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Sample records for mononuclear iron enzyme

  1. Go it alone: four-electron oxidations by mononuclear non-heme iron enzymes.

    Science.gov (United States)

    Peck, Spencer C; van der Donk, Wilfred A

    2017-04-01

    This review discusses the current mechanistic understanding of a group of mononuclear non-heme iron-dependent enzymes that catalyze four-electron oxidation of their organic substrates without the use of any cofactors or cosubstrates. One set of enzymes acts on α-ketoacid-containing substrates, coupling decarboxylation to oxygen activation. This group includes 4-hydroxyphenylpyruvate dioxygenase, 4-hydroxymandelate synthase, and CloR involved in clorobiocin biosynthesis. A second set of enzymes acts on substrates containing a thiol group that coordinates to the iron. This group is comprised of isopenicillin N synthase, thiol dioxygenases, and enzymes involved in the biosynthesis of ergothioneine and ovothiol. The final group of enzymes includes HEPD and MPnS that both carry out the oxidative cleavage of the carbon-carbon bond of 2-hydroxyethylphosphonate but generate different products. Commonalities amongst many of these enzymes are discussed and include the initial substrate oxidation by a ferric-superoxo-intermediate and a second oxidation by a ferryl species.

  2. Mononuclear non-heme iron enzymes with the 2-His-1-carboxylate facial triad: recent developments in enzymology and modeling studies

    NARCIS (Netherlands)

    Bruijnincx, P.C.A.; van Koten, G.; Klein Gebbink, R.J.M.

    2008-01-01

    Iron-containing enzymes are one of Nature’s main means of effecting key biological transformations. The mononuclear non-heme iron oxygenases and oxidases have received the most attention recently, primarily because of the recent availability of crystal structures of many different enzymes and the st

  3. X-ray absorption spectroscopic studies of mononuclear non-heme iron enzymes

    Energy Technology Data Exchange (ETDEWEB)

    Westre, T.E.

    1996-01-01

    Fe-K-edge X-ray absorption spectroscopy (XAS) has been used to investigate the electronic and geometric structure of the iron active site in non-heme iron enzymes. A new theoretical extended X-ray absorption fine structure (EXAFS) analysis approach, called GNXAS, has been tested on data for iron model complexes to evaluate the utility and reliability of this new technique, especially with respect to the effects of multiple-scattering. In addition, a detailed analysis of the 1s{yields}3d pre-edge feature has been developed as a tool for investigating the oxidation state, spin state, and geometry of iron sites. Edge and EXAFS analyses have then been applied to the study of non-heme iron enzyme active sites.

  4. X-ray absorption spectroscopic studies of mononuclear non-heme iron enzymes

    Energy Technology Data Exchange (ETDEWEB)

    Westre, Tami E. [Stanford Univ., CA (United States)

    1996-01-01

    Fe-K-edge X-ray absorption spectroscopy (XAS) has been used to investigate the electronic and geometric structure of the iron active site in non-heme iron enzymes. A new theoretical extended X-ray absorption fine structure (EXAFS) analysis approach, called GNXAS, has been tested on data for iron model complexes to evaluate the utility and reliability of this new technique, especially with respect to the effects of multiple-scattering. In addition, a detailed analysis of the 1s→3d pre-edge feature has been developed as a tool for investigating the oxidation state, spin state, and geometry of iron sites. Edge and EXAFS analyses have then been applied to the study of non-heme iron enzyme active sites.

  5. Mononuclear non-heme iron enzymes with the 2-His-1-carboxylate facial triad: recent developments in enzymology and modeling studies.

    Science.gov (United States)

    Bruijnincx, Pieter C A; van Koten, Gerard; Klein Gebbink, Robertus J M

    2008-12-01

    Iron-containing enzymes are one of Nature's main means of effecting key biological transformations. The mononuclear non-heme iron oxygenases and oxidases have received the most attention recently, primarily because of the recent availability of crystal structures of many different enzymes and the stunningly diverse oxidative transformations that these enzymes catalyze. The wealth of available structural data has furthermore established the so-called 2-His-1-carboxylate facial triad as a new common structural motif for the activation of dioxygen. This superfamily of mononuclear iron(ii) enzymes catalyzes a wide range of oxidative transformations, ranging from the cis-dihydroxylation of arenes to the biosynthesis of antibiotics such as isopenicillin and fosfomycin. The remarkable scope of oxidative transformations seems to be even broader than that associated with oxidative heme enzymes. Not only are many of these oxidative transformations of key biological importance, many of these selective oxidations are also unprecedented in synthetic organic chemistry. In this critical review, we wish to provide a concise background on the chemistry of the mononuclear non-heme iron enzymes characterized by the 2-His-1-carboxylate facial triad and to discuss the many recent developments in the field. New examples of enzymes with unique reactivities belonging to the superfamily have been reported. Furthermore, key insights into the intricate mechanistic details and reactive intermediates have been obtained from both enzyme and modeling studies. Sections of this review are devoted to each of these subjects, i.e. the enzymes, biomimetic models, and reactive intermediates (225 references).

  6. Iron metabolism in the mononuclear phagocyte system

    Institute of Scientific and Technical Information of China (English)

    Weina Kong; Xianglin Duan; Zhenhua Shi; Yanzhong Chang

    2008-01-01

    The maintenance of body iron homeostasis requires the coordination of multiple regulatory mechanisms of iron metabolism.The mononuclear phagocyte system (MPS,composed of monocytes,macrophages,and their precursor cells) is crucial in the maintenance of iron homeostasis.Recycling of iron is carried out by specialized macrophages via engulfment of aged erythrocytes.The iron stores of macrophages depend on the levels of recovered and exported iron.However,the molecular mechanisms underlying iron homeostasis in macrophages are poorly understood.Recent studies characterizing the function and regulation of natural resistance-associated macrophage protein 1 (Nrampl),divalent metal transporter 1 (DMTI),HLA-linked hemechromatosis gene (HFE),ferroportin 1 (FPN1),and hepcidin are rapidly expanding our knowledge on the molecular level of MPS iron handling.These studies are deepening our understanding about the molecular mechanism of iron homeostasis and iron-related diseases.

  7. The structural basis of cephalosporin formation in a mononuclear ferrous enzyme

    NARCIS (Netherlands)

    Valegård, Karin; Terwisscha van Scheltinga, Anke C.; Dubus, Alain; Ranghino, Graziella; Öster, Linda M.; Hajdu, Janos; Andersson, Inger

    2004-01-01

    Deacetoxycephalosporin-C synthase (DAOCS) is a mononuclear ferrous enzyme that transforms penicillins into cephalosporins by inserting a carbon atom into the penicillin nucleus. In the first half-reaction, dioxygen and 2-oxoglutarate produce a reactive iron-oxygen species, succinate and CO2. The oxi

  8. The structural basis of cephalosporin formation in a mononuclear ferrous enzyme

    NARCIS (Netherlands)

    Valegård, Karin; Terwisscha van Scheltinga, Anke C.; Dubus, Alain; Ranghino, Graziella; Öster, Linda M.; Hajdu, Janos; Andersson, Inger

    2004-01-01

    Deacetoxycephalosporin-C synthase (DAOCS) is a mononuclear ferrous enzyme that transforms penicillins into cephalosporins by inserting a carbon atom into the penicillin nucleus. In the first half-reaction, dioxygen and 2-oxoglutarate produce a reactive iron-oxygen species, succinate and CO2. The

  9. 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.

  10. 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.

  11. Crystal Structure of Mammalian Cysteine dioxygenase: A Novel Mononuclear Iron Center for Cysteine Thiol Oxidation

    Energy Technology Data Exchange (ETDEWEB)

    Simmons,C.; Liu, Q.; Huang, Q.; Hao, Q.; Begley, T.; Karplus, P.; Stipanuk, M.

    2006-01-01

    Cysteine dioxygenase is a mononuclear iron-dependent enzyme responsible for the oxidation of cysteine with molecular oxygen to form cysteinesulfinate. This reaction commits cysteine to either catabolism to sulfate and pyruvate or to the taurine biosynthetic pathway. Cysteine dioxygenase is a member of the cupin superfamily of proteins. The crystal structure of recombinant rat cysteine dioxygenase has been determined to 1.5 Angstroms resolution, and these results confirm the canonical cupin {beta}-sandwich fold and the rare cysteinyl-tyrosine intramolecular crosslink (between Cys93 and Tyr157) seen in the recently reported murine cysteine dioxygenase structure. In contrast to the catalytically inactive mononuclear Ni(II) metallocenter present in the murine structure, crystallization of a catalytically competent preparation of rat cysteine dioxygenase revealed a novel tetrahedrally coordinated mononuclear iron center involving three histidines (His86, His88, and His140) and a water molecule. Attempts to acquire a structure with bound ligand using either co-crystallization or soaks with cysteine revealed the formation of a mixed disulfide involving Cys164 near the active site, which may explain previously observed substrate inhibition. This work provides a framework for understanding the molecular mechanisms involved in thiol dioxygenation and sets the stage for exploring the chemistry of both the novel mononuclear iron center and the catalytic role of the cysteinyl-tyrosine linkage.

  12. Characterization of a paramagnetic mononuclear nonheme iron-superoxo complex.

    Science.gov (United States)

    Chiang, Chien-Wei; Kleespies, Scott T; Stout, Heather D; Meier, Katlyn K; Li, Po-Yi; Bominaar, Emile L; Que, Lawrence; Münck, Eckard; Lee, Way-Zen

    2014-08-01

    O2 bubbling into a THF solution of Fe(II)(BDPP) (1) at -80 °C generates a reversible bright yellow adduct 2. Characterization by resonance Raman and Mössbauer spectroscopy provides complementary insights into the nature of 2. The former shows a resonance-enhanced vibration at 1125 cm(-1), which can be assigned to the ν(O-O) of a bound superoxide, while the latter reveals the presence of a high-spin iron(III) center that is exchange-coupled to the superoxo ligand, like the Fe(III)-O2(-) pair found for the O2 adduct of 4-nitrocatechol-bound homoprotocatechuate 2,3-dioxygenase. Lastly, 2 oxidizes dihydroanthracene to anthracene, supporting the notion that Fe(III)-O2(-) species can carry out H atom abstraction from a C-H bond to initiate the 4-electron oxidation of substrates proposed for some nonheme iron enzymes.

  13. Structure and reactivity of a mononuclear non-haem iron(III)–peroxo complex

    OpenAIRE

    Cho, Jaeheung; Jeon, Sujin; Wilson, Samuel A.; Liu, Lei V.; Kang, Eun A; Braymer, Joseph J.; Lim, Mi Hee; Hedman, Britt; Hodgson, Keith O.; Valentine, Joan Selverstone; Solomon, Edward I.; Nam, Wonwoo

    2011-01-01

    Oxygen-containing mononuclear iron species—iron(III)–peroxo, iron(III)–hydroperoxo and iron(IV)–oxo—are key intermediates in the catalytic activation of dioxygen by iron-containing metalloenzymes1–7. It has been difficult to generate synthetic analogues of these three active iron–oxygen species in identical host complexes, which is necessary to elucidate changes to the structure of the iron centre during catalysis and the factors that control their chemical reactivities with substrates. Here ...

  14. EPR of Mononuclear Non-Heme Iron Proteins

    OpenAIRE

    Gaffney, Betty J.

    2009-01-01

    Flexible geometry of three- to six-protein side-chain ligands to non-heme iron in proteins is the basis for widely diverse reactivites ranging from iron transport to redox chemistry. The gap between fixed states determined by x-ray analysis can be filled by spectroscopic study of trapped intermediates. EPR is a versatile and relatively quick approach to defining intermediate states in terms of the geometry and electronic structures of iron. A number of examples in which the iron chemistry of ...

  15. Synthesis and spectroscopic characterization of high-spin mononuclear iron(II) p-semiquinonate complexes.

    Science.gov (United States)

    Baum, Amanda E; Park, Heaweon; Lindeman, Sergey V; Fiedler, Adam T

    2014-12-01

    Two mononuclear iron(II) p-semiquinonate (pSQ) complexes have been generated via one-electron reduction of precursor complexes containing a substituted 1,4-naphthoquinone ligand. Detailed spectroscopic and computational analysis confirmed the presence of a coordinated pSQ radical ferromagnetically coupled to the high-spin Fe(II) center. The complexes are intended to model electronic interactions between (semi)quinone and iron cofactors in biology.

  16. Synthesis and Spectroscopic Characterization of High-Spin Mononuclear Iron(II) p-Semiquinonate Complexes

    OpenAIRE

    Baum, Amanda E.; Park, Heaweon; Lindeman, Sergey V.; Fiedler, Adam T.

    2014-01-01

    Two mononuclear iron(II) p-semiquinonate (pSQ) complexes have been generated via one-electron reduction of precursor complexes containing a substituted 1,4-naphthoquinone ligand. Detailed spectroscopic and computational analysis confirmed the presence of a coordinated pSQ radical ferromagnetically coupled to the high-spin FeII center. The complexes are intended to model electronic interactions between (semi)quinone and iron cofactors in biology.

  17. A comparative DFT study of oxygen reduction reaction on mononuclear and binuclear cobalt and iron phthalocyanines

    Science.gov (United States)

    Chen, Xin; Li, Mengke; Yu, Zongxue; Ke, Qiang

    2016-12-01

    The oxygen reduction reaction (ORR) catalyzed by mononuclear and planar binuclear cobalt (CoPc) and iron phthalocyanine (FePc) catalysts is investigated in detail by density functional theory (DFT) methods. The calculation results indicate that the ORR activity of Fe-based Pcs is much higher than that of Co-based Pcs, which is due to the fact that the former could catalyze 4e- ORRs, while the latter could catalyze only 2e- ORRs from O2 to H2O2. The original high activities of Fe-based Pcs could be attributed to their high energy level of the highest occupied molecular orbital (HOMO), which could lead to the stronger adsorption energy between catalysts and ORR species. Nevertheless, the HOMO of Co-based Pcs is the ring orbital, not the 3 d Co orbital, thereby inhibiting the electron transfer from metal to adsorbates. Furthermore, compared with mononuclear FePc, the planar binuclear FePc has more stable structure in acidic medium and more suitable adsorption energy of ORR species, making it a promising non-precious electrocatalyst for ORR.

  18. Mononuclear, Dinuclear, and Trinuclear Iron Complexes Featuring a New Monoanionic SNS Thiolate Ligand.

    Science.gov (United States)

    Das, Uttam K; Daifuku, Stephanie L; Gorelsky, Serge I; Korobkov, Ilia; Neidig, Michael L; Le Roy, Jennifer J; Murugesu, Muralee; Baker, R Tom

    2016-01-19

    The new tridentate ligand, S(Me)N(H)S = 2-(2-methylthiophenyl)benzothiazolidine, prepared in a single step from commercial precursors in excellent yield, undergoes ring-opening on treatment with Fe(OTf)2 in the presence of base affording a trinuclear iron complex, [Fe3(μ2-S(Me)NS(-))4](OTf)2 (1) which is fully characterized by structural and spectroscopic methods. X-ray structural data reveal that 1 contains four S(Me)NS(-) ligands meridionally bound to two pseudooctahedral iron centers each bridged by two thiolates to a distorted tetrahedral central iron. The combined spectroscopic (UV-vis, Mössbauer, NMR), magnetic (solution and solid state), and computational (DFT) studies indicate that 1 includes a central, high-spin Fe(II) (S = 2) with two low-spin (S = 0) peripheral Fe(II) centers. Complex 1 reacts with excess PMePh2, CNxylyl (2,6-dimethylphenyl isocyanide), and P(OMe)3 in CH3CN to form diamagnetic, thiolate-bridged, dinuclear Fe(II) complexes {[Fe(μ-S(Me)NS(-))L2]2}(OTf)2 (2-4). These complexes are characterized by elemental analysis; (1)H NMR, IR, UV-vis, and Mössbauer spectroscopy; and single crystal X-ray diffraction. Interestingly, addition of excess P(OMe)3 to complex 1 in CH2Cl2 produces primarily the diamagnetic, mononuclear Fe(II) complex, {Fe(S(Me)NS(-))[P(OMe)3]3}(OTf) (5).

  19. Effect of pancreatic enzyme supplements on iron absorption.

    Science.gov (United States)

    Zempsky, W T; Rosenstein, B J; Carroll, J A; Oski, F A

    1989-08-01

    Iron deficiency has been reported in one third of patients with cystic fibrosis. There are data that suggest that iron absorption is increased with exocrine pancreatic deficiency and that administration of pancreatic enzymes may impair oral iron absorption. We compared oral iron absorption over a 3-hour period in the presence and absence of exogenous pancreatic enzymes in 13 stable young-adult patients with cystic fibrosis and 9 age-matched control patients. Although none of the patients with cystic fibrosis had a hemoglobin level less than 119 g/L, serum ferritin levels were less than 25 micrograms/L in 5 of the 13 patients, and the mean corpuscular volume was significantly lower in the patient group (86.1 +/- 2.7 vs 90.9 +/- 5 fL). Baseline mean serum iron levels were higher in controls (18.9 +/- 5.9 mumol/L) than in patients (11.9 +/- 6.3 mumol/L). There was no difference in iron absorption in the absence of exogenous pancreatic enzymes. Significant impairment of iron absorption was detected in both patients with cystic fibrosis and controls after administration of a preparation of pancreatic enzymes. There was an inverse relationship between iron stores, as measured by serum ferritin, and iron absorption. These findings suggest that long-term consumption of pancreatic enzymes by patients with cystic fibrosis may contribute to iron deficiency.

  20. Interaction between Non-Heme Iron of Lipoxygenases and Cumene Hydroperoxide: Basis for Enzyme Activation, Inactivation, and Inhibition

    Energy Technology Data Exchange (ETDEWEB)

    Vahedi-Faridi, Ardeshir; Brault, Pierre-Alexandre; Shah, Priya; Kim, Yong-Wah; Dunham, William R.; Funk, Jr., Max O. (Toledo)

    2010-11-16

    Lipoxygenase catalysis depends in a critical fashion on the redox properties of a unique mononuclear non-heme iron cofactor. The isolated enzyme contains predominantly, if not exclusively, iron(II), but the catalytically active form of the enzyme has iron(III). The activating oxidation of the iron takes place in a reaction with the hydroperoxide product of the catalyzed reaction. In a second peroxide-dependent process, lipoxygenases are also inactivated. To examine the redox activation/inactivation dichotomy in lipoxygenase chemistry, the interaction between lipoxygenase-1 (and -3) and cumene hydroperoxide was investigated. Cumene hydroperoxide was a reversible inhibitor of the reaction catalyzed by lipoxygenase-1 under standard assay conditions at high substrate concentrations. Reconciliation of the data with the currently held kinetic mechanism requires simultaneous binding of substrate and peroxide. The enzyme also was both oxidized and largely inactivated in a reaction with the peroxide in the absence of substrate. The consequences of this reaction for the enzyme included the hydroxylation at C{beta} of two amino acid side chains in the vicinity of the cofactor, Trp and Leu. The modifications were identified by mass spectrometry and X-ray crystallography. The peroxide-induced oxidation of iron was also accompanied by a subtle rearrangement in the coordination sphere of the non-heme iron atom. Since the enzyme retains catalytic activity, albeit diminished, after treatment with cumene hydroperoxide, the structure of the iron site may reflect the catalytically relevant form of the cofactor.

  1. Interaction between non-heme iron of lipoxygenases and cumene hydroperoxide: basis for enzyme activation, inactivation, and inhibition.

    Science.gov (United States)

    Vahedi-Faridi, Ardeshir; Brault, Pierre-Alexandre; Shah, Priya; Kim, Yong-Wah; Dunham, William R; Funk, Max O

    2004-02-25

    Lipoxygenase catalysis depends in a critical fashion on the redox properties of a unique mononuclear non-heme iron cofactor. The isolated enzyme contains predominantly, if not exclusively, iron(II), but the catalytically active form of the enzyme has iron(III). The activating oxidation of the iron takes place in a reaction with the hydroperoxide product of the catalyzed reaction. In a second peroxide-dependent process, lipoxygenases are also inactivated. To examine the redox activation/inactivation dichotomy in lipoxygenase chemistry, the interaction between lipoxygenase-1 (and -3) and cumene hydroperoxide was investigated. Cumene hydroperoxide was a reversible inhibitor of the reaction catalyzed by lipoxygenase-1 under standard assay conditions at high substrate concentrations. Reconciliation of the data with the currently held kinetic mechanism requires simultaneous binding of substrate and peroxide. The enzyme also was both oxidized and largely inactivated in a reaction with the peroxide in the absence of substrate. The consequences of this reaction for the enzyme included the hydroxylation at C beta of two amino acid side chains in the vicinity of the cofactor, Trp and Leu. The modifications were identified by mass spectrometry and X-ray crystallography. The peroxide-induced oxidation of iron was also accompanied by a subtle rearrangement in the coordination sphere of the non-heme iron atom. Since the enzyme retains catalytic activity, albeit diminished, after treatment with cumene hydroperoxide, the structure of the iron site may reflect the catalytically relevant form of the cofactor.

  2. Electrochemical evidence that pyranopterin redox chemistry controls the catalysis of YedY, a mononuclear Mo enzyme

    OpenAIRE

    Adamson, Hope; Simonov, Alexandr N.; Kierzek, Michelina; Rothery, Richard A.; Weiner, Joel H.; Bond, Alan M.; Parkin, Alison

    2015-01-01

    A long-standing contradiction in the field of mononuclear Mo enzyme research is that small-molecule chemistry on active-site mimic compounds predicts ligand participation in the electron transfer reactions, but biochemical measurements only suggest metal-centered catalytic electron transfer. With the simultaneous measurement of substrate turnover and reversible electron transfer that is provided by Fourier-transformed alternating-current voltammetry, we show that Escherichia coli YedY is a mo...

  3. Electrochemical evidence that pyranopterin redox chemistry controls the catalysis of YedY, a mononuclear Mo enzyme.

    Science.gov (United States)

    Adamson, Hope; Simonov, Alexandr N; Kierzek, Michelina; Rothery, Richard A; Weiner, Joel H; Bond, Alan M; Parkin, Alison

    2015-11-24

    A long-standing contradiction in the field of mononuclear Mo enzyme research is that small-molecule chemistry on active-site mimic compounds predicts ligand participation in the electron transfer reactions, but biochemical measurements only suggest metal-centered catalytic electron transfer. With the simultaneous measurement of substrate turnover and reversible electron transfer that is provided by Fourier-transformed alternating-current voltammetry, we show that Escherichia coli YedY is a mononuclear Mo enzyme that reconciles this conflict. In YedY, addition of three protons and three electrons to the well-characterized "as-isolated" Mo(V) oxidation state is needed to initiate the catalytic reduction of either dimethyl sulfoxide or trimethylamine N-oxide. Based on comparison with earlier studies and our UV-vis redox titration data, we assign the reversible one-proton and one-electron reduction process centered around +174 mV vs. standard hydrogen electrode at pH 7 to a Mo(V)-to-Mo(IV) conversion but ascribe the two-proton and two-electron transition occurring at negative potential to the organic pyranopterin ligand system. We predict that a dihydro-to-tetrahydro transition is needed to generate the catalytically active state of the enzyme. This is a previously unidentified mechanism, suggested by the structural simplicity of YedY, a protein in which Mo is the only metal site.

  4. Electrochemical evidence that pyranopterin redox chemistry controls the catalysis of YedY, a mononuclear Mo enzyme

    Science.gov (United States)

    Adamson, Hope; Simonov, Alexandr N.; Kierzek, Michelina; Rothery, Richard A.; Weiner, Joel H.; Bond, Alan M.

    2015-01-01

    A long-standing contradiction in the field of mononuclear Mo enzyme research is that small-molecule chemistry on active-site mimic compounds predicts ligand participation in the electron transfer reactions, but biochemical measurements only suggest metal-centered catalytic electron transfer. With the simultaneous measurement of substrate turnover and reversible electron transfer that is provided by Fourier-transformed alternating-current voltammetry, we show that Escherichia coli YedY is a mononuclear Mo enzyme that reconciles this conflict. In YedY, addition of three protons and three electrons to the well-characterized “as-isolated” Mo(V) oxidation state is needed to initiate the catalytic reduction of either dimethyl sulfoxide or trimethylamine N-oxide. Based on comparison with earlier studies and our UV-vis redox titration data, we assign the reversible one-proton and one-electron reduction process centered around +174 mV vs. standard hydrogen electrode at pH 7 to a Mo(V)-to-Mo(IV) conversion but ascribe the two-proton and two-electron transition occurring at negative potential to the organic pyranopterin ligand system. We predict that a dihydro-to-tetrahydro transition is needed to generate the catalytically active state of the enzyme. This is a previously unidentified mechanism, suggested by the structural simplicity of YedY, a protein in which Mo is the only metal site. PMID:26561582

  5. Mononuclear non-heme iron(III) complexes of linear and tripodal tridentate ligands as functional models for catechol dioxygenases: Effect of -alkyl substitution on regioselectivity and reaction rate

    Indian Academy of Sciences (India)

    Mallayan Palaniandavar; Kusalendiran Visvaganesan

    2011-03-01

    Catechol dioxygenases are responsible for the last step in the biodegradation of aromatic molecules in the environment. The iron(II) active site in the extradiol-cleaving enzymes cleaves the C-C bond adjacent to the hydroxyl group, while the iron(III) active site in the intradiol-cleaving enzymes cleaves the C-C bond in between two hydroxyl groups. A series of mononuclear iron(III) complexes of the type [Fe(L)Cl3], where L is the linear -alkyl substituted bis(pyrid-2-ylmethyl)amine, -alkyl substituted -(pyrid-2-ylmethyl)ethylenediamine, linear tridentate 3N ligands containing imidazolyl moieties and tripodal ligands containing pyrazolyl moieties have been isolated and studied as structural and functional models for catechol dioxygenase enzymes. All the complexes catalyse the cleavage of catechols using molecular oxygen to afford both intra- and extradiol cleavage products. The rate of oxygenation depends on the solvent and the Lewis acidity of iron(III) center as modified by the sterically demanding -alkyl groups. Also, our studies reveal that stereo-electronic factors like the Lewis acidity of the iron(III) center and the steric demand of ligands, as regulated by the -alkyl substituents, determine the regioselectivity and the rate of dioxygenation. In sharp contrast to all these complexes, the pyrazole-containing tripodal ligand complexes yield mainly the oxidized product benzoquinone.

  6. Mononuclear Nonheme Iron(III)-Iodosylarene and High-Valent Iron-Oxo Complexes in Olefin Epoxidation Reactions.

    Science.gov (United States)

    Wang, Bin; Lee, Yong-Min; Seo, Mi Sook; Nam, Wonwoo

    2015-09-28

    High-spin iron(III)-iodosylarene complexes are highly reactive in the epoxidation of olefins, in which epoxides are formed as the major products with high stereospecificity and enantioselectivity. The reactivity of the iron(III)-iodosylarene intermediates is much greater than that of the corresponding iron(IV)-oxo complex in these reactions. The iron(III)-iodosylarene species-not high-valent iron(IV)-oxo and iron(V)-oxo species-are also shown to be the active oxidants in catalytic olefin epoxidation reactions. The present results are discussed in light of the long-standing controversy on the one oxidant versus multiple oxidants hypothesis in oxidation reactions.

  7. An active lifestyle induces positive antioxidant enzyme modulation in peripheral blood mononuclear cells of overweight/obese postmenopausal women.

    Science.gov (United States)

    Farinha, Juliano Boufleur; De Carvalho, Nélson Rodrigues; Steckling, Flávia Mariel; De Vargas, Liziane Da Silva; Courtes, Aline Alves; Stefanello, Sílvio Terra; Martins, Caroline Curry; Bresciani, Guilherme; Dos Santos, Daniela Lopes; Soares, Félix Alexandre Antunes

    2015-01-15

    The aim of this study was to investigate the effects of an active lifestyle on mitochondrial functioning, viability, bioenergetics, and redox status markers in peripheral blood mononuclear cells (PBMC) of overweight/ obese postmenopausal women. We performed a cross-sectional study with postmenopausal women aged 45–64 years and body mass index N 25 kg/m2, divided into physically active (n = 23) and sedentary (n = 12) groups. Mitochondria functioning and viability, bioenergetics and redox status parameters were assessed in PBMC with spectrophotometric and fluorometric assays. No differences were found in the enzyme activity of complexes I and II of the electron transport chain (ETC), mitochondrial superoxide dismutase (MnSOD) activity, methyl-tetrazolium reduction levels and reduced glutathione and oxidized glutathione levels between the groups. However, the physically active group presented higher levels of reactive oxygen species (ROS) (P= 0.04) and increased catalase (CAT) (P= 0.029), total (P= 0.011) and cytosolic SOD (CuZnSOD) (P= 0.009) activities. An active lifestyle that includes aerobic exercise for at least 30 min, three times per week may improve antioxidant enzyme activities in PBMC in overweight/obese postmenopausal women, without changes in the activity of the ETC enzymes. However, this low intensity physical activity is not able to induce relevant mitochondrial adaptations.

  8. Invited award contribution for ACS Award in Inorganic Chemistry. Geometric and electronic structure contributions to function in bioinorganic chemistry: active sites in non-heme iron enzymes.

    Science.gov (United States)

    Solomon, E I

    2001-07-16

    Spectroscopy has played a major role in the definition of structure/function correlations in bioinorganic chemistry. The importance of spectroscopy combined with electronic structure calculations is clearly demonstrated by the non-heme iron enzymes. Many members of this large class of enzymes activate dioxygen using a ferrous active site that has generally been difficult to study with most spectroscopic methods. A new spectroscopic methodology has been developed utilizing variable temperature, variable field magnetic circular dichroism, which enables one to obtain detailed insight into the geometric and electronic structure of the non-heme ferrous active site and probe its reaction mechanism on a molecular level. This spectroscopic methodology is presented and applied to a number of key mononuclear non-heme iron enzymes leading to a general mechanistic strategy for O2 activation. These studies are then extended to consider the new features present in the binuclear non-heme iron enzymes and applied to understand (1) the mechanism of the two electron/coupled proton transfer to dioxygen binding to a single iron center in hemerythrin and (2) structure/function correlations over the oxygen-activating enzymes stearoyl-ACP Delta9-desaturase, ribonucleotide reductase, and methane monooxygenase. Electronic structure/reactivity correlations for O2 activation by non-heme relative to heme iron enzymes will also be developed.

  9. Coordination and conformational isomers in mononuclear iron complexes with pertinence to the [FeFe] hydrogenase active site.

    Science.gov (United States)

    Orthaber, Andreas; Karnahl, Michael; Tschierlei, Stefanie; Streich, Daniel; Stein, Matthias; Ott, Sascha

    2014-03-21

    A series of six mononuclear iron complexes of the type [Fe(X-bdt)(P(R)2N(Ph)2)(CO)] (P(R)2N(Ph)2 = 1,5-diaza-3,7-diphosphaoctane, bdt = benzenedithiolate with X = H, Cl2 or Me and R = Ph, Bn, Cyc or tert-Bu) was prepared. This new class of penta-coordinate iron complexes contains a free coordination site and a pendant base as essential structural features of the [FeFe]-hydrogenase active site. The bidentate nature of the P(R)2N(Ph)2 ligands was found to be crucial for the preferential formation of coordinatively unsaturated penta-coordinate complexes, which is supported by first principle calculations. IR-spectroscopic data suggest the presence of coordination isomers around the metal center, as well as multiple possible conformers of the P(R)2N(Ph)2 ligand. This finding is further corroborated by X-ray crystallographic and computational studies. (31)P{(1)H}-NMR- and IR-spectroscopic as well as electrochemical measurements show that the electronic properties of the complexes are strongly, and independently, influenced by the P-substituents at the P(R)2N(Ph)2 ligand as well as by modifications of the bdt bridge. These results illustrate the advantages of this modular platform, which allows independent and selective tuning through site specific modifications. Potential catalytic intermediates, namely singly reduced and protonated complexes, have been further investigated by spectroscopic methods and exhibit remarkable stability. Finally, their general capacity for electro-catalytic reduction of protons to molecular hydrogen was verified.

  10. 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.

  11. Drug metabolizing enzymes and transporters mRNA in peripheral blood mononuclear cells of healthy subjects: biological variations and importance of pre-analytical steps.

    Science.gov (United States)

    Siest, Gérard; Jeannesson, Elise; Marteau, Jean-Brice; Samara, Anastasia; Pfister, Michèle; Visvikis-Siest, Sophie

    2009-05-01

    Quantification in peripheral blood mononuclear cells of mRNA of drug metabolizing enzymes or drug targets could give interesting, new information in the field of pharmacogenomics and molecular mechanisms. However, for the interpretation of these data, it is necessary to know mRNA biological variations. In this review, we propose a strategy based on the production and interpretation of clinical chemistry reference values. We discuss the concept of reference values; the necessity to master pre-analytical variations of CYP and ABC transporters; the choice of the analytical methods and of the reference genes; and finally the biological variations themselves. In particular, we focus on the importance of considering homogeneity for age, sex, degree of adiposity, tobacco and alcohol intake, food habits, and drug consumption, including their inductive effects, at the phase of subject recruitment. All this information is useful to define the partition and exclusion factors to obtain mRNA reference limits.

  12. Determination of Dietary Iron Requirements by Full Expression of Iron-Containing Enzymes in Various Tissues of Broilers.

    Science.gov (United States)

    Ma, Xinyan; Liao, Xiudong; Lu, Lin; Li, Sufen; Zhang, Liyang; Luo, Xugang

    2016-11-01

    The current dietary iron requirement (80 mg/kg) of broilers is mainly based on growth, hemoglobin concentration, or hematocrit data obtained in a few early studies; however, expressions of iron-containing enzymes might be more sensitive novel criteria to evaluate dietary iron requirements. The objective of this study was to determine dietary iron requirements of broilers for the full expression of succinate dehydrogenase (SDH), catalase, and cytochrome c oxidase (COX) in various tissues. A total of 336 1-d-old Arbor Acres male chicks were randomly assigned to 1 of 7 treatments with 6 replicates and fed a basal corn and soybean-meal diet (control, containing 67 mg Fe/kg) and the basal diet supplemented with 20, 40, 60, 80, 100, or 120 mg Fe/kg from FeSO4 ⋅ 7H2O for 21 d. Regression analysis was performed to estimate the optimal dietary iron concentration with the use of broken-line or quadratic models. SDH activity in the liver and heart, COX and catalase activity in the liver, Sdh mRNA levels in the liver, and Cox mRNA levels in the liver and heart of broilers were affected (P requirements estimated on the basis of fitted broken-line or quadratic-curve models (P requirements of broilers, and the dietary iron requirements would be 97-136 mg/kg to support the full expression of the above iron-containing enzymes in various tissues of broiler chicks from 1 to 21 d of age, which are higher than the current NRC iron requirement. © 2016 American Society for Nutrition.

  13. The mRNA expression of apolipoprotein B mRNA-editing enzyme-catalytic polypeptide-like 3G in peripheral blood mononuclear cells in patients with chronic hepatitis C and its regulation by interferon-α

    Institute of Scientific and Technical Information of China (English)

    蔡卫平

    2013-01-01

    Objective To study the mRNA expression of apolipoprotein B mRNA-editing enzyme-catalytic polypeptide-like 3G(APOBEC3G) in the peripheral blood mononuclear cells(PBMC) in patients with chronic hepatitis C(CHC) and its regulation by exogenous interferon-α

  14. 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

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

    Directory of Open Access Journals (Sweden)

    Susann Neiser

    2016-07-01

    Full Text Available 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

  16. 2008 GRC Iron Sulfur Enzymes-Conference to be held June 8-13, 2008

    Energy Technology Data Exchange (ETDEWEB)

    Stephen Cramer, Nancy Ryan Gray

    2009-01-01

    Iron-sulfur proteins are among the most common and ancient enzymes and electron-transfer agents in nature. They play key roles in photosynthesis, respiration, and the metabolism of small molecules such as H2, CO, and N2. The Iron Sulfur Enzyme Gordon Research Conference evolved from an earlier GRC on Nitrogen Fixation that began in 1994. The scope of the current meeting has broadened to include all enzymes or metalloproteins in which Fe-S bonds play a key role. This year's meeting will focus on the biosynthesis of Fe-S clusters, as well as the structure and mechanism of key Fe-S enzymes such as hydrogenase, nitrogenase and its homologues, radical SAM enzymes, and aconitase-related enzymes. Recent progress on the role of Fe-S enzymes in health, disease, DNA/RNA-processing, and alternative bio-energy systems will also be highlighted. This conference will assemble a broad, diverse, and international group of biologists and chemists who are investigating fundamental issues related to Fe-S enzymes, on atomic, molecular, organism, and environmental scales. The topics to be addressed will include: Biosynthesis & Genomics of Fe-S Enzymes; Fundamental Fe-S Chemistry; Hydrogen and Fe-S Enzymes; Nitrogenase & Homologous Fe-S Enzymes; Fe-S Enzymes in Health & Disease; Radical SAM and Aconitase-Related Fe-S Enzymes; Fe-S Enzymes and Synthetic Analogues in BioEnergy; and Fe-S Enzymes in Geochemistry and the Origin of Life.

  17. DNA binding and cleavage activity by a mononuclear iron(II)Schiff base complex: Synthesis and structural characterization

    Indian Academy of Sciences (India)

    Abhijit Pal; Bhaskar Biswas; Merry Mitra; Subramaniyam Rajalakshmi; Chandra Shekhar Purohit; Soumitra Hazra; Gopinatha Suresh Kumar; Balachandran Unni Nair; Rajarshi Ghosh

    2013-09-01

    Synthesis and characterization of a mononuclear Fe(II) compound [Fe(L)](ClO4)2 (1) [L = N-(1-pyridin-2-yl-phenylidene)-N'-[2-({2-[(1-pyridin-2-ylphenylidene)amino]ethyl}amino)ethyl] ethane-1,2-diamine] (1) is reported. 1 crystallizes in P-1 space group with a = 11.9241(3) Å, b = 12.1994(3) Å and c = 13.0622(4) Å. The binding property of the complex with DNA has been investigated using absorption and emission studies, thermal melting, viscosity experiments and circular dichroism studies. The binding constant (b) and the linear Stern-Volmer quenching constant (sv) of the complex have been determined as 3.5 × 103M-1 and 2.73 × 104M-1, respectively. Spectroscopic and hydrodynamic investigations revealed intercalative mode of binding of 1 with DNA. 1 is also found to induce oxidative cleavage of the supercoiled pUC 18 DNA to its nicked circular form in a concentration dependent manner.

  18. Synthesis of short-chain diols and unsaturated alcohols from secondary alcohol substrates by the Rieske nonheme mononuclear iron oxygenase MdpJ.

    Science.gov (United States)

    Schäfer, Franziska; Schuster, Judith; Würz, Birgit; Härtig, Claus; Harms, Hauke; Müller, Roland H; Rohwerder, Thore

    2012-09-01

    The Rieske nonheme mononuclear iron oxygenase MdpJ of the fuel oxygenate-degrading bacterial strain Aquincola tertiaricarbonis L108 has been described to attack short-chain tertiary alcohols via hydroxylation and desaturation reactions. Here, we demonstrate that also short-chain secondary alcohols can be transformed by MdpJ. Wild-type cells of strain L108 converted 2-propanol and 2-butanol to 1,2-propanediol and 3-buten-2-ol, respectively, whereas an mdpJ knockout mutant did not show such activity. In addition, wild-type cells converted 3-methyl-2-butanol and 3-pentanol to the corresponding desaturation products 3-methyl-3-buten-2-ol and 1-penten-3-ol, respectively. The enzymatic hydroxylation of 2-propanol resulted in an enantiomeric excess of about 70% for the (R)-enantiomer, indicating that this reaction was favored. Likewise, desaturation of (R)-2-butanol to 3-buten-2-ol was about 2.3-fold faster than conversion of the (S)-enantiomer. The biotechnological potential of MdpJ for the synthesis of enantiopure short-chain alcohols and diols as building block chemicals is discussed.

  19. Effects of iron deficiency on free radical scavenging enzymes in muscles of diabetic rats

    Energy Technology Data Exchange (ETDEWEB)

    Morrow, S.; Hegarty, P.V.J.

    1986-03-05

    Catalase, superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) prevent free-radical mediated tissue damage. Diabetes increases, and low dietary intakes of iron decreases catalase activity in muscles. Therefore, the combined effects of diabetes and iron deficiency on the free radical enzyme scavenging system was studied. Male, weanling rats were injected with streptozotocin (65 mg/kg, I.V.) and fed diets containing either 35 ppm (Db+Fe) or 8 ppm (Db-Fe) iron. Sham-injected animals served as iron adequate (C+Fe) or iron deficient (C-Fe) controls. Heart, gastrocnemius, soleus and anterior tibialis muscles were dissected, weighed and analyzed for catalase, SOD and GSH-Px activities after 1,3 or 6 weeks on the respective diets. Muscles in Db+Fe and Db-Fe groups had elevated catalase activity after one week in the diabetic state. Conversely, catalase activity was depressed in the C-Fe animals. SOD and GSH-Px activities did not differ from control values for any experimental group. Treatment with insulin and/or iron returned catalase activity to control levels. These data indicate that iron deficiency does not inhibit responses of muscle catalase to the diabetic condition, and the diabetic condition exerts an effect on catalase which is independent of SOD and GSH-Px.

  20. Stabilization of the Low-Spin State in a Mononuclear Iron(II) Complex and High-Temperature Cooperative Spin Crossover Mediated by Hydrogen Bonding.

    Science.gov (United States)

    Zheng, Sipeng; Reintjens, Niels R M; Siegler, Maxime A; Roubeau, Olivier; Bouwman, Elisabeth; Rudavskyi, Andrii; Havenith, Remco W A; Bonnet, Sylvestre

    2016-01-04

    The tetrapyridyl ligand bbpya (bbpya=N,N-bis(2,2'-bipyrid-6-yl)amine) and its mononuclear coordination compound [Fe(bbpya)(NCS)2 ] (1) were prepared. According to magnetic susceptibility, differential scanning calorimetry fitted to Sorai's domain model, and powder X-ray diffraction measurements, 1 is low-spin at room temperature, and it exhibits spin crossover (SCO) at an exceptionally high transition temperature of T1/2 =418 K. Although the SCO of compound 1 spans a temperature range of more than 150 K, it is characterized by a wide (21 K) and dissymmetric hysteresis cycle, which suggests cooperativity. The crystal structure of the LS phase of compound 1 shows strong NH⋅⋅⋅S intermolecular H-bonding interactions that explain, at least in part, the cooperative SCO behavior observed for complex 1. DFT and CASPT2 calculations under vacuum demonstrate that the bbpya ligand generates a stronger ligand field around the iron(II) core than its analogue bapbpy (N,N'-di(pyrid-2-yl)-2,2'-bipyridine-6,6'-diamine); this stabilizes the LS state and destabilizes the HS state in 1 compared with [Fe(bapbpy)(NCS)2 ] (2). Periodic DFT calculations suggest that crystal-packing effects are significant for compound 2, in which they destabilize the HS state by about 1500 cm(-1) . The much lower transition temperature found for the SCO of 2 compared to 1 appears to be due to the combined effects of the different ligand field strengths and crystal packing.

  1. Geometric and electronic structure contributions to function in non-heme iron enzymes.

    Science.gov (United States)

    Solomon, Edward I; Light, Kenneth M; Liu, Lei V; Srnec, Martin; Wong, Shaun D

    2013-11-19

    Mononuclear non-heme Fe (NHFe) enzymes play key roles in DNA repair, the biosynthesis of antibiotics, the response to hypoxia, cancer therapy, and many other biological processes. These enzymes catalyze a diverse range of oxidation reactions, including hydroxylation, halogenation, ring closure, desaturation, and electrophilic aromatic substitution (EAS). Most of these enzymes use an Fe(II) site to activate dioxygen, but traditional spectroscopic methods have not allowed researchers to insightfully probe these ferrous active sites. We have developed a methodology that provides detailed geometric and electronic structure insights into these NHFe(II) active sites. Using these data, we have defined a general mechanistic strategy that many of these enzymes use: they control O2 activation (and limit autoxidation and self-hydroxylation) by allowing Fe(II) coordination unsaturation only in the presence of cosubstrates. Depending on the type of enzyme, O2 activation either involves a 2e(-) reduced Fe(III)-OOH intermediate or a 4e(-) reduced Fe(IV)═O intermediate. Nuclear resonance vibrational spectroscopy (NRVS) has provided the geometric structure of these intermediates, and magnetic circular dichroism (MCD) has defined the frontier molecular orbitals (FMOs), the electronic structure that controls reactivity. This Account emphasizes that experimental spectroscopy is critical in evaluating the results of electronic structure calculations. Therefore these data are a key mechanistic bridge between structure and reactivity. For the Fe(III)-OOH intermediates, the anticancer drug activated bleomycin (BLM) acts as the non-heme Fe analog of compound 0 in heme (e.g., P450) chemistry. However BLM shows different reactivity: the low-spin (LS) Fe(III)-OOH can directly abstract a H atom from DNA. The LS and high-spin (HS) Fe(III)-OOHs have fundamentally different transition states. The LS transition state goes through a hydroxyl radical, but the HS transition state is activated for

  2. Enantioselective, intermolecular benzylic C-H amination catalysed by an engineered iron-haem enzyme

    Science.gov (United States)

    Prier, Christopher K.; Zhang, Ruijie K.; Buller, Andrew R.; Brinkmann-Chen, Sabine; Arnold, Frances H.

    2017-07-01

    C-H bonds are ubiquitous structural units of organic molecules. Although these bonds are generally considered to be chemically inert, the recent emergence of methods for C-H functionalization promises to transform the way synthetic chemistry is performed. The intermolecular amination of C-H bonds represents a particularly desirable and challenging transformation for which no efficient, highly selective, and renewable catalysts exist. Here we report the directed evolution of an iron-containing enzymatic catalyst—based on a cytochrome P450 monooxygenase—for the highly enantioselective intermolecular amination of benzylic C-H bonds. The biocatalyst is capable of up to 1,300 turnovers, exhibits excellent enantioselectivities, and provides access to valuable benzylic amines. Iron complexes are generally poor catalysts for C-H amination: in this catalyst, the enzyme's protein framework confers activity on an otherwise unreactive iron-haem cofactor.

  3. Ammonium nitrate and iron nutrition effects on some nitrogen assimilation enzymes and metabolites in Spirulina platensis.

    Science.gov (United States)

    Esen, Merve; Ozturk Urek, Raziye

    2015-01-01

    The effect of various concentrations of ammonium nitrate (5-60 mM), an economical nitrogen source, on the growth, nitrate-ammonium uptake rates, production of some pigments and metabolites, and some nitrogen assimilation enzymes such as nitrate reductase (NR), nitrite reductase (NiR), glutamine synthetase (GS), and glutamate synthase (GOGAT) in Spirulina platensis (Gamont) Geitler was investigated. Ten millimolars of ammonium nitrate stimulated the growth, production of pigments and the other metabolites, and enzyme activities, whereas 30 and 60 mM ammonium nitrate caused inhibition. In the presence of 10 mM ammonium nitrate, different concentrations of iron were tried in the growth media of S. platensis. After achieving the best growth, levels of metabolite and pigment production, and enzyme activities in the presence of 10 mM ammonium nitrate as a nitrogen source, different iron concentrations (10-100 µM) were tried in the growth medium of S. platensis. The highest growth, pigment and metabolite levels, and enzyme activities were determined in the medium containing 50 µM iron and 10 mM ammonium nitrate. In this optimum condition, the highest dry biomass level, chlorophyll a, and pyruvate contents were obtained as 55.42 ± 3.8 mg mL(-1) , 93.114 ± 7.9 µg g(-1) , and 212.5 ± 18.7 µg g(-1) , respectively. The highest NR, NiR, GS, and GOGAT activities were 67.16 ± 5.1, 777.92 ± 52, 0.141 ± 0.01, and 44.45 ± 3.6, respectively. Additionally, 10 mM ammonium nitrate is an economical and efficient nitrogen source for nitrogen assimilation of S. platensis, and 50 µM iron is optimum for the growth of S. platensis. © 2014 International Union of Biochemistry and Molecular Biology, Inc.

  4. Stabilization of the Low-Spin State in a Mononuclear Iron(II) Complex and High-Temperature Cooperative Spin Crossover Mediated by Hydrogen Bonding

    NARCIS (Netherlands)

    Zheng, Sipeng; Reintjens, Niels R. M.; Siegler, Maxime A.; Roubeau, Olivier; Bouwman, Elisabeth; Rudavskyi, Andrii; Havenith, Remco W. A.; Bonnet, Sylvestre

    2016-01-01

    The tetrapyridyl ligand bbpya (bbpya=N,N-bis(2,2'-bipyrid-6-yl)amine) and its mononuclear coordination compound [Fe(bbpya)(NCS)(2)] (1) were prepared. According to magnetic susceptibility, differential scanning calorimetry fitted to Sorai's domain model, and powder X-ray diffraction measurements, 1

  5. Antioxidant enzymes and oxidative stress in the erythrocytes of iron deficiency anemic patients supplemented with vitamins.

    Science.gov (United States)

    Madhikarmi, Nirjala Laxmi; Murthy, Kora Rudraiah Siddalinga

    2014-01-01

    Iron deficiency anemia is one of the major causes of morbidity and mortality worldwide. Evidences from epidemiological and clinical studies suggest a possible correlation between antioxidant levels and the anemic disease risk. The present work is to investigate antioxidant levels and lipid peroxidation in anemic patients. A number of 30 patients (15 males and 15 females) were selected for the study. Likewise, 30 age- and gender-matched healthy volunteers (15 males and 15 females) were selected with their informed consent. Patients and healthy subjects were supplemented with vitamins C and E for 15 days. The lipid peroxidation both in plasma and erythrocyte lysates was determined by thiobarbituric acid reactive substances and lipid peroxides. The antioxidant vitamins A, C, and E and total antioxidant activity were also analyzed. The antioxidant enzyme superoxide dismutase, catalase, and glutathione peroxidase were also determined. Based on analysis, we found that the increase in lipid peroxidation was higher in the anemic subjects before vitamin supplementation, which was statistically significant at Pantioxidant enzymes were higher in the patients before antioxidant supplementation when compared with patients after vitamin supplementation. Our data revealed higher oxidative stress before vitamin supplementation in iron deficiency anemic patients and after supplementation, lower lipid peroxidation and increased antioxidant vitamins were achieved.

  6. 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.

  7. 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...... in carboxylate conformations occurring during the O-2 reaction of this class of non-heme iron enzymes. Our procedure identifies and characterizes various possible candidates for peroxo intermediates experimentally observed along the ribonucleotide reductase dioxygen activation reaction. The study explores how...... water or a proton can bind to the di-iron site of ribonucleotide reductase and facilitate changes that affect the electronic structure of the iron sites and activate the site for further reaction. Two potential reaction pathways are presented: one where water adds to Fe1 of the cis-mu-1,2 peroxo...

  8. Effects of iron on growth, antioxidant enzyme activity, bound extracellular polymeric substances and microcystin production of Microcystis aeruginosa FACHB-905.

    Science.gov (United States)

    Wang, Chao; Wang, Xun; Wang, Peifang; Chen, Bin; Hou, Jun; Qian, Jin; Yang, Yangyang

    2016-10-01

    Toxic cyanobacterial blooms have occurred in various water bodies during recent decades and made serious health hazards to plants, animals and humans. Iron is an important micronutrient for algal growth and recently, the concentration of which has increased remarkably in freshwaters. In this paper, the cyanobacterium Microcystis aeruginosa FACHB-905 was cultivated under non-iron (0μM), iron-limited (10μM) and iron-replete (100μM) conditions to investigate the effects of iron on growth, antioxidant enzyme activity, EPS and microcystin production. The results showed that algal cell density and chlorophyll-a content were maximal at the highest iron concentration. Antioxidant enzymes activity increased notably under all three conditions in the early stage of experiment, of which the SOD activity recovered soon from oxidative stress in 10μM group. The productions of some protein-like substances and humic acid-like substances of bound EPS were inhibited in iron-containing groups in the early stage of experiment while promoted after the adaptation period of Microcystis aeruginosa. Iron addition is a factor affecting the formation of cyanobacterial blooms through its impact on the content of LB-EPS and the composition of TB-EPS. The intracellular MC-LR concentration and the productivity potential of MC-LR were the lowest in 0μM group and highest in 10μM group. No obvious extracellular release of MC-LR was observed during the cultivation time. Therefore, iron addition can promote the physiological activities of M. aeruginosa, but a greater harm could be brought into environment under iron-limited (10μM) condition than under iron-replete (100μM) condition.

  9. Modeling the 2-His-1-Carboxylate Facial Triad: Iron-Catecholato Complexes as Structural and Functional Models of the Extradiol Cleaving Dioxygenases

    NARCIS (Netherlands)

    Bruijnincx, P.C.A.; Lutz, M.; Spek, A.L.; Hagen, W.R.; Weckhuysen, B.M.; van Koten, G.; Klein Gebbink, R.J.M.

    2007-01-01

    Mononuclear iron(II)- and iron(III)-catecholato complexes with three members of a new 3,3-bis(1-alkylimidazol-2-yl)propionate ligand family have been synthesized as models of the active sites of the extradiol cleaving catechol dioxygenases. These enzymes are part of the superfamily of dioxygen-activ

  10. 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 Cγ,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.

  11. Facile, high efficiency immobilization of lipase enzyme on magnetic iron oxide nanoparticles via a biomimetic coating

    Directory of Open Access Journals (Sweden)

    He Lihong

    2011-06-01

    Full Text Available Abstract Background Immobilization of lipase on appropriate solid supports is one way to improve their stability and activity, and can be reused for large scale applications. A sample, cost- effective and high loading capacity method is still challenging. Results A facile method of lipase immobilization was developed in this study, by the use of polydopamine coated magnetic nanoparticles (PD-MNPs. Under optimal conditions, 73.9% of the available lipase was immobilized on PD-MNPs, yielding a lipase loading capacity as high as 429 mg/g. Enzyme assays revealed that lipase immobilized on PD-MNPs displayed enhanced pH and thermal stability compared to free lipase. Furthermore, lipase immobilized on PD-MNPs was easily isolated from the reaction medium by magnetic separation and retained more than 70% of initial activity after 21 repeated cycles of enzyme reaction followed by magnetic separation. Conclusions Immobilization of enzyme onto magnetic iron oxide nanoparticles via poly-dopamine film is economical, facile and efficient.

  12. Adsorption of Trametes versicolor laccase to soil iron and aluminum minerals: enzyme activity, kinetics and stability studies.

    Science.gov (United States)

    Wu, Yue; Jiang, Ying; Jiao, Jiaguo; Liu, Manqiang; Hu, Feng; Griffiths, Bryan S; Li, Huixin

    2014-02-01

    Laccases play an important role in the degradation of soil phenol or phenol-like substance and can be potentially used in soil remediation through immobilization. Iron and aluminum minerals can adsorb extracellular enzymes in soil environment. In the present study, we investigated the adsorptive interaction of laccase, from the white-rot fungus Trametes versicolor, with soil iron and aluminum minerals and characterized the properties of the enzyme after adsorption to minerals. Results showed that both soil iron and aluminum minerals adsorbed great amount of laccase, independent of the mineral specific surface areas. Adsorbed laccases retained 26-64% of the activity of the free enzyme. Compared to the free laccase, all adsorbed laccases showed higher Km values and lower Vmax values, indicating a reduced enzyme-substrate affinity and a lower rate of substrate conversion in reactions catalyzed by the adsorbed laccase. Adsorbed laccases exhibited increased catalytic activities compared to the free laccase at low pH, implying the suitable application of iron and aluminum mineral-adsorbed T. versicolor laccase in soil bioremediation, especially in acid soils. In terms of the thermal profiles, adsorbed laccases showed decreased thermal stability and higher temperature sensitivity relative to the free laccase. Moreover, adsorption improved the resistance of laccase to proteolysis and extended the lifespan of laccase. Our results implied that adsorbed T. versicolor laccase on soil iron and aluminum minerals had promising potential in soil remediation.

