WorldWideScience

Sample records for hemoglobin oxygen affinity

  1. MR Imaging-derived Oxygen-Hemoglobin Dissociation Curves and Fetal-Placental Oxygen-Hemoglobin Affinities.

    Science.gov (United States)

    Avni, Reut; Golani, Ofra; Akselrod-Ballin, Ayelet; Cohen, Yonni; Biton, Inbal; Garbow, Joel R; Neeman, Michal

    2016-07-01

    Purpose To generate magnetic resonance (MR) imaging-derived, oxygen-hemoglobin dissociation curves and to map fetal-placental oxygen-hemoglobin affinity in pregnant mice noninvasively by combining blood oxygen level-dependent (BOLD) T2* and oxygen-weighted T1 contrast mechanisms under different respiration challenges. Materials and Methods All procedures were approved by the Weizmann Institutional Animal Care and Use Committee. Pregnant mice were analyzed with MR imaging at 9.4 T on embryonic days 14.5 (eight dams and 58 fetuses; imprinting control region ICR strain) and 17.5 (21 dams and 158 fetuses) under respiration challenges ranging from hyperoxia to hypoxia (10 levels of oxygenation, 100%-10%; total imaging time, 100 minutes). A shorter protocol with normoxia to hyperoxia was also performed (five levels of oxygenation, 20%-100%; total imaging time, 60 minutes). Fast spin-echo anatomic images were obtained, followed by sequential acquisition of three-dimensional gradient-echo T2*- and T1-weighted images. Automated registration was applied to align regions of interest of the entire placenta, fetal liver, and maternal liver. Results were compared by using a two-tailed unpaired Student t test. R1 and R2* values were derived for each tissue. MR imaging-based oxygen-hemoglobin dissociation curves were constructed by nonlinear least square fitting of 1 minus the change in R2*divided by R2*at baseline as a function of R1 to a sigmoid-shaped curve. The apparent P50 (oxygen tension at which hemoglobin is 50% saturated) value was derived from the curves, calculated as the R1 scaled value (x) at which the change in R2* divided by R2*at baseline scaled (y) equals 0.5. Results The apparent P50 values were significantly lower in fetal liver than in maternal liver for both gestation stages (day 14.5: 21% ± 5 [P = .04] and day 17.5: 41% ± 7 [P hemoglobin dissociation curves with a shorter protocol that excluded the hypoxic periods was demonstrated. Conclusion MR imaging

  2. Modifiers of hemoglobin/oxygen affinity as sensitizers of tumors to radiation

    International Nuclear Information System (INIS)

    Hirst, D.G.; Wood, P.J.

    1987-01-01

    A powerful mechanism in the control of oxygen delivery to tissues is the allosteric modification of hemoglobin. Increased or decreased release of oxygen can be achieved by altering the affinity of hemoglobin for oxygen. Several studies have shown that tumor radiosensitivity is dependent on this relationship. The authors studied affinity changes produced in two distinctly different ways. Tumor bearing mice were given isovolemic exchange blood transfusions with the blood from donor mice which had been exposed to abnormal oxygen tensions, leading to increased or slightly decreased levels of 2,3-diphosphoglycerate (2,3 DPG) in their blood. When the recipient mice were irradiated, those receiving the blood with higher 2,3 DPG levels showed greater tumor sensitivity to radiation. An alternative strategy is the use of drugs which directly alter hemoglobin/oxygen affinity. The authors studied three antihyperlipoproteinemia drugs, all of which have produced markedly reduced affinities in vivo. Preliminary data indicate that the radiosensitization produced by at least one of these compounds is less than would have been expected from the 2,3 DPG experiments

  3. Action of carbon monoxide on the affinity of hemoglobin for oxygen

    Energy Technology Data Exchange (ETDEWEB)

    Vanuxem, D.; Weiller, P.J.; Guillot, C.; Grimaud, C.

    1982-01-01

    The authors have studied the action of carbon monoxide on the affinity of hemoglobin for oxygen by measuring P50 in whole blood and in stripped hemoglobin before and after exposition of blood samples from heavy smokers and polycythemic patients with high levels of HbCO to hyperbaric oxygen (2.2 ata). The concentration of 2,3-diphosphoglycerate was normal although P50 was significantly lowered, not only in whole blood but also in stripped hemoglobin. Hyperbaric oxygen normalized P50 by removing CO radicals from stripped hemoglobin. This may indicate that CO radicals exert a direct action on the hemoglobin molecule, at least at the HbCO levels studied in this work.

  4. Structure of Greyhound hemoglobin: origin of high oxygen affinity.

    Science.gov (United States)

    Bhatt, Veer S; Zaldívar-López, Sara; Harris, David R; Couto, C Guillermo; Wang, Peng G; Palmer, Andre F

    2011-05-01

    This study presents the crystal structure of Greyhound hemoglobin (GrHb) determined to 1.9 Å resolution. GrHb was found to crystallize with an α₁β₁ dimer in the asymmetric unit and belongs to the R2 state. Oxygen-affinity measurements combined with the fact that GrHb crystallizes in the R2 state despite the high-salt conditions used for crystallization strongly indicate that GrHb can serve as a model high-oxygen-affinity hemoglobin (Hb) for higher mammals, especially humans. Structural analysis of GrHb and its comparison with the R2-state of human Hb revealed several regions that can potentially contribute to the high oxygen affinity of GrHb and serve to rationalize the additional stability of the R2-state of GrHb. A previously well studied hydrophobic cluster of bar-headed goose Hb near α119 was also incorporated in the comparison between GrHb and human Hb. Finally, a structural comparison with generic dog Hb and maned wolf Hb was conducted, revealing that in contrast to GrHb these structures belong to the R state of Hb and raising the intriguing possibility of an additional allosteric factor co-purifying with GrHb that can modulate its quaternary structure.

  5. Hemoglobin affinity in Andean rodents

    Directory of Open Access Journals (Sweden)

    HRVOJ OSTOJIC

    2002-01-01

    Full Text Available Blood hemoglobin oxygen affinity (P50 was measured in three Andean species and in the laboratory rat (control, all raised near sea level. Chinchilla lanigera (Molina, 1792 has an altitudinal habitat range from low Andean slopes up to 3000 m., while Chinchilla brevicaudata (Waterhouse, 1848 has an altitudinal range from 3000 to 5000 m. The laboratory type guinea pig, wild type guinea pig (Cavia porcellus, (Waterhouse, 1748, and laboratory rat (Rattus norvegicus were also raised at sea level. The Andean species had high hemoglobin oxygen affinities (low P50 compared with the rat. Chinchilla brevicaudata had a higher affinity than Chinchilla lanigera. The wild type guinea pig had a higher affinity than the laboratory type. As has been shown in other species, this is another example of an inverse correlation between the altitude level and the P50 values. This is the first hemoglobin oxygen affinity study in Chinchilla brevicaudata.

  6. A theoretical model for the effects of reduced hemoglobin-oxygen affinity on tumor oxygenation

    International Nuclear Information System (INIS)

    Kavanagh, Brian D.; Secomb, Timothy W.; Hsu, Richard; Lin, P.-S.; Venitz, Jurgen; Dewhirst, Mark W.

    2002-01-01

    Purpose: To develop a theoretical model for oxygen delivery to tumors, and to use the model to simulate the effects of changing the affinity of hemoglobin for oxygen on tumor oxygenation. Methods and Materials: Hemoglobin affinity is expressed in terms of P 50 , the partial pressure of oxygen (Po 2 ) at half saturation. Effects of changing P 50 on arterial Po 2 are predicted using an effective vessel approach to describe diffusive oxygen transport in the lungs, assuming fixed systemic oxygen demand and fixed blood flow rate. The decline in oxygen content of blood as it flows through normal tissue before entering the tumor region is assumed fixed. The hypoxic fraction of the tumor region is predicted using a three-dimensional simulation of diffusion from a network of vessels whose geometry is derived from observations of tumor microvasculature in the rat. Results: In air-breathing rats, predicted hypoxic fraction decreases with moderate increases in P 50 , but increases with further increases of P 50 , in agreement with previous experimental results. In rats breathing hyperoxic gases, and in humans breathing either normoxic or hyperoxic gases, increased P 50 is predicted to improve tumor oxygenation. Conclusions: The results support the administration of synthetic agents to increase P 50 during radiation treatment of tumors

  7. Hemoglobin oxygen affinity in patients with cystic fibrosis.

    Directory of Open Access Journals (Sweden)

    Dieter Böning

    Full Text Available In patients with cystic fibrosis lung damages cause arterial hypoxia. As a typical compensatory reaction one might expect changes in oxygen affinity of hemoglobin. Therefore position (standard half saturation pressure P50st and slope (Hill's n of the O2 dissociation curve as well as the Bohr coefficients (BC for CO2 and lactic acid were determined in blood of 14 adult patients (8 males, 6 females and 14 healthy controls (6 males, 8 females. While Hill's n amounted to approximately 2.6 in all subjects, P50st was slightly increased by 1 mmHg in both patient groups (controls male 26.7 ± 0.2, controls female 27.0 ± 0.1, patients male 27.7 ± 0.5, patients female 28.0 ± 0.3 mmHg; mean and standard error, overall p<0.01. Main cause was a rise of 1-2 µmol/g hemoglobin in erythrocytic 2,3-biphosphoglycerate concentration. One patient only, clearly identified as an outlier and with the mutation G551D, showed a reduction of both P50st (24.5 mmHg and [2,3-biphosphoglycerate] (9.8 µmol/g hemoglobin. There were no differences in BCCO2, but small sex differences in the BC for lactic acid in the controls which were not detectable in the patients. Causes for the right shift of the O2 dissociation curve might be hypoxic stimulation of erythrocytic glycolysis and an increased red cell turnover both causing increased [2,3-biphosphoglycerate]. However, for situations with additional hypercapnia as observed in exercising patients a left shift seems to be a more favourable adaptation in cystic fibrosis. Additionally when in vivo PO2 values were corrected to the standard conditions they mostly lay left of the in vitro O2 dissociation curve in both patients and controls. This hints to unknown fugitive factors influencing oxygen affinity.

  8. Inhaled nitric oxide augments nitric oxide transport on sickle cell hemoglobin without affecting oxygen affinity

    OpenAIRE

    Gladwin, Mark T.; Schechter, Alan N.; Shelhamer, James H.; Pannell, Lewis K.; Conway, Deirdre A.; Hrinczenko, Borys W.; Nichols, James S.; Pease-Fye, Margaret E.; Noguchi, Constance T.; Rodgers, Griffin P.; Ognibene, Frederick P.

    1999-01-01

    Nitric oxide (NO) inhalation has been reported to increase the oxygen affinity of sickle cell erythrocytes. Also, proposed allosteric mechanisms for hemoglobin, based on S-nitrosation of β-chain cysteine 93, raise the possibilty of altering the pathophysiology of sickle cell disease by inhibiting polymerization or by increasing NO delivery to the tissue. We studied the effects of a 2-hour treatment, using varying concentrations of inhaled NO. Oxygen affinity, as measured by P50, did not respo...

  9. High affinity hemoglobin and Parkinson's disease.

    Science.gov (United States)

    Graham, Jeffrey; Hobson, Douglas; Ponnampalam, Arjuna

    2014-12-01

    Parkinson's disease (PD) is a neurodegenerative disorder characterized by the loss of dopaminergic neurons in the substantia nigra (SN) region of the midbrain. Oxidative damage in this region has been shown to play an important role in the pathogenesis of this disease. Human neurons have been discovered to contain hemoglobin, with an increased concentration seen in the neurons of the SN. High affinity hemoglobin is a clinical entity resulting from mutations that create a functional increase in the binding of hemoglobin to oxygen and an inability to efficiently unload it to tissues. This can result in a number of metabolic compensatory changes, including an elevation in circulating hemoglobin and an increase in the molecule 2,3-diphosphoglycerate (2,3-DPG). Population based studies have revealed that patients with PD have elevated hemoglobin as well as 2,3-DPG levels. Based on these observations, we hypothesize that the oxidative damage seen in PD is related to an underlying high affinity hemoglobin subtype. Copyright © 2014 Elsevier Ltd. All rights reserved.

  10. Changes in hemoglobin-oxygen affinity with shape variations of red blood cells

    Science.gov (United States)

    Chowdhury, Aniket; Dasgupta, Raktim; Majumder, Shovan K.

    2017-10-01

    Shape variations of red blood cells (RBCs) are known to occur upon exposure to various drugs or under diseased conditions. The commonly observed discocytic RBCs can be transformed to echinocytic or stomatocytic shape under such conditions. Raman spectra of the three major shape variations, namely discocyte, echinocyte, and stomatocyte, of RBCs were studied while subjecting the cells to oxygenated and deoxygenated conditions. Analysis of the recorded spectra suggests an increased level of hemoglobin (Hb)-oxygen affinity for the echinocytes. Also, some level of Hb degradation could be noticed for the deoxygenated echinocytes. The effects may arise from a reduced level of intracellular adenosine triphosphate in echinocytic cells and an increased fraction of submembrane Hb.

  11. Effect of 2,3-diphosphoglycerate on oxygen affinity of blood in sickle cell anemia

    Science.gov (United States)

    Charache, Samuel; Grisolia, Santiago; Fiedler, Adam J.; Hellegers, Andre E.

    1970-01-01

    Blood of patients with sickle cell anemia (SS) exhibits decreased affinity for oxygen, although the oxygen affinity of hemoglobin S is the same as that of hemoglobin A. SS red cells contain more 2,3-diphosphoglycerate (DPG) than normal erythrocytes. The oxygen affinity of hemolyzed red cells is decreased by added DPG, and hemolysates prepared from SS red cells do not differ from normal hemolysates in this regard. Reduction of oxygen affinity to the levels found in intact SS red cells required DPG concentrations in excess of those found in most SS patients. The same was true of oxygen affinity of patients with pyruvate kinase deficiency. Other organic phosphates, as well as inorganic ions, are known to alter the oxygen affinity of dilute solutions of hemoglobin. These substances, the state of aggregation of hemoglobin molecules, and cytoarchitectural factors probably play roles in determining oxygen affinity of both normal and SS red cells. PMID:5443181

  12. Alteration of the α1β2/α2β1 subunit interface contributes to the increased hemoglobin-oxygen affinity of high-altitude deer mice

    Energy Technology Data Exchange (ETDEWEB)

    Inoguchi, Noriko; Mizuno, Nobuhiro; Baba, Seiki; Kumasaka, Takashi; Natarajan, Chandrasekhar; Storz, Jay F.; Moriyama, Hideaki; Permyakov, Eugene A.

    2017-03-31

    Deer mice (Peromyscus maniculatus) that are native to high altitudes in the Rocky Mountains have evolved hemoglobins with an increased oxygen-binding affinity relative to those of lowland conspecifics. To elucidate the molecular mechanisms responsible for the evolved increase in hemoglobin-oxygen affinity, the crystal structure of the highland hemoglobin variant was solved and compared with the previously reported structure for the lowland variant. Highland hemoglobin yielded at least two crystal types, in which the longest axes were 507 and 230 Å. Using the smaller unit cell crystal, the structure was solved at 2.2 Å resolution. The asymmetric unit contained two tetrameric hemoglobin molecules. The analyses revealed that αPro50 in the highland hemoglobin variant promoted a stable interaction between αHis45 and heme that was not seen in the αHis50 lowland variant. The αPro50 mutation also altered the nature of atomic contacts at the α1β2/α2β1 intersubunit interfaces. These results demonstrate how affinity-altering changes in intersubunit interactions can be produced by mutations at structurally remote sites.

  13. ATP-induced temperature independence of hemoglobin-O2 affinity in heterothermic billfish

    DEFF Research Database (Denmark)

    Weber, Roy E.; Campbell, Kevin L.; Fago, Angela

    2010-01-01

    heterotherms, where it may hamper unloading (e.g. in cold extremities of arctic mammals) or increase the diffusive arterio-venous short-circuiting of O2 (e.g. in counter-current heat exchangers of warm swimming muscles of tuna). We hypothesized analogous blood specializations in heterothermic billfish, whose......The inverse relationship between temperature and hemoglobin-O2 affinity resulting from the exothermic nature of heme oxygenation favors O2 unloading from blood to warm, metabolically active tissues. However, this temperature sensitivity is maladaptive, and commonly countered in regional...... to allosterically modulating hemoglobin-O2 affinity, ATP diminishes its temperature sensitivity, reducing deleterious arterio-venous short-circuiting of oxygen in the cranial billfish heat exchangers. The mechanism underlying this reduction in oxygenation enthalpy differs fundamentally from that in tuna, supporting...

  14. Plant hemoglobins: Important players at the crossroads between oxygen and nitric oxide

    DEFF Research Database (Denmark)

    Gupta, Kapuganti J; Hebelstrup, Kim; Mur, Luis A J

    2011-01-01

    Plant hemoglobins constitute a diverse group of hemeproteins and evolutionarily belong to three different classes. Class 1 hemoglobins possess an extremely high affinity to oxygen and their main function consists in scavenging of nitric oxide (NO) at very low oxygen levels. Class 2 hemoglobins have...... at high O2 concentrations. Depending on their physical properties, hemoglobins belong either to hexacoordinate non-symbiotic or pentacoordinate symbiotic groups. Plant hemoglobins are plausible targets for improving resistance to multiple stresses....

  15. A new polyethyleneglycol-derivatized hemoglobin derivative with decreased oxygen affinity and limited toxicity.

    Science.gov (United States)

    Zolog, Oana; Mot, Augustin; Deac, Florina; Roman, Alina; Fischer-Fodor, Eva; Silaghi-Dumitrescu, Radu

    2011-01-01

    A new protocol is described for derivatization of hemoglobin with polyethyleneglycol (PEG) via reaction of the unmodified native hemoglobin with an activated amine-reacting polyethylene glycol derivative which, unlike protocols previously described, leads to formation of a peptide bond between hemoglobin and PEG. Dioxygen binding and peroxide reactivities of the derivatized hemoglobin are examined, and found to be within reasonable limits, with the particular observation that, unlike with a few other derivatization protocols, the dioxygen affinity is slightly lower than that of native Hb. In cell culture tests (human umbilical vein epithelial cells, HUVEC), the derivatization protocol induces no toxic effect. These results show promise towards applicability for production of hemoglobin-based blood substitutes.

  16. Single-cell measurement of red blood cell oxygen affinity

    OpenAIRE

    Caprio, Di; Stokes, Chris; Higgins, John M.; Schonbrun, Ethan

    2015-01-01

    Oxygen is transported throughout the body by hemoglobin in red blood cells. While the oxygen affinity of blood is well understood and is routinely assessed in patients by pulse oximetry, variability at the single-cell level has not been previously measured. In contrast, single-cell measurements of red blood cell volume and hemoglobin concentration are taken millions of times per day by clinical hematology analyzers and are important factors in determining the health of the hematologic system....

  17. Hemoglobin as a factor in the control of tumor oxygenation

    International Nuclear Information System (INIS)

    Hirst, D.G.

    1987-01-01

    The concentration of hemoglobin in the blood has been shown to have a market effect on the radiosensitivity of human and animal tumors. Experimental studies in mice indicate that radiosensitivity is influenced by a change in the hemoglobin level rather than by the absolute concentration. This dependence may be exploited to therapeutic advantage. Recent studies of hemoglobin/oxygen affinity have shown that the concentration of 2,3 diphosphoglycerate (2,3 DPG) affects tumor sensitivity to X-rays. Increased 2,3 DPG levels increase radiosensitivity in several mouse tumors. The time dependence of this effect remains to be established. The effective application of these effects in man may depend on the development of drugs which produce changes in hemoglobin affinity without the need for blood transfusions. Several drugs are currently being investigated

  18. Oxygen binding properties of hemoglobin from the white rhinoceros (beta 2-GLU) and the tapir.

    Science.gov (United States)

    Baumann, R; Mazur, G; Braunitzer, G

    1984-04-01

    The beta-chain of rhinoceros hemoglobin contains glutamic acid at position beta 2, and important site for the binding of organic phosphates. We have investigated the oxygen binding properties of this hemoglobin and its interaction with ATP, 2,3-diphosphoglycerate, CO2 and chloride. The results show that the presence of GLU at position beta 2 nearly abolishes the effect of organic phosphates and CO2, whereas the oxygen-linked binding of chloride is not affected. Thus rhinoceros hemoglobin has only protons and chloride anions as major allosteric effectors for the control of its oxygen affinity. From the results obtained with hemoglobin solutions it can be calculated that the blood oxygen affinity of the rhinoceros must be rather high with a P50 of about 20 torr at pH 7.4 and 37 degrees C, which conforms with observations obtained for other large mammals.

  19. Hemoglobin Rahere, a human hemoglobin variant with amino acid substitution at the 2,3-diphosphoglycerate binding site. Functional consequences of the alteration and effects of bezafibrate on the oxygen bindings.

    Science.gov (United States)

    Sugihara, J; Imamura, T; Nagafuchi, S; Bonaventura, J; Bonaventura, C; Cashon, R

    1985-09-01

    We encountered an abnormal hemoglobin (Rahere), with a threonine residue replacing the beta 82 (EF6) lysine residue at the binding site of 2,3-diphosphoglycerate, which was responsible for overt erythrocytosis in two individuals of a Japanese family. Hemoglobin Rahere shows a lower oxygen affinity on the binding of 2,3-diphosphoglycerate or chloride ions than hemoglobin A. Although a decrease in the positive charge density at the binding sites of 2,3-diphosphoglycerate in hemoglobin Rahere apparently shifts the allosteric equilibrium toward the low affinity state, it greatly diminishes the cofactor effects by anions. The oxygen affinity of the patient's erythrocytes is substantially lowered by the presence of bezafibrate, which combines with sites different from those of 2,3-diphosphoglycerate in either hemoglobin Rahere or hemoglobin A.

  20. Hemoglobin

    Science.gov (United States)

    1993-03-08

    affinity, which is less at low levels of hemoglobin saturation, increases markedly as fractional saturation increases. Thus, high affinity for 02 at... diphosphoglycerate (2,3-DPG), and carbon dioxide (Co 2). Since they are linked to 02 binding, they are called oxygen-linked effectors. The oxygen...hemoglobin molecule because of the negative charge of the ions. 2,3- Diphosphoglycerate is a molecule formed during the breakdown of sugar in normal human

  1. Oxygen Association-Dissociation and Stability Analysis on Mouse Hemoglobins with Mutant α- and β-Globins

    Science.gov (United States)

    D'Surney, S. J.; Popp, R. A.

    1992-01-01

    Oxygen association-dissociation and hemoglobin stability analysis were performed on mouse hemoglobins with amino acid substitutions in an α-globin (α89, His to Leu) and a β-globin (β59, Lys to Ile). The variant α-globin, designated chain 5(m) in the Hba(g2) haplotype, had a high oxygen affinity and was stable. The variant β-globin, (β(s2)) of the Hbb(s2) haplotype, also had an elevated oxygen affinity and in addition was moderately unstable in 19% isopropanol. Hemoglobins from the expected nine (Hba(g2)/Hba(g2);Hbb(s)/Hbb(s) X Hba(a)/Hba(a);Hbb(s2)/Hbb(s2)) F(2) genotypes can be grouped into five classes of P(50) values characterized by strict additivity and dependency on mutant globin gene dosage; physiologically, both globin variants gave indistinguishable effects on oxygen affinity. The hemoglobin of normal mice (Hba(a)/Hba(a);Hbb(s)/Hbb(s)) had a P(50) = 40 mm Hg and the hemoglobin of Hba(g2)/Hba(g2);Hbb(s2)/Hbb(s2) F(2) mice had a P(50) = 25 mm Hg (human P(50) = 26 mm Hg). Peripheral blood from Hba(g2)/Hba(g2);Hbb(s)/Hbb(s), Hba(a)/Hba(a);Hbb(s2)/Hbb(s2) and Hba(g2)/Hba(g2);Hbb(s2)/Hbb(s2) mice exhibited normal hematological values except for a slightly higher hematocrit for Hba(g2)/Hba(g2);Hbb(s)/Hbb(s) and Hba(g2)/Hba(g2);Hbb(s2)/Hbb(s2) mice, slightly elevated red cell counts for mice of the three mutant genotypes, and significantly lower values for the mean corpuscular volume and mean corpuscular hemoglobin for Hba(g2)/Hba(g2);Hbb(s2)/Hbb(s2) mice. PMID:1427042

  2. Single-cell measurement of red blood cell oxygen affinity.

    Science.gov (United States)

    Di Caprio, Giuseppe; Stokes, Chris; Higgins, John M; Schonbrun, Ethan

    2015-08-11

    Oxygen is transported throughout the body by hemoglobin (Hb) in red blood cells (RBCs). Although the oxygen affinity of blood is well-understood and routinely assessed in patients by pulse oximetry, variability at the single-cell level has not been previously measured. In contrast, single-cell measurements of RBC volume and Hb concentration are taken millions of times per day by clinical hematology analyzers, and they are important factors in determining the health of the hematologic system. To better understand the variability and determinants of oxygen affinity on a cellular level, we have developed a system that quantifies the oxygen saturation, cell volume, and Hb concentration for individual RBCs in high throughput. We find that the variability in single-cell saturation peaks at an oxygen partial pressure of 2.9%, which corresponds to the maximum slope of the oxygen-Hb dissociation curve. In addition, single-cell oxygen affinity is positively correlated with Hb concentration but independent of osmolarity, which suggests variation in the Hb to 2,3-diphosphoglycerate (2-3 DPG) ratio on a cellular level. By quantifying the functional behavior of a cellular population, our system adds a dimension to blood cell analysis and other measurements of single-cell variability.

  3. Oxygenation properties and isoform diversity of snake hemoglobins

    DEFF Research Database (Denmark)

    Storz, Jay F.; Natarajan, Chandrasekhar; Moriyama, Hideaki

    2015-01-01

    Available data suggest that snake hemoglobins (Hbs) are characterized by a combination of unusual structural and functional properties relative to the Hbs of other amniote vertebrates, including oxygenation-linked tetramer- dimer dissociation. However, standardized comparative data are lacking fo...... isoform of the South American rattlesnake is homologous to the minor HbD of other amniotes and, contrary to the pattern of Hb isoform differentiation in birds and turtles, exhibits a lower O2 affinity than the HbA isoform....

  4. Lanthanide ions induce hydrolysis of hemoglobin-bound 2,3-diphosphoglycerate (2,3-DPG), conformational changes of globin and bidirectional changes of 2,3-DPG-hemoglobin's oxygen affinity.

    Science.gov (United States)

    Cheng, Y; Lin, H; Xue, D; Li, R; Wang, K

    2001-02-14

    The changes in structure and function of 2,3-diphosphoglycerate-hemoglobin (2,3-DPG-Hb) induced by Ln(3+) binding were studied by spectroscopic methods. The binding of lanthanide cations to 2,3-DPG is prior to that to Hb. Ln(3+) binding causes the hydrolysis of either one from the two phosphomonoester bonds in 2,3-DPG non-specifically. The results using the ultrafiltration method indicate that Ln(3+) binding sites for Hb can be classified into three categories: i.e. positive cooperative sites (N(I)), non-cooperative strong sites (N(S)) and non-cooperative weak sites (N(W)) with binding constants in decreasing order: K(I)>K(S)>K(W). The total number of binding sites amounts to about 65 per Hb tetramer. Information on reaction kinetics was obtained from the change of intrinsic fluorescence in Hb monitored by stopped-flow fluorometry. Fluctuation of fluorescence dependent on Ln(3+) concentration and temperature was observed and can be attributed to the successive conformational changes induced by Ln(3+) binding. The results also reveal the bidirectional changes of the oxygen affinity of Hb in the dependence on Ln(3+) concentration. At the range of [Ln(3+)]/[Hb]<2, the marked increase of oxygen affinity (P(50) decrease) with the Ln(3+) concentration can be attributed to the hydrolysis of 2,3-DPG, while the slight rebound of oxygen affinity in higher Ln(3+) concentration can be interpreted by the transition to the T-state of the Hb tetramer induced by Ln(3+) binding. This was indicated by the changes in secondary structure characterized by the decrease of alpha-helix content.

  5. Dichloromethane as an antisickling agent in sickle cell hemoglobin

    Energy Technology Data Exchange (ETDEWEB)

    Schoenborn, B.P.; North, B.E.

    1977-01-01

    Observations are reported that show that dichloromethane (DCM) does have a significant effect on the oxygen binding properties of hemoglobin. At DCM pressures high enough to prevent or reverse sickling, DCM would lower the oxygen affinity of hemoglobin, therefore reducing oxygen transport at low oxygen pressure. This decrease in oxygen affinity might, however, increase the oxygen availability to tissue as long as a sufficiently large lung P/sub O/sub 2// is maintained. Crystallographic studies show that site D4 has a much lower affinity for DCM than site D3 while sites D1 and D2 show a higher affinity.

  6. High-affinity hemoglobin and blood oxygen saturation in diving emperor penguins.

    Science.gov (United States)

    Meir, Jessica U; Ponganis, Paul J

    2009-10-01

    The emperor penguin (Aptenodytes forsteri) thrives in the Antarctic underwater environment, diving to depths greater than 500 m and for durations longer than 23 min. To examine mechanisms underlying the exceptional diving ability of this species and further describe blood oxygen (O2) transport and depletion while diving, we characterized the O2-hemoglobin (Hb) dissociation curve of the emperor penguin in whole blood. This allowed us to (1) investigate the biochemical adaptation of Hb in this species, and (2) address blood O2 depletion during diving, by applying the dissociation curve to previously collected partial pressure of O2 (PO2) profiles to estimate in vivo Hb saturation (SO2) changes during dives. This investigation revealed enhanced Hb-O2 affinity (P50=28 mmHg, pH 7.5) in the emperor penguin, similar to high-altitude birds and other penguin species. This allows for increased O2 at low blood PO2 levels during diving and more complete depletion of the respiratory O2 store. SO2 profiles during diving demonstrated that arterial SO2 levels are maintained near 100% throughout much of the dive, not decreasing significantly until the final ascent phase. End-of-dive venous SO2 values were widely distributed and optimization of the venous blood O2 store resulted from arterialization and near complete depletion of venous blood O2 during longer dives. The estimated contribution of the blood O2 store to diving metabolic rate was low and highly variable. This pattern is due, in part, to the influx of O2 from the lungs into the blood during diving, and variable rates of tissue O2 uptake.

  7. Nitric oxide formation from the reaction of nitrite with carp and rabbit hemoglobin at intermediate oxygen saturations

    DEFF Research Database (Denmark)

    Jensen, Frank Bo

    2008-01-01

    The nitrite reductase activity of deoxyhemoglobin has received much recent interest because the nitric oxide produced in this reaction may participate in blood flow regulation during hypoxia. The present study used spectral deconvolution to characterize the reaction of nitrite with carp and rabbit...... hemoglobin at different constant oxygen tensions that generate the full range of physiological relevant oxygen saturations. Carp is a hypoxia-tolerant species with very high hemoglobin oxygen affinity, and the high R-state character and low redox potential of the hemoglobin is hypothesized to promote...... NO generation from nitrite. The reaction of nitrite with deoxyhemoglobin leads to a 1 : 1 formation of nitrosylhemoglobin and methemoglobin in both species. At intermediate oxygen saturations, the reaction with deoxyhemoglobin is clearly favored over that with oxyhemoglobin, and the oxyhemoglobin reaction...

  8. [Role of erythrocyte cytoplasmic structures in changes in the affinity of haemoglobin for oxygen].

    Science.gov (United States)

    Bryzgalova, N Iu; Brazhe, N A; Iusipovich, A U; Maksimov, G V; Rubin, A B

    2009-01-01

    Changes in the refractive index of the cytoplasm and the affinity of haemoporphyrin of erythrocyte haemoglobin to oxygen (pH, 2,3-diphosphoglycerate) have been investigated using laser interference microscopy and Raman spectroscopy. It has been established that a decrease in pH and an increase in the content of 2,3-diphosphoglycerate are accompanied by changes in both the form of the cell and the refractive index of the cytoplasm and the affinity of haemoporphyrin of hemoglobin to oxygen. It has been shown that as pH is reduced, the capacity of haemoporphyrin for binding oxygen decreases and as the concentration of 2,3-diphosphoglycerate is increased, the ability of haemoporphyrin for oxygen reabsorption increases.

  9. Hemoglobin Rahere, a human hemoglobin variant with amino acid substitution at the 2,3-diphosphoglycerate binding site. Functional consequences of the alteration and effects of bezafibrate on the oxygen bindings.

