes were found between patients and healthy subjects. Thus, this study supports the hypothesis that in vitiligo a systemic oxidative stress exists, and demonstrates for the first time the presence of oxidative alterations at the nuclear level. The increase in oxidative DNA damage shown in the mononuclear component of peripheral blood leukocytes from vitiligo patients was not particularly severe. However, these findings support an adjuvant role of antioxidant treatment in vitiligo

[Binding of the antileukemia drug Escherichia coli L-asparaginase to the plasma membrane of normal human mononuclear cells].

Science.gov (United States)

Mercado-Vianco, L; Arenas-Díaz, G

1999-06-01

To demonstrate that the enzyme L-asparaginase from Escherichia coli (EcA) binds to the plasma membranes of normal human lymphocytes and monocytes. Lymphocytes and monocytes were isolated from heparinized blood samples which came from healthy volunteer donors. The cells were incubated with EcA to detect a possible binding of the enzyme to the mononuclear cells by indirect immunofluorescence using confocal microscopy. Meanwhile, ultracentrifugation was used to obtain the erythrocyte ghost microsomal fraction (P100) which was then analyzed by Western blotting to determine if EcA binds the lipid bilayer unspecifically. For the immunoassays, monospecific polyclonal antibodies were obtained from ascitic tumors developed in mice immunized with commercial L-asparaginase. EcA bins the lymphocyte and monocyte plasma membranes. In monocytes, there occurs a capping phenomenon, that is, the accumulation of fluorescent marker in one region. The image analyzer highlights it clearly at a depth of 3.8 microns. This binding would be unspecific, that is, there is no mediation of a specific receptor that binds EcA. This arises from the ability of the enzyme to bind to the membranes of erythrocyte ghost, as evidenced by the ability of the molecule to associate with a hydrophobic medium. The antibodies against EcA obtained from ascitic tumours developed in mice do not show cross reactivity with Na+/K+ ATPase, aspartate aminotransferase, nor with extracts of blood cells, which would make it a specific tool for the detection of EcA in whole cells and in homogenates electrotransfered to nitrocellulose membranes. L-asparaginase from E. coli behaves as a lipoprotein due to its ability to insert itself into hydrophobic environments, in which it resembles an isozyme present in T. pyriformis. The binding of this enzyme to lymphocytes and monocytes, demonstrated in this work, would permit the modification of the antileukemic treatment injecting doses of EcA bound to patient's own isolated immune

Heme-containing enzymes and inhibitors for tryptophan metabolism.

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Yan, Daojing; Lin, Ying-Wu; Tan, Xiangshi

2017-09-20

Iron-containing enzymes such as heme enzymes play crucial roles in biological systems. Three distinct heme-containing dioxygenase enzymes, tryptophan 2,3-dioxygenase (TDO), indoleamine 2,3-dioxygenase 1 (IDO1) and indoleamine 2,3-dioxygenase 2 (IDO2) catalyze the initial and rate-limiting step of l-tryptophan catabolism through the kynurenine pathway in mammals. Overexpression of these enzymes causes depletion of tryptophan and the accumulation of metabolic products, which contributes to tumor immune tolerance and immune dysregulation in a variety of disease pathologies. In the past few decades, IDO1 has garnered the most attention as a therapeutic target with great potential in cancer immunotherapy. Many potential inhibitors of IDO1 have been designed, synthesized and evaluated, among which indoximod (d-1-MT), INCB024360, GDC-0919 (formerly NLG-919), and an IDO1 peptide-based vaccine have advanced to the clinical trial stage. However, recently, the roles of TDO and IDO2 have been elucidated in immune suppression. In this review, the current drug discovery landscape for targeting TDO, IDO1 and IDO2 is highlighted, with particular attention to the recent use of drugs in clinical trials. Moreover, the crystal structures of these enzymes, in complex with inhibitors, and the mechanisms of Trp catabolism in the first step, are summarized to provide information for facilitating the discovery of new enzyme inhibitors.

Inflammation and ER Stress Downregulate BDH2 Expression and Dysregulate Intracellular Iron in Macrophages

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Susu M. Zughaier

2014-01-01

Full Text Available Macrophages play a very important role in host defense and in iron homeostasis by engulfing senescent red blood cells and recycling iron. Hepcidin is the master iron regulating hormone that limits dietary iron absorption from the gut and limits iron egress from macrophages. Upon infection macrophages retain iron to limit its bioavailability which limits bacterial growth. Recently, a short chain butyrate dehydrogenase type 2 (BDH2 protein was reported to contain an iron responsive element and to mediate cellular iron trafficking by catalyzing the synthesis of the mammalian siderophore that binds labile iron; therefore, BDH2 plays a crucial role in intracellular iron homeostasis. However, BDH2 expression and regulation in macrophages have not yet been described. Here we show that LPS-induced inflammation combined with ER stress led to massive BDH2 downregulation, increased the expression of ER stress markers, upregulated hepcidin expression, downregulated ferroportin expression, caused iron retention in macrophages, and dysregulated cytokine release from macrophages. We also show that ER stress combined with inflammation synergistically upregulated the expression of the iron carrier protein NGAL and the stress-inducible heme degrading enzyme heme oxygenase-1 (HO-1 leading to iron liberation. This is the first report to show that inflammation and ER stress downregulate the expression of BDH2 in human THP-1 macrophages.

Manganese and iron oxidation by fungi isolated from building stone.

Science.gov (United States)

de la Torre, M A; Gomez-Alarcon, G

1994-01-01

Acid and nonacid generating fungal strains isolated from weathered sandstone, limestone, and granite of Spanish cathedrals were assayed for their ability to oxidize iron and manganese. In general, the concentration of the different cations present in the mineral salt media directly affected Mn(IV) oxide formation, although in some cases, the addition of glucose and nitrate to the culture media was necessary. Mn(II) oxidation in acidogenic strains was greater in a medium containing the highest concentrations of glucose, nitrate, and manganese. High concentrations of Fe(II), glucose, and mineral salts were optimal for iron oxidation. Mn(IV) precipitated as oxides or hydroxides adhered to the mycelium. Most of the Fe(III) remained in solution by chelation with organic acids excreted by acidogenic strains. Other metabolites acted as Fe(III) chelators in nonacidogenic strains, although Fe(III) deposits around the mycelium were also detected. Both iron and manganese oxidation were shown to involve extracellular, hydrosoluble enzymes, with maximum specific activities during exponential growth. Strains able to oxidize manganese were also able to oxidize iron. It is concluded that iron and manganese oxidation reported in this work were biologically induced by filamentous fungi mainly by direct (enzymatic) mechanisms.

Iron and stony-iron meteorites

DEFF Research Database (Denmark)

Benedix, Gretchen K.; Haack, Henning; McCoy, T. J.

2014-01-01

Without iron and stony-iron meteorites, our chances of ever sampling the deep interior of a differentiated planetary object would be next to nil. Although we live on a planet with a very substantial core, we will never be able to sample it. Fortunately, asteroid collisions provide us with a rich...... sampling of the deep interiors of differentiated asteroids. Iron and stony-iron meteorites are fragments of a large number of asteroids that underwent significant geological processing in the early solar system. Parent bodies of iron and some stony-iron meteorites completed a geological evolution similar...... to that continuing on Earth – although on much smaller length- and timescales – with melting of the metal and silicates; differentiation into core, mantle, and crust; and probably extensive volcanism. Iron and stony-iron meteorites are our only available analogues to materials found in the deep interiors of Earth...

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

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

2014-12-01

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

Mononuclear cell secretome protects from experimental autoimmune myocarditis.

Science.gov (United States)

Hoetzenecker, Konrad; Zimmermann, Matthias; Hoetzenecker, Wolfram; Schweiger, Thomas; Kollmann, Dagmar; Mildner, Michael; Hegedus, Balazs; Mitterbauer, Andreas; Hacker, Stefan; Birner, Peter; Gabriel, Christian; Gyöngyösi, Mariann; Blyszczuk, Przemyslaw; Eriksson, Urs; Ankersmit, Hendrik Jan

2015-03-14

Supernatants of serum-free cultured mononuclear cells (MNC) contain a mix of immunomodulating factors (secretome), which have been shown to attenuate detrimental inflammatory responses following myocardial ischaemia. Inflammatory dilated cardiomyopathy (iDCM) is a common cause of heart failure in young patients. Experimental autoimmune myocarditis (EAM) is a CD4+ T cell-dependent model, which mirrors important pathogenic aspects of iDCM. The aim of this study was to determine the influence of MNC secretome on myocardial inflammation in the EAM model. BALB/c mice were immunized twice with an alpha myosin heavy chain peptide together with Complete Freund adjuvant. Supernatants from mouse mononuclear cells were collected, dialysed, and injected i.p. at Day 0, Day 7, or Day 14, respectively. Myocarditis severity, T cell responses, and autoantibody formation were assessed at Day 21. The impact of MNC secretome on CD4+ T cell function and viability was evaluated using in vitro proliferation and cell viability assays. A single high-dose application of MNC secretome, injected at Day 14 after the first immunization, effectively attenuated myocardial inflammation. Mechanistically, MNC secretome induced caspase-8-dependent apoptosis in autoreactive CD4+ T cells. MNC secretome abrogated myocardial inflammation in a CD4+ T cell-dependent animal model of autoimmune myocarditis. This anti-inflammatory effect of MNC secretome suggests a novel and simple potential treatment concept for inflammatory heart diseases. © The Author 2013. Published by Oxford University Press on behalf of the European Society of Cardiology.

Effects of Dietary Iron and Gamma Radiation on the Rat Retina

Science.gov (United States)

Morgan, Jennifer; Marshall, Grace; Theriot, Corey A.; Chacon, Natalia; Zwart, Sara; Zanello, Susana B.

2012-01-01

A health risk of concern for NASA relates to radiation exposure and its synergistic effects with other space environmental factors, includi ng nutritional status of the crew. Astronauts consume almost three times the recommended daily allowance of iron due to the use of fortifie d foods aboard the International Space Station, with iron intake occa sionally exceeding six times the recommended values. Recently, NASA has become concerned with visual changes associated with spaceflight, a nd research is being conducted to elucidate the etiology of eye structure alterations in the spaceflight environment. Terrestrially, iron o verload is also associated with certain optic neuropathies. In additi on, due to its role in Fenton reactions, iron can potentiate oxidative stress, which is a recognized cause of cataract formation. As part o f a study investigating the combined effects of radiation exposure an d iron overload on multiple physiological systems, we focused on defining the effects of both treatments on eye biology. In this study, 12- week-old Sprague-Dawley rats were assigned to one of four experimental groups: normal iron/no radiation (Control/Sham), high iron/no radiat ion (Fe/Sham), normal iron/gamma radiation (3 Gy cumulative dose, fra ctionated at 0.375 Gy/d every other day for 16 d) (Control/Rad), and high iron/gamma radiation (Fe/Rad). Oxidative stress-induced DNA damag e, measured as concentration of the marker 8-hydroxy-2'-deoxyguanosine (8OHdG) in eye retinal tissue by enzyme-immunoanalysis did not show significant changes among treatments. However, there was an overall i ncrease in 8OHdG immunostaining density in retina sections due to radiation exposure (P = 0.05). Increased dietary iron and radiation expos ure had an interactive effect (P = 0.02) on 8OHdG immunostaining of t he retinal ganglion cell layer with iron diet increasing the signal in the group not exposed to radiation (P = 0.05). qPCR gene expression profiling of relevant target genes

Assessment of intake of iron and nutrients that affect bioavailability of daily food rations of girls

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Anna Broniecka

2014-06-01

Full Text Available INTRODUCTION AND AIM In a human body iron occurs at a level of 3 to 5 g, 60-70 % of which are in hemoglobin, ca. 10% in myoglobin, and ca. 3% are accumulated in enzymes of cellular respiration or enzymes degrading toxic hydrogen peroxide. The other part of iron is accumulated in liver, spleen, kidneys and bone marrow. The dietary deficiency of iron appears at its insufficient level in a diet and at impaired absorption of iron ions present in food products by a body. Groups at an especially high risk of iron deficiencies include, among others, menstruating girls in the pubescence period and women with heavy and irregular menstruations, as well as vegetarians and patients with chronic enteritis. The aim of this study was to evaluate the intake of iron and nutrients that affect its bioavailability from daily food rations of girls. MATERIAL AND METHODS The study included 159 girls aged 17-18, students of high schools in the city of Wroclaw. The study was conducted between November 2010 and ay 2011. Girls were divided into 3 subgroups according to the BMI score. Girls’ diets were analyzed with the method of a direct interview of the last 24 hours before the test and the interview was repeated seven times. RESULTS The present study demonstrated that the intake of iron from food rations of almost all the girls surveyed was below the requirements defined for this age group. Statistically significant differences were noted in the intake of energy and nutrients among the three distinguished subgroups of girls. CONCLUSIONS Food rations of the surveyed girls were characterized by a low, compared to dietary allowances, calorific value, which resulted in deficiencies of nutrients increasing iron bioavailability.

CORRELATION OF GALLSTONE FORMATION WITH SERUM IRON LEVELS

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Rohini Bipin Bhadre

2016-07-01

Full Text Available INTRODUCTION Gallstones are one of the most common problem associated with the gallbladder, affecting millions of people throughout the world. Bile is excreted from liver and gallbladder into Duodenum for digestion. After digestion, if the gallbladder is not emptied out completely, the Bile Juice that remains in the gallbladder can become too concentrated with cholesterol leading to gallstone formation. Cholesterol and calcium bilirubinate are the two main substances involved in gallstone formation. Gallstones derived from bile consists of mixture of cholesterol, bilirubin with or without calcium. Based on their chemical composition, gallstones found in the gallbladder are classified as cholesterol, pigmented or mixed stones. Iron deficiency has been shown to alter the activity of several hepatic enzymes, leading to increased gallbladder bile cholesterol saturation and promotion of cholesterol crystal formation. AIMS & OBJECTIVE Attempt to establish a correlation with gallstones and decreased serum iron levels. MATERIAL & METHODS This study was a prospective cohort study which included 100 consecutive patients with imaging studies suggestive of Cholelithiasis. The Gallstone surgically removed was crushed with mortar and pestle and then analysed for cholesterol, calcium, phosphate and bilirubin (pigment. Serum samples were analysed for Cholesterol, iron and iron binding capacity. RESULTS 86% patients had increased cholesterol levels (p=0.04 and 93% had decreased serum Iron levels (p=0.96. The most common type of gallstone was found to be Cholesterol type of gallstone followed by Mixed and Pigment gallstones. CONCLUSION Serum cholesterol levels were found to be raised in majority of the patients and serum iron was found to be low in these majority of the patients indicating iron deficiency may play a role in gallstone formation.

In vitro formation of osteoclasts from long-term cultures of bone marrow mononuclear phagocytes

International Nuclear Information System (INIS)

Burger, E.H.; Van der Meer, J.W.; van de Gevel, J.S.; Gribnau, J.C.; Thesingh, G.W.; van Furth, R.

1982-01-01

The origin of osteoclasts was studied in an in vitro model using organ cultures of periosteum-free embryonic mouse long-bone primordia, which were co-cultured with various cell populations. The bone rudiments were freed of their periosteum-perichondrium by collagenase treatment in a stage before cartilage erosion and osteoclast formation, and co-cultured for 7 d with either embryonic liver or mononuclear phagocytes from various sources. Light and electron microscopic examination of the cultures showed that mineralized matrix-resorbing osteoclasts developed only in bones co-cultured with embryonic liver or with cultured bone marrow mononuclear phagocytes but not when co-cultured with blood monocytes or resident or exudate peritoneal macrophages. Osteoclasts developed from the weakly adherent, but not from the strongly adherent cells of bone marrow cultures, whereas 1,000 rad irradiation destroyed the capacity of such cultures to form osteoclasts. In bone cultures to which no other cells were added, osteoclasts were virtually absent. Bone-resorbing activity of in vitro formed osteoclasts was demonstrated by 45 Ca release studies. These studies demonstrate that osteoclasts develop from cells present in cultures of proliferating mononuclear phagocytes and that, at least in our system, monocytes and macrophages are unable to form osteoclasts. The most likely candidates for osteoclast precursor cells seem to be monoblasts and promonocytes

Lactam hydrolysis catalyzed by mononuclear metallo-beta-lactamases: A density functional study

DEFF Research Database (Denmark)

Hemmingsen, Lars Bo Stegeager; Olsen, L.; Antony, J.

2003-01-01

Two central steps in the hydrolysis of lactam antibiotics catalyzed by mononuclear metallo-beta-lactamases, formation of the tetrahedral intermediate and its breakdown by proton transfer, are studied for model systems using the density functional B3LYP method. Metallo-beta-lactamases have two metal...

Hydrogen-Bonding Interactions Trigger a Spin-Flip in Iron(III) Porphyrin Complexes**

Science.gov (United States)

Sahoo, Dipankar; Quesne, Matthew G; de Visser, Sam P; Rath, Sankar Prasad

2015-01-01

A key step in cytochrome P450 catalysis includes the spin-state crossing from low spin to high spin upon substrate binding and subsequent reduction of the heme. Clearly, a weak perturbation in P450 enzymes triggers a spin-state crossing. However, the origin of the process whereby enzymes reorganize their active site through external perturbations, such as hydrogen bonding, is still poorly understood. We have thus studied the impact of hydrogen-bonding interactions on the electronic structure of a five-coordinate iron(III) octaethyltetraarylporphyrin chloride. The spin state of the metal was found to switch reversibly between high (S=5/2) and intermediate spin (S=3/2) with hydrogen bonding. Our study highlights the possible effects and importance of hydrogen-bonding interactions in heme proteins. This is the first example of a synthetic iron(III) complex that can reversibly change its spin state between a high and an intermediate state through weak external perturbations. PMID:26109743

Effect of nickel monolayer deposition on the structural and electronic properties of the low miller indices of (bcc) iron : A DFT study

NARCIS (Netherlands)

Kwawu, Caroline; Tia, Richard; Adei, Evans; Dzade, Nelson Y.; Catlow, Richard; de Leeuw, Nora H.

2017-01-01

Metal clusters of both iron (Fe) and nickel (Ni) have been found in nature as active electro-catalytic sites, for example in the enzyme carbon mono-oxide dehydrogenase found in autotrophic organisms. Thus, surface modification of iron with nickel could improve the surface work function to enhance

Modulation of the antioxidative response of Spartina densiflora against iron exposure.

Science.gov (United States)

Martínez Domínguez, David; Torronteras Santiago, Rafael; Córdoba García, Francisco

2009-06-01

Spartina densiflora, an invader cordgrass living in polluted salt marshes of the Odiel estuary (SW Spain), was collected and cultured under controlled laboratory conditions. After acclimation to non-polluted soils for 28 days, both metabolites and enzymes activities used as indicators of oxidative stress were reduced significantly. Then, plants were exposed to 500 and 1000 ppm Fe-ethylenediamine-N,N'-2-hydroxyphenyl acetic acid (EDDHA) for 28 days. Our data demonstrate that iron content in leaves was enhanced by iron exposure. This iron increase caused an enhancement in the concentration of H2O2, hydroperoxides and lipid peroxidation, and a decrease in chlorophyll levels. Thus, iron exposure led to oxidative stress conditions. However, oxidative indicators stabilised after first 2 weeks of exposure, although the highest iron levels in leaves were reached at the end of treatments. Iron exposure induced an enhancement of catalase, ascorbate peroxidase and guaiacol peroxidase activities, together with an increase in total and oxidised ascorbate. This response may be defensive against oxidative stress and thus help to explain why cell oxidative damages were stabilised. Thus, by using a sensitive long-time protocol, iron-dependent oxidative damages may be controlled and even reverted successfully by the activation of the antioxidative defences of S. densiflora. This efficient antioxidative system, rapidly modulated in response to excess iron and other environmental stressors, may account for S. densiflora's successful adaptation to stress conditions in its habitat.

[Dinitrosyl iron complexes are endogenous signaling agents in animal and human cells and tissues (a hypothesis)].

Science.gov (United States)

Vanin, A F

2004-01-01

The hypothesis was advanced that dinitrosyl iron complexes generated in animal and human cells and tissues producing nitric oxide can function as endogenous universal regulators of biochemical and physiological processes. This function is realized by the ability of dinitrosyl iron complexes to act as donors of free nitric oxide molecules interacting with the heme groups of proteins, nitrosonium ions, or Fe+(NO+)2 interacting with the thiol groups of proteins. The effect of dinitrosyl iron complexes on the activity of some enzymes and the expression of the genome at the translation and transcription levels was considered.

Enzyme technology for precision functional food ingredient processes.

Science.gov (United States)

Meyer, Anne S

2010-03-01

A number of naturally occurring dietary substances may exert physiological benefits. The production of enhanced levels or particularly tailored versions of such candidate functional compounds can be targeted by enzymatic catalysis. The recent literature contains examples of enhancing bioavailability of iron via enzyme-catalyzed degradation of phytate in wheat bran, increasing diacyl-glycerol and conjugated linoleic acid levels by lipase action, enhancing the absorption of the citrus flavonoid hesperetin via rhamnosidase treatment, and obtaining solubilized dietary fiber via enzymatic modification of potato starch processing residues. Such targeted enzyme-catalyzed reactions provide new invention opportunities for designing functional foods with significant health benefits. The provision of well-defined naturally structured compounds can, moreover, assist in obtaining the much-needed improved understanding of the physiological benefits of complex natural substances.

Nonanuclear Spin-Crossover Complex Containing Iron(II) and Iron(III) Based on a 2,6-Bis(pyrazol-1-yl)pyridine Ligand Functionalized with a Carboxylate Group.

Science.gov (United States)

Abhervé, Alexandre; Recio-Carretero, María José; López-Jordà, Maurici; Clemente-Juan, Juan Modesto; Canet-Ferrer, Josep; Cantarero, Andrés; Clemente-León, Miguel; Coronado, Eugenio

2016-09-19

The synthesis and magnetostructural characterization of [Fe(III)3(μ3-O)(H2O)3[Fe(II)(bppCOOH)(bppCOO)]6](ClO4)13·(CH3)2CO)6·(solvate) (2) are reported. This compound is obtained as a secondary product during synthesis of the mononuclear complex [Fe(II)(bppCOOH)2](ClO4)2 (1). The single-crystal X-ray diffraction structure of 2 shows that it contains the nonanuclear cluster of the formula [Fe(III)3(μ3-O)(H2O)3[Fe(II)(bppCOOH)(bppCOO)]6](13+), which is formed by a central Fe(III)3O core coordinated to six partially deprotonated [Fe(II)(bppCOOH)(bppCOO)](+) complexes. Raman spectroscopy studies on single crystals of 1 and 2 have been performed to elucidate the spin and oxidation states of iron in 2. These studies and magnetic characterization indicate that most of the iron(II) complexes of 2 remain in the low-spin (LS) state and present a gradual and incomplete spin crossover above 300 K. On the other hand, the Fe(III) trimer shows the expected antiferromagnetic behavior. From the structural point of view, 2 represents the first example in which bppCOO(-) acts as a bridging ligand, thus forming a polynuclear magnetic complex.

Iron as a risk factor in neurological diseases

Science.gov (United States)

Galazka-Friedman, Jolanta

2008-02-01

In this review the properties of iron in various human brain structures (e.g. Substantia nigra, globus pallidus, hippocampus) were analyzed to assess the possibility of initiation of oxidative stress leading to such diseases as Parkinson’s and Alzheimer’s disease, and progressive supranuclear palsy. Our own studies with the use of Mössbauer spectroscopy, electron microscopy and enzyme-linked immuno-absorbent assay (ELISA) were confronted with other methods used in other laboratories. Our results suggest that hippocampus is the most fragile for oxidative stress structure in human brain (the death of nervous cells in hippocampus leads to Alzheimer’s disease). Changes in iron metabolism were also found in substantia nigra (the death of nervous cells of this structure produces Parkinson’s disease) and in globus pallidus (neurodegeneration of this structure causes progressive supranuclear palsy).

Iron as a risk factor in neurological diseases

International Nuclear Information System (INIS)

Galazka-Friedman, Jolanta

2008-01-01

In this review the properties of iron in various human brain structures (e.g. Substantia nigra, globus pallidus, hippocampus) were analyzed to assess the possibility of initiation of oxidative stress leading to such diseases as Parkinson's and Alzheimer's disease, and progressive supranuclear palsy. Our own studies with the use of Moessbauer spectroscopy, electron microscopy and enzyme-linked immuno-absorbent assay (ELISA) were confronted with other methods used in other laboratories. Our results suggest that hippocampus is the most fragile for oxidative stress structure in human brain (the death of nervous cells in hippocampus leads to Alzheimer's disease). Changes in iron metabolism were also found in substantia nigra (the death of nervous cells of this structure produces Parkinson's disease) and in globus pallidus (neurodegeneration of this structure causes progressive supranuclear palsy).

Iron Refractory Iron Deficiency Anaemia: A Rare Cause of Iron Deficiency Anaemia

LENUS (Irish Health Repository)

McGrath, T

2018-01-01

We describe the case of a 17-month-old boy with a hypochromic microcytic anaemia, refractory to oral iron treatment. After exclusion of dietary and gastrointestinal causes of iron deficiency, a genetic cause for iron deficiency was confirmed by finding two mutations in the TMPRSS6 gene, consistent with a diagnosis of iron-refractory iron deficiency anaemia (IRIDA).

Antioxidative responses of Elodea nuttallii (Planch.) H. St. John to short-term iron exposure.

Science.gov (United States)

Xing, Wei; Li, Dunhai; Liu, Guihua

2010-01-01

Antioxidative responses of Elodea nuttallii (Planch.) H. St. John to short-term iron exposure were investigated in the study. Results showed that iron accumulation in E. nuttallii was concentration dependent. Growth of E. nuttallii was promoted by low iron concentration (1-10 mg L(-1) [Fe(3+)]), but growth inhibition was observed when iron concentration beyond 10 mg L(-1). The synthesis of protein and pigments increased within 1-10 mg L(-1) [Fe(3+)] range. The activities of superoxide dismutase (SOD), catalase (CAT), peroxidase (POD) and glutathione-S-transferase (GST) were up to maximal values at 10 mg L(-1) [Fe(3+)]. High iron concentration inhibited the synthesis of protein and pigments as well as activities of antioxidative enzymes, and accelerated degradation of pigment and production of ROS. Low iron concentration had no significant influences on PSII maximal quantum yield, activity of PSII and relative electron transport rate though PSII. Malondialdehyde (MDA) and proline concentrations were highest at 100 and 1 mg L(-1) [Fe(3+)], respectively. Copyright © 2010 Elsevier Masson SAS. All rights reserved.

Evaluation of renal allografts using {sup 99m} Tc mononuclear leukocytes; Avaliacao de transplantes renais utilizando-se {sup 99m} Tc-leucocitos mononucleares

Energy Technology Data Exchange (ETDEWEB)

Souza, Sergio Augusto Lopes de; Martins, Flavia Paiva Proenca; Carvalho, Antonio Carlos Pires; Gutfilen, Bianca [Universidade Federal, Rio de Janeiro, RJ (Brazil). Faculdade de Medicina. Dept. de Radiologia]. E-mail: sergioalsouza@ufrj.br; Goncalves, Renato Torres; Pontes, Daniela Salomao [Hospital Universitario Clementino Fraga Filho, Rio de Janeiro, RJ (Brazil). Servico de Nefrologia; Fonseca, Lea Mirian Barbosa da [Universidade Federal, Rio de Janeiro, RJ (Brazil). Faculdade de Medicina. Dept. de Medicina Nuclear

2004-02-01

Renal allograft acute rejection must be promptly diagnosed since its reversibility is related to the readiness in which treatment is initiated. The aim of this study was: to establish a quantitative method to evaluate kidney rejection and acute tubular necrosis (Attn); to assess the potential role of {sup 99m} Tc-mononuclear leukocytes scintigraphy in the diagnosis of renal rejection and differential diagnosis of Attn. One hundred and sixty studies were performed in 80 renal transplant patients at the first and fifth day after transplantation. Autologous cells were used for labeling. Images were obtained at 30 minutes, 3 hours and 24 hours after intravenous administration of 444 MBq (12 mCi) of labeled cells. There was abnormal labeled cells uptake in 27 of 31 cases of rejection and in 6 of 8 cases of Attn. The results of each patient were compared with clinical findings. Doppler scanning detected 18 of 31 cases of rejection. Rejection diagnosis sensitivity and specificity rates using scintigraphy were 87.1 per cent and 100 per cent, respectively, and 58.1 per cent and 100 per cent, respectively using ultrasound. Renal biopsy was performed in eight patients which demonstrated seven cases of rejection and one case of ATN. These results suggest that {sup 99m} Tc-mononuclear leukocytes imaging may be useful in the early diagnosis of rejection and in the differential diagnosis of ATN. (author)

Characterisation of citrate and iron citrate uptake by cultured rat hepatocytes

International Nuclear Information System (INIS)

Graham, R.M.; Morgan, E.H.; Baker, E.

1998-01-01

Background/Aims: the endogenous low molecular weight iron chelator, citrate, is considered to be an important contributor to iron transport and the liver the main site of uptake of iron citrate in subjects suffering from diseases of iron overload. Moreover, the citrate-metabolising enzyme, aconitase, is implicated in the regulation of cellular iron metabolism. This study was undertaken to determine the role of citrate and ferric citrate in the uptake of iron by rat hepatocytes. Methods: Cultured rat hepatocytes were incubated (37 deg. C, 15 min) with 100 μM [ 14 C]-citrate in the presence or absence of 1.0 μM 55 Fe. Membrane-bound and intracellular radiolabel were separated by incubation with the general protease, Pronase. Results: Our results suggest that ferric citrate uptake is mediated by a specific citrate binding site which exhibits a higher affinity for citrate in the presence of iron than in its absence. Citrate was internalised by hepatocytes, with at least 70% being oxidised to CO 2 within 15 min. Citrate uptake was pH-dependent, did not require the presence of sodium and increased with increasing iron concentration. Metabolic energy, anion channels, the Na + , K + -ATPase and vesicle acidification do not appear to play a role in uptake of ferric citrate, but functional sulphydryl groups may be involved. Conclusions: The data suggest either that ferric citrate complexes with higher molar ratios of iron to citrate relative to the incubation medium are bound preferentially to the membrane, or that once citrate has delivered its iron to the membrane, the complex dissociates and the components are internalised separately. (au)

Amyotrophic Lateral Sclerosis Multiprotein Biomarkers in Peripheral Blood Mononuclear Cells

OpenAIRE

Nardo, Giovanni; Pozzi, Silvia; Pignataro, Mauro; Lauranzano, Eliana; Spano, Giorgia; Garbelli, Silvia; Mantovani, Stefania; Marinou, Kalliopi; Papetti, Laura; Monteforte, Marta; Torri, Valter; Paris, Luca; Bazzoni, Gianfranco; Lunetta, Christian; Corbo, Massimo

2011-01-01

Background Amyotrophic lateral sclerosis (ALS) is a fatal progressive motor neuron disease, for which there are still no diagnostic/prognostic test and therapy. Specific molecular biomarkers are urgently needed to facilitate clinical studies and speed up the development of effective treatments. Methodology/Principal Findings We used a two-dimensional difference in gel electrophoresis approach to identify in easily accessible clinical samples, peripheral blood mononuclear cells (PBMC), a panel...

Proteome scale identification, classification and structural analysis of iron-binding proteins in bread wheat.