  13. Iron limitation effects a massive shift in iron and flavin based antioxidant enzyme systems and their substrates in the Chlorophyte alga Dunaliella tertiolecta

    Science.gov (United States)

    Traggis, H. M.

    2012-12-01

    Ubiquitous in the neritic ocean, it is now believed that iron-limitation is the most important factor controlling primary production in oceanic phytoplankton. To investigate the effects of iron deficiency, Dunaliella tertiolecta was cultured under limiting (100 nM Fe) and replete (1μM Fe) iron concentrations. The physiological status and the Water-Water antioxidant defense system were evaluated. Iron limitation effected a 21% drop in PSII efficiency (replete= 0.634± 0.012; limiting= 0.507± 0.012) concurrent with a 17.5% reduction in photosynthetic rates (replete= 265.8 umol 02/mg chl/hr ± 5.7; limiting= 219.3 umol 02/mg chl/hr ± 5.7). Both heme and non-heme based antioxidant enzyme activities were assessed. Heme-based Ascorbate peroxidase (APX), exhibits an 84% iron limited rate reduction (replete and limited = 36.23 and 5.72 umol ascorbate mg prot-1 hr-1 ±2.96, respectively). Conversely, the flavin-based Monodehydroascorbate reductase (MDHAR), exhibits a significant rate increase, 2.16±0.19 (replete) to 3.86±0.19 umol NADH mg prot-1 hr-1 under iron-limitation. Iron deficient cultures exhibit a 34% increase in total available ascorbate. These investigations suggest that D. tertiolecta is able to maintain a stable growth rate under iron limitation by re-allocating its subcellular usage of available iron and increasing the availability of total ascorbate. Further investigations will determine the presence of additional iron/flavin based molecules involved in the photosynthetic apparatus and anti-oxidant scavenging mechanisms.

  14. Synthesis and characterization of mononuclear iron silanethiolato complexes containing an unsupported Fe-S-Si bond system: X-ray crystal structure of CpFe(CO)2SSiPh3 and its reaction with SO2.

    Science.gov (United States)

    Kovács, István; Bélanger-Gariépy, Francine; Shaver, Alan

    2003-05-01

    Mononuclear iron silanethiolato complexes of the type CpFe(CO)(2)SSiR(3), where R = Ph (1a) and (i)()Pr (1b), were prepared via treatment of [CpFe(CO)(2)(THF)]BF(4) with LiSSiPh(3).Et(2)O and NaSSi(i)()Pr(3), respectively. The molecular structure of 1a was determined by X-ray crystallography. Complex 1a was reacted with 1 equiv of SO(2) to give the corresponding O-silyl thiosulfite, CpFe(CO)(2)SS(O)OSiPh(3) (2), via 1,2-insertion of SO(2) into the S-Si bond. This reaction models the activation of SO(2) in the homogeneously catalyzed Claus process.

  15. 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.

  16. 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

  17. 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 activ

  18. End-on and side-on peroxo derivatives of non-heme iron complexes with pentadentate ligands : Models for putative intermediates in biological iron/dioxygen chemistry

    NARCIS (Netherlands)

    Roelfes, G; Vrajmasu, [No Value; Ho, RYN; Rohde, JU; Zondervan, C; la Crois, RM; Schudde, EP; Lutz, M; Spek, AL; Hage, R; Feringa, BL; Munck, E; Que, L; Vrajmasu, Vladislav; Ho, Raymond Y.N.; Rohde, Jan-Uwe; Crois, Rene M. la; Spek, Anthony L.; Que, Jr.; Feringa, Bernard

    2003-01-01

    Mononuclear iron(III) species with end-on and side-on peroxide have been proposed or identified in the catalytic cycles of the antitumor drug bleomycin and a variety of enzymes, such as cytochrome P450 and Rieske dioxygenases, Only recently have biomimetic analogues of such reactive species been, ge

  19. 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 ...

  20. Iron

    Science.gov (United States)

    Iron is a mineral that our bodies need for many functions. For example, iron is part of hemoglobin, a protein which carries ... It helps our muscles store and use oxygen. Iron is also part of many other proteins and ...

  1. Iron

    Science.gov (United States)

    ... of iron stored in the body become low, iron deficiency anemia sets in. Red blood cells become smaller and ... from the lungs throughout the body. Symptoms of iron deficiency anemia include tiredness and lack of energy, GI upset, ...

  2. 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 CO2 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.

  3. [Effects of chlorophyllin-iron on osmotic adjustment and activities of antioxidantive enzymes in cucumber seedlings under suboptimal temperature].

    Science.gov (United States)

    Zhang, Meng; Wang, Xiu-feng; Zhang, Fan-yang; Wei, Min; Shi, Qing-hua; Yang, Feng-juan; Li, Yan

    2014-12-01

    Cucumber cultivar 'Jinyan 4' was subjected to suboptimal temperature treatment of 18/12 degrees C (day/night) in the growth chambers. A solution culture experiment was conducted to study the effect of exogenously spraying 5 mg x L(-1) chlorophyllin-iron solution on plant growth, the content of proline, soluble sugar, MDA and activity of peroxidase in the leaves of cucumber seedling under suboptimal temperature. Application of chlorophyllin-iron showed prominent effects on mitigating the stress of suboptimal temperature on growth of the cucumber seedlings, significantly increasing the plant height, leaf area, shoot dry mass, the contents of soluble sugar and proline and the activities of SOD, POD, CAT and APX. Exogenously spraying chlorophyllin-iron could promote the accumulation of proline and soluble sugar, raise the activities of antioxidant enzymes, decrease the membrane lipid peroxidation and improve the adaptability of cucumber seedlings under suboptimal temperature.

  4. Iron

    DEFF Research Database (Denmark)

    Hansen, Jakob Bondo; Moen, I W; Mandrup-Poulsen, T

    2014-01-01

    The interest in the role of ferrous iron in diabetes pathophysiology has been revived by recent evidence of iron as an important determinant of pancreatic islet inflammation and as a biomarker of diabetes risk and mortality. The iron metabolism in the β-cell is complex. Excess free iron is toxic......, but at the same time, iron is required for normal β-cell function and thereby glucose homeostasis. In the pathogenesis of diabetes, iron generates reactive oxygen species (ROS) by participating in the Fenton chemistry, which can induce oxidative damage and apoptosis. The aim of this review is to present...... 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...

  5. Structure and nuclearity of active sites in Fe-zeolites: comparison with iron sites in enzymes and homogeneous catalysts.

    Science.gov (United States)

    Zecchina, Adriano; Rivallan, Mickaël; Berlier, Gloria; Lamberti, Carlo; Ricchiardi, Gabriele

    2007-07-21

    Fe-ZSM-5 and Fe-silicalite zeolites efficiently catalyse several oxidation reactions which find close analogues in the oxidation reactions catalyzed by homogeneous and enzymatic compounds. The iron centres are highly dispersed in the crystalline matrix and on highly diluted samples, mononuclear and dinuclear structures are expected to become predominant. The crystalline and robust character of the MFI framework has allowed to hypothesize that the catalytic sites are located in well defined crystallographic positions. For this reason these catalysts have been considered as the closest and best defined heterogeneous counterparts of heme and non heme iron complexes and of Fenton type Fe(2+) homogeneous counterparts. On this basis, an analogy with the methane monooxygenase has been advanced several times. In this review we have examined the abundant literature on the subject and summarized the most widely accepted views on the structure, nuclearity and catalytic activity of the iron species. By comparing the results obtained with the various characterization techniques, we conclude that Fe-ZSM-5 and Fe-silicalite are not the ideal samples conceived before and that many types of species are present, some active and some other silent from adsorptive and catalytic point of view. The relative concentration of these species changes with thermal treatments, preparation procedures and loading. Only at lowest loadings the catalytically active species become the dominant fraction of the iron species. On the basis of the spectroscopic titration of the active sites by using NO as a probe, we conclude that the active species on very diluted samples are isolated and highly coordinatively unsaturated Fe(2+) grafted to the crystalline matrix. Indication of the constant presence of a smaller fraction of Fe(2+) presumably located on small clusters is also obtained. The nitrosyl species formed upon dosing NO from the gas phase on activated Fe-ZSM-5 and Fe-silicalite, have been analyzed

  6. Relation between iron metabolism and antioxidants enzymes and δ-ALA-D activity in rats experimentally infected by Fasciola hepatica.

    Science.gov (United States)

    Bottari, Nathieli B; Mendes, Ricardo E; Baldissera, Matheus D; Bochi, Guilherme V; Moresco, Rafael N; Leal, Marta L R; Morsch, Vera M; Schetinger, Maria R C; Christ, Ricardo; Gheller, Larissa; Marques, Éder J; Da Silva, Aleksandro S

    2016-06-01

    The aim of this study was to evaluate the iron metabolism in serum, as well as antioxidant enzymes, in addition to the Delta-Aminolevulinic Acid Dehydratase (δ-ALA-D) activity in the liver of rats experimentally infected by Fasciola hepatica. Thirty male adult rats (Wistar) specific pathogen free were divided into four groups: two uninfected group (CTRL 1 and CTRL 2) with five animals each and two infected groups (INF 1 and INF 2) with 10 animals each. Infection was performed orally with 20 metacercariae at day 1. On day 15 (CTRL 1 and INF 1 groups) and 87 PI (CTRL 2 and INF 2 groups) blood and bone marrow were collected and the animals were subsequently euthanized for liver sampling. Blood was allocated in tubes without anticoagulant for serum acquisition to measure iron, transferrin and unsaturated iron binding capacity (UIBC). δ-ALA-D, superoxide dismutase (SOD), and catalase (CAT) activities were measured in the liver. A decrease in iron, transferrin and UIBC levels was observed in all infected animals compared to control groups (P iron accumulation was observed in bone marrow of infected mice. Infected animals showed an increase in δ-ALA-D activity at 87 post-infection (PI) (INF 2) as well as in SOD activity at days 15 (INF 1) and 87 PI (INF 2). On the other hand, CAT activity was reduced in rats infected by F. hepatica during acute and chronic phase of fasciolosis (INF 1 and INF 2 groups), when moderate (acute) and severe necrosis in the liver histopathology were observed. These results may suggest that oxidative damage to tissues along with antioxidant mechanisms might have taken part in fasciolosis pathogenesis and are also involved in iron deficiency associated to changes in δ-ALA-D activity during chronic phase of disease.

  7. Malondialdehyde, antioxidant enzymes, and renal tubular functions in children with iron deficiency or iron-deficiency anemia.

    Science.gov (United States)

    Altun, Demet; Kurekci, Ahmet Emin; Gursel, Orhan; Hacıhamdioglu, Duygu Ovunc; Kurt, Ismail; Aydın, Ahmet; Ozcan, Okan

    2014-10-01

    We aimed to investigate the effects of iron deficiency (ID) or iron-deficiency anemia (IDA) on oxidative stress and renal tubular functions before and after treatment of children. A total of 30 children with a diagnosis of IDA constituted the IDA group and 32 children with a diagnosis of ID constituted the ID group. Control group consisted 38 age-matched children. Serum ferritin, soluble transferrin receptor (sTfR), serum, and urinary sodium (Na), potassium (K), calcium (Ca), phosphorus (P), creatinine (Cr), uric acid (UA), urinary N-acetyl-β-D-glucosaminidase (NAG) levels, and intra-erythrocyte malondialdehyde (MDA), catalase (CAT), superoxide dismutase (SOD), and glutathione peroxidase (GSH-Px) levels were measured before and after iron therapy in the IDA and ID groups, whereas it was studied once in the control group. We have divided the study group in groups according to age (infants <2 years, children 3-9 years, and adolescents 10-15 years). Patients with IDA (infant, adolescent) and ID (infant, children, and adolescent) had a significantly high level of MDA in post-treatment period in comparison to those of healthy control. Patients with IDA (children, adolescent) and ID (infant, children) had a significantly high level of pre-treatment GSH-Px than controls. Post-treatment SOD was lower in IDA (children and adolescent) groups than control and post-treatment CAT was lower in IDA and ID (adolescent) groups than control. These findings show that ferrous sulfate used in the treatment of ID or IDA could lead to oxidative stress; however, a marked deterioration of in proximal renal tubular functions was not seen.

  8. Redox-inactive metal ions modulate the reactivity and oxygen release of mononuclear non-haem iron(III)-peroxo complexes.

    Science.gov (United States)

    Bang, Suhee; Lee, Yong-Min; Hong, Seungwoo; Cho, Kyung-Bin; Nishida, Yusuke; Seo, Mi Sook; Sarangi, Ritimukta; Fukuzumi, Shunichi; Nam, Wonwoo

    2014-10-01

    Redox-inactive metal ions that function as Lewis acids play pivotal roles in modulating the reactivity of oxygen-containing metal complexes and metalloenzymes, such as the oxygen-evolving complex in photosystem II and its small-molecule mimics. Here we report the synthesis and characterization of non-haem iron(III)-peroxo complexes that bind redox-inactive metal ions, (TMC)Fe(III)-(μ,η(2):η(2)-O2)-M(n+) (M(n+) = Sr(2+), Ca(2+), Zn(2+), Lu(3+), Y(3+) and Sc(3+); TMC, 1,4,8,11-tetramethyl-1,4,8,11-tetraazacyclotetradecane). We demonstrate that the Ca(2+) and Sr(2+) complexes showed similar electrochemical properties and reactivities in one-electron oxidation or reduction reactions. However, the properties and reactivities of complexes formed with stronger Lewis acidities were found to be markedly different. Complexes that contain Ca(2+) or Sr(2+) ions were oxidized by an electron acceptor to release O2, whereas the release of O2 did not occur for complexes that bind stronger Lewis acids. We discuss these results in the light of the functional role of the Ca(2+) ion in the oxidation of water to dioxygen by the oxygen-evolving complex.

  9. Enhancement of the activity of enzyme immobilized on polydopamine-coated iron oxide nanoparticles by rational orientation of formate dehydrogenase.

    Science.gov (United States)

    Gao, Xin; Ni, Kefeng; Zhao, Chengcheng; Ren, Yuhong; Wei, Dongzhi

    2014-10-20

    Immobilization of enzymes onto nanoparticles and retention of their structure and activity, which may be related to the orientation of enzymes on nanoparticles, remain a challenge. Here, we developed a novel enzyme-orientation strategy to enhance the activity of formate dehydrogenase immobilized on polydopamine-coated iron oxide nanoparticles via site-directed mutation. Seven mutants were constructed based on homology modeling of formate dehydrogenase and immobilized on polydopamine-coated iron oxide nanoparticles to investigate the influence of these mutations on immobilization. The immobilized mutant C242A/C275V/C363V/K389C demonstrated the highest immobilization yield and retained 90% of its initial activity, which was about 3-fold higher than that of wild-type formate dehydrogenase. Moreover, co-immobilization of formate dehydrogenase and leucine dehydrogenase was performed for the synthesis of l-tert-leucine. The catalytic efficiency of the co-immobilized mutant C242A/C275V/C363V/K389C and leucine dehydrogenase increased by more than 4-fold compared to that of co-immobilized wild-type formate dehydrogenase and leucine dehydrogenase. Copyright © 2014 Elsevier B.V. All rights reserved.

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

    OpenAIRE

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

    2016-01-01

    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 int...

  11. Structural, Magnetic, and Photomagnetic Studies of a Mononuclear Iron(II) Derivative Exhibiting an Exceptionally Abrupt Spin Transition. Light-Induced Thermal Hysteresis Phenomenon.

    Science.gov (United States)

    Létard, Jean-François; Guionneau, Philippe; Rabardel, Louis; Howard, Judith A. K.; Goeta, Andres E.; Chasseau, Daniel; Kahn, Olivier

    1998-08-24

    The new spin-crossover compound Fe(PM-BiA)(2)(NCS)(2) with PM-BiA = N-(2-pyridylmethylene)aminobiphenyl has been synthesized. The temperature dependence of chi(M)T (chi(M) = molar magnetic susceptibility and T = temperature) has revealed an exceptionally abrupt transition between low-spin (LS) (S = 0) and high-spin (HS) (S = 2) states with a well-reproducible hysteresis loop of 5 K (T(1/2) downward arrow = 168 K and T(1/2) upward arrow = 173 K). The crystal structure has been determined both at 298 K in the HS state and at 140 K in the LS state. The spin transition takes place without change of crystallographic space group (Pccn with Z = 4). The determination of the intermolecular contacts in the LS and HS forms has revealed a two-dimensional structural character. The enthalpy and entropy variations, DeltaH and DeltaS, associated with the spin transition have been deduced from heat capacity measurements. DeltaS (= 58 J K(-)(1) mol(-)(1)) is larger than for other spin transition bis(thiocyanato) iron(II) derivatives. At 10 K the well-known LIESST (light-induced excited spin state trapping) effect has been observed within the SQUID cavity, by irradiating a single crystal or a powder sample with a Kr(+) laser coupled to an optical fiber. The magnetic behavior recorded under light irradiation in the warming and cooling modes has revealed a light-induced thermal hysteresis (LITH) effect with 35 LS relaxation after LIESST has been found to deviate from first-order kinetics. The kinetics has been investigated between 10 and 78 K. A thermally activated relaxation behavior at elevated temperatures and a nearly temperature independent tunneling mechanism at low temperatures have been observed. The slow rate of tunneling from the metastable HS state toward the ground LS state may be explained by the unusually large change in Fe-N bond lengths between these two states.

  12. Exogenous Nitric Oxide Alleviated the Inhibition of Photosynthesis and Antioxidant Enzyme Activities in Iron-Deficient Chinese Cabbage(Brassica chinensis L.)

    Institute of Scientific and Technical Information of China (English)

    DING Fei; WANG Xiu-feng; SHI Qing-hua; WANG Mei-ling; YANG Feng-juan; GAO Qing-hai

    2008-01-01

    The effects of exogenous nitric oxide(NO)on plant growth,chlorophyll contents,photosynthetic and chlorophyll fluorescence parameters as well as lipid peroxidation and activities of antioxidant enzymes were investigated in Chinese cabbage plants exposed to iron(Fe)deficiency.Iron deficiency led to serious chlorosis in Chinese cabbage leaves,and resulted in significant decrease in plant growth,photosynthetic pigments,net photosynthetic rate,Fv/Fm,ΦPsⅡand activities of antioxidant enzymes,and increase in lipid peroxidation.While treatment with SNP,a NO donor,it could revert the iron deficiency symptoms,increased photosynthetic rate as well as activities of antioxidant enzymes,and protected membrane from lipid peroxidation,as a result,the growth inhibition of Chinese cabbage by Fe deficiency was alleviated.

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

    OpenAIRE

    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 ...

  14. Mononuclear spin-transition materials based on the bapbpy scaffold

    NARCIS (Netherlands)

    Zheng, Sipeng

    2014-01-01

    Spin-crossover compounds showing thermal hysteresis exhibit magnetic and colourmetric bistablility, which is of interest for a number of applications such as information storage and optical displays. Mononuclear iron(II) complexes hold considerable potential in this field, and their cooperative prop

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

    Science.gov (United States)

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

    2012-09-07

    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.

  16. 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.

  17. Iron deficiency or anemia of inflammation?

    OpenAIRE

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

    2016-01-01

    Summary 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 ph...

  18. Gelatin-encapsulated iron oxide nanoparticles for platinum (IV) prodrug delivery, enzyme-stimulated release and MRI.

    Science.gov (United States)

    Cheng, Ziyong; Dai, Yunlu; Kang, Xiaojiao; Li, Chunxia; Huang, Shanshan; Lian, Hongzhou; Hou, Zhiyao; Ma, Pingan; Lin, Jun

    2014-08-01

    A facile method for transferring hydrophobic iron oxide nanoparticles (IONPs) from chloroform to aqueous solution via encapsulation of FITC-modified gelatin based on the hydrophobic-hydrophobic interaction is described in this report. Due to the existence of large amount of active groups such as amine groups in gelatin, the fluorescent labeling molecules of fluorescein isothiocyanate (FITC) and platinum (IV) prodrug functionalized with carboxylic groups can be conveniently conjugated on the IONPs. The nanoparticles carrying Pt(IV) prodrug exhibit good anticancer activities when the Pt(IV) complexes are reduced to Pt(II) in the intracellular environment, while the pure Pt(IV) prodrug only presents lower cytotoxicity on cancer cells. Meanwhile, fluorescence of FITC on the surface of nanoparticles was completely quenched due to the possible Förster Resonance Energy Transfer (FRET) mechanism and showed a fluorescence recovery after gelatin release and detachment from IONPs. Therefore FITC as a fluorescence probe can be used for identification, tracking and monitoring the drug release. In addition, adding pancreatic enzyme can effectively promote the gelatin release from IONPs owing to the degradation of gelatin. Noticeable darkening in magnetic resonance image (MRI) was observed at the tumor site after in situ injection of nanoparticles, indicating the IONPs-enhanced T2-weighted imaging. Our results suggest that the gelatin encapsulated Fe3O4 nanoparticles have potential applications in multi-functional drug delivery system for disease therapy, MR imaging and fluorescence sensor. Copyright © 2014 Elsevier Ltd. All rights reserved.

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

    Science.gov (United States)

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

    2010-01-01

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

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

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    Yasuo Miura

    2010-01-01

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

  1. Targeting of a human iron-sulfur cluster assembly enzyme, nifs, to different subcellular compartments is regulated through alternative AUG utilization.

    Science.gov (United States)

    Land, T; Rouault, T A

    1998-12-01

    Iron-sulfur clusters are prosthetic groups that are required for the function of numerous enzymes in the cell, including enzymes important in respiration, photosynthesis, and nitrogen fixation. Here we report cloning of the human homolog of NifS, a cysteine desulfurase that is proposed to supply the inorganic sulfur in iron-sulfur clusters. In human cells, different forms of NifS that localize either to mitochondria or to the cytosol and nucleus are synthesized from a single transcript through initiation at alternative inframe AUGs, and initiation site selection varies according to the pH of the medium or cytosol. Thus, a novel form of translational regulation permits rapid redistribution of NifS proteins into different compartments of the cell in response to changes in metabolic status.

  2. Enhanced and selective delivery of enzyme therapy to 9L-glioma tumor via magnetic targeting of PEG-modified, β-glucosidase-conjugated iron oxide nanoparticles.

    Science.gov (United States)

    Zhou, Jie; Zhang, Jian; Gao, Wenxi

    2014-01-01

    The stability of enzyme-conjugated magnetic iron oxide nanoparticles in plasma is of great importance for in vivo delivery of the conjugated enzyme. In this study, β-glucosidase was conjugated on aminated magnetic iron oxide nanoparticles using the glutaraldehyde method (β-Glu-MNP), and further PEGylated via N-hydroxysuccinimide chemistry. The PEG-modified, β-glucosidase-immobilized magnetic iron oxide nanoparticles (PEG-β-Glu-MNPs) were characterized by hydrodynamic diameter distribution, zeta potential, Fourier transform infrared spectroscopy, transmission electron microscopy, and a superconducting quantum interference device. The results showed that the multidomain structure and magnetization properties of these nanoparticles were conserved well throughout the synthesis steps, with an expected diameter increase and zeta potential shifts. The Michaelis constant was calculated to evaluate the activity of conjugated β-glucosidase on the magnetic iron oxide nanoparticles, indicating 73.0% and 65.4% of enzyme activity remaining for β-Glu-MNP and PEG-β-Glu-MNP, respectively. Both magnetophoretic mobility analysis and pharmacokinetics showed improved in vitro/in vivo stability of PEG-β-Glu-MNP compared with β-Glu-MNP. In vivo magnetic targeting of PEG-β-Glu-MNP was confirmed by magnetic resonance imaging and electron spin resonance analysis in a mouse model of subcutaneous 9L-glioma. Satisfactory accumulation of PEG-β-Glu-MNP in tumor tissue was successfully achieved, with an iron content of 627±45 nmol Fe/g tissue and β-glucosidase activity of 32.2±8.0 mU/g tissue.

  3. Effect of iron stress on Withania somnifera L.: antioxidant enzyme response and nutrient elemental uptake of in vitro grown plants.

    Science.gov (United States)

    Rout, Jyoti Ranjan; Behera, Sadhana; Keshari, Nitin; Ram, Shidharth Sankar; Bhar, Subhajit; Chakraborty, Anindita; Sudarshan, Mathummal; Sahoo, Santi Lata

    2015-03-01

    In the present study the response of antioxidant enzyme activities and the level of expression of their corresponding genes on bioaccumulation of iron (Fe) were investigated. In vitro germinated Withania somnifera L. were grown in Murashige and Skoog's liquid medium with increasing concentrations (0, 25, 50, 100 and 200 µM) of FeSO4 for 7 and 14 days. Root and leaf tissues analyzed for catalase (CAT, EC 1.11.1.6), superoxide dismutase (SOD, EC 1.15.1.1) and guaiacol peroxidase (GPX, EC 1.11.1.7), have shown an increase in content with respect to exposure time. Isoforms of CAT, SOD and GPX were separated using non-denaturing polyacrylamide gel electrophoresis and observed that the isoenzymes were greatly affected by higher concentrations of Fe. Reverse transcriptase polymerase chain reaction analysis performed by taking three pairs of genes of CAT (RsCat, Catalase1, Cat1) and SOD (SodCp, TaSOD1.2, MnSOD) to find out the differential expression of antioxidant genes under Fe excess. RsCat from CAT and MnSOD from SOD have exhibited high levels of gene expression under Fe stress, which was consistent with the changes of the activity assayed in solution after 7 days of treatment. Analysis by proton induced X-ray emission exhibited an increasing uptake of Fe in plants by suppressing and expressing of other nutrient elements. The results of the present study suggest that higher concentration of Fe causes disturbance in nutrient balance and induces oxidative stress in plant.

  4. Enhanced and selective delivery of enzyme therapy to 9L-glioma tumor via magnetic targeting of PEG-modified, ß-glucosidase- conjugated iron oxide nanoparticles

    Directory of Open Access Journals (Sweden)

    Zhou J

    2014-06-01

    Full Text Available Jie Zhou,1,* Jian Zhang,2,* Wenxi Gao11Department of Urology, Hubei Hospital of Traditional Chinese Medicine, Hubei University of Chinese Medicine, Wuhan, People’s Republic of China; 2Department of Pharmaceutical Sciences, College of Pharmacy, University of Michigan, Ann Arbor, MI, USA*These authors contributed equally to this workAbstract: The stability of enzyme-conjugated magnetic iron oxide nanoparticles in plasma is of great importance for in vivo delivery of the conjugated enzyme. In this study, ß-glucosidase was conjugated on aminated magnetic iron oxide nanoparticles using the glutaraldehyde method (ß-Glu-MNP, and further PEGylated via N-hydroxysuccinimide chemistry. The PEG-modified, ß-glucosidase-immobilized magnetic iron oxide nanoparticles (PEG-ß-Glu-MNPs were characterized by hydrodynamic diameter distribution, zeta potential, Fourier transform infrared spectroscopy, transmission electron microscopy, and a superconducting quantum interference device. The results showed that the multidomain structure and magnetization properties of these nanoparticles were conserved well throughout the synthesis steps, with an expected diameter increase and zeta potential shifts. The Michaelis constant was calculated to evaluate the activity of conjugated ß-glucosidase on the magnetic iron oxide nanoparticles, indicating 73.0% and 65.4% of enzyme activity remaining for ß-Glu-MNP and PEG-ß-Glu-MNP, respectively. Both magnetophoretic mobility analysis and pharmacokinetics showed improved in vitro/in vivo stability of PEG-ß-Glu-MNP compared with ß-Glu-MNP. In vivo magnetic targeting of PEG-ß-Glu-MNP was confirmed by magnetic resonance imaging and electron spin resonance analysis in a mouse model of subcutaneous 9L-glioma. Satisfactory accumulation of PEG-ß-Glu-MNP in tumor tissue was successfully achieved, with an iron content of 627±45 nmol Fe/g tissue and ß-glucosidase activity of 32.2±8.0 mU/g tissue.Keywords: ß-glucosidase, enzyme

  5. Effect of daily consumption of probiotic yoghurt on serum levels of calcium, iron and liver enzymes in pregnant women

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    Zatollah Asemi

    2013-01-01

    Conclusions: Consumption of probiotic yogurt among pregnant women resulted in maintaining serum calcium levels compared with the conventional yogurt; however, it could not affect serum iron, ALT and AST levels.

  6. LIVER IRON CONTENT (LIC IN ADULTS WITH NON-TRANSFUSION DEPENDENT SICKLE CELL DISEASE (NT-SCD. CORRELATION WITH SERUM FERRITIN AND LIVER ENZYMES CONCENTRATIONS

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    Vincenzo De Sanctis

    2017-06-01

    Full Text Available Abstract. Introduction: Sickle cell disease (SCD is an important cause of morbidity and mortality worldwide, causing damage and dysfunction in multiple organs. The complications of this disease are numerous, affect every organ and/or tissue in the body and vary considerably among patients over the time which challenge its management. Aim of our study: To determine the iron status of 17 patients with NT-SCD patients and 6 patients with TD- SCD using both serum ferritin level (SF and Ferriscan® evaluation of liver iron content (LIC and correlate values of LIC on the one hand with SF levels and some hepatic functions (ALT, AST, ALP and albumin.  Results: 17 adults with NT-SCD (n = 17, age: 32±15 years were studied.  Seven of NT-SCD had serum ferritin > 500 μg/L, 4 out of the seven had high liver iron measured by FerriScan®  (> 30 mg/kg/ tissue dry weight - DW.  Two patients had high liver iron content despite a concomitant serum ferritin concentration < 500 μg/L.  Two patients had high serum ferritin (1.117 μg/L and 675 μg/L while their LIC was normal (< 30 mg/kg/DW.  5 patients had elevated ALT and/or AST concentrations. In TD-SCD (n = 6, age = 25 ±11 years, 2 patients had serum ferritin <500 μg/L, one of them had high LIC (127 mg/kg/DW. Liver enzymes were high in two patients.  Serum ferritin concentration was correlated significantly with LIC  (r = 0.85, p < 0.001. Neither serum ferritin level, nor LIC was correlated significantly with hepatic enzyme levels. Conclusions:  A significant number of our patients with ND-SCD had high LIC , high serum ferritin and elevated hepatic enzymes (ALT and AST. Despite some  limitations of our study (small NT-SCD cohort,  these findings have important clinical implications. We recommend  to measure serum ferritin and LIC in NT-SCD patients to apply therapeutic preventive measures with iron chelation therapy in patients with high LIC.

  7. 10th NTES Conference: Nickel and Arsenic Compounds Alter the Epigenome of Peripheral Blood Mononuclear Cells.

    Science.gov (United States)

    Brocato, Jason; Costa, Max

    2015-01-01

    The mechanisms that underlie metal carcinogenesis are the subject of intense investigation; however, data from in vitro and in vivo studies are starting to piece together a story that implicates epigenetics as a key player. Data from our lab has shown that nickel compounds inhibit dioxygenase enzymes by displacing iron in the active site. Arsenic is hypothesized to inhibit these enzymes by diminishing ascorbate levels--an important co-factor for dioxygenases. Inhibition of histone demethylase dioxygenases can increase histone methylation levels, which also may affect gene expression. Recently, our lab conducted a series of investigations in human subjects exposed to high levels of nickel or arsenic compounds. Global levels of histone modifications in peripheral blood mononuclear cells (PBMCs) from exposed subjects were compared to low environmentally exposed controls. Results showed that nickel increased H3K4me3 and decreased H3K9me2 globally. Arsenic increased H3K9me2 and decreased H3K9ac globally. Other histone modifications affected by arsenic were sex-dependent. Nickel affected the expression of 2756 genes in human PBMCs and many of the genes were involved in immune and carcinogenic pathways. This review will describe data from our lab that demonstrates for the first time that nickel and arsenic compounds affect global levels of histone modifications and gene expression in exposed human populations.

  8. Lipid peroxidation, antioxidant enzymes and glutathione levels in human erythrocytes exposed to colloidal iron hydroxide in vitro

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    Ferreira A.L.A.

    1999-01-01

    Full Text Available The free form of the iron ion is one of the strongest oxidizing agents in the cellular environment. The effect of iron at different concentrations (0, 1, 5, 10, 50, and 100 µM Fe3+ on the normal human red blood cell (RBC antioxidant system was evaluated in vitro by measuring total (GSH and oxidized (GSSG glutathione levels, and superoxide dismutase (SOD, catalase, glutathione peroxidase (GSH-Px and reductase (GSH-Rd activities. Membrane lipid peroxidation was assessed by measuring thiobarbituric acid reactive substance (TBARS. The RBC were incubated with colloidal iron hydroxide and phosphate-buffered saline, pH 7.45, at 37oC, for 60 min. For each assay, the results for the control group were: a GSH = 3.52 ± 0.27 µM/g Hb; b GSSG = 0.17 ± 0.03 µM/g Hb; c GSH-Px = 19.60 ± 1.96 IU/g Hb; d GSH-Rd = 3.13 ± 0.17 IU/g Hb; e catalase = 394.9 ± 22.8 IU/g Hb; f SOD = 5981 ± 375 IU/g Hb. The addition of 1 to 100 µM Fe3+ had no effect on the parameters analyzed. No change in TBARS levels was detected at any of the iron concentrations studied. Oxidative stress, measured by GSH kinetics over time, occurs when the RBC are incubated with colloidal iron hydroxide at concentrations higher than 10 µM of Fe3+. Overall, these results show that the intact human RBC is prone to oxidative stress when exposed to Fe3+ and that the RBC has a potent antioxidant system that can minimize the potential damage caused by acute exposure to a colloidal iron hydroxide in vitro.

  9. 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.

  10. Iron-dependent hydrogenases of Entamoeba histolytica and Giardia lamblia: activity of the recombinant entamoebic enzyme and evidence for lateral gene transfer.

    Science.gov (United States)

    Nixon, Julie E J; Field, Jessica; McArthur, Andrew G; Sogin, Mitchell L; Yarlett, Nigel; Loftus, Brendan J; Samuelson, John

    2003-02-01

    Entamoeba histolytica and Spironucleus barkhanus have genes that encode short iron-dependent hydrogenases (Fe-hydrogenases), even though these protists lack hydrogenosomes. To understand better the biochemistry of the protist Fe-hydrogenases, we prepared a recombinant E. histolytica short Fe-hydrogenase and measured its activity in vitro. A Giardia lamblia gene encoding a short Fe-hydrogenase was identified from shotgun genomic sequences, and RT-PCR showed that cultured entamoebas and giardias transcribe short Fe-hydrogenase mRNAs. A second E. histolytica gene, which encoded a long Fe-hydrogenase, was identified from shotgun genomic sequences. Phylogenetic analyses suggested that the short Fe-hydrogenase genes of entamoeba and diplomonads share a common ancestor, while the long Fe-hydrogenase gene of entamoeba appears to have been laterally transferred from a bacterium. These results are discussed in the context of competing ideas for the origins of genes encoding fermentation enzymes of these protists.

  11. New route to the mixed valence semiquinone-catecholate based mononuclear FeIII and catecholate based dinuclear MnIII complexes: first experimental evidence of valence tautomerism in an iron complex.

    Science.gov (United States)

    Shaikh, Nizamuddin; Goswami, Sanchita; Panja, Anangamohan; Wang, Xin-Yi; Gao, Song; Butcher, Ray J; Banerjee, Pradyot

    2004-09-20

    The semiquinone-catecholate based mixed valence complex, [FeIII(bispicen)(Cl4Cat)(Cl4SQ)] x DMF (1), and catecholate based (H2bispictn)[Mn2III(Cl4Cat)4(DMF)2] (2) (bispicen = N,N'-bis(2-pyridylmethyl)-1,2-ethanediamine, bispictn = N,N'-bis(2-pyridylmethyl)-1,3-propanediamine, Cl4Cat = tetrachlorocatecholate dianion, and Cl4SQ = tetrachlorosemiquinone radical anion) were synthesized directly utilizing a facile route. Both the complexes have been characterized by single crystal X-ray diffraction study. The electronic structures have been elucidated by UV-vis-NIR absorption spectroscopy, cyclic voltammetry, EPR, and magnetic properties. The structural as well as spectroscopic features support the mixed valence tetrachlorosemiquinone-tetrachlorocatecholate charge distribution in 1. The ligand based mixed valence state was further confirmed by the presence of an intervalence charge transfer (IVCT) band in the 1900 nm region both in solution and in the solid. The intramolecular electron transfer, a phenomenon known as valence tautomerism (VT), has been followed by electronic absorption spectroscopy. For 1, the isomeric form [FeIII(bispicen)(Cl4Cat)(Cl4SQ)] is favored at low temperature, while at an elevated temperature, the [FeII(bispicen)(Cl4SQ)2] redox isomer dominates. Infrared as well as UV-vis-NIR spectral characterization for 2 suggest that the MnIII(Cat)2- moiety is admixed with its mixed valence semiquinone-catecholate isomer MnII(SQ)(Cat)-, and the electronic absorption spectrum is dominated by the mixed charged species. The origin of the intervalence charge transfer band in the 1900 nm range is associated with the mixed valence form, MnII(Cl4Cat)(Cl4SQ)-. The observation of VT in complex 1 is the first example where a mixed valence semiquinone-catecholate iron(III) complex undergoes intramolecular electron transfer similar to manganese and cobalt complexes.

  12. 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.

  13. Bacterial degradation of tert-amyl alcohol proceeds via hemiterpene 2-methyl-3-buten-2-ol by employing the tertiary alcohol desaturase function of the Rieske nonheme mononuclear iron oxygenase MdpJ.

    Science.gov (United States)

    Schuster, Judith; Schäfer, Franziska; Hübler, Nora; Brandt, Anne; Rosell, Mònica; Härtig, Claus; Harms, Hauke; Müller, Roland H; Rohwerder, Thore

    2012-03-01

    Tertiary alcohols, such as tert-butyl alcohol (TBA) and tert-amyl alcohol (TAA) and higher homologues, are only slowly degraded microbially. The conversion of TBA seems to proceed via hydroxylation to 2-methylpropan-1,2-diol, which is further oxidized to 2-hydroxyisobutyric acid. By analogy, a branched pathway is expected for the degradation of TAA, as this molecule possesses several potential hydroxylation sites. In Aquincola tertiaricarbonis L108 and Methylibium petroleiphilum PM1, a likely candidate catalyst for hydroxylations is the putative tertiary alcohol monooxygenase MdpJ. However, by comparing metabolite accumulations in wild-type strains of L108 and PM1 and in two mdpJ knockout mutants of strain L108, we could clearly show that MdpJ is not hydroxylating TAA to diols but functions as a desaturase, resulting in the formation of the hemiterpene 2-methyl-3-buten-2-ol. The latter is further processed via the hemiterpenes prenol, prenal, and 3-methylcrotonic acid. Likewise, 3-methyl-3-pentanol is degraded via 3-methyl-1-penten-3-ol. Wild-type strain L108 and mdpJ knockout mutants formed isoamylene and isoprene from TAA and 2-methyl-3-buten-2-ol, respectively. It is likely that this dehydratase activity is catalyzed by a not-yet-characterized enzyme postulated for the isomerization of 2-methyl-3-buten-2-ol and prenol. The vitamin requirements of strain L108 growing on TAA and the occurrence of 3-methylcrotonic acid as a metabolite indicate that TAA and hemiterpene degradation are linked with the catabolic route of the amino acid leucine, including an involvement of the biotin-dependent 3-methylcrotonyl coenzyme A (3-methylcrotonyl-CoA) carboxylase LiuBD. Evolutionary aspects of favored desaturase versus hydroxylation pathways for TAA conversion and the possible role of MdpJ in the degradation of higher tertiary alcohols are discussed.

  14. The ubiquity of iron.

    Science.gov (United States)

    Frey, Perry A; Reed, George H

    2012-09-21

    The importance of iron in living systems can be traced to the many complexes within which it is found, to its chemical mobility in undergoing oxidation-reduction reactions, and to the abundance of iron in Earth's crust. Iron is the most abundant element, by mass, in the Earth, constituting about 80% of the inner and outer cores of Earth. The molten outer core is about 8000 km in diameter, and the solid inner core is about 2400 km in diameter. Iron is the fourth most abundant element in Earth's crust. It is the chemically functional component of mononuclear iron complexes, dinuclear iron complexes, [2Fe-2S] and [4Fe-4S] clusters, [Fe-Ni-S] clusters, iron protophorphyrin IX, and many other complexes in protein biochemistry. Metals such as nickel, cobalt, copper, and manganese are present in the crust and could in principle function chemically in place of iron, but they are scarce in Earth's crust. Iron is plentiful because of its nuclear stability in stellar nuclear fusion reactions. It seems likely that other solid planets, formed by the same processes as Earth, would also foster the evolution of life and that iron would be similarly important to life on those planets as it is on Earth.

  15. Identification of enzymes involved in anaerobic benzene degradation by a strictly anaerobic iron-reducing enrichment culture.

    Science.gov (United States)

    Abu Laban, Nidal; Selesi, Draženka; Rattei, Thomas; Tischler, Patrick; Meckenstock, Rainer U

    2010-10-01

    Anaerobic benzene degradation was studied with a highly enriched iron-reducing culture (BF) composed of mainly Peptococcaceae-related Gram-positive microorganisms. The proteomes of benzene-, phenol- and benzoate-grown cells of culture BF were compared by SDS-PAGE. A specific benzene-expressed protein band of 60 kDa, which could not be observed during growth on phenol or benzoate, was subjected to N-terminal sequence analysis. The first 31 amino acids revealed that the protein was encoded by ORF 138 in the shotgun sequenced metagenome of culture BF. ORF 138 showed 43% sequence identity to phenylphosphate carboxylase subunit PpcA of Aromatoleum aromaticum strain EbN1. A LC/ESI-MS/MS-based shotgun proteomic analysis revealed other specifically benzene-expressed proteins with encoding genes located adjacent to ORF 138 on the metagenome. The protein products of ORF 137, ORF 139 and ORF 140 showed sequence identities of 37% to phenylphosphate carboxylase PpcD of A. aromaticum strain EbN1, 56% to benzoate-CoA ligase (BamY) of Geobacter metallireducens and 67% to 3-octaprenyl-4-hydroxybenzoate carboxy-lyase (UbiD/UbiX) of A. aromaticum strain EbN1 respectively. These genes are proposed as constituents of a putative benzene degradation gene cluster (∼ 17 kb) composed of carboxylase-related genes. The identified gene sequences suggest that the initial activation reaction in anaerobic benzene degradation is probably a direct carboxylation of benzene to benzoate catalysed by putative anaerobic benzene carboxylase (Abc). The putative Abc probably consists of several subunits, two of which are encoded by ORFs 137 and 138, and belongs to a family of carboxylases including phenylphosphate carboxylase (Ppc) and 3-octaprenyl-4-hydroxybenzoate carboxy-lyase (UbiD/UbiX).

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

    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...

  17. Shifting redox states of the iron center partitions CDO between crosslink formation or cysteine oxidation.

    Science.gov (United States)

    Njeri, Catherine W; Ellis, Holly R

    2014-09-15

    Cysteine dioxygenase (CDO) is a mononuclear iron-dependent enzyme that catalyzes the oxidation of L-cysteine to L-cysteine sulfinic acid. The mammalian CDO enzymes contain a thioether crosslink between Cys93 and Tyr157, and purified recombinant CDO exists as a mixture of the crosslinked and non crosslinked isoforms. The current study presents a method of expressing homogenously non crosslinked CDO using a cell permeative metal chelator in order to provide a comprehensive investigation of the non crosslinked and crosslinked isoforms. Electron paramagnetic resonance analysis of purified non crosslinked CDO revealed that the iron was in the EPR silent Fe(II) form. Activity of non crosslinked CDO monitoring dioxygen utilization showed a distinct lag phase, which correlated with crosslink formation. Generation of homogenously crosslinked CDO resulted in an ∼5-fold higher kcat/Km value compared to the enzyme with a heterogenous mixture of crosslinked and non crosslinked CDO isoforms. EPR analysis of homogenously crosslinked CDO revealed that this isoform exists in the Fe(III) form. These studies present a new perspective on the redox properties of the active site iron and demonstrate that a redox switch commits CDO towards either formation of the Cys93-Tyr157 crosslink or oxidation of the cysteine substrate.

  18. 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...

  19. Conditioning causes an increase in glucose transporter-4 levels in mononuclear cells in sled dogs.

    Science.gov (United States)

    Schnurr, Theresia M; Reynolds, Arleigh J; Gustafson, Sally J; Duffy, Lawrence K; Dunlap, Kriya L

    2014-10-01

    This study was designed to investigate the effects of physical conditioning on the expression of the insulin sensitive glucose transporter-4 protein (GLUT4) on mononuclear cells and HOMA-IR levels in dogs and compared to results reported in human skeletal muscle and the skeletal muscle of rodent models. Blood was sampled from conditioned dogs (n = 8) and sedentary dogs (n = 8). The conditioned dogs were exercised four months prior the experiment and were following a uniform training protocol, whereas the sedentary dogs were not. GLUT4 expression in mononuclear cells and plasma insulin levels were measured using commercially available enzyme-linked immunosorbent assay (ELISA). Blood glucose levels were determined using blood plasma. HOMA-IR was calculated using plasma insulin and blood glucose levels using the linear approximation formula. Our results indicate that the state of conditioning had a significant effect on the GLUT4 expression at the surface of mononuclear cells. HOMA-IR was also affected by conditioning in dogs. GLUT4 levels in mononuclear cells of sled dogs were inversely correlated with the homeostasis model assessment of insulin sensitivity. This study demonstrates that conditioning increases GLUT4 levels in mononuclear cells of sled dogs as it has been previously reported in skeletal muscle. Our results support the potential of white blood cells as a proxy tissue for studying insulin signaling and may lead to development of a minimally invasive and direct marker of insulin resistance. This may be the first report of GLUT4 in mononuclear cells in response to exercise and measured with ELISA.

  20. 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.

  1. Exploiting the versatility and selectivity of Mo enzymes with electrochemistry.

    Science.gov (United States)

    Bernhardt, Paul V

    2011-02-14

    This article covers recent advances in the electrochemical study of the mononuclear molybdenum enzymes. Virtually all of these enzymes catalyse a coupled 2-electron, O-atom transfer reaction on a substrate of either organic or inorganic origin. There is a remarkable commonality in structure, function and mechanism of the mononuclear Mo enzymes despite the diversity of their substrates; many that are important to environmental monitoring, food quality control and biomedical science. Mo enzymes routinely oxidise or reduce otherwise inert substrates for which there exist no rapid, simple and reliable analytical methods for their determination and as such represent a potentially rich source of proteins that may be applied in electrochemical biosensors.

  2. 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 reversible electrochemical response and offer potential application in electrochromic devices. On SnO2 films distinct spectral changes are observed in a narrow potential range (-0.5/0.9 V vs SCE) with switching times of the order of 0.8 s. (c) 2005 Elsevier B.V. All rights reserved....

  3. Comment on Neiser et al. Assessment of Dextran Antigenicity of Intravenous Iron Preparations with Enzyme-Linked Immunosorbent Assay (ELISA). Int. J. Mol. Sci. 2016, 17, 1185.

    Science.gov (United States)

    Strom, Claes C; Andreasen, Hans B

    2017-01-10

    All IV iron complexes carry a risk of potentially fatal allergic type hypersensitivity reactions. The mechanism(s) behind these reactions is unknown but the limited data available suggests that classic IgE mediated allergy is exceedingly rare, if ever occurring. Iron-carbohydrate molecules are complex nano-particles and trying to reduce the risk of serious hypersensitivity to antibody binding of an artificial antibody seems meaningless. A recently published analysis of safety data from randomized clinical trials confirms the method reported by Neiser to be useless to predict reaction risk. In conclusion, the study by Neiser et al. is biased, contains no new information, and has no clinical relevance. We are concerned that the association of the authors with a commercial entity has caused a conflict of interest that biases not only the results, but the entire experimental setup against competitors. (Comment on Neiser et al. Int. J. Mol. Sci. 2016, 17, 1185, doi:10.3390/ijms17071185).

  4. Comment on Neiser et al. Assessment of Dextran Antigenicity of Intravenous Iron Preparations with Enzyme-Linked Immunosorbent Assay (ELISA). Int. J. Mol. Sci. 2016, 17, 1185.

    OpenAIRE

    Claes C. Strom; Hans B. Andreasen

    2017-01-01

    All IV iron complexes carry a risk of potentially fatal allergic type hypersensitivity reactions. The mechanism(s) behind these reactions is unknown but the limited data available suggests that classic IgE mediated allergy is exceedingly rare, if ever occurring. Iron–carbohydrate molecules are complex nano-particles and trying to reduce the risk of serious hypersensitivity to antibody binding of an artificial antibody seems meaningless. A recently published analysis of safety data from random...

  5. Transcriptional regulation of mononuclear phagocyte development

    Directory of Open Access Journals (Sweden)

    Roxane eTussiwand

    2015-10-01

    Full Text Available IntroductionThe mononuclear-phagocyte system (MPS, which comprises dendritic cells (DCs, macrophages and monocytes, is a heterogeneous group of myeloid cells. The complexity of the MPS is equally reflected by the plasticity in function and phenotype that characterizes each subset depending on their location and activation state. Specialized subsets of Mononuclear Phagocytes (MP reside in defined anatomical locations, are critical for the homeostatic maintenance of tissues, and provide the link between innate and adaptive immune responses during infections. The ability of MP to maintain or to induce the correct tolerogenic or inflammatory milieu also resides in their complex subset specialization. Such subset heterogeneity is obtained through lineage diversification and specification, which is controlled by defined transcriptional networks and programs. Understanding the MP biology means to define their transcriptional signature, which is required during lineage commitment, and which characterizes each subset’s features. This review will focus on the transcriptional regulation of the MPS; in particular what determines lineage commitment and functional identity; we will emphasizes recent advances in the field of single cell analysis and highlight unresolved questions in the field.

  6. Iron mediates catalysis of nucleic acid processing enzymes: support for Fe(II) as a cofactor before the great oxidation event.

    Science.gov (United States)

    Okafor, C Denise; Lanier, Kathryn A; Petrov, Anton S; Athavale, Shreyas S; Bowman, Jessica C; Hud, Nicholas V; Williams, Loren Dean

    2017-03-15

    Life originated in an anoxic, Fe2+-rich environment. We hypothesize that on early Earth, Fe2+ was a ubiquitous cofactor for nucleic acids, with roles in RNA folding and catalysis as well as in processing of nucleic acids by protein enzymes. In this model, Mg2+ replaced Fe2+ as the primary cofactor for nucleic acids in parallel with known metal substitutions of metalloproteins, driven by the Great Oxidation Event. To test predictions of this model, we assay the ability of nucleic acid processing enzymes, including a DNA polymerase, an RNA polymerase and a DNA ligase, to use Fe2+ in place of Mg2+ as a cofactor during catalysis. Results show that Fe2+ can indeed substitute for Mg2+ in catalytic function of these enzymes. Additionally, we use calculations to unravel differences in energetics, structures and reactivities of relevant Mg2+ and Fe2+ complexes. Computation explains why Fe2+ can be a more potent cofactor than Mg2+ in a variety of folding and catalytic functions. We propose that the rise of O2 on Earth drove a Fe2+ to Mg2+ substitution in proteins and nucleic acids, a hypothesis consistent with a general model in which some modern biochemical systems retain latent abilities to revert to primordial Fe2+-based states when exposed to pre-GOE conditions.

  7. Iron Test

    Science.gov (United States)

    ... as: Serum Iron; Serum Fe Formal name: Iron, serum Related tests: Ferritin ; TIBC, UIBC and Transferrin ; Hemoglobin ; Hematocrit ; Complete Blood Count ; Reticulocyte Count ; Zinc Protoporphyrin ; Iron Tests ; Soluble Transferrin Receptor ... I should know? How is it used? Serum iron, total iron-binding capacity (TIBC) , and/or ...

  8. Homeostasis in the mononuclear phagocyte system.

    Science.gov (United States)

    Jenkins, Stephen J; Hume, David A

    2014-08-01

    The mononuclear phagocyte system (MPS) is a family of functionally related cells including bone marrow precursors, blood monocytes, and tissue macrophages. We review the evidence that macrophages and dendritic cells (DCs) are separate lineages and functional entities, and examine whether the traditional view that monocytes are the immediate precursors of tissue macrophages needs to be refined based upon evidence that macrophages can extensively self-renew and can be seeded from yolk sac/foetal liver progenitors with little input from monocytes thereafter. We review the role of the growth factor colony-stimulating factor (CSF)1, and present a model consistent with the concept of the MPS in which local proliferation and monocyte recruitment are connected to ensure macrophages occupy their well-defined niche in most tissues.

  9. Mononuclear Cells and Vascular Repair in HHT

    Directory of Open Access Journals (Sweden)

    Calinda eDingenouts

    2015-03-01

    Full Text Available Hereditary hemorrhagic telangiectasia (HHT or Rendu-Osler-Weber disease is a rare genetic vascular disorder known for its endothelial dysplasia causing arteriovenous malformations and severe bleedings. HHT-1 and HHT-2 are the most prevalent variants and are caused by heterozygous mutations in endoglin and ALK1, respectively. An undervalued aspect of the disease is that HHT patients experience persistent inflammation. Although endothelial and mural cells have been the main research focus trying to unravel the mechanism behind the disease, wound healing is a process with a delicate balance between inflammatory and vascular cells. Inflammatory cells are part of the mononuclear cells (MNCs fraction, and can, next to eliciting an immune response, also have angiogenic potential. This biphasic effect of MNC can hold a promising mechanism to further elucidate treatment strategies for HHT patients. Before MNC are able to contribute to repair, they need to home to and retain in ischemic and damaged tissue. Directed migration (homing of mononuclear cells following tissue damage is regulated by the stromal cell derived factor 1 (SDF1. MNCs that express the C-X-C chemokine receptor 4 (CXCR4 migrate towards the tightly regulated gradient of SDF1. This directed migration of monocytes and lymphocytes can be inhibited by dipeptidyl peptidase 4 (DPP4. Interestingly, MNC of HHT patients express elevated levels of DPP4 and show impaired homing towards damaged tissue. Impaired homing capacity of the MNCs might therefore contribute to the impaired angiogenesis and tissue repair observed in HHT patients. This review summarizes recent studies regarding the role of MNCs in the etiology of HHT and vascular repair, and evaluates the efficacy of DPP4 inhibition in tissue integrity and repair.

  10. Spectroscopic and computational studies of NTBC bound to the non-heme iron enzyme (4-hydroxyphenyl)pyruvate dioxygenase: active site contributions to drug inhibition.