    OpenAIRE

    Sugihara, J; Imamura, T; Nagafuchi, S; Bonaventura, J; Bonaventura, C; Cashon, R

    1985-01-01

    We encountered an abnormal hemoglobin (Rahere), with a threonine residue replacing the beta 82 (EF6) lysine residue at the binding site of 2,3-diphosphoglycerate, which was responsible for overt erythrocytosis in two individuals of a Japanese family. Hemoglobin Rahere shows a lower oxygen affinity on the binding of 2,3-diphosphoglycerate or chloride ions than hemoglobin A. Although a decrease in the positive charge density at the binding sites of 2,3-diphosphoglycerate in hemoglobin Rahere ap...

  10. [Effect of almitrine administered by the oral route on levels of 2,3-diphosphoglycerate and on the affinity of hemoglobin for oxygen in healthy subjects].

    Science.gov (United States)

    Clerbaux, T; Frans, A

    1985-02-01

    Clinical and pharmacological studies have shown that almitrine increased arterial blood oxygen partial pressure (PaO2) and tissular oxygenation. We have verified whether this drug could also increase the 2,3 diphosphoglycerate (DPG) level and so modify the oxyhemoglobin dissociation curve (ODC). Determinations performed 3 hours and 5 days after daily oral administration (1,5 mg/kg) of the drug showed no alterations of DPG and ODC in normal subjects. The presence of almitrine does not explain the observed PaO2 increase by means of a direct effect on the hemoglobin oxygen affinity. However, one cannot exclude almitrine long term effect; indeed, after 15 days, DPG levels and Hill coefficient increased significantly (p less than 0.05) but no the P50 (respectively + 1,5 mumole/gHb; +0.1 and 26.0 vs 26.5 mmHg).

  11. Hot atom labeling of myoglobin and hemoglobin and biophysical studies of oxygen and CO binding to carp hemoglobin

    International Nuclear Information System (INIS)

    Astatke, M.

    1992-01-01

    Human Hb, the monomeric Hb of Glycera dibranchiata and horse Mb were modified by replacement of the protoheme with 2,4-dibromodeuteroheme. Following neutron capture by 79 Br and 81 Br, the locations of radioactive Br were determined. Although human Hb had approximately four times the mass and volume of the other proteins, about 9% of the activated Br was inserted into each of the three globins. These results suggest that the insertion is short-range (within 15 angstrom) and that this method could be used to label target sites in various proteins and other biological structures. Carp Hb's containing proto-, meso-, deutero- and dibromoheme were prepared. Kinetic and thermodynamic parameters for oxygen and CO binding were determined at Ph 6 (+IHP) (T-state, low-affinity protein) and Ph 9 (R-state, high-affinity protein). Parameters for the binding of oxygen and CO were related to the properties of the four hemes to estimate the inductive and steric factors in the ligation process. The results suggest that the steric factors are more important for the T-state than for the R-state. The T-state carp Hbs were very readily oxidized. Two new procedures were developed for the rapid determination of oxygen equilibrium isotherms for the T-state carp Hbs. The kinetic and thermodynamic parameters for ligation of oxygen and CO with the isolated carp α-chains were determined. Carp α-chains are the only hemoglobin chains isolated to date that can be classified as T-state. The secondary thermodynamic parameter (δH degrees) was found to be essential for classifying hemoglobins as T- or R-state

  12. The effects of 2,3-diphosphoglycerate, adenosine triphosphate, and glycosylated hemoglobin on the hemoglobin-oxygen affinity of diabetic patients

    Directory of Open Access Journals (Sweden)

    Castilho E.M.

    2003-01-01

    Full Text Available The position of the oxygen dissociation curve (ODC is modulated by 2,3-diphosphoglycerate (2,3-DPG. Decreases in 2,3-DPG concentration within the red cell shift the curve to the left, whereas increases in concentration cause a shift to the right of the ODC. Some earlier studies on diabetic patients have reported that insulin treatment may reduce the red cell concentrations of 2,3-DPG, causing a shift of the ODC to the left, but the reports are contradictory. Three groups were compared in the present study: 1 nondiabetic control individuals (N = 19; 2 insulin-dependent diabetes mellitus (IDDM patients (on insulin treatment (N = 19; 3 non-insulin-dependent diabetes mellitus (NIDDM patients using oral hypoglycemic agents and no insulin treatment (N = 22. The overall position of the ODC was the same for the three groups despite an increase of the glycosylated hemoglobin fraction that was expected to shift the ODC to the left in both groups of diabetic patients (HbA1c: control, 4.6%; IDDM, 10.5%; NIDDM, 9.0%. In IDDM patients, the effect of the glycosylated hemoglobin fraction on the position of the ODC appeared to be counterbalanced by small though statistically significant increases in 2,3-DPG concentration from 2.05 (control to 2.45 µmol/ml blood (IDDM. Though not statistically significant, an increase of 2,3-DPG also occurred in NIDDM patients, while red cell ATP levels were the same for all groups. The positions of the ODC were the same for control subjects, IDDM and NIDDM patients. Thus, the PO2 at 50% hemoglobin-oxygen saturation was 26.8, 28.2 and 28.5 mmHg for control, IDDM and NIDDM, respectively. In conclusion, our data question the idea of adverse side effects of insulin treatment on oxygen transport. In other words, the shift to the left reported by others to be caused by insulin treatment was not detected.

  13. The effects of 2,3-diphosphoglycerate, adenosine triphosphate, and glycosylated hemoglobin on the hemoglobin-oxygen affinity of diabetic patients.

    Science.gov (United States)

    Castilho, E M; Glass, M L; Manço, J C

    2003-06-01

    The position of the oxygen dissociation curve (ODC) is modulated by 2,3-diphosphoglycerate (2,3-DPG). Decreases in 2,3-DPG concentration within the red cell shift the curve to the left, whereas increases in concentration cause a shift to the right of the ODC. Some earlier studies on diabetic patients have reported that insulin treatment may reduce the red cell concentrations of 2,3-DPG, causing a shift of the ODC to the left, but the reports are contradictory. Three groups were compared in the present study: 1) nondiabetic control individuals (N = 19); 2) insulin-dependent diabetes mellitus (IDDM) patients (on insulin treatment) (N = 19); 3) non-insulin-dependent diabetes mellitus (NIDDM) patients using oral hypoglycemic agents and no insulin treatment (N = 22). The overall position of the ODC was the same for the three groups despite an increase of the glycosylated hemoglobin fraction that was expected to shift the ODC to the left in both groups of diabetic patients (HbA1c: control, 4.6%; IDDM, 10.5%; NIDDM, 9.0%). In IDDM patients, the effect of the glycosylated hemoglobin fraction on the position of the ODC appeared to be counterbalanced by small though statistically significant increases in 2,3-DPG concentration from 2.05 (control) to 2.45 mol/ml blood (IDDM). Though not statistically significant, an increase of 2,3-DPG also occurred in NIDDM patients, while red cell ATP levels were the same for all groups. The positions of the ODC were the same for control subjects, IDDM and NIDDM patients. Thus, the PO2 at 50% hemoglobin-oxygen saturation was 26.8, 28.2 and 28.5 mmHg for control, IDDM and NIDDM, respectively. In conclusion, our data question the idea of adverse side effects of insulin treatment on oxygen transport. In other words, the shift to the left reported by others to be caused by insulin treatment was not detected.

  14. Decrease in the red cell cofactor 2,3-diphosphoglycerate increases hemoglobin oxygen affinity in the hibernating brown bear Ursus arctos.

    Science.gov (United States)

    Revsbech, Inge G; Malte, Hans; Fröbert, Ole; Evans, Alina; Blanc, Stéphane; Josefsson, Johan; Fago, Angela

    2013-01-01

    During winter hibernation, brown bears (Ursus arctos) reduce basal O(2) consumption rate to ∼25% compared with the active state, while body temperature decreases moderately (to ∼30°C), suggesting a temperature-independent component in their metabolic depression. To establish whether changes in O(2) consumption during hibernation correlate with changes in blood O(2) affinity, we took blood samples from the same six individuals of hibernating and nonhibernating free-ranging brown bears during winter and summer, respectively. A single hemoglobin (Hb) component was detected in all samples, indicating no switch in Hb synthesis. O(2) binding curves measured on red blood cell lysates at 30°C and 37°C showed a less temperature-sensitive O(2) affinity than in other vertebrates. Furthermore, hemolysates from hibernating bears consistently showed lower cooperativity and higher O(2) affinity than their summer counterparts, regardless of the temperature. We found that this increase in O(2) affinity was associated with a significant decrease in the red cell Hb-cofactor 2,3-diphosphoglycerate (DPG) during hibernation to approximately half of the summer value. Experiments performed on purified Hb, to which DPG had been added to match summer and winter levels, confirmed that the low DPG content was the cause of the left shift in the Hb-O(2) equilibrium curve during hibernation. Levels of plasma lactate indicated that glycolysis is not upregulated during hibernation and that metabolism is essentially aerobic. Calculations show that the increase in Hb-O(2) affinity and decrease in cooperativity resulting from decreased red cell DPG may be crucial in maintaining a fairly constant tissue oxygen tension during hibernation in vivo.

  15. Functional characterization of fetal and adult yak hemoglobins: an oxygen cascade and its molecular basis

    DEFF Research Database (Denmark)

    Weber, Roy E.; Braunitzer, Gerhard; Lalthantluanga, Ralte

    1988-01-01

    In contrast to most other mammals, the yak, which is native to high altitudes, has two major fetal and two or four major adult hemoglobin (Hb) components. We report the oxygen affinities and sensitivities to pH and 2,3-diphosphoglycerate of the two fetal and two adult Hbs commonly found in calves...

  16. Diffusion coefficients of oxygen and hemoglobin as obtained simultaneously from photometric determination of the oxygenation of layers of hemoglobin solutions

    NARCIS (Netherlands)

    Spaan, J. A.; Kreuzer, F.; van Wely, F. K.

    1980-01-01

    The oxygenation of layers of deoxygenated hemoglobin solutions after a sudden exposure to a gas containing oxygen at a partial pressure P1 has been studied by a photometric method. Layer thicknesses varied between 50 and 250 micron, hemoglobin concentrations between 0.1 and 0.34kg/l, and oxygen

  17. Interspecific variation and plasticity in hemoglobin nitrite reductase activity and its correlation with oxygen affinity in vertebrates

    DEFF Research Database (Denmark)

    Jensen, Frank B.; Kolind, Rasmus A. H.; Jensen, Natashia S.

    2017-01-01

    -dependent manner. The initial second order rate constant of the deoxyHb-mediated nitrite reduction showed a strong curvilinear correlation with oxygen affinity among all ectothermic vertebrates, and the relationship also applied to plastic variations of Hb properties via organic phosphates. The relationship...... determines oxygen affinity. In the present study we investigated nitrite reductase activity and O2 affinity in Hbs from ten different vertebrate species under identical conditions to disclose interspecific variations and allow an extended test for a correlation between the rate constant for nitrite reduction...... and O2 affinity. We also tested plastic changes in Hb properties via addition of T-structure-stabilizing organic phosphates (ATP and GTP). The decay in deoxyHb during its reaction with nitrite was exponential-like in ectotherms (Atlantic hagfish, carp, crucian carp, brown trout, rainbow trout, cane toad...

  18. Effect of altitude on oxygen binding by hemoglobin and on organic phosphate levels

    Science.gov (United States)

    Lenfant, Claude; Torrance, John; English, Eugenia; Finch, Clement A.; Reynafarje, Cesar; Ramos, Jose; Faura, Jose

    1968-01-01

    The relationship between oxygen dissociation and 2,3-diphosphoglycerate (2,3-DPG) in the red cell has been studied in subjects moving from low to high altitude and vice versa. Within 24 hr following the change in altitude there was a change in hemoglobin affinity for oxygen; this modification therefore represents an important rapid adaptive mechanism to anoxia. A parallel change occurred in the organic phosphate content of the red cell. While this study does not provide direct evidence of a cause-effect relationship, the data strongly suggest that with anoxia, the observed rise in organic phosphate content of the red cell is responsible for increased availability of oxygen to tissues. Images PMID:5725278

  19. The interaction of 2,3-diphosphoglycerate with various human hemoglobins

    Science.gov (United States)

    Bunn, H. Franklin; Briehl, Robin W.

    1970-01-01

    Oxygen equilibria were measured on a number of human hemoglobins, which had been “stripped” of organic phosphates and isolated by column chromatography. In the presence of 2 × 10-4 M 2,3-diphosphoglycerate (2,3-DPG), the P50 of hemoglobins A, A2, S, and C increased about twofold, signifying a substantial and equal decrease in oxygen affinity. Furthermore, hemoglobins Chesapeake and MMilwaukee-1 which have intrinsically high and low oxygen affinities, respectively, also showed a twofold increase in P50 in the presence of 2 × 10-4 M 2,3-DPG. In comparison to these, hemoglobins AIC and F were less reactive with 2,3-DPG while hemoglobin FI showed virtually no reactivity. The N-terminal amino of each β-chain of hemoglobin AIC is linked to a hexose. In hemoglobin FI the N-terminal amino of each γ-chain is acetylated. These results suggest that the N-terminal amino groups of the non-α-chains are involved in the binding of 2,3-DPG to hemoglobin. PMID:5422014

  20. Oxygen Measurements in Liposome Encapsulated Hemoglobin

    Science.gov (United States)

    Phiri, Joshua Benjamin

    Liposome encapsulated hemoglobins (LEH's) are of current interest as blood substitutes. An analytical methodology for rapid non-invasive measurements of oxygen in artificial oxygen carriers is examined. High resolution optical absorption spectra are calculated by means of a one dimensional diffusion approximation. The encapsulated hemoglobin is prepared from fresh defibrinated bovine blood. Liposomes are prepared from hydrogenated soy phosphatidylcholine (HSPC), cholesterol and dicetylphosphate using a bath sonication method. An integrating sphere spectrophotometer is employed for diffuse optics measurements. Data is collected using an automated data acquisition system employing lock-in -amplifiers. The concentrations of hemoglobin derivatives are evaluated from the corresponding extinction coefficients using a numerical technique of singular value decomposition, and verification of the results is done using Monte Carlo simulations. In situ measurements are required for the determination of hemoglobin derivatives because most encapsulation methods invariably lead to the formation of methemoglobin, a nonfunctional form of hemoglobin. The methods employed in this work lead to high resolution absorption spectra of oxyhemoglobin and other derivatives in red blood cells and liposome encapsulated hemoglobin (LEH). The analysis using singular value decomposition method offers a quantitative means of calculating the fractions of oxyhemoglobin and other hemoglobin derivatives in LEH samples. The analytical methods developed in this work will become even more useful when production of LEH as a blood substitute is scaled up to large volumes.

  1. In vivo integrated photoacoustic and confocal microscopy of hemoglobin oxygen saturation and oxygen partial pressure.

    Science.gov (United States)

    Wang, Yu; Hu, Song; Maslov, Konstantin; Zhang, Yu; Xia, Younan; Wang, Lihong V

    2011-04-01

    We developed dual-modality microscope integrating photoacoustic microscopy (PAM) and fluorescence confocal microscopy (FCM) to noninvasively image hemoglobin oxygen saturation (sO₂) and oxygen partial pressure (pO₂) in vivo in single blood vessels with high spatial resolution. While PAM measures sO₂ by imaging hemoglobin optical absorption at two wavelengths, FCM quantifies pO₂ using phosphorescence quenching. The variations of sO₂ and pO₂ values in multiple orders of vessel branches under hyperoxic (100% oxygen) and normoxic (21% oxygen) conditions correlate well with the oxygen-hemoglobin dissociation curve. In addition, the total concentration of hemoglobin is imaged by PAM at an isosbestic wavelength.

  2. Temperature-dependent enthalpy of oxygenation in Antarctic fish hemoglobins

    DEFF Research Database (Denmark)

    Fago, A.; Wells, R.M.G.; Weber, Roy E.

    1997-01-01

    The effect of temperature on the oxygen-binding properties of the hemoglobins of three cold-adapted Antarctic fish species, Dissostichus mawsoni, Pagothenia borchgrevinki and Trematomus, sp., has been investigated under different pH values and buffer conditions. A clear non linear van't Hoff plot...... (logP(50) vs 1/T) of D. mawsoni hemoglobin indicates that the enthalpy of oxygenation (slope of the plot) is temperature dependent and that at high temperatures oxygen-binding becomes less exothermic. Nearly linear relationships were found in the hemoglobins of the other two species. The data were...... oxygen binding. The degree of the temperature dependence of the heat of oxygenation observed in these hemoglobins seems to reflect the differences in their allosteric effects rather than a specific molecular adaptation to low temperatures. Moreover, this study indicates that the disagreement between...

  3. Hemoglobin Function in Stored Blood.

    Science.gov (United States)

    1974-08-01

    States during 1973. Several advantages over ACA) are important. Blood stored in CPD maintains higher ./ levels of 2,3-DPG (2,3- diphosphoglycerate ) and a...survival and ATP levels in stored blood is explained by the several functions of ATP which are necessary for cell viability. However, ATP levels do...not correlate with oxygen affinity during storage. Levels of 2,3-DPG determine oxygen affinity and thus hemoglobin function. (12,13) When normal levels

  4. Role of β/δ101Gln in Regulating the Effect of Temperature and Allosteric Effectors on Oxygen Affinity in Woolly Mammoth Hemoglobin†

    Science.gov (United States)

    Yuan, Yue; Byrd, Catherine; Shen, Tong-Jian; Simplaceanu, Virgil; Tam, Tsuey Chyi S.; Ho, Chien

    2013-01-01

    The oxygen affinity of woolly mammoth hemoglobin (rHb WM) is less affected by temperature change than that of Asian elephant hemoglobin (rHb AE) or human adult hemoglobin (Hb A). We report here a biochemical-biophysical study of Hb A, rHb AE, rHb WM and three rHb WM mutants with amino acid substitutions at β/δ101 (β/δ101Gln→Glu, Lys, or Asp) plus a double and a triple mutant, designed to clarify the role of the β/δ101 residue. The β/δ101Gln residue is important for responding to allosteric effectors, such as phosphate, inositol hexaphosphate (IHP), and chloride. The rHb WM mutants studied generally have higher affinity for oxygen under various conditions of pH, temperature, and salt concentration, and in the presence or absence of organic phosphate, than do rHb WM, rHb AE and Hb A. Titrations for the O2 affinity of these mutant rHbs as a function of chloride concentration indicate a lower heterotopic effect of this anion due to the replacement of β/δ101Gln in rHb WM. The alkaline Bohr effect of rHb WM and its mutants is reduced by 20–50% compared to that of Hb A and is independent of changes in temperature, in contrast to what has been observed in the hemoglobins of most mammalian species, including human. The results of our study on the temperature dependence of the O2 affinity of rHb WM and its mutant rHbs illustrate the important role of β/δ101Gln in regulating the functional properties of these hemoglobins. PMID:24228693

  5. Oxygenation properties and isoform diversity of snake hemoglobins.

    Science.gov (United States)

    Storz, Jay F; Natarajan, Chandrasekhar; Moriyama, Hideaki; Hoffmann, Federico G; Wang, Tobias; Fago, Angela; Malte, Hans; Overgaard, Johannes; Weber, Roy E

    2015-11-01

    Available data suggest that snake hemoglobins (Hbs) are characterized by a combination of unusual structural and functional properties relative to the Hbs of other amniote vertebrates, including oxygenation-linked tetramer-dimer dissociation. However, standardized comparative data are lacking for snake Hbs, and the Hb isoform composition of snake red blood cells has not been systematically characterized. Here we present the results of an integrated analysis of snake Hbs and the underlying α- and β-type globin genes to characterize 1) Hb isoform composition of definitive erythrocytes, and 2) the oxygenation properties of isolated isoforms as well as composite hemolysates. We used species from three families as subjects for experimental studies of Hb function: South American rattlesnake, Crotalus durissus (Viperidae); Indian python, Python molurus (Pythonidae); and yellow-bellied sea snake, Pelamis platura (Elapidae). We analyzed allosteric properties of snake Hbs in terms of the Monod-Wyman-Changeux model and Adair four-step thermodynamic model. Hbs from each of the three species exhibited high intrinsic O2 affinities, low cooperativities, small Bohr factors in the absence of phosphates, and high sensitivities to ATP. Oxygenation properties of the snake Hbs could be explained entirely by allosteric transitions in the quaternary structure of intact tetramers, suggesting that ligation-dependent dissociation of Hb tetramers into αβ-dimers is not a universal feature of snake Hbs. Surprisingly, the major Hb isoform of the South American rattlesnake is homologous to the minor HbD of other amniotes and, contrary to the pattern of Hb isoform differentiation in birds and turtles, exhibits a lower O2 affinity than the HbA isoform. Copyright © 2015 the American Physiological Society.

  6. Hb San Cataldo [β144(HC1)Lys→Thr; HBB: C.434A > C]: A New Hemoglobin Variant with Increased Affinity for Oxygen.

    Science.gov (United States)

    Vinciguerra, Margherita; Passarello, Cristina; Cassarà, Filippo; Leto, Filippo; Cannata, Monica; Crivello, Anna; Di Salvo, Veronica; Maggio, Aurelio; Giambona, Antonino

    2016-08-01

    A 59-year-old Italian woman came to our center for revaluation of a previous diagnosis of polycythemia vera. The patient presented with a lifelong history of polycythemia, no increase in white blood cells (WBCs) and platelets, and a negative bone marrow biopsy. Analysis of hemoglobin (Hb) fractions showed an abnormal fast moving Hb component. We aimed to determine if this variant was the cause of polycythemia in this patient. A complete blood count (CBC) was performed by an automated cell counter and Hb fractions were determined by high performance liquid chromatography (HPLC). Standard stability tests and oxygen affinity evaluation were also performed. Genomic DNA was extracted from peripheral blood leukocytes using the phenol chloroform method and the entire β-globin gene was analyzed by direct sequencing. At the hematological level, no anemia or hemolysis was observed but an abnormal Hb fraction was detected using cation exchange HPLC. Molecular analysis of the β-globin gene showed heterozygosity for an AAG > ACG substitution at codon 144, resulting in a Lys→Thr amino acid replacement. We demonstrated that this is a new Hb variant with increased oxygen affinity. Its altered physiology is caused by the reduction of 2,3-diphosphoglycerate (2,3-DPG) effects, due to an amino acid substitution in the central pocket near the C-terminal of the β chain. We called this new variant Hb San Cataldo for the native city of proband.

  7. Oxygen binding to partially nitrosylated hemoglobin.

    Science.gov (United States)

    Fago, Angela; Crumbliss, Alvin L; Hendrich, Michael P; Pearce, Linda L; Peterson, Jim; Henkens, Robert; Bonaventura, Celia

    2013-09-01

    Reactions of nitric oxide (NO) with hemoglobin (Hb) are important elements in protection against nitrosative damage. NO in the vasculature is depleted by the oxidative reaction with oxy Hb or by binding to deoxy Hb to generate partially nitrosylated Hb (Hb-NO). Many aspects of the formation and persistence of Hb-NO are yet to be clarified. In this study, we used a combination of EPR and visible absorption spectroscopy to investigate the interactions of partially nitrosylated Hb with O2. Partially nitrosylated Hb samples had predominantly hexacoordinate NO-heme geometry and resisted oxidation when exposed to O2 in the absence of anionic allosteric effectors. Faster oxidation occurred in the presence of 2,3-diphosphoglycerate (DPG) or inositol hexaphosphate (IHP), where the NO-heme derivatives had higher levels of pentacoordinate heme geometry. The anion-dependence of the NO-heme geometry also affected O2 binding equilibria. O2-binding curves of partially nitrosylated Hb in the absence of anions were left-shifted at low saturations, indicating destabilization of the low O2 affinity T-state of the Hb by increasing percentages of NO-heme, much as occurs with increasing levels of CO-heme. Samples containing IHP showed small decreases in O2 affinity, indicating shifts toward the low-affinity T-state and formation of inert α-NO/β-met tetramers. Most remarkably, O2-equilibria in the presence of the physiological effector DPG were essentially unchanged by up to 30% NO-heme in the samples. As will be discussed, under physiological conditions the interactions of Hb with NO provide protection against nitrosative damage without impairing O2 transport by Hb's unoccupied heme sites. This article is part of a Special Issue entitled: Oxygen Binding and Sensing Proteins. Copyright © 2013 Elsevier B.V. All rights reserved.

  8. TECHNIQUES OF EVALUATION OF HEMOGLOBIN OXYGEN SATURATION IN CLINICAL OPHTHALMOLOGY

    Directory of Open Access Journals (Sweden)

    S. Yu. Petrov

    2016-01-01

    Full Text Available Oxygen content in body fluids and tissues is an important indicator of life support functions. A number of ocular pathologies, e.g. glaucoma, are of presumable vascular origin which means altered blood supply and oxygen circulation. Most oxygen is transported in the blood in the association with hemoglobin. When passing through the capillaries, hemoglobin releases oxygen, converting from oxygenated form to deoxygenated form. This process is accompanied by the changes in spectral characteristics of hemoglobin which result in different colors of arterial and venous blood. Photometric technique for the measurement of oxygen saturation in blood is based on the differences in light absorption by different forms of hemoglobin. The measurement of saturation is called oximetry. Pulse oximetry with assessment of tissue oxygenation is the most commonly used method in medicine. The degree of hemoglobin oxygen saturation in the eye blood vessels is the most accessible for noninvasive studies during ophthalmoscopy and informative. Numerous studies showed the importance of this parameter for the diagnosis of retinopathy of various genesis, metabolic status analysis in hyperglycemia, diagnosis and control of treatment of glaucoma and other diseases involving alterations in eye blood supply. The specific method for evaluation of oxygen concentration is the measurement of pressure of oxygen dissolved in the blood, i.e. partial pressure of oxygen. In ophthalmological practice, this parameter is measured in anterior chamber fluid evaluating oxygen level for several ophthalmopathies including different forms of glaucoma, for instillations of hypotensive eye drops as well as in vitreous body near to the optic disc under various levels of intraocular pressure. Currently, monitoring of oxygen saturation in retinal blood vessels, i.e. retinal oximetry, is well developed. This technique is based on the assessment of light absorption by blood depending on

  9. Hemoglobin Kansas found by electrophoretic diagnosis in Brazil Hemoglobina Kansas diagnosticada através de eletroforese no Brasil

    Directory of Open Access Journals (Sweden)

    Claudia R. Bonini-Domingos

    2002-03-01

    Full Text Available Some hemoglobin variants with abnormal oxygen affinity have been reported so far from various regions of the world. They can be classified by their oxygen affinity and 15 variants with low oxygen affinity have been reported. A number of hemoglobin mutants which show an abnormal affinity for oxygen have been reported, but only few cases of hemoglobin Kansas. All cases reported so far are from Japan or in Japanese families. In this paper we describe a Brazilian patient with cyanosis and hemoglobin Kansas diagnosed by an electrophoretical procedure.Hemoglobinas variantes com afinidade anormal ao oxigênio têm sido encontradas em várias partes do mundo. Pela sua afinidade ao oxigênio, estas hemoglobinas variantes têm sido classificadas e 15 variantes com baixa afinidade relatadas. Numerosas hemoglobinas mutantes com afinidade anormal têm também sido relatadas, mas somente poucos casos de Hemoglobina Kansas. Os casos são de pacientes procedentes do Japão, ou de famílias com descendentes japoneses. Neste relato descrevemos um paciente com manifestações de cianose que teve o seu diagnóstico confirmado através da eletroforese.

  10. Genetically based low oxygen affinities of felid hemoglobins: lack of biochemical adaptation to high-altitude hypoxia in the snow leopard

    Science.gov (United States)

    Janecka, Jan E.; Nielsen, Simone S. E.; Andersen, Sidsel D.; Hoffmann, Federico G.; Weber, Roy E.; Anderson, Trevor; Storz, Jay F.; Fago, Angela

    2015-01-01

    ABSTRACT Genetically based modifications of hemoglobin (Hb) function that increase blood–O2 affinity are hallmarks of hypoxia adaptation in vertebrates. Among mammals, felid Hbs are unusual in that they have low intrinsic O2 affinities and reduced sensitivities to the allosteric cofactor 2,3-diphosphoglycerate (DPG). This combination of features compromises the acclimatization capacity of blood–O2 affinity and has led to the hypothesis that felids have a restricted physiological niche breadth relative to other mammals. In seeming defiance of this conjecture, the snow leopard (Panthera uncia) has an extraordinarily broad elevational distribution and occurs at elevations above 6000 m in the Himalayas. Here, we characterized structural and functional variation of big cat Hbs and investigated molecular mechanisms of Hb adaptation and allosteric regulation that may contribute to the extreme hypoxia tolerance of the snow leopard. Experiments revealed that purified Hbs from snow leopard and African lion exhibited equally low O2 affinities and DPG sensitivities. Both properties are primarily attributable to a single amino acid substitution, β2His→Phe, which occurred in the common ancestor of Felidae. Given the low O2 affinity and reduced regulatory capacity of feline Hbs, the extreme hypoxia tolerance of snow leopards must be attributable to compensatory modifications of other steps in the O2-transport pathway. PMID:26246610

  11. Correlation between Oxygen Saturation and Hemoglobin and Hematokrit Levels in Tetralogy of Fallot Patients

    Directory of Open Access Journals (Sweden)

    Farhatul Inayah Adiputri

    2016-03-01

    Full Text Available Background: Hemoglobin and hematocrit levels increase in Tetralogy of Fallot (TOF but the oxygen saturation declines. Reduced hemoglobin in circulating blood as a parameter of cyanosis does not indicate rising hemoglobin due to the ‘not-working’ hemoglobins that affect the oxygen saturation. Increasing hematocrit is the result of secondary erythrocytosis caused by declining oxygen level in blood, which is related to the oxygen saturation. This study was conducted to find the correlation between oxygen saturation and hemoglobin and hematocrite levels in TOF patients. Methods: This study was undertaken at Dr. Hasan Sadikin General Hospital in the period of January 2011 to December 2012 using the cross-sectional analytic method with total sampling technique. Inclusion criteria were medical records of TOF patients diagnosed based on echocardiography that included data on oxygen saturation, hemoglobin, and hematocrite. Exclusion criteria was the history of red blood transfusion. Results: Thirty medical records of TOF patiens from Dr. Hasan Sadikin General Hospital Bandung were included in this study. Due to skewed data distribution, Spearman correlation test was used to analyze the data. There was a significant negative correlation between oxygen saturation and hematocrit level (r= -0.412; p=0.024 and insignificant correlation between oxygen saturation and hemoglobin (r=-0.329; p= 0.076. Conclusions: There is a weak negative correlation between oxygen saturation and hematocrite levels

  12. A new β chain hemoglobin variant with increased oxygen affinity: Hb Santa Giusta Sardegna [β93(F9)Cys→Trp; HBB c.282T>G].

    Science.gov (United States)

    Fais, Antonella; Sollaino, Maria Carla; Barella, Susanna; Perseu, Lucia; Era, Benedetta; Corda, Marcella

    2012-01-01

    During a screening program for the identification of β-thalassemia (β-thal) carriers in Sardinia, Italy, we identified two subjects with increased hemoglobin (Hb) levels and an abnormal Hb variant. The same variant was detected in a family member. DNA sequencing revealed a TGT > TGG mutation at codon 93 of the β-globin gene. Structural analysis demonstrated that the cystine residue at position 93 of the β chain was substituted by tryptophan. Since this amino acid substitution had not yet been reported, we designated this variant Hb Santa Giusta Sardegna for the place of birth of the subjects. This amino acid substitution occurs at the tyrosine pocket of the β chain as well as at the α1β2/α2β1 contact of the quaternary structure of the molecule. The presence of this Hb in the hemolysate causes an increased oxygen affinity, a slightly reduced Bohr effect and a reduced heme-heme interaction (n(50), Hill's constant) in comparison with those of Hb A.

  13. Evidence that the low-affinity folate-binding protein in erythrocyte hemolysate is identical to hemoglobin

    International Nuclear Information System (INIS)

    Hansen, S.I.; Holm, J.; Lyngbye, J.