Science.gov (United States)

Verma, Shailender Kumar; Sharma, Ankita; Sandhu, Padmani; Choudhary, Neha; Sharma, Shailaja; Acharya, Vishal; Akhter, Yusuf

2017-05-01

Bread wheat is one of the major staple foods of worldwide population and iron plays a significant role in growth and development of the plant. In this report, we are presenting the genome wide identification of iron-binding proteins in bread wheat. The wheat genome derived putative proteome was screened for identification of iron-binding sequence motifs. Out of 602 putative iron-binding proteins, 130 were able to produce reliable structural models by homology techniques and further analyzed for the presence of iron-binding structural motifs. The computationally identified proteins appear to bind to ferrous and ferric ions and showed diverse coordination geometries. Glu, His, Asp and Cys amino acid residues were found to be mostly involved in iron binding. We have classified these proteins on the basis of their localization in the different cellular compartments. The identified proteins were further classified into their protein folds, families and functional classes ranging from structure maintenance of cellular components, regulation of gene expression, post translational modification, membrane proteins, enzymes, signaling and storage proteins. This comprehensive report regarding structural iron binding proteome provides useful insights into the diversity of iron binding proteins of wheat plants and further utilized to study their roles in plant growth, development and physiology. Copyright © 2017 Elsevier Inc. All rights reserved.

Autoimmune gastritis presenting as iron deficiency anemia in childhood.

Science.gov (United States)

Gonçalves, Cristina; Oliveira, Maria Emília; Palha, Ana M; Ferrão, Anabela; Morais, Anabela; Lopes, Ana Isabel

2014-11-14

corpus atrophic gastritis with lymphocytic infiltration (5/5), patchy oxyntic gland mononuclear cell infiltration (5/5), intestinal and/or pseudo-pyloric metaplasia in corpus mucosa (4/5), and enterochromaffin cell hyperplasia (4/5). Immunochemistry for gastrin on corpus biopsies was negative in all cases. Duodenal histology was normal. All biopsies were negative for H. pylori (Giemsa staining and cultural examination). We highlight autoimmune gastritis as a diagnosis to be considered when investigating refractory iron deficiency anemia in children, particularly in the setting of a personal/familial history of autoimmune disease, as well as the diagnostic contribution of a careful immunohistological evaluation.

Iron and Vitamin C Co-Supplementation Increased Serum Vitamin C Without Adverse Effect on Zinc Level in Iron Deficient Female Youth

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Mohammad Reza Khoshfetrat

2014-01-01

Full Text Available Background: Iron supplementation can decrease the absorption of zinc and influence other antioxidants levels such as vitamin C. This study aimed to investigate the effect of iron supplements alone and in combination with vitamin C on zinc and vitamin C status in iron deficient female students. Methods: In a double-blind randomized clinical trail, 60 iron deficient students were selected from 289 volunteers residing in dormitory. After matching, subjects were randomly assigned into two groups: Group I (50 mg elemental iron supplements and Group II (50 mg elemental iron + 500 mg ascorbic acid. Serum ferritin, iron, serum zinc, and plasma vitamin C concentrations were measured by using enzyme-linked immunosorbent assay, spectrophotometer, atomic absorption spectrometer, and colorimeter, respectively after 6 and 12 weeks supplementation. Student′s t-test and repeated measures analysis of variance were applied to analyze the data using SPSS software. Results: Serum zinc levels had no significant differences between 2 groups at the baseline; however, its concentration decreased from 80.9 ± 4.2-68.9 ± 2.7 μg/dl to 81.2 ± 4.5-66.1 ± 2.9 μg/dl (P < 0.001 in Groups I and II, respectively after 6 weeks of supplementation. Continuous supplementation increased serum zinc concentration to baseline levels (79.0 ± 2.9 μg/dl; P < 0.01 in Group I and 70.5 ± 3.1 μg/dl in Group II following 12 weeks of supplementation. Plasma vitamin C increased from 3 ± 0/1-3.3 ± 0.2 mg/dl to 2.7 ± 0. 1-4.2 ± 0.2 mg/dl (P < 0.01 in Groups I and II, respectively. At the end of study, plasma vitamin C significantly increased from 3.3 ± 0.3-4.7 ± 0.3 (P < 0.01 to 4.2 ± 0.2-7.1 ± 0.2 (P < 0.001 in Groups I and II, respectively. Conclusions: Iron supplementation with and without vitamin C led to reduction in serum Zn in iron-deficient female students after 6 weeks. However, the decreasing trend stops after repletion of iron stores and Zn levels returned to the

The metabolites in peripheral blood mononuclear cells showed greater differences between patients with impaired fasting glucose or type 2 diabetes and healthy controls than those in plasma.

Science.gov (United States)

Kim, Minjoo; Kim, Minkyung; Han, Ji Yun; Lee, Sang-Hyun; Jee, Sun Ha; Lee, Jong Ho

2017-03-01

To determine differences between peripheral blood mononuclear cells and the plasma metabolites in patients with impaired fasting glucose or type 2 diabetes and healthy controls. In all, 65 nononobese patients (aged 30-70 years) with impaired fasting glucose or type 2 diabetes and 65 nonobese sex-matched healthy controls were included, and fasting peripheral blood mononuclear cell and plasma metabolomes were profiled. The diabetic or impaired fasting glucose patients showed higher circulating and peripheral blood mononuclear cell lipoprotein phospholipase A 2 activities, high-sensitivity C-reactive protein and tumour necrosis factor-α than controls. Compared with controls, impaired fasting glucose or diabetic subjects showed increases in 11 peripheral blood mononuclear cell metabolites: six amino acids (valine, leucine, methionine, phenylalanine, tyrosine and tryptophan), l-pyroglutamic acid, two fatty acid amides containing palmitic amide and oleamide and two lysophosphatidylcholines. In impaired fasting glucose or diabetic patients, peripheral blood mononuclear cell lipoprotein phospholipase A 2 positively associated with peripheral blood mononuclear cell lysophosphatidylcholines and circulating inflammatory markers, including tumour necrosis factor-α, high-sensitivity C-reactive protein and lipoprotein phospholipase A 2 activities. In plasma metabolites between patients and healthy controls, we observed significant increases in only three amino acids (proline, valine and leucine) and decreases in only five lysophosphatidylcholines. This study demonstrates significant differences in the peripheral blood mononuclear cell metabolome in patients with impaired fasting glucose or diabetes compared with healthy controls. These differences were greater than those observed in the plasma metabolome. These data suggest peripheral blood mononuclear cells as a useful tool to better understand the inflammatory pathophysiology of diabetes.

The synthesis of chlorophyll-a biosynthetic precursors and methyl substituted iron porphyrins

International Nuclear Information System (INIS)

Matera, K.M.

1988-01-01

The biosynthetic intermediates were incubated in a plant system. The activity levels calculated show that magnesium 6-acrylate porphyrins and one of the magnesium 6-β-hydroxypropionate porphyrins are not intermediates. In addition, plant systems incubated with 18 O 2 were found to synthesize magnesium 2,4-divinyl pheoporphyrin-a 5 incorporated with 18 O at the 9-carbonyl oxygen. Mass spectroscopy confirmed the presence of the oxygen label, thus eliminating one of two hypothesized pathways to chlorophyll-a. An overall description is given of iron porphyrins and iron porphyrin containing proteins. The function of the propionic side chains of the heme prosthetic group during electron transport reactions will be investigated. The synthesis of a series of iron(III) hexamethyl porphyrins with increasingly longer substituents in the remaining two peripheral positions of the porphyrin is described. Models for NMR studies of iron chlorin containing enzymes are discussed. Iron(III) pyropheophorbide-a and methyl pyropheophorbide-a were synthesized in addition to 5-CD 3 , 10-CD 2 iron(III) pyropheophorbide-a and methyl pyropheophorbide-a. Together, these pyropheophorbides were used to assign NMR resonances and ultimately provide a model for other iron chlorins. The synthesis of nickel(II) anhydro-mesorhodoporphyrin from zinc(III) anhydromesorhodochlorin is described; this nickel porphyrin was used as a standard for ring current calculations of reduced nickel analogs of anhydromesorhodoporphyrin

Rapid Column-Free Enrichment of Mononuclear Cells from Solid Tissues

Science.gov (United States)

Scoville, Steven D.; Keller, Karen A.; Cheng, Stephanie; Zhang, Michael; Zhang, Xiaoli; Caligiuri, Michael A.; Freud, Aharon G.

2015-01-01

We have developed a rapid negative selection method to enrich rare mononuclear cells from human tissues. Unwanted and antibody-tethered cells are selectively depleted during a Ficoll separation step, and there is no need for magnetic-based reagents and equipment. The new method is fast, customizable, inexpensive, remarkably efficient, and easy to perform, and per sample the overall cost is less than one-tenth the cost associated with a magnetic column-based method. PMID:26223896

Electronic and spatial structures of water-soluble dinitrosyl iron complexes with thiol-containing ligands underlying their ability to act as nitric oxide and nitrosonium ion donors.

Science.gov (United States)

Vanin, Anatoly F; Burbaev, Dosymzhan Sh

2011-01-01

The ability of mononuclear dinitrosyl iron commplexes (M-DNICs) with thiolate ligands to act as NO donors and to trigger S-nitrosation of thiols can be explain only in the paradigm of the model of the [Fe(+)(NO(+))(2)] core ({Fe(NO)(2)}(7) according to the Enemark-Feltham classification). Similarly, the {(RS(-))(2)Fe(+)(NO(+))(2)}(+) structure describing the distribution of unpaired electron density in M-DNIC corresponds to the low-spin (S = 1/2) state with a d(7) electron configuration of the iron atom and predominant localization of the unpaired electron on MO(d(z2)) and the square planar structure of M-DNIC. On the other side, the formation of molecular orbitals of M-DNIC including orbitals of the iron atom, thiolate and nitrosyl ligands results in a transfer of electron density from sulfur atoms to the iron atom and nitrosyl ligands. Under these conditions, the positive charge on the nitrosyl ligands diminishes appreciably, the interaction of the ligands with hydroxyl ions or with thiols slows down and the hydrolysis of nitrosyl ligands and the S-nitrosating effect of the latter are not manifested. Most probably, the S-nitrosating effect of nitrosyl ligands is a result of weak binding of thiolate ligands to the iron atom under conditions favoring destabilization of M-DNIC.

Genetics Home Reference: iron-refractory iron deficiency anemia

Science.gov (United States)

... refractory iron deficiency anemia Iron-refractory iron deficiency anemia Printable PDF Open All Close All Enable Javascript ... expand/collapse boxes. Description Iron-refractory iron deficiency anemia is one of many types of anemia , which ...

Effects of simulated deposition of acid mist and iron ore particulate matter on photosynthesis and the generation of oxidative stress in Schinus terebinthifolius Radii and Sophora tomentosa L.

Science.gov (United States)

Kuki, Kacilda Naomi; Oliva, Marco Antônio; Pereira, Eduardo Gusmão; Costa, Alan Carlos; Cambraia, José

2008-09-15

Particulate matter is a natural occurrence in the environment, but some industries, such as the iron ore sector, can raise the total amount of particles in the atmosphere. This industry is primarily a source of iron and sulfur dioxide particulates. The effects of the pollutants from the iron ore industries on representatives of restinga vegetation in a Brazilian coastal ecosystem were investigated using physiological and biochemical measures. Two species, Schinus terebinthifolius and Sophora tomentosa, were exposed to simulated deposition of acid mist and iron ore particulate matter in acrylic chambers in a greenhouse. Parameters such as gas exchange, fluorescence emission, chlorophyll content, total iron content, antioxidant enzyme activity and malondialdehyde content were assessed in order to evaluate the responses of the two species. Neither treatment was capable of inducing oxidative stress in S. terebinthifolius. Nevertheless, the deposition of iron ore particulates on this species increased chlorophyll content, the maximum quantum efficiency of photosystem II and the electron transport rate, while iron content was unaltered. On the other hand, S. tomentosa showed a greater sensitivity to the treatments. Plants of S. tomentosa that were exposed to acid mist had a decrease in photosynthesis, while the deposition of iron particulate matter led to an increase in iron content and membrane permeability of the leaves. The activities of antioxidant enzymes, such as catalases and superoxide dismutase, were enhanced by both treatments. The results suggested that the two restinga species use different strategies to overcome the stressful conditions created by the deposition of particulate matter, either solid or wet. It seems that while S. terebinthifolius avoided stress, S. tomentosa used antioxidant enzyme systems to partially neutralize oxidative stress. The findings also point to the potential use of S. tomentosa as a biomarker species under field conditions.

Effects of simulated deposition of acid mist and iron ore particulate matter on photosynthesis and the generation of oxidative stress in Schinus terebinthifolius Radii and Sophora tomentosa L

Energy Technology Data Exchange (ETDEWEB)

Kuki, Kacilda Naomi [Departamento de Biologia Vegetal, Universidade Federal de Vicosa (Brazil)], E-mail: naomikuki@hotmail.com; Oliva, Marco Antonio; Pereira, Eduardo Gusmao; Costa, Alan Carlos [Departamento de Biologia Vegetal, Universidade Federal de Vicosa (Brazil); Cambraia, Jose [Departamento de Biologia Geral, Universidade Federal de Vicosa (Brazil)

2008-09-15

Particulate matter is a natural occurrence in the environment, but some industries, such as the iron ore sector, can raise the total amount of particles in the atmosphere. This industry is primarily a source of iron and sulfur dioxide particulates. The effects of the pollutants from the iron ore industries on representatives of restinga vegetation in a Brazilian coastal ecosystem were investigated using physiological and biochemical measures. Two species, Schinus terebinthifolius and Sophora tomentosa, were exposed to simulated deposition of acid mist and iron ore particulate matter in acrylic chambers in a greenhouse. Parameters such as gas exchange, fluorescence emission, chlorophyll content, total iron content, antioxidant enzyme activity and malondialdehyde content were assessed in order to evaluate the responses of the two species. Neither treatment was capable of inducing oxidative stress in S. terebinthifolius. Nevertheless, the deposition of iron ore particulates on this species increased chlorophyll content, the maximum quantum efficiency of photosystem II and the electron transport rate, while iron content was unaltered. On the other hand, S. tomentosa showed a greater sensitivity to the treatments. Plants of S. tomentosa that were exposed to acid mist had a decrease in photosynthesis, while the deposition of iron particulate matter led to an increase in iron content and membrane permeability of the leaves. The activities of antioxidant enzymes, such as catalases and superoxide dismutase, were enhanced by both treatments. The results suggested that the two restinga species use different strategies to overcome the stressful conditions created by the deposition of particulate matter, either solid or wet. It seems that while S. terebinthifolius avoided stress, S. tomentosa used antioxidant enzyme systems to partially neutralize oxidative stress. The findings also point to the potential use of S. tomentosa as a biomarker species under field conditions.

Effects of simulated deposition of acid mist and iron ore particulate matter on photosynthesis and the generation of oxidative stress in Schinus terebinthifolius Radii and Sophora tomentosa L

International Nuclear Information System (INIS)

Kuki, Kacilda Naomi; Oliva, Marco Antonio; Pereira, Eduardo Gusmao; Costa, Alan Carlos; Cambraia, Jose

2008-01-01

Particulate matter is a natural occurrence in the environment, but some industries, such as the iron ore sector, can raise the total amount of particles in the atmosphere. This industry is primarily a source of iron and sulfur dioxide particulates. The effects of the pollutants from the iron ore industries on representatives of restinga vegetation in a Brazilian coastal ecosystem were investigated using physiological and biochemical measures. Two species, Schinus terebinthifolius and Sophora tomentosa, were exposed to simulated deposition of acid mist and iron ore particulate matter in acrylic chambers in a greenhouse. Parameters such as gas exchange, fluorescence emission, chlorophyll content, total iron content, antioxidant enzyme activity and malondialdehyde content were assessed in order to evaluate the responses of the two species. Neither treatment was capable of inducing oxidative stress in S. terebinthifolius. Nevertheless, the deposition of iron ore particulates on this species increased chlorophyll content, the maximum quantum efficiency of photosystem II and the electron transport rate, while iron content was unaltered. On the other hand, S. tomentosa showed a greater sensitivity to the treatments. Plants of S. tomentosa that were exposed to acid mist had a decrease in photosynthesis, while the deposition of iron particulate matter led to an increase in iron content and membrane permeability of the leaves. The activities of antioxidant enzymes, such as catalases and superoxide dismutase, were enhanced by both treatments. The results suggested that the two restinga species use different strategies to overcome the stressful conditions created by the deposition of particulate matter, either solid or wet. It seems that while S. terebinthifolius avoided stress, S. tomentosa used antioxidant enzyme systems to partially neutralize oxidative stress. The findings also point to the potential use of S. tomentosa as a biomarker species under field conditions

DNA Damage: Quantum Mechanics/Molecular Mechanics Study on the Oxygen Binding and Substrate Hydroxylation Step in AlkB Repair Enzymes

Science.gov (United States)

Quesne, Matthew G; Latifi, Reza; Gonzalez-Ovalle, Luis E; Kumar, Devesh; de Visser, Sam P

2014-01-01

AlkB repair enzymes are important nonheme iron enzymes that catalyse the demethylation of alkylated DNA bases in humans, which is a vital reaction in the body that heals externally damaged DNA bases. Its mechanism is currently controversial and in order to resolve the catalytic mechanism of these enzymes, a quantum mechanics/molecular mechanics (QM/MM) study was performed on the demethylation of the N1-methyladenine fragment by AlkB repair enzymes. Firstly, the initial modelling identified the oxygen binding site of the enzyme. Secondly, the oxygen activation mechanism was investigated and a novel pathway was found, whereby the catalytically active iron(IV)–oxo intermediate in the catalytic cycle undergoes an initial isomerisation assisted by an Arg residue in the substrate binding pocket, which then brings the oxo group in close contact with the methyl group of the alkylated DNA base. This enables a subsequent rate-determining hydrogen-atom abstraction on competitive σ-and π-pathways on a quintet spin-state surface. These findings give evidence of different locations of the oxygen and substrate binding channels in the enzyme and the origin of the separation of the oxygen-bound intermediates in the catalytic cycle from substrate. Our studies are compared with small model complexes and the effect of protein and environment on the kinetics and mechanism is explained. PMID:24339041

Arecoline inhibits endothelial cell growth and migration and the attachment to mononuclear cells

Directory of Open Access Journals (Sweden)

Shuei-Kuen Tseng

2014-09-01

Conclusion: Arecoline impaired vascular endothelial cells by inhibiting their growth and migration and their adhesion to U937 mononuclear cells. These results reveal that arecoline may contribute to the pathogenesis of oral submucous fibrosis and cardiovascular diseases by affecting endothelial cell function in BQ chewers.

Effect of paricalcitol and GcMAF on angiogenesis and human peripheral blood mononuclear cell proliferation and signaling.

Science.gov (United States)

Pacini, Stefania; Morucci, Gabriele; Punzi, Tiziana; Gulisano, Massimo; Ruggiero, Marco; Amato, Marcello; Aterini, Stefano

2012-01-01

In addition to its role in calcium homeostasis and bone mineralization, vitamin D is involved in immune defence, cardiovascular function, inflammation and angiogenesis, and these pleiotropic effects are of interested in the treatment of chronic kidney disease. Here we investigated the effects of paricalcitol, a nonhypercalcemic vitamin D analogue, on human peripheral blood mononuclear cell proliferation and signaling, and on angiogenesis. These effects were compared with those of a known inhibitor of angiogenesis pertaining to the vitamin D axis, the vitamin D-binding protein-derived Gc-macrophage activating factor (GcMAF). Since the effects of vitamin D receptor agonists are associated with polymorphisms of the gene coding for the receptor, we measured the effects of both compounds on mononuclear cells harvested from subjects harboring different BsmI polymorphisms. Paricalcitol inhibited mononuclear cell viability with the bb genotype showing the highest effect. GcMAF, on the contrary, stimulated cell proliferation, with the bb genotype showing the highest stimulatory effect. Both compounds stimulated 3'-5'-cyclic adenosine monophosphate formation in mononuclear cells with the highest effect on the bb genotype. Paricalcitol and GcMAF inhibited the angiogenesis induced by proinflammatory prostaglandin E1. Polymorphisms of the vitamin D receptor gene, known to be associated with the highest responses to vitamin D receptor agonists, are also associated with the highest responses to GcMAF. These results highlight the role of the vitamin D axis in chronic kidney disease, an axis which includes vitamin D, its receptor and vitamin D-binding protein-derived GcMAF.

Effect of dietary iron source and iron status on iron bioavailability tests in the rat

International Nuclear Information System (INIS)

Zhang, D.; Hendricks, D.G.; Mahoney, A.W.

1986-01-01

Weanling male rats were made anemic in 7 days by feeding a low iron diet and bleeding. Healthy rats were fed the low iron diet supplemented with ferrous sulfate (29 ppm Fe). Each group was subdivided and fed for 10 days on test diets containing about 29 ppm iron that were formulated with meat:spinach mixtures or meat:soy mixtures to provided 100:0, 75:25, 50:50, 25:75, or 0:100% of the dietary iron from these sources or from a ferrous sulfate diet. After 3 days on the diets all rats were dosed orally with 2 or 5 micro curries of 59 Fe after a 18 hour fast and refeeding for 1.5 hours. Iron status influenced liver iron, carcass iron, liver radio activity and percent of radioactive dose retained. Diet influenced fecal iron and apparent absorption of iron. In iron bioavailability studies assessment methodology and iron status of the test subject greatly influences the estimates of the value of dietary sources of iron

Effects of lethal and non-lethal malaria on the mononuclear phagocyte system

Directory of Open Access Journals (Sweden)

Carlos Eduardo Tosta

1983-03-01

Full Text Available The effects ofone non-lethal species ofmalarialparasite, Plasmodium yoelii, and one lethal species, P. berghei, on the mononuclear phagocyte system (MPS of BALB/c mice were studied. P. yoelii caused a greater and more sustained expansion and activation of the MPS, and the two major populations of spleen phagocytic cells-red pulp and marginal zone macrophages - exhibited a greater increase in numbers in this infection. During the course of P. berghei mataria, the spleen was progressively occupied by haematopoietic tissue and, at the terminal stage of infection, an extensive depletion of lymphocytes and macrophages was apparent. The possibility was suggested that the outcome of mataria may be inftuenced by the particular way the parasite interacts with the MPS.Estudou-se o efeito da infecção causada por espécie letal (Plasmodium berghei e não- letal (P. yoelii de plasmódio sobre o sistema de fagócitos mononucleares de camundongo BALB/c. O P. yoelii causou maior e mais prolongada expansão e ativação do sistema de macrófagos. As duas mais importantes populações de fagócitos esplênicos - macrófagos de polpa vermelha e da zona marginal - exibiam maior aumento do número de células nesta infecção. Durante a evolução da malária por P. berghei, o baço foi progressivamente ocupado por tecido hematopoiético e, na fase terminal da infecção, observou-se significativa depleção dos linfócitos e macrófagos esplênicos. Os dados apresentados indicam que a evolução da malária depende do tipo de interação entre o plasmódio e o sistema de fagócitos mononucleares.

An Antioxidant Extract of the Insectivorous Plant Drosera burmannii Vahl. Alleviates Iron-Induced Oxidative Stress and Hepatic Injury in Mice.

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Nikhil Baban Ghate

Full Text Available Free iron typically leads to the formation of excess free radicals, and additional iron deposition in the liver contributes to the oxidative pathologic processes of liver disease. Many pharmacological properties of the insectivorous plant Drosera burmannii Vahl. have been reported in previous studies; however, there is no evidence of its antioxidant or hepatoprotective potential against iron overload. The antioxidant activity of 70% methanolic extract of D. burmannii (DBME was evaluated. DBME showed excellent DPPH, hydroxyl, hypochlorous, superoxide, singlet oxygen, nitric oxide, peroxynitrite radical and hydrogen peroxide scavenging activity. A substantial iron chelation (IC50 = 40.90 ± 0.31 μg/ml and supercoiled DNA protection ([P]50 = 50.41 ± 0.55 μg were observed. DBME also displayed excellent in vivo hepatoprotective activity in iron-overloaded Swiss albino mice compared to the standard desirox treatment. Administration of DBME significantly normalized serum enzyme levels and restored liver antioxidant enzymes levels. DBME lowered the raised levels of liver damage parameters, also reflected from the morphological analysis of the liver sections. DBME also reduced liver iron content by 115.90% which is also seen by Perls' staining. A phytochemical analysis of DBME confirms the presence of various phytoconstituents, including phenols, flavonoids, carbohydrates, tannins, alkaloids and ascorbic acid. Alkaloids, phenols and flavonoids were abundantly found in DBME. An HPLC analysis of DBME revealed the presence of purpurin, catechin, tannic acid, reserpine, methyl gallate and rutin. Purpurin, tannic acid, methyl gallate and rutin displayed excellent iron chelation but exhibited cytotoxicity toward normal (WI-38 cells; while DBME found to be non-toxic to the normal cells. These findings suggest that the constituents present in DBME contributed to its iron chelation activity. Additional studies are needed to determine if DBME can be used as a

Synthesis of 5-hydroxyectoine from ectoine: crystal structure of the non-heme iron(II and 2-oxoglutarate-dependent dioxygenase EctD.

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Klaus Reuter

2010-05-01

Full Text Available As a response to high osmolality, many microorganisms synthesize various types of compatible solutes. These organic osmolytes aid in offsetting the detrimental effects of low water activity on cell physiology. One of these compatible solutes is ectoine. A sub-group of the ectoine producer's enzymatically convert this tetrahydropyrimidine into a hydroxylated derivative, 5-hydroxyectoine. This compound also functions as an effective osmostress protectant and compatible solute but it possesses properties that differ in several aspects from those of ectoine. The enzyme responsible for ectoine hydroxylation (EctD is a member of the non-heme iron(II-containing and 2-oxoglutarate-dependent dioxygenases (EC 1.14.11. These enzymes couple the decarboxylation of 2-oxoglutarate with the formation of a high-energy ferryl-oxo intermediate to catalyze the oxidation of the bound organic substrate. We report here the crystal structure of the ectoine hydroxylase EctD from the moderate halophile Virgibacillus salexigens in complex with Fe(3+ at a resolution of 1.85 A. Like other non-heme iron(II and 2-oxoglutarate dependent dioxygenases, the core of the EctD structure consists of a double-stranded beta-helix forming the main portion of the active-site of the enzyme. The positioning of the iron ligand in the active-site of EctD is mediated by an evolutionarily conserved 2-His-1-carboxylate iron-binding motif. The side chains of the three residues forming this iron-binding site protrude into a deep cavity in the EctD structure that also harbours the 2-oxoglutarate co-substrate-binding site. Database searches revealed a widespread occurrence of EctD-type proteins in members of the Bacteria but only in a single representative of the Archaea, the marine crenarchaeon Nitrosopumilus maritimus. The EctD crystal structure reported here can serve as a template to guide further biochemical and structural studies of this biotechnologically interesting enzyme family.

Cold adaptation of the mononuclear molybdoenzyme periplasmic nitrate reductase from the Antarctic bacterium Shewanella gelidimarina

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Simpson, Philippa J.L. [School of Chemistry, University of Sydney, New South Wales 2006 (Australia); Codd, Rachel, E-mail: rachel.codd@sydney.edu.au [School of Chemistry, University of Sydney, New South Wales 2006 (Australia); School of Medical Sciences (Pharmacology) and Bosch Institute, University of New South Wales, New South Wales 2006 (Australia)

2011-11-04

mesophilic template with 66% amino acid identity showed the majority of substitutions occurred at the protein surface distal to the Mo-MGD cofactor. Two mesophilic {r_reversible} psychrophilic substitutions (Asn {r_reversible} His, Val {r_reversible} Trp) occurred in a region close to the surface of the NapA substrate funnel resulting in potential interdomain {pi}-{pi} and/or cation-{pi} interactions. Three mesophilic {r_reversible} psychrophilic substitutions occurred within 4.5 A of the Mo-MGD cofactor (Phe {r_reversible} Met, Ala {r_reversible} Ser, Ser {r_reversible} Thr) resulting in local regions that varied in hydrophobicity and hydrogen bonding networks. These results contribute to the understanding of thermal protein adaptation in a redox-active mononuclear molybdenum enzyme and have implications in optimizing the design of low-temperature environmental biosensors.

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)

Arabidopsis Glutaredoxin S17 Contributes to Vegetative Growth, Mineral Accumulation, and Redox Balance during Iron Deficiency

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Han Yu

2017-06-01

Full Text Available Iron (Fe is an essential mineral nutrient and a metal cofactor required for many proteins and enzymes involved in the processes of DNA synthesis, respiration, and photosynthesis. Iron limitation can have detrimental effects on plant growth and development. Such effects are mediated, at least in part, through the generation of reactive oxygen species (ROS. Thus, plants have evolved a complex regulatory network to respond to conditions of iron limitations. However, the mechanisms that couple iron deficiency and oxidative stress responses are not fully understood. Here, we report the discovery that an Arabidopsis thaliana monothiol glutaredoxin S17 (AtGRXS17 plays a critical role in the plants ability to respond to iron deficiency stress and maintain redox homeostasis. In a yeast expression assay, AtGRXS17 was able to suppress the iron accumulation in yeast ScGrx3/ScGrx4 mutant cells. Genetic analysis indicated that plants with reduced AtGRXS17 expression were hypersensitive to iron deficiency and showed increased iron concentrations in mature seeds. Disruption of AtGRXS17 caused plant sensitivity to exogenous oxidants and increased ROS production under iron deficiency. Addition of reduced glutathione rescued the growth and alleviates the sensitivity of atgrxs17 mutants to iron deficiency. These findings suggest AtGRXS17 helps integrate redox homeostasis and iron deficiency responses.

An iron-57 Moessbauer spectroscopic study of titania-supported iron- and iron-iridium catalysts

International Nuclear Information System (INIS)

Berry, F.J.; Jobson, S.

1992-01-01

57 Fe Moessbauer spectroscopy shows that titania-supported iron is reduced by treatment in hydrogen at significantly lower temperatures than corresponding silica- and alumina-supported catalysts. The metallic iron formed under hydrogen at 600deg C is partially converted to carbide by treatment in carbon monoxide and hydrogen. In contrast to its alumina- and silica-supported counterparts, the remainder of the titania-supported iron is unchanged by this gaseous mixture. The 57 Fe Moessbauer spectra of EXAFS show that iron and iridium in the titania-supported iron-iridium catalysts are reduced in hydrogen at even lower temperatures and, after treatment at 600deg C, are predominantly present as the iron-iridium alloy. The treatment of these reduced catalysts in carbon monoxide and hydrogen is shown by Moessbauer spectroscopy and EXAFS to induce the segregation of iron from the iron-iridium alloy and its conversion to iron oxide. (orig.)

Purification of PON1 from human serum and assessment of enzyme kinetics against metal toxicity.

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Ekinci, Deniz; Beydemir, Sükrü

2010-06-01

Paraoxonase-1 (PON1) is an organophosphate hydrolyser enzyme which has also antioxidant properties in metabolism. Due to its crucial functions, inhibition of the enzyme is undesirable and very dangerous. PON1 enzyme activity should not be altered in any case. Inhibitory investigations of this enzyme are therefore important and useful. Metal toxicology of enzymes has become popular in the recent years. Here, we report the in vitro inhibitory effects of some metal ions, including Pb(+2), Cr(+2), Fe(+2), and Zn(+2), on the activity of human serum PON1 (hPON1; EC 3.1.8.1.). For this purpose, we purified the enzyme from human serum and analyzed the alterations in the enzyme activity in the presence of metal ions. The results show that metal ions exhibit inhibitory effects on hPON1 at low concentrations with IC (50) values ranging from 0.838 to 7.410 mM. Metal ions showed different inhibition mechanisms: lead and iron were competitive, chrome was noncompetitive, and zinc was uncompetitive. Lead was determined to be the most effective inhibitor.