    Science.gov (United States)

    Neidig, Michael L; Decker, Andrea; Kavana, Michael; Moran, Graham R; Solomon, Edward I

    2005-12-01

    (4-Hydroxyphenyl)pyruvate dioxygenase (HPPD) is an alpha-keto-acid-dependent dioxygenase which catalyzes the conversion of (4-hydroxyphenyl)pyruvate (HPP) to homogentisate as part of tyrosine catabolism. While several di- and tri-ketone alkaloids are known as inhibitors of HPPD and used commercially as herbicides, one such inhibitor, [2-nitro-4-(trifluoromethyl)benzoyl]-1,3-cyclohexanedione (NTBC), has also been used therapeutically to treat type I tyrosinemia and alkaptonuria in humans. To gain further insight into the mechanism of inhibition by NTBC, a combination of CD/MCD spectroscopy and DFT calculations of HPPD/Fe(II)/NTBC has been performed to evaluate the contribution of the Fe(II)-NTBC bonding interaction to the high affinity of this drug for the enzyme. The results indicate that the bonding of NTBC to Fe(II) is very similar to that for HPP, both involving similar pi-backbonding interactions between NTBC/HPP and Fe(II). Combined with the result that the calculated binding energy of NTBC is, in fact, approximately 3 kcal/mol less than that for HPP, the bidentate coordination of NTBC to Fe(II) is not solely responsible for its extremely high affinity for the enzyme. Thus, the pi-stacking interactions between the aromatic rings of NTBC and two phenyalanine residues, as observed in the crystallography of the HPPD/Fe(II)/NTBC complex, appear to be responsible for the observed high affinity of drug binding.

  11. Comment on Neiser et al. Assessment of Dextran Antigenicity of Intravenous Iron Preparations with Enzyme-Linked Immunosorbent Assay (ELISA. Int. J. Mol. Sci. 2016, 17, 1185.

    Directory of Open Access Journals (Sweden)

    Claes C. Strom

    2017-01-01

    Full Text Available All IV iron complexes carry a risk of potentially fatal allergic type hypersensitivity reactions. The mechanism(s behind these reactions is unknown but the limited data available suggests that classic IgE mediated allergy is exceedingly rare, if ever occurring. Iron–carbohydrate molecules are complex nano-particles and trying to reduce the risk of serious hypersensitivity to antibody binding of an artificial antibody seems meaningless. A recently published analysis of safety data from randomized clinical trials confirms the method reported by Neiser to be useless to predict reaction risk. In conclusion, the study by Neiser et al. is biased, contains no new information, and has no clinical relevance. We are concerned that the association of the authors with a commercial entity has caused a conflict of interest that biases not only the results, but the entire experimental setup against competitors. (Comment on Neiser et al. Int. J. Mol. Sci. 2016, 17, 1185, doi:10.3390/ijms17071185.

  12. 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

  13. Spectroscopic and Kinetic Characterization of Peroxidase-Like π-Cation Radical Pinch-Porphyrin-Iron(III Reaction Intermediate Models of Peroxidase Enzymes

    Directory of Open Access Journals (Sweden)

    Samuel Hernández Anzaldo

    2016-06-01

    Full Text Available The spectroscopic and kinetic characterization of two intermediates from the H2O2 oxidation of three dimethyl ester [(proto, (meso, (deuteroporphyrinato (picdien]Fe(III complexes ([FePPPic], [FeMPPic] and [FeDPPic], respectively pinch-porphyrin peroxidase enzyme models, with s = 5/2 and 3/2 Fe(III quantum mixed spin (qms ground states is described herein. The kinetic study by UV/Vis at λmax = 465 nm showed two different types of kinetics during the oxidation process in the guaiacol test for peroxidases (1–3 + guaiacol + H2O2 → oxidation guaiacol products. The first intermediate was observed during the first 24 s of the reaction. When the reaction conditions were changed to higher concentration of pinch-porphyrins and hydrogen peroxide only one type of kinetics was observed. Next, the reaction was performed only between pinch-porphyrins-Fe(III and H2O2, resulting in only two types of kinetics that were developed during the first 0–4 s. After this time a self-oxidation process was observed. Our hypotheses state that the formation of the π-cation radicals, reaction intermediates of the pinch-porphyrin-Fe(III family with the ligand picdien [N,N’-bis-pyridin-2-ylmethyl-propane-1,3-diamine], occurred with unique kinetics that are different from the overall process and was involved in the oxidation pathway. UV-Vis, 1H-NMR and ESR spectra confirmed the formation of such intermediates. The results in this paper highlight the link between different spectroscopic techniques that positively depict the kinetic traits of artificial compounds with enzyme-like activity.

  14. Mycobacterium tuberculosis-specific immunospot assay of pleural exudate mononuclear cells is useful for the exclusion of tuberculous pleuritis in patients with lupus pleuritis.

    Science.gov (United States)

    Takase, K; Ohno, S; Ideguchi, H; Murakami, S; Takeno, M; Ishigatsubo, Y

    2009-02-01

    It is often difficult to make a diagnosis of pleuritis associated with rheumatic diseases because of lack of specific diagnostic tools. We report a patient with lupus pleuritis from which tuberculous pleuritis was distinguished by Mycobacterium tuberculosis-specific enzyme-linked immunospot assay of pleural exudate mononuclear cells. After the diagnosis of lupus pleuritis, the patient was successfully treated with prednisolone.

  15. Pectic enzymes

    NARCIS (Netherlands)

    Benen, J.A.E.; Voragen, A.G.J.; Visser, J.

    2003-01-01

    The pectic enzymes comprise a diverse group of enzymes. They consist of main-chain depolymerases and esterases active on methyl- and acetylesters of galacturonosyl uronic acid residues. The depolymerizing enzymes comprise hydrolases as wel as lyases

  16. Pectic enzymes

    NARCIS (Netherlands)

    Benen, J.A.E.; Voragen, A.G.J.; Visser, J.

    2003-01-01

    The pectic enzymes comprise a diverse group of enzymes. They consist of main-chain depolymerases and esterases active on methyl- and acetylesters of galacturonosyl uronic acid residues. The depolymerizing enzymes comprise hydrolases as wel as lyases

  17. Enzyme assays.

    Science.gov (United States)

    Reymond, Jean-Louis; Fluxà, Viviana S; Maillard, Noélie

    2009-01-07

    Enzyme assays are analytical tools to visualize enzyme activities. In recent years a large variety of enzyme assays have been developed to assist the discovery and optimization of industrial enzymes, in particular for "white biotechnology" where selective enzymes are used with great success for economically viable, mild and environmentally benign production processes. The present article highlights the aspects of fluorogenic and chromogenic substrates, sensors, and enzyme fingerprinting, which are our particular areas of interest.

  18. Iron deficiency.

    Science.gov (United States)

    Scrimshaw, N S

    1991-10-01

    The world's leading nutritional problem is iron deficiency. 66% of children and women aged 15-44 years in developing countries have it. Further, 10-20% of women of childbearing age in developed countries are anemic. Iron deficiency is identified with often irreversible impairment of a child's learning ability. It is also associated with low capacity for adults to work which reduces productivity. In addition, it impairs the immune system which reduces the body's ability to fight infection. Iron deficiency also lowers the metabolic rate and the body temperature when exposed to cold. Hemoglobin contains nearly 73% of the body's iron. This iron is always being recycled as more red blood cells are made. The rest of the needed iron does important tasks for the body, such as binds to molecules that are reservoirs of oxygen for muscle cells. This iron comes from our diet, especially meat. Even though some plants, such as spinach, are high in iron, the body can only absorb 1.4-7% of the iron in plants whereas it can absorb 20% of the iron in red meat. In many developing countries, the common vegetarian diets contribute to high rates of iron deficiency. Parasitic diseases and abnormal uterine bleeding also promote iron deficiency. Iron therapy in anemic children can often, but not always, improve behavior and cognitive performance. Iron deficiency during pregnancy often contributes to maternal and perinatal mortality. Yet treatment, if given to a child in time, can lead to normal growth and hinder infections. However, excess iron can be damaging. Too much supplemental iron in a malnourished child promotes fatal infections since the excess iron is available for the pathogens use. Many countries do not have an effective system for diagnosing, treating, and preventing iron deficiency. Therefore a concerted international effort is needed to eliminate iron deficiency in the world.

  19. Mononuclear diastereopure non-heme Fe(II) complexes of pentadentate ligands with pyrrolidinyl moieties: structural studies, and alkene and sulfide oxidation

    NARCIS (Netherlands)

    Gosiewska, S.; Lutz, M.; Spek, A.L.; Klein Gebbink, R.J.M.

    2007-01-01

    Mononuclear iron(II) complexes of enantiopure Py(ProOH)2 (2) and Py(ProPh2OH)2(3) ligands have been prepared with FeCl2 and Fe(OTf)2 . 2MeCN. Both ligands coordinate to the metal in a pentadentate fashion. Next to the meridional N,N',N-coordination of the ligand, additional coordination of the

  20. [Iron metabolism, overview and recent insights].

    Science.gov (United States)

    Omar, S; Feki, M; Kaabachi, N

    2006-01-01

    The paper is an up to date overview of knowledge on iron metabolism that integrate recent findings in this field. Significant advances were made in understanding the implication of protein factors (transporters, enzymes and regulation factors) in iron metabolism, as well as related genetic abnormalities. The research highlighted the complexity of mechanisms in charge of maintaining equilibrium of Fe in the body. The iron is vital to the life of cells, but its presence in excess is rather toxic. Iron is mostly required for hemoglobin synthesis. It is recycled between reticulo-endothelial macrophages and bone marrow that is the main user of iron. Intestinal absorption is a key step in determining iron capital in the body. Its rate is tightly controlled by several factors that act under influence of signals of unknown nature, which indicate iron needs and storage. The IRP/IRE (iron regulatory protein/iron responsive element) system controls cellular uptake, stores and exportation of iron, and heme synthesis. Mitochondrion is a dynamo of iron metabolism, being vital for heme synthesis and iron sulphur cluster genesis. The recent discovery of several mitochondrial proteins involved in iron metabolism resulted in better understanding mitochondrial iron movement, storage and exchange. Nevertheless, much remains to be known on the role of some actors such as HFE protein, hepcidin, hemojuvelin and transferrin receptor 2, and to determine the nature and mechanisms of signals regulating iron level in the body.

  1. Native iron

    DEFF Research Database (Denmark)

    Brooks, Charles Kent

    2015-01-01

    , a situation unique in the Solar System. In such a world, iron metal is unstable and, as we all know, oxidizes to the ferric iron compounds we call 'rust'. If we require iron metal it must be produced at high temperatures by reacting iron ore, usually a mixture of ferrous (Fe2+) and ferric (Fe3+) oxides (Fe2O3......, hematite, or FeO.Fe2O3, magnetite), with carbon in the form of coke. This is carried out in a blast furnace. Although the Earth's core consists of metallic iron, which may also be present in parts of the mantle, this is inaccessible to us, so we must make our own. In West Greenland, however, some almost...... unique examples of iron metal, otherwise called 'native iron' or 'telluric iron', occur naturally....

  2. 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.

  3. A Mononuclear Carboxylate-Rich Oxoiron(IV) Complex: a Structural and Functional Mimic of TauD Intermediate 'J'

    Science.gov (United States)

    McDonald, Aidan R; Guo, Yisong; Vu, Van V; Bominaar, Emile L; Münck, Eckard; Que, Lawrence

    2012-01-01

    The pentadentate ligand (n)Bu-P2DA (2(b), (n)Bu-P2DA = N-(1',1'-bis(2-pyridyl)pentyl)iminodiacetate) was designed to bind an iron center in a carboxylate-rich environment similar to that found in the active sites of TauD and other α-ketoglutarate-dependent mononuclear non-heme iron enzymes. The iron(II) complex (n)Bu(4)N[Fe(II)(Cl)((n)Bu-P2DA)] (3(b)-Cl) was synthesized and crystallographically characterized to have a 2-pyridine-2-carboxylate donor set in the plane perpendicular to the Fe-Cl bond. Reaction of 3(b)-Cl with N-heterocyclic amines such as pyridine or imidazole yielded the N-heterocyclic amine adducts [Fe(II)(N)((n)Bu-P2DA)]. These adducts in turn reacted with oxo-transfer reagents at -95 °C to afford a short-lived oxoiron(IV) complex [Fe(IV)(O)((n)Bu-P2DA)] (5(b)) in yields as high as 90% depending on the heterocycle used. Complex 5(b) exhibits near-IR absorption features (λ(max) = 770 nm) and Mossbauer parameters (δ = 0.04 mm/s; ΔE(Q) = 1.13 mm/s; D = 27±2 cm(-1)) characteristic of an S = 1 oxoiron(IV) species. Direct evidence for an Fe=O bond of 1.66 Å was found from EXAFS analysis. DFT calculations on 5(b) in its S =1 spin state afforded a geometry-optimized structure consistent with the EXAFS data. They further demonstrated that the replacement of two pyridine donors in [Fe(IV)(O)(N4Py)](2+) (N4Py = N,N-(bis(2-pyridyl)methyl)N-bis(2-pyridylmethyl)amine) with carboxylate donors in 5(b) decreased the energy gap between the ground S = 1 and the excited S = 2 states, reflecting the weaker equatorial ligand field of 5(b) and accounting for its larger D value. Complex 5(b) reacted readily with dihydrotoluene, methyldiphenylphosphine and ferrocene at -60 °C, and in all cases was approximately a 5-fold more reactive oxidant than [Fe(IV)(O)(N4Py)](2+). The reactivity differences between these two complexes may arise from a combination of electronic and steric factors. Carboxylate-rich 5(b) represents the closest structural mimic reported thus far of

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

    Energy Technology Data Exchange (ETDEWEB)

    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.

  5. Iron Homeostasis and Nutritional Iron Deficiency123

    OpenAIRE

    2011-01-01

    Nonheme food ferritin (FTN) iron minerals, nonheme iron complexes, and heme iron contribute to the balance between food iron absorption and body iron homeostasis. Iron absorption depends on membrane transporter proteins DMT1, PCP/HCP1, ferroportin (FPN), TRF2, and matriptase 2. Mutations in DMT1 and matriptase-2 cause iron deficiency; mutations in FPN, HFE, and TRF2 cause iron excess. Intracellular iron homeostasis depends on coordinated regulation of iron trafficking and storage proteins enc...

  6. Cytotoxicity of bovine and porcine collagen membranes in mononuclear cells.

    Science.gov (United States)

    Moura, Camilla Christian Gomes; Soares, Priscilla Barbosa Ferreira; Carneiro, Karine Fernandes; Souza, Maria Aparecida de; Magalhães, Denildo

    2012-01-01

    This study compared the cytotoxicity and the release of nitric oxide induced by collagen membranes in human mononuclear cells. Peripheral blood was collected from each patient and the separation of mononuclear cells was performed by Ficoll. Then, 2x10(5) cells were plated in 48-well culture plates under the membranes in triplicate. The polystyrene surface was used as negative control. Cell viability was assessed by measuring mitochondrial activity (MTT) at 4, 12 and 24 h, with dosage levels of nitrite by the Griess method for the same periods. Data had non-normal distribution and were analyzed by the Kruskal-Wallis test (pporcine membrane induced a higher release of nitrite compared with the control and bovine membrane, respectively (pporcine collagen membrane induces an increased production of proinflammatory mediators by mononuclear cells in the first hours of contact, decreasing with time.

  7. ACTIVATION OF HUMAN BLOOD MONONUCLEARS BY LIPOPOLYSACCHARIDE OF DIFFERENT COMPOSITION

    Directory of Open Access Journals (Sweden)

    S. V. Zubova

    2010-01-01

    Full Text Available Influence of lipopolysaccharide (LPS composition upon activation of human blood mononuclears was investigated, by measuring levels of pro-inflammatory TNFα and IL-6 cytokines released by the cells. It is shown that LPS from Rhodobacter capsulatus PG, in contrast to E. coli LPS, did not activate the target cells for synthesis of the cytokines.

  8. Iron load

    Directory of Open Access Journals (Sweden)

    Filippo Cassarà

    2013-03-01

    Full Text Available Recent research addressed the main role of hepcidin in the regulation of iron metabolism. However, while this mechanism could be relevant in causing iron load in Thalassemia Intermedia and Sickle-Cell Anemia, its role in Thalassemia Major (TM is marginal. This is mainly due to the high impact of transfusional requirement into the severe increase of body iron. Moreover, the damage of iron load may be worsened by infections, as HCV hepatitis, or liver and endocrinological damage. One of the most relevant associations was found between splenectomy and increase of risk for mortality due,probably, to more severe iron load. These issues suggest as morbidity and mortality of this group of patients they do not depend only by our ability in controlling heart damage but even in preventing or treating particular infections and complications. This finding is supported by the impairment of survival curves in patients with complications different from heart damage. However, because, during recent years different direct and indirect methods to detect iron overload in patients affected by secondary hemochromatosis have been implemented, our ability to maintain under control iron load is significantly improved. Anyway, the future in iron load management remains to be able to have an iron load map of our body for targeting chelation and other medical treatment according to the single organ damage.

  9. Iron refractory iron deficiency anemia

    OpenAIRE

    De Falco, Luigia; Sanchez, Mayka; Silvestri, Laura; Kannengiesser, Caroline; Muckenthaler, Martina U; Iolascon, Achille; Gouya, Laurent; Camaschella, Clara; Beaumont, Carole

    2013-01-01

    Iron refractory iron deficiency anemia is a hereditary recessive anemia due to a defect in the TMPRSS6 gene encoding Matriptase-2. This protein is a transmembrane serine protease that plays an essential role in down-regulating hepcidin, the key regulator of iron homeostasis. Hallmarks of this disease are microcytic hypochromic anemia, low transferrin saturation and normal/high serum hepcidin values. The anemia appears in the post-natal period, although in some cases it is only diagnosed in ad...

  10. Effects of heme iron enriched peptide on iron deficiency anemia in rats.

    Science.gov (United States)

    Tang, Ning; Chen, Le-qun; Zhuang, Hong

    2014-02-01

    The present study aims to investigate whether a daily intake of heme iron enriched peptide obtained from bovine hemoglobin is effective in alleviating iron deficiency anemia (IDA). Wistar rats were randomly divided into six groups: a control group, an anemic group not treated, and anemic groups treated with FeSO4 or with the heme iron enriched peptide at low, moderate or high doses. The rats in the anemic groups were fed on a low-iron diet to establish the iron deficiency anemia model. After the model had been established, different doses of heme iron enriched peptide were given to the rats once a day via intragastric administration. After the iron supplement administration, it was observed that heme iron enriched peptide had effective restorative action returning the hemoglobin, red blood cells, hematocrit, mean corpuscular volume, mean corpuscular hemoglobin concentration and serum iron in IDA animals to normal values or better. In addition, compared with FeSO4, higher Fe bioavailability and fewer side effects were observed. The rats in the moderate dose group had the highest apparent Fe absorption. Moreover, in vivo antioxidant activity was also observed, enhancing the activities of antioxidant enzymes and reduced malondialdehyde levels in IDA rats. Furthermore, the heme iron enriched peptide also exhibited strong in vitro antioxidant activities. In conclusion, heme iron enriched peptide significantly alleviated iron deficiency anemia, and exhibited strong in vitro and in vivo antioxidant activities. This suggests that heme iron enriched peptide might be exploited as a safe, efficient new iron supplement.

  11. 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...

  12. The role of ceruloplasmin in iron metabolism.

    Science.gov (United States)

    Roeser, H P; Lee, G R; Nacht, S; Cartwright, G E

    1970-12-01

    The importance of ceruloplasmin in iron metabolism was studied in swine made hypoceruloplasminemic by copper deprivation. When the plasma ceruloplasmin level fell below 1% of normal, cell-to-plasma iron flow became sufficiently impaired to cause hypoferremia, even though total body iron stores were normal. When ceruloplasmin was administered to such animals, plasma iron increased immediately and continued to rise at a rate proportional to the logarithm of the ceruloplasmin dose. The administration of inorganic copper induced increases in plasma iron only after ceruloplasmin appeared in the circulation. Thus, ceruloplasmin appeared to be essential to the normal movement of iron from cells to plasma. Studies designed to define the mechanism of action of ceruloplasmin were based on the in vitro observation that ceruloplasmin behaves as an enzyme (ferroxidase) that catalyzes oxidation of ferrous iron. Retention of injected ferrous iron in the plasma of ceruloplasmin-deficient swine was significantly less than that of ferric iron, reflecting impaired transferrin iron binding. Rat ceruloplasmin, which has little ferroxidase activity, was much less effective than porcine or human ceruloplasmin in inducing increases in plasma iron. These observations suggest that ceruloplasmin acts by virtue of its ferroxidase activity. Eight patients with Wilson's disease were evaluated in order to investigate iron metabolism in a disorder characterized by reduced ceruloplasmin levels. Evidence of iron deficiency was found in six of these, and in five of the six, plasma ceruloplasmin was less than 5% of normal. In comparison, the two patients without evidence of iron deficiency had ceruloplasmin levels of 11 and 18% of normal. It is suggested that iron deficiency tends to occur in those patients with Wilson's disease who have the severest degrees of hypoceruloplasminemia, possibly because of defective transfer of iron from intestinal mucosal cells to plasma.

  13. On the active site of mononuclear B1 metallo β-lactamases: a computational study

    Science.gov (United States)

    Sgrignani, Jacopo; Magistrato, Alessandra; Dal Peraro, Matteo; Vila, Alejandro J.; Carloni, Paolo; Pierattelli, Roberta

    2012-04-01

    Metallo-β-lactamases (MβLs) are Zn(II)-based bacterial enzymes that hydrolyze β-lactam antibiotics, hampering their beneficial effects. In the most relevant subclass (B1), X-ray crystallography studies on the enzyme from Bacillus Cereus point to either two zinc ions in two metal sites (the so-called `3H' and `DCH' sites) or a single Zn(II) ion in the 3H site, where the ion is coordinated by Asp120, Cys221 and His263 residues. However, spectroscopic studies on the B1 enzyme from B. Cereus in the mono-zinc form suggested the presence of the Zn(II) ion also in the DCH site, where it is bound to an aspartate, a cysteine, a histidine and a water molecule. A structural model of this enzyme in its DCH mononuclear form, so far lacking, is therefore required for inhibitor design and mechanistic studies. By using force field based and mixed quantum-classical (QM/MM) molecular dynamics (MD) simulations of the protein in aqueous solution we constructed such structural model. The geometry and the H-bond network at the catalytic site of this model, in the free form and in complex with two common β-lactam drugs, is compared with experimental and theoretical findings of CphA and the recently solved crystal structure of new B2 MβL from Serratia fonticola (Sfh-I). These are MβLs from the B2 subclass, which features an experimentally well established mono-zinc form, in which the Zn(II) is located in the DCH site. From our simulations the ɛɛδ and δɛδ protomers emerge as possible DCH mono-zinc reactive species, giving a novel contribution to the discussion on the MβL reactivity and to the drug design process.

  14. Supramolecular control of a mononuclear biomimetic copper(II) center: bowl complexes vs funnel complexes.

    Science.gov (United States)

    Gout, Jérôme; Višnjevac, Aleksandar; Rat, Stéphanie; Parrot, Arnaud; Hessani, Assia; Bistri, Olivia; Le Poul, Nicolas; Le Mest, Yves; Reinaud, Olivia

    2014-06-16

    Modeling the mononuclear site of copper enzymes is important for a better understanding of the factors controlling the reactivity of the metal center. A major difficulty stems from the difficult control of the nuclearity while maintaining free sites open to coordination of exogenous ligands. A supramolecular approach consists in associating a hydrophobic cavity to a tripodal ligand that will define the coordination spheres as well as access to the metal ion. Here, we describe the synthesis of a bowl Cu(II) complex based on the resorcinarene scaffold. This study supplements a previous work on Cu(I) coordination. It provides a complete picture of the cavity-copper system in its two oxidation states. The first XRD structure of such a bowl complex was obtained, evidencing a 5-coordinate Cu(II) ion with the three imidazole donors bound to the metal (two in the base of the pyramid, one in the apical position) and with an acetate anion, completing the base of the pyramid, and deeply included in the bowl. Solution studies conducted by EPR and UV-vis absorption spectroscopies as well as cyclic voltammetry highlighted interaction with coordinating solvents, various carboxylates that can sit either in the endo or in the exo position depending on their size as well as possible stabilization of hydroxo species in a mononuclear state. A comparison of the binding and redox properties of the bowl complex with funnel complexes based on the calix[6]arene core further highlights the importance of supramolecular features defining the first, second, and third coordination sphere for control of the metal ion.

  15. Bone marrow mononuclears from murine tibia after spaceflight on biosatellite

    Science.gov (United States)

    Andreeva, Elena; Roe, Maria; Buravkova, Ludmila; Andrianova, Irina; Goncharova, Elena; Gornostaeva, Alexandra

    Elucidation of the space flight effects on the adult stem and progenitor cells is an important goal in space biology and medicine. A unique opportunity for this is provided by project "BION -M1". The purpose of this study was to evaluate the effects of a 30-day flight on biosatellite "BION - M1" and the subsequent 7-day recovery on the quantity, viability, immunophenotype of mononuclears from murine tibia bone marrow. Also the in vitro characterization of functional capacity of multipotent mesenchymal stromal cells (MSCs) was scheduled. Under the project, the S57black/6 mice were divided into groups: spaceflight/vivarium control, recovery after spaceflight/ vivarium control to recovery. Bone marrow mononuclears were isolated from the tibia and immunophenotyped using antibodies against CD45, CD34, CD90 on a flow cytometer Epics XL (Beckman Coulter). A part of the each pool was frozen for subsequent estimation of hematopoietic colony-forming units (CFU), the rest was used for the evaluation of fibroblast CFU (CFUf) number, MSC proliferative activity and osteogenic potency. The cell number in the flight group was significantly lower than in the vivarium control group. There were no differences in this parameter between flight and control groups after 7 days of recovery. The mononuclears viability was more than 95 percent in all examined groups. Flow cytometric analysis showed no differences in the bone marrow cell immunophenotype (CD45, CD34, CD90.1 (Thy1)), but the flight animals had more large-sized CD45+mononuclears, than the control groups of mice. There was no difference in the CFUf number between groups. After 7 days in vitro the MSC number in flight group was twice higher than in vivarium group, after 10 days - 4 times higher. These data may indicate a higher proliferative activity of MSCs after spaceflight. MSCs showed the same and high alkaline phosphatase activity, both in flight and in the control groups, suggesting no effect of spaceflight factors on early

  16. METABOLISM OF IRON STORES

    OpenAIRE

    Saito, Hiroshi

    2014-01-01

    ABSTRACT Remarkable progress was recently achieved in the studies on molecular regulators of iron metabolism. Among the main regulators, storage iron, iron absorption, erythropoiesis and hepcidin interact in keeping iron homeostasis. Diseases with gene-mutations resulting in iron overload, iron deficiency, and local iron deposition have been introduced in relation to the regulators of storage iron metabolism. On the other hand, the research on storage iron metabolism has not advanced since th...

  17. Iron Dextran Injection

    Science.gov (United States)

    ... allergic to iron dextran injection; any other iron injections such as ferric carboxymaltose (Injectafer), ferumoxytol (Feraheme), iron sucrose (Venofer), or sodium ferric gluconate (Ferrlecit);any other ...

  18. Food Enzymes

    Science.gov (United States)

    McBroom, Rachel; Oliver-Hoyo, Maria T.

    2007-01-01

    Many students view biology and chemistry as two unrelated, separate sciences; how these courses are generally taught in high schools may do little to change that impression. The study of enzymes provide a great opportunity for both biology and chemistry teachers to share with students the interdisciplinary nature of science. This article describes…

  19. Food Enzymes

    Science.gov (United States)

    McBroom, Rachel; Oliver-Hoyo, Maria T.

    2007-01-01

    Many students view biology and chemistry as two unrelated, separate sciences; how these courses are generally taught in high schools may do little to change that impression. The study of enzymes provide a great opportunity for both biology and chemistry teachers to share with students the interdisciplinary nature of science. This article describes…

  20. Enzyme immunoassay

    DEFF Research Database (Denmark)

    Feldt-Rasmussen, B; Dinesen, B; Deckert, M

    1985-01-01

    An enzyme linked immunoadsorbent assay for urinary albumin using commercially available reagents is described. The assay range is 2.5-120 micrograms/l. When samples are analysed in two standard dilutions, the assayable albumin concentration range is 2.5-240 mg/l, covering the clinical range from...

  1. Dioxygen activation by a non-heme iron(II) complex: formation of an iron(IV)-oxo complex via C-H activation by a putative iron(III)-superoxo species.

    Science.gov (United States)

    Lee, Yong-Min; Hong, Seungwoo; Morimoto, Yuma; Shin, Woonsup; Fukuzumi, Shunichi; Nam, Wonwoo

    2010-08-11

    Iron(III)-superoxo intermediates are believed to play key roles in oxygenation reactions by non-heme iron enzymes. We now report that a non-heme iron(II) complex activates O(2) and generates its corresponding iron(IV)-oxo complex in the presence of substrates with weak C-H bonds (e.g., olefins and alkylaromatic compounds). We propose that a putative iron(III)-superoxo intermediate initiates the O(2)-activation chemistry by abstracting a H atom from the substrate, with subsequent generation of a high-valent iron(IV)-oxo intermediate from the resulting iron(III)-hydroperoxo species.

  2. Relationship between the expression of Toll-like receptor 2 and 4 in mononuclear cells and postoperative acute lung injury in orthotopic liver transplantation

    Institute of Scientific and Technical Information of China (English)

    CHI Xin-jin; CAI Jun; LUO Chen-fang; CHENG Nan; HEI Zi-qing; LI Shang-rong; LUO Gang-jian

    2009-01-01

    Background The aim of this study was to investigate the potential relationship between the dynamic expression of Toll-like receptor 2 and 4 (TLR2/4) in peripheral blood mononuclear cells as well as changes in serum concentration of inflammatory factors and acute lung injury (ALl) in patients after orthotopic liver transplantation (OLT).Methods The peripheral blood samples of 27 patients (23 men and 4 women with ASA Ⅲ to Ⅳ) who received OLT were collected for measurement of TLR2/4 at T1 (after induction of anesthesia), T2 (25 minutes after anhepatic phase), T3 (3 hours after graft reperfusion) and T4 (24 hours after graft reperfusion). The expression of TLR2/4 in mononuclear cells was measured by flow cytometry. The serum concentrations of tumor necrosis factor (TNF)-a, intedeukin (IL)-113 and IL-8 were measured by enzyme-linked irnmunosorbent assay (ELISA). Twenty-seven patients were assigned to ALI group (n=9) and non-ALI group (n=18) according to the diagnostic criteria of ALI. The expression of TLR2/4 in the ALl group or non-ALI group was analyzed.Results Compared to the non-ALI group, the volumes of blood loss, ascites, total output and transfused red blood cells were higher in the ALI group, and the anhepallc phase lasted longer (P0.05). The expression of TLR2/4 in mononuclear cells increased significantly at T3 and 14 in the ALI group (P<0.05, P<0.01). A positive correlation was noted between the expression of TLR4 in mononuclear cells and the serum concentrations of TNF-α, IL-1β (P=0.041, P=0.046) in the ALl group. In the non-ALI group, statistical results showed that the expression level of TLR2/4 in mononuclear cells was not significantly different during the peri-operative period of OLT (besides TLR4 expression at T4). Compared to the non-ALI group, the increasing amplitude of TLR2/4 expression in mononuclear cells was more significant in the ALI group. The patients whose TLR2/4 expression in mononuclear cells exceeded that at T1 by one time were

  3. Iron Sucrose Injection

    Science.gov (United States)

    Iron sucrose injection is used treat iron-deficiency anemia (a lower than normal number of red blood cells due ... and may cause the kidneys to stop working). Iron sucrose injection is in a class of medications called iron ...

  4. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... enough iron, your body starts using the iron it has stored. Soon, the stored iron gets used ... fewer red blood cells. The red blood cells it does make have less hemoglobin than normal. Iron- ...

  5. Fetal hemoglobin accumulation in vitro. Effect of adherent mononuclear cells.

    OpenAIRE

    Javid, J; Pettis, P K

    1983-01-01

    In clonal cultures of erythroid burst-forming units (BFU-E) obtained from blood, the accumulation of fetal and adult hemoglobins (Hb F and Hb A) was measured by radioligand immunoassay. Inclusion of adherent mononuclear cells in the culture promoted a striking increase in the relative amount of Hb F in each of 44 experiments with 14 donors. In two-thirds of the instances, this was accounted for by a selective increase in the absolute amount of Hb F. The differential effect on Hb F and Hb A ac...

  6. Iron deficiency

    DEFF Research Database (Denmark)

    Schou, Morten; Bosselmann, Helle; Gaborit, Freja

    2015-01-01

    BACKGROUND: Both iron deficiency (ID) and cardiovascular biomarkers are associated with a poor outcome in heart failure (HF). The relationship between different cardiovascular biomarkers and ID is unknown, and the true prevalence of ID in an outpatient HF clinic is probably overlooked. OBJECTIVES.......043). CONCLUSION: ID is frequent in an outpatient HF clinic. ID is not associated with cardiovascular biomarkers after adjustment for traditional confounders. Inflammation, but not neurohormonal activation is associated with ID in systolic HF. Further studies are needed to understand iron metabolism in elderly HF...

  7. Effect of iron supplementation on maximal oxygen uptake in female athletes

    OpenAIRE

    Rađen Slavica; Rađen Goran; Životić-Vanović Mirjana; Radaković Sonja; Vasiljević Nađa; Stojanović Dušica

    2011-01-01

    Background/Aim. Iron is a vital constituent of hemoglobin, myoglobin, and some mitochondrial enzymes; therefore, body iron deficiency may result in reduced aerobic capacity. The aim of this study was to evaluate the effects of daily oral iron supplementation on body iron status, and the maximal oxygen uptake (VO2max) in female athletes with latent iron deficiency, as well as with irondeficiency anemia. Methods. A total of 37 female volleyball players were included in the study. Seventeen fema...

  8. Amyotrophic lateral sclerosis multiprotein biomarkers in peripheral blood mononuclear cells.

    Directory of Open Access Journals (Sweden)

    Giovanni Nardo

    Full Text Available 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 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. CONCLUSIONS/SIGNIFICANCE: 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.

  9. Amyotrophic lateral sclerosis multiprotein biomarkers in peripheral blood mononuclear cells.

    Science.gov (United States)

    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; Mora, Gabriele; Bendotti, Caterina; Bonetto, Valentina

    2011-01-01

    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.

  10. 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.

  11. Microbial Community Composition Impacts Pathogen Iron Availability during Polymicrobial Infection.

    Directory of Open Access Journals (Sweden)

    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.

  12. Mechanisms of heme iron absorption: Current questions and controversies

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    Iron is a critical micronutrient, and iron derived from heme contributes a large proportion of the total iron absorbed in a typical Western diet. Heine iron is absorbed by different mechanisms than non-heine iron, but despite considerable study over many years these mechanisms remain poorly understood. This review provides an overview of the importance of heme iron in the diet and discusses the two prevailing hypotheses of heine absorption; namely receptor mediated endocytosis of heme, and direct transport into the intestinal enterocyte by recently discovered heine transporters. A specific emphasis is placed on the questions surrounding the site of heme catabolism and the identity of the enzyme that performs this task. Additionally, we present the hypothesis that a nonheme iron transport protein may be required for heine iron absorption and discuss the experiences of our laboratory in examining this hypothesis.

  13. Iron Homeostasis in Health and Disease

    Directory of Open Access Journals (Sweden)

    Raffaella Gozzelino

    2016-01-01

    Full Text Available Iron is required for the survival of most organisms, including bacteria, plants, and humans. Its homeostasis in mammals must be fine-tuned to avoid iron deficiency with a reduced oxygen transport and diminished activity of Fe-dependent enzymes, and also iron excess that may catalyze the formation of highly reactive hydroxyl radicals, oxidative stress, and programmed cell death. The advance in understanding the main players and mechanisms involved in iron regulation significantly improved since the discovery of genes responsible for hemochromatosis, the IRE/IRPs machinery, and the hepcidin-ferroportin axis. This review provides an update on the molecular mechanisms regulating cellular and systemic Fe homeostasis and their roles in pathophysiologic conditions that involve alterations of iron metabolism, and provides novel therapeutic strategies to prevent the deleterious effect of its deficiency/overload.

  14. Pancreatic Cancer Cell Lines Can Induce Prostaglandin E2 Production from Human Blood Mononuclear Cells

    Directory of Open Access Journals (Sweden)

    Svitlana P. Grekova

    2011-01-01

    Full Text Available Accumulating evidence suggests an important role for cyclooxygenase-2 (COX-2 in the pathogenesis of a wide range of malignancies. The protumorigenic properties of COX-2 are generally thought to be mediated by its product, PGE2, which is shown to promote tumor spread and growth by multiple mechanisms but most importantly through modulation of the local immune response in the tumor. Pancreatic tumor cells produce various amounts of PGE2, some of them being even deficient in COX enzymes or other PGE2 synthases. Here we describe that, beside pancreatic tumor cells or stromal fibroblasts, human peripheral blood mononuclear cells can also produce PGE2 upon coculture with pancreatic cancer cells. Stimulating of cellular cPLA2 within PBMCs by secreted factors, presumably sPLA2, from tumor cells appeared crucial, while the direct contact between PBMCs and PDACs seemed to be dispensable for this effect. Our data is emphasizing the complex interactions participating in the formation of the tolerogenic immune milieu within pancreatic tumors.

  15. Analysis of the Relationship between Antioxidant Enzyme Gene Polymorphisms and Their Activity in Post-Traumatic Gonarthrosis.

    Science.gov (United States)

    Vnukov, V V; Panina, S B; Milyutina, N P; Krolevets, I V; Zabrodin, M A

    2016-05-01

    Analysis of polymorphisms of genes encoding antioxidant enzymes SOD1 (G7958A), SOD2 (T58C), CAT (C-262T), and GSTP1 (Ile105Val) in 93 patients with post-traumatic gonarthrosis showed that GSTP1 Ile105Val polymorphism is often associated with heterozygous mutation in catalase gene CAT C-262T. In gonarthrosis, catalase activity in peripheral blood mononuclear cells in patients with CT genotype of the C-262T locus of CAT gene more than 2-fold surpassed that in CC genotype and more than 50% surpassed the normal. Changes in the balance of activity of antioxidant enzymes can affect viability of mononuclear cells.

  16. Immunohistochemical demonstration of lysozyme in normal, reactive and neoplastic cells of the mononuclear phagocyte system.

    Directory of Open Access Journals (Sweden)

    Motoi,Makoto

    1984-04-01

    Full Text Available Using the peroxidase antiperoxidase (PAP method, lysozyme (LZM was shown to exist in normal, reactive and neoplastic cells belonging to the mononuclear phagocyte system (MPS, but was not detected in histiocytosis X cells. Immunostaining for cytoplasmic LZM by the PAP method is useful for identification of mononuclear phagocytes and for diagnosis of the diseases in which these cells participate.

  17. Iron bioavailability from commercially available iron supplements

    OpenAIRE

    2015-01-01

    Purpose Iron deficiency anaemia (IDA) is a global public health problem. Treatment with the standard of care ferrous iron salts may be poorly tolerated, leading to non-compliance and ineffective correction of IDA. Employing supplements with higher bioavailability might permit lower doses of iron to be used with fewer side effects, thus improving treatment efficacy. Here, we compared the iron bioavailability of ferrous sulphate tablets with alternative commercial iron products, including th...

  18. 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

    HIV infection is characterized by the loss of CD4+ T cells as well as the loss of T-cell function, leading to severe immunodeficiency. The proliferative capacity of T cells measured in vitro as responses to antigens and mitogens is severely reduced during HIV infection. An increased level...... 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...

  19. Lactam hydrolysis catalyzed by mononuclear metallo-ß-bactamases

    DEFF Research Database (Denmark)

    Olsen, Lars; Antony, J; Ryde, U

    2003-01-01

    . For most studied systems, the tetrahedral structure is a stable intermediate. Moreover, the C-N bond in the lactam ring is intact in this intermediate, as well as in the following transition state-its cleavage is induced by proton transfer to the nitrogen atom in the lactam ring. However, for the model...... with Asp as a proton shuttle, attack of the zinc-bond hydroxide ion seems to be concerted with the proton transfer. We have also studied the effect of replacing one of the histidine ligands by an asparagine or glutamine residue, giving a zinc site representative of other subclasses of metallo......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...

  20. 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...... that 68.4% of CpG sites and 80% displayed allele-specific expression (ASE). These data demonstrate that ASM is a recurrent phenomenon and is highly correlated with ASE in human PBMCs. Together with recently reported similar studies, our study provides a comprehensive resource for future epigenomic...

  1. Characteristics of spontaneously proliferating mononuclear cells in rheumatoid arthritis.

    Science.gov (United States)

    Froebel, K; Dickson, R; Lewis, D; Jasani, M K; Sturrock, R D

    1984-10-01

    The phenomenon of increased spontaneous incorporation of 3H-thymidine (3H-TdR) into peripheral blood mononuclear cells in rheumatoid arthritis (RA) has been investigated. The activity was found to be short lived and affected less than 1% of cells. Using a Percoll density gradient we identified two populations of active cells. RA patients with active synovitis and increased 3H-TdR incorporation in the low density population of cells have higher overall 3H-TdR incorporation than normal controls and patients with inactive RA. The low density cell population is enriched for Ia+ cells. The data are consistent with raised spontaneous 3H-TdR incorporation being due to an in-vivo cell mediated immune response.

  2. Metabolic reprogramming of mononuclear phagocytes and progressive multiple sclerosis

    Directory of Open Access Journals (Sweden)

    Stefano ePluchino

    2015-03-01

    Full Text Available Multiple sclerosis (MS is an inflammatory and demyelinating disease of the central nervous system (CNS. Accumulation of brain damage in progressive MS is partly the result of mononuclear phagocytes (MPs attacking myelin sheaths in the CNS. Although there is no cure yet for MS, significant advances have been made in the development of disease modifying agents. Unfortunately, most of these drugs fail to reverse established neurological deficits and can have adverse effects. Recent evidence suggests that MPs polarisation is accompanied by profound metabolic changes, whereby pro-inflammatory MPs (M1 switch toward glycolysis, whereas anti-inflammatory MPs (M2 become more oxidative. It is therefore possible that reprogramming MPs metabolism could affect their function and repress immune cell activation. This minireview describes the metabolic changes underpinning macrophages polarisation and anticipates how metabolic re-education of MPs could be used for the treatment of MS.

  3. Use of cryopreserved peripheral mononuclear blood cells in biomonitoring

    DEFF Research Database (Denmark)

    Risom, Lotte; Knudsen, Lisbeth E.

    1999-01-01

    This study was performed to investigate the effect of storing blood samples by freezing on selected biomarkers and possible implications for biomonitoring. Comparative measurements were performed in order to investigate the use of cryopreserved vs. freshly separated peripheral mononuclear blood c....... We measured the DNA repair activity as dimethylsulfate induced unscheduled DNA synthesis (UDS) in PMBC incubated with either autologous plasma or fetal bovine serum (FBS). Comparison of the hprt mutant frequency by the T cell cloning assay was made in parallel. Finally the content of B....../T-lymphocytes and monocytes was measured in phytohemaglutinin (PHA)-stimulated cultures at different time intervals. The results showed a higher DNA repair activity in cryopreserved samples compared with fresh samples. We also found differences in mutant frequencies with higher values in fresh samples. A significant...

  4. Co-stimulation of cultured peripheral blood mononuclear cells from intrinsic asthmatics with exogenous recombinant IL-6 produce high levels of IL-4-dependent IgE.

    Science.gov (United States)

    Sánchez-Guerrero, I M; Herrero, N; Muro, M; Vegara, R P; Campos, M; García-Alonso, A M; Alvarez, M R

    1997-09-01

    Asthma is an inflammatory airway disorder, traditionally subdivided into extrinsic, immunoglobulin E (IgE)-mediated, and intrinsic asthma of unknown aetiology. IgE synthesis requires contact between T- and B-cells and a signal provided by interleukin (IL)-4, which can be modulated by IL-6. The objective of this study was to evaluate the effects of IL-4 and IL-6 on total IgE synthesis by peripheral blood mononuclear cells from intrinsic and extrinsic asthmatics. Peripheral blood mononuclear cells from intrinsic and extrinsic asthmatic patients and from healthy subjects were cultured and stimulated with pokeweed mitogen, recombinant IL-4 and IL-6. The IgE level in serum and supernatants was measured by an enzyme-linked immunoassay. Serum IgE was significantly lower in intrinsic asthma than in extrinsic asthma, but significantly higher than in control subjects. IgE production by cultured mononuclear cells from extrinsic asthmatics was not modified after exogenous IL-4 and IL-6 addition. However, intrinsic asthmatics showed enhancement of IgE synthesis in response to IL-4 stimulation, reaching a threefold increase of the spontaneous IgE values, when simultaneous recombinant IL-4 plus IL-6 stimulus was used. Our results indicate that exogenous recombinant interleukin-6 can significantly upregulate the interleukin-4-dependent immunoglobulin E synthesis in intrinsic asthma. This suggests that immunoglobulin E could also play a role in the pathogenesis of intrinsic asthma, in which an interleukin-6 threshold would be critical.

  5. Influence of acute renal failure on the mononuclear phagocytic system

    Directory of Open Access Journals (Sweden)

    V.R.A. Sousa

    2001-09-01

    Full Text Available Several studies show the ability of macrophages to remove particles injected into the bloodstream. This function seems to be increased in the presence of acute renal failure. The objective of the present study was to assess the phagocytic function of the main organs (spleen, liver and lung of the mononuclear phagocytic system in renal and postrenal failures. Fifteen rats (250-350 g were divided into three groups (N = 5: group I - control; group II - ligature of both ureters, and group III - bilateral nephrectomy. On the third postoperative day, all animals received an iv injection of 1 ml/kg 99mTc sulfur colloid. Blood samples were collected for the assessment of plasma urea, creatinine, sodium, and potassium concentrations and arterial gasometry. Samples of liver, spleen, lung and blood clots were obtained and radioactivity was measured. Samples of liver, spleen, lung and kidney were prepared for routine histopathological analysis. Plasma urea, creatinine and potassium concentrations in groups II and III were higher than in group I (P<0.05. Plasma sodium concentrations in groups II and III were lower than in group I (P<0.05. Compensated metabolic acidosis was observed in the presence of postrenal failure. Group II animals showed a lower level of radioactivity in the spleen (0.98 and lung (2.63, and a higher level in the liver (105.51 than control. Group III animals showed a lower level of radioactivity in the spleen (11.94 and a higher level in the liver (61.80, lung (11.30 and blood clot (5.13 than control. In groups II and III liver steatosis and bronchopneumonia were observed. Renal and postrenal failures seem to interfere with blood clearance by the mononuclear phagocytic system.

  6. 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.

  7. Transdermal iron replenishment therapy.

    Science.gov (United States)

    Modepalli, Naresh; Shivakumar, H N; Kanni, K L Paranjothy; Murthy, S Narasimha

    2015-01-01

    Iron deficiency anemia is one of the major nutritional deficiency disorders. Iron deficiency anemia occurs due to decreased absorption of iron from diet, chronic blood loss and other associated diseases. The importance of iron and deleterious effects of iron deficiency anemia are discussed briefly in this review followed by the transdermal approaches to deliver iron. Transdermal delivery of iron would be able to overcome the side effects associated with conventional oral and parenteral iron therapy and improves the patient compliance. During preliminary investigations, ferric pyrophosphate and iron dextran were selected as iron sources for transdermal delivery. Different biophysical techniques were explored to assess their efficiency in delivering iron across the skin, and in vivo studies were carried out using anemic rat model. Transdermal iron delivery is a promising approach that could make a huge positive impact on patients suffering with iron deficiency.

  8. 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...

  9. Iron and iron derived radicals

    Energy Technology Data Exchange (ETDEWEB)

    Borg, D.C.; Schaich, K.M.

    1987-04-01

    We have discussed some reactions of iron and iron-derived oxygen radicals that may be important in the production or treatment of tissue injury. Our conclusions challenge, to some extent, the usual lines of thought in this field of research. Insofar as they are born out by subsequent developments, the lessons they teach are two: Think fastexclamation Think smallexclamation In other words, think of the many fast reactions that can rapidly alter the production and fate of highly reactive intermediates, and when considering the impact of competitive reactions on such species, think how they affect the microenvironment (on the molecular scale) ''seen'' by each reactive molecule. 21 refs., 3 figs., 1 tab.

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

    Directory of Open Access Journals (Sweden)

    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

  11. 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...

  12. Genome and low-iron response of an oceanic diatom adapted to chronic iron limitation

    Science.gov (United States)

    2012-01-01

    Background Biogeochemical elemental cycling is driven by primary production of biomass via phototrophic phytoplankton growth, with 40% of marine productivity being assigned to diatoms. Phytoplankton growth is widely limited by the availability of iron, an essential component of the photosynthetic apparatus. The oceanic diatom Thalassiosira oceanica shows a remarkable tolerance to low-iron conditions and was chosen as a model for deciphering the cellular response upon shortage of this essential micronutrient. Results The combined efforts in genomics, transcriptomics and proteomics reveal an unexpected metabolic flexibility in response to iron availability for T. oceanica CCMP1005. The complex response comprises cellular retrenchment as well as remodeling of bioenergetic pathways, where the abundance of iron-rich photosynthetic proteins is lowered, whereas iron-rich mitochondrial proteins are preserved. As a consequence of iron deprivation, the photosynthetic machinery undergoes a remodeling to adjust the light energy utilization with the overall decrease in photosynthetic electron transfer complexes. Conclusions Beneficial adaptations to low-iron environments include strategies to lower the cellular iron requirements and to enhance iron uptake. A novel contribution enhancing iron economy of phototrophic growth is observed with the iron-regulated substitution of three metal-containing fructose-bisphosphate aldolases involved in metabolic conversion of carbohydrates for enzymes that do not contain metals. Further, our data identify candidate components of a high-affinity iron-uptake system, with several of the involved genes and domains originating from duplication events. A high genomic plasticity, as seen from the fraction of genes acquired through horizontal gene transfer, provides the platform for these complex adaptations to a low-iron world. PMID:22835381

  13. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... or an inability to absorb enough iron from food. Overview Iron-deficiency anemia is a common type ... of the condition. Treatments may include dietary changes, medicines, and surgery. Severe iron-deficiency anemia may require ...

  14. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... or an inability to absorb enough iron from food. Overview Iron-deficiency anemia is a common type ... condition. Treatments may include dietary changes, medicines, and surgery. Severe iron-deficiency anemia may require treatment in ...

  15. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... at highest risk for iron-deficiency anemia. Outlook Doctors usually can successfully treat iron-deficiency anemia. Treatment ... poor skin tone, dizziness, and depression. After her doctor diagnosed her with iron-deficiency anemia, Susan got ...

  16. Iron and Your Child

    Science.gov (United States)

    ... extra iron in their diets. People following a vegetarian diet might also need additional iron. What's Iron ... as Whole Milk? About Anemia Minerals What's a Vegetarian? Word! Anemia Anemia Food Labels Vitamins and Minerals ...

  17. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... Intramural Research Research Resources Research Meeting Summaries Technology Transfer Clinical Trials What Are Clinical Trials? Children & Clinical ... iron-deficiency anemia may require treatment in a hospital, blood transfusions , iron injections, or intravenous iron therapy. ...

  18. Iron-binding properties of sugar cane yeast peptides.

    Science.gov (United States)

    de la Hoz, Lucia; Ponezi, Alexandre N; Milani, Raquel F; Nunes da Silva, Vera S; Sonia de Souza, A; Bertoldo-Pacheco, Maria Teresa

    2014-01-01

    The extract of sugar-cane yeast (Saccharomyces cerevisiae) was enzymatically hydrolysed by Alcalase, Protex or Viscozyme. Hydrolysates were fractionated using a membrane ultrafiltration system and peptides smaller than 5kDa were evaluated for iron chelating ability through measurements of iron solubility, binding capacity and dialyzability. Iron-chelating peptides were isolated using immobilized metal affinity chromatography (IMAC). They showed higher content of His, Lys, and Arg than the original hydrolysates. In spite of poor iron solubility, hydrolysates of Viscozyme provided higher iron dialyzability than those of other enzymes. This means that more chelates of iron or complexes were formed and these kept the iron stable during simulated gastro-intestinal digestion in vitro, improving its dialyzability.

  19. Genetics Home Reference: iron-refractory iron deficiency anemia

    Science.gov (United States)

    ... refractory iron deficiency anemia iron-refractory iron deficiency anemia Enable Javascript to view the expand/collapse boxes. ... All Close All Description Iron-refractory iron deficiency anemia is one of many types of anemia , which ...

  20. 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....

  1. Iron-refractory iron deficiency anemia.

    Science.gov (United States)

    Yılmaz Keskin, Ebru; Yenicesu, İdil

    2015-03-05

    Iron is essential for life because it is indispensable for several biological reactions, such as oxygen transport, DNA synthesis, and cell proliferation. Over the past few years, our understanding of iron metabolism and its regulation has changed dramatically. New disorders of iron metabolism have emerged, and the role of iron as a cofactor in other disorders has begun to be recognized. The study of genetic conditions such as hemochromatosis and iron-refractory iron deficiency anemia (IRIDA) has provided crucial insights into the molecular mechanisms controlling iron homeostasis. In the future, these advances may be exploited to improve treatment of both genetic and acquired iron disorders. IRIDA is caused by mutations in TMPRSS6, the gene encoding matriptase-2, which downregulates hepcidin expression under conditions of iron deficiency. The typical features of this disorder are hypochromic, microcytic anemia with a very low mean corpuscular volume of erythrocytes, low transferrin saturation, no (or inadequate) response to oral iron, and only a partial response to parenteral iron. In contrast to classic iron deficiency anemia, serum ferritin levels are usually low-normal, and serum or urinary hepcidin levels are inappropriately high for the degree of anemia. Although the number of cases reported thus far in the literature does not exceed 100, this disorder is considered the most common of the "atypical" microcytic anemias. The aim of this review is to share the current knowledge on IRIDA and increase awareness in this field.

  2. Iron-Refractory Iron Deficiency Anemia

    Science.gov (United States)

    Yılmaz Keskin, Ebru; Yenicesu, İdil

    2015-01-01

    Iron is essential for life because it is indispensable for several biological reactions, such as oxygen transport, DNA synthesis, and cell proliferation. Over the past few years, our understanding of iron metabolism and its regulation has changed dramatically. New disorders of iron metabolism have emerged, and the role of iron as a cofactor in other disorders has begun to be recognized. The study of genetic conditions such as hemochromatosis and iron-refractory iron deficiency anemia (IRIDA) has provided crucial insights into the molecular mechanisms controlling iron homeostasis. In the future, these advances may be exploited to improve treatment of both genetic and acquired iron disorders. IRIDA is caused by mutations in TMPRSS6, the gene encoding matriptase-2, which downregulates hepcidin expression under conditions of iron deficiency. The typical features of this disorder are hypochromic, microcytic anemia with a very low mean corpuscular volume of erythrocytes, low transferrin saturation, no (or inadequate) response to oral iron, and only a partial response to parenteral iron. In contrast to classic iron deficiency anemia, serum ferritin levels are usually low-normal, and serum or urinary hepcidin levels are inappropriately high for the degree of anemia. Although the number of cases reported thus far in the literature does not exceed 100, this disorder is considered the most common of the “atypical” microcytic anemias. The aim of this review is to share the current knowledge on IRIDA and increase awareness in this field. PMID:25805669

  3. Liver iron transport

    Institute of Scientific and Technical Information of China (English)

    Ross M Graham; Anita CG Chua; Carly E Herbison; John K Olynyk; Debbie Trinder

    2007-01-01

    The liver plays a central role in iron metabolism. It is the major storage site for iron and also expresses a complex range of molecules which are involved in iron transport and regulation of iron homeostasis. An increasing number of genes associated with hepatic iron transport or regulation have been identified. These include transferrin receptors (TFR1 and 2), a ferrireductase (STEAP3), the transporters divalent metal transporter-1 (DMT1) and ferroportin (FPN) as well as the haemochromatosis protein, HFE and haemojuvelin (HJV),which are signalling molecules. Many of these genes also participate in iron regulatory pathways which focus on the hepatic peptide hepcidin. However, we are still only beginning to understand the complex interactions between liver iron transport and iron homeostasis. This review outlines our current knowledge of molecules of iron metabolism and their roles in iron transport and regulation of iron homeostasis.