    1981-01-01

    Gel filtration studies on erythrocyte hemolysate demonstrated the presence of a folate binding protein, apparently of the low-affinity type, that co-elutes with hemoglobin. Further, the folate binder eluted with a low salt concentration after DEAE-Sepharose CL-6B anion-exchange chromatography of erythrocyte hemolysate at pH 6.3. The chromatographic behavior of hemoglobin labeled with [3H]folate was so similar to that of the present binder as to suggest that the folate binder in erythrocytes is in fact hemoglobin

  14. Respiratory adaptations in carp blood. Influences of hypoxia, red cell organic phosphates, divalent cations and CO2 on hemoglobin-oxygen affinity

    DEFF Research Database (Denmark)

    Weber, Roy E.; Lykkeboe, G.

    1978-01-01

    This study concerns the adaptation of oxygen transporting function of carp blood to environment hypoxia, tracing the roles played by erythrocytic cofactors, inorganic cations, carbon dioxide and hemoglobin multiplicity. Carp acclimated to hypoxia ( 30 mmHg) display striking increases in blood oxy...

  15. Correlation of Oxygenated Hemoglobin Concentration and Psychophysical Amount on Speech Recognition

    Science.gov (United States)

    Nozawa, Akio; Ide, Hideto

    The subjective understanding on oral language understanding task is quantitatively evaluated by the fluctuation of oxygenated hemoglobin concentration measured by the near-infrared spectroscopy. The English listening comprehension test wihch consists of two difficulty level was executed by 4 subjects during the measurement. A significant correlation was found between the subjective understanding and the fluctuation of oxygenated hemoglobin concentration.

  16. Effects of whole-body gamma irradiation on oxygen transport by rat erythrocytes

    International Nuclear Information System (INIS)

    Thiriot, Christian; Kergonou, J.F.; Rocquet, Guy; Allary, Michel; Saint-Blancard, Jacques

    1982-01-01

    In this work, we studied the influence of whole-body gamma irradiation (8 Gy) upon oxygen transport by erythrocytes, through the erythrocyte count and related parameters, and through the factors affecting the oxygen affinity of hemoglobin. The oxygen affinity of hemoglobin is increased from day D + 5 after irradiation, and a severe erythropenia develops from day D + 8. These modifications probably result in tissue hypoxia via diminished oxygen transport from lungs to tissues, and decreased oxygen release from oxyhemoglobin in tissues

  17. The tyrosine B10 hydroxyl is crucial for oxygen avidity of Ascaris hemoglobin.

    Science.gov (United States)

    Kloek, A P; Yang, J; Mathews, F S; Frieden, C; Goldberg, D E

    1994-01-28

    The parasitic nematode Ascaris suum has a gene encoding a two-domain hemoglobin with remarkable oxygen avidity. The strong interaction with oxygen is a consequence of a particularly slow oxygen off-rate. The single polypeptide chain consists of two domains, each of which can be expressed separately in Escherichia coli as a globin-like protein exhibiting oxygen binding characteristics comparable with the native molecule. Site-directed mutagenesis was performed on the gene segment encoding domain one. The E7 position, involved in forming a hydrogen bond with the liganded oxygen in vertebrate globins, is a glutamine in both Ascaris domains. Conversion of this residue to leucine or alanine produced a hemoglobin variant with an oxygen off-rate 5- or 60-fold faster than that of unaltered domain one. Replacement of the tyrosine B10 with either phenylalanine or leucine (as found in vertebrate globins) yielded hemoglobin mutants with oxygen off-rates 280- or 570-fold faster, approaching rates found with vertebrate myoglobins. The data suggest that the distal glutamine hydrogen bonds with the liganded oxygen and that the tyrosine B10 hydroxyl contributes an additional hydrogen bond that appears substantially responsible for the extreme oxygen avidity of Ascaris hemoglobin.

  18. Effect of laser radiation on physicochemical and functional properties of human hemoglobin in vitro

    NARCIS (Netherlands)

    Irzhak, LI; Zotova, EA; Mamaeva, SA

    Exposure to laser radiation increases pH and isoelectric point of human hemoglobin solution, improves the acid-base properties, increases affinity for oxygen, and decreases the Bohr effect in comparison with intact hemoglobin. The mechanisms underlying these changes are discussed.

  19. Detection of anion-linked polymerization of the tetrameric hemoglobin from Scapharca inaequivalvis by 35Cl NMR spectroscopy

    International Nuclear Information System (INIS)

    Chiancone, E.; Univ. 'La Sapienza', Rome; Drakenberg, T.; Forsen, S.

    1988-01-01

    Ion binding to the hemoglobin components of Scaphara inaequivalvis has been measured directly in quadrupole relaxation experiments of 23 Na and 35 Cl. The dimeric and tetrameric hemoglobins interact weakly with sodium ions, but differ in their interaction with chloride ions. The dimeric hemoglobin binds chloride ions with low affinity, whereas the tetrameric protein has high affinity chloride binding sites. Binding of chloride ions to these high affinity sites brings about an oxygen-linked polymerization which manifests itself in an unusual dependence of the 35 Cl excess linewidth on the concentration of the anion. Polymerization is more pronounced in the deoxygenated than in the oxygenated derivative: in the former, it has been observed previously in sedimentation velocity experiments. The sensitivity of the 35 Cl excess linewidth on polymer formation indicates that the residence time of the transiently bound chloride on the tetrameric hemoglobin is not shorter than the correlation time of the molecule (2 X 10 -8 s -1 ). 17 refs.; 2 figs

  20. Aryloxyalkanoic Acids as Non-Covalent Modifiers of the Allosteric Properties of Hemoglobin

    Directory of Open Access Journals (Sweden)

    Abdelsattar M. Omar

    2016-08-01

    Full Text Available Hemoglobin (Hb modifiers that stereospecifically inhibit sickle hemoglobin polymer formation and/or allosterically increase Hb affinity for oxygen have been shown to prevent the primary pathophysiology of sickle cell disease (SCD, specifically, Hb polymerization and red blood cell sickling. Several such compounds are currently being clinically studied for the treatment of SCD. Based on the previously reported non-covalent Hb binding characteristics of substituted aryloxyalkanoic acids that exhibited antisickling properties, we designed, synthesized and evaluated 18 new compounds (KAUS II series for enhanced antisickling activities. Surprisingly, select test compounds showed no antisickling effects or promoted erythrocyte sickling. Additionally, the compounds showed no significant effect on Hb oxygen affinity (or in some cases, even decreased the affinity for oxygen. The X-ray structure of deoxygenated Hb in complex with a prototype compound, KAUS-23, revealed that the effector bound in the central water cavity of the protein, providing atomic level explanations for the observed functional and biological activities. Although the structural modification did not lead to the anticipated biological effects, the findings provide important direction for designing candidate antisickling agents, as well as a framework for novel Hb allosteric effectors that conversely, decrease the protein affinity for oxygen for potential therapeutic use for hypoxic- and/or ischemic-related diseases.

  1. Monitor hemoglobin concentration and oxygen saturation in living mouse tail using photoacoustic CT scanner

    Science.gov (United States)

    Liu, Bo; Kruger, Robert; Reinecke, Daniel; Stantz, Keith M.

    2010-02-01

    Purpose: The purpose of this study is to use PCT spectroscopy scanner to monitor the hemoglobin concentration and oxygen saturation change of living mouse by imaging the artery and veins in a mouse tail. Materials and Methods: One mouse tail was scanned using the PCT small animal scanner at the isosbestic wavelength (796nm) to obtain its hemoglobin concentration. Immediately after the scan, the mouse was euthanized and its blood was extracted from the heart. The true hemoglobin concentration was measured using a co-oximeter. Reconstruction correction algorithm to compensate the acoustic signal loss due to the existence of bone structure in the mouse tail was developed. After the correction, the hemoglobin concentration was calculated from the PCT images and compared with co-oximeter result. Next, one mouse were immobilized in the PCT scanner. Gas with different concentrations of oxygen was given to mouse to change the oxygen saturation. PCT tail vessel spectroscopy scans were performed 15 minutes after the introduction of gas. The oxygen saturation values were then calculated to monitor the oxygen saturation change of mouse. Results: The systematic error for hemoglobin concentration measurement was less than 5% based on preliminary analysis. Same correction technique was used for oxygen saturation calculation. After correction, the oxygen saturation level change matches the oxygen volume ratio change of the introduced gas. Conclusion: This living mouse tail experiment has shown that NIR PCT-spectroscopy can be used to monitor the oxygen saturation status in living small animals.

  2. Studies on radiation induced changes in bovine hemoglobin type A

    International Nuclear Information System (INIS)

    Wdzieczak, J.; Duda, W.; Leyko, W.

    1978-01-01

    In this paper the structural and functional changes of gamma irradiated bovine hemoglobin are presented. Aqueous solutions/1%/of HbO 2 were irradiated in air with doses ranging from 1 to 4 Mrad. Isoelectric focusing indicated change of the charge of irradiated hemoglobin. The isoelectric point of hemoglobin was displaced towards more acid values with increasing doses, up from 1 Mrad. Fingerprint analysis and peptide column chromatography of irradiated hemoglobin demonstrated disturbances increasing with the dose. These changes were confirmed by amino acid analysis which showed that Cys, Met, Trp, His, Pro and Tyr residues were destroyed or modified following irradiation. At doses exceeding 1 Mrad the irradiated solutions of hemoglobin showed a decrease of heme-heme interaction and an increase of affinity for oxygen. Differences observed in oxygen-dissociation curves seem to be correlated with the radiation induced destruction of amino acid residues which are responsible for the functional properties of hemoglobin. (auth.)

  3. The unique hemoglobin system of Pleuragramma antarcticum, an antarctic migratory teleost. Structure and function of the three components.

    Science.gov (United States)

    Tamburrini, M; D'Avino, R; Fago, A; Carratore, V; Kunzmann, A; Prisco, G

    1996-09-27

    Pleuragramma antarcticum (suborder Notothenioidei, family Nototheniidae) is the most abundant fish in the antarctic shelf. This pelagic species has a circum-antarctic distribution and is characterized by spawning migration. This species displays the highest multiplicity of major hemoglobins (three); the other notothenioids have a single one (except one species, having two) with relatively low oxygen affinity regulated by pH and organophosphates. The hemoglobins of P. antarcticum display strong Bohr and Root effects; however, they reveal important functional differences in subunit cooperativity and organophosphate regulation and, above all, in the response of oxygenation to temperature. Despite the substitution ValbetaE11 --> Ile found in Hb 2, which decreases the affinity in human mutants, the hemoglobins have similar oxygen affinity, higher than that of the other notothenioids. Hb 1 has the alpha chain in common with Hb 2 and the beta in common with Hb 3. The amino acid sequence of all four chains has been established. Thus the hematological features of P. antarcticum differ remarkably from those of antarctic notothenioids. This unique and sophisticated oxygen transport system may adequately meet the requirements of the unusual mode of life of this fish.

  4. Respiratory properties of blood and hemoglobin solutions from the piranha

    DEFF Research Database (Denmark)

    Wood, S.C.; Weber, Roy E.; Powers, D.

    1979-01-01

    1. Respiratory properties of piranha blood are distinguished from those of other fish primarily by the high CO2 buffering capacity (?HCO3/-?pH= 19.6mmol/l for oxygenated blood and 39.1 mmol/l for deoxygenated blood). 2. The concentration of nucleoside triphosphates (NTP) and the half-saturation t......) lowered the oxygen affinity of purified hemoglobin solutions, accounting for the size-dependent correlation ofP50 and NTP concentration in whole blood. 5. While similar in concentration in red cells, GTP is more potent than ATP as an allosteric modifier of hemoglobin function....

  5. Convergent evolution of hemoglobin switching in jawed and jawless vertebrates.

    Science.gov (United States)

    Rohlfing, Kim; Stuhlmann, Friederike; Docker, Margaret F; Burmester, Thorsten

    2016-02-01

    During development, humans and other jawed vertebrates (Gnathostomata) express distinct hemoglobin genes, resulting in different hemoglobin tetramers. Embryonic and fetal hemoglobin have higher oxygen affinities than the adult hemoglobin, sustaining the oxygen demand of the developing organism. Little is known about the expression of hemoglobins during development of jawless vertebrates (Agnatha). We identified three hemoglobin switches in the life cycle of the sea lamprey. Three hemoglobin genes are specifically expressed in the embryo, four genes in the filter feeding larva (ammocoete), and nine genes correspond to the adult hemoglobin chains. During the development from the parasitic to the reproductive adult, the composition of hemoglobin changes again, with a massive increase of chain aHb1. A single hemoglobin chain is expressed constitutively in all stages. We further showed the differential expression of other globin genes: Myoglobin 1 is most highly expressed in the reproductive adult, myoglobin 2 expression peaks in the larva. Globin X1 is restricted to the embryo; globin X2 was only found in the reproductive adult. Cytoglobin is expressed at low levels throughout the life cycle. Because the hemoglobins of jawed and jawless vertebrates evolved independently from a common globin ancestor, hemoglobin switching must also have evolved convergently in these taxa. Notably, the ontogeny of sea lamprey hemoglobins essentially recapitulates their phylogeny, with the embryonic hemoglobins emerging first, followed by the evolution of larval and adult hemoglobins.

  6. Using the MWC model to describe heterotropic interactions in hemoglobin

    Science.gov (United States)

    Rapp, Olga

    2017-01-01

    Hemoglobin is a classical model allosteric protein. Research on hemoglobin parallels the development of key cooperativity and allostery concepts, such as the ‘all-or-none’ Hill formalism, the stepwise Adair binding formulation and the concerted Monod-Wymann-Changuex (MWC) allosteric model. While it is clear that the MWC model adequately describes the cooperative binding of oxygen to hemoglobin, rationalizing the effects of H+, CO2 or organophosphate ligands on hemoglobin-oxygen saturation using the same model remains controversial. According to the MWC model, allosteric ligands exert their effect on protein function by modulating the quaternary conformational transition of the protein. However, data fitting analysis of hemoglobin oxygen saturation curves in the presence or absence of inhibitory ligands persistently revealed effects on both relative oxygen affinity (c) and conformational changes (L), elementary MWC parameters. The recent realization that data fitting analysis using the traditional MWC model equation may not provide reliable estimates for L and c thus calls for a re-examination of previous data using alternative fitting strategies. In the current manuscript, we present two simple strategies for obtaining reliable estimates for MWC mechanistic parameters of hemoglobin steady-state saturation curves in cases of both evolutionary and physiological variations. Our results suggest that the simple MWC model provides a reasonable description that can also account for heterotropic interactions in hemoglobin. The results, moreover, offer a general roadmap for successful data fitting analysis using the MWC model. PMID:28793329

  7. Possible heterogeneity of centres of binding 1,8-ANS in molecules of oxygenated hemoglobin

    International Nuclear Information System (INIS)

    Parul', D.A.; Bokut', S.B.; Milyutin, A.A.; Petrov, E.P.; Nemkovich, N.A.; Sobchuk, A.N.; Dzhagarov, B.M.

    1999-01-01

    Forming of oxygenated hemoglobin is one of effects of ionizing radiation action on organism. It was revealed heterogeneity of centers of binding of 1,8-ANS in intact molecule of oxygenated hemoglobin. Two types of binding centers possible reflect the existence of two regions in protein molecule with different accessibility to molecules of water

  8. EPR study of manganese(II) binding to 55'-ATP, hemoglobin, and hemocyanin

    Energy Technology Data Exchange (ETDEWEB)

    Chang, S.S. (Duquesne Univ., Pittsburgh); Li, N.C.; Pratt, D.W.

    1975-01-01

    Several divalent metal ions affect the oxygen affinity of hemoglobin and hemocyanin. It is important, therefore, to understand the nature of metal-ion binding to these proteins. By comparing the EPR spectra of Mn(II), 0.001 M, in the absence and presence of carboxyhemoglobin or Limulus oxyhemocyanin (pH 7.3, Trizma buffer), the number of Mn binding sites, n, and the binding constant, K, can be determined. For carboxyhemoglobin, HbCO, we find 0.5 Mn binding sites per heme, K = 450 M/sup -1/. Each hemoglobin tetramer therefore binds two manganous ions suggesting that Mn(II), like Cu(II), may bind preferentially to one of the two types of subunits in hemoglobin. For hemocyanin, HcO/sub 2/, we find n = 5.8, K = 1.55 x 10/sup 3/ M/sup -1/. Each oxyhemocyanine therefore binds approximately six manganous ions, and the binding constant is three times larger than that for HbCO. We have also carried out similar experiments on 5'-ATP, and on solutions of HbCO and ATP containing McCl/sub 2/ or ZnCl/sub 2/. Zn(II) effectively competes with Mn(II) in binding hemoglobin and ATP, whereas Mg(II) does not, in accord with expectations from data on oxygen affinity of hemoglobin. (auth)

  9. Asthma and hemoglobinopathy: when is supplemental oxygen required?

    Science.gov (United States)

    Joseph, Leon; Brickner-Braun, Inbal; Pinshow, Berry; Goldberg, Shmuel; Miskin, Hagit; Picard, Elie

    2013-10-01

    Asthma is the most common reason for referral to the emergency department in childhood. In severe attacks, supplemental O2 is given when oxygen saturation level is asthma attack. Simultaneously, P(a)O2 was normal. A diagnosis of abnormal hemoglobin with decreased oxygen affinity (hemoglobin Seattle) was made on hemoglobin electrophoresis and genetic analysis. To ascertain when supplemental oxygen was needed, an oxygen dissociation curve was plotted using the tonometer technique, and it was found that an S(p)O2 of 70% is parallel to a P(a)O2 of 60 mmHg. Plotting an oxygen dissociation curve is a simple reproducible method to determine when supplemental oxygen is required for a child with a hemoglobinopathy. © 2013 The Authors. Pediatrics International © 2013 Japan Pediatric Society.

  10. Myoglobin oxygen affinity in aquatic and terrestrial birds and mammals.

    Science.gov (United States)

    Wright, Traver J; Davis, Randall W

    2015-07-01

    Myoglobin (Mb) is an oxygen binding protein found in vertebrate skeletal muscle, where it facilitates intracellular transport and storage of oxygen. This protein has evolved to suit unique physiological needs in the muscle of diving vertebrates that express Mb at much greater concentrations than their terrestrial counterparts. In this study, we characterized Mb oxygen affinity (P50) from 25 species of aquatic and terrestrial birds and mammals. Among diving species, we tested for correlations between Mb P50 and routine dive duration. Across all species examined, Mb P50 ranged from 2.40 to 4.85 mmHg. The mean P50 of Mb from terrestrial ungulates was 3.72±0.15 mmHg (range 3.70-3.74 mmHg). The P50 of cetaceans was similar to terrestrial ungulates ranging from 3.54 to 3.82 mmHg, with the exception of the melon-headed whale, which had a significantly higher P50 of 4.85 mmHg. Among pinnipeds, the P50 ranged from 3.23 to 3.81 mmHg and showed a trend for higher oxygen affinity in species with longer dive durations. Among diving birds, the P50 ranged from 2.40 to 3.36 mmHg and also showed a trend of higher affinities in species with longer dive durations. In pinnipeds and birds, low Mb P50 was associated with species whose muscles are metabolically active under hypoxic conditions associated with aerobic dives. Given the broad range of potential globin oxygen affinities, Mb P50 from diverse vertebrate species appears constrained within a relatively narrow range. High Mb oxygen affinity within this range may be adaptive for some vertebrates that make prolonged dives. © 2015. Published by The Company of Biologists Ltd.

  11. A comparison of blood nitric oxide metabolites and hemoglobin functional properties among diving mammals

    DEFF Research Database (Denmark)

    Fago, Angela; Parraga, Daniel Garcia; Petersen, Elin E

    2017-01-01

    examined oxygen affinity, sensitivity to 2,3-diphosphoglycerate (DPG) and nitrite reductase activity of the hemoglobin (Hb) to search for possible adaptive variations in these functional properties. We found levels of plasma and red blood cells nitrite similar to those reported for terrestrial mammals...... in blood oxygen affinity among diving mammals likely derive from phenotypic variations in red blood cell DPG levels. The nitrite reductase activities of the Hbs were overall slightly higher than that of human Hb, with the Hb of beluga whale, capable of longest dives, having the highest activity. Taken...

  12. Hemoglobin system of Sparus aurata: Changes in fishes farmed under extreme conditions

    International Nuclear Information System (INIS)

    Campo, Salvatore; Nastasi, Giancarlo; D'Ascola, Angela; Campo, Giuseppe M.; Avenoso, Angela; Traina, Paola; Calatroni, Alberto; Burrascano, Emanuele; Ferlazzo, Alida; Lupidi, Giulio; Gabbianelli, Rosita; Falcioni, Giancarlo

    2008-01-01

    In order to gain more knowledge on the stress responses of gilhead seabream (Sparus aurata) under extreme conditions, this study investigated the functional properties of the hemoglobin system and globin gene expression under hypoxia and low salinity. The oxygen affinity for the two hemoglobin components present inside the S. aurata erythrocyte was practically identical as was the influence of protons and organic phosphates (Root effect). The quantification of S. aurata hemoglobin fractions performed by HPLC and the data on gene expression of globin chains assayed by PCR indicate that under hypoxia and low salinity there is a change in the ratio between the two different hemoglobin components. The result indicating that the distinct hemoglobins present in S. aurata erythrocyte have almost identical functional properties, does not explain the adaptive response (expression change) following exposure of the animal to hypoxia or low salinity on the basis of their function as oxygen transporter. We hypothesize that other parallel biological functions that the hemoglobin molecule is known to display within the erythrocyte are involved in adaptive molecular mechanisms. The autoxidation-reduction cycle of hemoglobin could be involved in the response to particular living conditions

  13. Validation of NIRS in measuring tissue hemoglobin concentration and oxygen saturation on ex vivo and isolated limb models

    Science.gov (United States)

    Xu, Xiaorong; Zhu, Wen; Padival, Vikram; Xia, Mengna; Cheng, Xuefeng; Bush, Robin; Christenson, Linda; Chan, Tim; Doherty, Tim; Iatridis, Angelo

    2003-07-01

    Photonify"s tissue spectrometer uses Near-Infrared Spectroscopy for real-time, noninvasive measurement of hemoglobin concentration and oxygen saturation [SO2] of biological tissues. The technology was validated by a series of ex vivo and animal studies. In the ex vivo experiment, a close loop blood circulation system was built, precisely controlling the oxygen saturation and the hemoglobin concentration of a liquid phantom. Photonify"s tissue spectrometer was placed on the surface of the liquid phantom for real time measurement and compared with a gas analyzer, considered the gold standard to measure oxygen saturation and hemoglobin concentration. In the animal experiment, the right hind limb of each dog accepted onto the study was surgically removed. The limb was kept viable by connecting the femoral vein and artery to a blood-primed extracorporeal circuit. Different concentrations of hemoglobin were obtained by adding designated amount of saline solution into the perfusion circuit. Photonify"s tissue spectrometers measured oxygen saturation and hemoglobin concentration at various locations on the limb and compared with gas analyzer results. The test results demonstrated that Photonify"s tissue spectrometers were able to detect the relative changes in tissue oxygen saturation and hemoglobin concentration with a high linear correlation compared to the gas analyzer

  14. Location of the higher affinity copper site on human hemoglobin by the use of the spin label technique

    International Nuclear Information System (INIS)

    Tabak, M.; Louro, S.R.W.

    1983-11-01

    Addition of copper (II) ions to Cys β-93 maleimide spin-labelled human hemoglobin A produces a dramatic decrease in the amplitude of the spin-label ESR spectra. This effect was analyzed in the framework of Leigh's theory which permits interspin distances to be deduced from the effect of dipolar coupling on the ESR spectra and led to an estimate of 9A as the distance between the label and the higher affinity copper site. Taking into account the previous results which suggest that four nitrogen atoms coordinate with copper, and that the N terminal val β-1 and His β-2 residues are involved, the location of the higher affinity copper site is proposed to be at the β 1 β 2 interface of the hemoglobin molecule, involving the N terminal of one β subunit and the C terminal of the other. (Author) [pt

  15. Highly sensitive voltammetric biosensor for nitric oxide based on its high affinity with hemoglobin

    International Nuclear Information System (INIS)

    Fan Chunhai; Liu Xinjian; Pang Jiantao; Li Genxi; Scheer, Hugo

    2004-01-01

    Although heme protein-based, amperometric nitric oxide (NO) biosensors have been well documented in previous studies, most have been conducted in anaerobic conditions. Herein we report a novel hemoglobin-based NO biosensor that is not only very sensitive but also usable in air. The heme protein was entrapped in a sodium montmorillonite film, which was immobilized at a pyrolytic graphite electrode surface. Film-entrapped hemoglobin can directly exchange electrons with the electrode, and this process has proven to favor the catalytic reduction of oxygen. In addition, NO induced a cathodic potential shift of the catalytic reduction peak of oxygen. This potential shift was proportional to the logarithm of NO concentration ranging from 4.0 x 10 -11 to 5.0 x 10 -6 mol/L. The detection limit has been estimated to be 20 pM, approximately four orders lower than previously reported amperometric detectors

  16. Coinheritance of High Oxygen Affinity Hb Helsinki [HBB: c.248A>T; β82(EF6)Lys→Met] with Hb H Disease.

    Science.gov (United States)

    Lee, Shir-Ying; Goh, Jia-Hui; Tan, Karen M L; Liu, Te-Chih

    2017-05-01

    Hb Helsinki [HBB: c.248A>T; β82(EF6)Lys→Met] is a high oxygen affinity hemoglobin (Hb) causing polycythemia, whereas Hb H (β4) disease causes mild to severe chronic hemolytic anemia. The clinical characteristics, gel electrophoresis, capillary electrophoresis (CE) and molecular genotyping of a case of Hb Helsinki coinherited with Hb H disease in an ethnic Malay is described, illustrating the interaction between the β-globin variant and coinheritance of three α gene deletions. The proband was asymptomatic, exhibited microcytosis and a normal with Hb value.

  17. Electron transfer reactions, cyanide and O2 binding of truncated hemoglobin from Bacillus subtilis

    DEFF Research Database (Denmark)

    Fernandez, Esther; Larsson, Jonas T.; McLean, Kirsty J.

    2013-01-01

    The truncated hemoglobin from Bacillus subtilis (trHb-Bs) possesses a surprisingly high affinity for oxygen and resistance to (auto)oxidation; its physiological role in the bacterium is not understood and may be connected with its very special redox and ligand binding reactions. Electron transfer...

  18. A 13C-NMR study of mutant hemoglobins with altered oxygen affinity

    International Nuclear Information System (INIS)

    Smith, M.L.; Norden, B.; Edlund, U.; Paul, K.-G.

    1986-01-01

    The 13 CO-NMR spectra of carbonylhemoglobins Saint Mande (β 102Asn → Tyr), Malmo (β 97His → Gln), Hotel Dieu (β 99Asp → Gly) and A o have been determined. The positions of the 13 CO resonances for hemoglobins A o , Malmo and Hotel Dieu were similar indicating similar ligand environments for all. The 13 CO resonance for the β-subunit of Saint Mande was upfield-shifted compared to the others. This is evidence that structural changes at the β102 position directly affect iron-ligand bonding as well as quaternary structure. (Auth.)

  19. 32P and acute leukemia: development of leukemia in a patient with hemoglobin Yakima

    International Nuclear Information System (INIS)

    Bagby, G.C. Jr.; Richert-Boe, K.; Koler, R.D.

    1978-01-01

    In 1954 a then 31-yr-old male was found to have erythrocytosis. Over the ensuing decade he received 72 mCi 32 P. In 1964 his daughters were found to have erythrocytosis. Further investigation led to the discovery of hemoglobin Yakima, a variant with high oxygen affinity. He received no further therapy and was well until 1975, when he developed the preleukemic syndrome. Within 12 mo he developed acute nonlymphocytic leukemia accompanied by fetal erythropoiesis. Because the initial discovery of this type of hemoglobinopathy came 27 yr after the introduction of 32 P for use in the treatment of polycythemia vera, and because there are now known to be more than 39 different high-oxygen-affinity hemoglobins, we anticipate that more patients such as ours have been exposed to 32 P. The exposed population should be closely followed, since this will likely permit assessment of the risk of 32 P-induced leukemia in a nonneoplastic condition

  20. Protonation states of histidine and other key residues in deoxy normal human adult hemoglobin by neutron protein crystallography

    International Nuclear Information System (INIS)

    Kovalevsky, Andrey; Chatake, Toshiyuki; Shibayama, Naoya; Park, Sam-Yong; Ishikawa, Takuya; Mustyakimov, Marat; Fisher, S. Zoe; Langan, Paul; Morimoto, Yukio

    2010-01-01

    Using neutron diffraction analysis, the protonation states of 35 of 38 histidine residues were determined for the deoxy form of normal human adult hemoglobin. Distal and buried histidines may contribute to the increased affinity of the deoxy state for hydrogen ions and its decreased affinity for oxygen compared with the oxygenated form. The protonation states of the histidine residues key to the function of deoxy (T-state) human hemoglobin have been investigated using neutron protein crystallography. These residues can reversibly bind protons, thereby regulating the oxygen affinity of hemoglobin. By examining the OMIT F o − F c and 2F o − F c neutron scattering maps, the protonation states of 35 of the 38 His residues were directly determined. The remaining three residues were found to be disordered. Surprisingly, seven pairs of His residues from equivalent α or β chains, αHis20, αHis50, αHis58, αHis89, βHis63, βHis143 and βHis146, have different protonation states. The protonation of distal His residues in the α 1 β 1 heterodimer and the protonation of αHis103 in both subunits demonstrates that these residues may participate in buffering hydrogen ions and may influence the oxygen binding. The observed protonation states of His residues are compared with their ΔpK a between the deoxy and oxy states. Examination of inter-subunit interfaces provided evidence for interactions that are essential for the stability of the deoxy tertiary structure

  1. Can the hemoglobin characteristics of vesicomyid clam species influence their distribution in deep-sea sulfide-rich sediments? A case study in the Angola Basin

    Science.gov (United States)

    Decker, C.; Zorn, N.; Le Bruchec, J.; Caprais, J. C.; Potier, N.; Leize-Wagner, E.; Lallier, F. H.; Olu, K.; Andersen, A. C.

    2017-08-01

    Vesicomyids live in endosymbiosis with sulfur-oxidizing bacteria and therefore need hydrogen sulfide to survive. They can nevertheless live in a wide range of sulfide and oxygen levels and depths, which may explain the exceptional diversity of this clam family in deep-sea habitats. In the Gulf of Guinea, nine species of vesicomyid clams are known to live in cold-seep areas with pockmarks from 600 to 3200 m deep, as well as in the organic-rich sediments of the Congo deep-sea fan at 5000 m deep. Our previous study showed that two species living in a giant pockmark have different oxygen carriers, suggesting different adaptations to hypoxia. Here, we studied the hemoglobin structure and oxygen affinity in three other species, Calyptogena valdiviae, Elenaconcha guiness and Abyssogena southwardae to determine whether the characteristics of their oxygen carriers contribute to their distribution in sulfide-rich sediments at a regional scale. Documenting pairwise species associations in various proportions, we give a semi-quantitative account of their local distribution and oxygen and sulfide measurements at seven sites. Mass spectrometry showed that each vesicomyid species has four intracellular monomeric hemoglobin molecules of 15-16 kDa, all differing in their molecular mass. As expected, the monomers showed no cooperativity in oxygen binding. Their oxygen affinities were very high (below 1 Torr), but differed significantly. C. valdiviae had the highest affinity and was dominant in the Harp pockmark, the site with the lowest oxygen content (half the value of fully oxygenated water). A. southwardae dominated in the Congo Lobe area, the site with the deepest sulfides. We discuss how hemoglobin may favor an active, vertical distribution of vesicomyids in sulfide-rich sediments.

  2. Oxygenation level and hemoglobin concentration in experimental tumor estimated by diffuse optical spectroscopy

    Science.gov (United States)

    Orlova, A. G.; Kirillin, M. Yu.; Volovetsky, A. B.; Shilyagina, N. Yu.; Sergeeva, E. A.; Golubiatnikov, G. Yu.; Turchin, I. V.

    2017-07-01

    Using diffuse optical spectroscopy the level of oxygenation and hemoglobin concentration in experimental tumor in comparison with normal muscle tissue of mice have been studied. Subcutaneously growing SKBR-3 was used as a tumor model. Continuous wave fiber probe diffuse optical spectroscopy system was employed. Optical properties extraction approach was based on diffusion approximation. Decreased blood oxygen saturation level and increased total hemoglobin content were demonstrated in the neoplasm. The main reason of such differences between tumor and norm was significant elevation of deoxyhemoglobin concentration in SKBR-3. The method can be useful for diagnosis of tumors as well as for study of blood flow parameters of tumor models with different angiogenic properties.