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

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

2017-05-01

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

Iron and thiols as two major players in carcinogenesis: friends or foes?

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Toyokuni, Shinya

2014-01-01

Iron is the most abundant metal in the human body and mainly works as a cofactor for proteins such as hemoglobin and various enzymes. No independent life forms on earth can survive without iron. However, excess iron is intimately associated with carcinogenesis by increasing oxidative stress via its catalytic activity to generate hydroxyl radicals. Biomolecules with redox-active sulfhydryl function(s) (thiol compounds) are necessary for the maintenance of mildly reductive cellular environments to counteract oxidative stress, and for the execution of redox reactions for metabolism and detoxification. Involvement of glutathione S-transferase and thioredoxin has long attracted the attention of cancer researchers. Here, I update recent findings on the involvement of iron and thiol compounds during carcinogenesis and in cancer cells. It is now recognized that the cystine/glutamate transporter (antiporter) is intimately associated with ferroptosis, an iron-dependent, non-apoptotic form of cell death, observed in cancer cells, and also with cancer stem cells; the former with transporter blockage but the latter with its stabilization. Excess iron in the presence of oxygen appears the most common known mutagen. Ironically, the persistent activation of antioxidant systems via genetic alterations in Nrf2 and Keap1 also contributes to carcinogenesis. Therefore, it is difficult to conclude the role of iron and thiol compounds as friends or foes, which depends on the quantity/distribution and induction/flexibility, respectively. Avoiding further mutation would be the most helpful strategy for cancer prevention, and myriad of efforts are being made to sort out the weaknesses of cancer cells.

A New Synthetic Compound, 2-OH, Enhances Interleukin-2 and Interferon-γ Gene Expression in Human Peripheral Blood Mononuclear Cells

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Woan-Fang Tzeng

2009-07-01

Full Text Available A new synthetic compound, 6-hydroxy-2-tosylisoquinolin-1(2H-one (2-OH, was selected for immunopharmacological activity tests. The effects of 2-OH on human peripheral blood mononuclear cell (PBMC proliferation were determined by tritiated thymidine uptake. Compared to phytohemagglutinin (PHA; 5 μg/mL stimulation, 2-OH significantly enhanced PBMC proliferation in a dose-dependent manner. The 50% enhancement activity (EC50 for 2-OH was 4.4±0.1 μM. In addition, effects of 2-OH on interleukin-2 (IL-2 and interferon-γ (IFN-γ production in PBMC were determined by enzyme immunoassay. Results demonstrated that 2-OH stimulated IL-2 and IFN-γ production in PBMC. Data from reverse transcription-polymerase chain reaction (RT-PCR and real-time PCR indicated that IL-2 and IFN-γ mRNA expression in PBMC could be induced by 2-OH. Therefore, 2-OH enhanced IL-2 and IFN-γ production in PBMC by modulation their gene expression. We suggest that 2-OH may be an immunomodulatory agent.

Phenotypic characterization of mononuclear inflammatory cells following equine hydroxyapatite/collagen block grafting in rats

International Nuclear Information System (INIS)

Alsuwaiyan, Asim; Wang, Bing-Yan; Cohen, Robert E

2012-01-01

To measure the inflammatory changes associated with the implantation of an equine hydroxyapatite and collagen-containing block graft (eHAC block) in a rodent model system, an eHAC block graft was implanted subcutaneously in rats. Control groups included saline, turpentine oil, and human mineralized particulate allograft (hMPA). Animals were sacrificed and tissue samples obtained after three days, as well as after 1, 2, 4 and 8 weeks. A panel of immunologic probes was used to identify circulatory monocytic cells (ED1), resident mononuclear phagocytes (ED2), mononuclear phagocytes of lymphoid origin (ED3), expression of Ia antigen (OX6), T-cells (OX19), and B-cells (OX33). Immunocytochemical localization was performed and mononuclear cells localized with each immunologic probe counted. Rat sera obtained after eight weeks were used for nitrocellulose dot-blotting to assess circulating anti-equine immunoglobulins. Statistical analysis was performed using two-way analysis of variance, in conjunction with the Bonferroni correction to account for multiple comparisons. A transient increase in monocytes at 3 days and 1 week was observed in all groups, but was significantly higher in the turpentine control (P < 0.0001). A significant increase in the numbers of mononuclear cells detected with clones ED2 and ED3 was observed in specimens from the turpentine group, in contrast to the other groups in the 3 day to 4 week interval (P < 0.0001), as well as within all time periods (P < 0.0001). A statistically significant difference in numbers of ED3-positive cells was observed in the hMPA group compared to the saline and the eHAC block groups after one week (P < 0.0001). Significantly more OX6-positive cells were observed in the turpentine group, compared to other groups (3 days to 1 week; P < 0.0001). T-lymphocytes were essentially absent except for rats given turpentine (after 1 week). No B-lymphocyte response was found and none of the rats developed systemic anti

Adrenaline and triiodothyronine modify the iron handling in the freshwater air-breathing fish Anabas testudineus Bloch: role of ferric reductase in iron acquisition.

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Rejitha, V; Peter, M C Subhash

2013-01-15

The effects of in vivo adrenaline and triiodothyronine (T(3)) on ferric reductase (FR) activity, a membrane-bound enzyme that reduces Fe(III) to Fe(II) iron, were studied in the organs of climbing perch (Anabas testudineus Bloch). Adrenaline injection (10 ng g(-1)) for 30 min produced significant inhibition of FR activity in the liver and kidney and that suggests a role for this stress hormone in iron acquisition in this fish. Short-term T(3) injection (40 ng g(-1)) reduced FR activity in the gills of fed fish but not in the unfed fish. Similar reduction of FR activity was also obtained in the intestine and kidney of fed fish after T(3) injection. Feeding produced pronounced decline in FR activity in the spleen but T(3) challenge in fed and unfed fish increased its activity in this iron storing organ and that point to the sensitivity of FR system to feeding activity. The in vitro effects of Fe on FR activity in the gill explants of freshwater fish showed correlations of FR with Na(+), K(+)-ATPase and H(+)-ATPase activities. Substantial increase in the FR activity was found in the gill explants incubated with all the tested doses of Fe(II) iron (1.80, 3.59 and 7.18 μM) and Fe(III) iron (1.25, 2.51 and 5.02 μM) and this indicate that FR and Na pump activity are positively correlated. On the contrary, substantial reduction of gill H(+)-ATPase activity was found in the gill explants incubated with Fe(II) iron and Fe(III) iron indicating that perch gills may not require a high acidic microenvironment for the reduction of Fe(III) iron. Accumulation of iron in the gill explants after Fe(III) iron incubation implies a direct relationship between Fe acquisition and FR activity in this tissue. The inverse correlation between FR activity and H(+)-ATPase activity in Fe(II) or Fe(III) loaded gills and the significant positive correlations of FR activity with total [Fe] content in the Fe(III) loaded gills substantiate that FR which shows sensitivity to sodium and proton pumps

Clues to pathogenesis of spondyloarthropathy derived from synovial fluid mononuclear cell gene expression profiles

NARCIS (Netherlands)

Gu, Jieruo; Rihl, Markus; Märker-Hermann, Elisabeth; Baeten, Dominique; Kuipers, Jens G.; Song, Yeong Wook; Maksymowych, Walter P.; Burgos-Vargas, Ruben; Veys, Eric M.; de Keyser, Filip; Deister, Helmuth; Xiong, Momiao; Huang, Feng; Tsai, Wen Chan; Yu, David Tak Yan

2002-01-01

OBJECTIVE: To use gene expression profiles of spondyloarthropathy (SpA) synovial fluid mononuclear cells (SFMC) to determine if there are transcripts that support the unfolded protein response (UPR) hypothesis, and to identify which cytokines/chemokines are being expressed and which cell fractions

Fototerapia causa danos ao DNA de leucócitos mononucleares periféricos em recém-nascidos a termo Phototherapy causes DNA damage in peripheral mononuclear leukocytes in term infants

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Ali Aycicek

2008-04-01

Full Text Available OBJETIVO: Determinar se a fita de DNA de leucócitos mononucleares endógenos é alvo de fototerapia. MÉTODOS: O estudo incluiu 65 recém-nascidos a termo com idades entre 3 e 10 dias que haviam sido expostos a fototerapia intensiva (n = 23 ou convencional (n = 23 por pelo menos 48 horas devido à icterícia neonatal, além de um grupo controle (n = 19. Dano ao DNA foi avaliado por eletroforese alcalina em gel de célula única (ensaio cometa. A capacidade antioxidante total plasmática e os níveis de estado oxidativo total também foram medidos, e a correlação entre danos ao DNA e estresse oxidativo foi investigada. RESULTADOS: Os valores médios de escores de danos ao DNA nos grupos de fototerapia intensiva e convencional foram significativamente maiores do que os do grupo controle (p 0,05. Não houve correlações significativas entre escores de danos ao DNA e bilirrubina, estado oxidante total e níveis de estresse oxidativo entre os grupos de fototerapia (p > 0,05. CONCLUSÕES: Tanto a fototerapia intensiva quanto a convencional causam danos ao DNA dos leucócitos mononucleares endógenos em recém-nascidos a termo com icterícia.OBJECTIVE: Our aim was to determine whether endogenous mononuclear leukocyte DNA strand is a target of phototherapy. METHODS: The study included 65 term infants aged between 3-10 days that had been exposed to intensive (n = 23 or conventional (n = 23 phototherapy for at least 48 hours due to neonatal jaundice, and a control group (n = 19. DNA damage was assayed by single-cell alkaline gel electrophoresis (comet assay. Plasma total antioxidant capacity and total oxidant status levels were also measured, and correlation between DNA damage and oxidative stress was investigated. RESULTS: Mean values of DNA damage scores in both the intensive and conventional phototherapy groups were significantly higher than those in the control group (p 0.05. There were no significant correlations between DNA damage scores and

Correlations between iron content in knee joint tissues and chosen indices of peripheral blood morphology.

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Brodziak-Dopierała, Barbara; Roczniak, Wojciech; Jakóbik-Kolon, Agata; Kluczka, Joanna; Koczy, Bogdan; Kwapuliński, Jerzy; Babuśka-Roczniak, Magdalena

2017-10-01

Iron as a cofactor of enzymes takes part in the synthesis of the bone matrix. Severe deficiency of iron reduces the strength and mineral density of bones, whereas its excess may increase oxidative stress. In this context, it is essential to determine the iron content in knee joint tissues. The study objective was to determine the level of iron in the tissues of the knee joint, i.e., in the femoral bone, tibia and meniscus. Material for analysis was obtained during endoprosthetic surgery of the knee joint. Within the knee joint, the tibia, femur and meniscus were analyzed. Samples were collected from 50 patients, including 36 women and 14 men. The determination of iron content was performed with the ICP-AES method, using Varian 710-ES. The lowest iron content was in the tibia (27.04 μg/g), then in the meniscus (38.68 μg/g) and the highest in the femur (41.93 μg/g). Statistically significant differences were noted in the content of iron in knee joint tissues. In patients who underwent endoprosthesoplasty of the knee joint, statistically significant differences were found in the levels of iron in various components of the knee joint. The highest iron content was found in the femoral bone of the knee joint and then in the meniscus, the lowest in the tibia. The differences in iron content in the knee joint between women and men were not statistically significant.

Higher iron bioavailability of a human-like collagen iron complex.

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Zhu, Chenhui; Yang, Fan; Fan, Daidi; Wang, Ya; Yu, Yuanyuan

2017-07-01

Iron deficiency remains a public health problem around the world due to low iron intake and/or bioavailability. FeSO 4 , ferrous succinate, and ferrous glycinate chelate are rich in iron but have poor bioavailability. To solve the problem of iron deficiency, following previous research studies, a thiolated human-like collagen-ironcomplex supplement with a high iron content was prepared in an anaerobic workstation. In addition, cell viability tests were evaluated after conducting an MTT assay, and a quantitative analysis of the thiolated human-like collagen-iron digesta samples was performed using the SDS-PAGE method coupled with gel filtration chromatography. The iron bioavailability was assessed using Caco-2 cell monolayers and iron-deficiency anemia mice models. The results showed that (1) one mole of thiolated human-like collagen-iron possessed approximately 35.34 moles of iron; (2) thiolated human-like collagen-iron did not exhibit cytotoxity and (3) thiolated human-like collagen- iron digesta samples had higher bioavailability than other iron supplements, including FeSO 4 , ferrous succinate, ferrous glycine chelate and thiolated human-like collagen-Fe iron. Finally, the iron bioavailability was significantly enhanced by vitamin C. These results indicated that thiolated human-like collagen-iron is a promising iron supplement for use in the future.

Suppression of leukocyte inhibitory factor (LIF) production and [3H]thymidine incorporation by concanavalin A-activated mononuclear cells

International Nuclear Information System (INIS)

Lomnitzer, R.; Rabson, A.R.

1979-01-01

The capacity of human mononuclear (MN) cells pretreated with concanavalin A (Con A) to suppress the activity of fresh phytohemagglutinin (PHA)-pulsed mononuclear cells was assessed. Con A-pretreated MN cells suppressed leukocyte inhibitory factor (LIF) activity in supernatants of PHA-pulsed cell cultures and [ 3 H]thymidine incorporation by these cells. Suppression was obtained in both allogeneic and autologous systems with mitomycin-treated, irradiated, or untreated Con A-induced cells. Lymphocytes from two patients that, following treatment with Con A, did not suppress mitogen-induced proliferative response of normal cells also did not suppress LIF production

Iron

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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 ...

A cascade of iron-containing proteins governs the genetic iron starvation response to promote iron uptake and inhibit iron storage in fission yeast.

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Javier Encinar del Dedo

2015-03-01

Full Text Available Iron is an essential cofactor, but it is also toxic at high levels. In Schizosaccharomyces pombe, the sensor glutaredoxin Grx4 guides the activity of the repressors Php4 and Fep1 to mediate a complex transcriptional response to iron deprivation: activation of Php4 and inactivation of Fep1 leads to inhibition of iron usage/storage, and to promotion of iron import, respectively. However, the molecular events ruling the activity of this double-branched pathway remained elusive. We show here that Grx4 incorporates a glutathione-containing iron-sulfur cluster, alone or forming a heterodimer with the BolA-like protein Fra2. Our genetic study demonstrates that Grx4-Fra2, but not Fep1 nor Php4, participates not only in iron starvation signaling but also in iron-related aerobic metabolism. Iron-containing Grx4 binds and inactivates the Php4 repressor; upon iron deprivation, the cluster in Grx4 is probably disassembled, the proteins dissociate, and Php4 accumulates at the nucleus and represses iron consumption genes. Fep1 is also an iron-containing protein, and the tightly bound iron is required for transcriptional repression. Our data suggest that the cluster-containing Grx4-Fra2 heterodimer constitutively binds to Fep1, and upon iron deprivation the disassembly of the iron cluster between Grx4 and Fra2 promotes reverse metal transfer from Fep1 to Grx4-Fra2, and de-repression of iron-import genes. Our genetic and biochemical study demonstrates that the glutaredoxin Grx4 independently governs the Php4 and Fep1 repressors through metal transfer. Whereas iron loss from Grx4 seems to be sufficient to release Php4 and allow its nuclear accumulation, total or partial disassembly of the Grx4-Fra2 cluster actively participates in iron-containing Fep1 activation by sequestering its iron and decreasing its interaction with promoters.

Arene activation by a nonheme iron(III)-hydroperoxo complex: pathways leading to phenol and ketone products.

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Faponle, Abayomi S; Banse, Frédéric; de Visser, Sam P

2016-07-01

Iron(III)-hydroperoxo complexes are found in various nonheme iron enzymes as catalytic cycle intermediates; however, little is known on their catalytic properties. The recent work of Banse and co-workers on a biomimetic nonheme iron(III)-hydroperoxo complex provided evidence of its involvement in reactivity with arenes. This contrasts the behavior of heme iron(III)-hydroperoxo complexes that are known to be sluggish oxidants. To gain insight into the reaction mechanism of the biomimetic iron(III)-hydroperoxo complex with arenes, we performed a computational (density functional theory) study. The calculations show that iron(III)-hydroperoxo reacts with substrates via low free energies of activation that should be accessible at room temperature. Moreover, a dominant ketone reaction product is observed as primary products rather than the thermodynamically more stable phenols. These product distributions are analyzed and the calculations show that charge interaction between the iron(III)-hydroxo group and the substrate in the intermediate state pushes the transferring proton to the meta-carbon atom of the substrate and guides the selectivity of ketone formation. These studies show that the relative ratio of ketone versus phenol as primary products can be affected by external interactions of the oxidant with the substrate. Moreover, iron(III)-hydroperoxo complexes are shown to selectively give ketone products, whereas iron(IV)-oxo complexes will react with arenes to form phenols instead.

Dietary iron intake, iron status, and gestational diabetes.

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Zhang, Cuilin; Rawal, Shristi

2017-12-01

Pregnant women are particularly vulnerable to iron deficiency and related adverse pregnancy outcomes and, as such, are routinely recommended for iron supplementation. Emerging evidence from both animal and population-based studies, however, has raised potential concerns because significant associations have been observed between greater iron stores and disturbances in glucose metabolism, including increased risk of type 2 diabetes among nonpregnant individuals. Yet, the evidence is uncertain regarding the role of iron in the development of gestational diabetes mellitus (GDM), a common pregnancy complication which has short-term and long-term adverse health ramifications for both women and their children. In this review, we critically and systematically evaluate available data examining the risk of GDM associated with dietary iron, iron supplementation, and iron status as measured by blood concentrations of several indicators. We also discuss major methodologic concerns regarding the available epidemiologic studies on iron and GDM. © 2017 American Society for Nutrition.

Studies on the pathogenesis in iron deficiency anemia Part 1. Urinary iron excretion in iron deficiency anemia patients and rats in various iron states

OpenAIRE

中西,徳彦

1991-01-01

In the "iron excretion test" , urinary iron excretion after injection of saccharated iron oxide has been reported to be accelerated in relapsing idiopathic iron deficiency anemia. To determine the relevance of urinary iron excretion to clinical factors other than iron metabolism, 15 clinical parameters were evaluated. The serum creatinine level was positively and the serum albumin level was negatively correlated with urinary iron excretion, showing coefficients of r＝0.97,－0.86 respectively, a...

A new portable device for automatic controlled-gradient cryopreservation of blood mononuclear cells.

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Hviid, L; Albeck, G; Hansen, B; Theander, T G; Talbot, A

1993-01-04

Protection of the functional integrity of mononuclear cells stored in liquid N2 requires careful control of the freezing procedure. Consequently, optimal quality of cryopreserved cells is usually assured by freezing according to a specified time-temperature gradient generated by computer-controlled freezing devices. While such equipment offers large capacity and secures maximum survival and functional integrity of the lymphocytes upon thawing, it is quite costly and strictly stationary. We have previously developed and tested an alternative, manual device for controlled-gradient lymphocyte freezing, which has proved suitable for field conditions. We report here the development and testing of a similar micro-controller regulated device, allowing unattended and automatic controlled-gradient cell freezing. The equipment exploits the temperature gradient present between the liquid N2 surface and the neck in an ordinary liquid N2 refrigerator. The lymphocyte samples are placed in a small elevator, which is moved through the N2 gas phase by a stepper motor. Time and temperature are measured at regular intervals, and the position of the samples adjusted to ensure that the actual measurements closely match encoded ideal values. Results of assays of the functional integrity and phenotypic composition of human mononuclear cells frozen by the new system were comparable to those obtained when using cells frozen by a commercially available, stationary cell-freezing equipment, or fresh autologous cell samples tested in parallel. Furthermore, there was a good correlation between functional and phenotypic data obtained using frozen and autologous fresh samples of mononuclear cells. The equipment described is low weight and has low N2 consumption, and is thus suitable for the collection and cryopreservation of lymphocytes under field conditions. Furthermore, the technique provides an inexpensive alternative for researchers with a limited requirement for the simultaneous freezing of

Evolutionary Expansion of the Amidohydrolase Superfamily in Bacteria in Response to the Synthetic Compounds Molinate and Diuron

Science.gov (United States)

Sugrue, Elena; Fraser, Nicholas J.; Hopkins, Davis H.; Carr, Paul D.; Khurana, Jeevan L.; Oakeshott, John G.; Scott, Colin

2015-01-01

The amidohydrolase superfamily has remarkable functional diversity, with considerable structural and functional annotation of known sequences. In microbes, the recent evolution of several members of this family to catalyze the breakdown of environmental xenobiotics is not well understood. An evolutionary transition from binuclear to mononuclear metal ion coordination at the active sites of these enzymes could produce large functional changes such as those observed in nature, but there are few clear examples available to support this hypothesis. To investigate the role of binuclear-mononuclear active-site transitions in the evolution of new function in this superfamily, we have characterized two recently evolved enzymes that catalyze the hydrolysis of the synthetic herbicides molinate (MolA) and phenylurea (PuhB). In this work, the crystal structures, mutagenesis, metal ion analysis, and enzyme kinetics of both MolA and PuhB establish that these enzymes utilize a mononuclear active site. However, bioinformatics and structural comparisons reveal that the closest putative ancestor of these enzymes had a binuclear active site, indicating that a binuclear-mononuclear transition has occurred. These proteins may represent examples of evolution modifying the characteristics of existing catalysts to satisfy new requirements, specifically, metal ion rearrangement leading to large leaps in activity that would not otherwise be possible. PMID:25636851

Amyotrophic lateral sclerosis multiprotein biomarkers in peripheral blood mononuclear cells.

Directory of Open Access Journals (Sweden)

Giovanni Nardo

Full Text Available Amyotrophic lateral sclerosis (ALS is a fatal progressive motor neuron disease, for which there are still no diagnostic/prognostic test and therapy. Specific molecular biomarkers are urgently needed to facilitate clinical studies and speed up the development of effective treatments.We used a two-dimensional difference in gel electrophoresis approach to identify in easily accessible clinical samples, peripheral blood mononuclear cells (PBMC, a panel of protein biomarkers that are closely associated with ALS. Validations and a longitudinal study were performed by immunoassays on a selected number of proteins. The same proteins were also measured in PBMC and spinal cord of a G93A SOD1 transgenic rat model. We identified combinations of protein biomarkers that can distinguish, with high discriminatory power, ALS patients from healthy controls (98%, and from patients with neurological disorders that may resemble ALS (91%, between two levels of disease severity (90%, and a number of translational biomarkers, that link responses between human and animal model. We demonstrated that TDP-43, cyclophilin A and ERp57 associate with disease progression in a longitudinal study. Moreover, the protein profile changes detected in peripheral blood mononuclear cells of ALS patients are suggestive of possible intracellular pathogenic mechanisms such as endoplasmic reticulum stress, nitrative stress, disturbances in redox regulation and RNA processing.Our results indicate that PBMC multiprotein biomarkers could contribute to determine amyotrophic lateral sclerosis diagnosis, differential diagnosis, disease severity and progression, and may help to elucidate pathogenic mechanisms.

Iron from Zealandic bog iron ore -

DEFF Research Database (Denmark)

Lyngstrøm, Henriette Syrach

2011-01-01

og geologiske materiale, metallurgiske analyser og eksperimentel arkæologiske forsøg - konturerne af en jernproduktion med udgangspunkt i den sjællandske myremalm. The frequent application by archaeologists of Werner Christensen’s distribution map for the occurrence of bog iron ore in Denmark (1966...... are sketched of iron production based on bog iron ore from Zealand....

Response to parenteral iron therapy distinguish unexplained refractory iron deficiency anemia from iron-refractory iron deficiency anemia.

Science.gov (United States)

Akin, M; Sarbay, H; Guler, S; Balci, Y I; Polat, A

2016-04-01

We evaluated that response to parenteral iron therapy could be helpful in distinguishing the types of iron deficiency anemia. This study analyzed responses to IV iron sucrose therapy of 15 children with unexplained refractory iron deficiency anemia (URIDA). We compared the results at diagnosis, 6 weeks and 6 months after the therapy. Results were compared with responses of 11 patients' results with iron-refractory iron deficiency anemia (IRIDA) from our previous study. Six weeks after the start of treatment, ferritin, MCV, MCH and Hb values were in normal range in 10 patients. The increase in Hb, MCH, MCV, and ferritin values ranged 2.6-3.5 g/dL, 1.7-4.2 pg, 2-9 fL, and 13-25 ng/mL, respectively. In five patients, Hb, MCH, and MCV mean (range) values [11.2 g/dL (11-12.2), 24.5 pg (24-25.6), and 67 fL (65-70)] were nearly normal but ferritin mean (range) values [9.8 ng/mL (8-11)] were below normal. Six weeks after the start of treatment, Hb, MCH, MCV and ferritin values of patients with IRIDA were increased. The increase in Hb, MCH, MCV, and ferritin values ranged 0.8-2.7 g/dL, 1.7-4.2 pg, 2-9 fL, and 13-25 ng/mL, respectively. IRIDA is only partially responsive to parenteral iron supplementation. In conclusion, this study demonstrated that the response to intravenous iron therapy for the URIDA cases improved blood parameters more effectively than hereditary IRIDA. Response to parenteral iron therapy would be helpful to distinguish unexplained refractory IDA from hereditary IRIDA for clinicians who do not have access to hepcidin or TMPRS6 mutation analysis. © 2016 John Wiley & Sons Ltd.

Towards a Mechanistic Understanding of Anaerobic Nitrate Dependent Iron Oxidation: Balancing Electron Uptake and Detoxification

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Hans Karl Carlson

2012-02-01

Full Text Available The anaerobic oxidation of Fe(II by subsurface microorganisms is an important part of biogeochemical cycling in the environment, but the biochemical mechanisms used to couple iron oxidation to nitrate respiration are not well understood. Based on our own work and the evidence available in the literature, we propose a mechanistic model for anaerobic nitrate dependent iron oxidation. We suggest that anaerobic iron oxidizing microorganisms likely exist along a continuum including: 1 bacteria that inadvertently oxidize Fe(II by abiotic or biotic reactions with enzymes or chemical intermediates in their metabolic pathways (e.g. denitrification and suffer from toxicity or energetic penalty, 2 Fe(II tolerant bacteria that gain little or no growth benefit from iron oxidation but can manage the toxic reactions, and 3 bacteria that efficiently accept electrons from Fe(II to gain a growth advantage while preventing or mitigating the toxic reactions. Predictions of the proposed model are highlighted and experimental approaches are discussed.

Complex interaction of deferasirox and Pythium insidiosum: iron-dependent attenuation of growth in vitro and immunotherapy-like enhancement of immune responses in vivo.

Directory of Open Access Journals (Sweden)

Régis A Zanette

Full Text Available Pythium insidiosum iron acquisition mechanisms are unknown. We previously showed that the iron chelator deferasirox had weak activity in vitro and in rabbits with experimental pythiosis. Here we show that deferasirox causes damage to P. insidiosum hyphae in vitro, but that activity is diminished in the presence of exogenous iron. The tissue activity of the proinflammatory enzyme adenosine deaminase and the histological pattern observed in pythiosis lesions of rabbits treated with deferasirox were similar to the ones in animals treated with immunotherapy.

Iron isomaltoside 1000: a new intravenous iron for treating iron deficiency in chronic kidney disease

DEFF Research Database (Denmark)

Wikström, Björn; Bhandari, Sunil; Barany, Peter

2011-01-01

Patients with chronic kidney disease (CKD) often suffer from iron deficiency anemia necessitating treatment with intravenous iron. This study was designed to assess the safety of iron isomaltoside 1000 (Monofer) in CKD patients. The secondary objective was to assess its effect on iron deficiency...... anemia....

Immunomodulatory capacity of fungal proteins on the cytokine production of human peripheral blood mononuclear cells

NARCIS (Netherlands)

Jeurink, P.V.; Lull Noguera, C.; Savelkoul, H.F.J.; Wichers, H.J.

2008-01-01

Immunomodulation by fungal compounds can be determined by the capacity of the compounds to influence the cytokine production by human peripheral blood mononuclear cells (hPBMC). These activities include mitogenicity, stimulation and activation of immune effector cells. Eight mushroom strains

The Effect Of Local Coal And Smelting Sponge Iron On Iron Content Of Pig Iron

Science.gov (United States)

Oediyani, Soesaptri; Juwita Sari, Pramita; Hadi P, Djoko

2018-03-01

The new regulation on mineral resources was announced by Ministry of Energy and Mineral resources (ESDM) of Indonesia at 2014 which it called Permen ESDM No 1/2014. Therefore, this research was conducted to add the value of local iron ores by using smelting technology. The objective of the research is to produce pig iron that meet the requirement of the new regulation of mineral resources such as 90% Fe. First, iron ores and coal mixed together with lime as a flux, then smelted in a Electric Arc Furnace at 1800°C. The process variables are (1; 1.25; 1.5; 1.75; 2.0) and the composition of coal (0.8%, 1.6%, 3.0%). The type of coal that used in this research was bituminous coal from Kalimantan and also the iron ores from Kalimantan. The products of the smelting technology are Pig iron and slag. Both pig iron and slag then analyzed by SEM-EDS to measure the iron content. The result shows that the maximum iron content on pig iron is about 95.04% meanwhile the minimum iron content on slag is about 3.66%. This result achieved at 1.6% coal and 2.0.

Nuclear thyroid hormone receptor binding in human mononuclear blood cells after goitre resection

DEFF Research Database (Denmark)

Kvetny, J; Matzen, L E; Blichert-Toft, M

1989-01-01

Nuclear thyroxine and triiodothyronine receptor-binding in human mononuclear blood cells were examined in 14 euthyroid persons prior to and 1, 6, 24 and 53 weeks after goitre resection. One week after resection decreased serum T3 from 1.47 nmol/l to 1.14 nmol/l (P less than 0.05), FT4I from 103 a...

Iron biomineralization by anaerobic neutrophilic iron-oxidizing bacteria

DEFF Research Database (Denmark)

Miot, Jennyfer; Benzerara, Karim; Morin, Guillaume

2009-01-01

Minerals formed by bio-oxidation of ferrous iron (Fe(II)) at neutral pH, their association with bacterial ultrastructures as well as their impact on the metabolism of iron-oxidizing bacteria remain poorly understood. Here, we investigated iron biomineralization by the anaerobic nitrate-dependent ......Minerals formed by bio-oxidation of ferrous iron (Fe(II)) at neutral pH, their association with bacterial ultrastructures as well as their impact on the metabolism of iron-oxidizing bacteria remain poorly understood. Here, we investigated iron biomineralization by the anaerobic nitrate...... precipitation in the periplasm (in a few tens of minutes), followed by the formation of surface-bound globules. Moreover, we frequently observed an asymmetric mineral thickening at the cell poles. In parallel, the evolution of iron oxidation was quantified by STXM: iron both contained in the bacteria...... and in the extracellular precipitates reached complete oxidation within 6 days. While a progressive oxidation of Fe in the bacteria and in the medium could be observed, spatial redox (oxido-reduction state) heterogeneities were detected at the cell poles and in the extracellular precipitates after 1 day. All...