  4. Aqueous extracts of two varieties of ginger (Zingiber officinale) inhibit angiotensin I-converting enzyme, iron(II), and sodium nitroprusside-induced lipid peroxidation in the rat heart in vitro.

    Science.gov (United States)

    Akinyemi, Ayodele J; Ademiluyi, Adedayo O; Oboh, Ganiyu

    2013-07-01

    Ginger has reportedly been used in folk medicine for the management and prevention of hypertension and other cardiovascular diseases. Therefore, this study sought to investigate the inhibitory effect of aqueous extracts of two varieties of ginger on a key enzyme linked to hypertension (angiotensin I-converting enzyme [ACE]), and on pro-oxidants [Fe(2+) and sodium nitroprusside (SNP)] which have been shown to induce lipid peroxidation in the rat's isolated heart in vitro. Aqueous extracts (0.05 mg/mL) of red ginger (Zingiber officinale var. Rubra) and white ginger (Zingiber officinale Roscoe) were prepared and the ability of the extracts to inhibit ACE along with Fe(2+)- and SNP-induced lipid peroxidation was determined in rat's heart in vitro. Results revealed that both extracts inhibited ACE in a dose-dependent manner (25-125 μg/mL). However, red ginger extract (EC50=27.5 μg/mL) had a significantly (Pginger extract (EC50=87.0 μg/mL). Furthermore, incubation of the rat's heart in the presence of Fe(2+) and SNP caused a significant increase (Pginger extracts (78-313 μg/mL) caused a dose-dependent decrease in the MDA content of the stressed heart homogenates. This suggests that the possible mechanism through which ginger exerts its antihypertensive properties may be through inhibition of ACE activity and prevention of lipid peroxidation in the heart. Furthermore, red ginger showed stronger inhibition of ACE than white ginger. Additionally, it should be noted that these protective properties of the ginger varieties could be attributed to their polyphenol contents.

  5. Conflicting effects of BMI and waist circumference on iron status.

    Science.gov (United States)

    Choma, Solomon Simon Ramphai; Alberts, Marianne; Modjadji, Sewela Elizabeth Perpetua

    2015-10-01

    The association between obesity and iron status has a long history and is still receiving attention. However comparative analysis of the association between general obesity (BMI) and visceral obesity (waist circumference) with iron status has not been extensively researched. The aim of the present study is thus to determine if body mass index and waist circumference have the same correlation with iron status. One thousand one hundred and thirty people (225 men and 905 women) aged 30 years and above participated in this study. Anthropometric parameters, haemoglobin, iron and total iron binding capacity concentrations were measured using standard methods. Percentage transferrin saturation was calculated and ferritin concentrations were measured using an enzyme linked immunosorbent assay. Obese or overweight women had significantly lower iron and transferrin saturation concentration when compared to non-obese women. In contrast, women with high waist circumference had comparable plasma iron and transferrin saturation to women with normal waist circumference. Partial correlation analysis and linear regression analysis showed that BMI is negatively and significantly associated with plasma iron, transferrin saturation, Hb and ferritin concentration, whilst waist circumference is positively but insignificantly associated with plasma iron, transferrin saturation, Hb and ferritin concentration. Binary regression analysis showed that obese or overweight people are more likely to have iron deficiency, whilst those with raised waist circumference are more likely to have iron overload. Multivariate analysis showed that body mass index is negatively and significantly associated with low iron status, while waist circumference is positively and insignificantly associated with iron status. This is supported by a comparison of plasma iron, transferrin saturation and ferritin concentrations in participants with high body mass index and normal waist circumference and participants with

  6. Fish peripheral blood mononuclear cells preparation for future monitoring applications.

    Science.gov (United States)

    Pierrard, Marie-Aline; Roland, Kathleen; Kestemont, Patrick; Dieu, Marc; Raes, Martine; Silvestre, Frédéric

    2012-07-15

    Fish species possess many specific characteristics that support their use in ecotoxicology. Widely used in clinical research, peripheral blood mononuclear cells (PBMCs) can reasonably be exploited as relevant target cells in the assessment of environmental chemical toxicity. The current article focuses on the methods necessary to isolate, characterize, and culture fish PBMCs. These procedures were successfully applied on an endangered species, the European eel (Anguilla anguilla L.), and on an economically important and worldwide exported species, the Asian catfish (Pangasianodon hypophthalmus S.). Proteomic approaches can be useful to screen xenobiotic exposure at the protein expression level, giving the opportunity to develop early warning signals thanks to molecular signatures of toxicity. To date, a major limitation of proteomic analyses is that most protein expression profiles often reveal the same predominant and frequently differentially expressed families of proteins regardless of the experimental stressing conditions. The current study describes a methodology to get a postnuclear fraction of high quality isolated from fish PBMCs in order to perform subsequent subproteomic analyses. Applied on samples from eel, the subproteomic analysis (two-dimensional differential in-gel electrophoresis) allowed the identification by liquid chromatography-tandem mass spectrometry and searches in the full NCBInr (National Center for Biotechnology Information nonredundant) database of 66 proteins representing 36 different proteins validated through Peptide and Protein Prophet of Scaffold software.

  7. The DNA methylome of human peripheral blood mononuclear cells.

    Directory of Open Access Journals (Sweden)

    Yingrui Li

    Full Text Available 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 that 68.4% of CpG sites and 80% displayed allele-specific expression (ASE. These data demonstrate that ASM is a recurrent phenomenon and is highly correlated with ASE in human PBMCs. Together with recently reported similar studies, our study provides a comprehensive resource for future epigenomic research and confirms new sequencing technology as a paradigm for large-scale epigenomics studies.

  8. MicroRNA Expression in Alzheimer Blood Mononuclear Cells

    Directory of Open Access Journals (Sweden)

    Hyman M. Schipper

    2007-01-01

    Full Text Available Various coding genes representing multiple functional categories are downregulated in blood mononuclear cells (BMC of patients with sporadic Alzheimer disease (AD. Noncoding microRNAs (miRNA regulate gene expression by degrading messages or inhibiting translation. Using BMC as a paradigm for the study of systemic alterations in AD, we investigated whether peripheral miRNA expression is altered in this condition. MicroRNA levels were assessed using the microRNA microarray (MMChip containing 462 human miRNA, and the results validated by real time PCR. Sixteen AD patients and sixteen normal elderly controls (NEC were matched for ethnicity, age, gender and education. The expression of several BMC miRNAs was found to increase in AD relative to NEC levels, and may differ between AD subjects bearing one or two APOE4 alleles. As compared to NEC, miRNAs signifi cantly upregulated in AD subjects and confi rmed by qPCR were miR-34a and 181b. Predicted target genes downregulated in Alzheimer BMC that correlated with the upregulated miRNAs were largely represented in the functional categories of Transcription/Translation and Synaptic Activity. Several miRNAs targeting the same genes were within the functional category of Injury response/Redox homeostasis. Taken together, induction of microRNA expression in BMC may contribute to the aberrant systemic decline in mRNA levels in sporadic AD.

  9. Autologous Bone Marrow Mononuclear Cells Intrathecal Transplantation in Chronic Stroke

    Directory of Open Access Journals (Sweden)

    Alok Sharma

    2014-01-01

    Full Text Available Cell therapy is being widely explored in the management of stroke and has demonstrated great potential. It has been shown to assist in the remodeling of the central nervous system by inducing neurorestorative effect through the process of angiogenesis, neurogenesis, and reduction of glial scar formation. In this study, the effect of intrathecal administration of autologous bone marrow mononuclear cells (BMMNCs is analyzed on the recovery process of patients with chronic stroke. 24 patients diagnosed with chronic stroke were administered cell therapy, followed by multidisciplinary neurorehabilitation. They were assessed on functional independence measure (FIM objectively, along with assessment of standing and walking balance, ambulation, and hand functions. Out of 24 patients, 12 improved in ambulation, 10 in hand functions, 6 in standing balance, and 9 in walking balance. Further factor analysis was done. Patients of the younger groups showed higher percentage of improvement in all the areas. Patients who underwent cell therapy within 2 years after the stroke showed better changes. Ischemic type of stroke had better recovery than the hemorrhagic stroke. This study demonstrates the potential of autologous BMMNCs intrathecal transplantation in improving the prognosis of functional recovery in chronic stage of stroke. Further clinical trials are recommended. This trial is registered with NCT02065778.

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

    Science.gov (United States)

    Yu, Nan; Yan, Wenjie; Yin, Tailang; Wang, Yaqin; Guo, Yue; Zhou, Danni; Xu, Mei; Ding, Jinli; Yang, Jing

    2015-01-01

    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.

  11. Divalent metal transporter, iron, and Parkinson's disease:A pathological relationship

    Institute of Scientific and Technical Information of China (English)

    Hyun-pil Lee; Xiongwei Zhu; Gang Liu; Shu G Chen; George Perry; Mark A Smith; Hyoung-gon Lee

    2010-01-01

    @@ Iron is an essential component of oxidative metabolism and a cofactor for a variety of enzymes. Because of its chemical properties as a transition metal, iron can serve both as an electron donor and acceptor and, as such, excess levels of free iron are toxic. Given this potential for toxicity, a number of pro-teins, including transferrin, transferrin receptor, and ferritin, tightly control iron transport, uptake, and storage in the central nervous system.

  12. Activation of Human Complement System by Dextran-Coated Iron Oxide Nanoparticles Is Not Affected by Dextran/Fe Ratio, Hydroxyl Modifications, and Crosslinking

    DEFF Research Database (Denmark)

    Wang, Guankui; Chen, Fangfang; Banda, Nirmal K

    2016-01-01

    , whereas opsonization with C3 fragments promotes rapid recognition and clearance of nanomaterials by mononuclear phagocytes. We used dextran-coated superparamagnetic iron oxide nanoparticles (SPIO), which are potent activators of the complement system, to study the role of nanoparticle surface chemistry...

  13. [Iron-refractory iron deficiency anemia].

    Science.gov (United States)

    Kawabata, Hiroshi

    2016-02-01

    The major causes of iron deficiency anemia (IDA) include iron loss due to bleeding, increased iron requirements, and decreased iron absorption by the intestine. The most common cause of IDA in Japanese women is iron loss during menstruation. Autoimmune atrophic gastritis and Helicobacter pylori infection can also cause IDA by reducing intestinal iron absorption. In addition to these common etiologies, germline mutations of TMPRSS6 can cause iron-refractory IDA (IRIDA). TMPRSS6 encodes matriptase-2, a membrane-bound serine protease primarily expressed in the liver. Functional loss of matriptase-2 due to homozygous mutations results in an increase in the expression of hepcidin, which is the key regulator of systemic iron homeostasis. The serum hepcidin increase in turn leads to a decrease in iron supply from the intestine and macrophages to erythropoietic cells. IRIDA is microcytic and hypochromic, but decreased serum ferritin is not observed as in IDA. IRIDA is refractory to oral iron supplementation, but does respond to intravenous iron supplementation to some extent. Because genetic testing is required for the diagnoses of IRIDA, a considerable number of cases may go undiagnosed and may thus be overlooked.

  14. 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

  15. 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 ...

  16. 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

  17. 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.

  18. Iron stress in plants.

    Science.gov (United States)

    Connolly, Erin L; Guerinot, Mary

    2002-07-30

    Although iron is an essential nutrient for plants, its accumulation within cells can be toxic. Plants, therefore, respond to both iron deficiency and iron excess by inducing expression of different gene sets. Here, we review recent advances in the understanding of iron homeostasis in plants gained through functional genomic approaches

  19. Iron stress in plants

    OpenAIRE

    Connolly, Erin L.; Guerinot, Mary Lou

    2002-01-01

    Although iron is an essential nutrient for plants, its accumulation within cells can be toxic. Plants, therefore, respond to both iron deficiency and iron excess by inducing expression of different gene sets. Here, we review recent advances in the understanding of iron homeostasis in plants gained through functional genomic approaches.

  20. Evaluating the influence of National Research Council levels of copper, iron, manganese, and zinc using organic (Bioplex) minerals on resulting tissue mineral concentrations, metallothionein, and liver antioxidant enzymes in grower-finisher swine diets.

    Science.gov (United States)

    Gowanlock, D W; Mahan, D C; Jolliff, J S; Hill, G M

    2015-03-01

    Graded levels of a trace mineral premix containing an organic (Bioplex) source of Cu, Fe, Mn, and Zn was evaluated with additional treatments containing organic Zn or Fe. Grower-finisher pigs were fed from 25 to 115 kg BW. The number of pigs in the experiment, the breeding/genetics of the pigs, the management, and the average age of the pigs were previously reported. The experiment was conducted as a randomized complete block design in 7 replicates. Treatments were 1) basal diet without supplemental Cu, Fe, Mn, and Zn; 2) basal diet + 2.5 mg/kg Cu, 50 mg/kg Fe, 1.5 mg/kg Mn, and 40 mg/kg Zn (50% NRC); 3) basal diet + 5 mg/kg Cu, 100 mg/kg Fe, 3 mg/kg Mn, and 80 mg/kg Zn (100% NRC); 4) basal diet + 25 mg Zn/kg; 5) basal diet + 50 mg Zn/kg; and 6) basal diet + 50 mg Fe/kg. Selenium and I were added to all diets at 0.3 and 0.14 mg/kg, respectively. Diets were composed of corn-soybean meal, dicalcium phosphate, and limestone with phytase added to enhance mineral availability. Three pigs per pen were bled at 55, 80, and 115 kg BW and plasma was analyzed for microminerals. When the average replicate BW was 115 kg, 3 pigs per pen of an equal gender ratio were killed. The liver, kidney, and heart were removed and analyzed for microminerals. Liver, duodenum, and jejunal metallothionein and the antioxidant enzymes in the liver containing these microminerals were determined. The results demonstrated that plasma minerals were unaffected at the 3 BW intervals. Liver and duodenum metallothionein protein were greater ( dietary micromineral levels increased but jejunum metallothionein did not change as microminerals increased. The activity of Cu/Zn superoxide dismutase (SOD) was not affected as the levels of the micromineral increased, whereas the activity of Mn SOD increased slightly ( dietary micromineral levels increased and also when Zn was added singly to the diet. Liver, kidney, and heart Cu and Mn concentrations were similar at the various micromineral levels. The

  1. Enzyme detection by microfluidics

    DEFF Research Database (Denmark)

    2013-01-01

    Microfluidic-implemented methods of detecting an enzyme, in particular a DNA-modifying enzyme, are provided, as well as methods for detecting a cell, or a microorganism expressing said enzyme. The enzyme is detected by providing a nucleic acid substrate, which is specifically targeted...... by that enzyme...

  2. Urinary iron excretion test in iron deficiency anemia.

    Directory of Open Access Journals (Sweden)

    Kimura,Ikuro

    1980-02-01

    Full Text Available A urinary iron excretion test was carried out in 22 patients with iron deficiency anemia. The iron excretion index was significantly higher in patients with intractable iron deficiency anemia compared with normal subjects and anemic patients who were responsive to iron therapy. The findings suggest that iron excretion may be a factor that modulates the response of patients to iron therapy.

  3. Transcriptional Profiling of Human Peripheral Blood Mononuclear Cells Exposed to Bacillus anthracis in vitro

    Science.gov (United States)

    2013-03-11

    Bacillus cereus group of bacteria, are attributed to poly- γ-D-glutamate acid (PGA) capsule, lethal toxin (LT) and edema toxin (ET) [10-12]. These toxins...M, Hellman M, Muhie S, et al. (2013) Transcriptional Profiling of Human Peripheral Blood Mononuclear Cells Exposed to Bacillus anthracis in vitro...author and source are credited. Transcriptional Profiling of Human Peripheral Blood Mononuclear Cells Exposed to Bacillus anthracis in vitro Rasha

  4. 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.

  5. Genetic/metabolic effect of iron metabolism and rare anemias

    Directory of Open Access Journals (Sweden)

    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.

  6. 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.

  7. The Markers of Glutamate Metabolism in Peripheral Blood Mononuclear Cells and Neurological Complications in Lung Cancer Patients

    Directory of Open Access Journals (Sweden)

    Slawomir Michalak

    2016-01-01

    Full Text Available Objective. To evaluate the involvement of glutamate metabolism in peripheral blood mononuclear cells (PBMC in the development of neurological complications in lung cancer and during chemotherapy. Methods. The prospective study included 221 lung cancer patients treated with chemotherapeutics. Neurological status and cognitive functions were evaluated at baseline and after 6-month follow-up. Glutamate level, the activities of glutaminase- (GLS- glutamate synthetizing enzyme, glutamate dehydrogenase (GDH, and glutamate decarboxylase catalyzing glutamate degradation were analyzed in PBMC and in sera of lung cancer patients by means of spectrophotometric and colorimetric methods. Results. Chemotherapy of lung neoplasms induced increase of glutamate content in PBMC and its concentration in serum increased the activity of GDH in PBMC and decreased activity of glutaminase in PBMC. The changes in glutamate metabolism markers were associated with initial manifestation of neurological deficit in lung cancer patients and with new symptoms, which appear as a complication of chemotherapy. Moreover, the analyzed parameters of glutamate control correlated with a spectrum of cognitive functions measures in lung cancer patients. Conclusion. We have demonstrated dysregulation in glutamate and glutamate metabolism controlling enzymes as promising indicators of risk for chemotherapy-induced neurological complications in lung cancer patients with particular emphasis on cognitive impairment.

  8. Magnetic tumor targeting of β-Glucosidase immobilized iron oxide nanoparticles

    OpenAIRE

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

    2013-01-01

    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, difficult to be monitored. In current 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 (MNP), abbreviated as β-Glu...

  9. Elevated Liver Enzymes

    Science.gov (United States)

    Symptoms Elevated liver enzymes By Mayo Clinic Staff Elevated liver enzymes may indicate inflammation or damage to cells in the liver. Inflamed or ... than normal amounts of certain chemicals, including liver enzymes, into the bloodstream, which can result in elevated ...

  10. Absence of peripheral blood mononuclear cells priming in hemodialysis patients

    Directory of Open Access Journals (Sweden)

    Santos B.C.

    2003-01-01

    Full Text Available As a consequence of the proinflammatory environment occurring in dialytic patients, cytokine overproduction has been implicated in hemodialysis co-morbidity. However, there are discrepancies among the various studies that have analyzed TNF-alpha synthesis and the presence of peripheral blood mononuclear cell (PBMC priming in this clinical setting. We measured bioactive cytokine by the L929 cell bioassay, and evaluated PBMC TNF-alpha production by 32 hemodialysis patients (HP and 51 controls. No difference in TNF-alpha secretion was observed between controls and HP (859 ± 141 vs 697 ± 130 U/10(6 cells. Lipopolysaccharide (5 µg/ml did not induce any further TNF-alpha release, showing no PBMC priming. Paraformaldehyde-fixed HP PBMC were not cytotoxic to L929 cells, suggesting the absence of membrane-anchored TNF-alpha. Cycloheximide inhibited PBMC cytotoxicity in HP and controls, indicating lack of a PBMC TNF-alpha pool, and dependence on de novo cytokine synthesis. Actinomycin D reduced TNF-alpha production in HP, but had no effect on controls. Therefore, our data imply that TNF-alpha production is an intrinsic activity of normal PBMC and is not altered in HP. Moreover, TNF-alpha is a product of de novo synthesis by PBMC and is not constitutively expressed on HP cell membranes. The effect of actinomycin D suggests a putative tighter control of TNF-alpha mRNA turnover in HP. This increased dependence on TNF-alpha RNA transcription in HP may reflect an adaptive response to hemodialysis stimuli.

  11. Redox properties of a mononuclear copper(II)-superoxide complex.

    Science.gov (United States)

    Tano, Tetsuro; Okubo, Yuri; Kunishita, Atsushi; Kubo, Minoru; Sugimoto, Hideki; Fujieda, Nobutaka; Ogura, Takashi; Itoh, Shinobu

    2013-09-16

    Redox properties of a mononuclear copper(II) superoxide complex, (L)Cu(II)-OO(•), supported by a tridentate ligand (L = 1-(2-phenethyl)-5-[2-(2-pyridyl)ethyl]-1,5-diazacyclooctane) have been examined as a model compound of the putative reactive intermediate of peptidylglycine α-hydroxylating monooxygenase (PHM) and dopamine β-monooxygenase (DβM) (Kunishita et al. J. Am. Chem. Soc. 2009, 131, 2788-2789; Inorg. Chem. 2012, 51, 9465-9480). On the basis of the reactivity toward a series of one-electron reductants, the reduction potential of (L)Cu(II)-OO(•) was estimated to be 0.19 ± 0.07 V vs SCE in acetone at 298 K (cf. Tahsini et al. Chem.-Eur. J. 2012, 18, 1084-1093). In the reaction of TEMPO-H (2,2,6,6-tetramethylpiperidine-N-hydroxide), a simple HAT (hydrogen atom transfer) reaction took place to give the corresponding hydroperoxide complex LCu(II)-OOH, whereas the reaction with phenol derivatives ((X)ArOH) gave the corresponding phenolate adducts, LCu(II)-O(X)Ar, presumably via an acid-base reaction between the superoxide ligand and the phenols. The reaction of (L)Cu(II)-OO(•) with a series of triphenylphosphine derivatives gave the corresponding triphenylphosphine oxides via an electrophilic ionic substitution mechanism with a Hammett ρ value as -4.3, whereas the reaction with thioanisole (sulfide) only gave a copper(I) complex. These reactivities of (L)Cu(II)-OO(•) are different from those of a similar end-on superoxide copper(II) complex supported by a tetradentate TMG3tren ligand (1,1,1-Tris{2-[N(2)-(1,1,3,3-tetramethylguanidino)]ethyl}amine (Maiti et al. Angew. Chem., Int. Ed. 2008, 47, 82-85).

  12. Computational redesign of a mononuclear zinc metalloenzyme for organophosphate hydrolysis

    DEFF Research Database (Denmark)

    Khare, Sagar D.; Kipnis, Yakov; Greisen, Per Junior;

    2012-01-01

    The ability to redesign enzymes to catalyze noncognate chemical transformations would have wide-ranging applications. We developed a computational method for repurposing the reactivity of metalloenzyme active site functional groups to catalyze new reactions. Using this method, we engineered a zinc...

  13. 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.

  14. Effect of ionic strength on ligand exchange kinetics between a mononuclear ferric citrate complex and siderophore desferrioxamine B

    Science.gov (United States)

    Ito, Hiroaki; Fujii, Manabu; Masago, Yoshifumi; Waite, T. David; Omura, Tatsuo

    2015-04-01

    The effect of ionic strength (I) on the ligand exchange reaction between a mononuclear ferric citrate complex and the siderophore, desferrioxamine B (DFB), was examined in the NaCl concentration range of 0.01-0.5 M, particularly focusing on the kinetics and mechanism of ligand exchange under environmentally relevant conditions. Overall ligand exchange rate constants were determined by spectrophotometrically measuring the time course of ferrioxamine B formation at a water temperature of 25 °C, pH 8.0, and citrate/Fe molar ratios of 500-5000. The overall ligand exchange rate decreased by 2-11-fold (depending on the citrate/Fe molar ratios) as I increased from approximately 0.01 to 0.5 M. In particular, a relatively large decrease was observed at lower I (dissociation of citrate from the parent complexes) dominates in ferrioxamine formation under the experimental conditions used. The model also predicts that the higher rate of ligand exchange at lower I is associated with the decrease in the ferric dicitrate complex stability because of the relatively high electrical repulsion between ferric monocitrate and free citrate at lower I (note that the reactivity of ferric dicitrate with DFB is smaller than that for the monocitrate complex). Overall, the findings of this study contribute to the understanding of the potential effect of I on ligand exchange kinetics in natural waters and provide fundamental knowledge on iron transformation and bioavailability.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    1988-03-01

    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.

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

    Directory of Open Access Journals (Sweden)

    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.

  17. Enzyme detection by microfluidics

    DEFF Research Database (Denmark)

    2013-01-01

    Microfluidic-implemented methods of detecting an enzyme, in particular a DNA-modifying enzyme, are provided, as well as methods for detecting a cell, or a microorganism expressing said enzyme. The enzyme is detected by providing a nucleic acid substrate, which is specifically targeted...

  18. Ocean iron cycle

    Science.gov (United States)

    Boyd, Philip W.

    Interest in the biogeochemical cycle of iron has grown rapidly over the last two decades, due to the potential role of this element in modulating global climate in the geological past and ocean productivity in the present day. This trace metal has a disproportionately large effect (1 × 105 C:Fe) on photosynthetic carbon fixation by phytoplankton. In around one third of the open ocean, so-called high-nitrate low-chlorophyll (HNLC) regions, the resident phytoplankton have low growth rates despite an abundance of plant nutrients. This is due to the low supply of iron. Iron is present in the ocean in three phases, dissolved, colloidal, and particulate (biogenic and lithogenic). However, iron chemistry is complex with interactions between chemistry and biology such as the production of iron-binding siderophores by oceanic bacteria. This results in the interplay of inorganic chemistry, photochemistry, and organic complexation. Sources of new iron include dust deposition, upwelling of iron-rich deep waters, and the resuspension and lateral transport of sediments. Sinks for iron are mainly biological as evidenced by the vertical nutrient-like profile for dissolved iron in the ocean. Iron is rapidly recycled by the upper ocean biota within a so-called "ferrous wheel." The fe ratio [(new iron)/(new + regenerated iron)] provides an index of the relative supply of iron to the biota by new versus recycled iron. Over the last 15 years, interest in the potential role of iron in shaping climate in the geological past resulted in some of the most ambitious experiments in oceanography: large-scale (i.e., 50-1000 km2) iron enrichment of HNLC waters. They have provided valuable insights into how iron supply influences the biogeochemical cycles of elements such as carbon, sulfur, silicon, nitrogen, and phosphate.

  19. Concurrent repletion of iron and zinc reduces intestinal oxidative damage in iron-and zinc-deficient rats

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    AIM: To understand the interactions between iron and zinc during absorption in iron- and zinc-deficient rats,and their consequences on intestinal oxidant-antioxidant balance.METHODS: Twenty-four weanling Wistar-Kyoto rats fed an iron- and zinc-deficient diet (< 6.5 mg Fe and 4.0 mg Zn/kg diet) for 4 wk were randomly divided into three groups (n = 8, each) and orally gavaged with 4 mg iron, 3.3 mg zinc, or 4 mg iron + 3.3 mg zinc for 2wk. At the last day of repletion, 3 h before the animals were sacrificed, they received either 37 mBq of 55Fe or 65Zn, to study their localization in the intestine, using microautoradiography. Hemoglobin, iron and zinc content in plasma and liver were measured as indicators of iron and zinc status. Duodenal sections were used for immunochemical staining of ferritin and metallothionein.Duodenal homogenates (mitochondrial and cytosolic fractions), were used to assess aconitase activity,oxidative stress, functional integrity and the response of antioxidant enzymes.RESULTS: Concurrent repletion of iron- and zinc-deficient rats showed reduced localization of these minerals compared to rats that were teated with iron or zinc alone;these data provide evidence for antagonistic interactions.This resulted in reduced formation of lipid and protein oxidation products and better functional integrity of the intestinal mucosa. Further, combined repletion lowered iron-associated aconitase activity and ferritin expression,but significantly elevated metallothionein and glutathione levels in the intestinal mucosa. The mechanism of interactions during combined supplementation and its subsequent effects appeared to be due to through modulation of cytosolic aconitase, which in turn influenced the labile iron pool and metallothionein levels, and hence reduced intestinal oxidative damage.CONCLUSION: Concurrent administration of iron and zinc corrects iron and zinc deficiency, and also reduces the intestinal oxidative damage associated with iron

  20. Naive Treg-like CCR7(+) mononuclear cells indicate unfavorable prognosis in hepatocellular carcinoma.

    Science.gov (United States)

    Shi, Jie-Yi; Duan, Meng; Sun, Qi-Man; Yang, Liuxiao; Wang, Zhi-Chao; Mynbaev, Ospan A; He, Yi-Feng; Wang, Ling-Yan; Zhou, Jian; Tang, Qi-Qun; Cao, Ya; Fan, Jia; Wang, Xiao-Ying; Gao, Qiang

    2016-07-01

    Chemokine receptor-like 1 (CCRL1) has the potential in creating a low level of CCL19 and CCL21 to hinder CCR7(+) cell tracking to tumor tissue. Previously, we found a tumor suppressive role of CCRL1 by impairing CCR7-related chemotaxis of tumor cells in human hepatocellular carcinoma (HCC). Here, we reported a contribution of CCR7(+) mononuclear cells in the tumor microenvironment to the progression of disease. Immunohistochemistry was used to investigate the distribution and clinical significance of CCR7(+) cells in a cohort of 240 HCC patients. Furthermore, the phenotype, composition, and functional status of CCR7(+) cells were determined by flow cytometry, immunofluorescence, and in vitro co-culture assays. We found that CCR7(+) mononuclear cells were dispersed around tumor tissue and negatively related to tumoral expression of CCRL1 (P CCR7(+) mononuclear cells positively correlated with the absence of tumor capsule, vascular invasion, and poor differentiation (P CCR7(+) mononuclear cells was significantly associated with worse survival and increased recurrence. We found that CCR7(+) mononuclear cells featured a naive Treg-like phenotype (CD45RA(+)CD25(+)FOXP3(+)) and possessed tumor-promoting potential by producing TGF-β1. Moreover, CCR7(+) cells were also composed of several immunocytes, a third of which were CD8(+) T cells. CCR7(+) Treg-like cells facilitate tumor growth and indicate unfavorable prognosis in HCC patients, but fortunately, their tracking to tumor tissue is under the control of CCRL1.

  1. Heterogeneity of lung mononuclear phagocytes during pneumonia: contribution of chemokine receptors.

    Science.gov (United States)

    Chen, Lanlin; Zhang, Zhimin; Barletta, Kathryn E; Burdick, Marie D; Mehrad, Borna

    2013-11-15

    Bacterial pneumonia is a common and dangerous illness. Mononuclear phagocytes, which comprise monocyte, resident and recruited macrophage, and dendritic cell subsets, are critical to antimicrobial defenses, but the dynamics of their recruitment to the lungs in pneumonia is not established. We hypothesized that chemokine-mediated traffic of mononuclear phagocytes is important in defense against bacterial pneumonia. In a mouse model of Klebsiella pneumonia, circulating Ly6C(hi) and, to a lesser extent, Ly6C(lo) monocytes expanded in parallel with accumulation of inflammatory macrophages and CD11b(hi) dendritic cells and plasmacytoid dendritic cells in the lungs, whereas numbers of alveolar macrophages remained constant. CCR2 was expressed by Ly6C(hi) monocytes, recruited macrophages, and airway dendritic cells; CCR6 was prominently expressed by airway dendritic cells; and CX3CR1 was ubiquitously expressed by blood monocytes and lung CD11b(hi) dendritic cells during infection. CCR2-deficient, but not CCL2-, CX3CR1-, or CCR6-deficient animals exhibited worse outcomes of infection. The absence of CCR2 had no detectable effect on neutrophils but resulted in reduction of all subsets of lung mononuclear phagocytes in the lungs, including alveolar macrophages and airway and plasmacytoid dendritic cells. In addition, absence of CCR2 skewed the phenotype of lung mononuclear phagocytes, abrogating the appearance of M1 macrophages and TNF-producing dendritic cells in the lungs. Taken together, these data define the dynamics of mononuclear phagocytes during pneumonia.

  2. Relationship of iron and extracellular virulence factors to Pseudomonas aeruginosa lung infections.

    Science.gov (United States)

    Sokol, P A; Woods, D E

    1984-08-01

    The iron concentration in the culture medium used to prepare the inocula influenced the virulence of Pseudomonas aeruginosa in a chronic pulmonary infection model in rats. Groups of rats were given transtracheal inocula of agar beads in which were embedded c.10(4) cfu of P. aeruginosa strain PAO and the mutants of strain PAO, Fe5 and Fe18. When strain PAO was grown in low-iron medium before infection, it caused severe parenchymal changes including a dense mononuclear cell infiltration in the alveolar spaces, as well as intra- and peribronchial inflammation. When strain PAO was grown in high-iron medium, the pathological changes in lungs were restricted to intra- and peribronchial inflammation. Strain Fe5, in which the effect of iron on yields of elastase is deregulated, produced similar pathological changes regardless of whether it was grown in low- or high-iron media. All rats infected with strain Fe18, in which the effect of iron on yields of toxin A is deregulated, died within 48 h after infection. These data indicate that the iron concentration of the culture medium can influence the pathogenesis of P. aeruginosa in a chronic respiratory infection. These studies also suggest that the regulation of extracellular virulence factors by iron is important in the determination of P. aeruginosa virulence.

  3. Microarray-based gene expression profiling of peripheral blood mononuclear cells in dairy cows with experimental hypocalcemia and milk fever

    National Research Council Canada - National Science Library

    Sasaki, K; Yamagishi, N; Kizaki, K; Sasaki, K; Devkota, B; Hashizume, K

    2014-01-01

    .... Therefore, peripheral blood mononuclear cells from dairy cows with experimentally induced hypocalcemia or spontaneous milk fever were subjected to oligo-microarray analysis to identify specific biomarker genes...

  4. Amelioration of iron overload-induced liver toxicity by a potent antioxidant and iron chelator, Emblica officinalis Gaertn.

    Science.gov (United States)

    Sarkar, Rhitajit; Hazra, Bibhabasu; Mandal, Nripendranath

    2015-07-01

    In liver, the major site of iron storage, iron overload is associated with oxidative damage of protein, lipid, and DNA and causes protein oxidation, lipid peroxidation, and rupture of hepatocytes, leading to cell death. Serum ferritin and liver iron content are the main forecasters of moderate to severe iron overload in the liver. The sequels of excess iron deposition in the liver are fibrosis and enhanced levels of serum enzymes and bilirubin markers. Emblica officinalis (EO) fruit extract was found efficient in lessening intraperitoneally injected iron dextran-induced liver toxicity in Swiss albino mice. Mice administered with different doses of 70% methanol extract of EO (50, 100, and 200 mg kg(-1) body weight) showed significant decrease in liver iron, serum ferritin, and serum enzyme levels, along with the decrease in lipid peroxidation, protein oxidation, and collagen content. The activity was further supported by its considerable iron chelation with half-maximal inhibitory concentration of 70.24 ± 2.74 μg ml(-1) and the protection on ferrous ion-mediated DNA breakdown with 50% protection ([P]50) of 1.04 ± 0.01 μg ml(-1). Simultaneously, the extract effectively induced the antioxidant enzyme levels and also exhibited the potential activity of reductive release of ferritin iron. These findings suggest that the EO extract may be used as a potent drug for the treatment of pathological sequences arisen in the iron overload-induced liver damage. © The Author(s) 2013.

  5. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... This Content: NEXT >> Featured Video Living With and Managing Iron-Deficiency Anemia 05/18/2011 This video— ... treatment. For more information about living with and managing iron-deficiency anemia, go to the Health Topics ...

  6. Iron in diet

    Science.gov (United States)

    ... meat (especially beef) Oysters Poultry, dark red meat Salmon Tuna Whole grains Reasonable amounts of iron are ... iron up to three times. Foods rich in vitamin C ( such as citrus, strawberries, tomatoes, and potatoes) ...

  7. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... iron-rich protein that carries oxygen from the lungs to the rest of the body. Iron-deficiency ... 2011 This video—presented by the National Heart, Lung, and Blood Institute, part of the National Institutes ...

  8. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... deficiency anemia may require treatment in a hospital, blood transfusions , iron injections, or intravenous iron therapy. Rate This ... video—presented by the National Heart, Lung, and Blood Institute, part of the National ...

  9. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... easily treated condition that occurs if you don't have enough iron in your body. Low iron ... can occur if your red blood cells don't contain enough hemoglobin (HEE-muh-glow-bin). Hemoglobin ...

  10. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... muh-glow-bin). Hemoglobin is an iron-rich protein that carries oxygen from the lungs to the ... other complications. Infants and young children and women are the two groups at highest risk for iron- ...

  11. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... severity of the condition. Treatments may include dietary changes, medicines, and surgery. Severe iron-deficiency anemia may require treatment in a hospital, blood ... With and Managing Iron-Deficiency Anemia 05/18/2011 This video— ...

  12. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... Events Spokespeople Email Alerts E-Newsletters About NHLBI Organization NHLBI Director Budget, Planning, & Legislative Advisory Committees Jobs ... the body. Iron-deficiency anemia usually develops over time if your body doesn't have enough iron ...

  13. Iron supplements (image)

    Science.gov (United States)

    The mineral iron is an essential nutrient for humans because it is part of blood cells, which carry oxygen to all body cells. There is no conclusive evidence that iron supplements contribute to heart attacks.

  14. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... easily treated condition that occurs if you don't have enough iron in your body. Low iron ... can occur if your red blood cells don't contain enough hemoglobin (HEE-muh-glow-bin). Hemoglobin ...

  15. Iron age: novel targets for iron overload.

    Science.gov (United States)

    Casu, Carla; Rivella, Stefano

    2014-12-05

    Excess iron deposition in vital organs is the main cause of morbidity and mortality in patients affected by β-thalassemia and hereditary hemochromatosis. In both disorders, inappropriately low levels of the liver hormone hepcidin are responsible for the increased iron absorption, leading to toxic iron accumulation in many organs. Several studies have shown that targeting iron absorption could be beneficial in reducing or preventing iron overload in these 2 disorders, with promising preclinical data. New approaches target Tmprss6, the main suppressor of hepcidin expression, or use minihepcidins, small peptide hepcidin agonists. Additional strategies in β-thalassemia are showing beneficial effects in ameliorating ineffective erythropoiesis and anemia. Due to the suppressive nature of the erythropoiesis on hepcidin expression, these approaches are also showing beneficial effects on iron metabolism. The goal of this review is to discuss the major factors controlling iron metabolism and erythropoiesis and to discuss potential novel therapeutic approaches to reduce or prevent iron overload in these 2 disorders and ameliorate anemia in β-thalassemia.

  16. Iron deficiency anemia

    OpenAIRE

    Naigamwalla, Dinaz Z.; Webb, Jinelle A.; Giger, Urs

    2012-01-01

    Iron is essential to virtually all living organisms and is integral to multiple metabolic functions. The most important function is oxygen transport in hemoglobin. Iron deficiency anemia in dogs and cats is usually caused by chronic blood loss and can be discovered incidentally as animals may have adapted to the anemia. Severe iron deficiency is characterized by a microcytic, hypochromic, potentially severe anemia with a variable regenerative response. Iron metabolism and homeostasis will be ...

  17. Iron-Deficiency Anemia

    Science.gov (United States)

    ... page from the NHLBI on Twitter. What Is Iron-Deficiency Anemia? Español Iron-deficiency anemia is a common, ... Content: NEXT >> Featured Video Living With and Managing Iron-Deficiency Anemia 05/18/2011 This video—presented by ...

  18. Iron-Deficiency Anemia

    Science.gov (United States)

    ... the NHLBI on Twitter. What Is Iron-Deficiency Anemia? Español Iron-deficiency anemia is a common, easily ... Featured Video Living With and Managing Iron-Deficiency Anemia 05/18/2011 This video—presented by the ...

  19. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... the NHLBI on Twitter. What Is Iron-Deficiency Anemia? Español Iron-deficiency anemia is a common, easily ... Featured Video Living With and Managing Iron-Deficiency Anemia 05/18/2011 This video—presented by the ...

  20. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... the NHLBI on Twitter. What Is Iron-Deficiency Anemia? Español Iron-deficiency anemia is a common, easily ... Featured Video Living With and Managing Iron-Deficiency Anemia 05/18/2011 This video—presented by the ...

  1. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... blood transfusions , iron injections, or intravenous iron therapy. Rate This Content: NEXT >> Featured Video Living With and Managing Iron-Deficiency Anemia 05/18/2011 This video—presented by the National Heart, Lung, and Blood Institute, part of the National ...

  2. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... blood transfusions , iron injections, or intravenous iron therapy. Rate This Content: NEXT >> Featured Video Living With and Managing Iron-Deficiency Anemia 05/18/2011 This video—presented by the National Heart, Lung, and Blood Institute, part of the National ...

  3. 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...... as a cellular model for in vitro measurement of total 86rubidium uptake to give an index of sodium-potassium pump activity. Four groups of subjects were evaluated, 28 normotensive and 20 borderline hypertensive offspring of hypertensives, and 12 borderline hypertensives and 28 normotensives with normotensive...... parents. 86Rubidium uptake was significantly increased in the borderline hypertensive subjects, especially in the borderline hypertensive offspring of hypertensive patients. Our results indicate that the sodium-potassium pump is activated in mononuclear leucocytes from borderline hypertensives...

  4. High doses of vitamin A impair iron absorption

    Directory of Open Access Journals (Sweden)

    Gabriel FR

    2012-10-01

    Full Text Available Fabíola Rainato Gabriel, Vivian MM Suen, Julio Sergio Marchini, José Eduardo Dutra de OliveiraDivision of Clinical Nutrition, Department of Internal Medicine, Ribeirão Preto School of Medicine, São Paulo University, São Paulo, BrazilObjective: The present study aimed to determine the influence of vitamin A on iron absorption when vitamin A and iron are administered together orally compared with the administration of iron alone.Methods: This was a randomized double-blind clinical trial conducted on healthy men with normal red blood cell indices. Five experiments were performed, with iron (10 mg; iron (10 mg plus vitamin A (450, 900 and 1800 µg, and placebo. After an 8-hour fast, basal (T0 blood samples were collected: basal (T0, 2 hours (T1, and 4 hours (T2 after the ingestion of the compounds to be studied. Iron was determined by inductively coupled plasma mass spectrometry. Serum ferritin was determined by an immunometric method, ie, by chemoluminescent enzyme immunoassay. Plasma retinol was measured by high-pressure liquid chromatography. Serum curves and the sum of the area under the curve adjusted to the mixed effects linear model were determined (P < 0.05.Results: Vitamin A at the doses of 450 and 900 µg had a stimulating effect, which, however, did not differ significantly from that of experiment 1 in which iron was used alone. At the dose of 1800 µg, vitamin A had a negative effect on iron absorption.Conclusion: High doses of vitamin A may cause lower serum iron levels, whereas a low dose favors iron absorption.Keywords: iron absorption, serum iron, vitamin A, oral iron, oral supplement

  5. Correlation of liver enzymes with serum ferritin levels in AND#946;-thalassemia major

    OpenAIRE

    Rameshwar L. Suman; Anuradha Sanadhya; Pradeep Meena; Suresh Goyal

    2016-01-01

    Background: Liver is the earliest site of iron deposition in transfusion dependent beta -thalassemia major and iron induced liver injury is the common cause of morbidity. Liver enzymes are raised and indicative of liver injury in transfusion dependant beta-thalassemia major patients. Objective of the study was to find out the correlation of serum ferritin with liver enzymes serum glutamic oxalocetic transaminase (SGOT) and serum glutamic pyruvic transaminase (SGPT) in thalassemia major childr...

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

    Directory of Open Access Journals (Sweden)

    Anne S. Meyer

    2013-08-01

    Full Text Available 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.

  7. Serum transferrin receptor levels in the evaluation of iron deficiency in the neonate.

    Science.gov (United States)

    Rusia, U; Flowers, C; Madan, N; Agarwal, N; Sood, S K; Sikka, M

    1996-10-01

    Iron deficiency anemia (IDA) is a major global problem. Early onset of iron deficiency in developing countries makes it imperative to identify iron deficiency in neonates. Most conventional laboratory parameters of iron status fail to distinguish neonates with iron deficient erythropoiesis. Serum transferrin receptor (STFR) levels are a recent sensitive measure of iron deficiency and the present study was carried out to evaluate the usefulness of cord serum transferrin receptors in identifying iron deficient erythropoiesis in neonates. A complete hemogram, red cell indices, iron profile: serum iron (SI), percent transferrin saturation (TS%) and serum ferritin (SF) was carried out in 100 full-term neonates and their mothers at parturition. Cord and maternal STFR levels were estimated using a sensitive enzyme-linked immunosorbent assay (ELISA) technique. Anemic women had a significantly lower SI, their TS% and high STFR levels suggesting that iron deficiency was responsible for the anemia. In the neonates of iron deficient mothers, cord SI, TS% and cord ferritin were not significantly different from those of neonates born to non-anemic mothers. Cord STFR level correlated well with hemoglobin (Hb) and laboratory parameters of iron status, and its level was significantly higher in neonates born to anemic mothers than in those born to non-anemic mothers. It was the only laboratory parameter to differentiate between neonates born to anemic and non-anemic mothers. Therefore, STFR is a sensitive index of iron status in neonates and identifies neonates with iron deficient erythropoiesis.

  8. Effects of iron manipulation on trace elements level in a model of colitis in rats

    Institute of Scientific and Technical Information of China (English)

    M Barollo; R D'Inc(a); M Scarpa; V Medici; R Cardin; M Bortolami; C Ruffolo; I Angriman; GC Sturniolo

    2005-01-01

    AIM: Trace elements (TE) metabolism is altered in inflammatory bowel diseases. TE (zinc and copper) are constituents of antioxidant enzymes. Iron is involved in the pathogenesis of chronic inflammation. The aim was to evaluate zinc and copper status and the effects of iron manipulation in experimental colitis.METHODS: Twenty-four male Sprague-Dawley rats were divided into four groups: standard diet, iron-deprived diet,iron-supplemented diet, and sham-treated controls.Macroscopic damage was scored. DNA adducts were measured in the colon. Liver and colonic concentration of TE were measured.RESULTS: Macroscopic damage was reduced in irondeprived groups and increased in iron-supplemented rats.Damage to the DNA was reduced in iron-deprived groups and increased in iron-supplemented groups. Liver and colonic iron concentrations were reduced in iron-deprived and increased in iron-supplemented rats. Liver zinc concentration was reduced after supplementation whereas colonic levels were similar in controls and treated rats. Liver copper concentration was reduced in all the colitic groups except in the iron-supplemented group whereas colonic concentration was increased in iron-deprived rats.CONCLUSION: Iron deprivation diminishes the severity of DNBS colitis while supplementation worsens colitis. Zinc and copper status are modified by iron manipulation.

  9. Studies of biological properties of Uncaria tomentosa extracts on human blood mononuclear cells.

    Science.gov (United States)

    Bors, Milena; Michałowicz, Jaromir; Pilarski, Radosław; Sicińska, Paulina; Gulewicz, Krzysztof; Bukowska, Bożena

    2012-08-01

    Uncaria tomentosa (Willd.) DC is a lignified climbing plant from South and Central America, which (under the name of "vilcacora" or "cat's claw") has become highly popular in many countries due to its proven immunostimmulatory and anti-inflammatory activities and also with respect to its anticancer and antioxidative effects. There are insufficient data on the mechanism of U. tomentosa action on normal blood mononuclear cells. The aim of the study was to analyze the impact of ethanol and aqueous extracts from bark and leaves of Uncaria tomentosa on the structure and function of human mononuclear cells and to find out whether the kind of extractant used modulates biological activity of the extracts studied. Plant material consisted of four different extracts: (1) ethanol extract from leaves, (2) aqueous extract from leaves, (3) ethanol extract from bark and (4) aqueous extract from bark. The effect of these extracts on protein damage as well as on free-radical formation in human peripheral blood mononuclear cells was analyzed. Moreover, changes in viability, size, and granularity as well as apoptotic alterations in human blood mononuclear cells exposed to U. tomentosa extracts were investigated. The oxidative changes were observed in mononuclear blood cells exposed to both ethanol and aqueous extracts obtained from bark and leaves. Moreover, in the cells studied the extracts from U. tomentosa induced apoptosis and a decrease in viability of mononuclear blood cells, with the exception of aqueous extract from leaves. Additionally, no statistically significant changes in the cell size were observed both for aqueous extracts from leaves and bark. Changes in the blood mononuclear cell granularity were observed at 250 μg/mL for all extracts examined. The strongest changes were observed for the ethanol extract of the bark, which increased cell granularity at 50 μg/mL and changed cell size at 100 μg/mL. The conducted research showed differences in biological activity

  10. A hitchhiker's guide to myeloid cell subsets: practical implementation of a novel mononuclear phagocyte classification system

    Directory of Open Access Journals (Sweden)

    Martin eGuilliams

    2015-08-01

    Full Text Available The classification of mononuclear phagocytes as either dendritic cells or macrophages has been mainly based on morphology, the expression of surface markers and assumed functional specialization. We have recently proposed a novel classification system of mononuclear phagocytes based on their ontogeny. Here we discuss the practical application of such a classification system through a number of prototypical examples we have encountered while hitchhiking from one subset to another, across species and between steady state and inflammatory settings. Finally, we discuss the advantages and drawbacks of such a classification system and propose a number of improvements to move from theoretical concepts to concrete guidelines.

  11. p-Cresol affects reactive oxygen species generation, cell cycle arrest, cytotoxicity and inflammation/atherosclerosis-related modulators production in endothelial cells and mononuclear cells.

    Directory of Open Access Journals (Sweden)

    Mei-Chi Chang

    Full Text Available AIMS: Cresols are present in antiseptics, coal tar, some resins, pesticides, and industrial solvents. Cresol intoxication leads to hepatic injury due to coagulopathy as well as disturbance of hepatic circulation in fatal cases. Patients with uremia suffer from cardiovascular complications, such as atherosclerosis, thrombosis, hemolysis, and bleeding, which may be partly due to p-cresol toxicity and its effects on vascular endothelial and mononuclear cells. Given the role of reactive oxygen species (ROS and inflammation in vascular thrombosis, the objective of this study was to evaluate the effect of p-cresol on endothelial and mononuclear cells. METHODS: EA.hy926 (EAHY endothelial cells and U937 cells were exposed to different concentrations of p-cresol. Cytotoxicity was evaluated by 3-(4,5-Dimethylthiazol-2-yl-2,5 -diphenyltetrazolium bromide (MTT assay and trypan blue dye exclusion technique, respectively. Cell cycle distribution was analyzed by propidium iodide flow cytometry. Endothelial cell migration was studied by wound closure assay. ROS level was measured by 2',7'-dichlorofluorescein diacetate (DCF fluorescence flow cytometry. Prostaglandin F2α (PGF2α, plasminogen activator inhibitor-1 (PAI-1, soluble urokinase plasminogen activator receptor (suPAR, and uPA production were determined by Enzyme-linked immunosorbant assay (ELISA. RESULTS: Exposure to 100-500 µM p-cresol decreased EAHY cell number by 30-61%. P-cresol also decreased the viability of U937 mononuclear cells. The inhibition of EAHY and U937 cell growth by p-cresol was related to induction of S-phase cell cycle arrest. Closure of endothelial wounds was inhibited by p-cresol (>100 µM. P-cresol (>50 µM also stimulated ROS production in U937 cells and EAHY cells but to a lesser extent. Moreover, p-cresol markedly stimulated PAI-1 and suPAR, but not PGF2α, and uPA production in EAHY cells. CONCLUSIONS: p-Cresol may contribute to atherosclerosis and thrombosis in patients with

  12. The Relationship between Iron Dyshomeostasis and Amyloidogenesis in Alzheimer’s Disease: Two Sides of the Same Coin

    OpenAIRE

    Peters, Douglas G.; Connor, James R.; Meadowcroft, Mark D.

    2015-01-01

    The dysregulation of iron metabolism in Alzheimer’s disease is not accounted for in the current framework of the amyloid cascade hypothesis. Accumulating evidence suggests that impaired iron homeostasis is an early event in Alzheimer’s disease progression. Iron dyshomeostasis leads to a loss of function in several enzymes requiring iron as a cofactor, the formation of toxic oxidative species, and the elevated production of beta-amyloid proteins. Several common genetic polymorphisms that cause...

  13. Macrophages and Iron Metabolism.

    Science.gov (United States)

    Soares, Miguel P; Hamza, Iqbal

    2016-03-15

    Iron is a transition metal that due to its inherent ability to exchange electrons with a variety of molecules is essential to support life. In mammals, iron exists mostly in the form of heme, enclosed within an organic protoporphyrin ring and functioning primarily as a prosthetic group in proteins. Paradoxically, free iron also has the potential to become cytotoxic when electron exchange with oxygen is unrestricted and catalyzes the production of reactive oxygen species. These biological properties demand that iron metabolism is tightly regulated such that iron is available for core biological functions while preventing its cytotoxic effects. Macrophages play a central role in establishing this delicate balance. Here, we review the impact of macrophages on heme-iron metabolism and, reciprocally, how heme-iron modulates macrophage function.

  14. [Iron function and carcinogenesis].

    Science.gov (United States)

    Akatsuka, Shinya; Toyokuni, Shinya

    2016-07-01

    Though iron is an essential micronutrient for humans, the excess state is acknowledged to be associated with oncogenesis. For example, iron overload in the liver of the patients with hereditary hemocromatosis highly increases the risk of hepatocellular carcinoma. Also, as to asbestos-related mesothelioma, such kinds of asbestos with a higher iron content are considered to be more carcinogenic. Iron is a useful element, which enables fundamental functions for life such as oxygen carrying and electron transport. However, in the situation where organisms are unable to have good control of it, iron turns into a dangerous element which catalyzes generation of reactive oxygen. In this review, I first outline the relationships between iron and cancer in general, then give an explanation about iron-related animal carcinogenesis models.

  15. Interleukin-6 infusion during human endotoxaemia inhibits in vitro release of the urokinase receptor from peripheral blood mononuclear cells

    DEFF Research Database (Denmark)

    Ostrowski, S R; Plomgaard, P; Fischer, C P

    2005-01-01

    Leucocyte expression of the urokinase receptor [urokinase-type plasminogen activator receptor (uPAR)] is regulated by inflammatory mediators. This study investigated the in vivo effect of endotoxin, interleukin (IL)-6 and tumour necrosis factor (TNF)-alpha on uPAR-release in vivo and in vitro...... in humans. Healthy subjects received intravenous endotoxin injection [high-dose, 2 ng/kg (n=8) and low-dose, 0.06 ng/kg (n=7)], coadministration of 0.06 ng/kg endotoxin and 3 h recombinant human (rh)IL-6 infusion (n=7) or 3 h infusion of rhIL-6 (n=6), rhTNF-alpha (n=6) or NaCl (n=5). Soluble uPAR (su......PAR) was measured by enzyme-linked immunosorbent assay in plasma and supernatants from unstimulated and phytohaemagglutinin and lipopolysaccharide-stimulated peripheral blood mononuclear cell (PBMC) cultures incubated for 24 h. The spontaneous and stimulated uPAR-release from PBMC cultures was enhanced 5 h after...

  16. Hydrolytic protein cleavage mediated by unusual mononuclear copper(II) complexes: X-ray structures and solution studies.