  3. Spectral filtering modulation method for estimation of hemoglobin concentration and oxygenation based on a single fluorescence emission spectrum in tissue phantoms.

    Science.gov (United States)

    Liu, Quan; Vo-Dinh, Tuan

    2009-10-01

    Hemoglobin concentration and oxygenation in tissue are important biomarkers that are useful in both research and clinical diagnostics of a wide variety of diseases such as cancer. The authors aim to develop simple ratiometric method based on the spectral filtering modulation (SFM) of fluorescence spectra to estimate the total hemoglobin concentration and oxygenation in tissue using only a single fluorescence emission spectrum, which will eliminate the need of diffuse reflectance measurements and prolonged data processing as required by most current methods, thus enabling rapid clinical measurements. The proposed method consists of two steps. In the first step, the total hemoglobin concentration is determined by comparing a ratio of fluorescence intensities at two emission wavelengths to a calibration curve. The second step is to estimate oxygen saturation by comparing a double ratio that involves three emission wavelengths to another calibration curve that is a function of oxygen saturation for known total hemoglobin concentration. Theoretical derivation shows that the ratio in the first step is linearly proportional to the total hemoglobin concentrations and the double ratio in the second step is related to both total hemoglobin concentration and hemoglobin oxygenation for the chosen fiber-optic probe geometry. Experiments on synthetic fluorescent tissue phantoms, which included hemoglobin with both constant and varying oxygenation as the absorber, polystyrene spheres as scatterers, and flavin adenine dinucleotide as the fluorophore, were carried out to validate the theoretical prediction. Tissue phantom experiments confirm that the ratio in the first step is linearly proportional to the total hemoglobin concentration and the double ratio in the second step is related to both total hemoglobin concentrations and hemoglobin oxygenation. Furthermore, the relations between the two ratios and the total hemoglobin concentration and hemoglobin oxygenation are insensitive

  4. Lack of conventional oxygen-linked proton and anion binding sites does not impair allosteric regulation of oxygen binding in dwarf caiman hemoglobin

    Science.gov (United States)

    Fago, Angela; Malte, Hans; Storz, Jay F.; Gorr, Thomas A.

    2013-01-01

    In contrast to other vertebrate hemoglobins (Hbs) whose high intrinsic O2 affinities are reduced by red cell allosteric effectors (mainly protons, CO2, organic phosphates, and chloride ions), crocodilian Hbs exhibit low sensitivity to organic phosphates and high sensitivity to bicarbonate (HCO3−), which is believed to augment Hb-O2 unloading during diving and postprandial alkaline tides when blood HCO3− levels and metabolic rates increase. Examination of α- and β-globin amino acid sequences of dwarf caiman (Paleosuchus palpebrosus) revealed a unique combination of substitutions at key effector binding sites compared with other vertebrate and crocodilian Hbs: β82Lys→Gln, β143His→Val, and β146His→Tyr. These substitutions delete positive charges and, along with other distinctive changes in residue charge and polarity, may be expected to disrupt allosteric regulation of Hb-O2 affinity. Strikingly, however, P. palpebrosus Hb shows a strong Bohr effect, and marked deoxygenation-linked binding of organic phosphates (ATP and DPG) and CO2 as carbamate (contrasting with HCO3− binding in other crocodilians). Unlike other Hbs, it polymerizes to large complexes in the oxygenated state. The highly unusual properties of P. palpebrosus Hb align with a high content of His residues (potential sites for oxygenation-linked proton binding) and distinctive surface Cys residues that may form intermolecular disulfide bridges upon polymerization. On the basis of its singular properties, P. palpebrosus Hb provides a unique opportunity for studies on structure-function coupling and the evolution of compensatory mechanisms for maintaining tissue O2 delivery in Hbs that lack conventional effector-binding residues. PMID:23720132

  5. Overproduction of alpha chains provides a proton-insensitive component to the bluefish hemoglobin system.

    Science.gov (United States)

    Bonaventura, Celia; Godette, Gerald; Stevens, Robert; Brenowitz, Michael; Henkens, Robert

    2005-12-09

    Expression of alpha and beta chains and their post-translational assembly into alpha(2)beta(2) tetramers is fundamental to the formation and function of most vertebrate hemoglobins. There is a strong evolutionary bias that favors expression of equal amounts of the two types of chains, because cooperativity, pH sensitivity, and anionic control of function occurs only for the alpha(2)beta(2) tetramers. Remarkably, an over-production of alpha chains, as in the pathological condition known as beta thalassemia in humans, is adaptive rather than pathological in the bluefish hemoglobin system. The thalassemia of the bluefish is a novel means of providing for oxygen uptake and delivery when low pH conditions incapacitate the highly pH-sensitive Root effect hemoglobins of the fish. Although fish often have pH-insensitive along with highly pH-sensitive hemoglobins, having pH-insensitive alpha chain monomers in circulation is an unusual structural variation. The role of bluefish alpha chains in oxygen transport is enabled by their remarkably lower oxygen affinity relative to human alpha chains. This is the first reported case of a thalassemic condition that is maintained in a species as an adaptive advantage.

  6. The Oxygen Dissociation Curve of Hemoglobin: Bridging the Gap between Biochemistry and Physiology

    Science.gov (United States)

    Gómez-Cambronero, Julian

    2001-06-01

    Cooperativity is a very difficult concept for biochemistry students in the health sciences. An analogy between breaking salt bonds and tearing apart a block of four stamps has been proposed for hemoglobin (Hb). However, since tearing is equated to binding of molecules, two intrinsically contradictory terms, students still have difficulty. I apply the pictorial analogy to the releasing of oxygen instead of the binding, thus bridging biochemistry (cooperativity) with physiology (oxygen dissociation). I embark on an imaginary journey from the lungs (saturation at 100 mmHg) to the oxygen-starved tissues. The stamps represent fully loaded Hb. By making two cuts the first "oxygen" is released. For the second, only one cut is needed. With one final cut, the last two stamps are separated. This means that less energy is needed to unload oxygen: just small drops in partial pressure do the trick in the right place (tissues) but not in the wrong one (lungs). In doing this, I use the three main models of learning: association, discovery and mentoring. Additionally, by guiding students to discover the truth by themselves, I can use hemoglobin as a wonderful excuse to apply the "Socratic method" in the classroom.

  7. EPR spectral changes of nitrosil hemes and their relation to the hemoglobin T-R transition

    International Nuclear Information System (INIS)

    Louro, S.R.W.; Ribeiro, P.C.; Bemski, G.

    1980-09-01

    EPR spectra of nitrosil-hemes were used to study the quaternary structure of hemoglobin. Human adult hemoglobin has been titrated with nitric oxide at pH 7.0 and 25 0 C. After the equilibration of NO among the α and β subunits the samples were frozen for EPR measurements. The spectra were fitted by linear combinations of three standard signals: the first arising from NO - β hemes and the other two arising from NO - α hemes of molecules in the high and low affinity conformations. The fractional amounts of α subunits exhibiting the high affinity spectrum fitted the two-state model with L = 7 x 10 6 , and csup(α) sub(NO) and csup(β) sub(NO) approximately 0.01. Hemoglobin has been marked with nitric oxide at one chain using low-saturation amounts of nitric oxide. The EPR spectra were studied as a function of oxygen saturation. Linear combinations of the three standard signals above fitted these spectra. The fractions of molecules exhibiting the high affinity spectrum fitted the two-state model with L = 7 x 10 6 , csub(O 2 ) = 0.0033 and csup(α) sub(NO) = 0.08, instead of csup(α) sub(NO) = 0.01.Thus, the two state model is not adequate to describe the conformational transition of these hybrids. The results are evidence of the nonequivalence between oxygen and nitric oxide as ligands. (Author) [pt

  8. Hemoglobin C disease

    Science.gov (United States)

    Clinical hemoglobin C ... Hemoglobin C is an abnormal type of hemoglobin, the protein in red blood cells that carries oxygen. It is ... Americans. You are more likely to have hemoglobin C disease if someone in your family has had ...

  9. Site-specific semisynthetic variant of human hemoglobin

    International Nuclear Information System (INIS)

    Hefta, S.A.; Lyle, S.B.; Busch, M.R.; Harris, D.E.; Matthew, J.B.; Gurd, F.R.N.

    1988-01-01

    A single round of Edman degradation was employed to remove the NH 2 -terminal valine from isolated α chains of human hemoglobin. Reconstitution of normal β chains with truncated or substituted α chains was used to form truncated (des-Val 1 -α1) and substituted ([[1- 13 C]Gly 1 ]α1) tetrameric hemoglobin analogs. Structural homology of the analogs with untreated native hemoglobin was established by using several spectroscopic and physical methods. Functional studies indicate that the reconstituted tetrameric protein containing des-Val 1 -α chains has a higher affinity for oxygen, is less influenced by chloride ions or 2,3-biphosphoglycerate, and shows lower cooperativity than native hemoglobin. These results confirm the key functional role of the α-chain NH 2 terminus in mediating cooperative oxygen binding across the dimer interface. The NH 2 -terminal pK/sub 1/2/ value was determined for the [ 13 C]glycine-substituted analog to be 7.46 +/- 0.09 at 15 0 C in the carbon monoxide-liganded form. This value, measured directly by 13 C NMR, agrees with the determination made by the less-direct 13 CO 2 method and confirms the role of this residue as a contributor to the alkaline Bohr effect; however, it is consistent with the presence of an NH 2 -terminal salt bridge to the carboxylate of Arg-141 of the α chain in the liganded form

  10. A Bovine Hemoglobin-Based Oxygen Carrier as Pump Prime for Cardiopulmonary Bypass: Reduced Systemic Lactic Acidosis and Improved Cerebral Oxygen Metabolism During Low-flow in a Porcine Model

    Science.gov (United States)

    2010-11-10

    1 A bovine hemoglobin-based oxygen carrier as pump prime for cardiopulmonary bypass: reduced systemic lactic acidosis and improved cerebral...2010 2. REPORT TYPE Final Report 3. DATES COVERED (From - To) June 2007 - November 2010 4. TITLE AND SUBTITLE A bovine hemoglobin-based oxygen...carrier as pump prime for cardiopulmonary bypass: reduced systemic lactic acidosis and improved cerebral oxygen metabolism during low-flow in a

  11. Characterization and Expression of the Lucina pectinata Oxygen and Sulfide Binding Hemoglobin Genes

    Science.gov (United States)

    López-Garriga, Juan; Cadilla, Carmen L.

    2016-01-01

    The clam Lucina pectinata lives in sulfide-rich muds and houses intracellular symbiotic bacteria that need to be supplied with hydrogen sulfide and oxygen. This clam possesses three hemoglobins: hemoglobin I (HbI), a sulfide-reactive protein, and hemoglobin II (HbII) and III (HbIII), which are oxygen-reactive. We characterized the complete gene sequence and promoter regions for the oxygen reactive hemoglobins and the partial structure and promoters of the HbI gene from Lucina pectinata. We show that HbI has two mRNA variants, where the 5’end had either a sequence of 96 bp (long variant) or 37 bp (short variant). The gene structure of the oxygen reactive Hbs is defined by having 4-exons/3-introns with conservation of intron location at B12.2 and G7.0 and the presence of pre-coding introns, while the partial gene structure of HbI has the same intron conservation but appears to have a 5-exon/ 4-intron structure. A search for putative transcription factor binding sites (TFBSs) was done with the promoters for HbII, HbIII, HbI short and HbI long. The HbII, HbIII and HbI long promoters showed similar predicted TFBSs. We also characterized MITE-like elements in the HbI and HbII gene promoters and intronic regions that are similar to sequences found in other mollusk genomes. The gene expression levels of the clam Hbs, from sulfide-rich and sulfide-poor environments showed a significant decrease of expression in the symbiont-containing tissue for those clams in a sulfide-poor environment, suggesting that the sulfide concentration may be involved in the regulation of these proteins. Gene expression evaluation of the two HbI mRNA variants indicated that the longer variant is expressed at higher levels than the shorter variant in both environments. PMID:26824233

  12. Effects of Hemoglobin-Based Oxygen Carriers on Blood Coagulation

    Directory of Open Access Journals (Sweden)

    Kimia Roghani

    2014-12-01

    Full Text Available For many decades, Hemoglobin-based oxygen carriers (HBOCs have been central in the development of resuscitation agents that might provide oxygen delivery in addition to simple volume expansion. Since 80% of the world population lives in areas where fresh blood products are not available, the application of these new solutions may prove to be highly beneficial (Kim and Greenburg 2006. Many improvements have been made to earlier generation HBOCs, but various concerns still remain, including coagulopathy, nitric oxide scavenging, platelet interference and decreased calcium concentration secondary to volume expansion (Jahr et al. 2013. This review will summarize the current challenges faced in developing HBOCs that may be used clinically, in order to guide future research efforts in the field.

  13. Cerebral time domain-NIRS: Reproducibility analysis, optical properties, hemoglobin species and tissue oxygen saturation in a cohort of adult subjects

    OpenAIRE

    Giacalone, Giacomo; Zanoletti, Marta; Contini, Davide; Rebecca, Re; Spinelli, Lorenzo; Roveri, Luisa; Torricelli, Alessandro

    2017-01-01

    The reproducibility of cerebral time-domain near-infrared spectroscopy (TD-NIRS) has not been investigated so far. Besides, reference intervals of cerebral optical properties, of absolute concentrations of deoxygenated-hemoglobin (HbR), oxygenated-hemoglobin (HbO), total hemoglobin (HbT) and tissue oxygen saturation (StO2) and their variability have not been reported. We have addressed these issues on a sample of 88 adult healthy subjects. TD-NIRS measurements at 690, 785, 830 nm were fitted ...

  14. Three-state combinatorial switch models as applied to the binding of oxygen by human hemoglobin.

    Science.gov (United States)

    Straume, M; Johnson, M L

    1988-02-23

    We have generated a series of all 6561 unique, discrete three-state combinatorial switch models to describe the partitioning of the cooperative oxygen-binding free change among the 10 variously ligated forms of human hemoglobin tetramers. These models were inspired by the experimental observation of Smith and Ackers that the cooperative free energy of the intersubunit contact regions of the 10 possible ligated forms of human hemoglobin tetramers can be represented by a particular distribution of three distinct energy levels [Smith, F. R., & Ackers, G. K. (1985) Proc. Natl. Acad. Sci. U.S.A. 82, 5347-5351]. A statistical thermodynamic formulation accounting for both dimer-tetramer equilibria and ligand binding properties of hemoglobin solutions as a function of oxygen and protein concentrations was utilized to exhaustively test these thermodynamic models. In this series of models each of the 10 ligated forms of the hemoglobin tetramer can exist in one, and only one, of three possible energy levels; i.e., each ligated form was assumed to be associated with a discrete energy state. This series of models includes all possible ways that the 10 ligation states of hemoglobin can be distributed into three distinct cooperative energy levels. The mathematical models, as presented here, do not permit equilibria between energy states to exist for any of the 10 unique ligated forms of hemoglobin tetramers. These models were analyzed by nonlinear least-squares estimation of the free energy parameters characteristic of this statistical thermodynamic development.(ABSTRACT TRUNCATED AT 250 WORDS)

  15. Heme orientational disorder in human adult hemoglobin reconstituted with a ring fluorinated heme and its functional consequences

    International Nuclear Information System (INIS)

    Nagao, Satoshi; Hirai, Yueki; Kawano, Shin; Imai, Kiyohiro; Suzuki, Akihiro; Yamamoto, Yasuhiko

    2007-01-01

    A ring fluorinated heme, 13,17-bis(2-carboxylatoethyl)-3,8-diethyl-2-fluoro-7,12, 18-trimethyl-porphyrin-atoiron(III), has been incorporated into human adult hemoglobin (Hb A). The heme orientational disorder in the individual subunits of the protein has been readily characterized using 19 F NMR and the O 2 binding properties of the protein have been evaluated through the oxygen equilibrium analysis. The equilibrated orientations of hemes in α- and β- subunits of the reconstituted protein were found to be almost completely opposite to each other, and hence were largely different from those of the native and the previously reported reconstituted proteins [T. Jue, G.N. La Mar, Heme orientational heterogeneity in deuterohemin-reconstituted horse and human hemoglobin characterized by proton nuclear magnetic resonance spectroscopy, Biochem. Biophys. Res. Commun. 119 (1984) 640-645]. Despite the large difference in the degree of the heme orientational disorder in the subunits of the proteins, the O 2 affinity and the cooperativity of the protein reconstituted with 2-MF were similar to those of the proteins reconstituted with a series of hemes chemically modified at the heme 3- and 8-positions [K. Kawabe, K. Imaizumi, Z. Yoshida, K. Imai, I. Tyuma, Studies on reconstituted myoglobins and hemoglobins II. Role of the heme side chains in the oxygenation of hemoglobin, J. Biochem. 92 (1982) 1713-1722], whose O 2 affinity and cooperativity were higher and lower, respectively, relative to those of native protein. These results indicated that the heme orientational disorder could exert little effect, if any, on the O 2 affinity properties of Hb A. This finding provides new insights into structure-function relationship of Hb A

  16. Structure and stability of human hemoglobin microparticles prepared with a double emulsion technique.

    Science.gov (United States)

    Cedrati, N; Bonneaux, F; Labrude, P; Maincent, P

    1997-09-01

    Hemoglobin solutions can be used as blood substitutes but they present some disadvantages often due to their rapid removal from the bloodstream after injection. A possible way of overcoming this problem is to trap hemoglobin inside particles. This study deals with the preparation, structure and stability of poly(lactic acid) and ethylcellulose microparticles containing human hemoglobin obtained with a double emulsion technique. We investigated the manufacturing process of these particles in order to increase the encapsulation ratio of hemoglobin. For this purpose, some parameters involved in the procedure were optimized, such as hemoglobin concentration and duration of stirring: hemoglobin loading increases with its concentration in the preparation and well-defined stirring time avoids a leakage of hemoglobin. Hemoglobin concentration, surfactant concentration i.e. poly(vinylic alcohol), amounts of polymer and solvent (methylene chloride), duration and speed of stirring. The microparticles were prepared with satisfactory yields (60 to 73%). They were spherical and their mean size was lower than 200 microns. The functional properties of entrapped hemoglobin were studied. The encapsulation did not alter hemoglobin and the oxygen affinity of the hemoglobin remained unmodified (P50 about 13.9 mm Hg in a Bis-Tris buffer pH 7.4 at 37 degrees C). Moreover, only low levels of methemoglobin could be detected (less than 3%). Besides, about 90% of encapsulated hemoglobin could be released from microparticles, with a speed related to the internal structure of the particles. The prepared microparticles were stored during one month at +4 degrees C. No degradation of the particle structure occurred and the functional properties of hemoglobin were preserved. These particles could provide a potential source of oxygen in the field of biotechnologies but any application for a transfusional purpose would first require a drastic reduction in particle size.

  17. Oxygen binding to nitric oxide marked hemoglobin

    International Nuclear Information System (INIS)

    Louro, S.R.W.; Ribeiro, P.C.; Bemski, G.

    1979-04-01

    Electron spin resonance spectra of organic phosphate free human hemoglobin marked with nitric oxide at the sixth coordination position of one of the four hemes allow to observe the transition from the tense (T) to the relaxed (R) conformation, as a function of parcial oxygen pressure. The spectra are composites of contributions from α sub(T), α sub(R) and β chains spectra, showing the presence of only two conformations: T and R. In the absence of organic phosphates NO binds to α and β chains with the same probability, but in the presence of phosphates NO combines preferentially with α chains. The dissociation of NO proceeds at least an order of magnitude faster in T than in R configuration. (author) [pt

  18. Normalization of hemoglobin-based oxygen carrier-201 induced vasoconstriction: targeting nitric oxide and endothelin.

    Science.gov (United States)

    Taverne, Yannick J; de Wijs-Meijler, Daphne; Te Lintel Hekkert, Maaike; Moon-Massat, Paula F; Dubé, Gregory P; Duncker, Dirk J; Merkus, Daphne

    2017-05-01

    Hemoglobin-based oxygen carrier (HBOC)-201 is a cell-free modified hemoglobin solution potentially facilitating oxygen uptake and delivery in cardiovascular disorders and hemorrhagic shock. Clinical use has been hampered by vasoconstriction in the systemic and pulmonary beds. Therefore, we aimed to 1 ) determine the possibility of counteracting HBOC-201-induced pressor effects with either adenosine (ADO) or nitroglycerin (NTG); 2 ) assess the potential roles of nitric oxide (NO) scavenging, reactive oxygen species (ROS), and endothelin (ET) in mediating the observed vasoconstriction; and 3 ) compare these effects in resting and exercising swine. Chronically instrumented swine were studied at rest and during exercise after administration of HBOC-201 alone or in combination with ADO. The role of NO was assessed by supplementation with NTG or administration of the eNOS inhibitor N ω -nitro-l-arginine. Alternative vasoactive pathways were investigated via intravenous administration of the ET A /ET B receptor blocker tezosentan or a mixture of ROS scavengers. The systemic and to a lesser extent the pulmonary pressor effects of HBOC-201 could be counteracted by ADO; however, dosage titration was very important to avoid systemic hypotension. Similarly, supplementation of NO with NTG negated the pressor effects but also required titration of the dose. The pressor response to HBOC-201 was reduced after eNOS inhibition and abolished by simultaneous ET A /ET B receptor blockade, while ROS scavenging had no effect. In conclusion, the pressor response to HBOC-201 is mediated by vasoconstriction due to NO scavenging and production of ET. Further research should explore the effect of longer-acting ET receptor blockers to counteract the side effect of hemoglobin-based oxygen carriers. NEW & NOTEWORTHY Hemoglobin-based oxygen carrier (HBOC)-201 can disrupt hemodynamic homeostasis, mimicking some aspects of endothelial dysfunction, resulting in elevated systemic and pulmonary blood

  19. Removal of cellular-type hemoglobin-based oxygen carrier (hemoglobin-vesicles) from blood using centrifugation and ultrafiltration.

    Science.gov (United States)

    Sakai, Hiromi; Sou, Keitaro; Horinouchi, Hirohisa; Tsuchida, Eishun; Kobayashi, Koichi

    2012-02-01

    The hemoglobin-vesicle (HbV) is an artificial oxygen carrier encapsulating a concentrated hemoglobin solution in a phospholipid vesicle (liposome). During or after transporting oxygen, macrophages capture HbVs in the reticuloendothelial system (RES) with an approximate circulation half-life of 3 days. Animal studies show transient splenohepatomegaly after large doses, but HbVs were completely degraded, and the components were excreted in a few weeks. If a blood substitute is used for emergency use until red blood cell transfusion becomes available or for temporary use such as a priming fluid for an extracorporeal circuit, then one option would be to remove HbVs from the circulating blood without waiting a few weeks for removal by the RES. Using a mixture of beagle dog whole blood and HbV, we tested the separation of HbV using a centrifugal Fresenius cell separator and an ultrafiltration system. The cell separator system separated the layers of blood cell components from the HbV-containing plasma layer by centrifugal force, and then the HbV was removed from plasma phase by the ultrafiltration system. The HbVs (250-280 nm) are larger than plasma proteins (blood cell components (> 3 µm). The size of HbVs is advantageous to be separated from the original blood components, and the separated blood components can be returned to circulation. © 2011, Copyright the Authors. Artificial Organs © 2011, International Center for Artificial Organs and Transplantation and Wiley Periodicals, Inc.

  20. Effects of Cyanate and 2,3-Diphosphoglycerate on Sickling RELATIONSHIP TO OXYGENATION

    Science.gov (United States)

    Jensen, Michael; Bunn, H. Franklin; Halikas, George; Kan, Yuet Wai; Nathan, David G.

    1973-01-01

    Cyanate and 2,3-diphosphoglycerate (2,3-DPG) both influence the oxygen affinity of hemoglobin. The studies presented here concern the effects of these compounds on the sickling phenomenon. The inhibitory effect of cyanate on sickling is largely due to the fact that it increases the percentage of oxyhemoglobin S at a given oxygen tension. In addition, cyanate inhibits sickling by a mechanism that is independent of oxygenation. In this paper, we have demonstrated that the viscosity of carbamylated sickle blood was lower than that of non-carbamylated controls at the same oxygen saturation. Furthermore, carbamylation resulted in an increase in the minimum concentration of deoxy-sickle hemoglobin required for gelation. Like cyanate, 2,3-DPG affected sickling of intact erythrocytes by two mechanisms. Since 2,3-DPG decreases the percentage of oxyhemoglobin S at a given oxygen tension, sickling is enhanced. In addition, 2,3-DPG had a direct effect. When the intracellular 2,3-DPG concentration was increased in vitro, a greater percentage of cells were sickled at a given oxygen saturation. Conversely, sickling was inhibited in cells in which 2,3-DPG was artificially lowered. These data indicate that the enhancement of sickling by 2,3-DPG is in part independent of its influence on oxygen affinity. PMID:4729047

  1. Expression of fully functional tetrameric human hemoglobin in Escherichia coli

    International Nuclear Information System (INIS)

    Hoffman, S.J.; Looker, D.L.; Roehrich, J.M.; Cozart, P.E.; Durfee, S.L.; Tedesco, J.L.; Stetler, G.L.

    1990-01-01

    Synthesis genes encoding the human α- and β-globin polypeptides have been expressed from a single operon in Escherichia coli. The α- and β-globin polypeptides associate into soluble tetramers, incorporate heme, and accumulate to >5% of the total cellular protein. Purified recombinant hemoglobin has the correct stoichiometry of α- and β-globin chains and contains a full complement of heme. Each globin chain also contains an additional methionine as an extension to the amino terminus. The recombinant hemoglobin has a C 4 reversed-phase HPLC profile essentially identical to that of human hemoglobin A 0 and comigrates with hemoglobin A 0 on SDS/PAGE. The visible spectrum and oxygen affinity are similar to that of native human hemoglobin A 0 . The authors have also expressed the α- and β-globin genes separately and found that the expression of the α-globin gene alone results in a marked decrease in the accumulation of α-globin in the cell. Separate expression of the β-globin gene results in high levels of insoluble β-globin. These observations suggest that the presence of α- and β-globin in the same cell stabilizes α-globin and aids the correct folding of β-globin. This system provides a simple method for expressing large quantities of recombinant hemoglobin and allows facile manipulation of the genes encoding hemoglobin to produce functionally altered forms of this protein

  2. Feasibility of direct oxygenation of primary-cultured rat hepatocytes using polyethylene glycol-decorated liposome-encapsulated hemoglobin (LEH).

    Science.gov (United States)

    Naruto, Hirosuke; Huang, Hongyun; Nishikawa, Masaki; Kojima, Nobuhiko; Mizuno, Atsushi; Ohta, Katsuji; Sakai, Yasuyuki

    2007-10-01

    We tested the short-term efficacy of liposome-encapsulated hemoglobin (LEH) in cultured rat hepatocytes. Supplementation with LEH (20% of the hemoglobin concentration of blood) did not lower albumin production in static culture, and completely reversed the cell death and deterioration in albumin production caused by an oxygen shortage in 2D flat-plate perfusion bioreactors.

  3. Engineering the oxygen sensing regulation results in an enhanced recombinant human hemoglobin production by Saccharomyces cerevisiae

    DEFF Research Database (Denmark)

    Martinez Ruiz, José Luis; Liu, Lifang; Petranovic, Dina

    2015-01-01

    Efficient production of appropriate oxygen carriers for transfusions (blood substitutes or artificial blood) has been pursued for many decades, and to date several strategies have been used, from synthetic polymers to cell-free hemoglobin carriers. The recent advances in the field of metabolic en...... the transcription factor HAP1, which resulted in an increase of the final recombinant active hemoglobin titer exceeding 7% of the total cellular protein....

  4. Effect of gamma irradiation on the structure and function of bovine hemoglobin A

    International Nuclear Information System (INIS)

    Wdzieczak, J.

    1979-01-01

    The aim of this work was to establish the nature of the radiation damage and to discuss the relationship between structural and functional changes of gamma irradiated hemoglobin. Bovine HbA has been irradiated in dilute aqueous solution with 60 Co-rays (1-4 Mrad). The microzonal electrophoresis and isoelectric focusing indicated changes in the electric charge of hemoglobin molecules. At the same time for the doses exceeding 2 Mrad disturbances in fingerprinting separation were found. These changes were confirmed by amino acid analysis. It was stated that His, Trp, Cys, Met, Tyr and Pro were the main residues affected. The decrease of amino acids content was accompanied by the lowering of heme-heme interaction and the increase of oxygen affinity. It is probably connected with the injuries of amino acids responsible for the functional properties of hemoglobin. (author)

  5. High impact of uranyl ions on carrying-releasing oxygen capability of hemoglobin-based blood substitutes

    Energy Technology Data Exchange (ETDEWEB)

    Duan, Li; Du, Lili; Liu, Wenyuan; Liu, Zhichao [Northwest Institute of Nuclear Technology, Xi' an, Shaanxi (China); Jia, Yi; Li, Junbai [Beijing National Laboratory for Molecular Sciences, CAS Key Laboratory of Colloid Interface and Chemical Thermodynamics, Institute of Chemistry, Chinese Academy of Sciences, Beijing (China)

    2015-01-07

    The effect of radioactive UO{sub 2}{sup 2+} on the oxygen-transporting capability of hemoglobin-based oxygen carriers has been investigated in vitro. The hemoglobin (Hb) microspheres fabricated by the porous template covalent layer-by-layer (LbL) assembly were utilized as artificial oxygen carriers and blood substitutes. Magnetic nanoparticles of iron oxide (Fe{sub 3}O{sub 4}) were loaded in porous CaCO{sub 3} particles for magnetically assisted chemical separation (MACS). Through the adsorption spectrum of magnetic Hb microspheres after adsorbing UO{sub 2}{sup 2+}, it was found that UO{sub 2}{sup 2+} was highly loaded in the magnetic Hb microspheres, and it shows that the presence of UO{sub 2}{sup 2+} in vivo destroys the structure and oxygen-transporting capability of Hb microspheres. In view of the high adsorption capacity of UO{sub 2}{sup 2+}, the as-assembled magnetic Hb microspheres can be considered as a novel, highly effective adsorbent for removing metal toxins from radiation-contaminated bodies, or from nuclear-power reactor effluent before discharge into the environment. (copyright 2015 WILEY-VCH Verlag GmbH and Co. KGaA, Weinheim)

  6. Design, synthesis, and activity of 2,3-diphosphoglycerate analogs as allosteric modulators of hemoglobin O2 affinity.

    Science.gov (United States)

    Kassa, Tigist W; Zhang, Ning; Palmer, Andre F; Matthews, Jason Shastri

    2013-04-01

    Four phosphonate derivates of 2,3-diphosphoglycerate (2,3-DPG), in which the phosphate group is replaced by a methylene or difluoromethylene, were successfully synthesized for use as allosteric modulators of hemoglobin (Hb) O2 affinity. The syntheses were accomplished in four steps and the reagents were converted to their potassium salts to allow for effective binding with Hb in aqueous media. O2 equilibrium measurements of the chemically modified Hbs exhibited P50 values in the range 8.9-12.8 with Hill coefficients in the range of 1.5-2.4.

  7. The Greenland shark Somniosus microcephalus-Hemoglobins and ligand-binding properties.

    Directory of Open Access Journals (Sweden)

    Roberta Russo

    Full Text Available A large amount of data is currently available on the adaptive mechanisms of polar bony fish hemoglobins, but structural information on those of cartilaginous species is scarce. This study presents the first characterisation of the hemoglobin system of one of the longest-living vertebrate species (392 ± 120 years, the Arctic shark Somniosus microcephalus. Three major hemoglobins are found in its red blood cells and are made of two copies of the same α globin combined with two copies of three very similar β subunits. The three hemoglobins show very similar oxygenation and carbonylation properties, which are unaffected by urea, a very important compound in marine elasmobranch physiology. They display identical electronic absorption and resonance Raman spectra, indicating that their heme-pocket structures are identical or highly similar. The quaternary transition equilibrium between the relaxed (R and the tense (T states is more dependent on physiological allosteric effectors than in human hemoglobin, as also demonstrated in polar teleost hemoglobins. Similar to other cartilaginous fishes, we found no evidence for functional differentiation among the three isoforms. The very similar ligand-binding properties suggest that regulatory control of O2 transport may be at the cellular level and that it may involve changes in the cellular concentrations of allosteric effectors and/or variations of other systemic factors. The hemoglobins of this polar shark have evolved adaptive decreases in O2 affinity in comparison to temperate sharks.