The treatment of iron deficiency without anaemia (in otherwise healthy persons).

Science.gov (United States)

Clénin, German E

2017-06-21

Iron deficiency is the most widespread and frequent nutritional disorder in the world. It affects a high proportion of children and women in developing countries and is also significantly prevalent in the industrialised world, with a clear predominance in adolescents and menstruating females. Iron is essential for optimal cognitive function and physical performance, not only as a binding site of oxygen but also as a critical constituent of many enzymes. Therefore iron deficiency at all its levels - nonanaemic iron deficiency, iron deficiency with microcytosis or hypochromia and iron deficiency anaemia - should be treated. In the presence of normal stores, however, preventative iron administration is inefficient, has side effects and seems to be harmful. In symptomatic patients with fatigue or in a population at risk for iron deficiency (adolescence, heavy or prolonged menstruation, high performance sport, vegetarian or vegan diet, eating disorder, underweight), a baseline set of blood tests including haemoglobin concentration, haematocrit, mean cellular volume, mean cellular haemoglobin, percentage of hypochromic erythrocytes and serum ferritin levels are important to monitor iron deficiency. To avoid false negative results (high ferritin levels in spite of iron deficiency), an acute phase reaction should be excluded by history and measurement of C-reactive protein. An algorithm leads through this diagnostic process and the decision making for a possible treatment. For healthy males and females aged >15 years, a ferritin cut-off of 30 µg/l is appropriate. For children from 6-12 years and younger adolescents from 12-15 years, cut-offs of 15 and 20 µg/l, respectively, are recommended. As a first step in treatment, counselling and oral iron therapy are usually combined. Integrating haem and free iron regularly into the diet, looking for enhancers and avoiding inhibitors of iron uptake is beneficial. In order to prevent reduced compliance, mainly as a result of

46 CFR 56.60-10 - Cast iron and malleable iron.

Science.gov (United States)

2010-10-01

... 46 Shipping 2 2010-10-01 2010-10-01 false Cast iron and malleable iron. 56.60-10 Section 56.60-10... APPURTENANCES Materials § 56.60-10 Cast iron and malleable iron. (a) The low ductility of cast iron and malleable iron should be recognized and the use of these metals where shock loading may occur should be...

A Bacillus paralicheniformis Iron-Containing Urease Reduces Urea Concentrations in Rice Wine.

Science.gov (United States)

Liu, Qingtao; Chen, Yuqi; Yuan, Minglai; Du, Guocheng; Chen, Jian; Kang, Zhen

2017-09-01

Urease, a nickel-containing metalloenzyme, was the first enzyme to be crystallized and has a prominent position in the history of biochemistry. In the present study, we identified a nickel urease gene cluster, ureABCEFGDH , in Bacillus paralicheniformis ATCC 9945a and characterized it in Escherichia coli Enzymatic assays demonstrate that this oxygen-stable urease is also an iron-containing acid urease. Heterologous expression assays of UreH suggest that this accessory protein is involved in the transmembrane transportation of nickel and iron ions. Moreover, this iron-containing acid urease has a potential application in the degradation of urea in rice wine. The present study not only enhances our understanding of the mechanism of activation of urease but also provides insight into the evolution of metalloenzymes. IMPORTANCE An iron-containing, oxygen-stable acid urease from B. paralicheniformis ATCC 9945a with good enzymatic properties was characterized. This acid urease shows activities toward both urea and ethyl carbamate. After digestion with 6 U/ml urease, approximately 92% of the urea in rice wine was removed, suggesting that this urease has great potential in the food industry. Copyright © 2017 American Society for Microbiology.

The DNA methylome of human peripheral blood mononuclear cells

DEFF Research Database (Denmark)

Li, Yingrui; Zhu, Jingde; Tian, Geng

2010-01-01

DNA methylation plays an important role in biological processes in human health and disease. Recent technological advances allow unbiased whole-genome DNA methylation (methylome) analysis to be carried out on human cells. Using whole-genome bisulfite sequencing at 24.7-fold coverage (12.3-fold per...... strand), we report a comprehensive (92.62%) methylome and analysis of the unique sequences in human peripheral blood mononuclear cells (PBMC) from the same Asian individual whose genome was deciphered in the YH project. PBMC constitute an important source for clinical blood tests world-wide. We found...... research and confirms new sequencing technology as a paradigm for large-scale epigenomics studies....

Characterization of a tricationic trigonal bipyramidal iron(IV) cyanide complex, with a very high reduction potential, and its iron(II) and iron(III) congeners.

Science.gov (United States)

England, Jason; Farquhar, Erik R; Guo, Yisong; Cranswick, Matthew A; Ray, Kallol; Münck, Eckard; Que, Lawrence

2011-04-04

Currently, there are only a handful of synthetic S = 2 oxoiron(IV) complexes. These serve as models for the high-spin (S = 2) oxoiron(IV) species that have been postulated, and confirmed in several cases, as key intermediates in the catalytic cycles of a variety of nonheme oxygen activating enzymes. The trigonal bipyramidal complex [Fe(IV)(O)(TMG(3)tren)](2+) (1) was both the first S = 2 oxoiron(IV) model complex to be generated in high yield and the first to be crystallographically characterized. In this study, we demonstrate that the TMG(3)tren ligand is also capable of supporting a tricationic cyanoiron(IV) unit, [Fe(IV)(CN)(TMG(3)tren)](3+) (4). This complex was generated by electrolytic oxidation of the high-spin (S = 2) iron(II) complex [Fe(II)(CN)(TMG(3)tren)](+) (2), via the S = 5/2 complex [Fe(III)(CN)(TMG(3)tren)](2+) (3), the progress of which was conveniently monitored by using UV-vis spectroscopy to follow the growth of bathochromically shifting ligand-to-metal charge transfer (LMCT) bands. A combination of X-ray absorption spectroscopy (XAS), Mössbauer and NMR spectroscopies was used to establish that 4 has a S = 0 iron(IV) center. Consistent with its diamagnetic iron(IV) ground state, extended X-ray absorption fine structure (EXAFS) analysis of 4 indicated a significant contraction of the iron-donor atom bond lengths, relative to those of the crystallographically characterized complexes 2 and 3. Notably, 4 has an Fe(IV/III) reduction potential of ∼1.4 V vs Fc(+/o), the highest value yet observed for a monoiron complex. The relatively high stability of 4 (t(1/2) in CD(3)CN solution containing 0.1 M KPF(6) at 25 °C ≈ 15 min), as reflected by its high-yield accumulation via slow bulk electrolysis and amenability to (13)C NMR at -40 °C, highlights the ability of the sterically protecting, highly basic peralkylguanidyl donors of the TMG(3)tren ligand to support highly charged high-valent complexes.

Quantification of body iron and iron absorption in the REDS-II Donor Iron Status Evaluation (RISE) study.

Science.gov (United States)

Kiss, Joseph E; Birch, Rebecca J; Steele, Whitney R; Wright, David J; Cable, Ritchard G

2017-07-01

Repeated blood donation alters the iron balance of blood donors. We quantified these effects by analyzing changes in body iron as well as calculating iron absorbed per day for donors enrolled in a prospective study. For 1308 donors who completed a final study visit, we calculated total body iron at the enrollment and final visits and the change in total body iron over the course of the study. Taking into account iron lost from blood donations during the study and obligate losses, we also calculated the average amount of iron absorbed per day. First-time/reactivated donors at enrollment had iron stores comparable to previous general population estimates. Repeat donors had greater donation intensity and greater mean iron losses than first-time/reactivated donors, yet they had little change in total body iron over the study period, whereas first-time/reactivated donors had an average 35% drop. There was higher estimated iron absorption in the repeat donors (men: 4.49 mg/day [95% confidence interval [CI], 4.41-4.58 mg/day]; women: 3.75 mg/day [95% CI, 3.67-3.84 mg/day]) compared with estimated iron absorption in first-time/reactivated donors (men: 2.89 mg/day [95% CI, 2.75-3.04 mg/day]; women: 2.76 mg/day [95% CI, 2.64-2.87 mg/day]). The threshold for negative estimated iron stores (below "0" mg/kg stores) was correlated with the development of anemia at a plasma ferritin value of 10 ng/mL. These analyses provide quantitative data on changes in estimated total body iron for a broad spectrum of blood donors. In contrast to using ferritin alone, this model allows assessment of the iron content of red blood cells and the degree of both iron surplus and depletion over time. © 2017 AABB.

Iron-Deficiency Anemia

Medline Plus

Full Text Available ... Research Home / < Back To Health Topics / Iron-Deficiency Anemia Iron-Deficiency Anemia Also known as Leer en español Iron-deficiency ... iron-deficiency anemia. Blood tests to screen for iron-deficiency anemia To screen for iron-deficiency anemia, your doctor ...

49 CFR 192.373 - Service lines: Cast iron and ductile iron.

Science.gov (United States)

2010-10-01

... 49 Transportation 3 2010-10-01 2010-10-01 false Service lines: Cast iron and ductile iron. 192.373... Regulators, and Service Lines § 192.373 Service lines: Cast iron and ductile iron. (a) Cast or ductile iron... cast iron pipe or ductile iron pipe is installed for use as a service line, the part of the service...

Influence of Ligand Architecture in Tuning Reaction Bifurcation Pathways for Chlorite Oxidation by Non-Heme Iron Complexes

NARCIS (Netherlands)

Barman, Prasenjit; Faponle, Abayomi S; Vardhaman, Anil Kumar; Angelone, Davide; Löhr, Anna-Maria; Browne, Wesley R; Comba, Peter; Sastri, Chivukula V; de Visser, Sam P

2016-01-01

Reaction bifurcation processes are often encountered in the oxidation of substrates by enzymes and generally lead to a mixture of products. One particular bifurcation process that is common in biology relates to electron transfer versus oxygen atom transfer by high-valent iron(IV)-oxo complexes,

Phenolic profiling and therapeutic potential of local flora of Azad Kashmir; In vitro enzyme inhibition and antioxidant

Directory of Open Access Journals (Sweden)

Raza Muhammad Asam

2017-12-01

Full Text Available The current study supports the phytochemical screening, evaluation of antioxidant and enzyme inhibition potential and correlations between antioxidant activities and phenolics of Rumex dentatus (Family: Polygonaceae, Mentha spicata (Family: Lamiaceae, Withania somnifera (Family: Solanaceae, Nerium indicum (Family: Apocynaceae and Artemisia scoparia (Family: Asteraceae. The herbal materials were extracted in ethanol (90% and partitioned between several solvents based on polarities. Total phenols were determined with FC method and ranged 21.33 ± 1.53 - 355.67 ± 6.03 mg GAE/ mg of the extract. Antioxidant activities (DPPH, total iron reducing capacity, phosphomolybdate assay & FRAP and enzyme inhibition potential (Protease, AChE & BChE were performed by the standard protocols. The results showed that all extracts exhibited significant DPPH activity ranging from 12.67 ± 2.08 - 92.67 ± 1.53%. The extracts that were active in DPPH activity also potrayed marvelous FRAP, total iron reducing and phosphomolybdate values. Correlation studies of antioxidant activities and the content of phenolic compounds in plant materials exhibited positive correlation between them. The outcome of enzyme inhibition activity exhibited that about 80% of the fractions under surveillance plants intimated more than 50% inhibition. Isolation of bioactive compounds from these plants is in progress.

Estradiol and Progesterone Strongly Inhibit the Innate Immune Response of Mononuclear Cells in Newborns ▿

Science.gov (United States)

Giannoni, Eric; Guignard, Laurence; Knaup Reymond, Marlies; Perreau, Matthieu; Roth-Kleiner, Matthias; Calandra, Thierry; Roger, Thierry

2011-01-01

Newborns are particularly susceptible to bacterial infections due to qualitative and quantitative deficiencies of the neonatal innate immune system. However, the mechanisms underlying these deficiencies are poorly understood. Given that fetuses are exposed to high concentrations of estradiol and progesterone during gestation and at time of delivery, we analyzed the effects of these hormones on the response of neonatal innate immune cells to endotoxin, bacterial lipopeptide, and Escherichia coli and group B Streptococcus, the two most common causes of early-onset neonatal sepsis. Here we show that at concentrations present in umbilical cord blood, estradiol and progesterone are as powerful as hydrocortisone for inhibition of cytokine production by cord blood mononuclear cells (CBMCs) and newborn monocytes. Interestingly, CBMCs and newborn monocytes are more sensitive to the effects of estradiol and progesterone than adult peripheral blood mononuclear cells and monocytes. This increased sensitivity is associated with higher expression levels of estrogen and membrane progesterone receptors but is independent of a downregulation of Toll-like receptor 2 (TLR2), TLR4, and myeloid differentiation primary response gene 88 in newborn cells. Estradiol and progesterone mediate their anti-inflammatory activity through inhibition of the NF-κB pathway but not the mitogen-activated protein kinase pathway in CBMCs. Altogether, these results suggest that elevated umbilical cord blood concentrations of estradiol and progesterone acting on mononuclear cells expressing high levels of steroid receptors contribute to impair innate immune responses in newborns. Therefore, intrauterine exposure to estradiol and progesterone may participate in increasing susceptibility to infection during the neonatal period. PMID:21518785

Contributions of molecular size, charge distribution, and specific amino acids to the iron-binding capacity of sea cucumber (Stichopus japonicus) ovum hydrolysates.

Science.gov (United States)

Sun, Na; Cui, Pengbo; Jin, Ziqi; Wu, Haitao; Wang, Yixing; Lin, Songyi

2017-09-01

This study investigated the contributions of molecular size, charge distribution and specific amino acids to the iron-binding capacity of sea cucumber (Stichopus japonicus) ovum hydrolysates (SCOHs), and further explored their iron-binding sites. It was demonstrated that enzyme type and degree of hydrolysis (DH) significantly influenced the iron-binding capacity of the SCOHs. The SCOHs produced by alcalase at a DH of 25.9% possessed the highest iron-binding capacity at 92.1%. As the hydrolysis time increased, the molecular size of the SCOHs decreased, the negative charges increased, and the hydrophilic amino acids were exposed to the surface, facilitating iron binding. Furthermore, the Fourier transform infrared spectra, combined with amino acid composition analysis, revealed that iron bound to the SCOHs primarily through interactions with carboxyl oxygen of Asp, guanidine nitrogen of Arg or nitrogen atoms in imidazole group of His. The formed SCOHs-iron complexes exhibited a fold and crystal structure with spherical particles. Copyright © 2017 Elsevier Ltd. All rights reserved.

Electroosmotic dewatering of chalk sludge, iron hydroxide sludge, wet fly ash and biomass

Energy Technology Data Exchange (ETDEWEB)

Hansen, H.K.; Kristensen, I.V.; Ottosen, L.M.; Villumsen, A. [Dept. of Geology and Geotechnical Engineering, The Technical Univ. of Denmark, Lyngby (Denmark)

2001-07-01

Electroosmotic dewatering has been tested in laboratory cells for 4 different porous materials: chalk sludge, iron hydroxide sludge, wet fly ash and biomass sludge from enzyme production. In all cases it was possible to remove water when passing electric DC current through the material. Casagrande's coefficients for the three materials where determined at different water contents. In the electroosmotic experiments shown in this work chalk can be dewatered from 40% to 79% DM (dry matter), fly ash from 75 to 82% DM, iron hydroxide sludge from 2.7 to 19% DM and biomass from 3 to 33% DM. The process was not optimised indicating that higher dry matter contents could be achieved. (orig.)

Improvement of the stability and activity of immobilized glucose oxidase on modified iron oxide magnetic nanoparticles

Energy Technology Data Exchange (ETDEWEB)

Abbasi, Mahboube, E-mail: mahbubeabbasi@yahoo.com; Amiri, Razieh, E-mail: razieh.amiri@gmail.com; Bordbar, Abdol-Kalegh, E-mail: bordbar@chem.ui.ac.ir; Ranjbakhsh, Elnaz, E-mail: e.ranjbakhsh@yahoo.com; Khosropour, Ahmad-Reza, E-mail: khosropour@chem.ui.ac.ir

2016-02-28

Graphical abstract: - Highlights: • Modified iron oxide magnetic nanoparticles were synthesized by co-precipitation method and characterized by TEM and XRD. • Covalent attachment of GOX to MIMNs was confirmed by FT-IR technique. • Optimization of the reaction time and initial amount of the GOX were carried out. • Improvement of activity and stability of immobilized GOX have been increased in comparison of free GOX. - Abstract: Immobilized proteins and enzymes are widely investigated in the medical field as well as the food and environmental fields. In this study, glucose oxidase (GOX) was covalently immobilized on the surface of modified iron oxide magnetic nanoparticles (MIMNs) to produce a bioconjugate complex. Transmission electron microscopy (TEM) and X-ray diffraction (XRD) were used to the size, shape and structure characterization of the MIMNs. Binding of GOX to these MIMNs was confirmed by using FT-IR spectroscopy. The stability of the immobilized and free enzyme at different temperature and pH values was investigated by measuring the enzymatic activity. These studies reveal that the enzyme's stability is enhanced by immobilization. Further experiments showed that the storage stability of the enzyme is improved upon binding to the MIMNs. The results of kinetic measurements suggest that the effect of the immobilization process on substrate and product diffusion is small. Such bioconjugates can be considered as a catalytic nanodevice for accelerating the glucose oxidation reaction for biotechnological purposes.

Mechanisms of pancreatic islet cell destruction. Dose-dependent cytotoxic effect of soluble blood mononuclear cell mediators on isolated islets of Langerhans

DEFF Research Database (Denmark)

Mandrup-Poulsen, T; Bendtzen, K; Nerup, J

1986-01-01

Supernatants of peripheral blood mononuclear cells from healthy human donors stimulated with recall antigen (purified protein derivative of tuberculin) or lectin (phytohaemagglutinin) markedly inhibited the insulin release from isolated human and rat islets of Langerhans, and decreased rat islet...... reconstituted with tuberculin or phytohaemagglutinin did not impair islet function. Electron microscopy demonstrated that supernatants were cytotoxic to islet cells. The cytotoxic mononuclear cell mediator(s) was non-dialysable, sensitive to heating to 56 degrees C, labile even when stored at -70 degrees C...

Comparative study of efficacy, tolerability and compliance of oral iron preparations (iron edetate, iron polymatose complex) and intramuscular iron sorbitol in iron deficiency anaemia in children

International Nuclear Information System (INIS)

Afzal, M.; Qureshi, S.M.; Lutafullah, M.

2009-01-01

To compare the efficacy, tolerability and compliance of oral iron preparations(iron edetate and Iron polymaltose complex) with each other and with intramuscular iron sorbitol in iron deficiency anaemia in children. A Randomized Controlled Trial (RCT) was carried out at the Paediatric Department of Combined Military Hospital (CMH) from January 2006 to December 2007. In total 146 children, up to 12 years age having haemoglobin (Hb%) less than 8 gm% were included. They were randomly distributed into three groups. Group A(64 cases) received oral sodium iron edetate (SIE), Group B (40 cases) received oral iron polymaltose complex (IPC) and group C (42 cases) received intramuscular iron sorbitol (IS) in recommended dosages. Rise in Hb%>10 gm% was kept as desired target. Maximum duration of treatment planned was 2 weeks for parenteral iron (group C) and 12 weeks for oral iron (groups A and B). Haematological parameters- Hb%, mean corpuscular volume (MCV), mean corpuscular haemoglobin (MCH), mean corpuscular haemoglobin concentration (MCHC) were measured at induction followed at 2 weeks, 4 weeks, 8 weeks and 12 weeks after start of treatment. Compliance and drop out rates were determined on each visit. Data was analyzed using SPSS version 10. ANOVA was used to analyze difference in rise in Hb% at various intervals. Statistically significant increase in mean Hb%, MCV, MCHC after 02 weeks was observed in group C (IS). Rise in these parameters became significant in group A (SIE) and B (IPC) after 04 weeks. Persistent rise was observed in oral groups at 08 and 12 weeks. Rise in Hb% was much faster in group C (IS). It took 2 weeks to achieve mean Hb% > 10 gm% and compliance rate was 40.5%, while to achieve same target, duration required was 8 weeks in group A (SIE) and 12 weeks in group B (IPC) and compliance rate was 39% and 30% respectively. Adverse effects were much more common with group A (SIE) as compared to other two groups. Intramuscular iron sorbitol is a reliable and

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

Science.gov (United States)

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

2017-12-01

Anemia affects up to 42% of gravidas. Neonatal iron deficiency is associated with low birth weight, delayed growth and development, and increased cognitive and behavioral abnormalities. While oral iron is convenient, up to 70% report significant gastrointestinal toxicity. Intravenous iron formulations allowing replacement in one visit with favorable side-effect profiles decrease rates of anemia with improved hemoglobin responses and maternal fetal outcomes. Seventy-four oral iron-intolerant, second- and third-trimester iron-deficient gravidas were questioned for oral iron intolerance and treated with intravenous iron. All received 1000 mg of low-molecular-weight iron dextran in 250 mL normal saline. Fifteen minutes after a test dose, the remainder was infused over the balance of 1 hour. Subjects were called at 1, 2, and 7 days to assess delayed reactions. Four weeks postinfusion or postpartum, hemoglobin levels and iron parameters were measured. Paired t test was used for hemoglobin and iron; 58/73 women were questioned about interval growth and development of their babies. Seventy-three of 74 enrolled subjects completed treatment. Sixty had paired pre- and posttreatment data. The mean pre- and posthemoglobin concentrations were 9.7 and 10.8 g/dL (P iron deficiency anemia. Intravenous iron has less toxicity and is more effective, supporting moving it closer to frontline therapy. Copyright © 2017 Elsevier Inc. All rights reserved.

Treatment with at Homeopathic Complex Medication Modulates Mononuclear Bone Marrow Cell Differentiation

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Beatriz Cesar

2011-01-01

Full Text Available A homeopathic complex medication (HCM, with immunomodulatory properties, is recommended for patients with depressed immune systems. Previous studies demonstrated that the medication induces an increase in leukocyte number. The bone marrow microenvironment is composed of growth factors, stromal cells, an extracellular matrix and progenitor cells that differentiate into mature blood cells. Mice were our biological model used in this research. We now report in vivo immunophenotyping of total bone marrow cells and ex vivo effects of the medication on mononuclear cell differentiation at different times. Cells were examined by light microscopy and cytokine levels were measured in vitro. After in vivo treatment with HCM, a pool of cells from the new marrow microenvironment was analyzed by flow cytometry to detect any trend in cell alteration. The results showed decreases, mainly, in CD11b and TER-119 markers compared with controls. Mononuclear cells were used to analyze the effects of ex vivo HCM treatment and the number of cells showing ring nuclei, niche cells and activated macrophages increased in culture, even in the absence of macrophage colony-stimulating factor. Cytokines favoring stromal cell survival and differentiation in culture were induced in vitro. Thus, we observe that HCM is immunomodulatory, either alone or in association with other products.

Studying Irony Detection Beyond Ironic Criticism: Let's Include Ironic Praise

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Richard Bruntsch

2017-04-01

Full Text Available Studies of irony detection have commonly used ironic criticisms (i.e., mock positive evaluation of negative circumstances as stimulus materials. Another basic type of verbal irony, ironic praise (i.e., mock negative evaluation of positive circumstances is largely absent from studies on individuals' aptitude to detect verbal irony. However, it can be argued that ironic praise needs to be considered in order to investigate the detection of irony in the variety of its facets. To explore whether the detection ironic praise has a benefit beyond ironic criticism, three studies were conducted. In Study 1, an instrument (Test of Verbal Irony Detection Aptitude; TOVIDA was constructed and its factorial structure was tested using N = 311 subjects. The TOVIDA contains 26 scenario-based items and contains two scales for the detection of ironic criticism vs. ironic praise. To validate the measurement method, the two scales of the TOVIDA were experimentally evaluated with N = 154 subjects in Study 2. In Study 3, N = 183 subjects were tested to explore personality and ability correlates of the two TOVIDA scales. Results indicate that the co-variance between the ironic TOVIDA items was organized by two inter-correlated but distinct factors: one representing ironic praise detection aptitude and one representing ironic criticism detection aptitude. Experimental validation showed that the TOVIDA items truly contain irony and that item scores reflect irony detection. Trait bad mood and benevolent humor (as a facet of the sense of humor were found as joint correlates for both ironic criticism and ironic praise detection scores. In contrast, intelligence, trait cheerfulness, and corrective humor were found as unique correlates of ironic praise detection scores, even when statistically controlling for the aptitude to detect ironic criticism. Our results indicate that the aptitude to detect ironic praise can be seen as distinct from the aptitude to detect ironic

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.

Centella asiatica modulates cancer cachexia associated inflammatory cytokines and cell death in leukaemic THP-1 cells and peripheral blood mononuclear cells (PBMC's).

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Naidoo, Dhaneshree Bestinee; Chuturgoon, Anil Amichund; Phulukdaree, Alisa; Guruprasad, Kanive Parashiva; Satyamoorthy, Kapaettu; Sewram, Vikash

2017-08-01

Cancer cachexia is associated with increased pro-inflammatory cytokine levels. Centella asiatica (C. asiatica) possesses antioxidant, anti-inflammatory and anti-tumour potential. We investigated the modulation of antioxidants, cytokines and cell death by C. asiatica ethanolic leaf extract (C LE ) in leukaemic THP-1 cells and normal peripheral blood mononuclear cells (PBMC's). Cytotoxcity of C LE was determined at 24 and 72 h (h). Oxidant scavenging activity of C LE was evaluated using the 2, 2-diphenyl-1 picrylhydrazyl (DPPH) assay. Glutathione (GSH) levels, caspase (-8, -9, -3/7) activities and adenosine triphosphate (ATP) levels (Luminometry) were then assayed. The levels of tumour necrosis factor-α (TNF-α), interleukin (IL)-6, IL-1β and IL-10 were also assessed using enzyme-linked immunosorbant assay. C LE decreased PBMC viability between 33.25-74.55% (24 h: 0.2-0.8 mg/ml C LE and 72 h: 0.4-0.8 mg/ml C LE ) and THP-1 viability by 28.404% (72 h: 0.8 mg/ml C LE ) (p cachexia.

Absorption of medicamental iron and iron from food

International Nuclear Information System (INIS)

Reizenstein, P.; Carlmark, B.; Ehn, L.; Forsberg, K.; Hoeglund, S.; Terpstra, T.

1976-01-01

Methods are reviewed for the measurement of iron absorption. The chemical balance method has been almost entirely supplanted by radioisotope methods, which include notably whole-body counting and measurement of incorporation of radioiron into red cells. A survey is also given of the various conditions that influence iron absorption, including chemical form of iron, amount of iron, accompanying diet. Absorption tests must be conducted under relevant conditions. (author)

New Insights into the Immunobiology of Mononuclear Phagocytic Cells and Their Relevance to the Pathogenesis of Cardiovascular Diseases

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Liliana Maria Sanmarco

2018-01-01

Full Text Available Macrophages are the primary immune cells that reside within the myocardium, suggesting that these mononuclear phagocytes are essential in the orchestration of cardiac immunity and homeostasis. Independent of the nature of the injury, the heart triggers leukocyte activation and recruitment. However, inflammation is harmful to this vital terminally differentiated organ with extremely poor regenerative capacity. As such, cardiac tissue has evolved particular strategies to increase the stress tolerance and minimize the impact of inflammation. In this sense, growing evidences show that mononuclear phagocytic cells are particularly dynamic during cardiac inflammation or infection and would actively participate in tissue repair and functional recovery. They respond to soluble mediators such as metabolites or cytokines, which play central roles in the timing of the intrinsic cardiac stress response. During myocardial infarction two distinct phases of monocyte influx have been identified. Upon infarction, the heart modulates its chemokine expression profile that sequentially and actively recruits inflammatory monocytes, first, and healing monocytes, later. In the same way, a sudden switch from inflammatory macrophages (with microbicidal effectors toward anti-inflammatory macrophages occurs within the myocardium very shortly after infection with Trypanosoma cruzi, the causal agent of Chagas cardiomyopathy. While in sterile injury, healing response is necessary to stop tissue damage; during an intracellular infection, the anti-inflammatory milieu in infected hearts would promote microbial persistence. The balance of mononuclear phagocytic cells seems to be also dynamic in atherosclerosis influencing plaque initiation and fate. This review summarizes the participation of mononuclear phagocyte system in cardiovascular diseases, keeping in mind that the immune system evolved to promote the reestablishment of tissue homeostasis following infection/injury, and

Iron-Deficiency Anemia

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... To Health Topics / Iron-Deficiency Anemia Iron-Deficiency Anemia Also known as Leer en español Iron-deficiency ... anemia. Blood tests to screen for iron-deficiency anemia To screen for iron-deficiency anemia, your doctor ...

Iron-Deficiency Anemia

Medline Plus

Full Text Available ... risk for iron-deficiency anemia, including: Vegetarian or vegan eating patterns. Not eating enough iron-rich foods, ... iron-fortified foods that have iron added. Vegetarian diets can provide enough iron if you choose nonmeat ...

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

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Arnab Pradhan

2017-05-01

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

Quantitative measurement of ultraviolet-induced damage in cellular DNA by an enzyme immunodot assay

International Nuclear Information System (INIS)

Wakizaka, A.; Nishizawa, Y.; Aiba, N.; Okuhara, E.; Takahashi, S.

1989-01-01

A simple enzyme immunoassay procedure was developed for the quantitative determination of 254-nm uv-induced DNA damage in cells. With the use of specific antibodies to uv-irradiated DNA and horseradish peroxidase-conjugated antibody to rabbit IgG, the extent of damaged DNA in uv-irradiated rat spleen mononuclear cells was quantitatively measurable. Through the use of this method, the amount of damaged DNA present in 2 X 10(5) cells irradiated at a dose of 75 J/m2 was estimated to be 7 ng equivalents of the standard uv-irradiated DNA. In addition, when the cells, irradiated at 750 J/m2, were incubated for 1 h, the antigenic activity of DNA decreased by 40%, suggesting that a repair of the damaged sites in DNA had proceeded to some extent in the cells

Iron-Deficiency Anemia

Medline Plus

Full Text Available ... Iron-Deficiency Anemia Iron-Deficiency Anemia Also known as Leer en español Iron-deficiency anemia is a ... address the cause of your iron deficiency, such as any underlying bleeding. If undiagnosed or untreated, iron- ...

Iron-Deficiency Anemia

Medline Plus

Full Text Available ... To Health Topics / Iron-Deficiency Anemia Iron-Deficiency Anemia Also known as Leer en español Iron-deficiency ... anemia. Blood tests to screen for iron-deficiency anemia To screen for iron-deficiency anemia, your doctor ...

A non-heme iron-mediated chemical demethylation in DNA and RNA.