    Science.gov (United States)

    de Oliveira, Mauricio C B; Scarpellini, Marciela; Neves, Ademir; Terenzi, Hernán; Bortoluzzi, Adailton J; Szpoganics, Bruno; Greatti, Alessandra; Mangrich, Antônio S; de Souza, Emanuel M; Fernandez, Pablo M; Soares, Marcia R

    2005-02-21

    The crystal structures and redox and UV-vis/EPR spectroscopic properties of two new mononuclear copper(II) complexes, [Cu(HL1)Cl2] (1) and [Cu(L1)Cl] (2), prepared through the reaction between copper(II) chloride and the ligand 2-[(bis(pyridylmethyl)amino)methyl]-4-methyl-6-formylphenol (HL1) under distinct base conditions, are reported along with solution studies. Also, we demonstrate that these CuII complexes are able to cleave unactivated peptide bonds from bovine serum albumin (BSA) and the thermostable enzyme Taq DNA polymerase at micromolar concentration, under mild pH and temperature conditions. The cleavage activity seems to be specific with defined proteolytic fragments appearing after protein treatment. The location of the specific cleavage sites was tentatively assigned to solvent-accessible portions of the protein. These are two of the most active Cu(II) complexes described to date, since their cleavage activity is detected in minutes and evidence is here presented for a hydrolytic mechanism mediating protein cleavage by these complexes.

  17. Reducing power and iron chelating property of Terminalia chebula (Retz. alleviates iron induced liver toxicity in mice

    Directory of Open Access Journals (Sweden)

    Sarkar Rhitajit

    2012-08-01

    Full Text Available Abstract Background The 70% methanol extract of Terminalia chebula Retz. fruit (TCME was investigated for its in vitro iron chelating property and in vivo ameliorating effect on hepatic injury of iron overloaded mice. Methods The effect of fruit extract on Fe2+-ferrozine complex formation and Fe2+ mediated pUC-18 DNA breakdown was studied in order to find the in vitro iron chelating activity. Thirty-six Swiss Albino mice were divided into six groups of: blank, patient control and treated with 50, 100, 200 mg/kg b.w. of TCME and desirox (standard iron chelator drug with Deferasirox as parent compound. Evaluations were made for serum markers of hepatic damage, antioxidant enzyme, lipid per oxidation and liver fibrosis levels. The reductive release of ferritin iron by the extract was further studied. Results In vitro results showed considerable iron chelation with IC50 of 27.19 ± 2.80 μg/ml, and a significant DNA protection with [P]50 of 1.07 ± 0.03 μg/ml along with about 86% retention of supercoiled DNA. Iron-dextran injection (i.p. caused significant increase in the levels of the serum enzymes, viz., alanine aminotransferase (ALAT, aspartate aminotransferase (ASAT, alkaline phosphatase (ALP and Bilirubin, which were subsequently lowered by oral administration of 200 mg/kg b.w. dose of the fruit extract by 81.5%, 105.88%, 188.08% and 128.31%, respectively. Similarly, treatment with the same dose of the extract was shown to alleviate the reduced levels of liver antioxidant enzyme superoxide dismutase, catalase, glutathione S-transferase and non-enzymatic reduced glutathione, by 49.8%, 53.5%, 35.4% and 11% respectively, in comparison to the iron overloaded mice. At the same time, the fruit extract effectively lowered the iron-overload induced raised levels of lipid per oxidation, protein carbonyl, hydroxyproline and liver iron by 49%, 67%, 67% and 26%, respectively, with oral treatment of 200 mg/kg b.w. dose of TCME. The fruit extract

  18. 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.

  19. Iron and a mixture of DHA and EPA supplementation, alone and in combination, affect bioactive lipid signalling and morbidity of iron deficient South African school children in a two-by-two randomised controlled trial.

    Science.gov (United States)

    Malan, L; Baumgartner, J; Zandberg, L; Calder, P C; Smuts, C M

    2016-02-01

    We recently reported that iron supplementation increased respiratory morbidity in iron deficient South African children. This increase, however, was attenuated when iron was provided in combination with a mixture of DHA/EPA. To explore potential underlying mechanisms, we examined the effects of iron and DHA/EPA, alone and in combination, on plasma lipid-derived immune modulator concentrations and related gene expression in peripheral blood mononuclear cells (PBMC). DHA/EPA decreased inflammatory 12-hydroxyeicosatetraenoic acid and tended to increase anti-inflammatory and pro-resolving 17-hydroxydocosahexaenoic acid (17-HDHA), while iron decreased 17-HDHA. However, in combination with iron, the anti-inflammatory effect of DHA/EPA was maintained. These biochemical changes may explain the prevention of iron-induced respiratory morbidity that we observed when iron was supplemented in combination with DHA/EPA during the 8.5 month randomised controlled trial and might lead to a safer approach of delivering iron supplementation. The study was registered at clinicaltrials.gov as NCT01092377.

  20. New rat models of iron sucrose-induced iron overload.

    Science.gov (United States)

    Vu'o'ng Lê, Bá; Khorsi-Cauet, Hafida; Villegier, Anne-Sophie; Bach, Véronique; Gay-Quéheillard, Jérôme

    2011-07-01

    The majority of murine models of iron sucrose-induced iron overload were carried out in adult subjects. This cannot reflect the high risk of iron overload in children who have an increased need for iron. In this study, we developed four experimental iron overload models in young rats using iron sucrose and evaluated different markers of iron overload, tissue oxidative stress and inflammation as its consequences. Iron overload was observed in all iron-treated rats, as evidenced by significant increases in serum iron indices, expression of liver hepcidin gene and total tissue iron content compared with control rats. We also showed that total tissue iron content was mainly associated with the dose of iron whereas serum iron indices depended essentially on the duration of iron administration. However, no differences in tissue inflammatory and antioxidant parameters from controls were observed. Furthermore, only rats exposed to daily iron injection at a dose of 75 mg/kg body weight for one week revealed a significant increase in lipid peroxidation in iron-treated rats compared with their controls. The present results suggest a correlation between iron overload levels and the dose of iron, as well as the duration and frequency of iron injection and confirm that iron sucrose may not play a crucial role in inflammation and oxidative stress. This study provides important information about iron sucrose-induced iron overload in rats and may be useful for iron sucrose therapy for iron deficiency anemia as well as for the prevention and diagnosis of iron sucrose-induced iron overload in pediatric patients.

  1. Enzyme inhibition by iminosugars

    DEFF Research Database (Denmark)

    López, Óscar; Qing, Feng-Ling; Pedersen, Christian Marcus

    2013-01-01

    Imino- and azasugar glycosidase inhibitors display pH dependant inhibition reflecting that both the inhibitor and the enzyme active site have groups that change protonation state with pH. With the enzyme having two acidic groups and the inhibitor one basic group, enzyme-inhibitor complexes...

  2. Antioxidant compounds in the seaweed Gelidiella acerosa protects human Peripheral Blood Mononuclear Cells against TCDD induced toxicity.

    Science.gov (United States)

    Ilavarasi, K; Chermakani, P; Arif Nisha, S; Sheeja Malar, D; Pandima Devi, K

    2015-04-01

    2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is a persistent environmental toxin formed as an unintentional by-product of incomplete combustion. Several therapeutic approaches have evolved to combat its toxicity since it elicits immunotoxicity, neurotoxicity, hepatotoxicity, carcinogenicity and lethality. Search for drugs from natural resources especially from seaweeds has become intense due to their enormous pharmacological potential. Hence, the present study aims at revealing the protective effect of methanolic extract of G. acerosa (MEGA) in Peripheral Blood Mononuclear Cells (PBMC) against TCDD induced toxicity, by assessing the antioxidant, anti-apoptotic and cytoprotective activities. The results of antioxidant assays suggests that MEGA reverted TCDD induced toxicity by causing an alteration in the levels of antioxidant enzymes (Catalase [CAT], Superoxide dismutase [SOD], Glutathione peroxidase [GPx], Glutathione-S-transferase [GST]) and Glutathione [GSH]. The results of lipid peroxidation assay and protein carbonyl content reveal that MEGA protects PBMC from TCDD induced macromolecular damage. MEGA was found to exhibit significant (p TCDD induced oxidative DNA damage. Levels of phase-I detoxification enzymes determined by EROD assay and semi-quantitative RT-PCR showed that TCDD up-regulates the expression of CYP1A1 and upon co-treatment with MEGA, the expression got slightly decreased suggesting its protective role. Preliminary phytochemical analysis demonstrates that the extract is rich in cardiac glycosides and terpenoids. LC-MS analysis revealed the presence of antioxidants including caffeic acid, phytol and mannoheptulose in MEGA, which could be attributed for the observed protective effect against TCDD induced toxicity.

  3. Modulation of transglutaminase activity in mononuclear phagocytes and macrophage-like tumor cell lines by differentiation agents

    Energy Technology Data Exchange (ETDEWEB)

    Goldman, R.

    1987-01-01

    The effect of glucocorticosteroids, retinoids, 1,25-dihydroxyvitamin D/sub 3/ (1,25(OH)/sub 2/D/sub 3/) and the tumor promoter phorbol myristate acetate (TPA) on the expression of transglutaminase activity in in vitro differentiating bone marrow-derived mouse and rat mononuclear phagocytes (BMDMP) and mouse and human myeloid leukemia cell lines was assessed. Dexamethasone was found to induce an increase of about 100% in transglutaminase activity in mouse and rat BMDMP. The effect was time- and dose-dependent, and specific for steroids with glucocorticoid activity. Retinoic acid (RA) suppressed transglutaminase activity in mouse BMDMP and enhanced it in rat BMDMP. In murine and human myeloid leukemia cell lines, dexamethasone enhanced transglutaminase activity to a varying degree, RA suppressed it in P388D1 cells and enhanced it in the other cell lines. 1,25(OH)/sub 2/D/sub 3/ induced a rather small augmentation of enzyme expression, whereas TPA suppressed enzyme expression (70-100%). The species-specific differences previously observed by the authors for the effect of RA, dexamethasone and 1,25(OH)/sub 2/D/sub 3/ on the formation of BMDMP from mouse and rat bone marrow progenitor cells are now shown to extend also to effects on expression of transglutaminase activity. From a mechanistic point of view it is of interest that dexamethasone uniformly enhanced transglutaminase activity, whereas TPA suppressed it. The data suggest that modulation of transglutaminase activity by the four agents occurs via disparate mechanisms.

  4. Olive oil and its phenolic constituent tyrosol attenuates dioxin-induced toxicity in peripheral blood mononuclear cells via an antioxidant-dependent mechanism.

    Science.gov (United States)

    Kalaiselvan, Ilavarasi; Dicson, Sheeja Malar; Kasi, Pandima Devi

    2015-01-01

    Olive oil (OO) and its phenolic compounds are reported to possess many potential biological effects, which are ascribed to its powerful antioxidant property. In this study, we have assessed whether OO and its phenolic compound tyrosol (TY) could mitigate 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) induced oxidative damages in peripheral blood mononuclear cells (PBMC). The results showed that exposure of PBMC to 10 nM TCDD caused significant cell death and elevated cellular concentrations of reactive oxygen species and lipid peroxidation. Comet assay indicated that OO and TY protected DNA damage against dioxin toxicity. In addition, alterations in levels of antioxidant enzymes were substantially prevented by OO and TY. TCDD-induced CYP1A1 activity and loss of mitochondrial membrane potential were significantly reduced by the administration of OO and TY. The results suggested that dietary modifications incorporating diets rich in OO and associated phenolics could prove beneficial in protecting individuals against toxicity induced by dioxins.

  5. Malabsorption of iron in children with iron deficiency.

    Science.gov (United States)

    Gross, S J; Stuart, M J; Swender, P T; Oski, F A

    1976-05-01

    Inability to absorb oral iron is believed to be an extremely rare cause of therapeutic failure in the treatment of iron deficiency anemia. Six patients who had failed to respond to oral iron therapy were studied by a simple oral absorption test and contrasted with 25 patients with untreated iron deficiency anemia and 10 normal subjects. All six of the patients who were therapeutic failures demonstrated impaired iron absorption in the absence of other clinical evidence of gastrointestinal disease. In the 25 newly diagnosed patients with iron deficiency. 24 demonstrated elevated iron absorptions while 10 ironreplete normal subjects had minimal elevations in their serum iron values following the administration of the test dose of 1 mg of elemental iron per kilogram. When the therapeutic failures were treated with parenteral iron, all had a therapeutic response. In addition, after treatment the impaired absorption of iron improved transiently. All children who absorbed iron readily responded to oral iron therapy.

  6. Biophysical Characterization of an Bifunctional Iron Regulating Enzyme

    Science.gov (United States)

    2002-05-01

    the explicit purpose of mass overexpression . The principal genetic tool used is a plasmid, a short, circular DNA fragment that once altered, is easily...viscous protein laden solution is collected and placed into about 40 cm sterile dialysis tubing. The tubing, which is made of cellulose , has pores... synthase and transferring receptor (Gray et al, 1993). The fourth domain is involved with the IRP binding to IRE. Arginines 728 and 732 contact the IRE

  7. Iron chelating agents for iron overload diseases

    Directory of Open Access Journals (Sweden)

    Guido Crisponi

    2014-09-01

    Full Text Available Although iron is an essential element for life, an excessive amount may become extremely toxic both for its ability to generate reactive oxygen species, and for the lack in humans of regulatory mechanisms for iron excretion. Chelation therapy has been introduced in clinical practice in the seventies of last century to defend thalassemic patients from the effects of iron overload and, in spite of all its limitations, it has dramatically changed both life expectancy and quality of life of patients. It has to be considered that the drugs in clinical use present some disadvantages too, this makes urgent new more suitable chelating agents. The requirements of an iron chelator have been better and better defined over the years and in this paper they will be discussed in detail. As a final point the most interesting ligands studied in the last years will be presented.

  8. A mononuclear iron(II) complex: cooperativity, kinetics and activation energy of the solvent-dependent spin transition.

    Science.gov (United States)

    Bushuev, Mark B; Pishchur, Denis P; Logvinenko, Vladimir A; Gatilov, Yuri V; Korolkov, Ilya V; Shundrina, Inna K; Nikolaenkova, Elena B; Krivopalov, Viktor P

    2016-01-07

    The system [FeL2](BF4)2 (1)-EtOH-H2O (L is 4-(3,5-dimethyl-1H-pyrazol-1-yl)-2-(pyridin-2-yl)-6-methylpyrimidine) shows a complicated balance between the relative stabilities of solvatomorphs and polymorphs of the complex [FeL2](BF4)2. New solvatomorphs, 1(LS)·EtOH·H2O and β-1(LS)·xH2O, were isolated in this system. They were converted into four daughter phases, 1(A/LS), 1(D/LS), 1(E/LS)·yEtOH·zH2O and 1(F/LS). On thermal cycling in sealed ampoules, the phases 1(LS)·EtOH·H2O and β-1(LS)·xH2O transform into the anhydrous phase 1(A/LS). The hysteresis loop width for the (A/LS) ↔ (A/HS) spin transition depends on the water and ethanol contents in the ampoule and varies from ca. 30 K up to 145 K. The reproducible hysteresis loop of 145 K is the widest ever reported one for a spin crossover complex. The phase 1(A/LS) combines the outstanding spin crossover properties with thermal robustness allowing for multiple cycling in sealed ampoules without degradation. The kinetics of the 1(A/LS) → 1(A/HS) transition is sigmoidal which is indicative of strong cooperative interactions. The cooperativity of the 1(A/LS) → 1(A/HS) transition is related to the formation of a 2D supramolecular structure of the phase 1(A/LS). The activation energy for the spin transition is very high (hundreds of kJ mol(-1)). The kinetics of the 1(A/HS) → 1(A/LS) transition can either be sigmoidal or exponential depending on the water and ethanol contents in the ampoule. The phases 1(D/LS) and 1(F/LS) show gradual crossover, whereas the phase 1(E/LS)·yEtOH·yH2O shows a reversible hysteretic transition associated with the solvent molecule release and uptake.

  9. Iron deficiency anaemia.

    Science.gov (United States)

    Lopez, Anthony; Cacoub, Patrice; Macdougall, Iain C; Peyrin-Biroulet, Laurent

    2016-02-27

    Anaemia affects roughly a third of the world's population; half the cases are due to iron deficiency. It is a major and global public health problem that affects maternal and child mortality, physical performance, and referral to health-care professionals. Children aged 0-5 years, women of childbearing age, and pregnant women are particularly at risk. Several chronic diseases are frequently associated with iron deficiency anaemia--notably chronic kidney disease, chronic heart failure, cancer, and inflammatory bowel disease. Measurement of serum ferritin, transferrin saturation, serum soluble transferrin receptors, and the serum soluble transferrin receptors-ferritin index are more accurate than classic red cell indices in the diagnosis of iron deficiency anaemia. In addition to the search for and treatment of the cause of iron deficiency, treatment strategies encompass prevention, including food fortification and iron supplementation. Oral iron is usually recommended as first-line therapy, but the most recent intravenous iron formulations, which have been available for nearly a decade, seem to replenish iron stores safely and effectively. Hepcidin has a key role in iron homoeostasis and could be a future diagnostic and therapeutic target. In this Seminar, we discuss the clinical presentation, epidemiology, pathophysiology, diagnosis, and acute management of iron deficiency anaemia, and outstanding research questions for treatment.

  10. 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...

  11. Administration of liposomal agents and blood clearance capacity of the mononuclear phagocyte system

    NARCIS (Netherlands)

    E.W.M. van Etten (Els); M.T. ten Kate (Marian); S.V. Snijders (Susan); I.A.J.M. Bakker-Woudenberg (Irma)

    1998-01-01

    textabstractAs liposomes are cleared from the circulation to a substantial extent by the phagocytic cells of the mononuclear phagocyte system (MPS), there is a question whether administration of liposome-based therapeutic agents interferes with clearance of infectious o

  12. SURFACE MODIFICATION OF NANOPARTICLES TO OPPOSE UPTAKE BY THE MONONUCLEAR PHAGOCYTE SYSTEM

    NARCIS (Netherlands)

    STORM, G; BELLIOT, SO; DAEMEN, T; LASIC, DD

    1995-01-01

    An overview of recent advances in the surface modification of colloidal particles to oppose uptake by the mononuclear phagocyte system (MPS) is presented. First, we describe the colloidal particles and hydrophilic coating materials investigated, with particular focus on the literature concerning par

  13. 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 (Agaric

  14. Slc27a2 expression in peripheral blood mononuclear cells as a marker for overweight development

    NARCIS (Netherlands)

    Caimari, A.; Oliver, P.; Rodenburg, W.; Keijer, J.; Palou, A.

    2010-01-01

    Background: Peripheral blood mononuclear cells (PBMC) can be collected easily and repeatedly. Their potential use to reflect the individual's biological status is increasingly explored. Obesity is becoming the most common health problem of the 21st century, being dietary intake an important determin

  15. Age and metabolic risk factors associated with oxidatively damaged DNA in human peripheral blood mononuclear cells

    DEFF Research Database (Denmark)

    Løhr, Mille; Jensen, Annie; Eriksen, Louise

    2015-01-01

    Aging is associated with oxidative stress-generated damage to DNA and this could be related to metabolic disturbances. This study investigated the association between levels of oxidatively damaged DNA in peripheral blood mononuclear cells (PBMCs) and metabolic risk factors in 1,019 subjects, aged...

  16. Evidence for a dual function of monocyte-derived mononuclear phagocytes during chronic intestinal inflammation

    DEFF Research Database (Denmark)

    Rivollier, Aymeric Marie Christian; Pool, Lieneke; Frising, Ulrika

    Mononuclear phagocytes derived from tissue-infiltrating monocytes play diverse roles in immunity, ranging from pathogen killing to immune regulation. We and others showed that, upon recruitment to the intestinal mucosa, the differentiation of Ly6Chi monocytes into phagocytes with anti- versus pro...... suggest a dual and time-restricted contribution of MDP during the development and healing phases of the disease....

  17. Four-site cooperative spin crossover in a mononuclear FeII complex

    DEFF Research Database (Denmark)

    Lennartson, Anders; Bond, Andrew; Piligkos, Stergios;

    2012-01-01

    Round and round: A mononuclear Fe(II) complex (see picture) with an N(4)S(2) coordination set has been characterized in four polymorphic forms. Two of the polymorphs display four-site cooperative spin crossover (SCO), shown conclusively by the crystal structure of a fully ordered 1:3 high-spin/lo...

  18. Intracoronary infusion of mononuclear cells after PCI-treated myocardial infarction and arrhythmogenesis : is it safe?

    NARCIS (Netherlands)

    Robbers, L. F. H. J.; Nijveldt, R.; Beek, A. M.; Kemme, M. J. B.; Delewi, R.; Hirsch, Alexander; van der Laan, A. M.; van der Vleuten, P. A.; Piek, J. J.; Zijlstra, F.; van Rossum, A. C.

    2012-01-01

    To reduce long-term morbidity after revascularised acute myocardial infarction, different therapeutic strategies have been investigated. Cell therapy with mononuclear cells from bone marrow (BMMC) or peripheral blood (PBMC) has been proposed to attenuate the adverse processes of remodelling and subs

  19. Role of mononuclear phagocyte function in endotoxin-induced tumor necrosis

    NARCIS (Netherlands)

    Hofhuis, F.M.A.; Bloksma, N.; Willers, J.M.N.

    1984-01-01

    The temporal susceptibility of tumors to induction of necrosis and regression by endotoxin was investigated further with a focus on the role of the putative mediator, tumor necrosis factor (TNF). Production of this factor was shown earlier to require prior activation of the mononuclear phagocytic sy

  20. 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.

  1. Interleukin-8 transcripts in mononuclear cells determine impaired graft function after kidney transplantation

    DEFF Research Database (Denmark)

    Borst, Christoffer; Xia, Shengqiang; Bistrup, Claus

    2015-01-01

    OBJECTIVE: Interleukin-8 (IL-8) has been associated with ischemia reperfusion injury after renal allograft transplantation. Impaired allograft function may cause major impact on patient morbidity and health care costs. We investigated whether transcript levels in mononuclear cells including IL-8 ...

  2. Variation of DNA damage levels in peripheral blood mononuclear cells isolated in different laboratories

    DEFF Research Database (Denmark)

    Godschalk, Roger W L; Ersson, Clara; Stępnik, Maciej

    2014-01-01

    This study investigated the levels of DNA strand breaks and formamidopyrimidine DNA glycosylase (FPG) sensitive sites, as assessed by the comet assay, in peripheral blood mononuclear cells (PBMC) from healthy women from five different countries in Europe. The laboratory in each country (referred ...

  3. Demonstration of the heterolytic O-O bond cleavage of putative nonheme iron(II)-OOH(R) complexes for Fenton and enzymatic reactions.

    Science.gov (United States)

    Bang, Suhee; Park, Sora; Lee, Yong-Min; Hong, Seungwoo; Cho, Kyung-Bin; Nam, Wonwoo

    2014-07-21

    One-electron reduction of mononuclear nonheme iron(III) hydroperoxo (Fe(III)-OOH) and iron(III) alkylperoxo (Fe(III)-OOR) complexes by ferrocene (Fc) derivatives resulted in the formation of the corresponding iron(IV) oxo complexes. The conversion rates were dependent on the concentration and oxidation potentials of the electron donors, thus indicating that the reduction of the iron(III) (hydro/alkyl)peroxo complexes to their one-electron reduced iron(II) (hydro/alkyl)peroxo species is the rate-determining step, followed by the heterolytic O-O bond cleavage of the putative iron(II) (hydro/alkyl)peroxo species to give the iron(IV) oxo complexes. Product analysis supported the heterolytic O-O bond-cleavage mechanism. The present results provide the first example showing the one-electron reduction of iron(III) (hydro/alkyl)peroxo complexes and the heterolytic O-O bond cleavage of iron(II) (hydro/alkyl)peroxo species to form iron(IV) oxo intermediates which occur in nonheme iron enzymatic and Fenton reactions.

  4. Vigorous, but differential mononuclear cell response of cirrhotic patients to bacterial ligands

    Institute of Scientific and Technical Information of China (English)

    Varenka J Barbero-Becerra; María Concepción Gutiérrez-Ruiz; Carmen Maldonado-Bernal; Félix I Téllez-Avila; Roberto Alfaro-Lara; Florencia Vargas-Vorácková

    2011-01-01

    AIM: To study the role of gram-positive and gram-negative bacteria in the pathogenesis of liver injury, specifically the activation of inflammatory mediators. METHODS: Peripheral blood mononuclear cells of 20 out-patients were studied, 10 of them with cirrhosis. Peripheral blood mononuclear cells were isolated and exposed to lipopolysaccharide or lipoteichoic acid. CD14, Toll-like receptor 2 and 4 expression was determined by flow cytometry, and tumor necrosis factor (TNF) α, interleukin (IL)-1β, IL-6, IL-12 and IL-10 secretion in supernatants was determined by ELISA. RESULTS: Higher CD14, Toll-like receptor 2 and 4 expression was observed in peripheral blood mononuclear cells from cirrhotic patients, (P < 0.01, P < 0.006, P < 0.111) respectively. Lipopolysaccharide and lipoteichoic acid induced a further increase in CD14 expression (P < 0.111 lipopolysaccharide, P < 0.013 lipoteichoic acid), and a decrease in Toll-like receptor 2 (P < 0.008 lipopolysaccharide, P < 0.008 lipoteichoic acid) and Toll-like receptor 4 (P < 0.008 lipopolysaccharide, P < 0.028 lipoteichoic acid) expression. With the exception of TNFα, absolute cytokine secretion of peripheral blood mononuclear cells was lower in cirrhotic patients under nonexposure conditions (P < 0.070 IL-6, P < 0.009 IL-1β, P < 0.022 IL-12). Once exposed to lipopolysaccharide or lipoteichoic acid, absolute cytokine secretion of peripheral blood mononuclear cells was similar in cirrhotic and non-cirrhotic patients, determining a more vigorous response in the former (P < 0.005 TNFα, IL-1β, IL-6, IL-2 and IL-10 lipopolysaccharide; P < 0.037 TNFα; P < 0.006 IL-1β; P < 0.005 IL-6; P < 0.007 IL-12; P < 0.014 IL-10 lipoteichoic acid). Response of peripheral blood mononuclear cells was more intense after lipopolysaccharide than after lipoteichoic acid exposure. CONCLUSION: Peripheral blood mononuclear cells of cirrhotic patients are able to respond to a sudden bacterial ligand exposure, particularly lipopolysaccharide

  5. Developing mononuclear copper-active-oxygen complexes relevant to reactive intermediates of biological oxidation reactions.

    Science.gov (United States)

    Itoh, Shinobu

    2015-07-21

    Active-oxygen species generated on a copper complex play vital roles in several biological and chemical oxidation reactions. Recent attention has been focused on the reactive intermediates generated at the mononuclear copper active sites of copper monooxygenases such as dopamine β-monooxygenase (DβM), tyramine β-monooxygenase (TβM), peptidylglycine-α-hydroxylating monooxygenase (PHM), and polysaccharide monooxygenases (PMO). In a simple model system, reaction of O2 and a reduced copper(I) complex affords a mononuclear copper(II)-superoxide complex or a copper(III)-peroxide complex, and subsequent H(•) or e(-)/H(+) transfer, which gives a copper(II)-hydroperoxide complex. A more reactive species such as a copper(II)-oxyl radical type species could be generated via O-O bond cleavage of the peroxide complex. However, little had been explored about the chemical properties and reactivity of the mononuclear copper-active-oxygen complexes due to the lack of appropriate model compounds. Thus, a great deal of effort has recently been made to develop efficient ligands that can stabilize such reactive active-oxygen complexes in synthetic modeling studies. In this Account, I describe our recent achievements of the development of a mononuclear copper(II)-(end-on)superoxide complex using a simple tridentate ligand consisting of an eight-membered cyclic diamine with a pyridylethyl donor group. The superoxide complex exhibits a similar structure (four-coordinate tetrahedral geometry) and reactivity (aliphatic hydroxylation) to those of a proposed reactive intermediate of copper monooxygenases. Systematic studies based on the crystal structures of copper(I) and copper(II) complexes of the related tridentate supporting ligands have indicated that the rigid eight-membered cyclic diamine framework is crucial for controlling the geometry and the redox potential, which are prerequisites for the generation of such a unique mononuclear copper(II)-(end-on)superoxide complex

  6. Whole-blood culture is a valid low-cost method to measure monocytic cytokines - A comparison of cytokine production in cultures of human whole-blood, mononuclear cells and monocytes

    DEFF Research Database (Denmark)

    Damsgaard, Camilla T.; Lauritzen, Lotte; Calder, Philip C.

    2009-01-01

    assessed the intra- and inter-individual variation in cytokine production. In 64 healthy men (age 19-40 years) IL-6, TNF and IL-10 were measured by enzyme-linked immunosorbent assay in supernatants from whole-blood, PBMC and monocytes cultured 24 h with lipopolysaccharide (LPS) or UV-killed L acidophilus......Whole-blood and peripheral blood mononuclear cell (PBMC) cultures are used as non-validated surrogate measures of monocytic cytokine production. The aim of this investigation was to compare ex vivo cytokine production from human whole-blood and PBMC with that from isolated monocytes. We also...

  7. Brain iron homeostasis.

    Science.gov (United States)

    Moos, Torben

    2002-11-01

    Iron is essential for virtually all types of cells and organisms. The significance of the iron for brain function is reflected by the presence of receptors for transferrin on brain capillary endothelial cells. The transport of iron into the brain from the circulation is regulated so that the extraction of iron by brain capillary endothelial cells is low in iron-replete conditions and the reverse when the iron need of the brain is high as in conditions with iron deficiency and during development of the brain. Whereas there is good agreement that iron is taken up by means of receptor-mediated uptake of iron-transferrin at the brain barriers, there are contradictory views on how iron is transported further on from the brain barriers and into the brain extracellular space. The prevailing hypothesis for transport of iron across the BBB suggests a mechanism that involves detachment of iron from transferrin within barrier cells followed by recycling of apo-transferrin to blood plasma and release of iron as non-transferrin-bound iron into the brain interstitium from where the iron is taken up by neurons and glial cells. Another hypothesis claims that iron-transferrin is transported into the brain by means of transcytosis through the BBB. This thesis deals with the topic "brain iron homeostasis" defined as the attempts to maintain constant concentrations of iron in the brain internal environment via regulation of iron transport through brain barriers, cellular iron uptake by neurons and glia, and export of iron from brain to blood. The first part deals with transport of iron-transferrin complexes from blood to brain either by transport across the brain barriers or by uptake and retrograde axonal transport in motor neurons projecting beyond the blood-brain barrier. The transport of iron and transport into the brain was examined using radiolabeled iron-transferrin. Intravenous injection of [59Fe-125]transferrin led to an almost two-fold higher accumulation of 59Fe than of

  8. Efficacy and safety of iron sucrose for iron deficiency in patients with dialysis-associated anemia: North American clinical trial.

    Science.gov (United States)

    Charytan, C; Levin, N; Al-Saloum, M; Hafeez, T; Gagnon, S; Van Wyck, D B

    2001-02-01

    Iron sucrose has been used to provide intravenous (IV) iron therapy to patients outside the United States for more than 50 years. In a multicenter North American clinical trial, we determined the efficacy and safety of iron sucrose therapy in patients with dialysis-associated anemia, evidence of iron deficiency, and below-target hemoglobin (Hgb) levels despite epoetin therapy. Evidence of iron deficiency included a transferrin saturation (Tsat) less than 20% and ferritin level less than 300 ng/mL, and below-target Hgb levels included values less than 11.0 g/dL. We administered iron sucrose in 10 doses, each administered undiluted as 100 mg IV push over 5 minutes, without a prior test dose. We assessed efficacy by determining the subsequent change in Hgb, Tsat, and ferritin values. We assessed safety by recording blood pressure and adverse events after iron sucrose injection and comparing results with those for the same patients during an observation control period. Results showed a significant increase in Hgb level that was first evident after three doses of iron sucrose and persisted at least 5 weeks after the 10th dose. Tsat and ferritin levels also increased significantly and remained elevated. In 77 enrolled patients, including those with previous iron dextran sensitivity, other drug allergies, or concurrent angiotensin-converting enzyme inhibitor use, we saw no serious adverse drug reactions and no change in intradialytic blood pressure associated with iron sucrose administration. We conclude that iron sucrose injection administered as 1,000 mg in 10 divided doses by IV push without a prior test dose is safe and effective for the treatment of iron deficiency in patients with dialysis-associated anemia.

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

    Directory of Open Access Journals (Sweden)

    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.

  10. Colour Metallography of Cast Iron

    Institute of Scientific and Technical Information of China (English)

    Zhou Jiyang; Liu Jincheng

    2010-01-01

    @@ Chapter 3 Spheroidal Graphite Cast Iron(I) Spheroidal Graphite Cast Iron, SG iron in short, refers to the cast iron in which graphite precipitates as spheroidal shape during solidification of liquid iron. The graphite in common commercial cast iron can only be changed from flake to spheroidal shape by spheroidising treatment. Since spheroidal graphite reduces the cutting effect of stress concentration, the metal matrix strength of SG iron can be applied around 70%-90%, thus the mechanical property of SG iron is significantly superior to other cast irons;even the tensile strength of SG iron is higher than that carbon steel.

  11. Iron and Stony-iron Meteorites

    Science.gov (United States)

    Haack, H.; McCoy, T. J.

    2003-12-01

    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 and other terrestrial planets. This fact has been recognized since the work of Chladni (1794), who argued that stony-iron meteorites must have originated in outer space and fallen during fireballs and that they provide our closest analogue to the material that comprises our own planet's core. This chapter deals with our current knowledge of these meteorites. How did they form? What can they tell us about the early evolution of the solar system and its solid bodies? How closely do they resemble the materials from planetary interiors? What do we know and don't we know?Iron and stony-iron meteorites constitute ˜6% of meteorite falls (Grady, 2000). Despite their scarcity among falls, iron meteorites are our only samples of ˜75 of the ˜135 asteroids from which meteorites originate ( Keil et al., 1994; Scott, 1979; Meibom and Clark, 1999; see also Chapter 1.05), suggesting that both differentiated asteroids and the geologic processes that produced them were common.Despite the highly evolved nature of iron and stony-iron meteorites, their chemistry provides important

  12. Colour Metallography of Cast Iron

    Institute of Scientific and Technical Information of China (English)

    Zhou Jiyang; Liu Jincheng

    2010-01-01

    @@ Spheroidal Graphite Cast Iron(Ⅳ) 3.7 Segregation of SG iron The non-uniform distribution of solute elements during solidification results in the micro segregation of SG iron.As for the redistribution of elements in the phases of the solidification structure,there is no intrinsic difference between SG iron and grey iron[132].

  13. Adult peripheral blood mononuclear cells transdifferentiate in vitro and integrate into the retina in vivo.

    Science.gov (United States)

    Liu, Qian; Guan, Liping; Huang, Bing; Li, Weihua; Su, Qiao; Yu, Minbin; Xu, Xiaoping; Luo, Ting; Lin, Shaochun; Sun, Xuerong; Chen, Mengfei; Chen, Xigu

    2011-06-01

    Adult peripheral blood-derived cells are able to differentiate into a variety of cell types, including nerve cells, liver-like cells and epithelial cells. However, their differentiation into retina-like cells is controversial. In the present study, transdifferentiation potential of human adult peripheral blood mononuclear cells into retina-like cells and integration into the retina of mice were investigated. Freshly isolated adult peripheral blood mononuclear cells were divided into two groups: cells in group I were cultured in neural stem cell medium, and cells in group II were exposed to conditioned medium from rat retinal tissue culture. After 5 days, several distinct cell morphologies were observed, including standard mononuclear, neurons with one or two axons and elongated glial-like cells. Immunohistochemical analysis of neural stem cell, neuron and retina cell markers demonstrated that cells in both groups were nestin-, MAP2 (microtubule-associated protein)- and GFAP (glial fibrillary acidic protein)-positive. Flow cytometry results suggested a significant increase in nestin-, MAP2- and CD16-positive cells in group I and nestin-, GFAP-, MAP2-, vimentin- and rhodopsin-positive cells in group II. To determine survival, migration and integration in vivo, cell suspensions (containing group I or group II cells) were injected into the vitreous or the peritoneum. Tissue specimens were obtained and immunostained 4 weeks after transplantation. We found that cells delivered by intravitreal injection integrated into the retina. Labelled cells were not detected in the retina of mice receiving differentiated cells by intraperitoneal injection, but cells (groups I and II) were detected in the liver and spleen. Our findings revealed that human adult peripheral blood mononuclear cells could be induced to transdifferentiate into neural precursor cells and retinal progenitor cells in vitro, and the differentiated peripheral blood mononuclear cells can migrate and integrate

  14. 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.

  15. Defining mononuclear phagocyte subset homology across several distant warm-blooded vertebrates through comparative transcriptomics

    Directory of Open Access Journals (Sweden)

    Thien eVu Manh

    2015-06-01

    Full Text Available Mononuclear phagocytes are organized in a complex system of ontogenically and functionally-distinct subsets, that has been best described in mouse and to some extent in human. Identification of homologous mononuclear phagocyte subsets in other vertebrate species of biomedical, economic and environmental interest is needed to improve our knowledge in physiologic and physio-pathologic processes, and to design intervention strategies against a variety of diseases, including zoonotic infections.We developed a streamlined approach combining refined cell sorting and integrated comparative transcriptomics analyses which revealed conservation of the mononuclear phagocyte organization across human, mouse, sheep, pigs and, in some respect, chicken. This strategy should help democratizing the use of omics analyses for the identification and study of cell types across tissues and species. Moreover we identified conserved gene signatures that enable robust identification and universal definition of these cell types. We identified new evolutionarily conserved gene candidates and gene interaction networks for the molecular regulation of the development or functions of these cell types, as well as conserved surface candidates for refined subset phenotyping throughout species. A phylogenetic analysis revealed that orthologous genes of the conserved signatures exist in teleost fishes and apparently not in Lamprey, indicating conservation of the genetic support for mononuclear phagocyte organization throughout jawed vertebrates but likely not in agnathans. Altogether this work provides molecular clues to the definition and functions of mononuclear phagocyte subsets across vertebrates which shall be useful to rigorously identify these cells and to design universal strategies to manipulate them in many target species towards the goal to reach and maintain global health.

  16. 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.

  17. Austempered Ductile Iron Machining

    Science.gov (United States)

    Pilc, Jozef; Šajgalík, Michal; Holubják, Jozef; Piešová, Marianna; Zaušková, Lucia; Babík, Ondrej; Kuždák, Viktor; Rákoci, Jozef

    2015-12-01

    This article deals with the machining of cast iron. In industrial practice, Austempered Ductile Iron began to be used relatively recently. ADI is ductile iron that has gone through austempering to get improved properties, among which we can include strength, wear resistance or noise damping. This specific material is defined also by other properties, such as high elasticity, ductility and endurance against tenigue, which are the properties, that considerably make the tooling characteristic worse.

  18. Iron and the athlete.

    Science.gov (United States)

    Suedekum, Natalie A; Dimeff, Robert J

    2005-08-01

    Iron is an important mineral necessary for many biologic pathways. Different levels of deficiency can occur in the athlete, resulting in symptoms that range from none to severe fatigue. Iron deficiency without anemia may adversely affect athletic performance. Causes of iron deficiency include poor intake, menstrual losses, gastrointestinal and genitourinary losses due to exercise-induced ischemia or organ movement, foot strike hemolysis, thermohemolysis, and sweat losses. A higher incidence of deficiency occurs in female athletes compared with males.

  19. Symmetry breaking and light-induced spin-state trapping in a mononuclear FeII complex with the two-step thermal conversion

    Science.gov (United States)

    Buron-Le Cointe, M.; Ould Moussa, N.; Trzop, E.; Moréac, A.; Molnar, G.; Toupet, L.; Bousseksou, A.; Létard, J. F.; Matouzenko, G. S.

    2010-12-01

    Crystallographic, magnetic, and Raman investigations of the mononuclear [FeII(Hpy-DAPP)](BF4)2 complex are presented. Its particular feature is a two-step thermal spin conversion in spite of a unique symmetry-independent iron site per unit cell. The plateau around 140 K is associated with a symmetry breaking visible by the appearance of weak (0k0) k odd Bragg peaks. Symmetries of the high-temperature high-spin state and of the low-temperature low-spin state are both monoclinic P21/c , so that the symmetry breaking on the plateau is associated with a reentrant phase transition. It is discussed in relation with Ising-type microscopic models. At the plateau level, the two symmetry-independent molecules differ both by their spin state and the conformation (chair versus twist-boat) of one metallocycle. At low-temperature photoinduced phenomena have been investigated: a partial phototransformation [light-induced excited spin-state trapping (LIESST) effect] is observed under visible red irradiation. Raman spectroscopy shows that the molecular photoinduced state is the high-spin one. Nevertheless, as no macroscopic symmetry breaking is observed, the unique average cationic [FeII(Hpy-DAPP)] state of the unit cell is intermediate between pure low-spin and high-spin states and presents a conformational disorder for one metallocycle. Reverse-LIESST has also been evidenced using near infrared excitation. Thus, the mononuclear [Fe(Hpy-DAPP)](BF4)2 compound offers the opportunity to discuss the interplay between spin conversion, molecular conformational change, and ordering processes.

  20. Enzyme kinetics of conjugating enzymes: PAPS sulfotransferase.

    Science.gov (United States)

    James, Margaret O

    2014-01-01

    The sulfotransferase (SULT) enzymes catalyze the formation of sulfate esters or sulfamates from substrates that contain hydroxy or amine groups, utilizing 3'-phosphoadenosyl-5'-phosphosulfate (PAPS) as the donor of the sulfonic group. The rate of product formation depends on the concentrations of PAPS and substrate as well as the sulfotransferase enzyme; thus, if PAPS is held constant while varying substrate concentration (or vice versa), the kinetic constants derived are apparent constants. When studied over a narrow range of substrate concentrations, classic Michaelis-Menten kinetics can be observed with many SULT enzymes and most substrates. Some SULT enzymes exhibit positive or negative cooperativity during conversion of substrate to product, and the kinetics fit the Hill plot. A characteristic feature of most sulfotransferase-catalyzed reactions is that, when studied over a wide range of substrate concentrations, the rate of product formation initially increases as substrate concentration increases, then decreases at high substrate concentrations, i.e., they exhibit substrate inhibition or partial substrate inhibition. This chapter gives an introduction to sulfotransferases, including a historical note, the nomenclature, a description of the function of SULTs with different types of substrates, presentation of examples of enzyme kinetics with SULTs, and a discussion of what is known about mechanisms of substrate inhibition in the sulfotransferases.

  1. Physics of iron

    Energy Technology Data Exchange (ETDEWEB)

    Anderson, O.

    1993-10-01

    This volume comprises papers presented at the AIRAPT Conference, June 28 to July 1993. The iron sessions at the meeting were identified as the Second Ironworkers Convention. The renewal of interest stems from advances in technologies in both diamond-anvil cell (DAC) and shock wave studies as well as from controversies arising from a lack of consensus among both experimentalists and theoreticians. These advances have produced new data on iron in the pressure-temperature regime of interest for phase diagrams and for temperatures of the core/mantle and inner-core/outer-core boundaries. Particularly interesting is the iron phase diagram inferred from DAC studies. A new phase, {beta}, with a {gamma}-{beta}-{epsilon} triple point at about 30 GPa and 1190 K, and possible sixth phase, {omega}, with an {epsilon}-{Theta}-melt triple point at about 190 GPa and 4000 K are deemed possible. The importance of the equation of state of iron in consideration of Earth`s heat budget and the origin of its magnetic field invoke the interest of theoreticians who argue on the basis of molecular dynamics and other first principles methods. While the major thrust of both meetings was on the physics of pure iron, there was notable contributions on iron alloys. Hydrogen-iron alloys, iron-sulfur liquids, and the comparability to rhenium in phase diagram studies are discussed. The knowledge of the physical properties of iron were increased by several contributions.

  2. Iron, Meat and Health

    Directory of Open Access Journals (Sweden)

    Catherine Geissler

    2011-02-01

    Full Text Available This article is a summary of the publication “Iron and Health” by the Scientific Advisory Committee on Nutrition (SACN to the U.K. Government (2010, which reviews the dietary intake of iron and the impact of different dietary patterns on the nutritional and health status of the U.K. population. It concludes that several uncertainties make it difficult to determine dose-response relationships or to confidently characterize the risks associated with iron deficiency or excess. The publication makes several recommendations concerning iron intakes from food, including meat, and from supplements, as well as recommendations for further research.

  3. Recalling the Iron Girls

    Institute of Scientific and Technical Information of China (English)

    1998-01-01

    The phrase "iron girl" is symbolic of an era. Widely used in the 1960s and the early 1970s, it was a term that described women who, in the spirit of sexual equality, found in themselves a physical strength that surpassed their psychologi cal expectations. With their might and power, they proved to society that women could do everything that men could. The title of "iron girl" was their pride.The well-known writer Fan Xiaoqing, was one such iron girl. She says the "iron girls" were nothing less than a quest for perfection.

  4. Iron overload and immunity

    Institute of Scientific and Technical Information of China (English)

    Gra(c)a Porto; Maria De Sousa

    2007-01-01

    Progress in the characterization of genes involved in the control of iron homeostasis in humans and in mice has improved the definition of iron overload and of the cells affected by it. The cell involved in iron overload with the greatest effect on immunity is the macrophage.Intriguing evidence has emerged, however, in the last 12 years indicating that parenchymal iron overload is linked to genes classically associated with the immune system. This review offers an update of the genes and proteins relevant to iron metabolism expressed in cells of the innate immune system, and addresses the question of how this system is affected in clinical situations of iron overload. The relationship between iron and the major cells of adaptive immunity, the T lymphocytes,will also be reviewed. Most studies addressing this last question in humans were performed in the clinical model of Hereditary Hemochromatosis. Data will also be reviewed demonstrating how the disruption of molecules essentially involved in adaptive immune responses result in the spontaneous development of iron overload and how they act as modifiers of iron overload.

  5. Iron-dependent changes in cellular energy metabolism: influence on citric acid cycle and oxidative phosphorylation.

    Science.gov (United States)

    Oexle, H; Gnaiger, E; Weiss, G

    1999-11-10

    Iron modulates the expression of the critical citric acid cycle enzyme aconitase via a translational mechanism involving iron regulatory proteins. Thus, the present study was undertaken to investigate the consequences of iron perturbation on citric acid cycle activity, oxidative phosphorylation and mitochondrial respiration in the human cell line K-562. In agreement with previous data iron increases the activity of mitochondrial aconitase while it is reduced upon addition of the iron chelator desferrioxamine (DFO). Interestingly, iron also positively affects three other citric acid cycle enzymes, namely citrate synthase, isocitric dehydrogenase, and succinate dehydrogenase, while DFO decreases the activity of these enzymes. Consequently, iron supplementation results in increased formation of reducing equivalents (NADH) by the citric acid cycle, and thus in increased mitochondrial oxygen consumption and ATP formation via oxidative phosphorylation as shown herein. This in turn leads to downregulation of glucose utilization. In contrast, all these metabolic pathways are reduced upon iron depletion, and thus glycolysis and lactate formation are significantly increased in order to compensate for the decrease in ATP production via oxidative phosphorylation in the presence of DFO. Our results point to a complex interaction between iron homeostasis, oxygen supply and cellular energy metabolism in human cells.

  6. Iron and oxidative stress in cardiomyopathy in thalassemia.

    Science.gov (United States)

    Berdoukas, Vasilios; Coates, Thomas D; Cabantchik, Zvi Ioav

    2015-11-01

    With repeated blood transfusions, patients with thalassemia major rapidly become loaded with iron, often surpassing hepatic metal accumulation capacity within ferritin shells and infiltrating heart and endocrine organs. That pathological scenario contrasts with the physiological one, which is characterized by an efficient maintenance of all plasma iron bound to circulating transferrin, due to a tight control of iron ingress into plasma by the hormone hepcidin. Within cells, most of the acquired iron becomes protein-associated, as once released from endocytosed transferrin, it is used within mitochondria for the synthesis of protein prosthetic groups or it is incorporated into enzyme active centers or alternatively sequestered within ferritin shells. A few cell types also express the iron extrusion transporter ferroportin, which is under the negative control of circulating hepcidin. However, that system only backs up the major cell regulated iron uptake/storage machinery that is poised to maintain a basal level of labile cellular iron for metabolic purposes without incurring potentially toxic scenarios. In thalassemia and other transfusion iron-loading conditions, once transferrin saturation exceeds about 70%, labile forms of iron enter the circulation and can gain access to various types of cells via resident transporters or channels. Within cells, they can attain levels that exceed their ability to chemically cope with labile iron, which has a propensity for generating reactive oxygen species (ROS), thereby inducing oxidative damage. This scenario occurs in the heart of hypertransfused thalassemia major patients who do not receive adequate iron-chelation therapy. Iron that accumulates in cardiomyocytes forms agglomerates that are detected by T2* MRI. The labile forms of iron infiltrate the mitochondria and damage cells by inducing noxious ROS formation, resulting in heart failure. The very rapid relief of cardiac dysfunction seen after intensive iron

  7. Benefits and harms of iron supplementation in iron-deficient and iron-sufficient children.

    Science.gov (United States)

    Domellöf, Magnus

    2010-01-01

    Due to high iron requirements, young children are at risk for iron deficiency anemia. Iron supplements are therefore often recommended, especially since iron deficiency anemia in children is associated with poor neurodevelopment. However, in contrast to most other nutrients, excess iron cannot be excreted by the human body and it has recently been suggested that excessive iron supplementation of young children may have adverse effects on growth, risk of infections, and even on cognitive development. Recent studies support that iron supplements are beneficial in iron-deficient children but there is a risk of adverse effects in those who are iron replete. In populations with a low prevalence of iron deficiency, general supplementation should therefore be avoided. Iron-fortified foods can still be generally recommended since they seem to be safer than medicinal iron supplements, but the level of iron fortification should be limited. General iron supplementation is recommended in areas with a high prevalence of iron deficiency, with the exception of malarious areas where a cautious supplementation approach needs to be adopted, based either on screening or a combination of iron supplements and infection control measures. More studies are urgently needed to better determine the risks and benefits of iron supplementation and iron-fortified foods given to iron-deficient and iron-sufficient children.

  8. Isocitrate ameliorates anemia by suppressing the erythroid iron restriction response.

    Science.gov (United States)

    Richardson, Chanté L; Delehanty, Lorrie L; Bullock, Grant C; Rival, Claudia M; Tung, Kenneth S; Kimpel, Donald L; Gardenghi, Sara; Rivella, Stefano; Goldfarb, Adam N

    2013-08-01

    The unique sensitivity of early red cell progenitors to iron deprivation, known as the erythroid iron restriction response, serves as a basis for human anemias globally. This response impairs erythropoietin-driven erythropoiesis and underlies erythropoietic repression in iron deficiency anemia. Mechanistically, the erythroid iron restriction response results from inactivation of aconitase enzymes and can be suppressed by providing the aconitase product isocitrate. Recent studies have implicated the erythroid iron restriction response in anemia of chronic disease and inflammation (ACDI), offering new therapeutic avenues for a major clinical problem; however, inflammatory signals may also directly repress erythropoiesis in ACDI. Here, we show that suppression of the erythroid iron restriction response by isocitrate administration corrected anemia and erythropoietic defects in rats with ACDI. In vitro studies demonstrated that erythroid repression by inflammatory signaling is potently modulated by the erythroid iron restriction response in a kinase-dependent pathway involving induction of the erythroid-inhibitory transcription factor PU.1. These results reveal the integration of iron and inflammatory inputs in a therapeutically tractable erythropoietic regulatory circuit.

  9. Enzymes for improved biomass conversion

    Science.gov (United States)

    Brunecky, Roman; Himmel, Michael E.

    2016-02-02

    Disclosed herein are enzymes and combinations of the enzymes useful for the hydrolysis of cellulose and the conversion of biomass. Methods of degrading cellulose and biomass using enzymes and cocktails of enzymes are also disclosed.

  10. Enzymes for improved biomass conversion

    Energy Technology Data Exchange (ETDEWEB)

    Brunecky, Roman; Himmel, Michael E.

    2016-02-02

    Disclosed herein are enzymes and combinations of the enzymes useful for the hydrolysis of cellulose and the conversion of biomass. Methods of degrading cellulose and biomass using enzymes and cocktails of enzymes are also disclosed.

  11. Profiling the orphan enzymes

    Science.gov (United States)

    2014-01-01

    The emergence of Next Generation Sequencing generates an incredible amount of sequence and great potential for new enzyme discovery. Despite this huge amount of data and the profusion of bioinformatic methods for function prediction, a large part of known enzyme activities is still lacking an associated protein sequence. These particular activities are called “orphan enzymes”. The present review proposes an update of previous surveys on orphan enzymes by mining the current content of public databases. While the percentage of orphan enzyme activities has decreased from 38% to 22% in ten years, there are still more than 1,000 orphans among the 5,000 entries of the Enzyme Commission (EC) classification. Taking into account all the reactions present in metabolic databases, this proportion dramatically increases to reach nearly 50% of orphans and many of them are not associated to a known pathway. We extended our survey to “local orphan enzymes” that are activities which have no representative sequence in a given clade, but have at least one in organisms belonging to other clades. We observe an important bias in Archaea and find that in general more than 30% of the EC activities have incomplete sequence information in at least one superkingdom. To estimate if candidate proteins for local orphans could be retrieved by homology search, we applied a simple strategy based on the PRIAM software and noticed that candidates may be proposed for an important fraction of local orphan enzymes. Finally, by studying relation between protein domains and catalyzed activities, it appears that newly discovered enzymes are mostly associated with already known enzyme domains. Thus, the exploration of the promiscuity and the multifunctional aspect of known enzyme families may solve part of the orphan enzyme issue. We conclude this review with a presentation of recent initiatives in finding proteins for orphan enzymes and in extending the enzyme world by the discovery of new

  12. Unhairing with enzymes

    OpenAIRE

    Crispim, A.; Mota, M.

    2003-01-01

    The use of enzymes in the leather industry is increasing and their application is being widened to include operations such as de-greasing, unhairing and other wet-end operations. Enzymes can also be used to assist with recycling leather wastes as well as to avoid pollution. The present work is devoted to illustrate the potential application of enzymes in unhairing without hair destruction. Enzymatic unhairing is based upon the weakening of the epidermis basal layer to which the hair is at...

  13. [Iron deficiency and digestive disorders].

    Science.gov (United States)

    Cozon, G J N

    2014-11-01

    Iron deficiency anemia still remains problematic worldwide. Iron deficiency without anemia is often undiagnosed. We reviewed, in this study, symptoms and syndromes associated with iron deficiency with or without anemia: fatigue, cognitive functions, restless legs syndrome, hair loss, and chronic heart failure. Iron is absorbed through the digestive tract. Hepcidin and ferroportin are the main proteins of iron regulation. Pathogenic micro-organisms or intestinal dysbiosis are suspected to influence iron absorption. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

  14. Potential of phytase-mediated iron release from cereal-based foods: a quantitative view

    DEFF Research Database (Denmark)

    Nielsen, Anne Veller Friis; 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...

  15. Adenylate-forming enzymes

    Science.gov (United States)

    Schmelz, Stefan; Naismith, James H.