  8. Fish hemoglobins

    Directory of Open Access Journals (Sweden)

    P.C. de Souza

    2007-06-01

    Full Text Available Vertebrate hemoglobin, contained in erythrocytes, is a globular protein with a quaternary structure composed of 4 globin chains (2 alpha and 2 beta and a prosthetic group named heme bound to each one. Having myoglobin as an ancestor, hemoglobin acquired the capacity to respond to chemical stimuli that modulate its function according to tissue requirements for oxygen. Fish are generally submitted to spatial and temporal O2 variations and have developed anatomical, physiological and biochemical strategies to adapt to the changing environmental gas availability. Structurally, most fish hemoglobins are tetrameric; however, those from some species such as lamprey and hagfish dissociate, being monomeric when oxygenated and oligomeric when deoxygenated. Fish blood frequently possesses several hemoglobins; the primary origin of this finding lies in the polymorphism that occurs in the globin loci, an aspect that may occasionally confer advantages to its carriers or even be a harmless evolutionary remnant. On the other hand, the functional properties exhibit different behaviors, ranging from a total absence of responses to allosteric regulation to drastic ones, such as the Root effect.

  9. Effect of Multiple Mutations in the Hemoglobin- and Hemoglobin-Haptoglobin-Binding Proteins, HgpA, HgpB, and HgpC, of Haemophilus influenzae Type b

    OpenAIRE

    Morton, Daniel J.; Whitby, Paul W.; Jin, Hongfan; Ren, Zhen; Stull, Terrence L.

    1999-01-01

    Haemophilus influenzae requires heme for growth and can utilize hemoglobin and hemoglobin-haptoglobin as heme sources. We previously identified two hemoglobin- and hemoglobin-haptoglobin-binding proteins, HgpA and HgpB, in H. influenzae HI689. Insertional mutation of hgpA and hgpB, either singly or together, did not abrogate the ability to utilize or bind either hemoglobin or the hemoglobin-haptoglobin complex. A hemoglobin affinity purification method was used to isolate a protein of approxi...

  10. Cerebral time domain-NIRS: reproducibility analysis, optical properties, hemoglobin species and tissue oxygen saturation in a cohort of adult subjects.

    Science.gov (United States)

    Giacalone, Giacomo; Zanoletti, Marta; Contini, Davide; Re, Rebecca; Spinelli, Lorenzo; Roveri, Luisa; Torricelli, Alessandro

    2017-11-01

    The reproducibility of cerebral time-domain near-infrared spectroscopy (TD-NIRS) has not been investigated so far. Besides, reference intervals of cerebral optical properties, of absolute concentrations of deoxygenated-hemoglobin (HbR), oxygenated-hemoglobin (HbO), total hemoglobin (HbT) and tissue oxygen saturation (StO 2 ) and their variability have not been reported. We have addressed these issues on a sample of 88 adult healthy subjects. TD-NIRS measurements at 690, 785, 830 nm were fitted with the diffusion model for semi-infinite homogenous media. Reproducibility, performed on 3 measurements at 5 minutes intervals, ranges from 1.8 to 6.9% for each of the hemoglobin species. The mean ± SD global values of HbR, HbO, HbT, StO 2 are respectively 24 ± 7 μM, 33.3 ± 9.5 μM, 57.4 ± 15.8 μM, 58 ± 4.2%. StO 2 displays the narrowest range of variability across brain regions.

  11. Near-simultaneous hemoglobin saturation and oxygen tension maps in mouse brain using an AOTF microscope.

    Science.gov (United States)

    Shonat, R D; Wachman, E S; Niu, W; Koretsky, A P; Farkas, D L

    1997-09-01

    A newly developed microscope using acousto-optic tunable filters (AOTFs) was used to generate in vivo hemoglobin saturation (SO2) and oxygen tension (PO2) maps in the cerebral cortex of mice. SO2 maps were generated from the spectral analysis of reflected absorbance images collected at different wavelengths, and PO2 maps were generated from the phosphorescence lifetimes of an injected palladium-porphyrin compound using a frequency-domain measurement. As the inspiratory O2 was stepped from hypoxia (10% O2), through normoxia (21% O2), to hyperoxia (60% O2), measured SO2 and PO2 levels rose accordingly and predictably throughout. A plot of SO2 versus PO2 in different arterial and venous regions of the pial vessels conformed to the sigmoidal shape of the oxygen-hemoglobin dissociation curve, providing further validation of the two mapping procedures. The study demonstrates the versatility of the AOTF microscope for in vivo physiologic investigation, allowing for the generation of nearly simultaneous SO2 and PO2 maps in the cerebral cortex, and the frequency-domain detection of phosphorescence lifetimes. This class of study opens up exciting new possibilities for investigating the dynamics of hemoglobin and O2 binding during functional activation of neuronal tissues.

  12. Structure and function of hemoglobin variants at an internal hydrophobic site: Consequences of mutations at the β 27 (B9) position

    International Nuclear Information System (INIS)

    Huang, Yue; Pagnier, J.; Magne, P.; Kister, J.; Poyart, C.; Baklouti, F.; Delaunay, J.; Fermi, G.; Perutz, M.F.

    1990-01-01

    The authors have studied the structure-function relationships in newly discovered hemoglobin (Hb) mutants with substitutions occurring at the tight and highly hydrophobic cluster between the B and G helices in the β chains, namely, Hb Knossos or β A27S and Hb Grange-Blanche or β A27V. The β A27S mutant has a 50% decrease in oxygen affinity relative to native human Hb A, while the β A27V mutant has an increased oxygen affinity. They have also engineered the artificial β A27T mutation through site-directed mutagenesis. This new mutant exhibits functional properties similar to those of Hb A. None of these mutants is unstable. X-ray analyses show that the substitution of Val for Ala may reduce the relative stability of the T structure of the molecule through packing effects in the β chains; for the β A27S mutant a new hydrogen bond between serine and the carbonyl O at β 23 (B5) Val is observed and is likely to increase the relative stability of the T structure in the mutant hemoglobin. However, no significant changes in the crystals were observed for these mutants between the quaternary R and T structures relative to native Hb A. They conclude that small tertiary structural changes in the tight hydrophobic B-G helix interface are sufficient to induce functional abnormalities resulting in either low or high intrinsic oxygen affinities

  13. Hemoglobin isoform differentiation and allosteric regulation of oxygen binding in the turtle, Trachemys scripta

    DEFF Research Database (Denmark)

    Damsgaard, Christian; Storz, Jay F.; Hoffmann, Federico G.

    2013-01-01

    When freshwater turtles acclimatize to winter hibernation, there is a gradual transition from aerobic to anaerobic metabolism, which may require adjustments of blood O2 transport before turtles become anoxic. Here, we report the effects of protons, anionic cofactors, and temperature on the O2......-binding properties of isolated hemoglobin (Hb) isoforms, HbA and HbD, in the turtle Trachemys scripta. We determined the primary structures of the constituent subunits of the two Hb isoforms, and we related the measured functional properties to differences in O2 affinity between untreated hemolysates from...... turtles that were acclimated to normoxia and anoxia. Our data show that HbD has a consistently higher O2 affinity compared with HbA, whereas Bohr and temperature effects, as well as thiol reactivity, are similar. Although sequence data show amino acid substitutions at two known β-chain ATP-binding site...

  14. Molecular controls of the oxygenation and redox reactions of hemoglobin.

    Science.gov (United States)

    Bonaventura, Celia; Henkens, Robert; Alayash, Abdu I; Banerjee, Sambuddha; Crumbliss, Alvin L

    2013-06-10

    The broad classes of O(2)-binding proteins known as hemoglobins (Hbs) carry out oxygenation and redox functions that allow organisms with significantly different physiological demands to exist in a wide range of environments. This is aided by allosteric controls that modulate the protein's redox reactions as well as its O(2)-binding functions. The controls of Hb's redox reactions can differ appreciably from the molecular controls for Hb oxygenation and come into play in elegant mechanisms for dealing with nitrosative stress, in the malarial resistance conferred by sickle cell Hb, and in the as-yet unsuccessful designs for safe and effective blood substitutes. An important basic principle in consideration of Hb's redox reactions is the distinction between kinetic and thermodynamic reaction control. Clarification of these modes of control is critical to gaining an increased understanding of Hb-mediated oxidative processes and oxidative toxicity in vivo. This review addresses emerging concepts and some unresolved questions regarding the interplay between the oxygenation and oxidation reactions of structurally diverse Hbs, both within red blood cells and under acellular conditions. Developing methods that control Hb-mediated oxidative toxicity will be critical to the future development of Hb-based blood substitutes.

  15. A comparison of blood nitric oxide metabolites and hemoglobin functional properties among diving mammals.

    Science.gov (United States)

    Fago, Angela; Parraga, Daniel Garcia; Petersen, Elin E; Kristensen, Niels; Giouri, Lea; Jensen, Frank B

    2017-03-01

    The ability of marine mammals to hunt prey at depth is known to rely on enhanced oxygen stores and on selective distribution of blood flow, but the molecular mechanisms regulating blood flow and oxygen transport remain unresolved. To investigate the molecular mechanisms that may be important in regulating blood flow, we measured concentration of nitrite and S-nitrosothiols (SNO), two metabolites of the vasodilator nitric oxide (NO), in the blood of 5 species of marine mammals differing in their dive duration: bottlenose dolphin, South American sea lion, harbor seal, walrus and beluga whale. We also examined oxygen affinity, sensitivity to 2,3-diphosphoglycerate (DPG) and nitrite reductase activity of the hemoglobin (Hb) to search for possible adaptive variations in these functional properties. We found levels of plasma and red blood cells nitrite similar to those reported for terrestrial mammals, but unusually high concentrations of red blood cell SNO in bottlenose dolphin, walrus and beluga whale, suggesting enhanced SNO-dependent signaling in these species. Purified Hbs showed similar functional properties in terms of oxygen affinity and sensitivity to DPG, indicating that reported large variations in blood oxygen affinity among diving mammals likely derive from phenotypic variations in red blood cell DPG levels. The nitrite reductase activities of the Hbs were overall slightly higher than that of human Hb, with the Hb of beluga whale, capable of longest dives, having the highest activity. Taken together, these results underscore adaptive variations in circulatory NO metabolism in diving mammals but not in the oxygenation properties of the Hb. Copyright © 2016 Elsevier Inc. All rights reserved.

  16. Nonlinear photoacoustic spectroscopy of hemoglobin

    Energy Technology Data Exchange (ETDEWEB)

    Danielli, Amos; Maslov, Konstantin; Favazza, Christopher P.; Xia, Jun; Wang, Lihong V., E-mail: LHWANG@WUSTL.EDU [Optical Imaging Laboratory, Department of Biomedical Engineering, Washington University in St. Louis, One Brookings Drive, St. Louis, Missouri 63130 (United States)

    2015-05-18

    As light intensity increases in photoacoustic imaging, the saturation of optical absorption and the temperature dependence of the thermal expansion coefficient result in a measurable nonlinear dependence of the photoacoustic (PA) signal on the excitation pulse fluence. Here, under controlled conditions, we investigate the intensity-dependent photoacoustic signals from oxygenated and deoxygenated hemoglobin at varied optical wavelengths and molecular concentrations. The wavelength and concentration dependencies of the nonlinear PA spectrum are found to be significantly greater in oxygenated hemoglobin than in deoxygenated hemoglobin. These effects are further influenced by the hemoglobin concentration. These nonlinear phenomena provide insights into applications of photoacoustics, such as measurements of average inter-molecular distances on a nm scale or with a tuned selection of wavelengths, a more accurate quantitative PA tomography.

  17. Nonlinear photoacoustic spectroscopy of hemoglobin.

    Science.gov (United States)

    Danielli, Amos; Maslov, Konstantin; Favazza, Christopher P; Xia, Jun; Wang, Lihong V

    2015-05-18

    As light intensity increases in photoacoustic imaging, the saturation of optical absorption and the temperature dependence of the thermal expansion coefficient result in a measurable nonlinear dependence of the photoacoustic (PA) signal on the excitation pulse fluence. Here, under controlled conditions, we investigate the intensity-dependent photoacoustic signals from oxygenated and deoxygenated hemoglobin at varied optical wavelengths and molecular concentrations. The wavelength and concentration dependencies of the nonlinear PA spectrum are found to be significantly greater in oxygenated hemoglobin than in deoxygenated hemoglobin. These effects are further influenced by the hemoglobin concentration. These nonlinear phenomena provide insights into applications of photoacoustics, such as measurements of average inter-molecular distances on a nm scale or with a tuned selection of wavelengths, a more accurate quantitative PA tomography.

  18. Nonlinear photoacoustic spectroscopy of hemoglobin

    International Nuclear Information System (INIS)

    Danielli, Amos; Maslov, Konstantin; Favazza, Christopher P.; Xia, Jun; Wang, Lihong V.

    2015-01-01

    As light intensity increases in photoacoustic imaging, the saturation of optical absorption and the temperature dependence of the thermal expansion coefficient result in a measurable nonlinear dependence of the photoacoustic (PA) signal on the excitation pulse fluence. Here, under controlled conditions, we investigate the intensity-dependent photoacoustic signals from oxygenated and deoxygenated hemoglobin at varied optical wavelengths and molecular concentrations. The wavelength and concentration dependencies of the nonlinear PA spectrum are found to be significantly greater in oxygenated hemoglobin than in deoxygenated hemoglobin. These effects are further influenced by the hemoglobin concentration. These nonlinear phenomena provide insights into applications of photoacoustics, such as measurements of average inter-molecular distances on a nm scale or with a tuned selection of wavelengths, a more accurate quantitative PA tomography

  19. Cloned Hemoglobin Genes Enhance Growth Of Cells

    Science.gov (United States)

    Khosla, Chaitan; Bailey, James E.

    1991-01-01

    Experiments show that portable deoxyribonucleic acid (DNA) sequences incorporated into host cells make them produce hemoglobins - oxygen-binding proteins essential to function of red blood cells. Method useful in several biotechnological applications. One, enhancement of growth of cells at higher densities. Another, production of hemoglobin to enhance supplies of oxygen in cells, for use in chemical reactions requiring oxygen, as additive to serum to increase transport of oxygen, and for binding and separating oxygen from mixtures of gases.

  20. Fish hemoglobins

    OpenAIRE

    Souza,P.C. de; Bonilla-Rodriguez,G.O.

    2007-01-01

    Vertebrate hemoglobin, contained in erythrocytes, is a globular protein with a quaternary structure composed of 4 globin chains (2 alpha and 2 beta) and a prosthetic group named heme bound to each one. Having myoglobin as an ancestor, hemoglobin acquired the capacity to respond to chemical stimuli that modulate its function according to tissue requirements for oxygen. Fish are generally submitted to spatial and temporal O2 variations and have developed anatomical, physiological and biochemica...

  1. Molecular Controls of the Oxygenation and Redox Reactions of Hemoglobin

    Science.gov (United States)

    Henkens, Robert; Alayash, Abdu I.; Banerjee, Sambuddha; Crumbliss, Alvin L.

    2013-01-01

    Abstract Significance: The broad classes of O2-binding proteins known as hemoglobins (Hbs) carry out oxygenation and redox functions that allow organisms with significantly different physiological demands to exist in a wide range of environments. This is aided by allosteric controls that modulate the protein's redox reactions as well as its O2-binding functions. Recent Advances: The controls of Hb's redox reactions can differ appreciably from the molecular controls for Hb oxygenation and come into play in elegant mechanisms for dealing with nitrosative stress, in the malarial resistance conferred by sickle cell Hb, and in the as-yet unsuccessful designs for safe and effective blood substitutes. Critical Issues: An important basic principle in consideration of Hb's redox reactions is the distinction between kinetic and thermodynamic reaction control. Clarification of these modes of control is critical to gaining an increased understanding of Hb-mediated oxidative processes and oxidative toxicity in vivo. Future Directions: This review addresses emerging concepts and some unresolved questions regarding the interplay between the oxygenation and oxidation reactions of structurally diverse Hbs, both within red blood cells and under acellular conditions. Developing methods that control Hb-mediated oxidative toxicity will be critical to the future development of Hb-based blood substitutes. Antioxid. Redox Signal. 18, 2298–2313. PMID:23198874

  2. Practical considerations in the development of hemoglobin-based oxygen therapeutics.

    Science.gov (United States)

    Kim, Hae Won; Estep, Timothy N

    2012-09-01

    The development of hemoglobin based oxygen therapeutics (HBOCs) requires consideration of a number of factors. While the enabling technology derives from fundamental research on protein biochemistry and biological interactions, translation of these research insights into usable medical therapeutics demands the application of considerable technical expertise and consideration and reconciliation of a myriad of manufacturing, medical, and regulatory requirements. The HBOC development challenge is further exacerbated by the extremely high intravenous doses required for many of the indications contemplated for these products, which in turn implies an extremely high level of purity is required. This communication discusses several of the important product configuration and developmental considerations that impact the translation of fundamental research discoveries on HBOCs into usable medical therapeutics.

  3. Role of Reversible Histidine Coordination in Hydroxylamine Reduction by Plant Hemoglobins (Phytoglobins).

    Science.gov (United States)

    Athwal, Navjot Singh; Alagurajan, Jagannathan; Andreotti, Amy H; Hargrove, Mark S

    2016-10-18

    Reduction of hydroxylamine to ammonium by phytoglobin, a plant hexacoordinate hemoglobin, is much faster than that of other hexacoordinate hemoglobins or pentacoordinate hemoglobins such as myoglobin, leghemoglobin, and red blood cell hemoglobin. The reason for differences in reactivity is not known but could be intermolecular electron transfer between protein molecules in support of the required two-electron reduction, hydroxylamine binding, or active site architecture favoring the reaction. Experiments were conducted with phytoglobins from rice, tomato, and soybean along with human neuroglobin and soybean leghemoglobin that reveal hydroxylamine binding as the rate-limiting step. For hexacoordinate hemoglobins, binding is limited by the dissociation rate constant for the distal histidine, while leghemoglobin is limited by an intrinsically low affinity for hydroxylamine. When the distal histidine is removed from rice phytoglobin, a hydroxylamine-bound intermediate is formed and the reaction rate is diminished, indicating that the distal histidine imidazole side chain is critical for the reaction, albeit not for electron transfer but rather for direct interaction with the substrate. Together, these results demonstrate that phytoglobins are superior at hydroxylamine reduction because they have distal histidine coordination affinity constants near 1, and facile rate constants for binding and dissociation of the histidine side chain. Hexacoordinate hemoglobins such as neuroglobin are limited by tighter histidine coordination that blocks hydroxylamine binding, and pentacoordinate hemoglobins have intrinsically lower hydroxylamine affinities.

  4. The conserved Phe GH5 of importance for hemoglobin intersubunit contact is mutated in gadoid fish

    Science.gov (United States)

    2014-01-01

    Background Functionality of the tetrameric hemoglobin molecule seems to be determined by a few amino acids located in key positions. Oxygen binding encompasses structural changes at the interfaces between the α1β2 and α2β1 dimers, but also subunit interactions are important for the oxygen binding affinity and stability. The latter packing contacts include the conserved Arg B12 interacting with Phe GH5, which is replaced by Leu and Tyr in the αA and αD chains, respectively, of birds and reptiles. Results Searching all known hemoglobins from a variety of gnathostome species (jawed vertebrates) revealed the almost invariant Arg B12 coded by the AGG triplet positioned at an exon-intron boundary. Rare substitutions of Arg B12 in the gnathostome β globins were found in pig, tree shrew and scaled reptiles. Phe GH5 is also highly conserved in the β globins, except for the Leu replacement in the β1 globin of five marine gadoid species, gilthead seabream and the Comoran coelacanth, while Cys and Ile were found in burbot and yellow croaker, respectively. Atlantic cod β1 globin showed a Leu/Met polymorphism at position GH5 dominated by the Met variant in northwest-Atlantic populations that was rarely found in northeast-Atlantic cod. Site-specific analyses identified six consensus codons under positive selection, including 122β(GH5), indicating that the amino acid changes identified at this position may offer an adaptive advantage. In fact, computational mutation analysis showed that the replacement of Phe GH5 with Leu or Cys decreased the number of van der Waals contacts essentially in the deoxy form that probably causes a slight increase in the oxygen binding affinity. Conclusions The almost invariant Arg B12 and the AGG codon seem to be important for the packing contacts and pre-mRNA processing, respectively, but the rare mutations identified might be beneficial. The Leu122β1(GH5)Met and Met55β1(D6)Val polymorphisms in Atlantic cod hemoglobin modify the

  5. Diphosphoglycerate and Inosine Hexaphosphate Control of Oxygen Binding by Hemoglobin: A Theoretical Interpretation of Experimental Data*

    Science.gov (United States)

    Ling, Gilbert N.

    1970-01-01

    A theoretical equation is presented for the control of cooperative adsorption on proteins and other linear macromolecules by hormones, drugs, ATP, and other „cardinal adsorbents.” With reasonable accuracy, this equation describes quantitatively the control of oxygen binding to hemoglobin by 2,3-diphosphoglycerate and by inosine hexaphosphate. PMID:5272319

  6. Crystallographic analysis of human hemoglobin elucidates the structural basis of the potent and dual antisickling activity of pyridyl derivatives of vanillin

    Energy Technology Data Exchange (ETDEWEB)

    Abdulmalik, Osheiza [The Children’s Hospital of Philadelphia, Philadelphia, PA 19104 (United States); Ghatge, Mohini S.; Musayev, Faik N.; Parikh, Apurvasena [Virginia Commonwealth University, Richmond, VA 23298 (United States); Chen, Qiukan; Yang, Jisheng [The Children’s Hospital of Philadelphia, Philadelphia, PA 19104 (United States); Nnamani, Ijeoma [Duke University Medical Center, Durham, NC 27710 (United States); Danso-Danquah, Richmond [Virginia Commonwealth University, Richmond, VA 23298 (United States); Eseonu, Dorothy N. [Virginia Union University, Richmond, VA 23220 (United States); Asakura, Toshio [Duke University Medical Center, Durham, NC 27710 (United States); Abraham, Donald J.; Venitz, Jurgen; Safo, Martin K., E-mail: msafo@vcu.edu [Virginia Commonwealth University, Richmond, VA 23298 (United States); The Children’s Hospital of Philadelphia, Philadelphia, PA 19104 (United States)

    2011-11-01

    Pyridyl derivatives of vanillin increase the fraction of the more soluble oxygenated sickle hemoglobin and/or directly increase the solubility of deoxygenated sickle hemoglobin. Crystallographic analysis reveals the structural basis of the potent and dual antisickling activity of these derivatives. Vanillin has previously been studied clinically as an antisickling agent to treat sickle-cell disease. In vitro investigations with pyridyl derivatives of vanillin, including INN-312 and INN-298, showed as much as a 90-fold increase in antisickling activity compared with vanillin. The compounds preferentially bind to and modify sickle hemoglobin (Hb S) to increase the affinity of Hb for oxygen. INN-312 also led to a considerable increase in the solubility of deoxygenated Hb S under completely deoxygenated conditions. Crystallographic studies of normal human Hb with INN-312 and INN-298 showed that the compounds form Schiff-base adducts with the N-terminus of the α-subunits to constrain the liganded (or relaxed-state) Hb conformation relative to the unliganded (or tense-state) Hb conformation. Interestingly, while INN-298 binds and directs its meta-positioned pyridine-methoxy moiety (relative to the aldehyde moiety) further down the central water cavity of the protein, that of INN-312, which is ortho to the aldehyde, extends towards the surface of the protein. These studies suggest that these compounds may act to prevent sickling of SS cells by increasing the fraction of the soluble high-affinity Hb S and/or by stereospecific inhibition of deoxygenated Hb S polymerization.

  7. Crystallographic analysis of human hemoglobin elucidates the structural basis of the potent and dual antisickling activity of pyridyl derivatives of vanillin

    International Nuclear Information System (INIS)

    Abdulmalik, Osheiza; Ghatge, Mohini S.; Musayev, Faik N.; Parikh, Apurvasena; Chen, Qiukan; Yang, Jisheng; Nnamani, Ijeoma; Danso-Danquah, Richmond; Eseonu, Dorothy N.; Asakura, Toshio; Abraham, Donald J.; Venitz, Jurgen; Safo, Martin K.

    2011-01-01

    Pyridyl derivatives of vanillin increase the fraction of the more soluble oxygenated sickle hemoglobin and/or directly increase the solubility of deoxygenated sickle hemoglobin. Crystallographic analysis reveals the structural basis of the potent and dual antisickling activity of these derivatives. Vanillin has previously been studied clinically as an antisickling agent to treat sickle-cell disease. In vitro investigations with pyridyl derivatives of vanillin, including INN-312 and INN-298, showed as much as a 90-fold increase in antisickling activity compared with vanillin. The compounds preferentially bind to and modify sickle hemoglobin (Hb S) to increase the affinity of Hb for oxygen. INN-312 also led to a considerable increase in the solubility of deoxygenated Hb S under completely deoxygenated conditions. Crystallographic studies of normal human Hb with INN-312 and INN-298 showed that the compounds form Schiff-base adducts with the N-terminus of the α-subunits to constrain the liganded (or relaxed-state) Hb conformation relative to the unliganded (or tense-state) Hb conformation. Interestingly, while INN-298 binds and directs its meta-positioned pyridine-methoxy moiety (relative to the aldehyde moiety) further down the central water cavity of the protein, that of INN-312, which is ortho to the aldehyde, extends towards the surface of the protein. These studies suggest that these compounds may act to prevent sickling of SS cells by increasing the fraction of the soluble high-affinity Hb S and/or by stereospecific inhibition of deoxygenated Hb S polymerization

  8. Theoretical model for optical oximetry at the capillary level: exploring hemoglobin oxygen saturation through backscattering of single red blood cells

    Science.gov (United States)

    Liu, Rongrong; Spicer, Graham; Chen, Siyu; Zhang, Hao F.; Yi, Ji; Backman, Vadim

    2017-02-01

    Oxygen saturation (sO2) of red blood cells (RBCs) in capillaries can indirectly assess local tissue oxygenation and metabolic function. For example, the altered retinal oxygenation in diabetic retinopathy and local hypoxia during tumor development in cancer are reflected by abnormal sO2 of local capillary networks. However, it is far from clear whether accurate label-free optical oximetry (i.e., measuring hemoglobin sO2) is feasible from dispersed RBCs at the single capillary level. The sO2-dependent hemoglobin absorption contrast present in optical scattering signal is complicated by geometry-dependent scattering from RBCs. We present a numerical study of backscattering spectra from single RBCs based on the first-order Born approximation, considering practical factors: RBC orientations, size variation, and deformations. We show that the oscillatory spectral behavior of RBC geometries is smoothed by variations in cell size and orientation, resulting in clear sO2-dependent spectral contrast. In addition, this spectral contrast persists with different mean cellular hemoglobin content and different deformations of RBCs. This study shows for the first time the feasibility of, and provides a theoretical model for, label-free optical oximetry at the single capillary level using backscattering-based imaging modalities, challenging the popular view that such measurements are impossible at the single capillary level.

  9. Hemoglobin fructation promotes heme degradation through the generation of endogenous reactive oxygen species

    Science.gov (United States)

    Goodarzi, M.; Moosavi-Movahedi, A. A.; Habibi-Rezaei, M.; Shourian, M.; Ghourchian, H.; Ahmad, F.; Farhadi, M.; Saboury, A. A.; Sheibani, N.

    2014-09-01

    Protein glycation is a cascade of nonenzymatic reactions between reducing sugars and amino groups of proteins. It is referred to as fructation when the reducing monosaccharide is fructose. Some potential mechanisms have been suggested for the generation of reactive oxygen species (ROS) by protein glycation reactions in the presence of glucose. In this state, glucose autoxidation, ketoamine, and oxidative advance glycation end products (AGEs) formation are considered as major sources of ROS and perhaps heme degradation during hemoglobin glycation. However, whether fructose mediated glycation produces ROS and heme degradation is unknown. Here we report that ROS (H2O2) production occurred during hemoglobin fructation in vitro using chemiluminescence methods. The enhanced heme exposure and degradation were determined using UV-Vis and fluorescence spectrophotometry. Following accumulation of ROS, heme degradation products were accumulated reaching a plateau along with the detected ROS. Thus, fructose may make a significant contribution to the production of ROS, glycation of proteins, and heme degradation during diabetes.

  10. TRUNCATED OR 2/2 HEMOGLOBINS : A NEW CLASS OF GLOBINS WITH NOVEL STRUCTURE AND FUNCTION

    Directory of Open Access Journals (Sweden)

    Amit Kumar

    2013-06-01

    Full Text Available Bright red hemoglobins, the most well-known paradigm in protein science, seem to be ubiquitous in nature. With advances in modern tools and techniques, discovery of new globins at a rapid pace has expanded this family. With every discovery, new insights emerged regarding their novel structure, function and several other characteristics previously not observed for hemoglobins. Even the classical function unanimously assigned to hemoglobinsoxygen transport and storage – needed re-evaluation. The ability of this class of proteins to show responses against various gaseous ligands, even the poisonous ones, indicate that it is obviously as ancient as life. As organisms evolved, hemoglobins also evolved, and accumulated a great degree of diversity in all aspects. The classical globin fold is very unique with 3-on-3 alpha helical bundle as observed in the traditional oxygen-transport hemoglobins like myoglobin, human blood hemoglobin and leghemoglobins in plants. However, a class of the newly discovered hemoglobins, which dominate the superfamily and appears ancient in origin mostly have 2-on-2 fold, commonly termed as “truncated” hemoglobins. These hemoglobins are phylogenetically distinct from their classical counterparts and are often shorter in their polypeptide length by 20-40 residues mainly due to a lack of short A helix, D helix and F helix. However, hemoglobins with 2-on-2 fold were also later found to have polypeptide chain lengths similar in size to classical globins. Disordered pre-F helix region, conserved glycine motifs and other key residues and apolar tunnels through their protein matrix for migration of ligands are some unique characteristics features of these truncated hemoglobins. Some of these are also hexacoordinated at heme iron where an amino acid from within the protein coordinates heme iron in absence of a ligand. These hemoglobins are well known for their high affinity towards ligand and have a diverse mechanism of

  11. Model analysis of local oxygen delivery with liposome-encapsulated hemoglobin.

    Science.gov (United States)

    Matsumoto, Takeshi; Mano, Katsuhiko; Ueha, Ryohei; Naito, Hisashi; Tanaka, Masao

    2009-03-01

    Liposome-encapsulated hemoglobins (LHs) are comparable to red blood cells (RBCs) in terms of oxygen (O(2))-carrying capacity. The smaller particle size of LHs than of platelets allows their homogeneous dispersion in circulating plasma. In this study, we evaluated the effect of LH transfusion on arterial O(2) delivery through vascular trees by simulation. A mathematical model was established on the basis of the coronary arterial anatomy, the conservation of flow and RBC flux, and Poiseuille's law. The Fåhraeus-Lindqvist, Fåhraeus, and phase separation effects were considered in the model. By assuming steady perfusion, the arterial flow and O(2) delivery were calculated for five model trees undergoing the isovolumic replacement of RBCs (0.3 mg hemoglobin (Hb)/mL) with LHs (0.2 mg Hb/mL) or a plasma volume expander (PVE). The RBC-LH exchange increased both the total flow and the total O(2) flux but had almost no effect on the relative distribution of O(2) flux. In contrast, the RBC-PVE exchange decreased the total O(2) flux and increased the proportion of regions receiving a relatively low O(2) supply. Thus, LH transfusion may compensate for an enhanced bias in RBC-associated O(2) flux under hemodilution and is expected to be beneficial for both total and local O(2) delivery.

  12. Oxygen affinity and acid-base status of human blood during exposure to hypoxia and carbon monoxide

    Energy Technology Data Exchange (ETDEWEB)

    Mulhausen, R.O.; Astrup, P.; Mellemgaard, K.

    1968-01-01

    Eight individuals exposed to hypoxia at altitude or simulated altitude in hypobaric chamber had hemoglobin with a decreased affinity for O/sub 2/ as shown by a shift in the dissociation curve to the right (about 4 mm at 3450 m). Acid-base changes could not explain shift. Intermittent CO doses to maintain approx. 15% carboxyhemoglobin produced the typical shift to the left. Acid-base changes were insignificant. Proposed adaptation mechanism for combating hypoxia does not work for CO poisoning.