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Yi, Chengqi; Yang, Cai-Guang; He, Chuan

2009-04-21

DNA methylation is arguably one of the most important chemical signals in biology. However, aberrant DNA methylation can lead to cytotoxic or mutagenic consequences. A DNA repair protein in Escherichia coli, AlkB, corrects some of the unwanted methylations of DNA bases by a unique oxidative demethylation in which the methyl carbon is liberated as formaldehyde. The enzyme also repairs exocyclic DNA lesions--that is, derivatives in which the base is augmented with an additional heterocyclic subunit--by a similar mechanism. Two proteins in humans that are homologous to AlkB, ABH2 and ABH3, repair the same spectrum of lesions; another human homologue of AlkB, FTO, is linked to obesity. In this Account, we describe our studies of AlkB, ABH2, and ABH3, including our development of a general strategy to trap homogeneous protein-DNA complexes through active-site disulfide cross-linking. AlkB uses a non-heme mononuclear iron(II) and the cofactors 2-ketoglutarate (2KG) and dioxygen to effect oxidative demethylation of the DNA base lesions 1-methyladenine (1-meA), 3-methylcytosine (3-meC), 1-methylguanine (1-meG), and 3-methylthymine (3-meT). ABH3, like AlkB, works better on single-stranded DNA (ssDNA) and is capable of repairing damaged bases in RNA. Conversely, ABH2 primarily repairs lesions in double-stranded DNA (dsDNA); it is the main housekeeping enzyme that protects the mammalian genome from 1-meA base damage. The AlkB-family proteins have moderate affinities for their substrates and bind DNA in a non-sequence-specific manner. Knowing that these proteins flip the damaged base out from the duplex DNA and insert it into the active site for further processing, we first engineered a disulfide cross-link in the active site to stabilize the Michaelis complex. Based on the detailed structural information afforded by the active-site cross-linked structures, we can readily install a cross-link away from the active site to obtain the native-like structures of these complexes

Alterations in bone marrow and blood mononuclear cell polyamine and methylglyoxal bis(guanylhydrazone) levels: phase I evaluation of alpha-difluoromethylornithine and methylglyoxal bis(guanylhydrazone) treatment of human hematological malignancies.

Science.gov (United States)

Maddox, A M; Freireich, E J; Keating, M J; Haddox, M K

1988-03-01

Nine patients with hematological malignancies were treated with difluoromethylornithine and methylglyoxal bis(guanylhydrazone). The number of circulating blast cells decreased in all of the patients treated with DFMO and MGBG for longer than 1 wk. Morphological evidence of myeloid maturation was evident in four patients with leukemia and the circulating M Protein decreased in one patient with multiple myeloma. The polyamine content of the mononuclear cells in both the peripheral blood and bone marrow was transiently increased after the initial MGBG dose. During administration of DFMO decreases were achieved in the peripheral blood mononuclear cell putrescine levels in 7 patients, spermidine levels in 5 patients, and spermine levels in 4 patients. Alterations in bone marrow mononuclear cell polyamine levels were similar to those which occurred in the peripheral cells. An average of 9 days of DFMO treatment was required to lower mononuclear cell polyamine levels. Three of the 4 evaluable patients receiving multiple MGBG doses had an increased mononuclear cell content of MGBG after DFMO pretreatment. Enhancement of cellular MGBG levels was not directly correlated to the degree of cellular polyamine depletion.

Serum iron and total iron binding capacity levels among the abo ...

African Journals Online (AJOL)

Iron deficiency anaemia is a common tropical disease. Iron plays a very important role in the human body. The understanding of the different blood groups ability to retain iron in their system can give an insight into their ability to handle the disease Iron deficiency anaemia. Serum Iron, Total Iron Binding Capacity (TIBC) and ...

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

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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.

The role of chloride in the mechanism of O(2) activation at the mononuclear nonheme Fe(II) center of the halogenase HctB.

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Pratter, Sarah M; Light, Kenneth M; Solomon, Edward I; Straganz, Grit D

2014-07-02

Mononuclear nonheme Fe(II) (MNH) and α-ketoglutarate (α-KG) dependent halogenases activate O2 to perform oxidative halogenations of activated and nonactivated carbon centers. While the mechanism of halide incorporation into a substrate has been investigated, the mechanism by which halogenases prevent oxidations in the absence of chloride is still obscure. Here, we characterize the impact of chloride on the metal center coordination and reactivity of the fatty acyl-halogenase HctB. Stopped-flow kinetic studies show that the oxidative transformation of the Fe(II)-α-KG-enzyme complex is >200-fold accelerated by saturating concentrations of chloride in both the absence and presence of a covalently bound substrate. By contrast, the presence of substrate, which generally brings about O2 activation at enzymatic MNH centers, only has an ∼10-fold effect in the absence of chloride. Circular dichroism (CD) and magnetic CD (MCD) studies demonstrate that chloride binding triggers changes in the metal center ligation: chloride binding induces the proper binding of the substrate as shown by variable-temperature, variable-field (VTVH) MCD studies of non-α-KG-containing forms and the conversion from six-coordinate (6C) to 5C/6C mixtures when α-KG is bound. In the presence of substrate, a site with square pyramidal five-coordinate (5C) geometry is observed, which is required for O2 activation at enzymatic MNH centers. In the absence of substrate an unusual trigonal bipyramidal site is formed, which accounts for the observed slow, uncoupled reactivity. Molecular dynamics simulations suggest that the binding of chloride to the metal center of HctB leads to a conformational change in the enzyme that makes the active site more accessible to the substrate and thus facilitates the formation of the catalytically competent enzyme-substrate complex. Results are discussed in relation to other MNH dependent halogenases.

Mammalian iron metabolism and its control by iron regulatory proteins☆

Science.gov (United States)

Anderson, Cole P.; Shen, Lacy; Eisenstein, Richard S.; Leibold, Elizabeth A.

2013-01-01

Cellular iron homeostasis is maintained by iron regulatory proteins 1 and 2 (IRP1 and IRP2). IRPs bind to iron-responsive elements (IREs) located in the untranslated regions of mRNAs encoding protein involved in iron uptake, storage, utilization and export. Over the past decade, significant progress has been made in understanding how IRPs are regulated by iron-dependent and iron-independent mechanisms and the pathological consequences of IRP2 deficiency in mice. The identification of novel IREs involved in diverse cellular pathways has revealed that the IRP–IRE network extends to processes other than iron homeostasis. A mechanistic understanding of IRP regulation will likely yield important insights into the basis of disorders of iron metabolism. This article is part of a Special Issue entitled: Cell Biology of Metals. PMID:22610083

Iron-binding haemerythrin RING ubiquitin ligases regulate plant iron responses and accumulation

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Kobayashi, Takanori; Nagasaka, Seiji; Senoura, Takeshi; Itai, Reiko Nakanishi; Nakanishi, Hiromi; Nishizawa, Naoko K.

2013-01-01

Iron is essential for most living organisms. Plants transcriptionally induce genes involved in iron acquisition under conditions of low iron availability, but the nature of the deficiency signal and its sensors are unknown. Here we report the identification of new iron regulators in rice, designated Oryza sativa Haemerythrin motif-containing Really Interesting New Gene (RING)- and Zinc-finger protein 1 (OsHRZ1) and OsHRZ2. OsHRZ1, OsHRZ2 and their Arabidopsis homologue BRUTUS bind iron and zinc, and possess ubiquitination activity. OsHRZ1 and OsHRZ2 are susceptible to degradation in roots irrespective of iron conditions. OsHRZ-knockdown plants exhibit substantial tolerance to iron deficiency, and accumulate more iron in their shoots and grains irrespective of soil iron conditions. The expression of iron deficiency-inducible genes involved in iron utilization is enhanced in OsHRZ-knockdown plants, mostly under iron-sufficient conditions. These results suggest that OsHRZ1 and OsHRZ2 are iron-binding sensors that negatively regulate iron acquisition under conditions of iron sufficiency. PMID:24253678

Extracting phosphoric iron under laboratorial conditions smelting bog iron ores

International Nuclear Information System (INIS)

Török, B; Thiele, A

2013-01-01

In recent years it has been indicated by archaeometric investigations that phosphoric-iron (P-iron, low carbon steel with 0,5-1,5wt% P), which is an unknown and unused kind of steel in the modern industry, was widely used in different parts of the world in medieval times. In this study we try to explore the role of phosphorus in the arhaeometallurgy of iron and answer some questions regarding the smelting bog iron ores with high P-content. XRF analyses were performed on bog iron ores collected in Somogy county. Smelting experiments were carried out on bog iron ores using a laboratory model built on the basis of previously conducted reconstructed smelting experiments in copies of excavated furnaces. The effect of technological parameters on P-content of the resulted iron bloom was studied. OM and SEM-EDS analyses were carried out on the extracted iron and slag samples. On the basis of the material analyses it can be stated that P-iron is usually extracted but the P-content is highly affected by technological parameters. Typical microstructures of P-iron and of slag could also be identified. It could also be established that arsenic usually solved in high content in iron as well

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.

Siderophore-mediated iron trafficking in humans is regulated by iron

Science.gov (United States)

Liu, Zhuoming; Lanford, Robert; Mueller, Sebastian; Gerhard, Glenn S.; Luscieti, Sara; Sanchez, Mayka; Devireddy, L.

2013-01-01

Siderophores are best known as small iron binding molecules that facilitate microbial iron transport. In our previous study we identified a siderophore-like molecule in mammalian cells and found that its biogenesis is evolutionarily conserved. A member of the short chain dehydrogenase family of reductases, 3-OH butyrate dehydrogenase (BDH2) catalyzes a rate-limiting step in the biogenesis of the mammalian siderophore. We have shown that depletion of the mammalian siderophore by inhibiting expression of bdh2 results in abnormal accumulation of cellular iron and mitochondrial iron deficiency. These observations suggest that the mammalian siderophore is a critical regulator of cellular iron homeostasis and facilitates mitochondrial iron import. By utilizing bioinformatics, we identified an iron-responsive element (IRE; a stem-loop structure that regulates genes expression post-transcriptionally upon binding to iron regulatory proteins or IRPs) in the 3′-untranslated region (3′-UTR) of the human BDH2 (hBDH2) gene. In cultured cells as well as in patient samples we now demonstrate that the IRE confers iron-dependent regulation on hBDH2 and binds IRPs in RNA electrophoretic mobility shift assays. In addition, we show that the hBDH2 IRE associates with IRPs in cells and that abrogation of IRPs by RNAi eliminates the iron-dependent regulation of hBDH2 mRNA. The key physiologic implication is that iron-mediated post-transcriptional regulation of hBDH2 controls mitochondrial iron homeostasis in human cells. These observations provide a new and an unanticipated mechanism by which iron regulates its intracellular trafficking. PMID:22527885

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.

Iron absorption studies

International Nuclear Information System (INIS)

Ekenved, G.

1976-01-01

The main objective of the present work was to study iron absorption from different iron preparations in different types of subjects and under varying therapeutic conditions. The studies were performed with different radioiron isotope techniques and with a serum iron technique. The preparations used were solutions of ferrous sulphate and rapidly-disintegrating tablets containing ferrous sulphate, ferrous fumarate and ferrous carbonate and a slow-release ferrous sulphate tablet of an insoluble matrix type (Duroferon Durules). The serum iron method was evaluated and good correlation was found between the serum iron response and the total amount of iron absorbed after an oral dose of iron given in solution or in tablet form. New technique for studying the in-vivo release properties of tablets was presented. Iron tablets labelled with a radio-isotope were given to healthy subjects. The decline of the radioactivity in the tablets was followed by a profile scanning technique applied to different types of iron tablets. The release of iron from the two types of tablets was shown to be slower in vivo than in vitro. It was found that co-administration of antacids and iron tablets led to a marked reduction in the iron absorption and that these drugs should not be administered sumultaneously. A standardized meal markedly decreased the absorbability of iron from iron tablets. The influence of the meal was more marked with rapidly-disintegrating than with slow-release ferrous sulphate tablets. The absorption from rapidly-disintegrating and slow-release ferrous sulphate tablets was compared under practical clinical conditions during an extended treatment period. The studies were performed in healthy subjects, blood donors and patients with iron deficiency anaemia and it was found that the absorption of iron from the slow-release tablets was significantly better than from the rapidly-disintegrating tablets in all three groups of subjects. (author)

A Program for Iron Economy during Deficiency Targets Specific Fe Proteins.

Science.gov (United States)

Hantzis, Laura J; Kroh, Gretchen E; Jahn, Courtney E; Cantrell, Michael; Peers, Graham; Pilon, Marinus; Ravet, Karl

2018-01-01

Iron (Fe) is an essential element for plants, utilized in nearly every cellular process. Because the adjustment of uptake under Fe limitation cannot satisfy all demands, plants need to acclimate their physiology and biochemistry, especially in their chloroplasts, which have a high demand for Fe. To investigate if a program exists for the utilization of Fe under deficiency, we analyzed how hydroponically grown Arabidopsis ( Arabidopsis thaliana ) adjusts its physiology and Fe protein composition in vegetative photosynthetic tissue during Fe deficiency. Fe deficiency first affected photosynthetic electron transport with concomitant reductions in carbon assimilation and biomass production when effects on respiration were not yet significant. Photosynthetic electron transport function and protein levels of Fe-dependent enzymes were fully recovered upon Fe resupply, indicating that the Fe depletion stress did not cause irreversible secondary damage. At the protein level, ferredoxin, the cytochrome- b 6 f complex, and Fe-containing enzymes of the plastid sulfur assimilation pathway were major targets of Fe deficiency, whereas other Fe-dependent functions were relatively less affected. In coordination, SufA and SufB, two proteins of the plastid Fe-sulfur cofactor assembly pathway, were also diminished early by Fe depletion. Iron depletion reduced mRNA levels for the majority of the affected proteins, indicating that loss of enzyme was not just due to lack of Fe cofactors. SufB and ferredoxin were early targets of transcript down-regulation. The data reveal a hierarchy for Fe utilization in photosynthetic tissue and indicate that a program is in place to acclimate to impending Fe deficiency. © 2018 American Society of Plant Biologists. All Rights Reserved.

Phototherapy causes DNA damage in peripheral mononuclear leukocytes in term infants.

Science.gov (United States)

Aycicek, Ali; Kocyigit, Abdurrahim; Erel, Ozcan; Senturk, Hakan

2008-01-01

Our aim was to determine whether endogenous mononuclear leukocyte DNA strand is a target of phototherapy. The study included 65 term infants aged between 3-10 days that had been exposed to intensive (n = 23) or conventional (n = 23) phototherapy for at least 48 hours due to neonatal jaundice, and a control group (n = 19). DNA damage was assayed by single-cell alkaline gel electrophoresis (comet assay). Plasma total antioxidant capacity and total oxidant status levels were also measured, and correlation between DNA damage and oxidative stress was investigated. Mean values of DNA damage scores in both the intensive and conventional phototherapy groups were significantly higher than those in the control group (p Total oxidant status levels in both the intensive and conventional phototherapy groups were significantly higher than those in the control group (p = 0.005). Mean (standard deviation) values were 18.1 (4.2), 16.9 (4.4), 13.5 (4.2) micromol H2O2 equivalent/L, respectively. Similarly, oxidative stress index levels in both the intensive and conventional phototherapy groups were significantly higher than those in the control group (p = 0.041). Plasma total antioxidant capacity and total bilirubin levels did not differ between the groups (p > 0.05). There were no significant correlations between DNA damage scores and bilirubin, total oxidant status and oxidative stress levels in either phototherapy group (p > 0.05). Both conventional phototherapy and intensive phototherapy cause endogenous mononuclear leukocyte DNA damage in jaundiced term infants.

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

Science.gov (United States)

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

2016-11-01

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

Effects of Selected Dietary Secondary Metabolites on Reactive Oxygen Species Production Caused by Iron(II Autoxidation

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Vladimir Chobot

2014-12-01

Full Text Available Iron is an essential co-factor for many enzymes that catalyze electron transfer reactions. It is well known that so-called “poorly liganded” iron can increase ROS concentrations and trigger oxidative stress that is capable of initiating apoptosis. Conversely, controlled ROS production has been recognized as an integral part of cellular signaling. Elevated ROS concentrations are associated with aging, inflammatory and degenerative diseases. Anti-aging properties have been attributed especially to antioxidant phenolic plant metabolites that represent food additives in our diet. Consequently, this study explores the effects of flavonoids (quercetin and rutin, several phenolic acids (caffeic, chlorogenic, and protocatechuic acid, and the alkaloid caffeine on iron(II autoxidation and ROS production in comparison to the standard antioxidants ascorbic acid and Trolox. The iron(II autoxidation assay was carried out in pH 6.0 (plant apoplast and inflamed human tissue and 7.4 (cell cytoplasm and human blood plasma. The obtained results accentuate phenolic acids as the more specific antioxidants compared to ascorbic acid and Trolox. Flavonoid redox chemistry depends more on the chemical milieu, specifically on pH. In vivo, the presence of iron cannot be ruled out and “wrongly” or “poorly” complexed iron has been pointed out as causative agent of various age-related diseases.

Cytokine secretion from human peripheral blood mononuclear cells cultured in vitro with metal particles.

Science.gov (United States)

Cachinho, Sandra C P; Pu, Fanrong; Hunt, John A

2013-04-01

The failure of implanted medical devices can be associated with changes in the production of cytokines by cells of the immune system. Cytokines released by peripheral blood mononuclear cells upon contact with metal particles were quantified to understand their role in implantation intergration and their importance as messengers in the recruitment of T-lymphocytes at the implantation site. Opsonization was utilised to understand the influence of serum proteins on particle-induced cytokine production and release. Different metal compositions were used in the particulate format, Titanium (Ti), Titanium alloy (Ti6Al4V), and Stainless Steel 316L (SS), and were cultured in vitro with a mixed population of monocytes/macrophages and lymphocytes. The cells were also exposed to an exogenous stimulant mixture of phytohemagglutinin-P and interferon-gamma (IFN-γ) and opsonized particles with human serum. Interleukins, IL-1α, IL-1β, IL-2, IL-4, IL-6, IL-8, IFN-γ, and tumor necrosis factor-alpha (TNF-α) were investigated using enzyme-linked immunosorbent assay as they are an indicator of the inflammation evoked by particulate metals. It has been experimentally evidenced that metal particles induced higher amounts of IL-6 and IL-1 but very low amounts of TNF-α. T-lymphocyte activation was evaluated by the quantification of IL-2 and IFN-γ levels. The results showed that nonopsonized and opsonized metal particles did not induce the release of increased levels of IL-2 and IFN-γ. Copyright © 2013 Wiley Periodicals, Inc.

Synthesis, characterization and single crystal x-ray analysis of a complex of iron(II) bis(2,4-dimethylphenyl)dithiophosphate with 4-ethylpyridine

Energy Technology Data Exchange (ETDEWEB)

Kumar, Sandeep; Andotra, Savit; Kaur, Mandeep [University of Jammu, Department of Chemistry (India); Gupta, Vivek K.; Kant, Rajni [Department of Physics and Electronics, University of Jammu, X-ray Crystallographic Laboratory (India); Pandey, Sushil K., E-mail: kpsushil@rediffmail.com [University of Jammu, Department of Chemistry (India)

2016-09-15

Complex of iron(II) bis(2,4-dimethylphenyl)dithiophosphate with 4-ethylpyridine [((2,4- (CH{sub 3}){sub 2}C{sub 6}H{sub 3}O)2PS2)2Fe(NC{sub 5}H{sub 4}(C{sub 2}H{sub 5})-4){sub 2}] is synthesized and characterized by elemental analysis, magnetic moment, IR spectroscopy and single crystal X-ray analysis. Complex crystallizes in the monoclinic sp. gr. P2{sub 1}/n, Z = 2. Crystal structure consists of mononuclear units with Fe(II) ion chelated by four S atoms of the two diphenyldithiophosphate ligands in bidentate manner. N atoms from two 4-ethylpyridine ligands are axially coordinated to the Fe(II) atom leading to an octahedral geometry.

Enzyme-controlled nitrogen-atom transfer enables regiodivergent C-H amination.

Science.gov (United States)

Hyster, Todd K; Farwell, Christopher C; Buller, Andrew R; McIntosh, John A; Arnold, Frances H

2014-11-05

We recently demonstrated that variants of cytochrome P450BM3 (CYP102A1) catalyze the insertion of nitrogen species into benzylic C-H bonds to form new C-N bonds. An outstanding challenge in the field of C-H amination is catalyst-controlled regioselectivity. Here, we report two engineered variants of P450BM3 that provide divergent regioselectivity for C-H amination-one favoring amination of benzylic C-H bonds and the other favoring homo-benzylic C-H bonds. The two variants provide nearly identical kinetic isotope effect values (2.8-3.0), suggesting that C-H abstraction is rate-limiting. The 2.66-Å crystal structure of the most active enzyme suggests that the engineered active site can preorganize the substrate for reactivity. We hypothesize that the enzyme controls regioselectivity through localization of a single C-H bond close to the iron nitrenoid.

Identification and Spectroscopic Characterization of Nonheme Iron(III) Hypochlorite Intermediates**

Science.gov (United States)

Draksharapu, Apparao; Angelone, Davide; Quesne, Matthew G; Padamati, Sandeep K; Gómez, Laura; Hage, Ronald; Costas, Miquel; Browne, Wesley R; de Visser, Sam P

2015-01-01

FeIII–hypohalite complexes have been implicated in a wide range of important enzyme-catalyzed halogenation reactions including the biosynthesis of natural products and antibiotics and post-translational modification of proteins. The absence of spectroscopic data on such species precludes their identification. Herein, we report the generation and spectroscopic characterization of nonheme FeIII–hypohalite intermediates of possible relevance to iron halogenases. We show that FeIII-OCl polypyridylamine complexes can be sufficiently stable at room temperature to be characterized by UV/Vis absorption, resonance Raman and EPR spectroscopies, and cryo-ESIMS. DFT methods rationalize the pathways to the formation of the FeIII-OCl, and ultimately FeIV=O, species and provide indirect evidence for a short-lived FeII-OCl intermediate. The species observed and the pathways involved offer insight into and, importantly, a spectroscopic database for the investigation of iron halogenases. PMID:25663379

Iron-Deficiency Anemia

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Full Text Available ... and severity. Treatments may include iron supplements, procedures, surgery, and dietary ... iron supplements, also called iron pills or oral iron, by mouth once or several times a ...

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.

HCG-Activated Human Peripheral Blood Mononuclear Cells (PBMC Promote Trophoblast Cell Invasion.

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Nan Yu

Full Text Available Successful embryo implantation and placentation depend on appropriate trophoblast invasion into the maternal endometrial stroma. Human chorionic gonadotropin (hCG is one of the earliest embryo-derived secreted signals in the peripheral blood mononuclear cells (PBMC that abundantly expresses hCG receptors. The aims of this study were to estimate the effect of human embryo-secreted hCG on PBMC function and investigate the role and underlying mechanisms of activated PBMC in trophoblast invasion. Blood samples were collected from women undergoing benign gynecological surgery during the mid-secretory phase. PBMC were isolated and stimulated with or without hCG for 0 or 24 h. Interleukin-1β (IL-1β and leukemia inhibitory factor (LIF expressions in PBMC were detected by enzyme-linked immunosorbent assay and real-time polymerase chain reaction (PCR. The JAR cell line served as a model for trophoblast cells and was divided into four groups: control, hCG only, PBMC only, and PBMC with hCG. JAR cell invasive and proliferative abilities were detected by trans-well and CCK8 assays and matrix metalloproteinase (MMP-2 (MMP-2, MMP-9, vascular endothelial growth factor (VEGF, tissue inhibitor of metalloproteinase (TIMP-1, and TIMP-2 expressions in JAR cells were detected by western blotting and real-time PCR analysis. We found that hCG can remarkably promote IL-1β and LIF promotion in PBMC after 24-h culture. PBMC activated by hCG significantly increased the number of invasive JAR cells in an invasion assay without affecting proliferation, and hCG-activated PBMC significantly increased MMP-2, MMP-9, and VEGF and decreased TIMP-1 and TIMP-2 expressions in JAR cells in a dose-dependent manner. This study demonstrated that hCG stimulates cytokine secretion in human PBMC and could stimulate trophoblast invasion.

Magnetically triggered clustering of biotinylated iron oxide nanoparticles in the presence of streptavidinylated enzymes

International Nuclear Information System (INIS)

Hodenius, Michael; De Cuyper, Marcel; Hieronymus, Thomas; Zenke, Martin; Becker, Christiane; Elling, Lothar; Bornemann, Jörg; Wong, John E; Richtering, Walter; Himmelreich, Uwe

2012-01-01

This work deals with the production and characterization of water-compatible, iron oxide based nanoparticles covered with functional poly(ethylene glycol) (PEG)–biotin surface groups (SPIO–PEG–biotin). Synthesis of the functionalized colloids occurred by incubating the oleate coated particles used as precursor magnetic fluid with anionic liposomes containing 14 mol% of a phospholipid–PEG–biotin conjugate. The latter was prepared by coupling dimyristoylphosphatidylethanolamine (DC 14:0 PE) to activated α-biotinylamido-ω –N-hydroxy-succinimidcarbonyl–PEG (NHS–PEG–biotin). Physical characterization of the oleate and PEG–biotin iron oxide nanocolloids revealed that they appear as colloidal stable clusters with a hydrodynamic diameter of 160 nm and zeta potentials of − 39 mV (oleate coated particles) and − 14 mV (PEG–biotin covered particles), respectively, as measured by light scattering techniques. Superconducting quantum interference device (SQUID) measurements revealed specific saturation magnetizations of 62–73 emu g −1 Fe 3 O 4 and no hysteresis was observed at 300 K. MR relaxometry at 3 T revealed very high r 2 relaxivities and moderately high r 1 values. Thus, both nanocolloids can be classified as small, superparamagnetic, negative MR contrast agents. The capacity to functionalize the particles was illustrated by binding streptavidin alkaline phosphatase (SAP). It was found, however, that these complexes become highly aggregated after capturing them on the magnetic filter device during high-gradient magnetophoresis, thereby reducing the accessibility of the SAP. (paper)

Iron-Deficiency Anemia

Medline Plus

Full Text Available ... iron-rich foods, especially during certain stages of life when more iron is needed, such as childhood and pregnancy. Good sources of iron are meat, poultry, fish, and iron- ...

Increased iron supplied through Fet3p results in replicative life span extension of Saccharomyces cerevisiae under conditions requiring respiratory metabolism.

Science.gov (United States)

Botta, Gabriela; Turn, Christina S; Quintyne, Nicholas J; Kirchman, Paul A

2011-10-01

We have previously shown that copper supplementation extends the replicative life span of Saccharomyces cerevisiae when grown under conditions forcing cells to respire. We now show that copper's effect on life span is through Fet3p, a copper containing enzyme responsible for high affinity transport of iron into yeast cells. Life span extensions can also be obtained by supplementing the growth medium with 1mM ferric chloride. Extension by high iron levels is still dependent on the presence of Fet3p. Life span extension by iron or copper requires growth on media containing glycerol as the sole carbon source, which forces yeast to respire. Yeast grown on glucose containing media supplemented with iron show no extension of life span. The iron associated with cells grown in media supplemented with copper or iron is 1.4-1.8 times that of cells grown without copper or iron supplementation. As with copper supplementation, iron supplementation partially rescues the life span of superoxide dismutase mutants. Cells grown with copper supplementation display decreased production of superoxide as measured by dihydroethidium staining. Copyright © 2011 Elsevier Inc. All rights reserved.

Measurement of iron absorption from meals contaminated with iron

International Nuclear Information System (INIS)

Hallberg, L.; Bjoern-Rasmussen, E.

1981-01-01

A method is described to measure in vitro the extent of isotopic exchange between the native nonheme food iron and added inorganic reduction to radioiron tracer. The food is digested with pepsin and trypsin in the presence of radioiron. The exchangeability of food iron is calculated from the specific activity in the food and in an extract of bathophenantroline in isoamyl alcohol obtained after digesting this food. The precision and accuracy of the method is illustrated by two kinds of studies, those in which different amounts of contamination iron are added to a meal and those evaluating contamination iron in natural meals. The present method will make it possible to measure validly iron absorption from meals contaminated with unknown amounts of iron of unknown exchangeability with the extrinsic radioiron tracer

Comparative biochemistry and physiology of iron-respiring bacteria from acidic and neutral-pH environments: Final Technical Report

Energy Technology Data Exchange (ETDEWEB)

Magnuson, T S

2009-04-07

Acidophilic dissimilatory iron-reducing bacteria (DIRB) are now being detected in a variety of ‘extreme’ low-pH, radionuclide- and heavy-metal contaminated habitats where Fe(III) reduction is taking place, and may represent a significant proportion of metal-transforming organisms in these environments. Acidiphilium cryptum is our model organism, a facultative iron-respiring Alphaproteobacterium. Major findings of this project have been 1) Discovery of novel outer-membrane and periplasmic cytochromes c in acidophiles that are reactive with Fe and Cr, 2) Discovery of Cr(VI) reduction mechanisms in acidophiles, mediated by c-type cytochromes and other reductase activity, 3) Development of enzyme detection methods specific for Cr-reducing enzymes, 4) Characterization of biofilm formation in A. cryptum, and 5) Annotation of the Acidiphilium cryptum genome (Magnuson, Kusel, and Cummings, DOE-JGI 2005-2006). Two manuscripts and one book chapter have been published, and several more mauscripts are prepared for submission.

Autologous Intravenous Mononuclear Stem Cell Therapy in Chronic Ischemic Stroke

Directory of Open Access Journals (Sweden)

Bhasin A

2012-01-01

Full Text Available Background: The regenerative potential of brain has led to emerging therapies that can cure clinico-motor deficits after neurological diseases. Bone marrow mononuclear cell therapy is a great hope to mankind as these cells are feasible, multipotent and aid in neurofunctional gains in Stroke patients. Aims: This study evaluates safety, feasibility and efficacy of autologous mononuclear (MNC stem cell transplantation in patients with chronic ischemic stroke (CIS using clinical scores and functional imaging (fMRI and DTI. Design: Non randomised controlled observational study Study: Twenty four (n=24 CIS patients were recruited with the inclusion criteria as: 3 months–2years of stroke onset, hand muscle power (MRC grade at least 2; Brunnstrom stage of recovery: II-IV; NIHSS of 4-15, comprehendible. Fugl Meyer, modified Barthel Index (mBI and functional imaging parameters were used for assessment at baseline, 8 weeks and at 24 weeks. Twelve patients were administered with mean 54.6 million cells intravenously followed by 8 weeks of physiotherapy. Twelve patients served as controls. All patients were followed up at 24 weeks. Outcomes: The laboratory and radiological outcome measures were within normal limits in MNC group. Only mBI showed statistically significant improvement at 24 weeks (p<0.05 whereas the mean FM, MRC, Ashworth tone scores in the MNC group were high as compared to control group. There was an increased number of cluster activation of Brodmann areas BA 4, BA 6 post stem cell infusion compared to controls indicating neural plasticity. Cell therapy is safe and feasible which may facilitate restoration of function in CIS.

Iron in diet

Science.gov (United States)

... Reasonable amounts of iron are also found in lamb, pork, and shellfish. Iron from vegetables, fruits, grains, ... strawberries, tomatoes, and potatoes) also increase iron absorption. Cooking foods in a cast-iron skillet can also ...

49 CFR 192.489 - Remedial measures: Cast iron and ductile iron pipelines.

Science.gov (United States)

2010-10-01

... 49 Transportation 3 2010-10-01 2010-10-01 false Remedial measures: Cast iron and ductile iron... for Corrosion Control § 192.489 Remedial measures: Cast iron and ductile iron pipelines. (a) General graphitization. Each segment of cast iron or ductile iron pipe on which general graphitization is found to a...

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...

Iron Dextran Injection

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Iron dextran injection is used to treat iron-deficiency anemia (a lower than normal number of red blood cells ... treated with iron supplements taken by mouth. Iron dextran injection is in a class of medications called ...

Iron-Deficiency Anemia

Medline Plus

Full Text Available ... to moderate iron-deficiency anemia, or red blood cell transfusion for severe iron-deficiency anemia. You may ... body needs iron to make healthy red blood cells. Iron-deficiency anemia usually develops over time because ...