    2012-01-01

    Thioesters, amides and esters are common chemical building blocks in a wide array of natural products. The formation of these bonds can be catalyzed in a variety of ways. For chemists, the use of an activating group is a common strategy and adenylate enzymes are exemplars of this approach. Adenylating enzymes activate the otherwise unreactive carboxylic acid by transforming the normal hydroxyl leaving group into adenosine monophosphate. Recently there have been a number of studies of such enzymes and in this review we suggest a new classification scheme. The review highlights the diversity in enzyme fold, active site architecture and metal coordination that has evolved to catalyze this particular reaction. PMID:19836944

  16. Food and feed enzymes.

    Science.gov (United States)

    Fraatz, Marco Alexander; Rühl, Martin; Zorn, Holger

    2014-01-01

    Humans have benefited from the unique catalytic properties of enzymes, in particular for food production, for thousands of years. Prominent examples include the production of fermented alcoholic beverages, such as beer and wine, as well as bakery and dairy products. The chapter reviews the historic background of the development of modern enzyme technology and provides an overview of the industrial food and feed enzymes currently available on the world market. The chapter highlights enzyme applications for the improvement of resource efficiency, the biopreservation of food, and the treatment of food intolerances. Further topics address the improvement of food safety and food quality.

  17. Microbial amylolytic enzymes.

    Science.gov (United States)

    Vihinen, M; Mäntsälä, P

    1989-01-01

    Starch-degrading, amylolytic enzymes are widely distributed among microbes. Several activities are required to hydrolyze starch to its glucose units. These enzymes include alpha-amylase, beta-amylase, glucoamylase, alpha-glucosidase, pullulan-degrading enzymes, exoacting enzymes yielding alpha-type endproducts, and cyclodextrin glycosyltransferase. Properties of these enzymes vary and are somewhat linked to the environmental circumstances of the producing organisms. Features of the enzymes, their action patterns, physicochemical properties, occurrence, genetics, and results obtained from cloning of the genes are described. Among all the amylolytic enzymes, the genetics of alpha-amylase in Bacillus subtilis are best known. Alpha-Amylase production in B. subtilis is regulated by several genetic elements, many of which have synergistic effects. Genes encoding enzymes from all the amylolytic enzyme groups dealt with here have been cloned, and the sequences have been found to contain some highly conserved regions thought to be essential for their action and/or structure. Glucoamylase appears usually in several forms, which seem to be the results of a variety of mechanisms, including heterogeneous glycosylation, limited proteolysis, multiple modes of mRNA splicing, and the presence of several structural genes.

  18. Inositol hexa phosphoric acid (phytic acid), a nutraceuticals, attenuates iron-induced oxidative stress and alleviates liver injury in iron overloaded mice.

    Science.gov (United States)

    Bhowmik, Anwesha; Ojha, Durbadal; Goswami, Debayan; Das, Rashmi; Chandra, Nidhi S; Chatterjee, Tapan K; Chakravarty, Amit; Chakravarty, Sudipa; Chattopadhyay, Debprasad

    2017-03-01

    Inositol hexa phosphoric acid (IP6) or Phytic acid, a natural antioxidant of some leguminous plants, known to act as a protective agent for seed storage in plants by suppressing iron catalyzed oxidative process. Following the same mechanism, we have tested the effect of IP6 on iron overloaded in vitro oxidative stress, and studied it's in vivo hepatoprotective ability in iron-dextran (injection)-induced iron overloaded liver injury in mice (intraperitoneal). Our results showed that IP6 had in vitro iron chelation (IC50 38.4μg/ml) activity, with the inhibition of iron-induced lipid peroxidation (IC50 552μg/ml), and deoxyribose sugar degrading hydroxyl radicals (IC50 448.6μg/ml). Oral administration of IP6 (0-200mg/kg) revealed significant decrease in biochemical markers such as serum iron, total iron binding, serum ferritin and serum enzymes. Histopathology of liver stained with hematoxylin-eosin and Prussian blue showed reduced hepatocellular necrosis, ballooning and inflammation, indicating the restoration of normal cellular integrity. Interestingly, the IP6 was found to down-regulate the mRNA expression of tumor necrosis factor (TNF)-α, Interleukin (IL)-1β, and IL-6 in iron overloaded liver tissues. Thus, we provide an insight that IP6, a natural food component, can serve as an iron chelator against iron overload diseases like Thalassemia, and also as a dietary hepatoprotective supplement.

  19. Effect of iron supplementation on maximal oxygen uptake in female athletes

    Directory of Open Access Journals (Sweden)

    Rađen Slavica

    2011-01-01

    Full Text Available Background/Aim. Iron is a vital constituent of hemoglobin, myoglobin, and some mitochondrial enzymes; therefore, body iron deficiency may result in reduced aerobic capacity. The aim of this study was to evaluate the effects of daily oral iron supplementation on body iron status, and the maximal oxygen uptake (VO2max in female athletes with latent iron deficiency, as well as with irondeficiency anemia. Methods. A total of 37 female volleyball players were included in the study. Seventeen female athletes had latent iron deficiency, and 20 ones iron deficiency anemia. Both groups were divided into the experimental and the control group. The experimental groups received a daily oral iron supplement (200 mg ferrous sulfate, for a two-month training course. Iron status was determined by serum parameters as follows: red blood cells count, hemoglobin concentration, serum iron and ferritin levels, an unsaturated iron binding capacity, total iron binding capacity and transferrin saturation. VO2max was determined by an indirect test. Results. Statistical difference between the latent iron deficient group versus the iron deficient anemic group was found regarding VO2max (p < 0.001. There were correlations between hemoglobin concentration and VO2max in the latent iron deficient group, as well as in the iron deficient anaemic group (p < 0.05. After two months, there was a significant increase in VO2max in all groups (from 7.0% to 18.2%. Values of VO2max at the end of training period were significantly different (45.98 ± 1.76 vs 42.40 ± 1.22 mL/kg/min; p <0.001 between the experimental and the control group only in female athletes with iron deficiency anemia. After the supplementation, markers of iron status were significantly higher in supplemented groups than in the controls. Conclusion. VO2max was significantly lower in the iron deficient anemic group versus the latent iron deficient group. Iron supplementation during a two-month training period

  20. Microcytic anemia and hepatic iron overload in a child with compound heterozygous mutations in DMT1 (SCL11A2).

    Science.gov (United States)

    Iolascon, Achille; d'Apolito, Maria; Servedio, Veronica; Cimmino, Flora; Piga, Antonio; Camaschella, Clara

    2006-01-01

    Divalent metal transporter 1 (DMT1) mediates apical iron uptake in duodenal enterocytes and iron transfer from the transferrin receptor endosomal cycle into the cytosol in erythroid cells. Both mk mice and Belgrade rats, which carry an identical DMT1 mutation, exhibit severe microcytic anemia at birth and defective intestinal iron use and erythroid iron use. We report the hematologic phenotype of a child, compound heterozygote for 2 DMT1 mutations, who was affected by severe anemia since birth and showed hepatic iron overload. The novel mutations were a 3-bp deletion in intron 4 (c.310-3_5del CTT) resulting in a splicing abnormality and a C>T transition at nucleotide 1246(p. R416C). A striking reduction of DMT1 protein in peripheral blood mononuclear cells was demonstrated by Western blot analysis. The proband required blood transfusions until erythropoietin treatment allowed transfusion independence when hemoglobin levels between 75 and 95 g/L (7.5 and 9.5 g/dL) were achieved. Hematologic data of this patient at birth and in the first years of life strengthen the essential role of DMT1 in erythropoiesis. The early onset of iron overload indicates that, as in animal models, DMT1 is dispensable for liver iron uptake, whereas its deficiency in the gut is likely bypassed by the up-regulation of other pathways of iron use.

  1. Colour Metallography of Cast Iron

    Institute of Scientific and Technical Information of China (English)

    Zhou Jiyang; Liu Jincheng

    2011-01-01

    White Cast Iron (Ⅰ) White cast iron or ‘white iron' refers to the type of cast iron in which all of the carbon exists as carbide;there is no graphite in the as-cast structure and the fractured surface shows a white colour.White cast iron can be divided in three classes:· Normal white cast iron — this iron contains only C,Si,Mn,P and S,with no other alloying elements.· Low-alloy white cast iron — the total mass fraction of alloying elements is less than 5%.

  2. Regulation of quinolinic acid neosynthesis in mouse, rat and human brain by iron and iron chelators in vitro.

    Science.gov (United States)

    Stachowski, Erin K; Schwarcz, Robert

    2012-02-01

    Several lines of evidence indicate that excess iron may play an etiologically significant role in neurodegenerative disorders. This idea is supported, for example, by experimental studies in animals demonstrating significant neuroprotection by iron chelation. Here, we tested whether this effect might be related to a functional link between iron and the endogenous excitotoxin quinolinic acid (QUIN), a presumed pathogen in several neurological disorders. In particular, the present in vitro study was designed to examine the effects of Fe(2+), a known co-factor of oxygenases, on the activity of QUIN's immediate biosynthetic enzyme, 3-hydroxyanthranilic acid dioxygenase (3HAO), in the brain. In crude tissue homogenate, addition of Fe(2+) (2-40 μM) stimulated 3HAO activity 4- to 6-fold in all three species tested (mouse, rat and human). The slope of the iron curve was steepest in rat brain where an increase from 6 to 14 μM resulted in a more than fivefold higher enzyme activity. In all species, the Fe(2+)-induced increase in 3HAO activity was dose-dependently attenuated by the addition of ferritin, the main iron storage protein in the brain. The effect of iron was also readily prevented by N,N'-bis(2-hydroxybenzyl) ethylenediamine-N,N'-diacetic acid (HBED), a synthetic iron chelator with neuroprotective properties in vivo. All these effects were reproduced using neostriatal tissue obtained postmortem from normal individuals and patients with end-stage Huntington's disease. Our results suggest that QUIN levels and function in the mammalian brain might be tightly controlled by endogenous iron and proteins that regulate the bioavailability of iron.

  3. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... Blood Tests Blood Transfusion Restless Legs Syndrome Send a link to NHLBI to someone by E-MAIL | ... Iron-Deficiency Anemia? Español Iron-deficiency anemia is a common, easily treated condition that occurs if you ...

  4. Total iron binding capacity

    Science.gov (United States)

    ... the intestines not properly absorbing vitamin B12 ( pernicious anemia ) Sickle cell anemia Risks There is very little risk involved with ... test Hemoglobin Hemolytic anemia Iron deficiency anemia Pernicious anemia Serum iron test Sickle cell anemia Review Date 2/11/2016 Updated by: ...

  5. Thin Wall Iron Castings

    Energy Technology Data Exchange (ETDEWEB)

    J.F. Cuttino; D.M. Stefanescu; T.S. Piwonka

    2001-10-31

    Results of an investigation made to develop methods of making iron castings having wall thicknesses as small as 2.5 mm in green sand molds are presented. It was found that thin wall ductile and compacted graphite iron castings can be made and have properties consistent with heavier castings. Green sand molding variables that affect casting dimensions were also identified.

  6. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... periods. By following her treatment plan and making smart lifestyle choices, Susan continues to feel better and see the benefits of treatment. For more information about living with and managing iron-deficiency anemia, go to the Health Topics Iron-Deficiency Anemia article. Updated: March 26, ...

  7. Iron deficiency in childhood

    NARCIS (Netherlands)

    Uijterschout, L.

    2015-01-01

    Iron deficiency (ID) is the most common micronutrient deficiency in the world. Iron is involved in oxygen transport, energy metabolism, immune response, and plays an important role in brain development. In infancy, ID is associated with adverse effects on cognitive, motor, and behavioral development

  8. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... Blood Tests Blood Transfusion Restless Legs Syndrome Send a link to NHLBI to someone by E-MAIL | ... Iron-Deficiency Anemia? Español Iron-deficiency anemia is a common, easily treated condition that occurs if you ...

  9. Iron deficiency in childhood

    NARCIS (Netherlands)

    Uijterschout, L.

    2015-01-01

    Iron deficiency (ID) is the most common micronutrient deficiency in the world. Iron is involved in oxygen transport, energy metabolism, immune response, and plays an important role in brain development. In infancy, ID is associated with adverse effects on cognitive, motor, and behavioral development

  10. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... Deficiency Anemia? Español Iron-deficiency anemia is a common, easily treated condition that occurs if you don' ... from food. Overview Iron-deficiency anemia is a common type of anemia . The term "anemia" usually refers ...

  11. 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.

  12. New strategies to target iron metabolism for the treatment of beta thalassemia.

    Science.gov (United States)

    Oikonomidou, Paraskevi Rea; Casu, Carla; Rivella, Stefano

    2016-03-01

    Iron is one of the most abundant elements in the Earth and a fundamental component of enzymes and other proteins that participate in a wide range of biological processes. As the human body has no mechanisms to eliminate the excess of iron, its metabolism needs to be tightly controlled in order to avoid all the sequelae associated with high iron levels. Iron overload is the main cause of morbidity and mortality in beta thalassemia. The master regulator of iron homeostasis, hepcidin, is chronically repressed in this disorder, leading to increased intestinal iron absorption and consequent iron overload. Many groups have focused on obtaining a better understanding of the pathways involved in iron regulation. New molecules have recently been synthesized and used in animal models of dysregulated iron metabolism, demonstrating their ability to target and reduce iron load. Antisense oligonucleotides, as well as lipid nanoparticle-formulated small interfering RNAs and minihepcidins peptides, are novel agents that have already proved to be efficient in modulating iron metabolism in mouse models and are therefore promising candidates for the treatment of patients affected by iron disorders.

  13. Microbes: mini iron factories.

    Science.gov (United States)

    Joshi, Kumar Batuk

    2014-12-01

    Microbes have flourished in extreme habitats since beginning of the Earth and have played an important role in geological processes like weathering, mineralization, diagenesis, mineral formation and destruction. Biotic mineralization is one of the most fascinating examples of how microbes have been influencing geological processes. Iron oxidizing and reducing bacteria are capable of precipitating wide varieties of iron oxides (magnetite), carbonates (siderite) and sulphides (greigite) via controlled or induced mineralization processes. Microbes have also been considered to play an important role in the history of evolution of sedimentary rocks on Earth from the formation of banded iron formations during the Archean to modern biotic bog iron and ochre deposits. Here, we discuss the role that microbes have been playing in precipitation of iron and the role and importance of interdisciplinary studies in the field of geology and biology in solving some of the major geological mysteries.

  14. A pentanuclear iron catalyst designed for water oxidation

    Science.gov (United States)

    Okamura, Masaya; Kondo, Mio; Kuga, Reiko; Kurashige, Yuki; Yanai, Takeshi; Hayami, Shinya; Praneeth, Vijayendran K. K.; Yoshida, Masaki; Yoneda, Ko; Kawata, Satoshi; Masaoka, Shigeyuki

    2016-02-01

    Although the oxidation of water is efficiently catalysed by the oxygen-evolving complex in photosystem II (refs 1 and 2), it remains one of the main bottlenecks when aiming for synthetic chemical fuel production powered by sunlight or electricity. Consequently, the development of active and stable water oxidation catalysts is crucial, with heterogeneous systems considered more suitable for practical use and their homogeneous counterparts more suitable for targeted, molecular-level design guided by mechanistic understanding. Research into the mechanism of water oxidation has resulted in a range of synthetic molecular catalysts, yet there remains much interest in systems that use abundant, inexpensive and environmentally benign metals such as iron (the most abundant transition metal in the Earth’s crust and found in natural and synthetic oxidation catalysts). Water oxidation catalysts based on mononuclear iron complexes have been explored, but they often deactivate rapidly and exhibit relatively low activities. Here we report a pentanuclear iron complex that efficiently and robustly catalyses water oxidation with a turnover frequency of 1,900 per second, which is about three orders of magnitude larger than that of other iron-based catalysts. Electrochemical analysis confirms the redox flexibility of the system, characterized by six different oxidation states between FeII5 and FeIII5; the FeIII5 state is active for oxidizing water. Quantum chemistry calculations indicate that the presence of adjacent active sites facilitates O-O bond formation with a reaction barrier of less than ten kilocalories per mole. Although the need for a high overpotential and the inability to operate in water-rich solutions limit the practicality of the present system, our findings clearly indicate that efficient water oxidation catalysts based on iron complexes can be created by ensuring that the system has redox flexibility and contains adjacent water-activation sites.

  15. 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)

  16. Iron and the endurance athlete.

    Science.gov (United States)

    Hinton, Pamela S

    2014-09-01

    Iron is a trace mineral that is highly significant to endurance athletes. Iron is critical to optimal athletic performance because of its role in energy metabolism, oxygen transport, and acid-base balance. Endurance athletes are at increased risk for suboptimal iron status, with potential negative consequences on performance, because of the combination of increased iron needs and inadequate dietary intake. This review paper summarizes the role of iron in maximal and submaximal exercise and describes the effects of iron deficiency on exercise performance. Mechanisms that explain the increased risk of iron deficiency in endurance athletes, including exercise-associated inflammation and hepcidin release on iron sequestration, are described. Information on screening athletes for iron deficiency is presented, and suggestions to increase iron intake through diet modification or supplemental iron are provided.

  17. Artificial Enzymes, "Chemzymes"

    DEFF Research Database (Denmark)

    Bjerre, Jeannette; Rousseau, Cyril Andre Raphaël; Pedersen, Lavinia Georgeta M

    2008-01-01

    Enzymes have fascinated scientists since their discovery and, over some decades, one aim in organic chemistry has been the creation of molecules that mimic the active sites of enzymes and promote catalysis. Nevertheless, even today, there are relatively few examples of enzyme models that successf......Enzymes have fascinated scientists since their discovery and, over some decades, one aim in organic chemistry has been the creation of molecules that mimic the active sites of enzymes and promote catalysis. Nevertheless, even today, there are relatively few examples of enzyme models...... that successfully perform Michaelis-Menten catalysis under enzymatic conditions (i.e., aqueous medium, neutral pH, ambient temperature) and for those that do, very high rate accelerations are seldomly seen. This review will provide a brief summary of the recent developments in artificial enzymes, so called...... "Chemzymes", based on cyclodextrins and other molecules. Only the chemzymes that have shown enzyme-like activity that has been quantified by different methods will be mentioned. This review will summarize the work done in the field of artificial glycosidases, oxidases, epoxidases, and esterases, as well...

  18. Enzymes in Fermented Fish.

    Science.gov (United States)

    Giyatmi; Irianto, H E

    Fermented fish products are very popular particularly in Southeast Asian countries. These products have unique characteristics, especially in terms of aroma, flavor, and texture developing during fermentation process. Proteolytic enzymes have a main role in hydrolyzing protein into simpler compounds. Fermentation process of fish relies both on naturally occurring enzymes (in the muscle or the intestinal tract) as well as bacteria. Fermented fish products processed using the whole fish show a different characteristic compared to those prepared from headed and gutted fish. Endogenous enzymes like trypsin, chymotrypsin, elastase, and aminopeptidase are the most involved in the fermentation process. Muscle tissue enzymes like cathepsins, peptidases, transaminases, amidases, amino acid decarboxylases, glutamic dehydrogenases, and related enzymes may also play a role in fish fermentation. Due to the decreased bacterial number during fermentation, contribution of microbial enzymes to proteolysis may be expected prior to salting of fish. Commercial enzymes are supplemented during processing for specific purposes, such as quality improvement and process acceleration. In the case of fish sauce, efforts to accelerate fermentation process and to improve product quality have been studied by addition of enzymes such as papain, bromelain, trypsin, pepsin, and chymotrypsin. © 2017 Elsevier Inc. All rights reserved.

  19. Effect of malaria components on blood mononuclear cells involved in immune response.

    Science.gov (United States)

    Punsawad, Chuchard

    2013-09-01

    During malaria infection, elevated levels of pro-inflammatory mediators and nitric oxide production have been associated with pathogenesis and disease severity. Previous in vitro and in vivo studies have proposed that both Plasmodium falciparum hemozoin and glycosylphosphatidylinositols are able to modulate blood mononuclear cells, contributing to stimulation of signal transduction and downstream regulation of the NF-κB signaling pathway, and subsequently leading to the production of pro-inflammatory cytokines, chemokines, and nitric oxide. The present review summarizes the published in vitro and in vivo studies that have investigated the mechanism of intracellular signal transduction and activation of the NF-κB signaling pathway in blood mononuclear cells after being inducted by Plasmodium falciparum malaria components. Particular attention is paid to hemozoin and glycosylphosphatidylinositols which reflect the important mechanism of signaling pathways involved in immune response.

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

    Science.gov (United States)

    Qin, Ling; Qiao, Wen-Cheng; Zuo, Wei-Juan; Zeng, Si-Ying; Mei, Cao; Liu, Chang-Jiang

    2016-07-01

    Two zinc coordination polymers {[Zn2(TPPBDA)(oba)2]·DMF·1.5H2O}n (1), {[Zn(TPPBDA)1/2(tpdc)]·DMF}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 [Zn2(CO2)4] clusters. Compound 2 can be defined as a five folded interpenetrating bbf topology with mononuclear Zn2+. 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.

  1. Effect of malaria components on blood mononuclear cells involved in immune response

    Institute of Scientific and Technical Information of China (English)

    Chuchard Punsawad

    2013-01-01

    During malaria infection, elevated levels of pro-inflammatory mediators and nitric oxide production have been associated with pathogenesis and disease severity. Previous in vitro and in vivo studies have proposed that both Plasmodium falciparum hemozoin and glycosylphosphatidylinositols are able to modulate blood mononuclear cells, contributing to stimulation of signal transduction and downstream regulation of the NF-κB signaling pathway, and subsequently leading to the production of pro-inflammatory cytokines, chemokines, and nitric oxide. The present review summarizes the published in vitro and in vivo studies that have investigated the mechanism of intracellular signal transduction and activation of the NF-κB signaling pathway in blood mononuclear cells after being inducted by Plasmodium falciparum malaria components. Particular attention is paid to hemozoin and glycosylphosphatidylinositols which reflect the important mechanism of signaling pathways involved in immune response.

  2. Reduced LAK cytotoxicity of peripheral blood mononuclear cells in patients with bladder cancer

    DEFF Research Database (Denmark)

    Hermann, G G; Petersen, K R; Steven, K

    1990-01-01

    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......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 51Cr-release assays. The PBMC subsets...

  3. Genetic and biochemical markers in patients with Alzheimer's disease support a concerted systemic iron homeostasis dysregulation.

    Science.gov (United States)

    Crespo, Ângela C; Silva, Bruno; Marques, Liliana; Marcelino, Erica; Maruta, Carolina; Costa, Sónia; Timóteo, Angela; Vilares, Arminda; Couto, Frederico Simões; Faustino, Paula; Correia, Ana Paula; Verdelho, Ana; Porto, Graça; Guerreiro, Manuela; Herrero, Ana; Costa, Cristina; de Mendonça, Alexandre; Costa, Luciana; Martins, Madalena

    2014-04-01

    Alzheimer's disease (AD) is the most common form of dementia in the elderly individuals, resulting from a complex interaction between environmental and genetic factors. Impaired brain iron homeostasis has been recognized as an important mechanism underlying the pathogenesis of this disease. Nevertheless, the knowledge gathered so far at the systemic level is clearly insufficient. Herein, we used an integrative approach to study iron metabolism in the periphery, at both genotypic and phenotypic levels, in a sample of 116 patients with AD and 89 healthy control subjects. To assess the potential impact of iron metabolism on the risk of developing AD, genetic analyses were performed along with the evaluation of the iron status profile in peripheral blood by biochemical and gene expression studies. The results obtained showed a significant decrease of serum iron, ferritin, and transferrin concentrations in patients compared with the control subjects. Also, a significant decrease of ferroportin (SLC40A1) and both transferrin receptors TFRC and TFR2 transcripts was found in peripheral blood mononuclear cells from patients. At the genetic level, significant associations with AD were found for single nucleotide polymorphisms in TF, TFR2, ACO1, and SLC40A1 genes. Apolipoprotein E gene, a well-known risk factor for AD, was also found significantly associated with the disease in this study. Taken together, we hypothesize that the alterations on systemic iron status observed in patients could reflect an iron homeostasis dysregulation, particularly in cellular iron efflux. The intracellular iron accumulation would lead to a rise in oxidative damage, contributing to AD pathophysiology.

  4. Genetics of iron storage and hemochromatosis.

    Science.gov (United States)

    Beutler, E; Felitti, V; Gelbart, T; Ho, N

    2001-04-01

    The regulation of total body iron is important to all organisms. In mammals, the iron content of the body is controlled almost entirely through regulation of absorption. The precise mechanism by which iron is absorbed and the manner in which the absorption is regulated is unknown, but a number of different proteins that are involved either in the transport process itself or its regulation have been identified. These include HFE, a class 1 HLA molecule involved in hereditary hemochromatosis, the divalent metal transporter (DMT-1), hephaestin, the transferrin receptor, and mobilferrin. Iron overload occurs in a number of hereditary disorders including atransferrinemia, aceruloplasminemia, X-linked hereditary sideroblastic anemia, thalassemia major, congenital dyserythropoietic anemia, and various red cell enzyme deficiencies. In Europeans, most cases of hereditary hemochromatosis are due to mutations of the HFE gene. There are two major mutations of this gene c.845G-->A (C282Y) and c.187C-->G (H63D). These mutations have extraordinarily high prevalence in northern Europe and approximately five in a thousand Europeans are homozygous for the 845A mutation. The penetrance of even the homozygous state for the 845A mutation is very low and that for the compound heterozygote 845A/187G, which is also associated with hemochromatosis, is even lower. The reason for the markedly variable penetrance that exists in this disorder remains unknown.

  5. 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

    2015-07-30

    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.

  6. 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

  7. UV/Vis, MCD and EPR Spectra of Mononuclear Manganese and Molybdenum Complexes

    OpenAIRE

    Westphal, Anne

    2012-01-01

    This PhD thesis deals with the spectroscopic characterization of the electronic structures of mononuclear manganese and molybdenum complexes. At this, in addition to UV/Vis absorption spectroscopy, electron paramagnetic resonance (EPR) and magnetic circular dichroism (MCD) spectroscopy were applied in this work. Additionally, new procedures for the general analysis of MCD C-term intensities were developed within the scope of this thesis. It is divided into four parts. Following a general p...

  8. Effects of carvedilol on oxidative stress in polymorphonuclear and mononuclear cells in patients with essential hypertension.

    Science.gov (United States)

    Yasunari, Kenichi; Maeda, Kensaku; Nakamura, Munehiro; Watanabe, Takanori; Yoshikawa, Junichi; Asada, Akira

    2004-04-01

    To compare the effects of carvedilol and propranolol on oxidative stress in leukocytes and C-reactive protein levels in patients with hypertension. Sixty hypertensive patients were randomly assigned to carvedilol (20 mg; n = 30) or propranolol (60 mg; n = 30) for 6 months. Thirty normotensive subjects who were given placebo served as controls. Oxidative stress in polymorphonuclear cells and mononuclear cells were measured by gated flow cytometry. C-reactive protein levels were measured by immunonephelometric assay. Oxidative stress in polymorphonuclear cells and mononuclear cells was increased significantly in hypertensive patients compared with in normotensive controls. After 6 months of treatment, carvedilol decreased oxidative stress significantly in polymorphonuclear cells by a mean of 45 arbitrary units (95% confidence interval [CI]: 32 to 59 arbitrary units; P <0.001) and propranolol decreased oxidative stress significantly by 20 arbitrary units (95% CI: 7 to 33 arbitrary units; P <0.003; P = 0.001 for difference between treatments). Carvedilol also decreased oxidative stress significantly in mononuclear cells by 23 arbitrary units (95% CI: 15 to 31 arbitrary units; P <0.001), whereas propranolol decreased oxidative stress by 2 arbitrary units (95% CI: 7 to 12 arbitrary units; P = 0.62; P = 0.002 for difference between treatments). Carvedilol decreased C-reactive protein levels significantly by a median of 0.073 mg/dL (interquartile range, 0.034 to 0.112 mg/dL; P <0.001), whereas propranolol decreased levels by 0.012 mg/dL (interquartile range, 0.009 to 0.032 mg/dL; P = 0.26; P = 0.003 for difference between treatments). These findings suggest that carvedilol inhibits oxidative stress in polymorphonuclear and mononuclear cells, as well as lowers C-reactive protein levels, to a greater extent than does propranolol in hypertensive patients.

  9. 21 CFR 310.518 - Drug products containing iron or iron salts.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 5 2010-04-01 2010-04-01 false Drug products containing iron or iron salts. 310... Drug products containing iron or iron salts. Drug products containing elemental iron or iron salts as...) that contains iron or iron salts for use as an iron source shall bear the following statement:...

  10. 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.

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

    Science.gov (United States)

    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.

  12. From Iron Bowl to Iron Stomach

    Institute of Scientific and Technical Information of China (English)

    MICHAEL; L.; O’NEAL

    2009-01-01

    A few decades ago, "Iron Bowl" referred to not having to go hungry in China if you were employed by the Agovernment. The government gave you a job that secured the filling of one’s rice bowl. This concept and practice did create loyalty, as the times were hard. China has moved far past those times to become the

  13. CHRONIC HEART FAILURE AND IRON-DEFICIENT ANEMIA

    Directory of Open Access Journals (Sweden)

    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.

  14. 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.

  15. Effects of estradiol and progesterone on the proinflammatory cytokine production by mononuclear cells from patients with chronic hepatitis C

    Institute of Scientific and Technical Information of China (English)

    Ying Yuan; Katsuyoshi Tamaki; Masayuki Shono; Tetsuji Takayama; Ichiro Shimizu; Mi Shen; Eriko Aoyagi; Hidetaka Takenaka; Tatuzo Itagaki; Marl Urata; Katsutaka Sannomiya; Nao Kohno

    2008-01-01

    AIM: To investigate the effects of estradiol (E2) and progesterone on the unstimulated and oxidative stressstimulated production of tumor necrosis factor (TNF)-α,interleukin (IL)-1β, IL-8, and macrophage chemotactic protein (ICP)-1 by peripheral blood mononuclear cells (PBMCs) from patients with chronic hepatitis C and healthy controls.METHODS: The PBMCs were separated from agematched 72 males and 71 females with and without chronic hepatitis C, who were divided into two groups based on a mean menopausal age of 50 years. Oxidative stress was induced by hydrogen peroxide in the cells incubated in serum-free media. CytokJnes in the culture supernatant were measured by an enzyme-linked immunosorbent assay.RESULTS: The highest levels of the spontaneous production of TNF-α, IL-1β, IL-8, and MCP-1 by the unstimulated PBMCs were in the older male patients with chronic hepatitis C and the lowest levels were in the premenopausal female-healthy controls. E2 inhibited the cytokine production by the unstimulated PBMCs from the older male and post-menopausal female patients, which was further stimulated by progesterone. The exposure to hydrogen peroxide in the PBMCs from the younger male and pre-menopausal female healthy subjects induced the production of cytokines. The change rates of the hydrogen peroxide-stimulated cytokine production were suppressed by E2 and enhanced by progesterone.CONCLUSION: These findings suggest that E2 may play a favorable role in the course of persistent liver injury by preventing the accumulation of monocytes-macrophages and by inhibiting proinflammatory cytokine production,whereas progesterone may counteract the favorable E2 effects.

  16. Study of the inhibition by polymorphonuclear leukocytes of TNF-α release from human mononuclear cells and its mechanism

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    The present study was undertaken to investigate the effect of human PMNs on the production of TNF-α by the human peripheral blood mononuclear cells (PBMCs) and to elucidate its tentative mechanism. Human PMNs and PBMCs were isolated from the venous blood of healthy donors by dextran sedimentation and density gradient centrifugation. In the presence of lipopolysaccharide (LPS), PMNs and PBMCs were cocultured at the ratio of 2:1 for 20 h and the concentration of TNF-α in the supernatant was measured by enzyme-linked immunosorbent assay. The binding rate of monocytes with the fluorescein isothiocyanate-labeled LPS (FITC-LPS) and the mean surface fluorescence intensity of monocytes were analyzed by flow cytometry. Results showed that PMNs were capable of inhibiting the TNF-α release from PBMCs (P<0.05). PMNs suppressed the TNF-α release from PBMCs by 45% on average when PMNs and PBMCs cocultured at the ratio of 2:1. Paraformaldehyde-fixed PMNs still demonstrated the same inhibition (P<0.05),which proved that the inhibition was dependent on cell-to-cell contact and suggested that effector molecules responsible for this effect existed on the cell surface of PMNs. In the presence of PMNs, the binding rate of monocytes with the FITC-LPS and the mean surface fluorescence intensity of monocytes were not affected compared with PBMCs alone (P>0.05). As incubation time was prolonged, the binding of FITC-LPS to monocytes increased (P<0.05). Thus PMNs did not block the binding of LPS with monocytes. It was concluded that PMNs suppressed the TNF-α release from PBMCs via cell-to-cell interaction. In a cell-contact dependent manner, PMNs might interfere with the signal transduction pathway through which LPS activated PBMCs, thus attenuating the response of PBMCs to LPS and downregulating the TNF-α release.

  17. Mononuclear Phenolate Diamine Zinc Hydride Complexes and Their Reactions With CO2.

    Science.gov (United States)

    Brown, Neil J; Harris, Jonathon E; Yin, Xinning; Silverwood, Ian; White, Andrew J P; Kazarian, Sergei G; Hellgardt, Klaus; Shaffer, Milo S P; Williams, Charlotte K

    2014-03-10

    The synthesis, characterization, and zinc coordination chemistry of the three proligands 2-tert-butyl-4-[tert-butyl (1)/methoxy (2)/nitro (3)]-6-{[(2'-dimethylaminoethyl)methylamino]methyl}phenol are described. Each of the ligands was reacted with diethylzinc to yield zinc ethyl complexes 4-6; these complexes were subsequently reacted with phenylsilanol to yield zinc siloxide complexes 7-9. Finally, the zinc siloxide complexes were reacted with phenylsilane to produce the three new zinc hydride complexes 10-12. The new complexes 4-12 have been fully characterized by NMR spectroscopy, mass spectrometry, and elemental analyses. The structures of the zinc hydride complexes have been probed using VT-NMR spectroscopy and X-ray diffraction experiments. These data indicate that the complexes exhibit mononuclear structures at 298 K, both in the solid state and in solution (d8-toluene). At 203 K, the NMR signals broaden, consistent with an equilibrium between the mononuclear and dinuclear bis(μ-hydrido) complexes. All three zinc hydride complexes react rapidly and quantitatively with carbon dioxide, at 298 K and 1 bar of pressure over 20 min, to form the new zinc formate complexes 13-15. The zinc formate complexes have been analyzed by NMR spectroscopy and VT-NMR studies, which reveal a temperature-dependent monomer-dimer equilibrium that is dominated by the mononuclear species at 298 K.

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

    Directory of Open Access Journals (Sweden)

    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.

  19. Modulation of adhesion molecules by cholesterol-lowering therapy in mononuclear cells from hypercholesterolemic patients.

    Science.gov (United States)

    Cerda, Alvaro; Rodrigues, Alice Cristina; Alves, Camila; Genvigir, Fabiana Dalla Vecchia; Fajardo, Cristina Moreno; Dorea, Egidio Lima; Gusukuma, Maria Cecilia; Pinto, Gelba Almeida; Hirata, Mario Hiroyuki; Hirata, Rosario Dominguez Crespo

    2015-08-01

    Cholesterol-lowering therapy has been related with several pleiotropic effects including anti-inflammatory action in vascular endothelium; however, their influence on monocyte adhesion molecules is poorly described. To investigate the effect of inhibitors of synthesis (statins) and absorption (ezetimibe) of cholesterol on expression of adhesion molecules L-selectin, PSGL-1, VLA-4, LFA-1, and Mac-1 in mononuclear cells in vivo and in vitro using THP-1 cells. The influence of simvastatin (10 mg/day), ezetimibe (10 mg/day), and their combination (10 mg each/day) on mRNA expression of adhesion molecules was analyzed in peripheral blood mononuclear cells (PBMC) from hypercholesterolemics. The effects of atorvastatin, simvastatin, and ezetimibe on mRNA and protein expression of adhesion molecules were also evaluated in THP-1 cells. Simvastatin/ezetimibe combination, but not the monotherapies, reduced the mRNA expression of the PSGL-1, LFA-1, and Mac-1 genes in PBMC from hypercholesterolemics. Total and LDL cholesterol in serum correlated with PSGL-1 mRNA expression, whereas HDL cholesterol negatively correlated with mRNA levels of L-selectin and VLA-4 genes (P molecules in PBMC from hypercholesterolemics and THP-1 cells. Simvastatin/ezetimibe combination gives more benefits by reducing to a larger extent the expression of adhesion molecules in mononuclear cells. © 2015 John Wiley & Sons Ltd.

  20. Defining Mononuclear Phagocyte Subset Homology Across Several Distant Warm-Blooded Vertebrates Through Comparative Transcriptomics.

    Science.gov (United States)

    Vu Manh, Thien-Phong; Elhmouzi-Younes, Jamila; Urien, Céline; Ruscanu, Suzana; Jouneau, Luc; Bourge, Mickaël; Moroldo, Marco; Foucras, Gilles; Salmon, Henri; Marty, Hélène; Quéré, Pascale; Bertho, Nicolas; Boudinot, Pierre; Dalod, Marc; Schwartz-Cornil, Isabelle

    2015-01-01

    Mononuclear phagocytes are organized in a complex system of ontogenetically and functionally distinct subsets, that has been best described in mouse and to some extent in human. Identification of homologous mononuclear phagocyte subsets in other vertebrate species of biomedical, economic, and environmental interest is needed to improve our knowledge in physiologic and physio-pathologic processes, and to design intervention strategies against a variety of diseases, including zoonotic infections. We developed a streamlined approach combining refined cell sorting and integrated comparative transcriptomics analyses which revealed conservation of the mononuclear phagocyte organization across human, mouse, sheep, pigs and, in some respect, chicken. This strategy should help democratizing the use of omics analyses for the identification and study of cell types across tissues and species. Moreover, we identified conserved gene signatures that enable robust identification and universal definition of these cell types. We identified new evolutionarily conserved gene candidates and gene interaction networks for the molecular regulation of the development or functions of these cell types, as well as conserved surface candidates for refined subset phenotyping throughout species. A phylogenetic analysis revealed that orthologous genes of the conserved signatures exist in teleost fishes and apparently not in Lamprey.

  1. 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.

  2. Study of the inhibition by polymorphonuclear leukocytes of TNF-α release from human mononuclear cells and its mechanism

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    @@ The present study was undertaken to investigate the effect of human PMNs on the production of TNF-α by the human peripheral blood mononuclear cells (PBMCs) and to elucidate its tentative mechanism.

  3. Cotton cellulose: enzyme adsorption and enzymic hydrolysis

    Energy Technology Data Exchange (ETDEWEB)

    Beltrame, P.L.; Carniti, P.; Focher, B.; Marzetti, A.; Cattaneo, M.

    1982-01-01

    The adsorption of a crude cellulase complex from Trichoderma viride on variously pretreated cotton cellulose samples was studied in the framework of the Langmuir approach at 2-8 degrees. The saturation amount of adsorbed enzyme was related to the susceptibility of the substrates to hydrolysis. In every case the adsorption process was faster by 2-3 orders of magnitude than the hydrolysis step to give end products. For ZnCl/sub 2/-treated cotton cellulose the Langmuir parameters correlated fairly well with the value of the Michaelis constant, measured for its enzymic hydrolysis, and the adsorptive complex was indistinguishable from the complex of the Michaelis-Menten model for the hydrolysis.

  4. Aggressive periodontitis and chronic arthritis: blood mononuclear cell gene expression and plasma protein levels of cytokines and cytokine inhibitors

    DEFF Research Database (Denmark)

    Sørensen, Lars K; Havemose-Poulsen, Anne; Bendtzen, Klaus

    2009-01-01

    BACKGROUND: Cytokines and cytokine inhibitors have been associated with many immunoinflammatory diseases. In the present study, we examined whether peripheral blood mononuclear cell (PBMC) gene expression mirrors the corresponding plasma levels of clinically important pro- and anti-inflammatory c......BACKGROUND: Cytokines and cytokine inhibitors have been associated with many immunoinflammatory diseases. In the present study, we examined whether peripheral blood mononuclear cell (PBMC) gene expression mirrors the corresponding plasma levels of clinically important pro- and anti...

  5. Remodeling of Membrane Lipids in Iron-starved Chlamydomonas*

    Science.gov (United States)

    Urzica, Eugen I.; Vieler, Astrid; Hong-Hermesdorf, Anne; Page, M. Dudley; Casero, David; Gallaher, Sean D.; Kropat, Janette; Pellegrini, Matteo; Benning, Christoph; Merchant, Sabeeha S.

    2013-01-01

    Chlamydomonas reinhardtii cells exposed to abiotic stresses (e.g. nitrogen, zinc, or phosphorus deficiency) accumulate triacylglycerols (TAG), which are stored in lipid droplets. Here, we report that iron starvation leads to formation of lipid droplets and accumulation of TAGs. This occurs between 12 and 24 h after the switch to iron-starvation medium. C. reinhardtii cells deprived of iron have more saturated fatty acid (FA), possibly due to the loss of function of FA desaturases, which are iron-requiring enzymes with diiron centers. The abundance of a plastid acyl-ACP desaturase (FAB2) is decreased to the same degree as ferredoxin. Ferredoxin is a substrate of the desaturases and has been previously shown to be a major target of the iron deficiency response. The increase in saturated FA (C16:0 and C18:0) is concomitant with the decrease in unsaturated FA (C16:4, C18:3, or C18:4). This change was gradual for diacylglyceryl-N,N,N-trimethylhomoserine (DGTS) and digalactosyldiacylglycerol (DGDG), whereas the monogalactosyldiacylglycerol (MGDG) FA profile remained stable during the first 12 h, whereas MGDG levels were decreasing over the same period of time. These changes were detectable after only 2 h of iron starvation. On the other hand, DGTS and DGDG contents gradually decreased until a minimum was reached after 24–48 h. RNA-Seq analysis of iron-starved C. reinhardtii cells revealed notable changes in many transcripts coding for enzymes involved in FA metabolism. The mRNA abundances of genes coding for components involved in TAG accumulation (diacylglycerol acyltransferases or major lipid droplet protein) were increased. A more dramatic increase at the transcript level has been observed for many lipases, suggesting that major remodeling of lipid membranes occurs during iron starvation in C. reinhardtii. PMID:23983122

  6. Remodeling of membrane lipids in iron-starved Chlamydomonas.

    Science.gov (United States)

    Urzica, Eugen I; Vieler, Astrid; Hong-Hermesdorf, Anne; Page, M Dudley; Casero, David; Gallaher, Sean D; Kropat, Janette; Pellegrini, Matteo; Benning, Christoph; Merchant, Sabeeha S

    2013-10-18

    Chlamydomonas reinhardtii cells exposed to abiotic stresses (e.g. nitrogen, zinc, or phosphorus deficiency) accumulate triacylglycerols (TAG), which are stored in lipid droplets. Here, we report that iron starvation leads to formation of lipid droplets and accumulation of TAGs. This occurs between 12 and 24 h after the switch to iron-starvation medium. C. reinhardtii cells deprived of iron have more saturated fatty acid (FA), possibly due to the loss of function of FA desaturases, which are iron-requiring enzymes with diiron centers. The abundance of a plastid acyl-ACP desaturase (FAB2) is decreased to the same degree as ferredoxin. Ferredoxin is a substrate of the desaturases and has been previously shown to be a major target of the iron deficiency response. The increase in saturated FA (C16:0 and C18:0) is concomitant with the decrease in unsaturated FA (C16:4, C18:3, or C18:4). This change was gradual for diacylglyceryl-N,N,N-trimethylhomoserine (DGTS) and digalactosyldiacylglycerol (DGDG), whereas the monogalactosyldiacylglycerol (MGDG) FA profile remained stable during the first 12 h, whereas MGDG levels were decreasing over the same period of time. These changes were detectable after only 2 h of iron starvation. On the other hand, DGTS and DGDG contents gradually decreased until a minimum was reached after 24-48 h. RNA-Seq analysis of iron-starved C. reinhardtii cells revealed notable changes in many transcripts coding for enzymes involved in FA metabolism. The mRNA abundances of genes coding for components involved in TAG accumulation (diacylglycerol acyltransferases or major lipid droplet protein) were increased. A more dramatic increase at the transcript level has been observed for many lipases, suggesting that major remodeling of lipid membranes occurs during iron starvation in C. reinhardtii.

  7. Colour Metallography of Cast Iron

    Institute of Scientific and Technical Information of China (English)

    Zhou Jiyang; Liu Jincheng

    2009-01-01

    @@ This book consists of five sections:Chapter 1 Introduction,Chapter 2 Grey Iron,Chapter 3 Ductile Iron,Chapter 4Vermicular Cast Iron,and Chapter 5 White Cast Iron. CHINA FOUNDRY publishs this book in several parts serially,starting from the first issue of 2009.

  8. Colour Metallography of Cast Iron

    Institute of Scientific and Technical Information of China (English)

    Zhou Jiyang; Ph.D Liu Jincheng

    2010-01-01

    @@ Note: This book consists of five sections: Chapter 1 Introduction, Chapter 2 Grey Iron, Chapter 3 Spheroidal Graphite Cast Iron, Chapter 4 Vermicular Cast Iron, and Chapter 5 White Cast Iron. CHINA FOUNDRY publishes this book in several parts serially, starting from the first issue of 2009.

  9. Synovial fluid mononuclear cells provide an environment for long-term survival of antibody-secreting cells and promote the spontaneous production of anti-citrullinated protein antibodies.

    Science.gov (United States)

    Kerkman, Priscilla F; Kempers, Ayla C; van der Voort, Ellen I H; van Oosterhout, Maikel; Huizinga, Tom W J; Toes, René E M; Scherer, Hans U

    2016-12-01

    In rheumatoid arthritis (RA), observations point to a crucial role for (autoreactive) B cells in disease pathogenesis. Here, we studied whether cells from the synovial environment impact on the longevity of autoreactive B cell responses against citrullinated antigens. Synovial fluid mononuclear cells and peripheral blood mononuclear cells (SFMC/PBMC) were obtained from patients with established RA and assessed for the presence of B cell subpopulations. Cells spontaneously secreting anti-citrullinated protein antibodies (ACPA-IgG) directly ex vivo were detected by antigen-specific Enzyme-Linked ImmunoSpot (ELISpot) assay. SFMC and PBMC were cultured to assess the degree of spontaneous ACPA-IgG secretion. Cells surviving for several weeks were characterised by carboxyfluorescein succinimidyl ester (CFSE) labelling and Ki-67 staining. Cells spontaneously secreting ACPA-IgG were readily detectable in peripheral blood and synovial fluid (SF) of patients with ACPA-positive RA. SFMC showed an up to 200-fold increase in ex vivo ACPA-IgG secretion compared with PBMC despite lower numbers of B cells in SFMC. ELISpot confirmed the presence of spontaneously ACPA-IgG-secreting cells, accounting for up to 50% (median 12%) of all IgG-secreting cells in SF. ACPA-IgG secretion was remarkably stable in SFMC cultures, maintained upon depletion of the CD20(+) B cell compartment and detectable for several months. CFSE labelling and Ki-67 staining confirmed the long-term survival of non-dividing plasma cells (PCs). This study demonstrates a high frequency of differentiated, spontaneously ACPA-IgG-secreting cells in SF. These cells are supported by SFMC for prolonged survival and autoantibody secretion, demonstrating that the synovial compartment is equipped to function as inflammatory niche for PC survival. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

  10. Asymptomatic individuals with high HDL-C levels overexpress ABCA1 and ABCG1 and present miR-33a dysregulation in peripheral blood mononuclear cells.

    Science.gov (United States)

    Scherrer, D Z; Zago, V H S; Parra, E S; Avansini, S; Panzoldo, N B; Alexandre, F; Baracat, J; Nakandakare, E R; Quintão, E C R; de Faria, E C

    2015-10-01

    Considering the growing knowledge and perspectives on microRNAs (miRNAs) that control high-density lipoprotein cholesterol (HDL-C) levels and metabolism, this study aimed at evaluating whether hsa-miR-33a and hsa-miR-128a are differentially expressed in peripheral blood mononuclear cells from asymptomatic individuals with low and high HDL-C, as well as at investigating the potential relationships with ATP binding cassete transporter A1 (ABCA1) expression, cholesterol efflux capacity and other parameters related with reverse cholesterol transport. In addition, the associations with cardiovascular risk were investigated by carotid-intima media thickness (cIMT). Asymptomatic volunteers of both genders (n=51) were classified according to HDL-C (mg/dL) in hypoalphalipoproteinemics (hypo, HDL-C ≤3 9), hyperalphalipoproteinemics (hyper, HDL-C ≥ 68) and controls (CTL, HDL-C ≥ 40HDL size and volume, C reactive protein and insulin were determined, as well as the activities of several proteins and enzymes related to HDL metabolism. In a subgroup of 19 volunteers the cellular cholesterol efflux and HDL composition were determined. Total RNA was extracted from peripheral blood mononuclear cells for relative quantification experiments. Hypo volunteers presented significantly higher levels of triglycerides, VLDL-C and insulin; in addition, HDL size and volume decreased when compared with CTL and hyper. Regarding gene expression analysis, the hyper group presented a decrease of 72% in hsa-miR-33a and higher mRNA expression of ABCA1 and ABCG1 when compared with CTL. No significant differences in hsa-miR-128a expression, cholesterol efflux, cIMT or plaques were found. Further studies are necessary to elucidate the mechanisms underlying the complex miRNA network, regulating cellular cholesterol homeostasis in humans and its clinical repercussions.

  11. Structural, vibrational, and electronic properties of an uncoordinated pseudoephedrine derivative and its mononuclear and trinuclear copper(II)-coordinated compounds: A combined theoretical and experimental study

    Science.gov (United States)

    Valencia, Israel; Ávila-Torres, Yenny; Barba-Behrens, Norah; Garzón, Ignacio L.

    2014-11-01

    Multicopper oxidases are fundamental in a variety of biological processes in bacteria, fungi and vertebrates. The catalytic center in these enzymes is formed basically by three copper ions, bridged by oxygen bonds. In order to get insights into the reactivity of these complex systems, biomimetic compounds are usually synthesized. Accordingly, in this work, we studied structural, vibrational, and electronic properties of an uncoordinated pseudoephedrine derivative, as well as its corresponding mononuclear and trinuclear copper(II)-coordinated complexes by means of density functional theory. The calculations are compared with experimental results using measurements of the infrared spectra. It is obtained that the molecular configuration of the pseudoephedrine amino-alcohol derivative is stabilized by hydrogen bonding Osbnd H⋯N and by Csbnd H⋯π interactions that are not present in the mononuclear and trinuclear compounds. The coordination compounds show octahedral and square pyramid geometries, respectively, which are slightly distorted by Jahn-Teller effects. The analysis of their theoretical and experimental IR spectra reveals signals related with hydrogen bonding as well as metal-ligand vibrational modes. Regarding the electronic structure, the density of states was calculated in order to analyze the atomic orbital contributions present in these compounds. This analysis would provide useful insights about the optical behavior, for example, in the visible region of the spectrum of the coordinated compounds. At these energies, the optical absorption would be influenced by the orbital interaction of the Cu2+d orbitals with sp ones of the ligand, reflecting a decrease of the HOMO-LUMO gap of the organic ligand due to the presence of the copper(II) ions.

  12. Iron deficiency anemia and increased urinary norepinephrine excretion.

    Science.gov (United States)

    Voorhess, M L; Stuart, M J; Stockman, J A; Oski, F A

    1975-04-01

    Chronic iron deficiency in rats resulted in decreased MAO activity both in vitro and in vivo. Since MAO is an important enzyme in inactivation of catecholamines, urinary excretion of DA, NE, E, MN-NMN, and VMA was measured in 24-hour samples from 11 iron-deficient children before and after treatment with intramuscular iron. Pretreatment NE excretion was abnormally high and returned to normal (P=0.001) within one week of therapy. VMA excretion also was higher before than after treatment (P greater than 0.05), but most values were within the normal range for healthy children of comparable size. There was no significant difference between DA, E, and MN-NMN excretion before and after iron therapy. Anemic, non-iron-deficient children had normal urinary NE, E, and VMA excretion before and after transfusion. These findings suggest that the irritability, lack of attentiveness, and low performance scores of iron-deficient children may be related to alterations in catecholamine metabolic pathways secondary to dependence of MAO on adequate iron stores.

  13. A quasi-quantitative dual multiplexed immunoblot method to simultaneously analyze ATM and H2AX Phosphorylation in human peripheral blood mononuclear cells.

    Science.gov (United States)

    Bakkenist, Christopher J; Czambel, R Kenneth; Hershberger, Pamela A; Tawbi, Hussein; Beumer, Jan H; Schmitz, John C

    2015-01-01

    Pharmacologic inhibition of DNA repair may increase the efficacy of many cytotoxic cancer agents. Inhibitors of DNA repair enzymes including APE1, ATM, ATR, DNA-PK and PARP have been developed and the PARP inhibitor olaparib is the first-in-class approved in Europe and the USA for the treatment of advanced BRCA-mutated ovarian cancer. Sensitive pharmacodynamic (PD) biomarkers are needed to further evaluate the efficacy of inhibitors of DNA repair enzymes in clinical trials. ATM is a protein kinase that mediates cell-cycle checkpoint activation and DNA double-strand break repair. ATM kinase activation at DNA double-strand breaks (DSBs) is associated with intermolecular autophosphorylation on serine-1981. Exquisite sensitivity and high stoichiometry as well as facile extraction suggest that ATM serine-1981 phosphorylation may be a highly dynamic PD biomarker for both ATM kinase inhibitors and radiation- and chemotherapy-induced DSBs. Here we report the pre-clinical analytical validation and fit-for-purpose biomarker method validation of a quasi-quantitative dual multiplexed immunoblot method to simultaneously analyze ATM and H2AX phosphorylation in human peripheral blood mononuclear cells (PBMCs). We explore the dynamics of these phosphorylations in PBMCs exposed to chemotherapeutic agents and DNA repair inhibitors in vitro, and show that ATM serine-1981 phosphorylation is increased in PBMCs in sarcoma patients treated with DNA damaging chemotherapy.

  14. Validation of using gene expression in mononuclear cells as a marker for hepatic cholesterol metabolism

    Directory of Open Access Journals (Sweden)

    Dutta Amrita

    2006-08-01

    Full Text Available Abstract HMG-CoA reductase and the LDL receptor are ubiquitously expressed in major tissues. Since the liver plays a major role in regulating circulating LDL, it is usually of interest to measure the effects of drug or dietary interventions on these proteins in liver. In humans, peripheral blood mononuclear cells have been used as a surrogate for liver to assess regulation of these genes, although there is concern regarding the validity of this approach. The purpose of this study was to evaluate the relationship between liver and mononuclear cell expression of HMG-CoA reductase and the LDL receptor in guinea pigs, a well established model for human cholesterol and lipoprotein metabolism. We extracted RNA from liver and mononuclear cells of guinea pigs from a previous study where the effects of rapamycin, an immunosuppresant drug used for transplant patients, on lipid metabolism were evaluated. Guinea pigs were assigned to three different diets containing the same amount of fat (15 g/100 g and cholesterol (0.08 g/100 g for a period of 3 weeks. The only difference among diets was the concentration of rapamycin: 0, 0.0028 or 0.028 g/100 g. There were no differences in plasma LDL cholesterol (LDL-C among groups. Values were 78.4 ± 14.3, 65.8 ± 17.2 and 68.4 ± 45.4 mg/dL (P > 0.05 for guinea pigs treated with 0, low or high doses of rapamycin, respectively. The mRNA abundance for the LDL receptor and HMG-CoA reductase was measured both in liver (n = 30 and mononuclear cells (n = 22 using reverse transcriptase PCR. In agreement with the finding of no changes in plasma LDL-C, there were also no differences for the expression of HMG-CoA reductase or the LDL receptor among groups. However, a positive correlation was found between liver and mononuclear cells for both HMG-CoA reductase (r = 0.613, P

  15. The EBI enzyme portal.

    Science.gov (United States)

    Alcántara, Rafael; Onwubiko, Joseph; Cao, Hong; Matos, Paula de; Cham, Jennifer A; Jacobsen, Jules; Holliday, Gemma L; Fischer, Julia D; Rahman, Syed Asad; Jassal, Bijay; Goujon, Mikael; Rowland, Francis; Velankar, Sameer; López, Rodrigo; Overington, John P; Kleywegt, Gerard J; Hermjakob, Henning; O'Donovan, Claire; Martín, María Jesús; Thornton, Janet M; Steinbeck, Christoph

    2013-01-01

    The availability of comprehensive information about enzymes plays an important role in answering questions relevant to interdisciplinary fields such as biochemistry, enzymology, biofuels, bioengineering and drug discovery. At the EMBL European Bioinformatics Institute, we have developed an enzyme portal (http://www.ebi.ac.uk/enzymeportal) to provide this wealth of information on enzymes from multiple in-house resources addressing particular data classes: protein sequence and structure, reactions, pathways and small molecules. The fact that these data reside in separate databases makes information discovery cumbersome. The main goal of the portal is to simplify this process for end users.