  13. Mechanisms controlling the oxygen consumption in experimentally induced hypochloremic alkalosis in calves.

    Science.gov (United States)

    Cambier, Carole; Clerbaux, Thierry; Amory, Hélène; Detry, Bruno; Florquin, Sandra; Marville, Vincent; Frans, Albert; Gustin, Pascal

    2002-01-01

    The study was carried out on healthy Friesian calves (n = 10) aged between 10 and 30 days. Hypochloremia and alkalosis were induced by intravenous administration of furosemide and isotonic sodium bicarbonate. The venous and arterial blood samples were collected repeatedly. 2,3-diphosphoglycerate (2,3-DPG), hemoglobin and plasmatic chloride concentrations were determined. The red blood cell chloride concentration was also calculated. pH, PCO2 and PO2 were measured in arterial and mixed venous blood. The oxygen equilibrium curve (OEC) was measured in standard conditions. The correspondence of the OEC to the arterial and mixed venous compartments was calculated, taking blood temperature, pH and PCO2 values into account. The oxygen exchange fraction (OEF%), corresponding to the degree of blood desaturation between the arterial and mixed venous compartments and the amount of oxygen released at the tissue level by 100 mL of blood (OEF Vol%) were calculated from the arterial and mixed venous OEC, combined with PO2 and hemoglobin concentration. Oxygen delivery (DO2) was calculated using the arterial oxygen content, the cardiac output measured by thermodilution, and the body weight of the animal. The oxygen consumption (VO2) was derived from the cardiac output, OEF Vol% and body weight values. Despite the plasma hypochloremia, the erythrocyte chloride concentration was not influenced by furosemide and sodium bicarbonate infusion. Due to the alkalosis-induced increase in the 2,3-DPG, the standard OEC was shifted to the right, allowing oxygen to dissociate from hemoglobin more rapidly. These changes opposed the increased affinity of hemoglobin for oxygen induced by alkalosis. Moreover, respiratory acidosis, hemoconcentration, and the slight decrease in the partial oxygen pressure in mixed venous blood (Pvo2) tended to improve the OEF Vol% and maintain the oxygen consumption in a physiological range while the cardiac output, and the oxygen delivery were significantly decreased

  14. Effects of gamma irradiation on the structure and function of human hemoglobin

    International Nuclear Information System (INIS)

    Szweda-Lewandowska, Z.; Puchala, M.; Leyko, W.

    1976-01-01

    In this paper physicochemical and functional properties of irradiated aqueous hemoglobin solutions are presented. HbO 2 solutions (5 percent) were irradiated in air with doses ranging from 0.5 to 5 Mrad at the efficiency of 1 Mrad/hr. At doses exceeding 1 Mrad, coagulation of small amounts of protein was observed. Hemoglobin which remained in the solution consisted of a mixture of HbO 2 and MetHb. At doses of 4 and 5 Mrad the presence of hemochromogen was established. The appropriate hydrodynamic parameters--molecular weight, sedimentation constant, and limiting viscosity value--do not differ from the control values up to a dose of 1 Mrad. At greater doses sedimentation constants and the limiting viscosity number increase. The decrease in the values of the second virial coefficient and the electrophoretic behavior in polyacrylamide gel suggest some changes in the electric charge of the molecules. Simultaneously, a considerable part of the molecules exhibits an increased affinity for oxygen and a decreased heme--heme interaction

  15. Expression of embryonic hemoglobin genes in mice heterozygous for α-thalassemia or β-duplication traits and in mice heterozygous for both traits

    International Nuclear Information System (INIS)

    Popp, R.A.; Marsh, C.L.; Skow, L.C.

    1981-01-01

    Hemoglobins of mouse embryos at 11.5 through 16.5 days of gestation were separated by electrophoresis on cellulose acetate and quantitated by a scanning densitometer to study the effects of two radiation-induced mutations on the expression of embryonic hemoglobin genes in mice. Normal mice produce three kinds of embryonic hemoglobins. In heterozygous α-thalassemic embryos, expression of EI (x 2 y 2 ) and EII (α 2 y 2 ) is deficient because the x- and α-globin genes of one of the allelic pairs of Hba on chromosome 11 was deleted or otherwise inactivated by X irradiation. Simultaneous inactivation of the x- and α-globin genes indicates that these genes must be closely linked. Reduced x- and α-chain synthesis results in an excess of y chains that associate as homotetramers. This unique y 4 hemoglobin also appears in β-duplication embryos where excess y chains are produced by the presence of three rather than two functional alleles of y- and β-globin genes. In double heterozygotes, which have a single functional allele of x- and α-globin genes and three functional alleles of y- and β-globin genes, synthesis of α and non-α chains is severely imbalanced and half of the total hemoglobin is y 4 . Mouse y 4 has a high affinity for oxygen, P 50 of less than 10 mm Hg, but it lacks cooperativity so is inefficient for oxygen transport. The death of double heterozygotes in late fetal or neonatal life may be in large part to oxygen deprivation to the tissues

  16. Interplay between up-regulation of cytochrome-c-oxidase and hemoglobin oxygenation induced by near-infrared laser

    Science.gov (United States)

    Wang, Xinlong; Tian, Fenghua; Soni, Sagar S.; Gonzalez-Lima, F.; Liu, Hanli

    2016-08-01

    Photobiomodulation, also known as low-level laser/light therapy (LLLT), refers to the use of red-to-near-infrared light to stimulate cellular functions for physiological or clinical benefits. The mechanism of LLLT is assumed to rely on photon absorption by cytochrome c oxidase (CCO), the terminal enzyme in the mitochondrial respiratory chain that catalyzes the reduction of oxygen for energy metabolism. In this study, we used broadband near-infrared spectroscopy (NIRS) to measure the LLLT-induced changes in CCO and hemoglobin concentrations in human forearms in vivo. Eleven healthy participants were administered with 1064-nm laser and placebo treatments on their right forearms. The spectroscopic data were analyzed and fitted with wavelength-dependent, modified Beer-Lambert Law. We found that LLLT induced significant increases of CCO concentration (Δ[CCO]) and oxygenated hemoglobin concentration (Δ[HbO]) on the treated site as the laser energy dose accumulated over time. A strong linear interplay between Δ[CCO] and Δ[HbO] was observed for the first time during LLLT, indicating a hemodynamic response of oxygen supply and blood volume closely coupled to the up-regulation of CCO induced by photobiomodulation. These results demonstrate the tremendous potential of broadband NIRS as a non-invasive, in vivo means to study mechanisms of photobiomodulation and perform treatment evaluations of LLLT.

  17. Phenotypic plasticity in blood–oxygen transport in highland and lowland deer mice

    Science.gov (United States)

    Tufts, Danielle M.; Revsbech, Inge G.; Cheviron, Zachary A.; Weber, Roy E.; Fago, Angela; Storz, Jay F.

    2013-01-01

    SUMMARY In vertebrates living at high altitude, arterial hypoxemia may be ameliorated by reversible changes in the oxygen-carrying capacity of the blood (regulated by erythropoiesis) and/or changes in blood–oxygen affinity (regulated by allosteric effectors of hemoglobin function). These hematological traits often differ between taxa that are native to different elevational zones, but it is often unknown whether the observed physiological differences reflect fixed, genetically based differences or environmentally induced acclimatization responses (phenotypic plasticity). Here, we report measurements of hematological traits related to blood–O2 transport in populations of deer mice (Peromyscus maniculatus) that are native to high- and low-altitude environments. We conducted a common-garden breeding experiment to assess whether altitude-related physiological differences were attributable to developmental plasticity and/or physiological plasticity during adulthood. Under conditions prevailing in their native habitats, high-altitude deer mice from the Rocky Mountains exhibited a number of pronounced hematological differences relative to low-altitude conspecifics from the Great Plains: higher hemoglobin concentrations, higher hematocrits, higher erythrocytic concentrations of 2,3-diphosphoglycerate (an allosteric regulator of hemoglobin–oxygen affinity), lower mean corpuscular hemoglobin concentrations and smaller red blood cells. However, these differences disappeared after 6 weeks of acclimation to normoxia at low altitude. The measured traits were also indistinguishable between the F1 progeny of highland and lowland mice, indicating that there were no persistent differences in phenotype that could be attributed to developmental plasticity. These results indicate that the naturally occurring hematological differences between highland and lowland mice are environmentally induced and are largely attributable to physiological plasticity during adulthood. PMID

  18. Simultaneous estimation of transcutaneous bilirubin, hemoglobin, and melanin based on diffuse reflectance spectroscopy

    Science.gov (United States)

    Nishidate, Izumi; Abdul, Wares MD.; Ohtsu, Mizuki; Nakano, Kazuya; Haneishi, Hideaki

    2018-02-01

    We propose a method to estimate transcutaneous bilirubin, hemoglobin, and melanin based on the diffuse reflectance spectroscopy. In the proposed method, the Monte Carlo simulation-based multiple regression analysis for an absorbance spectrum in the visible wavelength region (460-590 nm) is used to specify the concentrations of bilirubin (Cbil), oxygenated hemoglobin (Coh), deoxygenated hemoglobin (Cdh), and melanin (Cm). Using the absorbance spectrum calculated from the measured diffuse reflectance spectrum as a response variable and the extinction coefficients of bilirubin, oxygenated hemoglobin, deoxygenated hemoglobin, and melanin, as predictor variables, multiple regression analysis provides regression coefficients. Concentrations of bilirubin, oxygenated hemoglobin, deoxygenated hemoglobin, and melanin, are then determined from the regression coefficients using conversion vectors that are numerically deduced in advance by the Monte Carlo simulations for light transport in skin. Total hemoglobin concentration (Cth) and tissue oxygen saturation (StO2) are simply calculated from the oxygenated hemoglobin and deoxygenated hemoglobin. In vivo animal experiments with bile duct ligation in rats demonstrated that the estimated Cbil is increased after ligation of bile duct and reaches to around 20 mg/dl at 72 h after the onset of the ligation, which corresponds to the reference value of Cbil measured by a commercially available transcutaneous bilirubin meter. We also performed in vivo experiments with rats while varying the fraction of inspired oxygen (FiO2). Coh and Cdh decreased and increased, respectively, as FiO2 decreased. Consequently, StO2 was dramatically decreased. The results in this study indicate potential of the method for simultaneous evaluation of multiple chromophores in skin tissue.

  19. The effects of 2,3-diphosphoglycerate, adenosine triphosphate, and glycosylated hemoglobin on the hemoglobin-oxygen affinity of diabetic patients

    OpenAIRE

    E.M. Castilho; M.L. Glass; J.C. Manço

    2003-01-01

    The position of the oxygen dissociation curve (ODC) is modulated by 2,3-diphosphoglycerate (2,3-DPG). Decreases in 2,3-DPG concentration within the red cell shift the curve to the left, whereas increases in concentration cause a shift to the right of the ODC. Some earlier studies on diabetic patients have reported that insulin treatment may reduce the red cell concentrations of 2,3-DPG, causing a shift of the ODC to the left, but the reports are contradictory. Three groups were compared in th...

  20. High blood oxygen affinity in the air-breathing swamp eel Monopterus albus.

    Science.gov (United States)

    Damsgaard, Christian; Findorf, Inge; Helbo, Signe; Kocagoz, Yigit; Buchanan, Rasmus; Huong, Do Thi Thanh; Weber, Roy E; Fago, Angela; Bayley, Mark; Wang, Tobias

    2014-12-01

    The Asian swamp eel (Monopterus albus, Zuiew 1793) is a facultative air-breathing fish with reduced gills. Previous studies have shown that gas exchange seems to occur across the epithelium of the buccopharyngeal cavity, the esophagus and the integument, resulting in substantial diffusion limitations that must be compensated by adaptations in others steps of the O₂ transport system to secure adequate O₂ delivery to the respiring tissues. We therefore investigated O₂ binding properties of whole blood, stripped hemoglobin (Hb), two major isoHb components and the myoglobin (Mb) from M. albus. Whole blood was sampled using indwelling catheters for blood gas analysis and determination of O₂ equilibrium curves. Hb was purified to assess the effects of endogenous allosteric effectors, and Mb was isolated from heart and skeletal muscle to determine its O₂ binding properties. The blood of M. albus has a high O₂ carrying capacity [hematocrit (Hct) of 42.4±4.5%] and binds O₂ with an unusually high affinity (P₅₀=2.8±0.4mmHg at 27°C and pH7.7), correlating with insensitivity of the Hb to the anionic allosteric effectors that normally decrease Hb-O₂ affinity. In addition, Mb is present at high concentrations in both heart and muscle (5.16±0.99 and 1.08±0.19mg ∙ g wet tissue⁻¹, respectively). We suggest that the high Hct and high blood O₂ affinity serve to overcome the low diffusion capacity in the relatively inefficient respiratory surfaces, while high Hct and Mb concentration aid in increasing the O₂ flux from the blood to the muscles. Copyright © 2014 Elsevier Inc. All rights reserved.

  1. Oxygenated hemoglobin diffuse reflectance ratio for in vitro detection of human gastric pre-cancer

    Science.gov (United States)

    Li, L. Q.; Wei, H. J.; Guo, Z. Y.; Yang, H. Q.; Wu, G. Y.; Xie, S. S.; Zhong, H. Q.; Li, X. Y.; Zhao, Q. L.; Guo, X.

    2010-07-01

    Oxygenated hemoglobin diffuse reflectance (DR) ratio (R540/R575) method based on DR spectral signatures is used for early diagnosis of malignant lesions of human gastric epithelial tissues in vitro. The DR spectra for four different kinds of gastric epithelial tissues were measured using a spectrometer with an integrating sphere detector in the spectral range from 400 to 650 nm. The results of measurement showed that the average DR spectral intensity for the epithelial tissues of normal stomach is higher than that for the epithelial tissues of chronic and malignant stomach and that for the epithelial tissues of chronic gastric ulcer is higher than that for the epithelial tissues of malignant stomach. The average DR spectra for four different kinds of gastric epithelial tissues show dips at 542 and 577 nm owing to absorption from oxygenated Hemoglobin (HbO2). The differences in the mean R540/R575 ratios of HbO2 bands are 6.84% between the epithelial tissues of normal stomach and chronic gastric ulcer, 14.7% between the epithelial tissues of normal stomach and poorly differentiated gastric adenocarcinoma and 22.6% between the epithelial tissues of normal stomach and undifferentiated gastric adenocarcinoma. It is evident from results that there were significant differences in the mean R540/R575 ratios of HbO2 bands for four different kinds of gastric epithelial tissues in vitro ( P < 0.01).

  2. The Effect of Chronic Hypercapnia on Oxygen Affinity and 2, 3 Diphosphoglycerate as Related to Submarine Exposure

    Science.gov (United States)

    The relationship between oxygen affinity and 2,3 diphosphoglycerate (2,3 DPG) in the red cell has been studied in chronic hypercapnia induced by...initial values after seven days of exposure. Both oxygen half-saturation pressure (P50) and the level of 2,3 DPG of the red cells followed the time

  3. In vivo detection of hemoglobin oxygen saturation and carboxyhemoglobin saturation with multiwavelength photoacoustic microscopy.

    Science.gov (United States)

    Chen, Zhongjiang; Yang, Sihua; Xing, Da

    2012-08-15

    A method for noninvasively detecting hemoglobin oxygen saturation (SO2) and carboxyhemoglobin saturation (SCO) in subcutaneous microvasculature with multiwavelength photoacoustic microscopy is presented. Blood samples mixed with different concentrations of carboxyhemoglobin were used to test the feasibility and accuracy of photoacoustic microscopy compared with the blood-gas analyzer. Moreover, fixed-point detection of SO2 and SCO in mouse ear was obtained, and the changes from normoxia to carbon monoxide hypoxia were dynamically monitored in vivo. Experimental results demonstrate that multiwavelength photoacoustic microscopy can detect SO2 and SCO, which has future potential clinical applications.

  4. Erythrocyte signal transduction pathways, their oxygenation dependence and functional significance.

    Science.gov (United States)

    Barvitenko, Nadezhda N; Adragna, Norma C; Weber, Roy E

    2005-01-01

    Erythrocytes play a key role in human and vertebrate metabolism. Tissue O2 supply is regulated by both hemoglobin (Hb)-O2 affinity and erythrocyte rheology, a key determinant of tissue perfusion. Oxygenation-deoxygenation transitions of Hb may lead to re-organization of the cytoskeleton and signalling pathways activation/deactivation in an O2-dependent manner. Deoxygenated Hb binds to the cytoplasmic domain of the anion exchanger band 3, which is anchored to the cytoskeleton, and is considered a major mechanism underlying the oxygenation-dependence of several erythrocyte functions. This work discusses the multiple modes of Hb-cytoskeleton interactions. In addition, it reviews the effects of Mg2+, 2,3-diphosphoglycerate, NO, shear stress and Ca2+, all factors accompanying the oxygenation-deoxygenation cycle in circulating red cells. Due to the extensive literature on the subject, the data discussed here, pertain mainly to human erythrocytes whose O2 affinity is modulated by 2,3-diphosphoglycerate, ectothermic vertebrate erythrocytes that use ATP, and to bird erythrocytes that use inositol pentaphosphate. Copyright 2005 S. Karger AG, Basel.

  5. Intraerythrocytic organic phosphates and hemoglobins of skua - Catharacta maccormicki (Stercoraridae: at two different stages of the year in relation to Antartic migration

    Directory of Open Access Journals (Sweden)

    Gustavo Fraga Landini

    2013-08-01

    Full Text Available Catharacta maccormicki blood samples were collected in the winter (October and in the summer (February in order to study the intraerythrocytic organic phosphates, hemoglobin (Hb electrophoretic patterns, oxygen blood equilibrium and stripped Hbs, as well as the effect of 2,3-biphosphoglycerate (BPG and inositol hexaphosphate (IHP on oxygen affinity. All the samples (five from the winter and five from the summer showed the same electrophoretic pattern: one minor fast component and one major slow one. No differences in oxygen affinity and Bohr effect in the samples collected in the winter and in the summer were found. Oxygen affinity was higher in the stripped Hb than in the blood. BPG seemed to have no effect on the functional properties of skua Hb while IHP does. No BPG was found in any sample. Both inositol pentaphosphate (IP5 and IHP were found in all the samples. The IP5/IHP ratio in the winter samples was 3.0 while in summer 3.5. Adenosine diphosphate (ADP was found in samples from both the seasons. Adenosine monophosphate (AMP and adenosine triphosphate (ATP were present only in the summer samples while guanosine triphosphate (GTP was found in the winter samples. Since IP5 and IHP are very powerful HB allosteric effectors, ATP and GTP might function as other protein modulators.

  6. Constraints on mutational pathways of hemoglobin evolution

    DEFF Research Database (Denmark)

    Kumar, Amit; Natarajan, Chandrasekhar; Moriyama, Hideaki

    2016-01-01

    amino acid substitutions that occurred during an evolutionary reduction in hemoglobin (Hb)-O2 affinity in nightjars (nocturnal birds in the family Caprimulgidae).We selected nightjar Hbs for experimental study because ancestral sequence reconstructions indicated that the evolved reduction in Hb-O2...

  7. Non-site-specific allosteric effect of oxygen on human hemoglobin under high oxygen partial pressure.

    Science.gov (United States)

    Takayanagi, Masayoshi; Kurisaki, Ikuo; Nagaoka, Masataka

    2014-04-08

    Protein allostery is essential for vital activities. Allosteric regulation of human hemoglobin (HbA) with two quaternary states T and R has been a paradigm of allosteric structural regulation of proteins. It is widely accepted that oxygen molecules (O2) act as a "site-specific" homotropic effector, or the successive O2 binding to the heme brings about the quaternary regulation. However, here we show that the site-specific allosteric effect is not necessarily only a unique mechanism of O2 allostery. Our simulation results revealed that the solution environment of high O2 partial pressure enhances the quaternary change from T to R without binding to the heme, suggesting an additional "non-site-specific" allosteric effect of O2. The latter effect should play a complementary role in the quaternary change by affecting the intersubunit contacts. This analysis must become a milestone in comprehensive understanding of the allosteric regulation of HbA from the molecular point of view.

  8. High-altitude adaptations in vertebrate hemoglobins

    DEFF Research Database (Denmark)

    Weber, Roy E.

    2007-01-01

    Vertebrates at high altitude are subjected to hypoxic conditions that challenge aerobic metabolism. O2 transport from the respiratory surfaces to tissues requires matching between the O2 loading and unloading tensions and theO2-affinity of blood, which is an integrated function of hemoglobin......, birds and ectothermic vertebrates at high altitude....

  9. Simultaneous, noninvasive, in vivo, continuous monitoring of hematocrit, vascular volume, hemoglobin oxygen saturation, pulse rate and breathing rate in humans and other animal models using a single light source

    Science.gov (United States)

    Dent, Paul; Tun, Sai Han; Fillioe, Seth; Deng, Bin; Satalin, Josh; Nieman, Gary; Wilcox, Kailyn; Searles, Quinn; Narsipur, Sri; Peterson, Charles M.; Goodisman, Jerry; Mostrom, James; Steinmann, Richard; Chaiken, J.

    2018-02-01

    We previously reported a new algorithm "PV[O]H" for continuous, noninvasive, in vivo monitoring of hematocrit changes in blood and have since shown its utility for monitoring in humans during 1) hemodialysis, 2) orthostatic perturbations and 3) during blood loss and fluid replacement in a rat model. We now show that the algorithm is sensitive to changes in hemoglobin oxygen saturation. We document the phenomenology of the effect and explain the effect using new results obtained from humans and rat models. The oxygen sensitivity derives from the differential absorption of autofluorescence originating in the static tissues by oxy and deoxy hemoglobin. Using this approach we show how to perform simultaneous, noninvasive, in vivo, continuous monitoring of hematocrit, vascular volume, hemoglobin oxygen saturation, pulse rate and breathing rate in mammals using a single light source. We suspect that monitoring of changes in this suite of vital signs can be provided with improved time response, sensitivity and precision compared to existing methodologies. Initial results also offer a more detailed glimpse into the systemic oxygen transport in the circulatory system of humans.

  10. INTRINSIC REGULATION OF HEMOGLOBIN EXPRESSION BY VARIABLE SUBUNIT INTERFACE STRENGTHS

    Science.gov (United States)

    Manning, James M.; Popowicz, Anthony M.; Padovan, Julio C.; Chait, Brian T.; Manning, Lois R.

    2012-01-01

    SUMMARY The expression of the six types of human hemoglobin subunits over time is currently considered to be regulated mainly by transcription factors that bind to upstream control regions of the gene (the “extrinsic” component of regulation). Here we describe how subunit pairing and further assembly to tetramers in the liganded state is influenced by the affinity of subunits for one another (the “intrinsic” component of regulation). The adult hemoglobin dimers have the strongest subunit interfaces and the embryonic hemoglobins are the weakest with fetal hemoglobins of intermediate strength, corresponding to the temporal order of their expression. These variable subunit binding strengths and the attenuating effects of acetylation contribute to the differences with which these hemoglobin types form functional O2-binding tetramers consistent with gene switching. PMID:22129306

  11. Assessing the impacts of deoxygenation on marine species using blood-oxygen binding thresholds as proxies for hypoxia tolerance in the water column

    Science.gov (United States)

    Smith-Mislan, A.; Deutsch, C.; Dunne, J. P.; Sarmiento, J. L.

    2016-02-01

    Oxygen and temperature decrease, often rapidly, from shallow to deeper depths, restricting the ability of marine species to use the vertical habitat. One physiological trait that determines the tolerance of organisms to low oxygen is the oxygen affinity of respiratory pigments, hemoglobin and hemocyanin, in the blood. Oxygen affinity is sensitive to temperature because the reversible reaction between oxygen and blood pigments absorbs or releases energy, called the heat of oxygenation. To quantify the range of oxygen affinities for marine species, we surveyed the literature for measurements of oxygen binding to blood at multiple temperatures. Oxygen affinity is mapped within the ocean environment using the depth at which oxygen pressure decreases to the point at which the blood is 50% oxygenated (P50 depth) as organisms move from the surface to depth in the ocean water column. We calculate P50 depths for hydrographic observations and model simulations and find that vertical gradients in both temperature and oxygen impact the vertical position and areal extent of P50 depths. Shifts in P50 due to temperature cause physiological types with the same P50 in the surface ocean to have different P50 depths and physiological types with different P50's in the surface ocean to have the same P50 depth. The vertical distances between P50 depths are spatially variable, which may determine the frequency of ecological interactions, such as competition and predation. P50 depths provide new insights into the historical and future impacts of changing hypoxic zones on species living in pelagic habitats.

  12. Interaction of thyroid hormone and hemoglobin: nature of the interaction and effect of hemoglobin on thyroid hormone radioimmunoassay

    International Nuclear Information System (INIS)

    Davis, P.J.; Yoshida, K.; Schoenl, M.

    1980-01-01

    Gel filtration of human erythrocyte (RBC) lysate incubated with labeled thyroxine (Tu) or triiodothyronine (Tt) revealed co-elution of a major iodothyronine-binding fraction (R-2) and hemoglobin. Solutions of purified human hemoglobin and Tt also showed co-elution of hormone and hemoglobin. Because hematin and protoporphyrin were shown to bind labeled Tt, the oxygen-binding site on hemoglobin was excluded as the site of iodothyronine-hemoglobin interaction. Analysis of hormone binding by heme and globin moieties showed Tt binding to be limited to the heme fraction. Addition of excess unlabeled Tt to hemoglobin or heme incubated with labeled Tt indicated 75% to 90% of hormone binding was poorly dissociable. These observations suggested that the presence of hemoglobin in RBC lysate or in serum could influence the measurement of Tu and Tt by specific radioimmunoassay (RIA). Subsequent studies of the addition to serum of human hemoglobin revealed a significant reduction in Tt and Tu detectable by RIA in the presence of this protein. The effect was influenced by the concentration of hemoglobin and by duration and temperature of incubations of hemoglobin and serum prior to RIA

  13. EPR studies of cooperative binding of Cu (II) to hemoglobin

    International Nuclear Information System (INIS)

    Louro, S.R.W.; Tabak, M.

    1983-07-01

    The investigation of the relative affinities of the two pairs of hemoglobin copper sites by monitoring the EPR spectra of the complexes formed by the reaction of copper with deoxyhemoglobin is reported. A model in which two sites are assumed to accept copper ions in a noncooperative way is not able to predict the experimental results. Thus it is conclude that the binding of these ions to hemoglobin is a cooperative phenomenon. (Author) [pt

  14. Led Astray by Hemoglobin A1c

    Directory of Open Access Journals (Sweden)

    Jean Chen MD

    2016-01-01

    Full Text Available Hemoglobin A1c (A1c is used frequently to diagnose and treat diabetes mellitus. Therefore, it is important be aware of factors that may interfere with the accuracy of A1c measurements. This is a case of a rare hemoglobin variant that falsely elevated a nondiabetic patient’s A1c level and led to a misdiagnosis of diabetes. A 67-year-old male presented to endocrine clinic for further management after he was diagnosed with diabetes based on an elevated A1c of 10.7%, which is approximately equivalent to an average blood glucose of 260 mg/dL. Multiple repeat A1c levels remained >10%, but his home fasting and random glucose monitoring ranged from 92 to 130 mg/dL. Hemoglobin electrophoresis and subsequent genetic analysis diagnosed the patient with hemoglobin Wayne, a rare hemoglobin variant. This variant falsely elevates A1c levels when A1c is measured using cation-exchange high-performance liquid chromatography. When the boronate affinity method was applied instead, the patient’s A1c level was actually 4.7%. Though hemoglobin Wayne is clinically silent, this patient was erroneously diagnosed with diabetes and started on an antiglycemic medication. Due to this misdiagnosis, the patient was at risk of escalation in his “diabetes management” and hypoglycemia. Therefore, it is important that providers are aware of factors that may result in hemoglobin A1c inaccuracy including hemoglobin variants.

  15. The Nernst equation applied to oxidation-reduction reactions in myoglobin and hemoglobin. Evaluation of the parameters.

    Science.gov (United States)

    Saroff, Harry A

    Analyses of the binding of oxygen to monomers such as myoglobin employ the Mass Action equation. The Mass Action equation, as such, is not directly applicable for the analysis of the binding of oxygen to oligomers such as hemoglobin. When the binding of oxygen to hemoglobin is analyzed, models incorporating extensions of mass action are employed. Oxidation-reduction reactions of the heme group in myoglobin and hemoglobin involve the binding and dissociation of electrons. This reaction is described with the Nernst equation. The Nernst equation is applicable only to a monomeric species even if the number of electrons involved is greater than unity. To analyze the oxidation-reduction reaction in a molecule such as hemoglobin a model is required which incorporates extensions of the Nernst equation. This communication develops models employing the Nernst equation for oxidation-reduction reactions analogous to those employed for hemoglobin in the analysis of the oxygenation (binding of oxygen) reaction.

  16. γ irradiation of aqueous solutions of human hemoglobin in atmospheres of air and argon

    International Nuclear Information System (INIS)

    Puchala, M.; Szweda-Lewandowska, Z.; Leyko, W.

    1979-01-01

    In this study, the degrees of destruction of hemoglobin irradiated in atmospheres of air and argon were compared. Hemoglobin preparations were irradiated in the forms: oxyhemoglobin (HbO 2 ) deoxyhemoglobin (Hb 2+ ) and methemoglobin (MetHb) applying doses of 0.5 to 5 Mrad. The degree of hemoglobin destruction was estimate on the basis of changes in the values of the absorption coefficient at the Soret band, the absorption ratio A 505 /A 563 determined after conversion of irradiated preparations into MetHb, absorption coefficinets for pyridine hemochromogen obtained from irradiated preparations, and changes in parameters characterizing the hemoglobin oxygenation reaction (log p/sub 1/2/O 2 and the Hill n coefficient). The calculated oxygen enhancement ratios S were generally higher than 1 for the parameters estimated. This indicates that the presence of oxygen during irradiation enhances hemoglobin destruction

  17. A review of variant hemoglobins interfering with hemoglobin A1c measurement.

    Science.gov (United States)

    Little, Randie R; Roberts, William L

    2009-05-01

    Hemoglobin A1c (HbA1c) is used routinely to monitor long-term glycemic control in people with diabetes mellitus, as HbA1c is related directly to risks for diabetic complications. The accuracy of HbA1c methods can be affected adversely by the presence of hemoglobin (Hb) variants or elevated levels of fetal hemoglobin (HbF). The effect of each variant or elevated HbF must be examined with each specific method. The most common Hb variants worldwide are HbS, HbE, HbC, and HbD. All of these Hb variants have single amino acid substitutions in the Hb beta chain. HbF is the major hemoglobin during intrauterine life; by the end of the first year, HbF falls to values close to adult levels of approximately 1%. However, elevated HbF levels can occur in certain pathologic conditions or with hereditary persistence of fetal hemoglobin. In a series of publications over the past several years, the effects of these four most common Hb variants and elevated HbF have been described. There are clinically significant interferences with some methods for each of these variants. A summary is given showing which methods are affected by the presence of the heterozygous variants S, E, C, and D and elevated HbF. Methods are divided by type (immunoassay, ion-exchange high-performance liquid chromatography, boronate affinity, other) with an indication of whether the result is artificially increased or decreased by the presence of a Hb variant. Laboratorians should be aware of the limitations of their method with respect to these interferences. 2009 Diabetes Technology Society.

  18. The amphibious fish Kryptolebias marmoratus uses different strategies to maintain oxygen delivery during aquatic hypoxia and air exposure.

    Science.gov (United States)

    Turko, Andy J; Robertson, Cayleih E; Bianchini, Kristin; Freeman, Megan; Wright, Patricia A

    2014-11-15

    Despite the abundance of oxygen in atmospheric air relative to water, the initial loss of respiratory surface area and accumulation of carbon dioxide in the blood of amphibious fishes during emersion may result in hypoxemia. Given that the ability to respond to low oxygen conditions predates the vertebrate invasion of land, we hypothesized that amphibious fishes maintain O2 uptake and transport while emersed by mounting a co-opted hypoxia response. We acclimated the amphibious fish Kryptolebias marmoratus, which are able to remain active for weeks in both air and water, for 7 days to normoxic brackish water (15‰, ~21kPa O2; control), aquatic hypoxia (~3.6kPa), normoxic air (~21 kPa) or aerial hypoxia (~13.6kPa). Angiogenesis in the skin and bucco-opercular chamber was pronounced in air- versus water-acclimated fish, but not in response to hypoxia. Aquatic hypoxia increased the O2-carrying capacity of blood via a large (40%) increase in red blood cell density and a small increase in the affinity of hemoglobin for O2 (P50 decreased 11%). In contrast, air exposure increased the hemoglobin O2 affinity (decreased P50) by 25% without affecting the number of red blood cells. Acclimation to aerial hypoxia both increased the O2-carrying capacity and decreased the hemoglobin O2 affinity. These results suggest that O2 transport is regulated both by O2 availability and also, independently, by air exposure. The ability of the hematological system to respond to air exposure independent of O2 availability may allow extant amphibious fishes, and may also have allowed primitive tetrapods to cope with the complex challenges of aerial respiration during the invasion of land. © 2014. Published by The Company of Biologists Ltd.