Iron-Deficiency Anemia

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Full Text Available ... you are diagnosed with iron-deficiency anemia. Risk Factors You may have an increased risk for iron- ... iron-deficiency anemia if you have certain risk factors , including pregnancy. To prevent iron-deficiency anemia, your ...

Iron-Deficiency Anemia

Medline Plus

Full Text Available ... from developing iron-deficiency anemia. Foods that are good sources of iron include dried beans, dried fruits, ... iron is needed, such as childhood and pregnancy. Good sources of iron are meat, poultry, fish, and ...

Iron-Deficiency Anemia

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Full Text Available ... enough iron-rich foods, such as meat and fish, may result in you getting less than the ... pregnancy. Good sources of iron are meat, poultry, fish, and iron-fortified foods that have iron added. ...

Iron-Deficiency Anemia

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Full Text Available ... that are good sources of iron include dried beans, dried fruits, eggs, lean red meat, salmon, iron- ... of iron, including iron-fortified breads and cereals, beans, tofu, dried fruits, and spinach and other dark ...

Iron-Deficiency Anemia

Medline Plus

Full Text Available ... developing iron-deficiency anemia. Foods that are good sources of iron include dried beans, dried fruits, eggs, ... is needed, such as childhood and pregnancy. Good sources of iron are meat, poultry, fish, and iron- ...

Iron-Deficiency Anemia

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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 ...

Iron-Deficiency Anemia

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Full Text Available ... develop new therapies for conditions that affect the balance of iron in the body and lead to ... Disease Control and Prevention) Iron - Health Professional Fact Sheet (NIH) Iron Dietary Supplement Fact Sheet (NIH) Iron- ...

Mineralogy and geochemistry of banded iron formation and iron ...

Indian Academy of Sciences (India)

The geological complexities of banded iron formation (BIF) and associated iron ores of Jilling–. Langalata iron ore ...... sure to sea water. Uranium in these samples varies ..... Ce oxidation and removal (Elderfield and Greaves. 1982; De Baar et ...

Efficacy of iron fortification compared to iron supplementation among Vietnamese schoolchildren

Directory of Open Access Journals (Sweden)

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.

Iron-regulated transcription of the pvdA gene in Pseudomonas aeruginosa: effect of Fur and PvdS on promoter activity.

OpenAIRE

Leoni, L; Ciervo, A; Orsi, N; Visca, P

1996-01-01

The pvdA gene, encoding the enzyme L-ornithine N5-oxygenase, catalyzes a key step of the pyoverdin biosynthetic pathway in Pseudomonas aeruginosa. Expression studies with a promoter probe vector made it possible to identify three tightly iron-regulated promoter regions in the 5.9-kb DNA fragment upstream of pvdA. The promoter governing pvdA expression was located within the 154-bp sequence upstream of the pvdA translation start site. RNA analysis showed that expression of PvdA is iron regulat...

Iron-Deficiency Anemia

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Full Text Available ... for your body to absorb iron from the gastrointestinal tract (GI tract). Blood loss When you lose blood, ... iron deficiency. Endurance athletes lose iron through their gastrointestinal tracts. They also lose iron through the breakdown of ...

Iron-Deficiency Anemia

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Full Text Available ... Home / < Back To Health Topics / Iron-Deficiency Anemia Iron-Deficiency Anemia Also known as Leer en español ... bleeding Consuming less than recommended daily amounts of iron Iron-deficiency anemia can be caused by getting ...

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

Iron-Deficiency Anemia

Medline Plus

Full Text Available ... blocks the intestine from taking up iron. Other medical conditions Other medical conditions that may lead to iron-deficiency anemia ... daily amount of iron. If you have other medical conditions that cause iron-deficiency anemia , such as ...

Serum iron test

Science.gov (United States)

Fe+2; Ferric ion; Fe++; Ferrous ion; Iron - serum; Anemia - serum iron; Hemochromatosis - serum iron ... A blood sample is needed. Iron levels are highest in the morning. Your health care provider will likely have you do this test in the morning.

Liver Iron Contents in Rats after Administration of Certain Iron ...

African Journals Online (AJOL)

The effect of consumption of certain iron compounds on liver iron deposition was ... extra iron probably depends on the type of food prepared, .... main groups. Each main group consisted of 4 subgroups. (8 rats per subgroup) which received the same basic diet but differing amounts of iron of a specific type. Each animal was ...

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

IRON CONTENT OF FOOD COOKED IN IRON UTENSILS: A TRADITIONAL INDIAN WAY

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Bibifatima Bawakhan

2016-08-01

Full Text Available BACKGROUND Since most of the Indian population depends on vegetarian diet, prevalence of iron deficiency status is higher in India compared to other developing countries. In spite of many national programs and treatment options available in correcting this, the incidence is increasing due to poor patient compliance and intolerance to treatment. This study was an effort to show how iron content of Indian food can be increased just by following the traditional way of cooking. OBJECTIVE To compare the iron levels in the Jowar roti cooked in iron and non-iron utensils. METHODOLOGY A cross-sectional study was conducted at KIMS, Hubli. Jowar rotis were prepared from equal quantity of jowar flour in iron and non-iron tawa. Another sample of roti was prepared in iron tawa after treating with lemon juice. Six samples were homogenised and filtered. The filtrates were replicated and analysed for iron levels by FerroZine method. RESULTS In the present study, we found no change in iron levels in the roti prepared in non-iron utensil, 1.45 and 1.94 fold increase in the roti prepared in new iron tawa without water boiled in it and with water boiled in it for dough preparation respectively when compared with iron levels of plain jowar flour. There was 5.77 fold rise in iron levels in lemon juice treated roti which signifies the bioavailability of iron in food. The study showed statistical significance at ‘p’- value < 0.05. CONCLUSION Several studies have shown the similar results and this was done to strengthen the findings in our staple food. Hence, the daily iron requirement can be met easily and effectively by taking the food cooked with lemon juice in iron utensils.

Nutritional iron deficiency

NARCIS (Netherlands)

Zimmermann, M.B.; Hurrell, R.F.

2007-01-01

Iron deficiency is one of the leading risk factors for disability and death worldwide, affecting an estimated 2 billion people. Nutritional iron deficiency arises when physiological requirements cannot be met by iron absorption from diet. Dietary iron bioavailability is low in populations consuming

Compacted graphite iron: Cast iron makes a comeback

Science.gov (United States)

Dawson, S.

1994-08-01

Although compacted graphite iron has been known for more than four decades, the absence of a reliable mass-production technique has resulted in relatively little effort to exploit its operational benefits. However, a proven on-line process control technology developed by SinterCast allows for series production of complex components in high-quality CGI. The improved mechanical properties of compacted graphite iron relative to conventional gray iron allow for substantial weight reduction in gasoline and diesel engines or substantial increases in horsepower, or an optimal combination of both. Concurrent with these primary benefits, CGI also provides significant emissions and fuel efficiency benefits allowing automakers to meet legislated performance standards. The operational and environmental benefits of compacted graphite iron together with its low cost and recyclability reinforce cast iron as a prime engineering material for the future.

Colour Metallography of Cast Iron - Chapter 2: Grey Iron (Ⅱ

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Zhou Jiyang

2009-08-01

Full Text Available Cast iron, as a traditional metal material, has advantages of low total cost, good castability and machinability, good wear resistance and low notch sensitivity, and is still facing tough challenge in quality, property and variety of types etc. Experts and engineers studying and producing iron castings all around world extremely concern this serious challenge. Over more than 30 years, a great of research work has been carried out on how to further improve its property, expand its application and combine cast iron technology with some hi-techs (for example, computer technology. Nevertheless, cast iron is a multi-element and multi-phase alloy and has complex and variety of structures and still has great development potential in structure and property. For further studying and developing cast iron, theoretical research work is important promise, and the study on solidification process and control mechanism of graphite morphology is fundamental for improving property of cast iron and developing new type of cast iron. Metallography of cast iron normally includes two sections: liquid phase transformation and solid phase transformation. The book, Colour Metallography of Cast Iron, uses colour metallography technique to study solidification structures of cast irons: graphite, carbides, austenite and eutectics; and focuses on solidification processes. With progress of modern solidification theory, the control of material solidification process becomes important measure for improving traditional materials and developing new materials. Solidification structure not only influences mechanical and physical properties of cast iron, but also affects its internal quality. The book uses a large amount of colour photos to describe the formation of solidification structures and their relations. Crystallization phenomena, which cannot be displayed with traditional metallography, are presented and more phase transformation information is obtained from these colour

Microarray profiling of mononuclear peripheral blood cells identifies novel candidate genes related to chemoradiation response in rectal cancer.

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Pablo Palma

Full Text Available Preoperative chemoradiation significantly improves oncological outcome in locally advanced rectal cancer. However there is no effective method of predicting tumor response to chemoradiation in these patients. Peripheral blood mononuclear cells have emerged recently as pathology markers of cancer and other diseases, making possible their use as therapy predictors. Furthermore, the importance of the immune response in radiosensivity of solid organs led us to hypothesized that microarray gene expression profiling of peripheral blood mononuclear cells could identify patients with response to chemoradiation in rectal cancer. Thirty five 35 patients with locally advanced rectal cancer were recruited initially to perform the study. Peripheral blood samples were obtained before neaodjuvant treatment. RNA was extracted and purified to obtain cDNA and cRNA for hybridization of microarrays included in Human WG CodeLink bioarrays. Quantitative real time PCR was used to validate microarray experiment data. Results were correlated with pathological response, according to Mandard´s criteria and final UICC Stage (patients with tumor regression grade 1-2 and downstaging being defined as responders and patients with grade 3-5 and no downstaging as non-responders. Twenty seven out of 35 patients were finally included in the study. We performed a multiple t-test using Significance Analysis of Microarrays, to find those genes differing significantly in expression, between responders (n = 11 and non-responders (n = 16 to CRT. The differently expressed genes were: BC 035656.1, CIR, PRDM2, CAPG, FALZ, HLA-DPB2, NUPL2, and ZFP36. The measurement of FALZ (p = 0.029 gene expression level determined by qRT-PCR, showed statistically significant differences between the two groups. Gene expression profiling reveals novel genes in peripheral blood samples of mononuclear cells that could predict responders and non-responders to chemoradiation in patients with

Beneficial effects of non-matched allogeneic cord blood mononuclear cells upon patients with idiopathic osteoporosis

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Li Jun

2012-05-01

Full Text Available Abstract Background Immunological arguments and historical examples have shown that treatment with cord blood for non-hematopoietic activities, such as growth factor production and stimulation of angiogenesis, may not require matching or immune suppression. Methods To study the benefit of blood mononuclear cell therapy, 8 patients with idiopathic osteoporosis were given intermittent treatments with non-matched allogeneic cord blood mononuclear cells for 3 months. Morning fasting samples were collected for measuring urine N telopeptide of type-1 collagen, serum bone-specific alkaline phosphatase, and insulin-like growth factor 1 during one-year study. Results Clinical response was striking. Serum insulin-like growth factor 1 significantly increased in all patients at 3 months compared with baseline values, from 264.1 ± 107.0 to 384.4 ± 63.1 ng/mL (P = 0.002, with a tendency to return to baseline values at 12 months (312.9 ± 75.5 ng/mL, P = 0.083. In contrast, differences in serum bone-specific alkaline phosphatase and urine N telopeptide of type-1 collagen were not significant at 3 (P = 0.765, P = 0.057 or 12 months (P = 0.889, P = 0.122. A beneficial effect on bone density was observed in all patients at the lumbar spine. The mean bone mineral density calculated during therapy (0.6811 ± 0.1442 g/cm2 tended higher than baseline values (0.6239 ± 0.1362 g/cm2, P  Conclusions The findings indicate that for these patients with idiopathic osteoporosis, treatment with cord blood mononuclear cells led to a significant increase in insulin-like growth factor 1 levels, which favors the increase in bone mineral density.

Iron-Deficiency Anemia

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Full Text Available ... peas, tofu, dried fruits, and dark green leafy vegetables. Foods rich in vitamin C, such as oranges, strawberries, ... iron are meat, poultry, fish, and iron-fortified foods that have iron ... green leafy vegetables. You can also take an iron supplement. Follow ...

Iron deficiency anemia

Science.gov (United States)

Anemia - iron deficiency ... iron from old red blood cells. Iron deficiency anemia develops when your body's iron stores run low. ... You may have no symptoms if the anemia is mild. Most of the time, ... slowly. Symptoms may include: Feeling weak or tired more often ...

Iron metabolism and toxicity

International Nuclear Information System (INIS)

Papanikolaou, G.; Pantopoulos, K.

2005-01-01

Iron is an essential nutrient with limited bioavailability. When present in excess, iron poses a threat to cells and tissues, and therefore iron homeostasis has to be tightly controlled. Iron's toxicity is largely based on its ability to catalyze the generation of radicals, which attack and damage cellular macromolecules and promote cell death and tissue injury. This is lucidly illustrated in diseases of iron overload, such as hereditary hemochromatosis or transfusional siderosis, where excessive iron accumulation results in tissue damage and organ failure. Pathological iron accumulation in the liver has also been linked to the development of hepatocellular cancer. Here we provide a background on the biology and toxicity of iron and the basic concepts of iron homeostasis at the cellular and systemic level. In addition, we provide an overview of the various disorders of iron overload, which are directly linked to iron's toxicity. Finally, we discuss the potential role of iron in malignant transformation and cancer

Peripheral mononuclear cell resistin mRNA expression is increased in type 2 diabetic women.

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Tsiotra, Panayoula C; Tsigos, Constantine; Anastasiou, Eleni; Yfanti, Eleni; Boutati, Eleni; Souvatzoglou, Emmanouil; Kyrou, Ioannis; Raptis, Sotirios A

2008-01-01

Resistin has been shown to cause insulin resistance and to impair glucose tolerance in rodents, but in humans its physiological role still remains elusive. The aim of this study was to examine whether resistin mRNA expression in human peripheral mononuclear cells (PBMCs) and its corresponding plasma levels are altered in type 2 diabetes. Resistin mRNA levels were easily detectable in human PBMC, and found to be higher in DM2 compared to healthy women (P = .05). Similarly, mononuclear mRNA levels of the proinflammatory cytokines IL-1beta, TNF-alpha, and IL-6 were all significantly higher in DM2 compared to control women (P DM2 women (P = .051), and overall, they correlated significantly with BMI (r = 0.406, P = .010) and waist circumference (r = 0.516, P = .003), but not with fasting insulin levels or HOMA-IR. Resistin mRNA expression is increased in PBMC from DM2 women, together with increased expression of the inflammatory cytokines IL-1beta, TNF-alpha, and IL-6, independent of obesity. These results suggest that resistin and cytokines might contribute to the low-grade inflammation and the increased atherogenic risk observed in these patients.

Utilization of microbial iron assimilation processes for the development of new antibiotics and inspiration for the design of new anticancer agents.

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Miller, Marvin J; Zhu, Helen; Xu, Yanping; Wu, Chunrui; Walz, Andrew J; Vergne, Anne; Roosenberg, John M; Moraski, Garrett; Minnick, Albert A; McKee-Dolence, Julia; Hu, Jingdan; Fennell, Kelley; Kurt Dolence, E; Dong, Li; Franzblau, Scott; Malouin, Francois; Möllmann, Ute

2009-02-01

Pathogenic microbes rapidly develop resistance to antibiotics. To keep ahead in the "microbial war", extensive interdisciplinary research is needed. A primary cause of drug resistance is the overuse of antibiotics that can result in alteration of microbial permeability, alteration of drug target binding sites, induction of enzymes that destroy antibiotics (ie., beta-lactamase) and even induction of efflux mechanisms. A combination of chemical syntheses, microbiological and biochemical studies demonstrate that the known critical dependence of iron assimilation by microbes for growth and virulence can be exploited for the development of new approaches to antibiotic therapy. Iron recognition and active transport relies on the biosyntheses and use of microbe-selective iron-chelating compounds called siderophores. Our studies, and those of others, demonstrate that siderophores and analogs can be used for iron transport-mediated drug delivery ("Trojan Horse" antibiotics) and induction of iron limitation/starvation (Development of new agents to block iron assimilation). Recent extensions of the use of siderophores for the development of novel potent and selective anticancer agents are also described.

EXPRESSION OF GENETIC LOCI IN THE PERIPHERAL BLOOD MONONUCLEAR FRACTION FROM PATIENTS WITH PROSTATE CANCER

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M. I. Kogan

2014-08-01

Full Text Available The early diagnosis and radical treatment of aggressive prostate cancers (PC is an effective way of improving survival and quality of life in patients. To develop mini-invasive tests is one of the ways of solving the problem. The cells of a peripheral blood mononuclear fraction in the expression patterns of their genetic loci reflect the presence or absence of cancers, including information on therapeutic effectiveness. RT-PRC was used to study the relative expression of 15 genetic loci in a chromosome and one locus of mitochondrial DNA in the cells of the peripheral blood mononuclear fraction in patients with PC or benign prostate hyperplasia and in healthy men. The genetic locus patterns whose change may be of informative value for differential diagnosis in patients with different stages of PC were revealed. The authors studied the relationship and showed the prognostic role and non-relationship of the altered transcriptional activity of loci in the TP53, GSTP1, and IL10 genes in PC to the changes in prostate-specific antigen the level with 90 % specificity and 93 % specificity.

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

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

2017-09-01

Erythropoiesis-stimulating agents (ESAs) are often used in treatment of patients with chemotherapy-induced anemia. Many studies have demonstrated an improved hemoglobin (Hb) response when ESA is combined with intravenous iron supplementation and a higher effectiveness of intravenous iron over traditional oral iron formulations. A new formulation of oral sucrosomial iron featuring an increased bioavailability compared to traditional oral formulations has recently become available and could provide a valid alternative to those by intravenous (IV) route. Our study evaluated the performance of sucrosomial iron versus intravenous iron in increasing hemoglobin in anemic cancer patients receiving chemotherapy and darbepoetin alfa, as well as safety, need of transfusion, and quality of life (QoL). The present study considered a cohort of 64 patients with chemotherapy-related anemia (Hb >8 g/dL iron deficiency, scheduled to receive chemotherapy and darbepoetin. All patients received darbepoetin alfa 500 mcg once every 3 weeks and were randomly assigned to receive 8 weeks of IV ferric gluconate 125 mg weekly or oral sucrosomial iron 30 mg daily. The primary endpoint was to demonstrate the performance of oral sucrosomial iron in improving Hb response, compared to intravenous iron. The Hb response was defined as the Hb increase ≥2 g/dL from baseline or the attainment Hb ≥ 12 g/dL. There was no difference in the Hb response rate between the two treatment arms. Seventy one percent of patients treated with IV iron achieved an erythropoietic response, compared to 70% of patients treated with oral iron. By conventional criteria, this difference is considered to be not statistically significant. There were also no differences in the proportion of patients requiring red blood cell transfusions and changes in QoL. Sucrosomial oral iron was better tolerated. In cancer patients with chemotherapy-related anemia receiving darbepoetin alfa, sucrosomial oral iron provides

Preparation and chemical stability of iron-nitride-coated iron microparticles

International Nuclear Information System (INIS)

Luo Xin; Liu Shixiong

2007-01-01

Iron-nitride-coated iron microparticles were prepared by nitridation of the surface of iron microparticles with ammonia gas at a temperature of 510 deg. C. The phases, composition, morphology, magnetic properties, and chemical stability of the particles were studied. The phases were α-Fe, ε-Fe 3 N, and γ-Fe 4 N. The composition varied from the core to the surface, with 99.8 wt% Fe in the core, and 93.8 wt% Fe and 6 wt% N in the iron-nitride coating. The thickness of the iron-nitride coating was about 0.28 μm. The chemical stability of the microparticles was greatly improved, especially the corrosion resistance in corrosive aqueous media. The saturation magnetization and the coercive force were 17.1x10 3 and 68 kA/m, respectively. It can be concluded that iron-nitride-coated iron microparticles will be very useful in many fields, such as water-based magnetorheological fluids and polishing fluids

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

Science.gov (United States)

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

2014-02-01

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

Proteomic analysis reveals that iron availability alters the metabolic status of the pathogenic fungus Paracoccidioides brasiliensis.

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Ana F A Parente

Full Text Available Paracoccidioides brasiliensis is a thermodimorphic fungus and the causative agent of paracoccidioidomycosis (PCM. The ability of P. brasiliensis to uptake nutrients is fundamental for growth, but a reduction in the availability of iron and other nutrients is a host defense mechanism many pathogenic fungi must overcome. Thus, fungal mechanisms that scavenge iron from host may contribute to P. brasiliensis virulence. In order to better understand how P. brasiliensis adapts to iron starvation in the host we compared the two-dimensional (2D gel protein profile of yeast cells during iron starvation to that of iron rich condition. Protein spots were selected for comparative analysis based on the protein staining intensity as determined by image analysis. A total of 1752 protein spots were selected for comparison, and a total of 274 out of the 1752 protein spots were determined to have changed significantly in abundance due to iron depletion. Ninety six of the 274 proteins were grouped into the following functional categories; energy, metabolism, cell rescue, virulence, cell cycle, protein synthesis, protein fate, transcription, cellular communication, and cell fate. A correlation between protein and transcript levels was also discovered using quantitative RT-PCR analysis from RNA obtained from P. brasiliensis under iron restricting conditions and from yeast cells isolated from infected mouse spleens. In addition, western blot analysis and enzyme activity assays validated the differential regulation of proteins identified by 2-D gel analysis. We observed an increase in glycolytic pathway protein regulation while tricarboxylic acid cycle, glyoxylate and methylcitrate cycles, and electron transport chain proteins decreased in abundance under iron limiting conditions. These data suggest a remodeling of P. brasiliensis metabolism by prioritizing iron independent pathways.

Endogenous superoxide is a key effector of the oxygen sensitivity of a model obligate anaerobe.

Science.gov (United States)

Lu, Zheng; Sethu, Ramakrishnan; Imlay, James A

2018-04-03

It has been unclear whether superoxide and/or hydrogen peroxide play important roles in the phenomenon of obligate anaerobiosis. This question was explored using Bacteroides thetaiotaomicron , a major fermentative bacterium in the human gastrointestinal tract. Aeration inactivated two enzyme families-[4Fe-4S] dehydratases and nonredox mononuclear iron enzymes-whose homologs, in contrast, remain active in aerobic Escherichia coli Inactivation-rate measurements of one such enzyme, B. thetaiotaomicron fumarase, showed that it is no more intrinsically sensitive to oxidants than is an E. coli fumarase. Indeed, when the E. coli enzymes were expressed in B. thetaiotaomicron , they no longer could tolerate aeration; conversely, the B. thetaiotaomicron enzymes maintained full activity when expressed in aerobic E. coli Thus, the aerobic inactivation of the B. thetaiotaomicron enzymes is a feature of their intracellular environment rather than of the enzymes themselves. B. thetaiotaomicron possesses superoxide dismutase and peroxidases, and it can repair damaged enzymes. However, measurements confirmed that the rate of reactive oxygen species production inside aerated B. thetaiotaomicron is far higher than in E. coli Analysis of the damaged enzymes recovered from aerated B. thetaiotaomicron suggested that they had been inactivated by superoxide rather than by hydrogen peroxide. Accordingly, overproduction of superoxide dismutase substantially protected the enzymes from aeration. We conclude that when this anaerobe encounters oxygen, its internal superoxide levels rise high enough to inactivate key catabolic and biosynthetic enzymes. Superoxide thus comprises a major element of the oxygen sensitivity of this anaerobe. The extent to which molecular oxygen exerts additional direct effects remains to be determined.

Dinitrosyl iron complexes with thiol-containing ligands as a "working form" of endogenous nitric oxide.

Science.gov (United States)

Vanin, Anatoly F

2016-04-01

The material presented herein is an overview of the results obtained by our research team during the many years' study of biological activities and occurrence of dinitrosyl iron complexes (DNIC) with thiol-containing ligands in human and animal organisms. With regard to their dose dependence and vast diversity of biological activities, DNIC are similar to the system of endogenous NO, one of the most universal regulators of biological processes. The role of biologically active components in DNIC is played by their iron-dinitrosyl fragments, [Fe(NO)2], endowed with the ability to generate neutral NO molecules and nitrosonium ions (NO(+)). Their release is effected by heme-and thiol-containing proteins, which fulfill the function of biological targets and acceptors of NO and NO(+). Beneficial regulatory effects of DNIC on physiological and metabolic processes are numerous and diverse and include, among other things, lowering of arterial pressure and accelerated healing of skin wounds. In the course of fast decomposition of their Fe(NO)2 fragments (e.g., in the presence of iron chelators), DNIC produce adverse (cytotoxic) effects, which can best be exemplified by their ability to suppress the development of experimental endometriosis in animals. In animal tissues, DNIC with thiol-containing ligands are predominantly represented by the binuclear form, which, contrary to mononuclear DNIC detectable by the 2.03 signal, is EPR-silent. The ample body of evidence on biological activities and occurrence of DNIC gained so far clearly demonstrates that in human and animal organisms DNIC with thiol-containing ligands represent a "working form" of the system of endogenous NO responsible for its accumulation and stabilization in animal tissues as well as its further transfer to its biological targets. Copyright © 2016 Elsevier Inc. All rights reserved.

Iron-biofortified rice improves the iron stores of nonanemic Filipino women.

Science.gov (United States)

Haas, Jere D; Beard, John L; Murray-Kolb, Laura E; del Mundo, Angelita M; Felix, Angelina; Gregorio, Glenn B

2005-12-01

Iron deficiency is endemic in much of the world, and food system-based approaches to eradication may be viable with new plant breeding approaches to increase the micronutrient content in staple crops. It is thought that conventional plant breeding approaches provide varieties of rice that have 400-500% higher iron contents than varieties commonly consumed in much of Asia. The efficacy of consuming high-iron rice was tested during a 9-mo feeding trial with a double-blind dietary intervention in 192 religious sisters living in 10 convents around metro Manila, the Philippines. Subjects were randomly assigned to consume either high-iron rice (3.21 mg/kg Fe) or a local variety of control rice (0.57 mg/kg Fe), and daily food consumption was monitored. The high-iron rice contributed 1.79 mg Fe/d to the diet in contrast to 0.37 mg Fe/d from the control rice. The 17% difference in total dietary iron consumption compared with controls (10.16 +/- 1.06 vs. 8.44 +/- 1.82 mg/d) resulted in a modest increase in serum ferritin (P = 0.10) and total body iron (P = 0.06) and no increase in hemoglobin (P = 0.59). However, the response was greater in nonanemic subjects for ferritin (P = 0.02) and body iron (P = 0.05), representing a 20% increase after controlling for baseline values and daily rice consumption. The greatest improvements in iron status were seen in those nonanemic women who had the lowest baseline iron status and in those who consumed the most iron from rice. Consumption of biofortified rice, without any other changes in diet, is efficacious in improving iron stores of women with iron-poor diets in the developing world.

Iron Supplementation, Response in Iron-Deficiency Anemia: Analysis of Five Trials.

Science.gov (United States)

Okam, Maureen M; Koch, Todd A; Tran, Minh-Ha

2017-08-01

Oral iron-replacement therapy is the mainstay of treatment for iron-deficiency anemia, but it is often poorly tolerated or ineffective. Hemoglobin response at day 14 of oral iron may be useful in assessing whether and when to transition patients from oral to intravenous (IV) iron. Pooled data from 5 randomized trials were analyzed to compare oral and IV iron-replacement therapy for iron-deficiency anemia. Treatment criteria and assignment to oral versus IV iron were defined per protocol; this analysis included only subjects receiving oral iron. Responders were subjects with ≥1.0-g/dL increases in hemoglobin at day 14, and nonresponders were those with smaller increases. Demographic and clinical characteristics were evaluated for association with hemoglobin response at multiple timepoints. Most subjects (72.8%) were classified as responders. The proportion of subjects with hemoglobin increases ≥1.0, ≥2.0, and ≥3.0 g/dL was greatest among those with postpartum anemia, intermediate among those with heavy uterine bleeding or gastrointestinal-related causes of anemia, and lowest among those with other causes; this proportion was also significantly greater among responders than nonresponders. A ≥1.0-g/dL increase in hemoglobin on day 14 most accurately predicted satisfactory overall hemoglobin response to oral iron on day 42/56 (sensitivity 90.1%; specificity 79.3%; positive and negative predictive values of 92.9% and 72.7%, respectively). Iron-replacement therapy improved quality of life and reduced fatigue. Hemoglobin responses <1.0 g/dL at day 14 of oral iron identify subjects with iron-deficiency anemia who should be transitioned to IV iron supplementation. Copyright © 2017 Elsevier Inc. All rights reserved.

Iron homeostasis during pregnancy.

Science.gov (United States)

Fisher, Allison L; Nemeth, Elizabeta

2017-12-01

During pregnancy, iron needs to increase substantially to support fetoplacental development and maternal adaptation to pregnancy. To meet these iron requirements, both dietary iron absorption and the mobilization of iron from stores increase, a mechanism that is in large part dependent on the iron-regulatory hormone hepcidin. In healthy human pregnancies, maternal hepcidin concentrations are suppressed in the second and third trimesters, thereby facilitating an increased supply of iron into the circulation. The mechanism of maternal hepcidin suppression in pregnancy is unknown, but hepcidin regulation by the known stimuli (i.e., iron, erythropoietic activity, and inflammation) appears to be preserved during pregnancy. Inappropriately increased maternal hepcidin during pregnancy can compromise the iron availability for placental transfer and impair the efficacy of iron supplementation. The role of fetal hepcidin in the regulation of placental iron transfer still remains to be characterized. This review summarizes the current understanding and addresses the gaps in knowledge about gestational changes in hematologic and iron variables and regulatory aspects of maternal, fetal, and placental iron homeostasis. © 2017 American Society for Nutrition.

Iron-Deficiency Anemia

Medline Plus

Full Text Available ... also are hoping to determine which iron supplements work best to treat iron-deficiency anemia in children who do not consume the daily recommended amount of iron. Read less Participate in NHLBI Clinical Trials We lead or sponsor many studies related to iron-deficiency anemia. See if you ...

Comparison of response between food supplemented with powdered iron and iron in syrup form for iron deficiency anemia

International Nuclear Information System (INIS)

Ahmed, P.

2003-01-01

Objective: To evaluate and compare the response between food supplemented with iron in powdered and iron in syrup forms for the treatment of iron deficiency anemia in children aged 1-5 years. Results: Over half (51 %) of the patients were between 1-2 years of age. One hundred thirty-two were males and 68 females. Most of the patients belonged to poor socioeconomic class. The iron in powder form was better tolerated than iron syrup as this group witnessed fewer episodes of gastrointestinal disturbances. The rise in mean Hb level after 6 weeks of treatment in group A and B was 1.6 g/dl and 1.9 g/dl respectively. Hemoglobin rise in group B was more than group A but this was statistically non-significant (p>0.05). There was small but significant (p<0.05) rise in serum ferritin in both the groups. There was no significant difference between the two groups for response to the two forms of iron administration. Conclusion: The powdered form of iron is a cost-effective and better tolerated method of iron administration in children and can be considered as an alternate option for the treatment of iron deficiency anemia in children. (author)

M cells and granular mononuclear cells in Peyer's patch domes of mice depleted of their lymphocytes by total lymphoid irradiation

International Nuclear Information System (INIS)

Ermak, T.H.; Steger, H.J.; Strober, S.; Owen, R.L.