  16. Enzyme molecules as nanomotors.

    Science.gov (United States)

    Sengupta, Samudra; Dey, Krishna K; Muddana, Hari S; Tabouillot, Tristan; Ibele, Michael E; Butler, Peter J; Sen, Ayusman

    2013-01-30

    Using fluorescence correlation spectroscopy, we show that the diffusive movements of catalase enzyme molecules increase in the presence of the substrate, hydrogen peroxide, in a concentration-dependent manner. Employing a microfluidic device to generate a substrate concentration gradient, we show that both catalase and urease enzyme molecules spread toward areas of higher substrate concentration, a form of chemotaxis at the molecular scale. Using glucose oxidase and glucose to generate a hydrogen peroxide gradient, we induce the migration of catalase toward glucose oxidase, thereby showing that chemically interconnected enzymes can be drawn together.

  17. The relationship between iron dyshomeostasis and amyloidogenesis in Alzheimer's disease: Two sides of the same coin.

    Science.gov (United States)

    Peters, Douglas G; Connor, James R; Meadowcroft, Mark D

    2015-09-01

    The dysregulation of iron metabolism in Alzheimer's disease is not accounted for in the current framework of the amyloid cascade hypothesis. Accumulating evidence suggests that impaired iron homeostasis is an early event in Alzheimer's disease progression. Iron dyshomeostasis leads to a loss of function in several enzymes requiring iron as a cofactor, the formation of toxic oxidative species, and the elevated production of beta-amyloid proteins. Several common genetic polymorphisms that cause increased iron levels and dyshomeostasis have been associated with Alzheimer's disease but the pathoetiology is not well understood. A full picture is necessary to explain how heterogeneous circumstances lead to iron loading and amyloid deposition. There is evidence to support a causative interplay between the concerted loss of iron homeostasis and amyloid plaque formation. We hypothesize that iron misregulation and beta-amyloid plaque pathology are synergistic in the process of neurodegeneration and ultimately cause a downward cascade of events that spiral into the manifestation of Alzheimer's disease. In this review, we amalgamate recent findings of brain iron metabolism in healthy versus Alzheimer's disease brains and consider unique mechanisms of iron transport in different brain cells as well as how disturbances in iron regulation lead to disease etiology and propagate Alzheimer's pathology.

  18. Iron deficiency and iron deficiency anemia in women.

    Science.gov (United States)

    Coad, Jane; Pedley, Kevin

    2014-01-01

    Iron deficiency is one of the most common nutritional problems in the world and disproportionately affects women and children. Stages of iron deficiency can be characterized as mild deficiency where iron stores become depleted, marginal deficiency where the production of many iron-dependent proteins is compromised but hemoglobin levels are normal and iron deficiency anemia where synthesis of hemoglobin is decreased and oxygen transport to the tissues is reduced. Iron deficiency anemia is usually assessed by measuring hemoglobin levels but this approach lacks both specificity and sensitivity. Failure to identify and treat earlier stages of iron deficiency is concerning given the neurocognitive implications of iron deficiency without anemia. Most of the daily iron requirement is derived from recycling of senescent erythrocytes by macrophages; only 5-10 % comes from the diet. Iron absorption is affected by inhibitors and enhancers of iron absorption and by the physiological state. Inflammatory conditions, including obesity, can result in iron being retained in the enterocytes and macrophages causing hypoferremia as a strategic defense mechanism to restrict iron availability to pathogens. Premenopausal women usually have low iron status because of iron loss in menstrual blood. Conditions which further increase iron loss, compromise absorption or increase demand, such as frequent blood donation, gastrointestinal lesions, athletic activity and pregnancy, can exceed the capacity of the gastrointestinal tract to upregulate iron absorption. Women of reproductive age are at particularly high risk of iron deficiency and its consequences however there is a controversial argument that evolutionary pressures have resulted in an iron deficient phenotype which protects against infection.

  19. Colour Metallography of Cast Iron

    Institute of Scientific and Technical Information of China (English)

    Zhou Jiyang; Liu Jincheng

    2011-01-01

    @@ Vermicular graphite cast iron(VG iron for short in the following sections)is a type of cast iron in which the graphite is intermediate in shape between flake and spheroidal.Compared with the normal flake graphite in grey iron, the graphite in VG iron is shorter and thicker and shows a curved, more rounded shape.Because its outer contour is exactly like a worm, hence it is called vermicular graphite.

  20. Iron-Air Rechargeable Battery

    Science.gov (United States)

    Narayan, Sri R. (Inventor); Prakash, G.K. Surya (Inventor); Kindler, Andrew (Inventor)

    2014-01-01

    Embodiments include an iron-air rechargeable battery having a composite electrode including an iron electrode and a hydrogen electrode integrated therewith. An air electrode is spaced from the iron electrode and an electrolyte is provided in contact with the air electrode and the iron electrodes. Various additives and catalysts are disclosed with respect to the iron electrode, air electrode, and electrolyte for increasing battery efficiency and cycle life.

  1. Ocean iron fertilization

    Digital Repository Service at National Institute of Oceanography (India)

    Naqvi, S.W.A.; Smetacek, V.

    In 2009 and 2010, an Indo-German scientific expedition dusted the ocean with iron to stimulate the biological pump that captures atmosphereic carbon dioxide. Two onboard scientists tell the story of this controversial project. Besides raising...

  2. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... Events Spokespeople Email Alerts E-Newsletters About NHLBI Organization NHLBI Director Budget, Planning, & Legislative Advisory Committees Jobs ... severity of the condition. Treatments may include dietary changes, medicines, and surgery. Severe iron-deficiency anemia may ...

  3. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... of Intramural Research Research Resources Research Meeting Summaries Technology Transfer Clinical Trials What Are Clinical Trials? Children & ... of the condition. Treatments may include dietary changes, medicines, and surgery. Severe iron-deficiency anemia may require ...

  4. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... CAUSES WHO IS AT RISK SIGNS & SYMPTOMS DIAGNOSIS TREATMENTS PREVENTION LIVING WITH CLINICAL TRIALS LINKS Related Topics ... Doctors usually can successfully treat iron-deficiency anemia. Treatment will depend on the cause and severity of ...

  5. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... such as tiredness, poor skin tone, dizziness, and depression. After her doctor diagnosed her with iron-deficiency ... to stop her monthly periods. By following her treatment plan and making smart lifestyle choices, Susan continues ...

  6. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... Deficiency Anemia What Is... CAUSES WHO IS AT RISK SIGNS & SYMPTOMS DIAGNOSIS TREATMENTS PREVENTION LIVING WITH CLINICAL ... and women are the two groups at highest risk for iron-deficiency anemia. Outlook Doctors usually can ...

  7. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... chest pain, and other symptoms. Severe iron-deficiency anemia can lead to heart problems, infections, problems with growth and development in children, and other complications. Infants and young children and ...

  8. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... Events Spokespeople Email Alerts E-Newsletters About NHLBI Organization NHLBI Director Budget, Planning, & Legislative Advisory Committees Jobs ... food. Overview Iron-deficiency anemia is a common type of anemia . The term "anemia" usually refers to ...

  9. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... Deficiency Anemia Explore Iron-Deficiency Anemia What Is... CAUSES WHO IS AT RISK SIGNS & SYMPTOMS DIAGNOSIS TREATMENTS ... Google+ SITE INDEX ACCESSIBILITY PRIVACY STATEMENT FOIA NO FEAR ACT OIG CONTACT US National Institutes of Health ...

  10. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... chest pain, and other symptoms. Severe iron-deficiency anemia can lead to heart problems, infections, problems with growth and development in children, and other complications. Infants and young children and ...

  11. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... CAUSES WHO IS AT RISK SIGNS & SYMPTOMS DIAGNOSIS TREATMENTS PREVENTION LIVING WITH CLINICAL TRIALS LINKS Related Topics ... Doctors usually can successfully treat iron-deficiency anemia. Treatment will depend on the cause and severity of ...

  12. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... a waste product) from your body. Anemia also can occur if your red blood cells don't ... have less hemoglobin than normal. Iron-deficiency anemia can cause fatigue (tiredness), shortness of breath, chest pain, ...

  13. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... symptoms. Severe iron-deficiency anemia can lead to heart problems, infections, problems with growth and development in ... 18/2011 This video—presented by the National Heart, Lung, and Blood Institute, part of the National ...

  14. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... of breath, chest pain, and other symptoms. Severe iron-deficiency anemia can lead to heart problems, infections, problems with growth and development in children, and other complications. Infants and young children and ...

  15. Iron and Your Child

    Science.gov (United States)

    ... red blood cell that carries oxygen from the lungs to the body. Iron gives hemoglobin the strength ... dried beans and peas dried fruits leafy dark green ... serving coffee or tea at mealtime — both contain tannins that reduce the ...

  16. Ferrous Sulfate (Iron)

    Science.gov (United States)

    Ferrous sulfate provides the iron needed by the body to produce red blood cells. It is used ... Ferrous sulfate comes as regular, coated, and extended-release (long-acting) tablets; regular and extended-release capsules; ...

  17. 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.

  18. Microarray analysis of iron deficiency chlorosis in near-isogenic soybean lines

    Directory of Open Access Journals (Sweden)

    Cianzio Silvia R

    2007-12-01

    grown under iron sufficient and iron limited conditions. Iron inefficient plants failed to respond to decreased iron availability with increased activity of Fe reductase. Conclusion These experiments have identified genes involved in the soybean iron deficiency chlorosis response under iron deficient conditions. Single linkage cluster analysis suggests iron limited soybeans mount a general stress response as well as a specialized iron deficiency stress response. Root membrane bound reductase capacity is often correlated with iron efficiency. Under iron-limited conditions, the iron efficient plant had high root bound membrane reductase capacity while the iron inefficient plants reductase levels remained low, further limiting iron uptake through the root. Many of the genes up-regulated in the iron inefficient NIL are involved in known stress induced pathways. The most striking response of the iron inefficient genotype to iron deficiency stress was the induction of a profusion of signaling and regulatory genes, presumably in an attempt to establish and maintain cellular homeostasis. Genes were up-regulated that point toward an increased transport of molecules through membranes. Genes associated with reactive oxidative species and an ROS-defensive enzyme were also induced. The up-regulation of genes involved in DNA repair and RNA stability reflect the inhospitable cellular environment resulting from iron deficiency stress. Other genes were induced that are involved in protein and lipid catabolism; perhaps as an effort to maintain carbon flow and scavenge energy. The under-expression of a key glycolitic gene may result in the iron-inefficient genotype being energetically challenged to maintain a stable cellular environment. These experiments have identified candidate genes and processes for further experimentation to increase our understanding of soybeans' response to iron deficiency stress.

  19. 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...

  20. Enzymes in Analytical Chemistry.

    Science.gov (United States)

    Fishman, Myer M.

    1980-01-01

    Presents tabular information concerning recent research in the field of enzymes in analytic chemistry, with methods, substrate or reaction catalyzed, assay, comments and references listed. The table refers to 128 references. Also listed are 13 general citations. (CS)

  1. Enzymic lactose hydrolysis

    Energy Technology Data Exchange (ETDEWEB)

    Miller, J.J.; Brand, J.C.

    1980-01-01

    Acid or enzymic hydrolysis can be used to hydrolyze lactose. Advantages of both are compared and details of enzymic hydrolysis using yeast or fungal enzymes given. The new scheme outlined involves recycling lactase. Because lactose and lactase react to ultrafiltration (UF) membranes differently separation is possible. Milk or milk products are ultrafiltered to separate a concentrate from a lactose-rich permeate which is treated with lactase in a reactor until hydrolysis reaches a required level. The lactase can be removed by UF as it does not permeate the membrane, and it is recycled back to the reactor. Permeate from the second UF stage may or may not be recombined with the concentrate from the first stage to produce a low lactose product (analysis of a typical low-lactose dried whole milk is given). Batch or continuous processes are explained and a batch process without enzyme recovery is discussed. (Refs. 4).

  2. Membrane Assisted Enzyme Fractionation

    DEFF Research Database (Denmark)

    Yuan, Linfeng

    . In this thesis, separations using crossflow elecro-membrane filtration (EMF) of amino acids, bovine serum albumin (BSA) and industrial enzymes from Novozymes were performed. The main objective of this study was to investigate the technological feasibility of EMF in the application of industrial enzyme...... fractionation, such as removal of a side activity from the main enzyme activity. As a proof-of-concept, amino acids were used as model solution to test the feasibility of EMF in the application of amphoteric molecule separation. A single amino acid was used to illustrate the effect of an electric field...... on the separation performance were very small in the investigated range. The mass transport of each enzyme can be well explained by the Extended-Nernst-Planck equation. Better separation was observed at lower feed concentration, higher solution pH in the investigated range and with a polysulfone (PS) MF membrane...

  3. Indicators: Sediment Enzymes

    Science.gov (United States)

    Sediment enzymes are proteins that are produced by microorganisms living in the sediment or soil. They are indicators of key ecosystem processes and can help determine which nutrients are affecting the biological community of a waterbody.

  4. Starch Biorefinery Enzymes.

    Science.gov (United States)

    Läufer, Albrecht

    2017-03-07

    Nature uses enzymes to build and convert biomass; mankind uses the same enzymes and produces them on a large scale to make optimum use of biomass in biorefineries. Bacterial α-amylases and fungal glucoamylases have been the workhorses of starch biorefineries for many decades. Pullulanases were introduced in the 1980s. Proteases, cellulases, hemicellulases, and phytases have been on the market for a few years as process aids, improving yields, performance, and costs. Detailed studies of the complex chemical structures of biomass and of the physicochemical limitations of industrial biorefineries have led enzyme developers to produce novel tailor-made solutions for improving yield and profitability in the industry. This chapter reviews the development of enzyme applications in the major starch biorefining processes.

  5. Membrane Assisted Enzyme Fractionation

    DEFF Research Database (Denmark)

    Yuan, Linfeng

    . In this thesis, separations using crossflow elecro-membrane filtration (EMF) of amino acids, bovine serum albumin (BSA) and industrial enzymes from Novozymes were performed. The main objective of this study was to investigate the technological feasibility of EMF in the application of industrial enzyme...... fractionation, such as removal of a side activity from the main enzyme activity. As a proof-of-concept, amino acids were used as model solution to test the feasibility of EMF in the application of amphoteric molecule separation. A single amino acid was used to illustrate the effect of an electric field...... on the separation performance were very small in the investigated range. The mass transport of each enzyme can be well explained by the Extended-Nernst-Planck equation. Better separation was observed at lower feed concentration, higher solution pH in the investigated range and with a polysulfone (PS) MF membrane...

  6. Microbes: Mini Iron Factories

    OpenAIRE

    Joshi, Kumar Batuk

    2014-01-01

    Microbes have flourished in extreme habitats since beginning of the Earth and have played an important role in geological processes like weathering, mineralization, diagenesis, mineral formation and destruction. Biotic mineralization is one of the most fascinating examples of how microbes have been influencing geological processes. Iron oxidizing and reducing bacteria are capable of precipitating wide varieties of iron oxides (magnetite), carbonates (siderite) and sulphides (greigite) via con...

  7. Impairment of interrelated iron- and copper homeostatic mechanisms in brain contributes to the pathogenesis of neurodegenerative disorders

    DEFF Research Database (Denmark)

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

    2012-01-01

    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......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...... 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...

  8. RNA-modifying enzymes.

    Science.gov (United States)

    Ferré-D'Amaré, Adrian R

    2003-02-01

    A bewildering number of post-transcriptional modifications are introduced into cellular RNAs by enzymes that are often conserved among archaea, bacteria and eukaryotes. The modifications range from those with well-understood functions, such as tRNA aminoacylation, to widespread but more mysterious ones, such as pseudouridylation. Recent structure determinations have included two types of RNA nucleobase modifying enzyme: pseudouridine synthases and tRNA guanine transglycosylases.

  9. Overproduction of ligninolytic enzymes

    Energy Technology Data Exchange (ETDEWEB)

    Elisashvili, Vladimir; Kachlishvili, Eva; Torok, Tamas

    2014-06-17

    Methods, compositions, and systems for overproducing ligninolytic enzymes from the basidiomycetous fungus are described herein. As described, the method can include incubating a fungal strain of Cerrena unicolor IBB 303 in a fermentation system having growth medium which includes lignocellulosic material and then cultivating the fungal strain in the fermentation system under conditions wherein the fungus expresses the ligninolytic enzymes. In some cases, the lignocellulosic material is mandarin peel, ethanol production residue, walnut pericarp, wheat bran, wheat straw, or banana peel.

  10. Iron-Refractory Iron Deficiency Anemia

    OpenAIRE

    Ebru Yılmaz Keskin; İdil Yenicesu

    2015-01-01

    Demir, oksijenin taşınması, DNA sentezi ve hücre çoğalması gibi çeşitli biyolojik reaksiyonlar için vazgeçilmez olduğundan, yaşam için zorunludur. Demir metabolizması ve bu elementin düzenlenmesiyle ilgili bilgilerimiz, son yıllarda belirgin şekilde değişmiştir. Demir metabolizması ile ilgili yeni bozukluklar tanımlanmış ve demirin başka bozuklukların kofaktörü olduğu anlaşılmaya başlamıştır. Hemokromatozis ve demir tedavisine dirençli demir eksikliği anemisi (IRIDA; “iron-refractory iron def...

  11. Intravenous Iron Sucrose for Children With Iron Deficiency Anemia.

    Science.gov (United States)

    Kaneva, Kristiyana; Chow, Erika; Rosenfield, Cathy G; Kelly, Michael J

    2017-07-01

    Iron deficiency anemia (IDA) is the most common nutritional deficiency in children. Most children with IDA are treated with oral iron preparations. However, intravenous (IV) iron is an alternative for children with severe IDA who have difficulty in adhering to or absorbing oral iron. We sought to describe the safety and effectiveness of IV iron sucrose for treatment of IDA in children. Pharmacy records of children who received IV iron sucrose at a children's hospital between 2004 and 2014 were reviewed. Laboratory markers of anemia and iron studies were obtained and preinfusion and postinfusion values were compared. Records were also reviewed for adverse reactions. A total of 142 patients received IV iron sucrose over 10 years. The mean age was 11 years, 9 months. One patient of 142 developed cough and wheezing during the infusion. No other adverse events were found. IV iron sucrose resulted in a statistically significant and clinically meaningful increase in hemoglobin, mean corpuscular volume, serum iron, ferritin, and % iron saturation, with a corresponding decrease in total iron binding capacity. The use of IV iron sucrose in pediatric patients with IDA is safe and leads to a moderate increase in hemoglobin and substantial improvement in iron studies.

  12. Organometallic iron complexes as potential cancer therapeutics.

    Science.gov (United States)

    Mojžišová, Gabriela; Mojžiš, Ján; Vašková, Janka

    2014-01-01

    Metal-containing drugs have long been used for medicinal purposes in more or less empirical way. The potential of these anticancer agents has only been fully realised and explored since the discovery of the biological activity of cisplatin. Cisplatin and carboplatin have been two of the most successful anti-cancer agents ever developed, and are currently used to treat ovarian, lung and testicular cancers. They share certain side effects, so their clinical use is severely limited by dose-limiting toxicity. Inherent or acquired resistance is a second problem often associated with platinum-based drugs, with further limits of their clinical use. These problems have prompted chemists to employ different strategies in development of the new metal-based anticancer agents with different mechanisms of action. There are various metal complexes still under development and investigation for the future cancer treatment use. In the search for novel bio-organometallic molecules, iron containing anti-tumoral agents are enjoying an increasing interest and appear very promising as the potential drug candidates. Iron, as an essential cofactor in a number of enzymes and physiological processes, may be less toxic than non essential metals, such as platinum. Up to now, some of iron complexes have been tested as cytotoxic agents and found to be endowed with an antitumor activity in several in vitro tests (on cultured cancer cell lines) and few in vivo experiments (e. g. on Ehrlich's ascites carcinoma). Although the precise molecular mechanism is yet to be defined, a number of observations suggest that the reactive oxygen species can play important role in iron-induced cytotoxicty. This review covers some relevant examples of research on the novel iron complexes.

  13. Effect of nutrient deficiencies on in vitro Th1 and Th2 cytokine response of peripheral blood mononuclear cells to Plasmodium falciparum infection

    Directory of Open Access Journals (Sweden)

    McCall Matthew

    2010-06-01

    Full Text Available Abstract Background An appropriate balance between pro-inflammatory and anti-inflammatory cytokines that mediate innate and adaptive immune responses is required for effective protection against human malaria and to avoid immunopathology. In malaria endemic countries, this immunological balance may be influenced by micronutrient deficiencies. Methods Peripheral blood mononuclear cells from Tanzanian preschool children were stimulated in vitro with Plasmodium falciparum-parasitized red blood cells to determine T-cell responses to malaria under different conditions of nutrient deficiencies and malaria status. Results The data obtained indicate that zinc deficiency is associated with an increase in TNF response by 37%; 95% CI: 14% to 118% and IFN-γ response by 74%; 95% CI: 24% to 297%. Magnesium deficiency, on the other hand, was associated with an increase in production of IL-13 by 80%; 95% CI: 31% to 371% and a reduction in IFN-γ production. These results reflect a shift in cytokine profile to a more type I cytokine profile and cell-cell mediated responses in zinc deficiency and a type II response in magnesium deficiency. The data also reveal a non-specific decrease in cytokine production in children due to iron deficiency anaemia that is largely associated with malaria infection status. Conclusions The pathological sequels of malaria potentially depend more on the balance between type I and type II cytokine responses than on absolute suppression of these cytokines and this balance may be influenced by a combination of micronutrient deficiencies and malaria status.

  14. 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.

  15. Evidence Suggesting a Role of Iron in a Mouse Model of Nephrogenic Systemic Fibrosis.

    Directory of Open Access Journals (Sweden)

    Chhanda Bose

    Full Text Available Nephrogenic systemic fibrosis is associated with gadolinium contrast exposure in patients with reduced kidney function and carries high morbidity and mortality. We have previously demonstrated that gadolinium contrast agents induce in vivo systemic iron mobilization and in vitro differentiation of peripheral blood mononuclear cells into ferroportin (iron exporter-expressing fibrocytic cells. In the present study we examined the role of iron in a mouse model of nephrogenic systemic fibrosis. Chronic kidney disease was induced in 8-week-old male Balb/C mice with a two-step 5/6 nephrectomy surgery. Five groups of mice were studied: control (n = 5, sham surgery control (n = 5, chronic kidney disease control (n = 4, chronic kidney disease injected with 0.5 mmol/kg body weight of Omniscan 3 days per week, for a total of 10 injections (n = 8, and chronic kidney disease with Omniscan plus deferiprone, 125 mg/kg, in drinking water (n = 9. Deferiprone was continued for 16 weeks until the end of the experiment. Mice with chronic kidney disease injected with Omniscan developed skin changes characteristic of nephrogenic systemic fibrosis including hair loss, reddening, ulceration, and skin tightening by 10 to 16 weeks. Histopathological sections demonstrated dermal fibrosis with increased skin thickness (0.25±0.06 mm, sham; 0.34±+0.3 mm, Omniscan-injected. Additionally, we observed an increase in tissue infiltration of ferroportin-expressing, fibrocyte-like cells accompanied by tissue iron accumulation in the skin of the Omniscan-treated mice. The deferiprone-treated group had significantly decreased skin thickness (p<0.05 and significantly decreased dermal fibrosis compared to the Omniscan-only group. In addition, iron chelation prevented tissue infiltration of ferroportin-expressing, fibrocyte-like cells. Our in vitro experiments demonstrated that exposure to Omniscan resulted in the release of catalytic iron and this was prevented by the iron chelator

  16. IFN-{gamma} gene expression in pancreatic islet-infiltrating mononuclear cells correlates with autoimmune diabetes in nonobese diabetic mice

    Energy Technology Data Exchange (ETDEWEB)

    Rabinovitch, A.; Suarez-Pinzon, W.L.; Sorensen, O. [Univ. of Alberta, Edmonton (Canada)] [and others

    1995-05-01

    Insulin-dependent diabetes mellitus in nonobese diabetic (NOD) mice results from selective destruction of pancreatic islet {beta}-cells following islet filtration by mononuclear leukocytes. Cytokines produced by islet-infiltrating mononuclear cells may be involved in {beta}-cell destruction. Therefore, we analyzed cytokine mRNA expression, by reverse-transcriptase PCR (RT-PCR) assay, in mononuclear leukocytes isolated from pancreatic islets of four groups of mice: diabetes-prone female NOD mice; female NOD mice protected from diabetes by injection of CFA at an early age; male NOD mice with a low diabetes incidence; and female BALB/c mice that do not develop diabetes. We found that mRNA levels of IL-1{beta}, IL-2, IL-4, IL-10, and IFN-{gamma} in mononuclear cells from islets of diabetes-prone female NOD mice increased progressively as these cells infiltrated the islets from age 5 wk to diabetes onset (>13 wk). However, only IFN-{gamma} mRNA levels were significantly higher in islet mononuclear cells from 12-wk-old diabetes-prone female NOD mice than from less diabetes-prone NOD mice (CFA-treated females, and males) and normal mice (BALB/c). In contrast, IL-4 mRNA levels were lower in islet mononuclear cells from diabetes-prone female NOD mice than from NOD mice with low diabetes incidence (CFA-treated females and males). Splenic cell mRNA levels of IFN-{gamma} and IL-4 were not different in the four groups of mice. These results suggest that islet {beta}-cell destruction and diabetes in female NOD mice are dependent upon intra-islet IFN-{gamma} production by mononuclear cells, and that CFA-treated female NOD mice and male NOD mice may be protected from diabetes development by down-regulation of IFN-{gamma} production in the islets. 56 refs., 4 figs., 3 tabs.

  17. Iron Absorption in Drosophila melanogaster

    Directory of Open Access Journals (Sweden)

    Fanis Missirlis

    2013-05-01

    Full Text Available The way in which Drosophila melanogaster acquires iron from the diet remains poorly understood despite iron absorption being of vital significance for larval growth. To describe the process of organismal iron absorption, consideration needs to be given to cellular iron import, storage, export and how intestinal epithelial cells sense and respond to iron availability. Here we review studies on the Divalent Metal Transporter-1 homolog Malvolio (iron import, the recent discovery that Multicopper Oxidase-1 has ferroxidase activity (iron export and the role of ferritin in the process of iron acquisition (iron storage. We also describe what is known about iron regulation in insect cells. We then draw upon knowledge from mammalian iron homeostasis to identify candidate genes in flies. Questions arise from the lack of conservation in Drosophila for key mammalian players, such as ferroportin, hepcidin and all the components of the hemochromatosis-related pathway. Drosophila and other insects also lack erythropoiesis. Thus, systemic iron regulation is likely to be conveyed by different signaling pathways and tissue requirements. The significance of regulating intestinal iron uptake is inferred from reports linking Drosophila developmental, immune, heat-shock and behavioral responses to iron sequestration.

  18. Iron Absorption in Drosophila melanogaster

    Science.gov (United States)

    Mandilaras, Konstantinos; Pathmanathan, Tharse; Missirlis, Fanis

    2013-01-01

    The way in which Drosophila melanogaster acquires iron from the diet remains poorly understood despite iron absorption being of vital significance for larval growth. To describe the process of organismal iron absorption, consideration needs to be given to cellular iron import, storage, export and how intestinal epithelial cells sense and respond to iron availability. Here we review studies on the Divalent Metal Transporter-1 homolog Malvolio (iron import), the recent discovery that Multicopper Oxidase-1 has ferroxidase activity (iron export) and the role of ferritin in the process of iron acquisition (iron storage). We also describe what is known about iron regulation in insect cells. We then draw upon knowledge from mammalian iron homeostasis to identify candidate genes in flies. Questions arise from the lack of conservation in Drosophila for key mammalian players, such as ferroportin, hepcidin and all the components of the hemochromatosis-related pathway. Drosophila and other insects also lack erythropoiesis. Thus, systemic iron regulation is likely to be conveyed by different signaling pathways and tissue requirements. The significance of regulating intestinal iron uptake is inferred from reports linking Drosophila developmental, immune, heat-shock and behavioral responses to iron sequestration. PMID:23686013

  19. A proline-based aminophenol ligand: synthesis, iron complexation, magnetic, electronic and redox investigation.

    Science.gov (United States)

    Sheykhi, Hamid; Safaei, Elham

    2014-01-24

    A new proline-based aminophenol ligand was synthesized by a convenient procedure. The ligand was characterized by (1)H NMR, (13)C NMR and IR spectroscopies, elemental analysis and optical activity measurements. Mononuclear iron(III) complex (FeL(Pro)) of this ligand was synthesized and characterized by IR, UV-vis, ESI-MS, magnetic susceptibility studies and cyclic voltammetry techniques. The equilibrium formation constant of FeL(Pro) and the pure UV-vis spectral profile of the complex was determined by multivariate hard modeling method. The molecular structure of FeL(Pro) determined by ESI-MS consist of two aminophenolate ligands. The variation of magnetic susceptibility with temperature indicates paramagnetic iron(III) in the monomeric complex. FeL(Pro) complex undergo metal-centered reduction, and ligand-centered oxidation. Copyright © 2013 Elsevier B.V. All rights reserved.

  20. A bioinspired iron catalyst for nitrate and perchlorate reduction.

    Science.gov (United States)

    Ford, Courtney L; Park, Yun Ji; Matson, Ellen M; Gordon, Zachary; Fout, Alison R

    2016-11-11

    Nitrate and perchlorate have considerable use in technology, synthetic materials, and agriculture; as a result, they have become pervasive water pollutants. Industrial strategies to chemically reduce these oxyanions often require the use of harsh conditions, but microorganisms can efficiently reduce them enzymatically. We developed an iron catalyst inspired by the active sites of nitrate reductase and (per)chlorate reductase enzymes. The catalyst features a secondary coordination sphere that aids in oxyanion deoxygenation. Upon reduction of the oxyanions, an iron(III)-oxo is formed, which in the presence of protons and electrons regenerates the catalyst and releases water.

  1. 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; de Oliveira, Giovanna Medeiros Tavares; Bogo, Maurício Reis; Carli, Geraldo Atillio De; Macedo, Alexandre José; Tasca, Tiana

    2015-01-01

    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. PMID:25946243

  2. 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.

  3. 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.

  4. Random-walk enzymes.

    Science.gov (United States)

    Mak, Chi H; Pham, Phuong; Afif, Samir A; Goodman, Myron F

    2015-09-01

    Enzymes that rely on random walk to search for substrate targets in a heterogeneously dispersed medium can leave behind complex spatial profiles of their catalyzed conversions. The catalytic signatures of these random-walk enzymes are the result of two coupled stochastic processes: scanning and catalysis. Here we develop analytical models to understand the conversion profiles produced by these enzymes, comparing an intrusive model, in which scanning and catalysis are tightly coupled, against a loosely coupled passive model. Diagrammatic theory and path-integral solutions of these models revealed clearly distinct predictions. Comparison to experimental data from catalyzed deaminations deposited on single-stranded DNA by the enzyme activation-induced deoxycytidine deaminase (AID) demonstrates that catalysis and diffusion are strongly intertwined, where the chemical conversions give rise to new stochastic trajectories that were absent if the substrate DNA was homogeneous. The C→U deamination profiles in both analytical predictions and experiments exhibit a strong contextual dependence, where the conversion rate of each target site is strongly contingent on the identities of other surrounding targets, with the intrusive model showing an excellent fit to the data. These methods can be applied to deduce sequence-dependent catalytic signatures of other DNA modification enzymes, with potential applications to cancer, gene regulation, and epigenetics.

  5. Random-walk enzymes

    Science.gov (United States)

    Mak, Chi H.; Pham, Phuong; Afif, Samir A.; Goodman, Myron F.

    2015-09-01

    Enzymes that rely on random walk to search for substrate targets in a heterogeneously dispersed medium can leave behind complex spatial profiles of their catalyzed conversions. The catalytic signatures of these random-walk enzymes are the result of two coupled stochastic processes: scanning and catalysis. Here we develop analytical models to understand the conversion profiles produced by these enzymes, comparing an intrusive model, in which scanning and catalysis are tightly coupled, against a loosely coupled passive model. Diagrammatic theory and path-integral solutions of these models revealed clearly distinct predictions. Comparison to experimental data from catalyzed deaminations deposited on single-stranded DNA by the enzyme activation-induced deoxycytidine deaminase (AID) demonstrates that catalysis and diffusion are strongly intertwined, where the chemical conversions give rise to new stochastic trajectories that were absent if the substrate DNA was homogeneous. The C →U deamination profiles in both analytical predictions and experiments exhibit a strong contextual dependence, where the conversion rate of each target site is strongly contingent on the identities of other surrounding targets, with the intrusive model showing an excellent fit to the data. These methods can be applied to deduce sequence-dependent catalytic signatures of other DNA modification enzymes, with potential applications to cancer, gene regulation, and epigenetics.

  6. Random-walk enzymes

    Science.gov (United States)

    Mak, Chi H.; Pham, Phuong; Afif, Samir A.; Goodman, Myron F.

    2015-01-01

    Enzymes that rely on random walk to search for substrate targets in a heterogeneously dispersed medium can leave behind complex spatial profiles of their catalyzed conversions. The catalytic signatures of these random-walk enzymes are the result of two coupled stochastic processes: scanning and catalysis. Here we develop analytical models to understand the conversion profiles produced by these enzymes, comparing an intrusive model, in which scanning and catalysis are tightly coupled, against a loosely coupled passive model. Diagrammatic theory and path-integral solutions of these models revealed clearly distinct predictions. Comparison to experimental data from catalyzed deaminations deposited on single-stranded DNA by the enzyme activation-induced deoxycytidine deaminase (AID) demonstrates that catalysis and diffusion are strongly intertwined, where the chemical conversions give rise to new stochastic trajectories that were absent if the substrate DNA was homogeneous. The C → U deamination profiles in both analytical predictions and experiments exhibit a strong contextual dependence, where the conversion rate of each target site is strongly contingent on the identities of other surrounding targets, with the intrusive model showing an excellent fit to the data. These methods can be applied to deduce sequence-dependent catalytic signatures of other DNA modification enzymes, with potential applications to cancer, gene regulation, and epigenetics. PMID:26465508

  7. Intra-arterial Infusion of Autologous Bone Marrow Mononuclear Stem Cells in Subacute Ischemic Stroke Patients.

    Science.gov (United States)

    Ghali, Azza Abass; Yousef, Mohamed Khalil; Ragab, Osama AbdAllah; ElZamarany, Enas Arafa

    2016-01-01

    Based on many preclinical and small clinical trials, stem cells can help stroke patient with the possibility of replacing the cells and supporting the remaining cells. The aim of this study was to evaluate the safety and feasibility of bone marrow mononuclear (BMMN) stem cell transplantation in subacute ischemic stroke patients. Thirty-nine (n = 39) patients with subacute ischemic cerebral infarct due to large artery occlusion in the middle cerebral artery (MCA) territory were recruited. They were distributed into two groups: first group (n = 21) served as an experimental group, which received intra-arterial (IA) mononuclear stem cells (bone marrow-derived mononuclear cell), while the other group (n = 18) served as a control group. All the patients were evaluated clinically by National Institutes of Health Stroke Scale, modified Rankin Scale, Barthel Index, modified and standardized Arabic version of the Comprehensive Aphasia Test, and radiological for 12 months. The stem cell-treated group showed better improvement, but it was not significant when compared with the non-treated group. The volume of infarction changes at the end of the study was non-significant between both the groups. There was no, or minimal, adverse reactions in stem cell-treated group. The study results suggest that autologous BMMN stem cell IA transplantation in subacute MCA ischemic stroke patients is safe with very minimal hazards, but no significant improvement of motor, language disturbance, or infarction volume was detected in stem cell-treated group compared with the non-treated group.

  8. Usefulness of liver infiltrating CD86-positive mononuclear cells for diagnosis of autoimmune hepatitis

    Institute of Scientific and Technical Information of China (English)

    Kazutaka Kurokohchi; Shigeki Kuriyama; Tsutomu Masaki; Takashi Himoto; Akihiro Deguchi; Seiji Nakai; Asahiro Morishita; Hirohito Yoneyama; Yasuhiko Kimura; Seishiro Watanabe

    2006-01-01

    AIM: Although the pathogenic mechanism underlying autoimmune hepatitis (AIH) remains unclear, the immune system is thought to be critical for the progression of the disease. Cellular immune responses may be linked to the hepatocellular damage in AIH. Recently, much attention has been focused on the critical functions of costimulatory molecules expressed on mononuclear cells in the generation of effective T cell-mediated immune responses. Analysis of costimulatory molecule expressed on mononuclear cells from the patients with AIH may give us insight into the pathogenic mechanism of hepatocellular damage in AIH.METHODS: Peripheral blood mononuclear cells (PBMC)were taken from the patients with AIH (34 cases) and healthy controls (25 cases). Liver infiltrating mononuclear cells (LIMCs) were taken from the patients with AIH (18 cases), the patient with chronic hepatitis C (CH-C) (13 cases) and the patients with fatty liver (2 cases).Using flow cytometry, the cells were analyzed for the expression of costimulatory molecules, such as CD80,CD86, and CD152 (CTLA-4). The results were compared with clinical data such as the level of gammaglobulin,histological grade, presence or absence of corticosteroids administration and the response to corticosteroids.RESULTS: The levels of CD80+, CD86+ and CD152+PBMC were significantly reduced in the patients with AIH as compared with healthy controls. By contrast,those cells were significantly higher in LTMC than in PBMC of the patients with AIH. Especially, the level of CD86+ LIMC showed a marked increase irrespective of the degree of disease activity in the patients with ATH,although CD86+ cells were rarely present in PBMC. The levels of CD86+ cells were present in significantly higher frequency in patients with AIH than in the patients with CH-C. Furthermore, the patients with AIH with high levels of CD86+ LIMC showed good responses to corticosteroids, whereas 2 cases of AIH with low levels of CD86+ LIMC did not respond well

  9. Generation of iPS Cells from Human Peripheral Blood Mononuclear Cells Using Episomal Vectors.

    Science.gov (United States)

    Su, Ruijun Jeanna; Neises, Amanda; Zhang, Xiao-Bing

    2016-01-01

    Peripheral blood is the easy-to-access, minimally invasive, and the most abundant cell source to use for cell reprogramming. The episomal vector is among the best approaches for generating integration-free induced pluripotent stem (iPS) cells due to its simplicity and affordability. Here we describe the detailed protocol for the efficient generation of integration-free iPS cells from peripheral blood mononuclear cells. With this optimized protocol, one can readily generate hundreds of iPS cell colonies from 1 ml of peripheral blood.

  10. Age and gender effects on DNA strand break repair in peripheral blood mononuclear cells

    DEFF Research Database (Denmark)

    Garm, Christian; Moreno-Villanueva, Maria; Bürkle, Alexander;

    2013-01-01

    single-strand breaks (SSBs) and double-strand breaks (DSBs) in human peripheral blood mononuclear cells (PBMCs). Of these lesions, DSBs are the least frequent but the most dangerous for cells. We have measured the level of endogenous SSBs, SSB repair capacity, γ-H2AX response, and DSB repair capacity...... in a study population consisting of 216 individuals from a population-based sample of twins aged 40-77 years. Age in this range did not seem to have any effect on the SSB parameters. However, γ-H2AX response and DSB repair capacity decreased with increasing age, although the associations did not reach...

  11. Enzyme recycling in lignocellulosic biorefineries

    DEFF Research Database (Denmark)

    Jørgensen, Henning; Pinelo, Manuel

    2017-01-01

    platform. Cellulases are the most important enzymes required in this process, but the complex nature of lignocellulose requires several other enzymes (hemicellulases and auxiliary enzymes) for efficient hydrolysis. Enzyme recycling increases the catalytic productivity of the enzymes by reusing them...... upscaled and tested in industrial settings, mainly because of many difficulties with recycling of enzymes from the complex lignocellulose hydrolyzate at industrially relevant conditions, i.e., high solids loadings. The challenges are associated with the large number of different enzymes required...... for efficient hydrolysis, enzyme stability, and the detrimental interaction between enzyme and lignin. This review provides a comprehensive overview of the various methods for enzyme recovery and recycling, for example recycling of free enzymes, readsorption to fresh material, recycling of solids, membrane...

  12. Serum Hepcidin Levels, Iron Dyshomeostasis and Cognitive Loss in Alzheimer’s Disease

    Science.gov (United States)

    Sternberg, Zohara; Hu, Zihua; Sternberg, Daniel; Waseh, Shayan; Quinn, Joseph F.; Wild, Katharine; Jeffrey, Kaye; Zhao, Lin; Garrick, Michael

    2017-01-01

    This pilot study examined the status of the master iron regulatory peptide, hepcidin, and peripheral related iron parameters in Alzheimer’s disease (AD) and mild cognitive impairment patients, and evaluated the relationship between iron dyshomeostasis and amyloid-beta (Aβ), cognitive assessment tests, neuroimaging and clinical data. Frozen serum samples from the Oregon Tissue Bank were used to measure serum levels of hepcidin, ferritin, Aβ40, Aβ42 using enzyme-linked immunosorbent assay. Serum transferrin levels were determined indirectly as total iron binding capacity, serum iron was measured and the percent saturation of transferrin calculated. The study variables were correlated with the patients’ existing cognitive assessment tests, neuroimaging, and clinical data. Hepcidin, and iron-related proteins tended to be higher in AD patients than controls, reaching statistical significance for ferritin, whereas Aβ40, Aβ42 serum levels tended to be lower. Patients with pure AD had three times higher serum hepcidin levels than controls; gender differences in hepcidin and iron-related proteins were observed. Patient stratification based on clinical dementia rating-sum of boxes revealed significantly higher levels of iron and iron-related proteins in AD patients in the upper 50% as compared to controls, suggesting that iron dyshomeostasis worsens as cognitive impairment increases. Unlike Aβ peptides, iron and iron-related proteins showed significant association with cognitive assessment tests, neuroimaging, and clinical data. Hepcidin and iron-related proteins comprise a group of serum biomarkers that relate to AD diagnosis and AD disease progression. Future studies should determine whether strategies targeted to diminishing hepcidin synthesis/secretion and improving iron homeostasis could have a beneficial impact on AD progression. PMID:28400987

  13. Iron replacement therapy

    DEFF Research Database (Denmark)

    Nielsen, Ole Haagen; Coskun, Mehmet; Weiss, Günter

    2016-01-01

    PURPOSE OF REVIEW: Approximately, one-third of the world's population suffers from anemia, and at least half of these cases are because of iron deficiency. With the introduction of new intravenous iron preparations over the last decade, uncertainty has arisen when these compounds should be admini...... treatment, when to follow-up for relapse, which dosage and type of therapy should be recommended or not recommended, and if some patients should not be treated....... be administered and under which circumstances oral therapy is still an appropriate and effective treatment. RECENT FINDINGS: Numerous guidelines are available, but none go into detail about therapeutic start and end points or how iron-deficiency anemia should be best treated depending on the underlying cause...... of iron deficiency or in regard to concomitant underlying or additional diseases. SUMMARY: The study points to major issues to be considered in revisions of future guidelines for the true optimal iron replacement therapy, including how to assess the need for treatment, when to start and when to stop...

  14. [Iron deficiency and iron deficiency anemia are global health problems].

    Science.gov (United States)

    Dahlerup, Jens; Lindgren, Stefan; Moum, Björn

    2015-03-10

    Iron deficiency and iron deficiency anemia are global health problems leading to deterioration in patients' quality of life and more serious prognosis in patients with chronic diseases. The cause of iron deficiency and anemia is usually a combination of increased loss and decreased intestinal absorption and delivery from iron stores due to inflammation. Oral iron is first line treatment, but often hampered by intolerance. Intravenous iron is safe, and the preferred treatment in patients with chronic inflammation and bowel diseases. The goal of treatment is normalisation of hemoglobin concentration and recovery of iron stores. It is important to follow up treatment to ensure that these objectives are met and also long-term in patients with chronic iron loss and/or inflammation to avoid recurrence of anemia.

  15. Thermostable lipoxygenase, a key enzyme in bioconversion of linoleic acid to trihycroxy-octadecenoic acid by Pseudomonas aeruginosa PR3

    Science.gov (United States)

    Lipoxygenases, enzymes that contain non-heme iron, catalyze the oxidation of unsaturated fatty acids with a (1Z,4Z)-pentadiene moiety leading to conjugated (Z,E)-hydroperoxydienoic acids. These enzymes are widely distributed in plants and animals, and a few microorganisms are reported as well. It ...

  16. Prevalence of Iron deficiency anemia in children with liver cirrhosis: A cross-sectional study

    Science.gov (United States)

    Zareifar, Soheila; Dehghani, Seyed Mohsen; Rahanjam, Najmeh; Farahmand Far, Mohammad Reza

    2015-01-01

    Background: Among the many complications reported for cirrhosis, iron deficiency anemia (IDA) has attracted much attention. This type of anemia, in contrast to other types of anemia, is easy to treat prophylactically, but if left untreated can lead to a poor quality of life. The aim of this study was to estimate the hemoglobin and serum iron levels among patients with liver cirrhosis for the early diagnosis of IDA and to avoid unnecessary testing and iron supplementation. Subjects and Methods: In this cross-sectional study, 88 children diagnosed with cirrhosis were included, and the values of hemoglobin, serum iron levels and relationship between serum iron (SI), total iron-binding capacity (TIBC), prothrombine time (PT), international normalization ratio (INR), total and direct bilirubin and hepatic enzymes were estimated using paired t test, Mann-Whitney, Chi-square and Kruskal-Wallis tests. Results: Forty-six (52.3%) of 88 children were girls and 42 (47.7%) were boys. Forty-eight (54.5%) patients had anemia and 8 (9%) had iron deficiency anemia (5 boys, 5.6%, and 3 girls, 3.4%). No relationships were observed between iron deficiency anemia and the patient’s age or gender, whereas there was a relationship between iron deficiency and severity and duration of the disease, although the correlation was not statistically significant. Conclusion: The high frequency of iron deficiency anemia in children with cirrhosis (9%) suggests that timely screening should be used for early diagnosis and treatment. PMID:26261697

  17. A randomized trial of iron isomaltoside versus iron sucrose in patients with iron deficiency anemia.

    Science.gov (United States)

    Derman, Richard; Roman, Eloy; Modiano, Manuel R; Achebe, Maureen M; Thomsen, Lars L; Auerbach, Michael

    2017-03-01

    Iron deficiency anemia (IDA) is common in many chronic diseases, and intravenous (IV) iron offers a rapid and efficient iron correction. This trial compared the efficacy and safety of iron isomaltoside and iron sucrose in patients with IDA who were intolerant of, or unresponsive to, oral iron. The trial was an open-label, comparative, multi-center trial. Five hundred and eleven patients with IDA from different causes were randomized 2:1 to iron isomaltoside or iron sucrose and followed for 5 weeks. The cumulative dose of iron isomaltoside was based on body weight and hemoglobin (Hb), administered as either a 1000 mg infusion over more than 15 minutes or 500 mg injection over 2 minutes. The cumulative dose of iron sucrose was calculated according to Ganzoni and administered as repeated 200 mg infusions over 30 minutes. The mean cumulative dose of iron isomaltoside was 1640.2 (standard deviation (SD): 357.6) mg and of iron sucrose 1127.9 (SD: 343.3) mg. The primary endpoint was the proportion of patients with a Hb increase ≥2 g/dL from baseline at any time between weeks 1-5. Both non-inferiority and superiority were confirmed for the primary endpoint, and a shorter time to Hb increase ≥2 g/dL was observed with iron isomaltoside. For all biochemical efficacy parameters, faster and/or greater improvements were found with iron isomaltoside. Both treatments were well tolerated; 0.6% experienced a serious adverse drug reaction. Iron isomaltoside was more effective than iron sucrose in achieving a rapid improvement in Hb. Furthermore, iron isomaltoside has an advantage over iron sucrose in allowing higher cumulative dosing in fewer administrations. Both treatments were well tolerated in a broad population with IDA.

  18. Entropy and Enzyme Catalysis.

    Science.gov (United States)

    Åqvist, Johan; Kazemi, Masoud; Isaksen, Geir Villy; Brandsdal, Bjørn Olav

    2017-02-21

    The role played by entropy for the enormous rate enhancement achieved by enzymes has been debated for many decades. There are, for example, several confirmed cases where the activation free energy is reduced by around 10 kcal/mol due to entropic effects, corresponding to a rate enhancement of ∼10(7) compared to the uncatalyzed reaction. However, despite substantial efforts from both the experimental and theoretical side, no real consensus has been reached regarding the origin of such large entropic contributions to enzyme catalysis. Another remarkable instance of entropic effects is found in enzymes that are adapted by evolution to work at low temperatures, near the freezing point of water. These cold-adapted enzymes invariably show a more negative entropy and a lower enthalpy of activation than their mesophilic orthologs, which counteracts the exponential damping of reaction rates at lower temperature. The structural origin of this universal phenomenon has, however, remained elusive. The basic problem with connecting macroscopic thermodynamic quantities, such as activation entropy and enthalpy derived from Arrhenius plots, to the 3D protein structure is that the underlying detailed (microscopic) energetics is essentially inaccessible to experiment. Moreover, attempts to calculate entropy contributions by computer simulations have mostly focused only on substrate entropies, which do not provide the full picture. We have recently devised a new approach for accessing thermodynamic activation parameters of both enzyme and solution reactions from computer simulations, which turns out to be very successful. This method is analogous to the experimental Arrhenius plots and directly evaluates the temperature dependence of calculated reaction free energy profiles. Hence, by extensive molecular dynamics simulations and calculations of up to thousands of independent free energy profiles, we are able to extract activation parameters with sufficient precision for making

  19. Angiotensin-converting enzyme

    DEFF Research Database (Denmark)

    Sørensen, P G; Rømer, F K; Cortes, D

    1984-01-01

    In order to evaluate bleomycin-associated lung damage in humans, lung function parameters and serum levels of the endothelial-bound angiotensin-converting enzyme (ACE) were determined by serial measurements in 11 patients who were treated for testicular cancer. None developed clinical or radiolog......In order to evaluate bleomycin-associated lung damage in humans, lung function parameters and serum levels of the endothelial-bound angiotensin-converting enzyme (ACE) were determined by serial measurements in 11 patients who were treated for testicular cancer. None developed clinical...

  20. Conserved balance of hepatocyte nuclear DNA content in mononuclear and binuclear hepatocyte populations during the course of chronic viral hepatitis

    Institute of Scientific and Technical Information of China (English)

    Hidenori Toyoda; Takashi Kumada; Olivier Bregerie; Christian Brechot; Chantal Desdouets

    2006-01-01

    AIM: To analyze the percentages of hepatocytes with increased nuclear DNA content, i.e., tetraploid (4n) and octoploid (8n) nuclei, and then compared mononuclear and binuclear hepatocyte populations:METHODS: The percentages of mononuclear diploid(2n), 4n, and 8n hepatocytes and those of binuclear 2× 2n, 2 × 4n, and 2 × 8n hepatocytes were determined with a method that can simultaneously measure hepatocyte nuclear DNA content and binuclearity in 62patients with chronic hepatitis B or C. The percentage of 4n and 8n hepatocytes in the mononuclear hepatocyte population was compared with the percentage of 2 ×4n and 2 × 8n hepatocytes in the binuclear hepatocyte population.RESULTS: The percentages of 4n and 8n hepatocytes in mononuclear hepatocytes and 2 × 4n and 2 × 8n hepatocytes in binuclear hepatocytes were similar,regardless of the activity or fibrosis grade of chronic hepatitis and regardless of the infecting virus.CONCLUSION: The distribution of nuclear DNA content within mononuclear and binuclear hepatocyte populations was conserved during the course of chronic viral hepatitis.

  1. Therapeutic angiogenesis in Buerger's disease (thromboangiitis obliterans) patients with critical limb ischemia by autologous transplantation of bone marrow mononuclear cells.

    Science.gov (United States)

    Motukuru, Vishnu; Suresh, Kalkunte R; Vivekanand, Vivekanand; Raj, Sumanth; Girija, K R

    2008-12-01

    Peripheral arterial disease is a significant problem worldwide. In developing countries such as India, the increased incidence of smoking and other forms of nicotine intake has resulted in a large proportion of young individuals with Buerger's disease. The results of surgical and endovascular treatment for this condition have not been very rewarding. Hence, we focused on providing alternative therapies. Neovascularization by autologous bone marrow mononuclear cell transplantation is being tried as an alternative therapeutic option. We have reviewed our series of patients who underwent autologous bone marrow mononuclear cell transplantation during the last 2 years. We enrolled 38 patients who were chosen to undergo autologous bone marrow mononuclear cell transplantation for nonreconstructible Buerger's disease. We injected the bone marrow mononuclear cells into the calf muscles of the affected limbs in 36 patients. We monitored ulcer healing, ankle-brachial index (ABI), and transcutaneous oximetry (TcPo(2)) level. No procedurally related complications occurred, although one injected sample of bone marrow aspirate later revealed infestation with Strongyloides stercoralis. Two patients were seropositive on the Venereal Disease Research Laboratory test and were not injected with the bone marrow mononuclear cells. Three patients (12%) underwent major amputations disease who have critical limb ischemia.

  2. Iron deficiency and cognitive functions

    Directory of Open Access Journals (Sweden)

    Jáuregui-Lobera I

    2014-11-01

    Full Text Available Ignacio Jáuregui-Lobera Department of Nutrition and Bromatology, Pablo de Olavide University, Seville, Spain Abstract: Micronutrient deficiencies, especially those related to iodine and iron, are linked to different cognitive impairments, as well as to potential long-term behavioral changes. Among the cognitive impairments caused by iron deficiency, those referring to attention span, intelligence, and sensory perception functions are mainly cited, as well as those associated with emotions and behavior, often directly related to the presence of iron deficiency anemia. In addition, iron deficiency without anemia may cause cognitive disturbances. At present, the prevalence of iron deficiency and iron deficiency anemia is 2%–6% among European children. Given the importance of iron deficiency relative to proper cognitive development and the alterations that can persist through adulthood as a result of this deficiency, the objective of this study was to review the current state of knowledge about this health problem. The relevance of iron deficiency and iron deficiency anemia, the distinction between the cognitive consequences of iron deficiency and those affecting specifically cognitive development, and the debate about the utility of iron supplements are the most relevant and controversial topics. Despite there being methodological differences among studies, there is some evidence that iron supplementation improves cognitive functions. Nevertheless, this must be confirmed by means of adequate follow-up studies among different groups. Keywords: iron deficiency, anemia, cognitive functions, supplementation

  3. How Is Iron-Deficiency Anemia Treated?

    Science.gov (United States)

    ... the NHLBI on Twitter. How Is Iron-Deficiency Anemia Treated? Treatment for iron-deficiency anemia will depend ... may be advised. Treatments for Severe Iron-Deficiency Anemia Blood Transfusion If your iron-deficiency anemia is ...