  19. An Alternative to the Human Hemoglobin Test in the Investigation of Bloodstains Treated with Active Oxygen: The Human Glycophorin A Test

    Directory of Open Access Journals (Sweden)

    Ana Castelló

    2011-01-01

    Full Text Available In criminal investigations, there are three stages involved when studying bloodstains: search and orientation, confirmation, and individualization. Confirmatory tests have two aims: to show that the stain contains a human biological fluid and to confirm the type of biological fluid. The need to determine the nature of the evidence is reflected in the latest bibliography, where the possibility of employing mRNA and miRNA markers for this purpose is proposed. While these new proposals are being investigated, the kits for determining human hemoglobin currently provide a simple solution for resolving this issue. With these kits, the possibility of obtaining false positives and false negatives is well known. However, recently, a new problem has been detected. This involves the interference caused by new cleaning products that contain sodium percarbonate (or active oxygen when determining human hemoglobin. With the aim to resolve this problem, this work studied the ability of the human glycophorin A test to determine human blood in samples that have been treated with active oxygen. Our results show that the human glycophorin A test has a greater resistance to the destructive effect of the new detergents containing active oxygen; consequently, it provides an alternative to be taken into consideration in the confirmatory diagnoses of bloodstains.

  20. Selection of aptamers specific for glycated hemoglobin and total hemoglobin using on-chip SELEX.

    Science.gov (United States)

    Lin, Hsin-I; Wu, Ching-Chu; Yang, Ching-Hsuan; Chang, Ko-Wei; Lee, Gwo-Bin; Shiesh, Shu-Chu

    2015-01-21

    Blood glycated hemoglobin (HbA1c) levels reflecting average glucose concentrations over the past three months are fundamental for the diagnosis, monitoring, and risk assessment of diabetes. It has been hypothesized that aptamers, which are single-stranded DNAs or RNAs that demonstrate high affinity to a large variety of molecules ranging from small drugs, metabolites, or proteins, could be used for the measurement of HbA1c. Aptamers are selected through an in vitro process called systematic evolution of ligands by exponential enrichment (SELEX), and they can be chemically synthesized with high reproducibility at relatively low costs. This study therefore aimed to select HbA1c- and hemoglobin (Hb)-specific single-stranded DNA aptamers using an on-chip SELEX protocol. A microfluidic SELEX chip was developed to continuously and automatically carry out multiple rounds of SELEX to screen specific aptamers for HbA1c and Hb. HbA1c and Hb were first coated onto magnetic beads. Following several rounds of selection and enrichment with a randomized 40-mer DNA library, specific oligonucleotides were selected. The binding specificity and affinity were assessed by competitive and binding assays. Using the developed microfluidic system, the incubation and partitioning times were greatly decreased, and the entire process was shortened dramatically. Both HbA1c- and Hb-specific aptamers selected by the microfluidic system showed high specificity and affinity (dissociation constant, Kd = 7.6 ± 3.0 nM and 7.3 ± 2.2 nM for HbA1c and Hb, respectively). With further refinements in the assay, these aptamers may replace the conventional antibodies for in vitro diagnostics applications in the near future.

  1. Phylogeny of Echinoderm Hemoglobins.

    Directory of Open Access Journals (Sweden)

    Ana B Christensen

    Full Text Available Recent genomic information has revealed that neuroglobin and cytoglobin are the two principal lineages of vertebrate hemoglobins, with the latter encompassing the familiar myoglobin and α-globin/β-globin tetramer hemoglobin, and several minor groups. In contrast, very little is known about hemoglobins in echinoderms, a phylum of exclusively marine organisms closely related to vertebrates, beyond the presence of coelomic hemoglobins in sea cucumbers and brittle stars. We identified about 50 hemoglobins in sea urchin, starfish and sea cucumber genomes and transcriptomes, and used Bayesian inference to carry out a molecular phylogenetic analysis of their relationship to vertebrate sequences, specifically, to assess the hypothesis that the neuroglobin and cytoglobin lineages are also present in echinoderms.The genome of the sea urchin Strongylocentrotus purpuratus encodes several hemoglobins, including a unique chimeric 14-domain globin, 2 androglobin isoforms and a unique single androglobin domain protein. Other strongylocentrotid genomes appear to have similar repertoires of globin genes. We carried out molecular phylogenetic analyses of 52 hemoglobins identified in sea urchin, brittle star and sea cucumber genomes and transcriptomes, using different multiple sequence alignment methods coupled with Bayesian and maximum likelihood approaches. The results demonstrate that there are two major globin lineages in echinoderms, which are related to the vertebrate neuroglobin and cytoglobin lineages. Furthermore, the brittle star and sea cucumber coelomic hemoglobins appear to have evolved independently from the cytoglobin lineage, similar to the evolution of erythroid oxygen binding globins in cyclostomes and vertebrates.The presence of echinoderm globins related to the vertebrate neuroglobin and cytoglobin lineages suggests that the split between neuroglobins and cytoglobins occurred in the deuterostome ancestor shared by echinoderms and vertebrates.

  2. Haptoglobin-related protein is a high-affinity hemoglobin-binding plasma protein

    DEFF Research Database (Denmark)

    Nielsen, Marianne Jensby; Petersen, Steen Vang; Jacobsen, Christian

    2006-01-01

    Haptoglobin-related protein (Hpr) is a primate-specific plasma protein associated with apolipoprotein L-I (apoL-I)-containing high-density lipoprotein (HDL) particles shown to be a part of the innate immune defense. Despite the assumption hitherto that Hpr does not bind to hemoglobin, the present...

  3. Oxidative stress in preeclampsia and the role of free fetal hemoglobin

    Directory of Open Access Journals (Sweden)

    Stefan Rocco Hansson

    2015-01-01

    Full Text Available Preeclampsia is a leading cause of pregnancy complications and affects 3–7 % of pregnant women. This review summarizes the current knowledge of a new potential etiology of the disease, with a special focus on hemoglobin-induced oxidative stress. Furthermore, we also suggest hemoglobin as a potential target for therapy. Gene and protein profiling studies have shown increased expression and accumulation of free fetal hemoglobin in the preeclamptic placenta. Predominantly due to oxidative damage to the placental barrier, fetal hemoglobin leaks over to the maternal circulation. Free hemoglobin and its metabolites are toxic in several ways; a ferrous hemoglobin (Fe2+ binds strongly to the vasodilator nitric oxide and reduces the availability of free nitric oxide, which results in vasoconstriction, b hemoglobin (Fe2+ with bound oxygen spontaneously generates free oxygen radicals and c the heme groups create an inflammatory response by inducing activation of neutrophils and cytokine production. The endogenous protein α1-microglobulin, with radical and heme binding properties, has shown both ex vivo and in vivo to have the ability to counteract free hemoglobin-induced placental and kidney damage. Oxidative stress in general, and more specifically fetal hemoglobin-induced oxidative stress, could play a key role in the pathology of preeclampsia seen both in the placenta and ultimately in the maternal endothelium.

  4. Optical noninvasive calculation of hemoglobin components concentrations and fractional oxygen saturation using a ring-scattering pulse oximeter

    Science.gov (United States)

    Abdallah, Omar; Stork, Wilhelm; Muller-Glaser, Klaus

    2004-06-01

    The deficiencies of the currently used pulse oximeter are discussed in diverse literature. A hazardous pitfalls of this method is that the pulse oximeter will not detect carboxyhemoglobin (COHb) and methemoglobin (metHb) concentrations. This leads to incorrect measurement of oxygen saturation by carbon monoxide poisoning and methemoglobinemia. Also the total hemoglobin concentration will not be considered and can only be measured in-vitro up to now. A second pitfall of the standard pulse oximetry is that it will not be able to show a result by low perfusion of tissues. This case is available inter alia when the patient is under shock or has a low blood pressure. The new non-invasive system we designed measures the actual (fractional) oxygen saturation and hemoglobin concentration. It will enable us also to measure COHb and metHb. The measurement can be applied at better perfused body central parts. Four or more light emitting diodes (LEDs) or laser diodes (LDs) and five photodiodes (PDs) are used. The reflected light signal detected by photodiodes is processed using a modified Lambert-Beer law (I=I0×e-α.d ). According to this law, when a non scattering probe is irradiated with light having the incident intensity I0, the intensity of transmitted light I decays exponentially with the absorption coefficient a of that probe and its thickness d. Modifications of this law have been performed following the theoretical developed models in literature, Monte Carlo simulation and experimental measurement.

  5. Extension arm facilitated pegylation of alphaalpha-hemoglobin with modifications targeted exclusively to amino groups: functional and structural advantages of free Cys-93(beta) in the PEG-Hb adduct.

    Science.gov (United States)

    Li, Dongxia; Hu, Tao; Manjula, Belur N; Acharya, Seetharama A

    2009-11-01

    Cys-93(beta) of hemoglobin (Hb) was reversibly protected as a mixed disulfide with thiopyridine during extension arm facilitated (EAF) PEGylation and its influence on the structural and functional properties of the EAF-PEG-Hb has been investigated. Avoiding PEGylation of Cys-93(beta) in the EAF-PEG-Hb lowers the level of perturbation of heme pocket, alpha1beta2 interface, autoxidation, heme loss, and the O(2) affinity, as compared to the EAF-PEG-Hb with PEGylation of Cys-93(beta).The structural and functional advantages of reversible protection of Cys-93(beta) during EAF PEGylation of oxy-Hb has been compared with Euro PEG-Hb generated by EAF PEGylation of deoxy Hb where Cys-93(beta) is free in the final product. The alphaalpha-fumaryl cross-linking and EAF PEGylation targeted exclusively to Lys residues has been combined together for generation of second-generation EAF-PEG-Hb with lower oxygen affinity. The PEG chains engineered on Lys as well as PEGylation of Cys-93(beta) independently contribute to the stabilization of oxy conformation of Hb and hence increase the oxygen affinity of Hb. However, oxygen affinity of the EAF-PEG-alphaalpha-Hb is more sensitive to the presence of PEGylation on Cys-93(beta) than that of the EAF-PEG-Hb. The present modified EAF PEGylation platform is expected to facilitate the design of novel versions of the EAF-PEG-Hbs that can now integrate the advantages of avoiding PEGylation of Cys-93(beta).

  6. A study on the structures of hemoglobin of diabetic patients by EXAFS technique

    International Nuclear Information System (INIS)

    Wang Yinsong; Tan Mingguang; Zhang Guilin

    2001-01-01

    Hemoglobin was the carrier of oxygen in blood circulation. For the patients with diabetes mellitus the enhancement of glycidate hemoglobin in blood causes the decrease of oxygen transmission function. The local atomic structures of iron in hemoglobin were determined by EXAFS techniques. The relationship between diabetes mellitus and hemoglobin structures was observed. The blood samples were taken from normal people, slight and serious diabetic patients. The results show that the coordination number of iron atoms and Fe-O bond length were almost the same for the three samples. However, for the samples of serious diabetic patients the Fe-N bond length increases by about 0.002 nm, the possible reasons were the increase of deoxyhemoglobin contents in their blood

  7. Megalin and cubilin are endocytic receptors involved in renal clearance of hemoglobin

    DEFF Research Database (Denmark)

    Gburek, Jakub; Verroust, Pierre J; Willnow, Thomas E

    2002-01-01

    -Sepharose affinity chromatography of solubilized renal brush-border membranes. Apparent dissociation constants of 1.7 microM for megalin and 4.1 microM for cubilin were determined by surface plasmon resonance analysis. The binding was calcium dependent in both cases. Uptake of fluorescence-labeled hemoglobin by BN......The kidney is the main site of hemoglobin clearance and degradation in conditions of severe hemolysis. Herein it is reported that megalin and cubilin, two epithelial endocytic receptors, mediate the uptake of hemoglobin in renal proximal tubules. Both receptors were purified by use of hemoglobin...... not affect the uptake. By use of immunohistochemistry, it was demonstrated that uptake of hemoglobin in proximal tubules of rat, mouse, and dog kidneys occurs under physiologic conditions. Studies on normal and megalin knockout mouse kidney sections showed that megalin is responsible for physiologic...

  8. Oxygen entry through multiple pathways in T-state human hemoglobin.

    Science.gov (United States)

    Takayanagi, Masayoshi; Kurisaki, Ikuo; Nagaoka, Masataka

    2013-05-23

    The heme oxygen (O2) binding site of human hemoglobin (HbA) is buried in the interior of the protein, and there is a debate over the O2 entry pathways from solvent to the binding site. As a first step to understand HbA O2 binding process at the atomic level, we detected all significant multiple O2 entry pathways from solvent to the binding site in the α and β subunits of the T-state tetramer HbA by utilizing ensemble molecular dynamics (MD) simulation. By executing 128 independent 8 ns MD trajectories in O2-rich aqueous solvent, we simulated the O2 entry processes and obtained 141 and 425 O2 entry events in the α and β subunits of HbA, respectively. We developed the intrinsic pathway identification by clustering method to achieve a persuasive visualization of the multiple entry pathways including both the shapes and relative importance of each pathway. The rate constants of O2 entry estimated from the MD simulations correspond to the experimentally observed values, suggesting that O2 ligands enter the binding site through multiple pathways. The obtained multiple pathway map can be utilized for future detailed analysis of HbA O2 binding process.

  9. [Peroxynitrite effect on the haemoglobin oxygen affinity in vitro in presence of different partial pressure of carbon dioxide].

    Science.gov (United States)

    Stepuro, T L; Zinchuk, V V

    2011-08-01

    Peroxynitrite (ONOO-) besides its toxic possesses regulatory action that includes the modulation of oxygen binding properties of blood. The aim of this work was to estimate ONOO- effect on the haemoglobin oxygen affinity (HOA) in vitro in presence of different partial pressure of carbon dioxide (CO2). The ONOO- presence in venous blood in conditions of hypercapnia induced oxyhaemoglobin dissociation curve shift leftward while in hypocapnic conditions the result of a different character was obtained. The revealed effect of ONOO- is realized, possibly, through various modifications ofhaemoglobin whose formation is dependent on the CO2 pressure. The ONOO- influences the HOA in different manner that can be important in regulation of blood oxygenation in lungs and maintenance of oxygen consumption in tissues.

  10. Analytical interference of HBOC-201 (Hemopure, a synthetic hemoglobin-based oxygen carrier) on four common clinical chemistry platforms.

    Science.gov (United States)

    Korte, Erik A; Pozzi, Nicole; Wardrip, Nina; Ayyoubi, M Tayyeb; Jortani, Saeed A

    2018-07-01

    There are 13 million blood transfusions each year in the US. Limitations in the donor pool, storage capabilities, mass casualties, access in remote locations and reactivity of donors all limit the availability of transfusable blood products to patients. HBOC-201 (Hemopure®) is a second-generation glutaraldehyde-polymer of bovine hemoglobin, which can serve as an "oxygen bridge" to maintain oxygen carrying capacity while transfusion products are unavailable. Hemopure presents the advantages of extended shelf life, ambient storage, and limited reactive potential, but its extracellular location can also cause significant interference in modern laboratory analyzers similar to severe hemolysis. Observed error in 26 commonly measured analytes was determined on 4 different analytical platforms in plasma from a patient therapeutically transfused Hemopure as well as donor blood spiked with Hemopure at a level equivalent to the therapeutic loading dose (10% v/v). Significant negative error ratios >50% of the total allowable error (>0.5tAE) were reported in 23/104 assays (22.1%), positive bias of >0.5tAE in 26/104 assays (25.0%), and acceptable bias between -0.5tAE and 0.5tAE error ratio was reported in 44/104 (42.3%). Analysis failed in the presence of Hemopure in 11/104 (10.6%). Observed error is further subdivided by platform, wavelength, dilution and reaction method. Administration of Hemopure (or other hemoglobin-based oxygen carriers) presents a challenge to laboratorians tasked with analyzing patient specimens. We provide laboratorians with a reference to evaluate patient samples, select optimal analytical platforms for specific analytes, and predict possible bias beyond the 4 analytical platforms included in this study. Copyright © 2018 Elsevier B.V. All rights reserved.

  11. Assessment of Microcirculatory Hemoglobin Levels in Normal and Diabetic Subjects using Diffuse Reflectance Spectroscopy in the Visible Region — a Pilot Study

    Science.gov (United States)

    Sujatha, N.; Anand, B. S. Suresh; Nivetha, K. Bala; Narayanamurthy, V. B.; Seshadri, V.; Poddar, R.

    2015-07-01

    Light-based diagnostic techniques provide a minimally invasive way for selective biomarker estimation when tissues transform from a normal to a malignant state. Spectroscopic techniques based on diffuse reflectance characterize the changes in tissue hemoglobin/oxygenation levels during the tissue transformation process. Recent clinical investigations have shown that changes in tissue oxygenation and microcirculation are observed in diabetic subjects in the initial and progressive stages. In this pilot study, we discuss the potential of diffuse reflectance spectroscopy (DRS) in the visible (Vis) range to differentiate the skin microcirculatory hemoglobin levels between normal and advanced diabetic subjects with and without neuropathy. Average concentration of hemoglobin as well as hemoglobin oxygen saturation within the probed tissue volume is estimated for a total of four different sites in the foot sole. The results indicate a statistically significant decrease in average total hemoglobin and increase in hemoglobin oxygen saturation levels for diabetic foot compared with a normal foot. The present study demonstrates the ability of reflectance spectroscopy in the Vis range to determine and differentiate the changes in tissue hemoglobin and hemoglobin oxygen saturation levels in normal and diabetic subjects.

  12. Detection of haemoglobins with abnormal oxygen affinity by single blood gas analysis and 2,3-diphosphoglycerate measurement.

    Science.gov (United States)

    Guerrini, G; Morabito, A; Samaja, M

    2000-10-01

    The aim is to determine if a single measurement of blood 2,3-diphosphoglycerate combined with gas analysis (pH, PCO2, PO2 and saturation) can identify the cause of an altered blood-oxygen affinity: the presence of an abnormal haemoglobin or a red cell disorder. The population (n=94) was divided into healthy controls (A, n=14), carriers of red cell disorders (B, n=72) and carriers of high oxygen affinity haemoglobins (C, n=8). Those variables were measured both in samples equilibrated at selected PCO2 and PO2 and in venous blood. In the univariable approach applied to equilibrated samples, we correctly identified C subjects in 93.6% or 96.8% of the cases depending on the selected variable, the standard P50 (PO2 at which 50% of haemoglobin is oxygenated) or a composite variable calculated from the above measurements. After introducing the haemoglobin concentration as a further discriminating variable, the A and B subjects were correctly identified in 91.9% or 94.2% of the cases, respectively. These figures become 93.0% or 86.1%, and 93.7% or 94.9% of the cases when using direct readings from venous blood, thereby avoiding the blood equilibration step. This test is feasible also in blood samples stored at 4 degrees C for 48 h, or at room temperature for 8 h.

  13. Biophysical basis of hypoxic radioprotection by deoxygenated dextran-hemoglobin

    International Nuclear Information System (INIS)

    Wong, J.T.; Hill, R.P.

    1986-01-01

    Perfusion with deoxygenated dextran-hemoglobin provides an effective method for inducing hypoxic radioprotection of normal tissues during radiation treatment of tumors. In this study, the dependence of P50, the half-saturation pressure of oxygen binding to dextran-hemoglobin, was analyzed as a function of solution temperature and pH. The variation of attainable radioprotection with P50, and with the amount of collateral blood entering into the perfused region, was calculated. Upon perfusion of canine gracilis muscle with deoxygenated dextran-hemoglobin, a rapid onset of extensive venous hypoxia was observed

  14. Two-photon excited fluorescence emission from hemoglobin

    Science.gov (United States)

    Sun, Qiqi; Zeng, Yan; Zhang, Wei; Zheng, Wei; Luo, Yi; Qu, Jianan Y.

    2015-03-01

    Hemoglobin, one of the most important proteins in blood, is responsible for oxygen transportation in almost all vertebrates. Recently, we discovered two-photon excited hemoglobin fluorescence and achieved label-free microvascular imaging based on the hemoglobin fluorescence. However, the mechanism of its fluorescence emission still remains unknown. In this work, we studied the two-photon excited fluorescence properties of the hemoglobin subunits, heme/hemin (iron (II)/(III) protoporphyrin IX) and globin. We first studied the properties of heme and the similar spectral and temporal characteristics of heme and hemoglobin fluorescence provide strong evidence that heme is the fluorophore in hemoglobin. Then we studied the fluorescence properties of hemin, globin and methemoglobin, and found that the hemin may have the main effect on the methemoglobin fluorescence and that globin has tryptophan fluorescence like other proteins. Finally, since heme is a centrosymmetric molecule, that the Soret band fluorescence of heme and hemoglobin was not observed in the single photon process in the previous study may be due to the parity selection rule. The discovery of heme two-photon excited fluorescence may open a new window for heme biology research, since heme as a cofactor of hemoprotein has many functions, including chemical catalysis, electron transfer and diatomic gases transportation.

  15. Induction of nano pore in Agrobacterial hemoglobin

    Directory of Open Access Journals (Sweden)

    Mojtaba Tousheh

    2014-01-01

    Full Text Available Introduction: A variety of oxygen-transport and -binding proteins exist in organisms including bacteria, protozoans, and fungi all have hemoglobin-like proteins. In addition to dealing with transport and sensing of oxygen, they may also deal with NO2, CO2, sulfide compounds, and even O2 scavenging in environments. Also they detoxified chlorinated materials like P450 enzymes and peroxidases and use as a detector of nitrate and hydrogen peroxide. Pore-forming bacterial globins are interested for filtration. Materials and methods: Although there are data for bacterial toxin as a filter, here we used Agrobacterial hem to induce nano pore in the heme structure using point mutation. Results: Investigations showed that three amino acids leucine 76, alanine 83 and histidine 80 are important for pore formation in Agrobacterium hemoglobin. A point mutation on leucine 76 to glycine, histidine 80 to asparagine and alanine 83 to lysine step by step led to create the nano pore 0.7- 0.8 nm in the globin. Discussion and conclusion: These mutations in bacterial hemoglobin increase the stability when mutation is with it’s at pH7. This mutation decreases the aliphatic index however increase the stability index.

  16. Substitutions in woolly mammoth hemoglobin confer biochemical properties adaptive for cold tolerance

    DEFF Research Database (Denmark)

    Campbell, Kevin L.; Roberts, Jason E.E.; Watson, Laura N.

    2010-01-01

    We have genetically retrieved, resurrected and performed detailed structure-function analyses on authentic woolly mammoth hemoglobin to reveal for the first time both the evolutionary origins and the structural underpinnings of a key adaptive physiochemical trait in an extinct species. Hemoglobin...... binds and carries O2; however, its ability to offload O2 to respiring cells is hampered at low temperatures, as heme deoxygenation is inherently endothermic (that is, hemoglobin-O2 affinity increases as temperature decreases). We identify amino acid substitutions with large phenotypic effect...... the Pleistocene period. This powerful new approach to directly analyze the genetic and structural basis of physiological adaptations in an extinct species adds an important new dimension to the study of natural selection....

  17. Early resuscitation with polymerized bovine hemoglobin reverses acidosis, but not peripheral tissue oxygenation, in a severe hamster shock model.

    Science.gov (United States)

    Wettstein, Reto; Tsai, Amy G; Harder, Yves; Erni, Dominique; Intaglietta, Marcos

    2006-11-01

    Awake hamsters equipped with the dorsal window chamber preparation were subjected to hemorrhage of 50% of the estimated blood volume. Initial resuscitation (25% of estimated blood volume) with polymerized bovine hemoglobin (PBH) or 10% hydroxyethyl starch (HES) occurred in concert with an equivolumetric bleeding to simulate the early, prehospital setting (exchange transfusion). Resuscitation (25% of estimated blood volume) without bleeding was performed with PBH, HES, or autologous red blood cells (HES-RBCs). Peripheral microcirculation, tissue oxygenation, and systemic hemodynamic and blood gas parameters were assessed. After exchange transfusion, base deficit was -8.6 +/- 3.7 mmol/L (PBH) and -5.1 +/- 5.3 mmol/L (HES) (not significant). Functional capillary density was 17% +/- 6% of baseline (PBH) and 31% +/- 11% (HES) (P < 0.05) and arteriolar diameter 73% +/- 3% of baseline (PBH) and 90% + 5% (HES) (P < 0.01). At the end, hemoglobin levels were 3.7 +/- 0.3 g/dL with HES, 8.2 +/- 0.6 g/dL with PBH, and 10.4 +/- 0.8 g/dL with HES-RBCs (P < 0.01 HES vs. PBH and HES-RBCs, P < 0.05 PBH vs. HES-RBCs). Base excess was restored to baseline with PBH and HES-RBCs, but not with HES (P < 0.05). Functional capillary density was 46% +/- 5% of baseline (PBH), 62% + 20% (HES-RBCs), and 36% +/- 19% (HES) (P < 0.01 HES-RBCs vs. HES). Peripheral oxygen delivery and consumption was highest with HES-RBCs, followed by PBH (P < 0.05 HES-RBCs vs. PBH, P < 0.01 HES-RBCs and PBH vs. HES). In conclusion, the PBH led to a correction of base deficit comparable to blood transfusion. However, oxygenation of the peripheral tissue was inferior with PBH. This was attributed to its negative impact on the peripheral microcirculation caused by arteriolar vasoconstriction.

  18. Projections of climate-driven changes in tuna vertical habitat based on species-specific differences in blood oxygen affinity.

    Science.gov (United States)

    Mislan, K A S; Deutsch, Curtis A; Brill, Richard W; Dunne, John P; Sarmiento, Jorge L

    2017-10-01

    Oxygen concentrations are hypothesized to decrease in many areas of the ocean as a result of anthropogenically driven climate change, resulting in habitat compression for pelagic animals. The oxygen partial pressure, pO 2 , at which blood is 50% saturated (P 50 ) is a measure of blood oxygen affinity and a gauge of the tolerance of animals for low ambient oxygen. Tuna species display a wide range of blood oxygen affinities (i.e., P 50 values) and therefore may be differentially impacted by habitat compression as they make extensive vertical movements to forage on subdaily time scales. To project the effects of end-of-the-century climate change on tuna habitat, we calculate tuna P 50 depths (i.e., the vertical position in the water column at which ambient pO 2 is equal to species-specific blood P 50 values) from 21st century Earth System Model (ESM) projections included in the fifth phase of the Climate Model Intercomparison Project (CMIP5). Overall, we project P 50 depths to shoal, indicating likely habitat compression for tuna species due to climate change. Tunas that will be most impacted by shoaling are Pacific and southern bluefin tunas-habitat compression is projected for the entire geographic range of Pacific bluefin tuna and for the spawning region of southern bluefin tuna. Vertical shifts in P 50 depths will potentially influence resource partitioning among Pacific bluefin, bigeye, yellowfin, and skipjack tunas in the northern subtropical and eastern tropical Pacific Ocean, the Arabian Sea, and the Bay of Bengal. By establishing linkages between tuna physiology and environmental conditions, we provide a mechanistic basis to project the effects of anthropogenic climate change on tuna habitats. Published 2017. This article is a U.S. Government work and is in the public domain in the USA.

  19. Genetic differences in hemoglobin function between highland and lowland deer mice

    DEFF Research Database (Denmark)

    Storz, Jay F.; Runck, Amy M.; Moriyama, Hideaki

    2010-01-01

    In high-altitude vertebrates, adaptive changes in blood–O2 affinity may be mediated by modifications of hemoglobin (Hb) structure that affect intrinsic O2 affinity and/or responsiveness to allosteric effectors that modulate Hb–O2 affinity. This mode of genotypic specialization is considered typical...... of mammalian species that are high-altitude natives. Here we investigated genetically based differences in Hb–O2 affinity between highland and lowland populations of the deer mouse (Peromyscus maniculatus), a generalist species that has the broadest altitudinal distribution of any North American mammal....... The results of a combined genetic and proteomic analysis revealed that deer mice harbor a high level of Hb isoform diversity that is attributable to allelic polymorphism at two tandemly duplicated -globin genes and two tandemly duplicated β-globin genes. This high level of isoHb diversity translates...

  20. Carbon monoxide reduces near-infrared spectroscopy determined 'total' hemoglobin

    DEFF Research Database (Denmark)

    Niemann, Mads J; Sørensen, Henrik; Siebenmann, Christoph

    2017-01-01

    with CO (1.5 mL kg-1) was added to the circuit. Two NIRS systems (NIRO-200NX and INVOS-5100) assessed ScO2 as the ratio of oxygenated to deoxygenated hemoglobin, while venous blood samples were analyzed for carboxyhemoglobin (COHb). After CO/O2 rebreathing COHb increased to 8.7% (IQR; 7.9-9.4; p = .004...... to normoxia (68.9 ± 6.9%; p hemoglobin decreased (by 19.7 μM (median; IQR 2.8-34.8; p = .016) and 37.3 μM (30.8-46.6; p = .004), respectively) during inhalation of CO/O2 compared...... to inhalation of O2. Therefore, NIRO-200NX determined 'total' hemoglobin (sum of O2Hb and HHb) decreased (by 62.1 μM; 44.5-78.2; p = .001). In conclusion, exposure to CO did not increase MCAVmean, and neither NIRO-200NX nor INVOS-5100 detected a change in ScO2 when CO was added to inhalation of oxygen...

  1. Separation and determination of reduced vitamin C in polymerized hemoglobin-based oxygen carriers of the human placenta.

    Science.gov (United States)

    Chen, Gang; Mo, Ling; Li, Shen; Zhou, Wentao; Wang, Hong; Liu, Jiaxin; Yang, Chengmin

    2015-06-01

    The molybdenum blue method was used to determine the content of reduced vitamin C (Vc) in a solution of polymerized hemoglobin-based oxygen carriers (HBOCs) of the human placenta. The conditions of absorption wavelength, HCl addition, and reaction time, were investigated. The results of validation experiments showed that under the optimized conditions, a standard curve was confirmed with good linearity of 0.9985, for the Vc amount ranging from 0-200 μg. The values for relative standard deviation (RSD) of the precision and repeatability were both below 5%. Vc recovery was in the range of 97-102%. The conclusion could be made that a reduction in Vc content could be tested effectively by the molybdenum blue method.

  2. Effect of hemodialysis on factors influencing oxygen transport.

    Science.gov (United States)

    Hirszel, P; Maher, J F; Tempel, G E; Mengel, C E

    1975-06-01

    Ten patients underwent 4 study hemodialyses, one with standard dialysis conditions, one with an isophosphate dialysate, one with simultaneous ammonium chloride loading, and other, after pretreatment, with sodium bicarbonate. Measurement of hemoglobin oxygen affinity (P-50), erythrocyte 2,3-DPG, blood-gasses, and serum chemistries revealed biochemically effective hemodialyses and slight changes in oxygen transport parameters. The P-50 (in vivo) values decreased slightly but significantly (p greater than 0.05) with dialysis. When corrected to pH 7.4, eliminating the Bohr effect, P-50 increased (p greater than 0.05). With unmodified dialysis elevated values of 2,3-DPG (in comparison to normal) decreased, a change that did not correlate with delta-p-50, delta-serum phosphate, or delta-serum creatinine. With standard and isophosphate dialyses Po-2 decreased significantly. The decrease correlated with delta-hydrogen ion concentration and did not occur with dialyses designed to maintain pH constant. Thus, hemodialysis influences many factors that affect oxygen transport in different and counterbalancing directions. These changes are not totally explained by alterations in 2,3-DPG, pH or serum phosphate. Maintenance of acidosis or hyperphosphatemia during dialysis is not recommended.