1989-01-01

The cytoarchitecture of Peyer's patches that were depleted of their lymphocytes by total lymphoid irradiation (TLI) was examined with particular attention to the effects on M cells in the follicle epithelium and on mononuclear cells in follicle domes underlying the epithelium. Five-month-old, specific pathogen-free Balb/c mice were irradiated with 200-250 rad/day, five times a week to a total dose of 3400-4250, and their Peyer's patches were either fixed for electron microscopy or frozen for immunohistochemistry 1-4 days after completion of irradiation. Control mice were examined at the same time intervals. Follicle domes of TLI mice had approximately one fourth the epithelial surface area of domes of control mice. Within the epithelium, lymphoid cells were virtually depleted after TLI, and yet the epithelium contained M cells. In control mice, most M cells were accompanied by lymphoid cells in invaginations of the apical-lateral cell membrane. In TLI mice, most M cells did not have such apical-lateral invaginations and were columnar shaped. Other than lacking lymphocytes, these cells appeared to be mature M cells. Some M cells did have lymphoid cells or granular mononuclear cells below their basal membranes, adjacent to the basal lamina. Below the epithelium, the proportion of granular mononuclear cells was greatly increased following TLI. The retention of M cells and the increase in proportion of granular mononuclear cells in follicle domes are consistent with selective depletion of lymphocytes following TLI. Persistence of M cells without lymphocytic invaginations after TLI suggests that M cells can differentiate in the absence of, or at least in the presence of very few, lymphocytes, and that invagination by lymphocytes is not necessary to maintain mature M cell morphology

Dietary Factors Modulate Iron Uptake in Caco-2 Cells from an Iron Ingot Used as a Home Fortificant to Prevent Iron Deficiency

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Ildefonso Rodriguez-Ramiro

2017-09-01

Full Text Available Iron deficiency is a major public health concern and nutritional approaches are required to reduce its prevalence. The aim of this study was to examine the iron bioavailability of a novel home fortificant, the “Lucky Iron Fish™” (LIF (www.luckyironfish.com/shop, Guelph, Canada and the impact of dietary factors and a food matrix on iron uptake from LIF in Caco-2 cells. LIF released a substantial quantity of iron (about 1.2 mM at pH 2 but this iron was only slightly soluble at pH 7 and not taken up by cells. The addition of ascorbic acid (AA maintained the solubility of iron released from LIF (LIF-iron at pH 7 and facilitated iron uptake by the cells in a concentration-dependent manner. In vitro digestion of LIF-iron in the presence of peas increased iron uptake 10-fold. However, the addition of tannic acid to the digestion reduced the cellular iron uptake 7.5-fold. Additionally, LIF-iron induced an overproduction of reactive oxygen species (ROS, similar to ferrous sulfate, but this effect was counteracted by the addition of AA. Overall, our data illustrate the major influence of dietary factors on iron solubility and bioavailability from LIF, and demonstrate that the addition of AA enhances iron uptake and reduces ROS in the intestinal lumen.

Overexpression of Drosophila frataxin triggers cell death in an iron-dependent manner.

Science.gov (United States)

Edenharter, Oliver; Clement, Janik; Schneuwly, Stephan; Navarro, Juan A

2017-12-01

Friedreich ataxia (FRDA) is the most important autosomal recessive ataxia in the Caucasian population. FRDA patients display severe neurological and cardiac symptoms that reflect a strong cellular and axonal degeneration. FRDA is caused by a loss of function of the mitochondrial protein frataxin which impairs the biosynthesis of iron-sulfur clusters and in turn the catalytic activity of several enzymes in the Krebs cycle and the respiratory chain leading to a diminished energy production. Although FRDA is due to frataxin depletion, overexpression might also be very helpful to better understand cellular functions of frataxin. In this work, we have increased frataxin expression in neurons to elucidate specific roles that frataxin might play in these tissues. Using molecular, biochemical, histological and behavioral methods, we report that frataxin overexpression is sufficient to increase oxidative phosphorylation, modify mitochondrial morphology, alter iron homeostasis and trigger oxidative stress-dependent cell death. Interestingly, genetic manipulation of mitochondrial iron metabolism by silencing mitoferrin successfully improves cell survival under oxidative-attack conditions, although enhancing antioxidant defenses or mitochondrial fusion failed to ameliorate frataxin overexpression phenotypes. This result suggests that cell degeneration is directly related to enhanced incorporation of iron into the mitochondria. Drosophila frataxin overexpression might also provide an alternative approach to identify processes that are important in FRDA such as changes in mitochondrial morphology and oxidative stress induced cell death.

In vitro expansion of Lin+ and Lin− mononuclear cells from human peripheral blood

International Nuclear Information System (INIS)

Norhaiza, H. Siti; Zarina, Z. A. Intan; Hisham, Z. A. Shahrul; Rohaya, M. A. W.

2013-01-01

Haematopoietic stem cells (HSCs) are used in the therapy of blood disorders due to the ability of these cells to reconstitute haematopoietic lineage cells when transplanted into myeloablative recipients. However, substantial number of cells is required in order for the reconstitution to take place. Since HSCs present in low frequency, larger number of donor is required to accommodate the demand of transplantable HSCs. Therefore, in vitro expansion of HSCs will have profound impact on clinical purposes. The aim of this study was to expand lineage negative (Lin − ) stem cells from human peripheral blood. Total peripheral blood mononuclear cells (PBMNCs) were fractionated from human blood by density gradient centrifugation. Subsequently, PBMNCs were subjected to magnetic assisted cell sorter (MACS) which depletes lineage positive (Lin + ) mononuclear cells expressing lineage positive markers such as CD2, CD3, CD11b, CD14, CD15, CD16, CD19, CD56, CD123, and CD235a to obtained Lin − cell population. The ability of Lin + and Lin − to survive in vitro was explored by culturing both cell populations in complete medium consisting of Alpha-Minimal Essential Medium (AMEM) +10% (v/v) Newborn Calf Serum (NBCS)+ 2% (v/v) pen/strep. In another experiment, Lin + and Lin − were cultured with complete medium supplemented with 10ng/mL of the following growth factors: stem cell factor (SCF), interleukin (IL)-3, granulocyte-macrophage colony stimulating factor (GM-CSF), 2IU/mL of Erythropoietin (Epo) and 20ng/mL of IL-6. Three samples were monitored in static culture for 22 days. The expansion potential was assessed by the number of total viable cells, counted by trypan blue exclusion assay. It was found that Lin + mononuclear cells were not able to survive either in normal proliferation medium or proliferation medium supplemented with cytokines. Similarly, Lin − stem cells were not able to survive in proliferation medium however, addition of cytokines into the proliferation

In vitro expansion of Lin+ and Lin- mononuclear cells from human peripheral blood

Science.gov (United States)

Norhaiza, H. Siti; Rohaya, M. A. W.; Zarina, Z. A. Intan; Hisham, Z. A. Shahrul

2013-11-01

Haematopoietic stem cells (HSCs) are used in the therapy of blood disorders due to the ability of these cells to reconstitute haematopoietic lineage cells when transplanted into myeloablative recipients. However, substantial number of cells is required in order for the reconstitution to take place. Since HSCs present in low frequency, larger number of donor is required to accommodate the demand of transplantable HSCs. Therefore, in vitro expansion of HSCs will have profound impact on clinical purposes. The aim of this study was to expand lineage negative (Lin-) stem cells from human peripheral blood. Total peripheral blood mononuclear cells (PBMNCs) were fractionated from human blood by density gradient centrifugation. Subsequently, PBMNCs were subjected to magnetic assisted cell sorter (MACS) which depletes lineage positive (Lin+) mononuclear cells expressing lineage positive markers such as CD2, CD3, CD11b, CD14, CD15, CD16, CD19, CD56, CD123, and CD235a to obtained Lin- cell population. The ability of Lin+ and Lin- to survive in vitro was explored by culturing both cell populations in complete medium consisting of Alpha-Minimal Essential Medium (AMEM) +10% (v/v) Newborn Calf Serum (NBCS)+ 2% (v/v) pen/strep. In another experiment, Lin+ and Lin- were cultured with complete medium supplemented with 10ng/mL of the following growth factors: stem cell factor (SCF), interleukin (IL)-3, granulocyte-macrophage colony stimulating factor (GM-CSF), 2IU/mL of Erythropoietin (Epo) and 20ng/mL of IL-6. Three samples were monitored in static culture for 22 days. The expansion potential was assessed by the number of total viable cells, counted by trypan blue exclusion assay. It was found that Lin+ mononuclear cells were not able to survive either in normal proliferation medium or proliferation medium supplemented with cytokines. Similarly, Lin- stem cells were not able to survive in proliferation medium however, addition of cytokines into the proliferation medium support Lin

Improvement of the stability and activity of immobilized glucose oxidase on modified iron oxide magnetic nanoparticles

Science.gov (United States)

Abbasi, Mahboube; Amiri, Razieh; Bordbar, Abdol-Kalegh; Ranjbakhsh, Elnaz; Khosropour, Ahmad-Reza

2016-02-01

Immobilized proteins and enzymes are widely investigated in the medical field as well as the food and environmental fields. In this study, glucose oxidase (GOX) was covalently immobilized on the surface of modified iron oxide magnetic nanoparticles (MIMNs) to produce a bioconjugate complex. Transmission electron microscopy (TEM) and X-ray diffraction (XRD) were used to the size, shape and structure characterization of the MIMNs. Binding of GOX to these MIMNs was confirmed by using FT-IR spectroscopy. The stability of the immobilized and free enzyme at different temperature and pH values was investigated by measuring the enzymatic activity. These studies reveal that the enzyme's stability is enhanced by immobilization. Further experiments showed that the storage stability of the enzyme is improved upon binding to the MIMNs. The results of kinetic measurements suggest that the effect of the immobilization process on substrate and product diffusion is small. Such bioconjugates can be considered as a catalytic nanodevice for accelerating the glucose oxidation reaction for biotechnological purposes.

Application of magnetic iron oxide nanoparticles in stabilization process of biological molecules

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Mohammad Hossien Salmani

2017-07-01

Conclusion: Co-precipitation method is an easy way to prepare magnetic nanoparticles of iron with a large surface and small particle size, which increases the ability of these particles to act as a suitable carrier for enzyme stabilization. Adequate modification of the surface of these nanoparticles enhances their ability to bind to biological molecules. The immobilized protein or enzyme on magnetic nanoparticles are more stable against structural changes, temperature and pH in comparison with un-stabilized structures, and it is widely used in various sciences, including protein isolation and purification, pharmaceutical science, and food analysis. Stabilization based on the covalent bonds and physical absorption is nonspecific, which greatly limits their functionality. The process of stabilization through bio-mediums provide a new method to overcome the selectivity problem.

In vitro evaluation of iron solubility and dialyzability of various iron fortificants and of iron-fortified milk products targeted for infants and toddlers.

Science.gov (United States)

Kapsokefalou, Maria; Alexandropoulou, Isidora; Komaitis, Michail; Politis, Ioannis

2005-06-01

The objectives of the present study were: to compare the solubility and dialyzability of various iron fortificants (iron pyrophosphate, ferrous bis-glycinate, ferrous gluconate, ferrous lactate, ferrous sulfate) added, in the presence of ascorbic acid, to pasteurized milk samples produced under laboratory conditions; and to compare the solubility and dialyzability of iron in commercial pasteurized, UHT and condensed milk products available in the Greek market fortified with various vitamins and minerals including iron and targeted towards infants (6-12 months old) and toddlers. Iron solubility and dialyzability were determined using a simulated gastrointestinal digestive system. Ferrous dialyzable iron (molecular weight lower than 8000) was used as an index for prediction of iron bioavailability. Ferrous dialyzable iron in pasteurized milk samples fortified with iron pyrophosphate, ferrous lactate and ferrous bis-glycinate was higher (P iron in products fortified with ferrous lactate was not different (P > 0.05) from those fortified with ferrous sulfate. Ferrous dialyzable iron in four condensed commercial milk products was higher (P iron was higher (P iron source, milk processing and the overall product composition affect formation of ferrous dialyzable iron and may determine the success and effectiveness of iron fortification of milk.

Helicobacter pylori dupA is polymorphic, and its active form induces proinflammatory cytokine secretion by mononuclear cells.

Science.gov (United States)

Hussein, Nawfal R; Argent, Richard H; Marx, Christian K; Patel, Sapna R; Robinson, Karen; Atherton, John C

2010-07-15

Infection with Helicobacter pylori possessing a newly described virulence factor--duodenal ulcer-promoting gene A (dupA)--has been associated with duodenal ulceration and increased gastric inflammation. The dupA locus of 34 strains was sequenced. A panel of dupA mutants was generated and cocultured with human gastric epithelial cells and peripheral blood mononuclear cells; proinflammatory cytokine release was measured. IL8 expression was measured in human gastric biopsy specimens and related to the dupA and cagA status of infecting strains. Most H. pylori strains had a dupA allele that was longer (1884 bp; dupA1) than previously described dupA alleles, although some had truncated versions (dupA2). Unlike the best-characterized H. pylori virulence determinant, the cag pathogenicity island (cag PaI), neither dupA type induced release of interleukin (IL)-8 from gastric epithelial cells. However, infections due to dupA-positive strains were associated with higher-level mucosal IL-8 messenger RNA expression in the human stomach than were infections due to dupA-negative strains. To explain this paradox, we found that dupA1 (but not dupA2 or the cag PaI) substantially increased H. pylori-induced IL-12p40 and IL-12p70 production from CD14(+) mononuclear cells. Other T helper 1-associated cytokines were also modestly induced. We suggest that virulent H. pylori strains cause inflammation by stimulating epithelial cells through cag-encoded proteins and mononuclear inflammatory cells through dupA1 products.

Intravenous Iron Therapy in Patients with Iron Deficiency Anemia: Dosing Considerations

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Todd A. Koch

2015-01-01

Full Text Available Objective. To provide clinicians with evidence-based guidance for iron therapy dosing in patients with iron deficiency anemia (IDA, we conducted a study examining the benefits of a higher cumulative dose of intravenous (IV iron than what is typically administered. Methods. We first individually analyzed 5 clinical studies, averaging the total iron deficit across all patients utilizing a modified Ganzoni formula; we then similarly analyzed 2 larger clinical studies. For the second of the larger studies (Study 7, we also compared the efficacy and retreatment requirements of a cumulative dose of 1500 mg ferric carboxymaltose (FCM to 1000 mg iron sucrose (IS. Results. The average iron deficit was calculated to be 1531 mg for patients in Studies 1–5 and 1392 mg for patients in Studies 6-7. The percentage of patients who were retreated with IV iron between Days 56 and 90 was significantly (p<0.001 lower (5.6% in the 1500 mg group, compared to the 1000 mg group (11.1%. Conclusions. Our data suggests that a total cumulative dose of 1000 mg of IV iron may be insufficient for iron repletion in a majority of patients with IDA and a dose of 1500 mg is closer to the actual iron deficit in these patients.

Preparation and properties of mononuclear and binuclear uranyl(VI), thorium(IV) and transition d ions complexes with multidentate Schiff bases

Energy Technology Data Exchange (ETDEWEB)

Vidali, M; Casellato, U; Vigato, P A; Doretti, L; Madalosso, F [Consiglio Nazionale delle Ricerche, Padua (Italy). Lab. di Chimica e Tecnologia dei Radioelementi

1977-01-01

The preparation, physical and chemical properties of a variety of mononuclear and binuclear complexes containing Schiff base ligands derived from 3-formylsalicylic acid and diamines are reported. The Schiff bases have six potential donor atoms and can function as tetrabasic ligands. In the mononuclear complexes the copper(II) and nickel(II) ions occupy the N/sub 2/O/sub 2/ donor set and the uranyl(VI) ion the O/sub 2/O/sub 2/ one. Both types of complexes can act as ligand toward transition metal ions to form complexes with a binuclear structure connected by two phenolic oxygens. The complexes have been characterized by magnetic measurements and by IR and visible spectral methods.

Anti frictional materials iron-pig iron-brass manufacture using shaving waste products of pig-iron

International Nuclear Information System (INIS)

Nasamov, S. N.; Krivij, N.; Gudenau, H. W.; Babich, A. I.; Garcia, L. L.; Formoso, A.; Cores, A.

2003-01-01

Parts based on iron and steel powders are widely used in the manufacture of automobile and domestic equipment. This work was done to study the anti-friction properties of iron-pig iron-brass compositions of materials which were obtained by pressing and sintering from a mix of iron powders and industrial by products of cast-iron turnings, brass, talc and technical sulphur. Experiments were performed using cold pressure technology in the flowing matrix of the powder composite without solid lubricants. The subsequent sintering was carried out at 1200 degree centigree under isothermal conditions in a nitrogen atmosphere in the sintering zone during 1 h. The physical-mechanical and anti-friction properties were almost double by the active drainage of the gases from the compression mould. The study of the microstructure of the sintered materials showed that free cementite existed between the particle limits and around the pores. large agglomerations of dark inclusions could be observed, consisting of graphite, zinc and iron oxides, which were points of tension in the materials that reduce its durability and, therefore, its wear resistance to dry friction. (Author) 34 refs

Enzyme-mediated quenching of the Pseudomonas quinolone signal (PQS promotes biofilm formation of Pseudomonas aeruginosa by increasing iron availability

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Beatrix Tettmann

2016-12-01

Full Text Available The 2-alkyl-3-hydroxy-4(1H-quinolone 2,4-dioxygenase HodC was previously described to cleave the Pseudomonas quinolone signal, PQS, which is exclusively used in the complex quorum sensing (QS system of Pseudomonas aeruginosa, an opportunistic pathogen employing QS to regulate virulence and biofilm development. Degradation of PQS by exogenous addition of HodC to planktonic cells of P. aeruginosa attenuated production of virulence factors, and reduced virulence in planta. However, proteolytic cleavage reduced the efficacy of HodC. Here, we identified the secreted protease LasB of P. aeruginosa to be responsible for HodC degradation. In static biofilms of the P. aeruginosa PA14 lasB::Tn mutant, the catalytic activity of HodC led to an increase in viable biomass in newly formed but also in established biofilms, and reduced the expression of genes involved in iron metabolism and siderophore production, such as pvdS, pvdL, pvdA and pvdQ. This is likely due to an increase in the levels of bioavailable iron by degradation of PQS, which is able to sequester iron from the surrounding environment. Thus, HodC, despite its ability to quench the production of virulence factors, is contraindicated for combating P. aeruginosa biofilms.

Assessment of polyphase sintered iron-cobalt-iron boride cermets

International Nuclear Information System (INIS)

Nowacki, J.; Pieczonka, T.

2004-01-01

Sintering of iron, cobalt and boron powders has been analysed. As a result iron-iron boride, Fe-Fe 2 B and iron/cobalt boride with a slight admixture of molybdenum, Fe - Co - (FeMoCo) 2 B cermets have been produced. Iron was introduced to the mixture as the Astalloy Mo Hoeganaes grade powder. Elemental amorphous boron powder was used, and formation of borides occurred both during heating and isothermal sintering periods causing dimensional changes of the sintered body. Dilatometry was chosen to control basic phenomena taking place during multiphase sintering of investigated systems. The microstructure and phase constituents of sintered compacts were controlled as well. The cermets produced were substituted to: metallographic tests, X-ray analysis, measurements of hardness and of microhardness, and of wear in the process of sliding dry friction. Cermets are made up of two phases; hard grains of iron - cobalt boride, (FeCo) 2 B (1800 HV) constituting the reinforcement and a relatively soft and plastic eutectic mixture Fe 2 B - Co (400-500 HV) constituting the matrix. (author)

Core-shell iron-iron oxide nanoparticles

DEFF Research Database (Denmark)

Kuhn, Luise Theil; Bojesen, A.; Timmermann, L.

2004-01-01

We present studies of the magnetic properties of core-shell iron-iron oxide nanoparticles. By combining Mossbauer and X-ray absorption spectroscopy we have been able to measure the change from a Fe3O4-like to a gamma-Fe2O3-like composition from the interface to the surface. Furthermore, we have...

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)

Autologous mononuclear bone marrow cells in the regeneration of tibial nerve of rabbits submitted to neurectomy: morphofunctional aspectsCélulas mononucleares autólogas de medula óssea na regeneração do nervo tibial de coelhos submetidos à neurectomia: aspectos morfofuncionais

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Camila França de Paula Orlando-Goulart

2013-10-01

Full Text Available The functional recovery after peripheral nerve injury is the main goal of therapeutic intervention. Therefore the aim of this study was to clinically evaluate functional recovery in rabbits after neurectomy and treatment with bone marrow mononuclear cells associated with the tubulization technique. For this, 24 New Zealand rabbits, were used. They were divided into two groups with 12 animals each, mononuclear cell group (MCG and saline group (SSG. The rabbits underwent right tibial nerve section and repair by the tubulization technique using silicone hollow tube, which received 0.1 ml of autologous mononuclear bone marrow cells (2 x 106 cells in the MCG and of saline solution in the SSG, in order to compare the evolution of functional recovery of the operated limbs. Gait and planimetry were performed. Planimetry of the pelvic limb footprint printed on paper with water-based ink applied to the plantar area, before (M0 and after 7 (M7, 15 (M15, 30 (M30, 45 (M45 and 60 (M60 days after surgery. The results showed no functional recovery of the tibial nerve in both groups, without differences between them in different times and among times within groups, except when compared to M0.A recuperação funcional de nervos periféricos após lesão é o principal objetivo da intervenção terapêutica. Por isso o objetivo deste estudo foi avaliar clinicamente a recuperação funcional de coelhos após neurectomia e tratamento com células mononucleares de medula óssea associada à técnica de tubulização. Foram utilizados para isto, 24 coelhos da raça Nova Zelândia, alocados em dois grupos com 12 animais cada, denominados grupo célula mononuclear (GCM e grupo solução salina (GSS. Os coelhos foram submetidos à secção do nervo tibial direito e reparação por meio da técnica de tubulização utilizando tubo oco de silicone, para então, receberem no interior do tubo, 0,1mL de suspensão de células mononucleares autólogas de medula óssea (2 x 106

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...

Characterization of Bone Marrow Mononuclear Cells on Biomaterials for Bone Tissue Engineering In Vitro

OpenAIRE

Henrich, Dirk; Verboket, René; Schaible, Alexander; Kontradowitz, Kerstin; Oppermann, Elsie; Brune, Jan C.; Nau, Christoph; Meier, Simon; Bonig, Halvard; Marzi, Ingo; Seebach, Caroline

2015-01-01

Bone marrow mononuclear cells (BMCs) are suitable for bone tissue engineering. Comparative data regarding the needs of BMC for the adhesion on biomaterials and biocompatibility to various biomaterials are lacking to a large extent. Therefore, we evaluated whether a surface coating would enhance BMC adhesion and analyze the biocompatibility of three different kinds of biomaterials. BMCs were purified from human bone marrow aspirate samples. Beta tricalcium phosphate (?-TCP, without coating or ...

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.

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...

Dual localized AtHscB involved in iron sulfur protein biogenesis in Arabidopsis.

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Xiang Ming Xu

2009-10-01

Full Text Available Iron-sulfur clusters are ubiquitous structures which act as prosthetic groups for numerous proteins involved in several fundamental biological processes including respiration and photosynthesis. Although simple in structure both the assembly and insertion of clusters into apoproteins requires complex biochemical pathways involving a diverse set of proteins. In yeast, the J-type chaperone Jac1 plays a key role in the biogenesis of iron sulfur clusters in mitochondria.In this study we demonstrate that AtHscB from Arabidopsis can rescue the Jac1 yeast knockout mutant suggesting a role for AtHscB in iron sulfur protein biogenesis in plants. In contrast to mitochondrial Jac1, AtHscB localizes to both mitochondria and the cytosol. AtHscB interacts with AtIscU1, an Isu-like scaffold protein involved in iron-sulfur cluster biogenesis, and through this interaction AtIscU1 is most probably retained in the cytosol. The chaperone AtHscA can functionally complement the yeast Ssq1knockout mutant and its ATPase activity is enhanced by AtHscB and AtIscU1. Interestingly, AtHscA is also localized in both mitochondria and the cytosol. Furthermore, AtHscB is highly expressed in anthers and trichomes and an AtHscB T-DNA insertion mutant shows reduced seed set, a waxless phenotype and inappropriate trichome development as well as dramatically reduced activities of the iron-sulfur enzymes aconitase and succinate dehydrogenase.Our data suggest that AtHscB together with AtHscA and AtIscU1 plays an important role in the biogenesis of iron-sulfur proteins in both mitochondria and the cytosol.

Glutathione, Glutaredoxins, and Iron.

Science.gov (United States)

Berndt, Carsten; Lillig, Christopher Horst

2017-11-20

Glutathione (GSH) is the most abundant cellular low-molecular-weight thiol in the majority of organisms in all kingdoms of life. Therefore, functions of GSH and disturbed regulation of its concentration are associated with numerous physiological and pathological situations. Recent Advances: The function of GSH as redox buffer or antioxidant is increasingly being questioned. New functions, especially functions connected to the cellular iron homeostasis, were elucidated. Via the formation of iron complexes, GSH is an important player in all aspects of iron metabolism: sensing and regulation of iron levels, iron trafficking, and biosynthesis of iron cofactors. The variety of GSH coordinated iron complexes and their functions with a special focus on FeS-glutaredoxins are summarized in this review. Interestingly, GSH analogues that function as major low-molecular-weight thiols in organisms lacking GSH resemble the functions in iron homeostasis. Since these iron-related functions are most likely also connected to thiol redox chemistry, it is difficult to distinguish between mechanisms related to either redox or iron metabolisms. The ability of GSH to coordinate iron in different complexes with or without proteins needs further investigation. The discovery of new Fe-GSH complexes and their physiological functions will significantly advance our understanding of cellular iron homeostasis. Antioxid. Redox Signal. 27, 1235-1251.

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)

Iron prophylaxis during pregnancy -- how much iron is needed? A randomized dose- response study of 20-80 mg ferrous iron daily in pregnant women

DEFF Research Database (Denmark)

Milman, Nils; Bergholt, Thomas; Eriksen, Lisbeth

2005-01-01

To determine the lowest dose of iron preventative of iron deficiency and iron deficiency anemia in pregnancy.......To determine the lowest dose of iron preventative of iron deficiency and iron deficiency anemia in pregnancy....

Pentraxin 3, long expression in mononuclear cells of patients with acute coronary syndrome: Correlation with C-reactive protein and matrix metalloproteinase-9 levels.

Science.gov (United States)

Ma, Ruilian; Zhang, Wei; Wang, Tiansong; He, Ximin; Huang, Zichong; Zhu, Jinguo; Yao, Zhen

2014-06-01

To investigate expression of pentraxin 3, long (PTX3) in patients with acute coronary syndrome (ACS) and its correlation with matrix metalloproteinase-9 (MMP-9) and C-reactive protein (CRP) levels. Patients with ACS were randomly assigned to the ACS group (subdivided into unstable angina pectoris [UAP] and acute myocardial infarction [AMI]). Healthy participants and patients with stable angina pectoris (SAP) were enrolled as controls. Mononuclear cell PTX3 expression, and serum MMP-9 and CRP levels, were measured by enzyme-linked immunosorbent assay. The ACS group comprised 200 patients (80 in the UAP subgroup; 120 in the AMI subgroup). The control group comprised 130 participants (80 healthy volunteers and 50 patients with SAP). PTX3 expression was significantly higher in the ACS group compared with controls (3.64 ± 0.49 versus 1.85 ± 0.65 ng/ml), and significantly higher in the AMI compared with the UAP subgroup (5.44 ± 0.47 versus 3.39 ± 0.59 ng/ml). Serum MMP-9 and CRP levels were significantly higher in the ACS group compared with controls (48.55 ± 14.22 versus 23.14 ± 0.62 ng/ml; 4.88 ± 1.76 versus 1.26 ± 0.19 ng/ml, respectively), and significantly higher in the AMI compared with the UAP subgroup (58.13 ± 7.24 versus 31.77 ± 3.61 ng/ml; 5.80 ± 1.46 versus 3.27 ± 0.83 ng/ml, respectively). PTX3 expression, and MMP-9 and CRP levels in the SAP subgroup, were not significantly different from the healthy participants. PTX3 expression positively correlated with MMP-9 and CRP levels. In patients with ACS, peripheral blood mononuclear cell PTX3 expression, and serum MMP-9 and CRP levels, were significantly enhanced compared with controls; in addition, PTX3 expression positively correlated with MMP-9 and CRP levels. PTX3 may be involved in ACS pathogenesis. © The Author(s) 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

Iron-Deficiency Anemia

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Full Text Available ... from developing iron-deficiency anemia. Foods that are good sources of iron include dried beans, dried fruits, eggs, lean red meat, ... signs of iron-deficiency anemia include: Brittle nails ...

Cast irons

CERN Document Server

1996-01-01

Cast iron offers the design engineer a low-cost, high-strength material that can be easily melted and poured into a wide variety of useful, and sometimes complex, shapes. This latest handbook from ASM covers the entire spectrum of one of the most widely used and versatile of all engineered materials. The reader will find the basic, but vital, information on metallurgy, solidification characteristics, and properties. Extensive reviews are presented on the low-alloy gray, ductile, compacted graphite, and malleable irons. New and expanded material has been added covering high-alloy white irons used for abrasion resistance and high-alloy graphitic irons for heat and corrosion resistance. Also discussed are melting furnaces and foundry practices such as melting, inoculation, alloying, pouring, gating and rising, and molding. Heat treating practices including stress relieving, annealing, normalizing, hardening and tempering, autempering (of ductile irons), and surface-hardening treatments are covered, too. ASM Spec...

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

Science.gov (United States)

Sjöberg, A; Hulthén, L

2015-04-01

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

Iron-Deficiency Anemia

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Full Text Available ... for iron-deficiency anemia. Lifestyle habits Certain lifestyle habits may increase your risk for iron-deficiency anemia, including: Vegetarian or vegan eating patterns. Not eating enough iron-rich foods, such ...

Use of radionuclides in the study of iron metabolism in iron deficient states

International Nuclear Information System (INIS)

Anatkov, A.; Karakostov, K.; Iliev, Z.; Dimitrov, L.

1977-01-01

A study of erythropoiesis in iron deficient anemias by simultaneous labelling with the radionuclides iron 59 and chromium 51 revealed accelerated iron circuit, higher percentage of daily hemolysis, severely reduced or even absent labile reserves, decreased volume of packed red cells with no decrease of blood volume. Adequate iron 59 utilization was observed after administration of large doses of iron (500 mg) in the treatment of iron deficient anemias. (author)

Prediction of reducible soil iron content from iron extraction data

NARCIS (Netherlands)

Bodegom, van P.M.; Reeven, van J.; Denier van der Gon, H.A.C.

2003-01-01

Soils contain various iron compounds that differ in solubility, reducibility and extractability. Moreover, the contribution of the various iron compounds to total iron (Fe) and total Fe concentrations differs highly among soils. As a result, the total reducible Fe content can also differ among

Long-chain PUFA in Granulocytes, Mononuclear Cells, and RBC in Patients With Cystic Fibrosis: Relation to Liver Disease

DEFF Research Database (Denmark)

Jorgensen, Marianne H.; Ott, Peter; Michaelsen, Kim F.