  4. Restoration of growth by manganese in a mutant strain of Escherichia coli lacking most known iron and manganese uptake systems

    DEFF Research Database (Denmark)

    Taudte, Nadine; German, Nadezhda; Zhu, Yong-Guan

    2016-01-01

    The interplay of manganese and iron homeostasis and oxidative stress in Escherichia coli can give important insights into survival of bacteria in the phagosome and under differing iron or manganese bioavailabilities. Here, we characterized a mutant strain devoid of all know iron/manganese......-uptake systems relevant for growth in defined medium. Based on these results an exit strategy enabling the cell to cope with iron depletion and use of manganese as an alternative for iron could be shown. Such a strategy would also explain why E. coli harbors some iron- or manganese-dependent iso......-enzymes such as superoxide dismutases or ribonucleotide reductases. The benefits for gaining a means for survival would be bought with the cost of less efficient metabolism as indicated in our experiments by lower cell densities with manganese than with iron. In addition, this strain was extremely sensitive to the metalloid...

  5. 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....

  6. The coproporphyrin ferrochelatase of Staphylococcus aureus : mechanistic insights into a regulatory iron binding site.

    Science.gov (United States)

    Hobbs, Charlie; Reid, J D; Shepherd, Mark

    2017-09-01

    The majority of characterised ferrochelatase enzymes catalyse the final step of classical haem synthesis, inserting ferrous iron into protoporphyrin IX. However, for the recently-discovered coproporphyrin-dependent pathway, ferrochelatase catalyses the penultimate reaction where ferrous iron is inserted into coproporphyrin III. Ferrochelatase enzymes from the bacterial phyla Firmicutes and Actinobacteria have previously been shown to insert iron into coproporphyrin, and those from Bacillus subtilis and Staphylococcus aureus are known to be inhibited by elevated iron concentrations. The work herein reports a Km (coproporphyrin III) for S. aureus ferrochelatase of 1.5 µM and it is shown that elevating the iron concentration increases the Km for coproporphyrin III, providing a potential explanation for the observed iron-mediated substrate inhibition. Together, structural modelling, site-directed mutagenesis, and kinetic analyses confirm residue Glu271 as being essential for the binding of iron to the inhibitory regulatory site on S. aureus ferrochelatase, providing a molecular explanation for the observed substrate inhibition patterns. This work therefore has implications for how haem biosynthesis in S. aureus is regulated by iron availability. ©2017 The Author(s).

  7. 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

  8. Tuning the transition temperature and cooperativity of bapbpy-based mononuclear spin-crossover compounds: interplay between molecular and crystal engineering.

    Science.gov (United States)

    Arcis-Castíllo, Zulema; Zheng, Sipeng; Siegler, Maxime A; Roubeau, Olivier; Bedoui, Salma; Bonnet, Sylvestre

    2011-12-23

    In this study, we show that 1) different isomers of the same mononuclear iron(II) complex give materials with different spin-crossover (hereafter SCO) properties, and 2) minor modifications of the bapbpy (bapbpy=N6,N6'-di(pyridin-2-yl)-2,2'-bipyridine-6,6'-diamine) ligand allows SCO to be obtained near room temperature. We also provide a qualitative model to understand the link between the structure of bapbpy-based ligands and the SCO properties of their iron(II) compounds. Thus, seven new trans-[Fe{R(2)(bapbpy)}(NCS)(2)] compounds were prepared, in which the R(2)bapbpy ligand bears picoline (9-12), quin-2-oline (13), isoquin-3-oline (14), or isoquin-1-oline (15) substituents. From this series, three compounds (12, 14, and 15) have SCO properties, one of which (15) occurs at 288 K. The crystal structures of compounds 11, 12, and 15 show that the intermolecular interactions in these materials are similar to those found in the parent compound [Fe(bapbpy)(NCS)(2)] (1), in which each iron complex interacts with its neighbors through weak N-H···S hydrogen bonding and π-π stacking. For compounds 12 and 15, hindering groups located near the N-H bridges weaken the N-S intermolecular interactions, which is correlated to non-cooperative SCO. For compound 14, the substitution is further away from the N-H bridges, and the SCO remains cooperative as in 1 with a hysteresis cycle. Optical microscopy photographs show the strikingly different spatio-temporal evolution of the phase transition in the noncooperative SCO compound 12 relative to that found in 1. Heat-capacity measurements were made for compounds 1, 12, 14, and 15 and fitted to the Sorai domain model. The number n of like-spin SCO centers per interacting domain, which is related to the cooperativity of the spin transition, was found high for compounds 1 and 14 and low for compounds 12 and 15. Finally, we found that although both pairs of compounds 11/12 and 14/15 are pairs of isomers their SCO properties are

  9. Iron deficiency anemia in children.

    Science.gov (United States)

    Subramaniam, Girish; Girish, Meenakshi

    2015-06-01

    Iron deficiency is not just anemia; it can be responsible for a long list of other manifestations. This topic is of great importance, especially in infancy and early childhood, for a variety of reasons. Firstly, iron need is maximum in this period. Secondly, diet in infancy is usually deficient in iron. Thirdly and most importantly, iron deficiency at this age can result in neurodevelopmental and cognitive deficits, which may not be reversible. Hypochromia and microcytosis in a complete blood count (CBC) makes iron deficiency anemia (IDA) most likely diagnosis. Absence of response to iron should make us look for other differential diagnosis like β thalassemia trait and anemia of chronic disease. Celiac disease is the most important cause of true IDA not responding to oral iron therapy. While oral ferrous sulphate is the cheapest and most effective therapy for IDA, simple nonpharmacological and pharmacological measures can go a long way in prevention of iron deficiency.

  10. Oral iron chelators.

    Science.gov (United States)

    Kwiatkowski, Janet L

    2010-02-01

    Effective chelation therapy can prevent or reverse organ toxicity related to iron overload, yet cardiac complications and premature death continue to occur, largely related to difficulties with compliance in patients who receive parenteral therapy. The use of oral chelators may be able to overcome these difficulties and improve patient outcomes. A chelator's efficacy at cardiac and liver iron removal and side-effect profile should be considered when tailoring individual chelation regimens. Broader options for chelation therapy, including possible combination therapy, should improve clinical efficacy and enhance patient care.

  11. The surface science of enzymes

    DEFF Research Database (Denmark)

    Rod, Thomas Holm; Nørskov, Jens Kehlet

    2002-01-01

    One of the largest challenges to science in the coming years is to find the relation between enzyme structure and function. Can we predict which reactions an enzyme catalyzes from knowledge of its structure-or from its amino acid sequence? Can we use that knowledge to modify enzyme function......? To solve these problems we must understand in some detail how enzymes interact with reactants from its surroundings. These interactions take place at the surface of the enzyme and the question of enzyme function can be viewed as the surface science of enzymes. In this article we discuss how to describe...... catalysis by enzymes, and in particular the analogies between enzyme catalyzed reactions and surface catalyzed reactions. We do this by discussing two concrete examples of reactions catalyzed both in nature (by enzymes) and in industrial reactors (by inorganic materials), and show that although analogies...

  12. Amperometric Enzyme Electrodes

    Science.gov (United States)

    1989-12-01

    form of carbon (glascy carbon, graphite, reticulated vitreous carbon, carbon paste, fiber or foil). Carbon is favored for enzyme immoblization...interference from spurious electroactive species in blood, t proprietary multilayer membranie that includes a cellulose acetate memirane and a Nucleopore

  13. ISFET based enzyme sensors

    NARCIS (Netherlands)

    van der Schoot, Bart H.; Bergveld, Piet

    1987-01-01

    This paper reviews the results that have been reported on ISFET based enzyme sensors. The most important improvement that results from the application of ISFETs instead of glass membrane electrodes is in the method of fabrication. Problems with regard to the pH dependence of the response and the

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

    Directory of Open Access Journals (Sweden)

    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.

  15. Catalytic water oxidation by mononuclear Ru complexes with an anionic ancillary ligand.

    Science.gov (United States)

    Tong, Lianpeng; Inge, A Ken; Duan, Lele; Wang, Lei; Zou, Xiaodong; Sun, Licheng

    2013-03-04

    Mononuclear Ru-based water oxidation catalysts containing anionic ancillary ligands have shown promising catalytic efficiency and intriguing properties. However, their insolubility in water restricts a detailed mechanism investigation. In order to overcome this disadvantage, complexes [Ru(II)(bpc)(bpy)OH2](+) (1(+), bpc = 2,2'-bipyridine-6-carboxylate, bpy = 2,2'-bipyridine) and [Ru(II)(bpc)(pic)3](+) (2(+), pic = 4-picoline) were prepared and fully characterized, which features an anionic tridentate ligand and has enough solubility for spectroscopic study in water. Using Ce(IV) as an electron acceptor, both complexes are able to catalyze O2-evolving reaction with an impressive rate constant. On the basis of the electrochemical and kinetic studies, a water nucleophilic attack pathway was proposed as the dominant catalytic cycle of the catalytic water oxidation by 1(+), within which several intermediates were detected by MS. Meanwhile, an auxiliary pathway that is related to the concentration of Ce(IV) was also revealed. The effect of anionic ligand regarding catalytic water oxidation was discussed explicitly in comparison with previously reported mononuclear Ru catalysts carrying neutral tridentate ligands, for example, 2,2':6',2″-terpyridine (tpy). When 2(+) was oxidized to the trivalent state, one of its picoline ligands dissociated from the Ru center. The rate constant of picoline dissociation was evaluated from time-resolved UV-vis spectra.

  16. High Insulin and Leptin Increase Resistin and Inflammatory Cytokine Production from Human Mononuclear Cells

    Directory of Open Access Journals (Sweden)

    Panayoula C. Tsiotra

    2013-01-01

    Full Text Available Resistin and the proinflammatory cytokines, such as TNF-α, IL-6, and IL-1β, produced by adipocytes, and macrophages, are considered to be important modulators of chronic inflammation contributing to the development of obesity and atherosclerosis. Human monocyte-enriched mononuclear cells, from ten healthy individuals, were exposed to high concentrations of insulin, leptin, and glucose (alone or in combination for 24 hours in vitro. Resistin, TNF-α, IL-6, and IL-1β production was examined and compared to that in untreated cells. High insulin and leptin concentrations significantly upregulated resistin and the cytokines. The subsequent addition of high glucose significantly upregulated resistin and TNF-α mRNA and protein secretion, while it did not have any effect on IL-6 or IL-1β production. By comparison, exposure to dexamethasone reduced TNF-α, IL-6, and IL-1β production, while at this time point it increased resistin protein secretion. These data suggest that the expression of resistin, TNF-α, IL-6, and IL-1β from human mononuclear cells, might be enhanced by the hyperinsulinemia and hyperleptinemia and possibly by the hyperglycemia in metabolic diseases as obesity, type 2 diabetes, and atherosclerosis. Therefore, the above increased production may contribute to detrimental effects of their increased adipocyte-derived circulating levels on systemic inflammation, insulin sensitivity, and endothelial function of these patients.

  17. Prevention of diabetic microangiopathy by prophylactic transplant of mobilized peripheral blood mononuclear cells

    Institute of Scientific and Technical Information of China (English)

    Bin ZHOU; Xiao-cang CAO; Zhi-hong FANG; Cui-lin ZHENG; Zhi-bo HAN; He REN; Man-chiu POON; Zhong-chao HAN

    2007-01-01

    Aim: To investigate whether the prophylactic local delivery of mobilized periph-eral blood mononuclear cells (M-PBMNC) could prevent peripheral microangio-pathy in diabetic nude mice. Methods: Diabetic nude mice were induced with intraperitoneal injections of streptozotocin. With the time course of diabetes, we detected the capillary and arteriole density of mice adductor muscles by immuno-histopathy. In situ apoptosis was detected by using TdT-mediated dUTP nick end labeling (TUNEL) methods. M-PBMNC were labeled and locally delivered to the adductor muscles. Mononuclear cells were also isolated and cultured in vitro for the detection and counting of endothelial progenitor cells(EPC). Results: Rarefication of capillaries and arterioles, enhanced apoptosis in adductor muscles,and reduced circulating EPC in diabetic nude mice. Prophylactic local delivery of M-PBMNC halted the progression of microvascular rarefaction in hind-limb skel-etal muscles by inhibiting apoptosis. We detected the survival, migration and incorporation of transplanted M-PBMNC into the murine vasculature in vivo. In addition, more EPC were available from M-PBMNC than non-mobilized cells.Conclusion: These results suggested that the prophylactic local delivery of M-PBMNC may represent a novel approach for the treatment of microvascular complications in diabetics.

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

    Directory of Open Access Journals (Sweden)

    M. I. Kogan

    2012-01-01

    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.

  19. Obesity alters the expression profile of clock genes in peripheral blood mononuclear cells

    Science.gov (United States)

    Tahira, Kazunobu; Fukuda, Noboru; Aoyama, Takahiko; Tsunemi, Akiko; Matsumoto, Siroh; Nagura, Chinami; Matsumoto, Taro; Soma, Masayoshi; Shimba, Shigeki; Matsumoto, Yoshiaki

    2011-01-01

    Introduction The aim of this study was to investigate the association between the variation in expression profile of clock genes and obesity using peripheral blood mononuclear (PMN) cells. Material and methods The subjects comprised 10 obese patients and 10 healthy volunteers. Blood was collected at different time-points during the day and levels of blood sugar, IRI, adiponectin and leptin were determined. Peripheral blood mononuclear cells were sampled, and expression levels of brain and muscle Arnt-like protein-1 (BMAL1), Period (PER)1, PER2, Cryptochrome (CRY)1, CRY2, and REV-ERBα mRNA were quantified. Results During the day, the expression levels of BMAL1, CRY1, CRY2 and PER2 genes in PMN cells of the obese group were all significantly higher compared to those in the non-obese group. In addition, expression of BMAL1, CRY1, CRY2 and PER2 genes in PMN cells increased between 12:00 and 21:00 in the obese group. In PMN cells of both groups, PER1 gene expression showed a bimodal pattern, with high expression at 9:00 and 18:00. Conclusions Differences were observed in the expression profile variation of clock genes between the obese and non-obese groups. This study reveals the differences in clock gene expression profiles between obese and non-obese subjects, with evidence for two distinct chronotypes, and suggests a contribution of these chronotypes to fat accumulation in humans. PMID:22328874

  20. Outcomes of autologous bone marrow mononuclear cells for cerebral palsy: an open label uncontrolled clinical trial.

    Science.gov (United States)

    Nguyen, Liem Thanh; Nguyen, Anh Tuan; Vu, Chinh Duy; Ngo, Doan V; Bui, Anh V

    2017-04-12

    Stem cell therapy has emerged as a promising method for improving motor function of patients with cerebral palsy. The aim of this study is to assess the safety and effectiveness of autologous bone marrow mononuclear stem cell transplantation in patients with cerebral palsy related to oxygen deprivation. An open label uncontrolled clinical trial was carried out at Vinmec International Hospital. The intervention consisted of two administrations of stem cells, the first at baseline and the second 3 months later. Improvement was monitored at 3 months and 6 months after the first administration of stem cells, using the Gross Motor Function Measure (GMFM) and Modified Ashworth Score which measures muscle tone. No severe complications were recorded during the study. After transplantation, 12 patients encountered fever without infections and 9 patients experienced vomiting which was easily managed with medications. Gross motor function was markedly improved 3 months or 6 months after stem cell transplantation than at baseline. The post-transplantation GMFM-88 total score, each of its domains and the GMFM-66 percentile were all significantly higher (p-value  0.05). Autologous bone marrow mononuclear cell transplantation appears to be a safe and effective therapy for patients with cerebral palsy. ClinicalTrials.gov Identifier: NCT02569775 . Retrospectively registered on October 15, 2015.

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

    Directory of Open Access Journals (Sweden)

    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.

  2. Effects of bone marrow ablation on compartmental prostaglandin synthesis by mononuclear phagocytes

    Energy Technology Data Exchange (ETDEWEB)

    Volkman, A.; Shibata, Y.; Dempsey, W.; Morahan, P.S.

    1988-01-01

    Mononuclear phagocyte functions were studied in mice selectively deprived of bone marrow and rendered profoundly monocytopenic by the administration of the bone seeking isotope, 89Sr. Characteristics of such mice include severe impairment of monocyte-M phi elicitation, ablation of C. parvum induction of PGSM but the persistence of resident peritoneal and pulmonary alveolar M phi populations; splenic M phi increase in number concomitantly with splenic hemopoiesis. Studies on compartmental regulation in this model suggest that the capacity of splenic M phi to synthesize and release PGE2 is dependent upon a function of the bone marrow and is not wholly determined by the local environment. The relationship of blood monocytes to PGSM is uncertain. In contrast to splenic M phi, the capacity of resident peritoneal M phi for eicosanoid synthesis appears to be independent of bone marrow function. Monocyte influx, moreover, does not appear necessary for the maintenance of the resident peritoneal and alveolar M phi populations. We do not yet know whether bone marrow ablation destroys a migratory precursor of PGSM or the source of a crucial regulatory agent. In conclusion, the observations discussed show that prostaglandin metabolism within the spleen is subject to extracompartmental influence. It is clearly important to determine the regulatory characteristics of individual M phi compartments and generalizations about functional properties of mononuclear phagocytes should be made with circumspection. 19 references.

  3. IL-23-mediated mononuclear phagocyte crosstalk protects mice from Citrobacter rodentium-induced colon immunopathology.

    Science.gov (United States)

    Aychek, Tegest; Mildner, Alexander; Yona, Simon; Kim, Ki-Wook; Lampl, Nardy; Reich-Zeliger, Shlomit; Boon, Louis; Yogev, Nir; Waisman, Ari; Cua, Daniel J; Jung, Steffen

    2015-03-12

    Gut homeostasis and mucosal immune defense rely on the differential contributions of dendritic cells (DC) and macrophages. Here we show that colonic CX3CR1(+) mononuclear phagocytes are critical inducers of the innate response to Citrobacter rodentium infection. Specifically, the absence of IL-23 expression in macrophages or CD11b(+) DC results in the impairment of IL-22 production and in acute lethality. Highlighting immunopathology as a death cause, infected animals are rescued by the neutralization of IL-12 or IFNγ. Moreover, mice are also protected when the CD103(+) CD11b(-) DC compartment is rendered deficient for IL-12 production. We show that IL-12 production by colonic CD103(+) CD11b(-) DC is repressed by IL-23. Collectively, in addition to its role in inducing IL-22 production, macrophage-derived or CD103(-) CD11b(+) DC-derived IL-23 is required to negatively control the otherwise deleterious production of IL-12 by CD103(+) CD11b(-) DC. Impairment of this critical mononuclear phagocyte crosstalk results in the generation of IFNγ-producing former TH17 cells and fatal immunopathology.

  4. Synthesis and structure of new mononuclear octahedral cobalt(III) dioximates derived from isonicotinic hydrazide

    Science.gov (United States)

    Cocu, Maria; Bulhac, Ion; Coropceanu, Eduard; Melnic, Elena; Shova, Sergiu; Ciobanica, Olga; Gutium, Victoria; Bourosh, Paulina

    2014-04-01

    New organic ligand L (1) resulting from isonicotinic hydrazide and 2,4-pentanedione has been prepared and investigated by physicochemical methods, including elemental analysis, 1H and 13C NMR, IR spectroscopy and X-ray studies. The X-ray investigation revealed that the condensation of 2,4-pentanedione with isonicotinic hydrazide is accompanied by the formation of a five-membered ring including three carbon atoms of 2,4-pentanedione and two nitrogen atoms of the isonicotinic hydrazide fragment. The reaction between [Co(DfgH)2Br(H2O)] (DfgH2 = diphenylglyoxime) and L resulted in the formation of the mononuclear octahedral complex [Co(DfgH)2BrL] (2) with the substitution of the water molecule in the apical position by the ligand L. The reaction starting from [Co(DmgH)2Cl(H2O)] (DmgH = dimethylglyoxime) and L resulted in the mononuclear octahedral Co(III) complex with the composition [Co(DmgH)2ClL‧] (3), where L‧ unexpectedly represents a dehydrated derivative of L. The two coordination compounds are characterized by X-ray diffraction method. The IR, 1H NMR spectral studies of new compounds are also reported.

  5. Mononuclear cells in subcutaneous haemorrhage with special consideration of myeloid percursor cells.

    Science.gov (United States)

    Oehmichen, M; Windisch, A; Meissner, C

    2000-10-01

    Various hematogenous markers were used to differentiate and quantify the types of mononuclear cells present in subcutaneous haemorrhages. Fifty samples of subcutaneous bleeding with a survival time of a few minutes to more than 48 hours were studied. The various cell types were detected using the following stains: Naphthol AS-D chloracetate esterase for myeloid cells, including mast cells; (alpha1-antichymotrypsin for monocytes/macrophages; UCHL1 for T-lymphocytes; and L26 for B lymphocytes. The percentage of monocytes/macrophages was found to increase in dependence on survival time, whereas T-lymphocytes declined. Within minutes of injury neutrophilic granulocytes had emigrated into the surrounding tissue and mast cell degranulation had occurred within the haemorrhagic zone. Esterase-positive mononuclear cells, namely metamyelocytes, were detected within minutes after injury and were still present after survival times exceeding 48 hours; however, no dependence on survival time or cause of death was found. Although the increasing number of monocytes/ macrophages and T-lymphocytes was expected, the sometimes high percentage of myeloid precursor cells within the wound were surprising. Possible explanations for this phenomenon are discussed.

  6. Autologous bone marrow mononuclear cell transplantation in Duchenne muscular dystrophy - a case report.

    Science.gov (United States)

    Sharma, Alok; Sane, Hemangi; Paranjape, Amruta; Bhagawanani, Khushboo; Gokulchandran, Nandini; Badhe, Prerna

    2014-01-01

    Male, 9 FINAL DIAGNOSIS: Duchenne muscular dystrophy Symptoms: Hyporeflexia • hypotonia • weaknes of lower limbs - Clinical Procedure: - Specialty: Neurology. Congenital defects/diseases. Duchenne muscular dystrophy (DMD) is a fatal, genetic, progressive, degenerating muscle disorder. Current treatment options are palliative. Newer options of cellular therapy promise to alter the disease process. Preclinical studies have successfully tested myogenic, neurogenic potential and dystrophin expression of bone marrow mononuclear cells. We treated a 9-year-old boy suffering from DMD with serial autologous bone marrow mononuclear cell transplantations followed by multidisciplinary rehabilitation. Brooke-Vignos score was 10 and he was wheelchair-bound. Over 36 months, gradual progressive improvement was noticed in muscle strength, ambulation with assistive devices, fine motor movements, Brooke-Vignos score, and functional independence measure score. Nine months after the transplantation, electromyography findings showed development of new normal motor unit potentials of the vastus medialis muscle. Magnetic resonance imaging scan of musculoskeletal systems showed no increase in fatty infiltration. This case report provides early investigative findings or the restorative effects of cellular therapy in DMD.

  7. Beryllium alters lipopolysaccharide-mediated intracellular phosphorylation and cytokine release in human peripheral blood mononuclear cells.

    Science.gov (United States)

    Silva, Shannon; Ganguly, Kumkum; Fresquez, Theresa M; Gupta, Goutam; McCleskey, T Mark; Chaudhary, Anu

    2009-12-01

    Beryllium exposure in susceptible individuals leads to the development of chronic beryllium disease, a lung disorder marked by release of inflammatory cytokine and granuloma formation. We have previously reported that beryllium induces an immune response even in blood mononuclear cells from healthy individuals. In this study, we investigate the effects of beryllium on lipopolysaccharide-mediated cytokine release in blood mononuclear and dendritic cells from healthy individuals. We found that in vitro treatment of beryllium sulfate inhibits the secretion of lipopolysaccharide-mediated interleukin 10, while the release of interleukin 1beta is enhanced. In addition, not all lipopolysaccharide-mediated responses are altered, as interleukin 6 release in unaffected upon beryllium treatment. Beryllium sulfate-treated cells show altered phosphotyrosine levels upon lipopolysaccharide stimulation. Significantly, beryllium inhibits the phosphorylation of signal transducer and activator of transducer 3, induced by lipopolysaccharide. Finally, inhibitors of phosphoinositide-3 kinase mimic the effects of beryllium in inhibition of interleukin 10 release, while they have no effect on interleukin 1beta secretion. This study strongly suggests that prior exposures to beryllium could alter host immune responses to bacterial infections in healthy individuals, by altering intracellular signaling.

  8. Hepcidin Suppresses Brain Iron Accumulation by Downregulating Iron Transport Proteins in Iron-Overloaded Rats.

    Science.gov (United States)

    Du, Fang; Qian, Zhong-Ming; Luo, Qianqian; Yung, Wing-Ho; Ke, Ya

    2015-08-01

    Iron accumulates progressively in the brain with age, and iron-induced oxidative stress has been considered as one of the initial causes for Alzheimer's disease (AD) and Parkinson's disease (PD). Based on the role of hepcidin in peripheral organs and its expression in the brain, we hypothesized that this peptide has a role to reduce iron in the brain and hence has the potential to prevent or delay brain iron accumulation in iron-associated neurodegenerative disorders. Here, we investigated the effects of hepcidin expression adenovirus (ad-hepcidin) and hepcidin peptide on brain iron contents, iron transport across the brain-blood barrier, iron uptake and release, and also the expression of transferrin receptor-1 (TfR1), divalent metal transporter 1 (DMT1), and ferroportin 1 (Fpn1) in cultured microvascular endothelial cells and neurons. We demonstrated that hepcidin significantly reduced brain iron in iron-overloaded rats and suppressed transport of transferrin-bound iron (Tf-Fe) from the periphery into the brain. Also, the peptide significantly inhibited expression of TfR1, DMT1, and Fpn1 as well as reduced Tf-Fe and non-transferrin-bound iron uptake and iron release in cultured microvascular endothelial cells and neurons, while downregulation of hepcidin with hepcidin siRNA retrovirus generated opposite results. We concluded that, under iron-overload, hepcidin functions to reduce iron in the brain by downregulating iron transport proteins. Upregulation of brain hepcidin by ad-hepcidin emerges as a new pharmacological treatment and prevention for iron-associated neurodegenerative disorders.

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

    Science.gov (United States)

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

    2016-03-01

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

  10. Computational enzyme design

    Science.gov (United States)

    Bolon, Daniel N.

    2002-08-01

    The long-term objective of computational enzyme design is the ability to generate efficient protein catalysts for any chemical reaction. This thesis develops and experimentally validates a general computational approach for the design of enzymes with novel function. In order to include catalytic mechanism in protein design, a high-energy state (HES) rotamer (side chain representation) was constructed. In this rotamer, substrate atoms are in a HES. In addition, at least one amino acid side chain is positioned to interact favorably with substrate atoms in their HES and facilitate the reaction. Including an amino acid side chain in the HES rotamer automatically positions substrate relative to a protein scaffold and allows protein design algorithms to search for sequences capable of interacting favorably with the substrate. Because chemical similarity exists between the transition state and the high-energy state, optimizing the protein sequence to interact favorably with the HES rotamer should lead to transition state stabilization. In addition, the HES rotamer model focuses the subsequent computational active site design on a relevant phase space where an amino acid is capable of interacting in a catalytically active geometry with substrate. Using a HES rotamer model of the histidine mediated nucleophilic hydrolysis of p-nitrophenyl acetate, the catalytically inert 108 residue E. coli thioredoxin as a scaffold, and the ORBIT protein design software to compute sequences, an active site scan identified two promising active site designs. Experimentally, both candidate ?protozymes? demonstrated catalytic activity significantly above background. In addition, the rate enhancement of one of these ?protozymes? was the same order of magnitude as the first catalytic antibodies. Because polar groups are frequently buried at enzyme-substrate interfaces, improved modeling of buried polar interactions may benefit enzyme design. By studying native protein structures, rules have been

  11. Colour Metallography of Cast Iron

    Institute of Scientific and Technical Information of China (English)

    Zhou Jiyang

    2009-01-01

    @@ Grey Iron(Ⅲ) 2.5 Crystallization of the LTF during final stage of eutectic solidification of grey iron In the final stage of eutectic solidification, eutectic cells grow gradually into large sizes; the liquid iron between the cells enters the last stage of solidification. At this time, the region of the remaining liquid iron is called last to freeze volume, LTF in short, as shown in Fig.2-39.

  12. Impairment of interrelated iron- and copper homeostatic mechanisms in brain contributes to the pathogenesis of neurodegenerative disorders

    Directory of Open Access Journals (Sweden)

    Tina eSkjørringe

    2012-09-01

    Full Text Available 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

  13. Increased iron export by ferroportin induces restriction of HIV-1 infection in sickle cell disease

    Science.gov (United States)

    Kumari, Namita; Ammosova, Tatiana; Diaz, Sharmin; Lin, Xionghao; Niu, Xiaomei; Ivanov, Andrey; Jerebtsova, Marina; Dhawan, Subhash; Oneal, Patricia; Nekhai, Sergei

    2017-01-01

    The low incidence of HIV-1 infection in patients with sickle cell disease (SCD) and inhibition of HIV-1 replication in vitro under the conditions of low intracellular iron or heme treatment suggests a potential restriction of HIV-1 infection in SCD. We investigated HIV-1 ex vivo infection of SCD peripheral blood mononuclear cells (PBMCs) and found that HIV-1 replication was inhibited at the level of reverse transcription (RT) and transcription. We observed increased expression of heme and iron-regulated genes, previously shown to inhibit HIV-1, including ferroportin, IKBα, HO-1, p21, and SAM domain and HD domain-containing protein 1 (SAMHD1). HIV-1 inhibition was less pronounced in hepcidin-treated SCD PBMCs and more pronounced in the iron or iron chelators treated, suggesting a key role of iron metabolism. In SCD PBMCs, labile iron levels were reduced and protein levels of ferroportin, HIF-1α, IKBα, and HO-1 were increased. Hemin treatment induced ferroportin expression and inhibited HIV-1 in THP-1 cells, mimicking the HIV-1 inhibition in SCD PBMCs, especially as hepcidin similarly prevented HIV-1 inhibition. In THP-1 cells with knocked down ferroportin, IKBα, or HO-1 genes but not HIF-1α or p21, HIV-1 was not inhibited by hemin. Activity of SAMHD1-regulatory CDK2 was decreased, and SAMHD1 phosphorylation was reduced in SCD PBMCs and hemin-treated THP-1 cells, suggesting SAMHD1-mediated HIV-1 restriction in SCD. Our findings point to ferroportin as a trigger of HIV-1 restriction in SCD settings, linking reduced intracellular iron levels to the inhibition of CDK2 activity, reduction of SAMHD1 phosphorylation, increased IKBα expression, and inhibition of HIV-1 RT and transcription.

  14. Iron deficiency anemia in children

    OpenAIRE

    Pochinok, T. V.

    2016-01-01

    In the article the role of iron in the human body is highlighted. The mechanism of development of iron deficiency states, their consequences and the basic principles of diagnosis and correction of children of different ages are shown.Key words: children, iron deficiency anemia, treatment.

  15. Iron deficiency and cardiovascular disease

    NARCIS (Netherlands)

    von Haehling, Stephan; Jankowska, Ewa A.; van Veldhuisen, Dirk J.; Ponikowski, Piotr; Anker, Stefan D.

    2015-01-01

    Iron deficiency affects up to one-third of the world's population, and is particularly common in elderly individuals and those with certain chronic diseases. Iron excess can be detrimental in cardiovascular illness, and research has now also brought anaemia and iron deficiency into the focus of card

  16. The Moderately Efficient Enzyme: Futile Encounters and Enzyme Floppiness.

    Science.gov (United States)

    Bar-Even, Arren; Milo, Ron; Noor, Elad; Tawfik, Dan S

    2015-08-18

    The pioneering model of Henri, Michaelis, and Menten was based on the fast equilibrium assumption: the substrate binds its enzyme reversibly, and substrate dissociation is much faster than product formation. Here, we examine this assumption from a somewhat different point of view, asking what fraction of enzyme-substrate complexes are futile, i.e., result in dissociation rather than product formation. In Knowles' notion of a "perfect" enzyme, all encounters of the enzyme with its substrate result in conversion to product. Thus, the perfect enzyme's catalytic efficiency, kcat/KM, is constrained by only the diffusion on-rate, and the fraction of futile encounters (defined as φ) approaches zero. The available data on >1000 different enzymes suggest that for ≥90% of enzymes φ > 0.99 and for the "average enzyme" φ ≥ 0.9999; namely, <1 of 10(4) encounters is productive. Thus, the "fast equilibrium" assumption holds for the vast majority of enzymes. We discuss possible molecular origins for the dominance of futile encounters, including the coexistence of multiple sub-states of an enzyme's active site (enzyme floppiness) and/or its substrate. Floppiness relates to the inherent flexibility of proteins, but also to conflicting demands, or trade-offs, between rate acceleration (the rate-determining chemical step) and catalytic turnover, or between turnover rate and accuracy. The study of futile encounters and active-site floppiness may contribute to a better understanding of enzyme catalysis, enzyme evolution, and improved enzyme design.

  17. Structure of dual function iron regulatory protein 1 complexed with ferritin IRE-RNA

    Energy Technology Data Exchange (ETDEWEB)

    Walden, William E.; Selezneva, Anna I.; Dupuy, Jérôme; Volbeda, Anne; Fontecilla-Camps, Juan C.; Theil, Elizabeth C.; Volz1, Karl (IBS); (CHORI); (UIC)

    2011-07-27

    Iron regulatory protein 1 (IRP1) binds iron-responsive elements (IREs) in messenger RNAs (mRNAs), to repress translation or degradation, or binds an iron-sulfur cluster, to become a cytosolic aconitase enzyme. The 2.8 angstrom resolution crystal structure of the IRP1:ferritin H IRE complex shows an open protein conformation compared with that of cytosolic aconitase. The extended, L-shaped IRP1 molecule embraces the IRE stem-loop through interactions at two sites separated by {approx}30 angstroms, each involving about a dozen protein:RNA bonds. Extensive conformational changes related to binding the IRE or an iron-sulfur cluster explain the alternate functions of IRP1 as an mRNA regulator or enzyme.

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

    Directory of Open Access Journals (Sweden)

    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

  19. Solving Biology's Iron Chemistry Problem with Ferritin Protein Nanocages.

    Science.gov (United States)

    Theil, Elizabeth C; Tosha, Takehiko; Behera, Rabindra K

    2016-05-17

    Ferritins reversibly synthesize iron-oxy(ferrihydrite) biominerals inside large, hollow protein nanocages (10-12 nm, ∼480 000 g/mol); the iron biominerals are metabolic iron concentrates for iron protein biosyntheses. Protein cages of 12- or 24-folded ferritin subunits (4-α-helix polypeptide bundles) self-assemble, experimentally. Ferritin biomineral structures differ among animals and plants or bacteria. The basic ferritin mineral structure is ferrihydrite (Fe2O3·H2O) with either low phosphate in the highly ordered animal ferritin biominerals, Fe/PO4 ∼ 8:1, or Fe/PO4 ∼ 1:1 in the more amorphous ferritin biominerals of plants and bacteria. While different ferritin environments, plant bacterial-like plastid organelles and animal cytoplasm, might explain ferritin biomineral differences, investigation is required. Currently, the physiological significance of plant-specific and animal-specific ferritin iron minerals is unknown. The iron content of ferritin in living tissues ranges from zero in "apoferritin" to as high as ∼4500 iron atoms. Ferritin biomineralization begins with the reaction of Fe(2+) with O2 at ferritin enzyme (Fe(2+)/O oxidoreductase) sites. The product of ferritin enzyme activity, diferric oxy complexes, is also the precursor of ferritin biomineral. Concentrations of Fe(3+) equivalent to 2.0 × 10(-1) M are maintained in ferritin solutions, contrasting with the Fe(3+) Ks ∼ 10(-18) M. Iron ions move into, through, and out of ferritin protein cages in structural subdomains containing conserved amino acids. Cage subdomains include (1) ion channels for Fe(2+) entry/exit, (2) enzyme (oxidoreductase) site for coupling Fe(2+) and O yielding diferric oxy biomineral precursors, and (3) ferric oxy nucleation channels, where diferric oxy products from up to three enzyme sites interact while moving toward the central, biomineral growth cavity (12 nm diameter) where ferric oxy species, now 48-mers, grow in ferric oxy biomineral. High ferritin protein

  20. Telomere Length in Peripheral Blood Mononuclear Cells of Patients on Chronic Hemodialysis Is Related With Telomerase Activity and Treatment Duration.

    Science.gov (United States)

    Stefanidis, Ioannis; Voliotis, Georgios; Papanikolaou, Vassilios; Chronopoulou, Ioanna; Eleftheriadis, Theodoros; Kowald, Axel; Zintzaras, Elias; Tsezou, Aspasia

    2015-09-01

    Telomere shortening to a critical limit is associated with replicative senescence. This process is prevented by the enzyme telomerase. Oxidative stress and chronic inflammation are factors accelerating telomere loss. Chronic hemodialysis, typically accompanied by oxidative stress and inflammation, may be also associated with replicative senescence. To test this hypothesis, we determined telomere length and telomerase activity in peripheral blood mononuclear cells (PBMCs) in a cross-sectional study. Hemodialysis patients at the University Hospital Larissa and healthy controls were studied. Telomere length was determined by the TeloTAGGG Telomere Length Assay and telomerase activity by Telomerase PCR-ELISA (Roche Diagnostics GmbH, Mannheim, Germany). We enrolled 43 hemodialysis patients (17 females; age 65.0 ± 12.7 years) and 23 controls (six females; age 62.1 ± 15.7 years). Between the two groups, there was no difference in telomere length (6.95 ± 3.25 vs. 7.31 ± 1.96 kb; P = 0.244) or in telomerase activity (1.82 ± 2.91 vs. 2.71 ± 3.0; P = 0.085). Telomere length correlated inversely with vintage of hemodialysis (r = -0.332, P = 0.030). In hemodialysis patients, positive telomerase activity correlated with telomere length (r = 0.443, P = 0.030). Only age, and neither telomere length nor telomerase activity, was an independent survival predictor (hazard ratio 1.116, 95% confidence interval 1.009-1.234, P = 0.033). In this study, telomere length and telomerase activity in PBMCs are not altered in hemodialysis patients compared with healthy controls. Long duration of hemodialysis treatment is associated with telomere shortening and positive telomerase activity with an increased telomere length in PBMCs of hemodialysis patients. The underlying mechanism and clinical implications of our findings require further investigation.

  1. Association of poly(ADP-ribose) polymerase activity in circulating mononuclear cells with myocardial dysfunction in patients with septic shock

    Institute of Scientific and Technical Information of China (English)

    Li Li; Hu Bangchuan; Gong Shijin; Yu Yihua; Dai Haiwen; Yan Jing

    2014-01-01

    Background Severe sepsis and septic shock are the leading causes of morbidity and mortality in hospitalized patients.This study aimed to investigate the association of poly(ADP-ribose) polymerase-1 (PARP-1) activity in circulating mononuclear cells with myocardial dysfunction in patients with septic shock.Methods A total of 64 patients with septic shock were divided into the survival group (n=41) and the nonsurvival group (n=23) according to mortality at 28 days after enrollments.PARP-1 activity in circulating mononuclear cells,brain natriuretic peptide,Acute Physiology and Chronic Health Evaluation Ⅱ score,the cardiac index (CI),the cardiac function index (CFI),global ejection fraction (GEF),and the left ventricular contractility index (dp/dt max) were measured after admission to the intensive care unit.Results PARP-1 activity in circulating mononuclear cells of nonsurvival patients with septic shock was significantly higher than that in survival patients.PARP-1 activity in circulating mononuclear cells was strongly,negatively correlated with the CI,the CFI,GEE and dp/dt max.Multiple Logistic regression analysis showed that PARP-1 activity in circulating mononuclear cells was an independent risk factor of myocardial dysfunction.The optimal cutoff point of PARP-1 activity for predicting 28-day mortality was 942 nmol/L with a sensibility of 78.2% and specificity of 65.1%.Conclusion PARP-1 activity in circulating mononuclear cells is significantly associated with myocardial dysfunction and may have prognostic value in patients with septic shock.

  2. Extracting phosphoric iron under laboratorial conditions smelting bog iron ores

    Science.gov (United States)

    Török, B.; Thiele, A.

    2013-12-01

    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.

  3. Disaccharidase levels in normal epithelium of the small intestine of rats with iron-deficiency anemia

    Directory of Open Access Journals (Sweden)

    M.I.M. Fernandes

    1997-07-01

    Full Text Available Iron-deficiency anemia is the nutritional deficiency most frequently occurring throughout the world, which manifests as a complex systemic disease involving all cells, affecting enzyme activities and modifying protein synthesis. In view of these considerations, the objective of the present study was to determine the effects of iron-deficiency anemia on disaccharidases and on the epithelial morphokinetics of the jejunal mucosa. Newly weaned male Wistar rats were divided into 4 groups of 10 animals each: C6w received a standard ration containing 36 mg elemental iron per kg ration for 6 weeks; E6w received an iron-poor ration (5-8 mg/kg ration for 6 weeks; C10w received an iron-rich ration (36 mg/kg ration for 10 weeks; E10w received an iron-poor ration for 6 weeks and then an iron-rich ration (36 mg/kg for an additional 4 weeks. Jejunal fragments were used to measure disaccharidase content and to study cell proliferation. The following results were obtained: 1 a significant reduction (P<0.001 of animal weight, hemoglobin (Hb, serum iron and total iron-binding capacity (TIBC in group E6w as compared to C6w; reversal of the alterations in Hb, serum iron and TIBC with iron repletion (E10w = C10w; animal weights continued to be significantly different in groups E10w and C10w. 2 Sucrase and maltase levels were unchanged; total and specific lactase levels were significantly lower in group E6w and this reduction was reversed by iron repletion (E10w = C10w. 3 The cell proliferation parameters did not differ between groups. On the basis of these results, we conclude that lactase production was influenced by iron deficiency and that this fact was not related to changes in cell population and proliferation in the intestinal mucosa

  4. Iron dominated magnets

    Energy Technology Data Exchange (ETDEWEB)

    Fischer, G.E.

    1985-07-01

    These two lectures on iron dominated magnets are meant for the student of accelerator science and contain general treatments of the subjects design and construction. The material is arranged in the categories: General Concepts and Cost Considerations, Profile Configuration and Harmonics, Magnetic Measurements, a few examples of ''special magnets'' and Materials and Practices. Extensive literature is provided.

  5. State of the iron

    DEFF Research Database (Denmark)

    Reinisch, Walter; Staun, Michael; Bhandari, Sunil

    2013-01-01

    Iron deficiency anemia (IDA) frequently occurs in patients suffering from inflammatory bowel disease (IBD) and negatively impacts their quality of life. Nevertheless, the condition appears to be both under-diagnosed and undertreated. Regular biochemical screening of patients with IBD for anemia...

  6. Development of iron aluminides

    Energy Technology Data Exchange (ETDEWEB)

    Viswanathan, S.; Sikka, V.K.; Andleigh, V.K. [and others

    1995-06-01

    The primary reason for the poor room-temperature ductility of Fe{sub 3}Al-based alloys is generally accepted to be environmental embrittlement due to hydrogen produced by the reaction of aluminum with water vapor present in the test atmosphere. In the as-cast condition, another possible reason for the low room-temperature ductility is the large grain size (0.5 to 3 mm) of the cast material. While recent studies on iron aluminides in the wrought condition have led to higher room-temperature ductility and increased high-temperature strength, limited studies have been conducted on iron aluminides in the as-cast condition. The purpose of this study was to induce grain refinement of the as-cast alloy through alloying additions to the melt and study the effect on room-temperature ductility as measured by the strain corresponding to the maximum stress obtained in a three-point bend test. A base charge of Fe-28% Al-5% Cr alloy was used; as in previous studies this ternary alloy exhibited the highest tensile ductility of several alloys tested. Iron aluminide alloys are being considered for many structural uses, especially for applications where their excellent corrosion resistance is needed. Several alloy compositions developed at ORNL have been licensed to commercial vendors for development of scale-up procedures. With the licensees and other vendors, several applications for iron aluminides are being pursued.

  7. The New Iron Man

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    Sinosteel wins a hard-fought victory in the marathon battle for Australia’s Midwest Sinosteel Corp.,one of China’s larg- est steelmakers,has finally clinched its AU$1.36 billion($1.31 billion) takeover of Midwest Corp.,a Perth (Australia)-based iron ore miner,after a

  8. Nutritional iron deficiency: the role of oral iron supplementation.

    Science.gov (United States)

    Lachowicz, J I; Nurchi, V M; Fanni, D; Gerosa, C; Peana, M; Zoroddu, M A

    2014-01-01

    Nutritional iron deficiency represents a relevant health problem mainly in developing countries. Children and pregnant women represent the main target of this disease, and the low amount of bio-available iron mostly depends on plant-based diets. Iron deficiency may have serious consequences, with severe impairment of the immune function leading to infectious diseases. The brain development in embryos and fetuses during gestation can be greatly affected by iron deficiency of the mother with heavy outcomes on the cognition status of children. A better understanding of molecular pathways involved in iron absorption and metabolism are the basis for new strategies for developing a therapy for iron deficiency. Different therapeutic strategies are summarized, and iron fortification appears the best tool.

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

    Science.gov (United States)

    Camaschella, Clara

    2017-02-13

    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.

  10. 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...

  11. The Role of Serum Copper and Iron in Oral Submucous Fibrosis

    Directory of Open Access Journals (Sweden)

    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.

  12. Iron-fortified milk can improve iron status in young women with low iron stores

    NARCIS (Netherlands)

    Scholz-Ahrens, K.E.; Schaafsma, G.; Kip, P.; Elbers, F.; Boeing, H.; Schrezenmeir, J.

    2004-01-01

    A considerable proportion of the populations of developing and industrialised nations does not meet the recommended daily allowance for iron and are thus at risk of chronic iron-deficiency anaemia. In a placebo-controlled, double-blind study we investigated whether supplementation with iron-enriched

  13. Iron-fortified milk can improve iron status in young women with low iron stores

    NARCIS (Netherlands)

    Scholz-Ahrens, K.E.; Schaafsma, G.; Kip, P.; Elbers, F.; Boeing, H.; Schrezenmeir, J.

    2004-01-01

    A considerable proportion of the populations of developing and industrialised nations does not meet the recommended daily allowance for iron and are thus at risk of chronic iron-deficiency anaemia. In a placebo-controlled, double-blind study we investigated whether supplementation with iron-enriched

  14. [Iron deficiency, thrombocytosis and thromboembolism].

    Science.gov (United States)

    Evstatiev, Rayko

    2016-10-01

    Iron deficiency, the most common nutritional deficiency worldwide, is often associated with reactive thrombocytosis. Although secondary thrombocytosis is commonly considered to be harmless, there is accumulating evidence that elevated platelet counts, especially in the setting of iron deficiency, can lead to an increased thromboembolic risk in both arterial and venous systems. Here we present the mechanisms of iron deficiency-induced thrombocytosis and summarize its clinical consequences especially in patients with inflammatory bowel diseases, chronic kidney disease or cancer. We hypothesize that iron deficiency is an underestimated thromboembolic risk factor, and that iron replacement therapy can become an effective preventive strategy in a variety of clinical settings.

  15. Tryptamine and dimethyltryptamine inhibit indoleamine 2,3 dioxygenase and increase the tumor-reactive effect of peripheral blood mononuclear cells.

    Science.gov (United States)

    Tourino, Melissa Cavalheiro; de Oliveira, Edson Mendes; Bellé, Luziane Potrich; Knebel, Franciele Hinterholz; Albuquerque, Renata Chaves; Dörr, Felipe Augusto; Okada, Sabrina Sayori; Migliorini, Silene; Soares, Irene Silva; Campa, Ana

    2013-07-01

    Indoleamine 2,3-dioxygenase (IDO) is an interferon-γ (IFN-γ)-induced tryptophan-degrading enzyme, producing kynurenine (KYN) that participates in the mechanism of tumor immune tolerance. Thus, IDO inhibition has been considered a strategy for anticancer therapy. The aim of this study was to identify whether the metabolites originated from the competitive routes of tryptophan metabolism, such as the serotonergic or N, N-dimethyltryptamine (DMT) pathways, have inhibitory effects on recombinant human IDO (rhIDO) activity. Serotonin and melatonin had no effect; on the other hand, tryptamine (TRY) and DMT modulated the activity of rhIDO as classical non-competitive inhibitors, with Ki values of 156 and 506 μM, respectively. This inhibitory effect was also observed on constitutively expressed or IFN-γ-induced IDO in the A172 human glioma cell line. TRY and DMT increased the cytotoxic activity of peripheral blood mononuclear cells (PBMCs) in co-culture assays. We conclude that the IDO inhibition by TRY and DMT contributed to a more effective tumor-reactive response by the PBMCs. Copyright © 2013 John Wiley & Sons, Ltd.

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

    Directory of Open Access Journals (Sweden)

    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.

  17. Constitutive Release of IFNγ and IL2 from Peripheral Blood Mononuclear Cells of Rhesus Macaques (Macaca mulatta) Infected with Simian T-Lymphotropic Virus Type 1

    Science.gov (United States)

    Yee, JoAnn L; Montiel, Nestor A; Ardeshr, Amir; Lerche, Nicholas W

    2013-01-01

    Simian T-cell lymphotropic viruses (STLV), the nonhuman primate counterparts of human T-cell lymphotropic viruses (HTLV), are endemic in many populations of African and Asian monkeys and apes. Although an etiologic link between STLV1 infection and lymphoproliferative disorders such as malignant lymphomas has been suggested in some nonhuman primate species, most STLV infections are inapparent, and infected animals remain clinically healthy. The retroviral transactivator, tax, is well known to increase transcription of viral and cellular genes, resulting in altered cytokine profiles. This study compared the cytokine profiles of peripheral blood mononuclear cell (PBMC) cultures from 25 STLV1-seropositive rhesus macaques (Macaca mulatta) with those of age- and sex-matched seronegative controls. IFNγ, TNFα, IL10, and IL2 levels in unstimulated PBMC culture supernatants were measured at 24, 48, and 72 h by using enzyme immunoassays. IFNγ concentrations were found significantly higher in the supernatants of PBMC cultures of seropositive monkeys as compared with seronegative controls. In addition, although IL2 concentrations were not significantly elevated in the supernatants of PBMC cultures of all seropositive monkeys as compared with all seronegative controls, IL2 levels were increased in a subset of 5 pairs. Increased constitutive cytokine release occurred in the absence of spontaneous proliferation. The increased constitutive release of IFNγ and IL2 suggests that STLV1 alters immune functions in infected but clinically healthy rhesus macaques and further characterizes STLV1 infection of rhesus macaques as a potential model for human HTLV1 infection. PMID:24326227

  18. Mono-nuclear copper complexes mimicking the intermediates for the binuclear copper center of the subunit II of cytochrome oxidase: a peptide based approach.

    Science.gov (United States)

    Dutta Gupta, Dwaipayan; Usharani, Dandamudi; Mazumdar, Shyamalava

    2016-11-28

    Three stable copper complexes of peptides derived from the copper ion binding loop of the subunit II of cytochrome c oxidase have been prepared and characterized by various spectroscopic techniques. These stable copper complexes of peptides were found to exhibit cysteine, histidine and/or methionine ligation, which has predominant σ-contribution in the Cys-Cu charge transfer. The copper(ii) peptide complexes showed type-2 EPR spectra, which is uncommon in copper-cysteinate complexes. UV-visible spectra, Raman and EPR results support a tetragonal structure of the coordination geometry around the copper ion. The copper complex of the 9-amino acid peptide suggested the formation of a 'red' copper center while the copper complexes of the 12- and 11-amino acid peptides showed the formation of a 'green' copper center. The results provide insights on the first stable models of the copper complexes formed in the peptide scaffold that mimic the mono-nuclear copper bound protein intermediates proposed during the formation of the binuclear Cu2S2 core of the enzyme. These three copper complexes of peptides derived from the metal ion binding loop of the CuA center of the subunit II of cytochrome c oxidase showed novel spectroscopic properties which have not so far been reported in any stable small complex.

  19. Changes in DNA Methylation and Chromatin Structure of Pro-inflammatory Cytokines Stimulated by LPS in Broiler Peripheral Blood Mononuclear Cells.

    Science.gov (United States)

    Shen, Jing; Liu, Yanli; Ren, Xiaochun; Gao, Kang; Li, Yulong; Li, Shizhao; Yao, Junhu; Yang, Xiaojun

    2016-07-01

    The pro-inflammatory cytokines IL-1β, IL-6, and tumor necrosis factor (TNF)-α mediate inflammation, which is a protective response by body to ensure removal of detrimental stimuli, as well as a healing process for repairing damaged tissue. The overproduction of pro-inflammatory cytokines can induce autoimmune diseases and can be fatal. The aim of this study was to investigate epigenetic mechanisms in the regulation of pro-inflammatory cytokines expression after lipopolysaccharide (LPS) stimulation of broiler peripheral blood mononuclear cells (PBMC). Gene expression, promoter DNA methylation, and chromatin accessibility of pro-inflammatory cytokines in untreated and LPS-treated PBMC were compared. The expression of epigenetic enzymes DNA methyltransferase (DNMT) 1, histone deacetylase (HDAC), and histone acetylase (HAT) were measured after LPS stimulation. The results showed the activated gene expression of pro-inflammatory cytokines in broiler PBMC stimulated 3 h by LPS. The demethylation of IL-6 gene - 302 and -264 cytosine-guanine (CpG) sites, as well as TNF-α gene -371 CpG site, occurred after LPS treatment (P pro-inflammatory cytokines.

  20. Expression of Caspase-1 Gene Transcript Variant mRNA in Peripheral Blood Mononuclear Cells of Patients with Primary Gout in Different TCM Syndromes

    Science.gov (United States)

    Dang, Wan-Tai; Xu, Dan; Xie, Wen-Guang; Zhou, Jing-Guo

    2015-01-01

    A large number of studies have shown that cysteinyl aspartate specific protease-1 (CASP1) played an important role in the inflammatory response of primary gout, but the decreased expression of different CASP1 transcript variant could inhibit the activation of IL-1β. Our study mainly analyzed the expression level and function of CASP1 gene transcript variant mRNA in peripheral blood mononuclear cells of patients with gout in different TCM syndromes. The expression of CASP1 gene transcript variant and IL-1β mRNA in PBMCs were detected in patients with PG [acute phase (AP: 44 cases); nonacute phase (NAP: 52 cases)] and healthy controls (HC: 30 cases) by reverse transcription-polymerase chain reaction and/or real-time quantitative polymerase chain reaction. The expressions of plasma IL-1β in patients with PG and HC were detected by enzyme-linked immunosorbent assay. Dysregulated expression of the CASP1 gene and its transcript variant, plasma proinflammatory cytokines in all patients with primary gout in different TCM syndromes, correlation analysis showed that there was negative correlation between the expression of CASP1-gamma gene transcript variant mRNA and IL-1β protein in APPG group. The study suggested that CASP1 gene and its transcript variant may play a critical role in the inflammatory response of patients with PG in different phases and TCM syndromes. PMID:26557856