2012-01-01

-related liver disease were matched with 20 CF patients without. Blood samples were analysed for liver biochemistry and haematology. Granulocytes, mononuclear cells, and RBC were separated by density gradient centrifugation, and fatty acid composition was measured by gas chromatography. Hepatic ultrasound...

Taking iron supplements

Science.gov (United States)

... medlineplus.gov/ency/article/007478.htm Taking iron supplements To use the sharing features on this page, ... levels. You may also need to take iron supplements as well to rebuild iron stores in your ...

Co-Immobilization of Enzymes and Magnetic Nanoparticles by Metal-Nucleotide Hydrogelnanofibers for Improving Stability and Recycling

Directory of Open Access Journals (Sweden)

Chunfang Li

2017-01-01

Full Text Available In this paper we report a facile method for preparing co-immobilized enzyme and magnetic nanoparticles (MNPs using metal coordinated hydrogel nanofibers. Candida rugosa lipase (CRL was selected as guest protein. For good aqueous dispersity, low price and other unique properties, citric acid-modified magnetic iron oxide nanoparticles (CA-Fe3O4 NPs have been widely used for immobilizing enzymes. As a result, the relative activity of CA-Fe3O4@Zn/AMP nanofiber-immobilized CRL increased by 8-fold at pH 10.0 and nearly 1-fold in a 50 °C water bath after 30 min, compared to free CRL. Moreover, the immobilized CRL had excellent long-term storage stability (nearly 80% releative activity after storage for 13 days. This work indicated that metal-nucleotide nanofibers could efficiently co-immobilize enzymes and MNPs simultaneously, and improve the stability of biocatalysts.

Cloning and expression of an iron-containing superoxide dismutase in the parasitic protist, Trichomonas vaginalis.

Science.gov (United States)

Viscogliosi, E; Delgado-Viscogliosi, P; Gerbod, D; Dauchez, M; Gratepanche, S; Alix, A J; Dive, D

1998-04-01

A superoxide dismutase (SOD) gene of the parasitic protist Trichomonas vaginalis was cloned, sequenced, expressed in Escherichia coli, and its gene product characterized. It is an iron-containing dimeric protein with a monomeric mass of 22,067 Da. Southern blots analyses suggested the presence of seven iron-containing (FeSOD) gene copies. Hydrophobic cluster analysis revealed some peculiarities in the 2D structure of the FeSOD from T. vaginalis and a strong structural conservation between prokaryotic and eukaryotic FeSODs. Phylogenetic reconstruction of the SOD sequences confirmed the dichotomy between FeSODs and manganese-containing SODs. FeSODs of protists appeared to group together with homologous proteobacterial enzymes suggesting a possible origin of eukaryotic FeSODs through an endosymbiotic event.

Peripheral Mononuclear Cell Resistin mRNA Expression Is Increased in Type 2 Diabetic Women

Directory of Open Access Journals (Sweden)

Panayoula C. Tsiotra

2008-01-01

Full Text Available Resistin has been shown to cause insulin resistance and to impair glucose tolerance in rodents, but in humans its physiological role still remains elusive. The aim of this study was to examine whether resistin mRNA expression in human peripheral mononuclear cells (PBMCs and its corresponding plasma levels are altered in type 2 diabetes. Resistin mRNA levels were easily detectable in human PBMC, and found to be higher in DM2 compared to healthy women (P=.05. Similarly, mononuclear mRNA levels of the proinflammatory cytokines IL-1β, TNF-α, and IL-6 were all significantly higher in DM2 compared to control women (P<.001. The corresponding plasma resistin levels were slightly, but not significantly, increased in DM2 women (P=.051, and overall, they correlated significantly with BMI (r=0.406, P=.010 and waist circumference (r=0.516, P=.003, but not with fasting insulin levels or HOMA-IR. Resistin mRNA expression is increased in PBMC from DM2 women, together with increased expression of the inflammatory cytokines IL-1β, TNF-α, and IL-6, independent of obesity. These results suggest that resistin and cytokines might contribute to the low-grade inflammation and the increased atherogenic risk observed in these patients.

Iron deficiency anaemia: with the conclusion of a need for iron reader

Science.gov (United States)

Lim, Wai Feng; Yap, Boon Kar; Lai, Mei I.; Talik, Noorazrina; Nasser, Ammar Ahmed; Al-Haiqi, Ahmed Mubarak Ahmed; Sankar Krishnan, Prajindra

2017-10-01

In our bloodstream, there are plenty of red blood cells (RBC), which function as an important oxygen carrier in our bodies. Each RBC consists of millions of haemoglobin (Hb), which is made up from globin and iron. If any deficiency/malfunction of any globin, it will lead to anaemia as indicated in low Hb level while iron deficiency anaemia (IDA) is anaemic due to the lacking of iron as indicated in low Hb and ferritin levels. IDA affects almost two billion people globally while anaemia without iron deficiency, such as thalassaemia, affects almost 4.5% in Malaysian population. These anaemic conditions have similar clinical symptoms like fatigue, dizziness, in which disturb their cognitive development and productivity in workplace. In areas without proper medical access, many anaemic individuals were misdiagnosed and treated with iron tablets because they were thought to have iron deficiency anaemia due to low Hb content. But, excess iron is toxic to the body. Misdiagnosis can be avoided by iron status assessment. We hereby review the currently available iron status parameters in laboratory and field study with the conclusion of demonstrating the importance of a need for iron reader, in the effort to reduce the prevalence of IDA globally.

Enzyme

Science.gov (United States)

Enzymes are complex proteins that cause a specific chemical change in all parts of the body. For ... use them. Blood clotting is another example of enzymes at work. Enzymes are needed for all body ...

Time-resolved fluorescence monitoring of cholesterol in peripheral blood mononuclear cells

Science.gov (United States)

Martinakova, Z.; Horilova, J.; Lajdova, I.; Marcek Chorvatova, A.

2014-12-01

Precise evaluation of intracellular cholesterol distribution is crucial for improving diagnostics of diseased states associated with cholesterol alteration. Time-resolved fluorescence techniques are tested for non-invasive investigation of cholesterol in living cells. Fluorescent probe NBD attached to cholesterol was employed to evaluate cholesterol distribution in peripheral blood mononuclear cells (PBMC) isolated from the human blood. Fluorescence Lifetime Imaging Microscopy (FLIM) was successfully applied to simultaneously monitor the spatial distribution and the timeresolved characteristics of the NBD-cholesterol fluorescence in PBMC. Gathered data are the first step in the development of a new perspective non-invasive diagnostic method for evaluation of cholesterol modifications in diseases associated with disorders of lipid metabolism.

Iron-Deficiency Anemia

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Full Text Available ... making new blood cells. Visit our Aplastic Anemia Health Topic to learn more. ... recommend that you take iron supplements, also called iron pills or oral iron, by mouth once or several times a ...

Iron-Deficiency Anemia

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Full Text Available ... ESAs are usually used with iron therapy or IV iron, or when iron therapy alone is not enough. Look for Living With will discuss what your doctor may recommend, including lifelong lifestyle changes ...

Muscular sufficiency, serum protein, enzymes and bioenergetic studies in chronic malnutrition

International Nuclear Information System (INIS)

Gupta, R.K.; Mittal, R.D.; Agarwal, K.N.; Agarwal, D.K.

1994-01-01

Muscle sufficiency was significantly lower in 1336 children with chronic malnutrition of moderate to severe degree. 18 children with a chronic moderate degree of malnutrition and 8 well-nourished age-matched controls were selected for biochemical and 31-phosphorus magnetic resonance spectroscopy (31-P MRS) studies. The results shows that: a) serum total protein, albumin, iron, calcium and inorganic phosphate were similar in both groups; b) serum enzyme levels were significantly increased in the malnuourished group; c) 31-P MRS showed significantly higher means for total ATP, β-ATP, α-ATP and inorganic phosphate for the malnourished compared to the control group. In chronic malnutrition, proteins are maintained by degradation in muscle resulting in release of amino acids and enzymes. 31-P MRS studies showing increases in total ATP, β-ATP and inorganic phosphate and a decrease in phosphocreatine suggest that ATP is maintained at the cost of phosphocreatine. 22 refs., 4 tabs. 1 fig

Quantitative Proteomic Analysis of Staphylococcus aureus Treated With Punicalagin, a Natural Antibiotic From Pomegranate That Disrupts Iron Homeostasis and Induces SOS.

Science.gov (United States)

Cooper, Bret; Islam, Nazrul; Xu, Yunfeng; Beard, Hunter S; Garrett, Wesley M; Gu, Ganyu; Nou, Xiangwu

2018-05-01

Staphylococcus aureus, a bacterial, food-borne pathogen of humans, can contaminate raw fruits and vegetables. While physical and chemical methods are available to control S. aureus, scientists are searching for inhibitory phytochemicals from plants. One promising compound from pomegranate is punicalagin, a natural antibiotic. To get a broader understanding of the inhibitory effect of punicalagin on S. aureus growth, high-throughput mass spectrometry and quantitative isobaric labeling was used to investigate the proteome of S. aureus after exposure to a sublethal dose of punicalagin. Nearly half of the proteins encoded by the small genome were interrogated, and nearly half of those exhibited significant changes in accumulation. Punicalagin treatment altered the accumulation of proteins and enzymes needed for iron acquisition, and it altered amounts of enzymes for glycolysis, citric acid cycling, protein biosynthesis, and purine and pyrimidine biosynthesis. Punicalagin treatment also induced an SOS cellular response to damaged DNA. Transcriptional comparison of marker genes shows that the punicalagin-induced iron starvation and SOS responses resembles those produced by EDTA and ciprofloxacin. These results show that punicalagin adversely alters bacterial growth by disrupting iron homeostasis and that it induces SOS, possibly through DNA biosynthesis inhibition. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Iron-Deficiency Anemia

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Full Text Available ... breastfeeding. Recommended daily iron intake for children and adults. The table lists the recommended amounts of iron, ... increased need for iron during growth spurts. Older adults, especially those over age 65. Unhealthy environments Children ...

Iron-Deficiency Anemia

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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 ...

Iron-Deficiency Anemia

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Full Text Available ... heart failure . Increased risk of infections Motor or cognitive development delays in children Pregnancy complications, such as ... iron-deficiency anemia may require intravenous (IV) iron therapy or a blood transfusion . Iron supplements Your doctor ...

Iron-Deficiency Anemia

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Full Text Available ... drinking black tea, which reduces iron absorption. Other treatments If you have chronic kidney disease and iron- ... and lifestyle changes to avoid complications. Follow your treatment plan Do not stop taking your prescribed iron ...

Iron-Deficiency Anemia

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Full Text Available ... diagnoses you with iron-deficiency anemia, your treatment will depend on the cause and severity of the ... of iron. The recommended daily amounts of iron will depend on your age, sex, and whether you ...

Iron-Deficiency Anemia

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Full Text Available ... girls. From birth to 6 months, babies need 0.27 mg of iron. This number goes up ... screen blood donors for low iron stores. Reliable point-of-care testing may help identify iron deficiency ...

Iron-Deficiency Anemia

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Full Text Available ... you do not have enough iron in your body. People with mild or moderate iron-deficiency anemia ... and where to find more information. Causes Your body needs iron to make healthy red blood cells. ...

Iron-Deficiency Anemia

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Full Text Available ... starch. Restless legs syndrome Shortness of breath Weakness Complications Undiagnosed or untreated iron-deficiency anemia may cause ... as complete blood count and iron studies. Prevent complications over your lifetime To prevent complications from iron- ...

Iron-Deficiency Anemia

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Full Text Available ... lean red meat, salmon, iron-fortified breads and cereals, peas, tofu, dried fruits, and dark green leafy ... sources of iron, including iron-fortified breads and cereals, beans, tofu, dried fruits, and spinach and other ...

Iron-Deficiency Anemia

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Full Text Available ... amount of iron, and medical conditions that make it hard for your body to absorb iron from ... hepcidin. Hepcidin prevents iron from leaving cells where it is stored or from being absorbed in the ...

Iron-Deficiency Anemia

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Full Text Available ... iron-fortified foods that have iron added. Vegetarian diets can provide enough iron if you choose nonmeat ... Anemia in Chronic Kidney Disease (National Institute of Diabetes and Digestive and Kidney Diseases) Avoiding Anemia (National ...

Iron-Deficiency Anemia

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Full Text Available ... bleeding. If undiagnosed or untreated, iron-deficiency anemia can cause serious complications, including heart failure and development ... iron is too low. Low intake of iron can happen because of blood loss, consuming less than ...

Iron-Deficiency Anemia

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Full Text Available ... fruits, eggs, lean red meat, salmon, iron-fortified breads and cereals, peas, tofu, dried fruits, and dark ... choose nonmeat sources of iron, including iron-fortified breads and cereals, beans, tofu, dried fruits, and spinach ...

Iron-Deficiency Anemia

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Full Text Available ... and pregnancy. Good sources of iron are meat, poultry, fish, and iron-fortified foods that have iron ... Anemia Restless Legs Syndrome Von Willebrand Disease Other Resources NHLBI resources Your Guide to Anemia [PDF, 1. ...

Whole-body iron-59 retention measurements for estimating the iron status of piglets

International Nuclear Information System (INIS)

Pfau, A.; Rudolphi, K.; Heinrich, H.C.; Gabbe, E.E.

1976-01-01

A large-volume, 4π whole-body liquid scintillation detector was used to determine 59 Fe absorption in 173 one-to-six-weeks-old piglets with normal and depleted iron stores. Values of intestinal absorption from a 10 μmole (corresponds to 0.558 mg) 59 Fe 2+ test dose were compared with levels of haemoglobin, haematocrit, and serum iron as well as with stainable diffuse iron of bone marrow reticuloendothelial cells, and the dose relationship of intestinal iron absorption from 59 Fe-labelled FeSO 4 and methaemoglobin was measured. The investigations indicated that neither blood parameters, cytochemical gradings nor absorption levels from the 59 Fe test dose alone were sufficient to describe quantitatively the various stages of iron deficiency in piglets. A synopsis of all parameters appeared to be necessary for defining normal iron status and prelatent, latent and manifest iron deficiency. Piglets fed on sows' milk only developed manifest iron deficiency within the first three weeks of age. After an access to soil and/or creep feed from the eighth day of age, or intramuscular injections of 200 mg Fe as iron-dextran at three days of age, or injections of 200 or 400 mg Fe combined with access to creep feed, stages of manifest, latent or prelatent iron deficiency could be observed. For an iron-dextran dose of 800 mg Fe injected in amounts of 400 mg Fe at 3 and 10 days of age, a normal iron status was obtained in three-week-old piglets. The iron dose relationship indicated that 20 mg Fe administered orally as FeSO 4 or 40 mg Fe as methaemoglobin-Fe daily should cover the iron requirement of piglets for the first three weeks of life, whereas a three-week total of iron given orally in a single dose would lead to unphysiological or fatal conditions in nursing pigs. (author)

Bioavailability of Iron, Zinc, Phytate and Phytase Activity during Soaking and Germination of White Sorghum Varieties

Science.gov (United States)

Afify, Abd El-Moneim M. R.; El-Beltagi, Hossam S.; Abd El-Salam, Samiha M.; Omran, Azza A.

2011-01-01

The changes in phytate, phytase activity and in vitro bioavailability of iron and zinc during soaking and germination of three white sorghum varieties (Sorghum bicolor L. Moench), named Dorado, Shandweel-6, and Giza-15 were investigated. Sorghum varieties were soaked for 20 h and germinated for 72 h after soaking for 20 h to reduce phytate content and increase iron and zinc in vitro bioavailability. The results revealed that iron and zinc content was significantly reduced from 28.16 to 32.16% and 13.78 to 26.69% for soaking treatment and 38.43 to 39.18% and 21.80 to 31.27% for germination treatments, respectively. Phytate content was significantly reduced from 23.59 to 32.40% for soaking treatment and 24.92 to 35.27% for germination treatments, respectively. Phytase enzymes will be activated during drying in equal form in all varieties. The results proved that the main distinct point is the change of phytase activity as well as specific activity during different treatment which showed no significant differences between the varieties used. The in vitro bioavailability of iron and zinc were significantly improved as a result of soaking and germination treatments. PMID:22003395

Cellular iron transport.

Science.gov (United States)

Garrick, Michael D; Garrick, Laura M

2009-05-01

Iron has a split personality as an essential nutrient that also has the potential to generate reactive oxygen species. We discuss how different cell types within specific tissues manage this schizophrenia. The emphasis in enterocytes is on regulating the body's supply of iron by regulating transport into the blood stream. In developing red blood cells, adaptations in transport manage the body's highest flux of iron. Hepatocytes buffer the body's stock of iron. Macrophage recycle the iron from effete red cells among other iron management tasks. Pneumocytes provide a barrier to prevent illicit entry that, when at risk of breaching, leads to a need to handle the dangers in a fashion essentially shared with macrophage. We also discuss or introduce cell types including renal cells, neurons, other brain cells, and more where our ignorance, currently still vast, needs to be removed by future research.

Phosphorylation of Akt by SC79 Prevents Iron Accumulation and Ameliorates Early Brain Injury in a Model of Experimental Subarachnoid Hemorrhage

Directory of Open Access Journals (Sweden)

Shuangying Hao

2016-03-01

Full Text Available Previous studies have demonstrated that activation of Akt may alleviate early brain injury (EBI following subarachnoid hemorrhage (SAH. This study is undertaken to determine whether iron metabolism is involved in the beneficial effect of Akt activation after SAH. Therefore, we used a novel molecule, SC79, to activate Akt in an experimental Sprague–Dawley rat model of SAH. Rats were randomly divided into four groups as follows: sham, SAH, SAH + vehicle, SAH + SC79. The results confirmed that SC79 effectively enhanced the defense against oxidative stress and alleviated EBI in the temporal lobe after SAH. Interestingly, we found that phosphorylation of Akt by SC79 reduced cell surface transferrin receptor-mediated iron uptake and promoted ferroportin-mediated iron transport after SAH. As a result, SC79 administration diminished the iron content in the brain tissue. Moreover, the impaired Fe-S cluster biogenesis was recovered and loss of the activities of the Fe-S cluster-containing enzymes were regained, indicating that injured mitochondrial functions are restored to healthy levels. These findings suggest that disrupted iron homeostasis could contribute to EBI and Akt activation may regulate iron metabolism to relieve iron toxicity, further protecting neurons from EBI after SAH.

Iron-Deficiency Anemia

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Full Text Available ... because your body’s intake of iron is too low. Low intake of iron can happen because of blood ... delivery or giving birth to a baby with low birth weight In people with chronic conditions, iron- ...

Iron-Deficiency Anemia

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Full Text Available ... for iron-deficiency anemia if you have certain risk factors , including pregnancy. To prevent iron-deficiency anemia, your doctor may recommend you eat heart-healthy foods or control other conditions that can cause iron-deficiency anemia. ...

Iron-Deficiency Anemia

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Full Text Available ... blood cells. Iron-deficiency anemia usually develops over time because your body’s intake of iron is too ... clamping of your newborn’s umbilical cord at the time of delivery. This may help prevent iron-deficiency ...

Iron-Deficiency Anemia

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Full Text Available ... severity of the condition. Your doctor may recommend healthy eating changes, iron supplements, intravenous iron therapy for mild ... you: Adopt healthy lifestyle changes such as heart-healthy eating patterns. Increase your daily intake of iron-rich ...

Iron-Deficiency Anemia

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Full Text Available ... different ages and stages of life. Until the teen years, the recommended amount of iron is the ... cow’s milk. Cow’s milk is low in iron. Teens, who have increased need for iron during growth ...

Reduced LAK cytotoxicity of peripheral blood mononuclear cells in patients with bladder cancer: Decreased LAK cytotoxicity caused by a low incidence of CD56+ and CD57+ mononuclear blood cells

International Nuclear Information System (INIS)

Hermann, G.G.; Petersen, K.R.; Steven, K.; Zeuthen, J.

1990-01-01

The cytotoxicity of unstimulated peripheral blood mononuclear cells (US-PBMC), phytohemagglutinin (PHA)-stimulated PBMC (PS-PBMC) and interleukin-2 (IL-2)-activated PBMC (LAK cells) was assessed in patients with noninvasive and invasive transitional-cell bladder cancer and compared with those determined in healthy controls. The differences in the cytotoxicities were correlated with specific changes in the subsets of peripheral blood mononuclear cells (PBMC). PBMC from 37 patients and 13 healthy controls were tested against the bladder cancer cell line T24 in 51 Cr-release assays. The PBMC subsets were analyzed using monoclonal antibodies against T cells, natural killer (NK) -cells, monocytes, and activation markers. The cytotoxicities of US-PBMC, PS-PBMC, and LAK cells were all significantly lower in the cancer patients than in the controls (P less than 0.05). The percentages of PBMC positive for the NK-cell markers CD56 and CD57 were lowest in the patients and were correlated to the decrease in cytotoxicity. Depletion of CD56+ or CD57+ cells from PBMC prior to or after 2 days stimulation with IL-2 demonstrated that these cells are the major source of LAK-cell cytotoxicity and showed that the reduced ability of bladder cancer patient PBMC to develop LAK-cell cytotoxicity is a result of a low incidence of CD56+ and CD57+ cells in the blood. These findings indicate that IL-2 therapy alone might not be a sufficient therapy of bladder cancer patients

Iron-Deficiency Anemia

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Full Text Available ... iron, in milligrams (mg) at different ages and stages of life. Until the teen years, the recommended amount of ... and choosing iron-rich foods, especially during certain stages of life when more iron is needed, such as childhood ...

Iron-Deficiency Anemia

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Full Text Available ... because your body’s intake of iron is too low. Low intake of iron can happen because of blood ... a lot of cow’s milk. Cow’s milk is low in iron. Teens, who have increased need for ...

Iron-Deficiency Anemia

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Full Text Available ... for iron-deficiency anemia. Lifestyle habits Certain lifestyle habits may increase your risk for iron-deficiency anemia, including: Vegetarian or vegan eating patterns. Not eating enough iron-rich foods, such as meat and fish, may result in ...

Iron-Deficiency Anemia

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Full Text Available ... bleeding or other abnormalities, such as growths or cancer of the lining of the colon. For this test, a ... that you take iron supplements, also called iron pills or oral iron, by mouth once or several times a ...

Carbohydrate restriction and dietary cholesterol modulate the expression of HMG-CoA reductase and the LDL receptor in mononuclear cells from adult men

Directory of Open Access Journals (Sweden)

Volek Jeff S

2007-11-01

Full Text Available Abstract The liver is responsible for controlling cholesterol homeostasis in the body. HMG-CoA reductase and the LDL receptor (LDL-r are involved in this regulation and are also ubiquitously expressed in all major tissues. We have previously shown in guinea pigs that there is a correlation in gene expression of HMG-CoA reductase and the LDL-r between liver and mononuclear cells. The present study evaluated human mononuclear cells as a surrogate for hepatic expression of these genes. The purpose was to evaluate the effect of dietary carbohydrate restriction with low and high cholesterol content on HMG-CoA reductase and LDL-r mRNA expression in mononuclear cells. All subjects were counseled to consume a carbohydrate restricted diet with 10–15% energy from carbohydrate, 30–35% energy from protein and 55–60% energy from fat. Subjects were randomly assigned to either EGG (640 mg/d additional dietary cholesterol or SUB groups [equivalent amount of egg substitute (0 dietary cholesterol contributions per day] for 12 weeks. At the end of the intervention, there were no changes in plasma total or LDL cholesterol (LDL-C compared to baseline (P > 0.10 or differences in plasma total or LDL-C between groups. The mRNA abundance for HMG-CoA reductase and LDL-r were measured in mononuclear cells using real time PCR. The EGG group showed a significant decrease in HMG-CoA reductase mRNA (1.98 ± 1.26 to 1.32 ± 0.92 arbitrary units P

The mechanism of stereospecific C-H oxidation by Fe(Pytacn) complexes: bioinspired non-heme iron catalysts containing cis-labile exchangeable sites.

Science.gov (United States)

Prat, Irene; Company, Anna; Postils, Verònica; Ribas, Xavi; Que, Lawrence; Luis, Josep M; Costas, Miquel

2013-05-17

A detailed mechanistic study of the hydroxylation of alkane C-H bonds using H2O2 by a family of mononuclear non heme iron catalysts with the formula [Fe(II)(CF3SO3)2(L)] is described, in which L is a tetradentate ligand containing a triazacyclononane tripod and a pyridine ring bearing different substituents at the α and γ positions, which tune the electronic or steric properties of the corresponding iron complexes. Two inequivalent cis-labile exchangeable sites, occupied by triflate ions, complete the octahedral iron coordination sphere. The C-H hydroxylation mediated by this family of complexes takes place with retention of configuration. Oxygen atoms from water are incorporated into hydroxylated products and the extent of this incorporation depends in a systematic manner on the nature of the catalyst, and the substrate. Mechanistic probes and isotopic analyses, in combination with detailed density functional theory (DFT) calculations, provide strong evidence that C-H hydroxylation is performed by highly electrophilic [Fe(V)(O)(OH)L] species through a concerted asynchronous mechanism, involving homolytic breakage of the C-H bond, followed by rebound of the hydroxyl ligand. The [Fe(V)(O)(OH)L] species can exist in two tautomeric forms, differing in the position of oxo and hydroxide ligands. Isotopic-labeling analysis shows that the relative reactivities of the two tautomeric forms are sensitively affected by the α substituent of the pyridine, and this reactivity behavior is rationalized by computational methods. Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Iron-57 and iridium-193 Moessbauer spectroscopic studies of supported iron-iridium catalysts

International Nuclear Information System (INIS)

Berry, F.J.; Jobson, S.

1988-01-01

57 Fe and 193 Ir Moessbauer spectroscopy shows that silica- and alumina-supported iron-iridium catalysts formed by calcination in air contain mixtures of small particle iron(III) oxide and iridium(IV) oxide. The iridium dioxide in both supported catalysts is reduced in hydrogen to metallic iridium. The α-Fe 2 O 3 in the silica supported materials is predominantly reduced in hydrogen to an iron-iridium alloy whilst in the alumina-supported catalyst the iron is stabilised by treatment in hydrogen as iron(II). Treatment of a hydrogen-reduced silica-supported iron catalyst in hydrogen and carbon monoxide is accompanied by the formation of iron carbides. Carbide formation is not observed when the iron-iridium catalysts are treated in similar atmospheres. The results from the bimetallic catalysts are discussed in terms of the hydrogenation of associatively adsorbed carbon monoxide and the selectivity of supported iron-iridium catalysts to methanol formation. (orig.)

Nicotianamine synthase overexpression positively modulates iron homeostasis-related genes in high iron rice

Directory of Open Access Journals (Sweden)

Meng eWang

2013-05-01

Full Text Available Nearly one-third of the world population, mostly women and children, suffer from iron malnutrition and its consequences, such as anemia or impaired mental development. Biofortification of rice, which is a staple crop for nearly half of the world’s population, can significantly contribute in alleviating iron deficiency. NFP rice (transgenic rice expressing nicotianamine synthase, ferritin and phytase genes has a more than six-fold increase in iron content in polished rice grains, resulting from the synergistic action of nicotianamine synthase (NAS and ferritin transgenes. We investigated iron homeostasis in NFP plants by analyzing the expression of 28 endogenous rice genes known to be involved in the homeostasis of iron and other metals, in iron-deficient and iron-sufficient conditions. RNA was collected from different tissues (roots, flag leaves, grains and at three developmental stages during grain filling. NFP plants showed increased sensitivity to iron-deficiency conditions and changes in the expression of endogenous genes involved in nicotianamine (NA metabolism, in comparison to their non-transgenic siblings. Elevated transcript levels were detected in NFP plants for several iron transporters. In contrast, expression of OsYSL2, which encodes a member of Yellow Stripe-like protein family, and a transporter of the NA-Fe(II complex was reduced in NFP plants under low iron conditions, indicating that expression of OsYSL2 is regulated by the endogenous iron status. Expression of the transgenes did not significantly affect overall iron homeostasis in NFP plants, which establishes the engineered push-pull mechanism as a suitable strategy to increase rice endosperm iron content.

Iron-Deficiency Anemia

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Full Text Available ... anemia, your doctor may order the following blood tests to diagnose iron-deficiency anemia: Complete blood count (CBC) to ... than normal when viewed under a microscope. Different tests help your doctor diagnose iron-deficiency anemia. In iron-deficiency anemia, blood ...

Iron enhances the peptidyl deformylase activity and biofilm formation in Staphylococcus aureus.

Science.gov (United States)

Swarupa, Vimjam; Chaudhury, Abhijit; Sarma, Potukuchi Venkata Gurunadha Krishna

2018-01-01

Staphylococcus aureus plays a major role in persistent infections and many of these species form structured biofilms on different surfaces which is accompanied by changes in gene expression profiles. Further, iron supplementation plays a critical role in the regulation of several protein(s)/enzyme function, which all aid in the development of active bacterial biofilms. It is well known that for each protein, deformylation is the most crucial step in biosynthesis and is catalyzed by peptidyl deformylase (PDF). Thus, the aim of the current study is to understand the role of iron in biofilm formation and deformylase activity of PDF. Hence, the PDF gene of S. aureus ATCC12600 was PCR amplified using specific primers and sequenced, followed by cloning and expression in Escherichia coli DH5α. The deformylase activity of the purified recombinant PDF was measured in culture supplemented with/without iron where the purified rPDF showed K m of 1.3 mM and V max of 0.035 mM/mg/min, which was close to the native PDF ( K m  = 1.4 mM, V max  = 0.030 mM/mg/min). Interestingly, the K m decreased and PDF activity increased when the culture was supplemented with iron, corroborating with qPCR results showing 100- to 150-fold more expression compared to control in S. aureus and its drug-resistant strains. Further biofilm-forming units (BU) showed an incredible increase (0.42 ± 0.005 to 6.3 ± 0.05 BU), i.e., almost 15-fold elevation in anaerobic conditions, indicating the significance of iron in S. aureus biofilms.

Iron Acquisition Mechanisms and Their Role in the Virulence of Burkholderia Species

Science.gov (United States)

Butt, Aaron T.; Thomas, Mark S.

2017-01-01

Burkholderia is a genus within the β-Proteobacteriaceae that contains at least 90 validly named species which can be found in a diverse range of environments. A number of pathogenic species occur within the genus. These include Burkholderia cenocepacia and Burkholderia multivorans, opportunistic pathogens that can infect the lungs of patients with cystic fibrosis, and are members of the Burkholderia cepacia complex (Bcc). Burkholderia pseudomallei is also an opportunistic pathogen, but in contrast to Bcc species it causes the tropical human disease melioidosis, while its close relative Burkholderia mallei is the causative agent of glanders in horses. For these pathogens to survive within a host and cause disease they must be able to acquire iron. This chemical element is essential for nearly all living organisms due to its important role in many enzymes and metabolic processes. In the mammalian host, the amount of accessible free iron is negligible due to the low solubility of the metal ion in its higher oxidation state and the tight binding of this element by host proteins such as ferritin and lactoferrin. As with other pathogenic bacteria, Burkholderia species have evolved an array of iron acquisition mechanisms with which to capture iron from the host environment. These mechanisms include the production and utilization of siderophores and the possession of a haem uptake system. Here, we summarize the known mechanisms of iron acquisition in pathogenic Burkholderia species and discuss the evidence for their importance in the context of virulence and the establishment of infection in the host. We have also carried out an extensive bioinformatic analysis to identify which siderophores are produced by each Burkholderia species that is pathogenic to humans. PMID:29164069