  3. THE BIOCHEMISTRY OF VITREOSCILLA HEMOGLOBIN

    Directory of Open Access Journals (Sweden)

    Benjamin C. Stark

    2012-10-01

    Full Text Available The hemoglobin (VHb from Vitreoscilla was the first bacterial hemoglobin discovered. Its structure and function have been extensively investigated, and engineering of a wide variety of heterologous organisms to express VHb has been performed to increase their growth and productivity. This strategy has shown promise in applications as far-ranging as the production of antibiotics and petrochemical replacements by microorganisms to increasing stress tolerance in plants. These applications of “VHb technology” have generally been of the “black box” variety, wherein the endpoint studied is an increase in the levels of a certain product or improved growth and survival. Their eventual optimization, however, will require a thorough understanding of the various functions and activities of VHb, and how VHb expression ripples to affect metabolism more generally. Here we review the current knowledge of these topics. VHb's functions all involve oxygen binding (and often delivery in one way or another. Several biochemical and structure-function studies have provided an insight into the molecular details of this binding and delivery. VHb activities are varied. They include supply of oxygen to oxygenases and the respiratory chain, particularly under low oxygen conditions; oxygen sensing and modulation of transcription factor activity; and detoxification of NO, and seem to require interactions of VHb with “partner proteins”. VHb expression affects the levels of ATP and NADH, although not enormously. VHb expression may affect the level of many compounds of intermediary metabolism, and, apparently, alters the levels of expression of many genes. Thus, the metabolic changes in organisms engineered to express VHb are likely to be numerous and complicated.

  4. No impaired hemoglobin oxygenation in forearm muscles of patients with chronic CRPS-1.

    Science.gov (United States)

    Brunnekreef, Jaap J J; Oosterhof, Jan; Wolff, André P; Crul, Ben J P; Wilder-Smith, Oliver H G; Oostendorp, Rob A B

    2009-01-01

    Physiotherapy is considered an important treatment option in patients with upper limb complex regional pain syndrome type-1 (CRPS-1). In case of chronic CRPS-1, exercise therapy of the affected limb forms an important part of the physiotherapeutic program. We investigated whether muscle loading in chronic CRPS-1 patients is associated with impairments in muscle circulation of the forearm of the affected limb. Thirty patients with chronic CRPS-1 unilaterally affecting their upper limbs, and 30 age-matched and sex-matched control participants were included in this study. Local muscle blood flow and hemoglobin oxygenation were measured by near infrared spectroscopy within the muscles of the forearm at rest, after 1-minute isometric handgrip exercises, and after arterial occlusion. Main outcome parameters were: local muscle blood flow, O2 consumption (mVO2), and postischemic reoxygenation (ReOx). We found no differences in baseline muscle blood flow, mVO2, and ReOx between the affected CRPS-1, unaffected CRPS-1, and control arms. After exercise, mVO2 of the affected CRPS-1 arms was not different from the clinically unaffected CRPS-1 arms. Furthermore, in comparison with the control arms, unaffected CRPS-1 arms showed no difference in mVO2 or ReOx. Muscle loading does not seems to be related to impairments in muscle oxygen uptake in forearm muscles of upper limbs affected by chronic CRPS-1. Our results suggest that exercise therapy can be safely used in physiotherapeutic training programs for chronic CRPS-1 of the upper limb.

  5. Strategies for Small Volume Resuscitation: Hyperosmotic-Hyperoncotic Solutions, Hemoglobin Based Oxygen Carriers and Closed-Loop Resuscitation

    Science.gov (United States)

    Kramer, George C.; Wade, Charles E.; Dubick, Michael A.; Atkins, James L.

    2004-01-01

    Introduction: Logistic constraints on combat casualty care preclude traditional resuscitation strategies which can require volumes and weights 3 fold or greater than hemorrhaged volume. We present a review of quantitative analyses of clinical and animal data on small volume strategies using 1) hypertonic-hyperosmotic solutions (HHS); 2) hemoglobin based oxygen carriers (HBOCs) and 3) closed-loop infusion regimens.Methods and Results: Literature searches and recent queries to industry and academic researchers have allowed us to evaluate the record of 81 human HHS studies (12 trauma trials), 19 human HBOCs studies (3trauma trials) and two clinical studies of closed-loop resuscitation.There are several hundreds animal studies and at least 82 clinical trials and reports evaluating small volume7.2%-7.5% hypertonic saline (HS) most often combined with colloids, e.g., dextran (HSD) or hetastarch(HSS). HSD and HSS data has been published for 1,108 and 392 patients, respectively. Human studies have documented volume sparing and hemodynamic improvements. Meta-analyses suggest improved survival for hypotensive trauma patients treated with HSD with significant reductions in mortality found for patients with blood pressure surgery. HSD and HSS have received regulatory approval in 14 and 3 countries, respectively, with 81,000+ units sold. The primary reported use was head injury and trauma resuscitation. Complications and reported adverse events are surprisingly rare and not significantly different from other solutions.HBOCs are potent volume expanders in addition to oxygen carriers with volume expansion greater than standard colloids. Several investigators have evaluated small volume hyperoncotic HBOCs or HS-HBOC formulations for hypotensive and normotensive resuscitation in animals. A consistent finding in resuscitation with HBOCs is depressed cardiac output. There is some evidence that HBOCs more efficiently unload oxygen from plasma hemoglobin as well as facilitate RBC

  6. Study of the interaction between bovine hemoglobin and analogs of biphenyldicarboxylate by spectrofluorimetry

    International Nuclear Information System (INIS)

    Wang, Ruiyong; Yin, Yujing; Wang, Ruiqiang; Xie, Yuanzhe; Ge, Baoyu; Li, Zhigang; Li, Zhen; Shi, Jie; Chang, Junbiao

    2013-01-01

    The interaction between bovine hemoglobin and analogs of Biphenyldicarboxylate was investigated by fluorescence, synchronous fluorescence, ultraviolet–vis absorbance, resonance light-scattering spectra and three-dimensional fluorescence spectra at pH 7.40. The quenching mechanism and binding constants were determined by the quenching of bovine hemoglobin fluorescence in presence of analogs. Results showed that the nature of the quenching was of static type. Both the van der Waals and hydrogen bonding played a major role in stabilizing the complex. The distance between donor and acceptors was obtained to be 2.11–2.25 nm according to Förster's theory. The influence of analogs on the conformation of bovine hemoglobin was investigated. -- Highlights: • The interactions between bovine hemoglobin and analogs of DDB have been investigated. • Results reveal that DDB has the strongest affinity for hemoglobin among four compounds. • The van der Waals and hydrogen bonding play major role in the binding process. • The influence of molecular structure on the binding aspects has been investigated

  7. Therapeutic effect of forearm low level light treatment on blood flow, oxygenation, and oxygen consumption

    Science.gov (United States)

    Wang, Pengbo; Sun, Jiajing; Meng, Lingkang; Li, Zebin; Li, Ting

    2018-02-01

    Low level light/laser therapy (LLLT) is considered as a novel, non-invasive, and potential therapy in a variety of psychological and physical conditions, due to its effective intricate photobiomodulation. The mechanism of LLLT is that when cells are stimulated by photons, mitochondria produce a large quantity of ATP, which accelerates biochemical responses in the cell. It is of great significance to gain a clear insight into the change or interplay of various physiological parameters. In this study, we used functional near-infrared spectroscopy (fNIRS) and venous-occlusion plethysmography to measure the LLLT-induced changes in blood flow, oxygenation, and oxygen consumption in human forearms in vivo. Six healthy human participants (4 males and 2 females) were administered with 810-nm light emitted by LED array in ten minutes and blood flow, oxygenation and oxygen consumption were detected in the entire experiment. We found that LLLT induced an increase of blood flow and oxygen consumption on the treated site. Meanwhile, LLLT took a good role in promoting oxygenation of regional tissue, which was indicated by a significant increase of oxygenated hemoglobin concentration (Δ[HbO2]), a nearly invariable deoxygenated hemoglobin concentration (Δ[Hb]) and a increase of differential hemoglobin concentration (Δ[HbD] = Δ[HbO2] - Δ[Hb]). These results not only demonstrate enormous potential of LLLT, but help to figure out mechanisms of photobiomodulation.

  8. Hemoglobin function and allosteric regulation in semi-fossorial rodents (family Sciuridae) with different altitudinal ranges

    Science.gov (United States)

    Revsbech, Inge G.; Tufts, Danielle M.; Projecto-Garcia, Joana; Moriyama, Hideaki; Weber, Roy E.; Storz, Jay F.; Fago, Angela

    2013-01-01

    SUMMARY Semi-fossorial ground squirrels face challenges to respiratory gas transport associated with the chronic hypoxia and hypercapnia of underground burrows, and such challenges are compounded in species that are native to high altitude. During hibernation, such species must also contend with vicissitudes of blood gas concentrations and plasma pH caused by episodic breathing. Here, we report an analysis of hemoglobin (Hb) function in six species of marmotine ground squirrels with different altitudinal distributions. Regardless of their native altitude, all species have high Hb–O2 affinities, mainly due to suppressed sensitivities to allosteric effectors [2,3-diphosphoglycerate (DPG) and chloride ions]. This suppressed anion sensitivity is surprising given that all canonical anion-binding sites are conserved. Two sciurid species, the golden-mantled and thirteen-lined ground squirrel, have Hb–O2 affinities that are characterized by high pH sensitivity and low thermal sensitivity relative to the Hbs of humans and other mammals. The pronounced Bohr effect is surprising in light of highly unusual amino acid substitutions at the C-termini that are known to abolish the Bohr effect in human HbA. Taken together, the high O2 affinity of sciurid Hbs suggests an enhanced capacity for pulmonary O2 loading under hypoxic and hypercapnic conditions, while the large Bohr effect should help to ensure efficient O2 unloading in tissue capillaries. In spite of the relatively low thermal sensitivities of the sciurid Hbs, our results indicate that the effect of hypothermia on Hb oxygenation is the main factor contributing to the increased blood–O2 affinity in hibernating ground squirrels. PMID:24172889

  9. Automatic labeling method for injectable 15O-oxygen using hemoglobin-containing liposome vesicles and its application for measurement of brain oxygen consumption by PET

    International Nuclear Information System (INIS)

    Tiwari, Vijay Narayan; Kiyono, Yasushi; Kobayashi, Masato; Mori, Tetsuya; Kudo, Takashi; Okazawa, Hidehiko; Fujibayashi, Yasuhisa

    2010-01-01

    Introduction: The aim of this study was to develop an injectable 15 O-O 2 system using hemoglobin-containing vesicles (HbV), a type of artificial red blood cell, and to investigate the feasibility of 15 O 2 -labeled HbV ( 15 O 2 -HbV) to measure cerebral metabolic rate of oxygen (CMRO 2 ) in rats. Methods: The direct bubbling method was combined with vortexing to enhance labeling efficiency of HbV with 15 O-O 2 gas. L-Cysteine was added as a reductant to protect hemoglobin molecules in HbV from oxidation at different concentrations, and labeling efficiencies were also compared. Measurement of cerebral blood flow (CBF) and CMRO 2 in five normal rats was performed using a small animal PET scanner after the injection of H 2 15 O and 15 O 2 -HbV to evaluate the precision of hemodynamic parameters quantitatively. Results: The labeling efficiency of HbV was significantly increased when vortexing and bubbling were combined compared with the simple bubbling method (P 15 O-O 2 combined with vortexing and the addition of 2.8 mM L-cysteine in HbV solution. The mean radioactivity of 214.4±7.8 MBq/mL HbV was obtained using this method. PET scans using 15 O 2 -HbV and H 2 15 O yielded a mean CMRO 2 value of 6.8±1.4 (mL/min per 100 g) in rats with normal CBF of 51.4±7.9 (mL/min per 100 g). Conclusion: Addition of L-cysteine to HbV and simple direct bubbling of 15 O-O 2 gas combined with vortexing was the most efficient method for preparation of 15 O 2 -HbV. The present injectable system using 15 O 2 -HbV was successfully utilized to measure CMRO 2 in rats, indicating that this new method could be useful for animal models to measure oxygen metabolism in the brain.

  10. Relationship of Hemoglobin to Arterial Oxygen Desaturation during Aeromedical Evacuation

    Science.gov (United States)

    2015-04-02

    2. REPORT TYPE Special Report 3. DATES COVERED (From – To) September 2012 – September 2014 4. TITLE AND SUBTITLE Relationship of Hemoglobin to...pressurized pulsatile, and hydrosurgery debridement methods for removing bacteria from fracture implants. Orthopedics. 2012; 35(7):e1046-e1050. 11. Burns TC

  11. Molecular Mechanism of AHSP-Mediated Stabilization of Alpha-Hemoglobin

    Energy Technology Data Exchange (ETDEWEB)

    Feng,L.; Gell, D.; Zhou, S.; Gu, L.; Kong, Y.; Li, J.; Hu, M.; Yan, N.; Lee, C.; et al.

    2005-01-01

    Hemoglobin A (HbA), the oxygen delivery system in humans, comprises two alpha and two beta subunits. Free alpha-hemoglobin (alphaHb) is unstable, and its precipitation contributes to the pathophysiology of beta thalassemia. In erythrocytes, the alpha-hemoglobin stabilizing protein (AHSP) binds alphaHb and inhibits its precipitation. The crystal structure of AHSP bound to Fe(II)-alphaHb reveals that AHSP specifically recognizes the G and H helices of alphaHb through a hydrophobic interface that largely recapitulates the alpha1-beta1 interface of hemoglobin. The AHSP-alphaHb interactions are extensive but suboptimal, explaining why beta-hemoglobin can competitively displace AHSP to form HbA. Remarkably, the Fe(II)-heme group in AHSP bound alphaHb is coordinated by the distal but not the proximal histidine. Importantly, binding to AHSP facilitates the conversion of oxy-alphaHb to a deoxygenated, oxidized [Fe(III)], nonreactive form in which all six coordinate positions are occupied. These observations reveal the molecular mechanisms by which AHSP stabilizes free alphaHb.

  12. Controlled safety study of a hemoglobin-based oxygen carrier, DCLHb, in acute ischemic stroke

    NARCIS (Netherlands)

    R. Saxena (Ruchi); A.D. Wijnhoud (Annemarie); H. Carton; W. Hacke (Werner); M. Kaste; R.J. Przybelski; K.N. Stern; P.J. Koudstaal (Peter Jan)

    1999-01-01

    textabstractBACKGROUND AND PURPOSE: Diaspirin cross-linked hemoglobin (DCLHb) is a purified, cell-free human hemoglobin solution. In animal stroke models its use led to a significant reduction in the extent of brain injury. The primary objective of this study was to evaluate the safety of DCLHb in

  13. Effects of mutations on the molecular dynamics of oxygen escape from the dimeric hemoglobin of Scapharca inaequivalvis [v1; ref status: indexed, http://f1000r.es/52d

    Directory of Open Access Journals (Sweden)

    Kevin Trujillo

    2015-03-01

    Full Text Available Like many hemoglobins, the structure of the dimeric hemoglobin from the clam Scapharca inaequivalvis is a “closed bottle” since there is no direct tunnel from the oxygen binding site on the heme to the solvent.  The proximal histidine faces the dimer interface, which consists of the E and F helicies.  This is significantly different from tetrameric vertebrate hemoglobins and brings the heme groups near the subunit interface. The subunit interface is also characterized by an immobile, hydrogen-bonded network of water molecules.  Although there is data which is consistent with the histidine gate pathway for ligand escape, these aspects of the structure would seem to make that pathway less likely. Locally enhanced sampling molecular dynamics are used here to suggest alternative pathways in the wild-type and six mutant proteins. In most cases the point mutations change the selection of exit routes observed in the simulations. Exit via the histidine gate is rarely seem although oxygen molecules do occasionally cross over the interface from one subunit to the other. The results suggest that changes in flexibility and, in some cases, creation of new cavities can explain the effects of the mutations on ligand exit paths.

  14. Localized increase of tissue oxygen tension by magnetic targeted drug delivery

    Science.gov (United States)

    Liong, Celine; Ortiz, Daniel; Ao-ieong, Eilleen; Navati, Mahantesh S.; Friedman, Joel M.; Cabrales, Pedro

    2014-07-01

    Hypoxia is the major hindrance to successful radiation therapy of tumors. Attempts to increase the oxygen (O2) tension (PO2) of tissue by delivering more O2 have been clinically disappointing, largely due to the way O2 is transported and released by the hemoglobin (Hb) within the red blood cells (RBCs). Systemic manipulation of O2 transport increases vascular resistance due to metabolic autoregulation of blood flow to prevent over oxygenation. This study investigates a new technology to increase O2 delivery to a target tissue by decreasing the Hb-O2 affinity of the blood circulating within the targeted tissue. As the Hb-O2 affinity decreases, the tissue PO2 to satisfy tissue O2 metabolic needs increases without increasing O2 delivery or extraction. Paramagnetic nanoparticles (PMNPs), synthetized using gadolinium oxide, were coated with the cell permeable Hb allosteric effector L35 (3,5-trichlorophenylureido-phenoxy-methylpropionic acid). L35 decreases Hb affinity for O2 and favors the release of O2. The L35-coated PMNPs (L35-PMNPs) were intravenously infused (10 mg kg-1) to hamsters instrumented with the dorsal window chamber model. A magnetic field of 3 mT was applied to localize the effects of the L35-PMNPs to the window chamber. Systemic O2 transport characteristics and microvascular tissue oxygenation were measured after administration of L35-PMNPs with and without magnetic field. The tissue PO2 in untreated control animals was 25.2 mmHg. L35-PMNPs without magnetic field decreased tissue PO2 to 23.4 mmHg, increased blood pressure, and reduced blood flow, largely due to systemic modification of Hb-O2 affinity. L35-PMNPs with magnetic field increased tissue PO2 to 27.9 mmHg, without systemic or microhemodynamic changes. These results indicate that localized modification of Hb-O2 affinity can increase PO2 of target tissue without affecting systemic O2 delivery or triggering O2 autoregulation mechanisms. This technology can be used to treat local hypoxia and to

  15. Boronate-Modified Interdigitated Electrode Array for Selective Impedance-Based Sensing of Glycated Hemoglobin

    DEFF Research Database (Denmark)

    Boonyasit, Yuwadee; Laiwattanapaisal, Wanida; Chailapakul, Orawon

    2016-01-01

    An impedance-based label-free affinity sensor was developed for the recognition of glycated hemoglobin (HbA1c). Interdigitated gold microelectrode arrays (IDA) were first modified with a self-assembled monolayer of cysteamine followed by cross-linking with glutaraldehyde and subsequent binding of 3......-aminophenylboronic acid (APBA), which selectively binds HbA1c via cis-diol interactions. Impedance sensing was demonstrated to be highly responsive to the clinically relevant HbA1c levels (0.1%-8.36%) with a detection limit of 0.024% (3σ). The specificity of the assay was evaluated with non-glycated hemoglobin (Hb...

  16. Importance of hemoglobin concentration to exercise: acute manipulations

    DEFF Research Database (Denmark)

    Calbet, José A L; Lundby, Carsten; Koskolou, Maria

    2006-01-01

    An acute reduction of blood hemoglobin concentration ([Hb]), even when the circulating blood volume is maintained, results in lower (.)V(O(2)(max) and endurance performance, due to the reduction of the oxygen carrying capacity of blood. Conversely, an increase of [Hb] is associated with enhanced...

  17. Non equivalence of the chains in the allosteric interaction of the hemoglobin

    International Nuclear Information System (INIS)

    Jacchieri, S.G.

    1983-01-01

    The importance, for the temperature dependence of the cooperative behaviour of hemoglobin, of the functional non equivalence of the polypeptide chains from which the hemoglobin molecule is built is studied. With such purpose thermodynamic allosteric parameters are introduced called 'mean allosteric parameters' which relate the last two oxygen bindings to the firsttwo ones. It is shown that the mean allosteric free energy is strongly correlated to the Hill parameter which is a classic measure of cooperativity; hence, the mean allosteric free energy measures the hemoglobin cooperativity. Recent experimental data show that the mean allosteric free energy decreasses with temperature; this is due to the mean allosteric enthalphy and entropy being positive quantities. To analise such behaviour in terms of thermodynamic's arguments equations are derived for the thermodynamic parameters of oxygen binding to hemoglobin in terms of those of its chains. Since the obtained equations have a great number of terms the same treatment is applied to a hypothetic dimer from which simpler relations are derived. From both cases it is concluded that the positive character of the mean allosteric enthalpy and entropy is due to the presence of cooperative and anticooperative terms. Since the last terms are absent in the equations of allosteric homoproteins, the characteristic temperature-dependence of hemoglobin's cooperativity depends on the presence of non-equivalent chains. (Author) [pt

  18. Rapid determination of oxygen saturation and vascularity for cancer detection.

    Directory of Open Access Journals (Sweden)

    Fangyao Hu

    Full Text Available A rapid heuristic ratiometric analysis for estimating tissue hemoglobin concentration and oxygen saturation from measured tissue diffuse reflectance spectra is presented. The analysis was validated in tissue-mimicking phantoms and applied to clinical measurements in head and neck, cervical and breast tissues. The analysis works in two steps. First, a linear equation that translates the ratio of the diffuse reflectance at 584 nm and 545 nm to estimate the tissue hemoglobin concentration using a Monte Carlo-based lookup table was developed. This equation is independent of tissue scattering and oxygen saturation. Second, the oxygen saturation was estimated using non-linear logistic equations that translate the ratio of the diffuse reflectance spectra at 539 nm to 545 nm into the tissue oxygen saturation. Correlations coefficients of 0.89 (0.86, 0.77 (0.71 and 0.69 (0.43 were obtained for the tissue hemoglobin concentration (oxygen saturation values extracted using the full spectral Monte Carlo and the ratiometric analysis, for clinical measurements in head and neck, breast and cervical tissues, respectively. The ratiometric analysis was more than 4000 times faster than the inverse Monte Carlo analysis for estimating tissue hemoglobin concentration and oxygen saturation in simulated phantom experiments. In addition, the discriminatory power of the two analyses was similar. These results show the potential of such empirical tools to rapidly estimate tissue hemoglobin in real-time spectral imaging applications.

  19. Coexpression of Human α- and Circularly Permuted β-Globins Yields a Hemoglobin with Normal R State but Modified T State Properties†

    Science.gov (United States)

    Asmundson, Anna L.; Taber, Alexandria M.; van der Walde, Adella; Lin, Danielle H.; Olson, John S.; Anthony-Cahill, Spencer J.

    2009-01-01

    For the first time, a circularly permuted human β-globin (cpβ) has been coexpressed with human α-globin in bacterial cells and shown to associate to form α-cpβ hemoglobin in solution. Flash photolysis studies of α-cpβ show markedly biphasic CO and O2 kinetics with the amplitudes for the fast association phases being dominant due the presence of large amounts of high-affinity liganded hemoglobin dimers. Extensive dimerization of liganded but not deoxygenated α-cpβ was observed by gel chromatography. The rate constants for O2 and CO binding to the R state forms of α-cpβ are almost identical to those of native HbA (k′R(CO) ≈ 5.0 μM−1 s−1; k′R(O2) ≈ 50 μM−1 s−1), and the rate of O2 dissociation from fully oxygenated α-cpβ is also very similar to that observed for HbA (kR(O2) ≈ 21–28 s−1). When the equilibrium deoxyHb form of α-cpβ is reacted with CO in rapid mixing experiments, the observed time courses are monophasic and the observed bimolecular association rate constant is ∼1.0 μM−1 s−1, which is intermediate between the R state rate measured in partial photolysis experiments (∼5 μM−1 s−1) and that observed for T state deoxyHbA (k′T(CO) ≈ 0.1 to 0.2 μM−1 s−1). Thus the deoxygenated permutated β subunits generate an intermediate, higher affinity, deoxyHb quaternary state. This conclusion is supported by equilibrium oxygen binding measurements in which α-cpβ exhibits a P50 of ∼1.5 mmHg and a low n-value (∼1.3) at pH 7, 20 °C, compared to 8.5 mmHg and n ≈ 2.8 for native HbA under identical, dilute conditions. PMID:19397368

  20. The role of nitric oxide and hemoglobin in plant development and morphogenesis

    DEFF Research Database (Denmark)

    Hebelstrup, Kim; Shah, Jay K; Igamberdiev, Abir U

    2013-01-01

    effects on control of plant growth and development, such as shoot and root architecture. All plants are able to express non-symbiotic hemoglobins at low concentration. Their function is generally not related to oxygen transport or storage; instead they effectively oxidize NO to NO3– and thereby control...... the local cellular NO concentration. In this review, we analyze available data on the role of NO and plant hemoglobins in morphogenetic processes in plants. The comparison of the data suggests that hemoglobin gene expression in plants modulates development and morphogenesis of organs, such as roots...... and shoots, through the localized control of NO, and that hemoglobin gene expression should always be considered a modulating factor in processes controlled directly or indirectly by NO in plants....

  1. Why are there two kinds of chain in tetrameric hemoglobins

    International Nuclear Information System (INIS)

    Ferreira, R.; Jacchieri, S.G.

    1981-01-01

    The homeotropic allosteric interactions responsible for the sigmoidal oxygen saturation curves of α 2 β 2 hemoglobins are shown to be larger than those of hypothetical hemoglobins obeying identical curves and built from equivalent chains, γ 4 . It is also shown that this ensures for the α 2 β 2 species a more dependable cooperativity, through a biologically significative temperature range. On the basis of these findings it is argued that the existence of two different globin chains is advantageous in an evolutionary sense. (Author) [pt

  2. Immunohistochemical detection of osteopontin in advanced head-and-neck cancer: Prognostic role and correlation with oxygen electrode measurements, hypoxia-inducible-factor-1α-related markers, and hemoglobin levels

    International Nuclear Information System (INIS)

    Bache, Matthias; Reddemann, Rolf; Said, Harun M.; Holzhausen, Hans-Juergen; Taubert, Helge; Becker, Axel; Kuhnt, Thomas; Haensgen, Gabriele; Dunst, Juergen; Vordermark, Dirk

    2006-01-01

    Purpose: The tumor-associated glycoprotein osteopontin (OPN) is discussed as a plasma marker of tumor hypoxia. However, the association of immunohistochemical OPN expression in tumor sections with tumor oxygenation parameters (HF5, median pO 2 ), the hypoxia-related markers hypoxia-inducible factor-1α (HIF-1α) and carbonic anhydrase IX (CAIX), or hemoglobin and systemic vascular endothelial growth factor (VEGF) levels has not been investigated. Methods and Materials: Tumor tissue sections of 34 patients with advanced head-and-neck cancer treated with radiotherapy were assessed by immunochemistry for the expression of OPN, HIF-1α, and CA IX. Relationship of OPN expression with tumor oxygenation parameters (HF5, median pO 2 ), HIF-1α and CA IX expression, hemoglobin and serum VEGF level, and clinical parameters was studied. Results: Bivariate analysis showed a significant correlation of positive OPN staining with low hemoglobin level (p = 0.02), high HIF-1α expression (p = 0.02), and high serum vascular endothelial growth factor level (p = 0.02) for advanced head-and-neck cancer. Furthermore, considering the 31 Stage IV patients, the median pO 2 correlated significantly with the OPN expression (p = 0.02). OPN expression alone had only a small impact on prognosis. However, in a univariate Cox proportional hazard regression model, the expression of either OPN or HIF-1α or CA IX was associated with a 4.1-fold increased risk of death (p = 0.02) compared with negativity of all three markers. Conclusion: Osteopontin expression detected immunohistochemically is associated with oxygenation parameters in advanced head-and-neck cancer. When the results of OPN, HIF-1α, and CA IX immunohistochemistry are combined into a hypoxic profile, a strong and statistically significant impact on overall survival is found

  3. Structural and functional properties of hemoglobins from unicellular organisms as revealed by resonance Raman spectroscopy.

    Science.gov (United States)

    Egawa, Tsuyoshi; Yeh, Syun-Ru

    2005-01-01

    Hemoglobins have been discovered in organisms from virtually all kingdoms. Their presence in unicellular organisms suggests that the gene for hemoglobin is very ancient and that the hemoglobins must have functions other than oxygen transport, in view of the fact that O2 delivery is a diffusion-controlled process in these organisms. Based on sequence alignment, three groups of hemoglobins have been characterized in unicellular organisms. The group-one hemoglobins, termed truncated hemoglobins, consist of proteins with 110-140 amino acid residues and a novel two-over-two alpha-helical sandwich motif. The group-two hemoglobins, termed flavohemoglobins, consist of a hemoglobin domain, with a classical three-over-three alpha-helical sandwich motif, and a flavin-containing reductase domain that is covalently attached to it. The group-three hemoglobins consist of myoglobin-like proteins that have high sequence homology and structural similarity to the hemoglobin domain of flavohemoglobins. In this review, recent resonance Raman studies of each group of these proteins are presented. Their implications are discussed in the context of the structural and functional properties of these novel hemoglobins.

  4. Hemoglobin E in Northeast India: A review on its origin, distribution, migration and health implication

    Directory of Open Access Journals (Sweden)

    Sikdar Mithun

    2016-09-01

    Full Text Available A systematic review of the studies on hemoglobin E in Northeast India has been carried out to understand the magnitude of research undertaken on this aspect during the last seven decades. Owing to the high prevalence of hemoglobin E in this part of India different authors have studied this hemoglobin from different perspectives and found conflicting results. However a systematic review of such studies is lacking from a holistic point of view. Most of the epidemiological, in vitro as well as in vivo studies show signatures of selection with this hemoglobin locus. However, how this polymorphism is maintained at different rates at different geographical region is still a matter of contention. This review will fill the gap from all perspectives starting from the frequency distribution of hemoglobin E and its spread in different parts of Northeast India, its relationship with malaria hypothesis, the population migration, population affinity and most importantly the health implication arising out of it. A probable origin of hemoglobin E among an Austroasiatic population of Northeast India has been postulated with the help of advance molecular anthropological knowledge like the deep rooted markers of mt DNA and Y-chromosome haplotypes.

  5. The narrow therapeutic window of glycated hemoglobin and assay variability.

    Science.gov (United States)

    Hosseini, S S; Bibler, I; Charles, M A

    1999-12-01

    Glycated hemoglobin is measured by a variety of assays, each of which has a unique normal level. Our purpose is to show that among the different assays available in the United States, using the same patient's blood sample, assay results may vary widely and may more or less easily achieve a glycated hemoglobin value within the normal range. The following assays were compared using the same patient's blood sample for each pair of assays: glycohemoglobin affinity assay (GHB Reader; Isolab, Akron, OH) versus gel electrophoresis assay (n = 76); Isolab versus ion capture assay (IMX; Abbott Laboratories, Irving, TX) (n = 57); monoclonal antibody assay (DCA2000; Bayer Diagnostics, Pittsburgh, PA) versus IMX (n = 100); and high-performance liquid chromatography (HPLC) assay (Bio-Rad Variant A1c; Bio-Rad Laboratories, Richmond, CA) versus IMX assay (n = 55). Our analyses indicate that a relative ranking can be established for the ease of achieving a normal glycated hemoglobin level. The ranking indicates that the most stringent or difficult assays for achieving a normal level are the Isolab and DCA2000 assays. The intermediate assays are the IMX and Bio-Rad Variant, and the easiest method for achieving a normal value is the gel electrophoresis assay. Our results indicate that various glycated hemoglobin assays vary widely and are associated with more or less difficulty for an individual patient to achieve a glycated hemoglobin level within the normal range. These results are especially significant with respect to (1) the clinically narrow therapeutic window of glycated hemoglobin values in type 1 diabetes to avoid rapidly advancing severe hypoglycemia rates and chronic microvascular complication rates, and (2) the glycated hemoglobin threshold for rapidly advancing macrovascular disease in both type 1 and type 2 patients.

  6. Stability and Application of Reactive Nitrogen and Oxygen Species-Induced Hemoglobin Modifications in Dry Blood Spots As Analyzed by Liquid Chromatography Tandem Mass Spectrometry.

    Science.gov (United States)

    Chen, Hauh-Jyun Candy; Fan, Chih-Huang; Yang, Ya-Fen

    2016-12-19

    Dried blood spot (DBS) is an emerging microsampling technique for the bioanalysis of small molecules, including fatty acids, metabolites, drugs, and toxicants. DBS offers many advantages as a sample format including easy sample collection and cheap sample shipment. Hemoglobin adducts have been recognized as a suitable biomarker for monitoring chemical exposure. We previously reported that certain modified peptides in hemoglobin derived from reactive chlorine, nitrogen, and oxygen species are associated with factors including smoking, diabetes mellitus, and aging. However, the stability of these oxidation-induced modifications of hemoglobin remains unknown and whether they can be formed artifactually during storage of DBS. To answer these questions, globin extracted from the DBS cards was analyzed, and the stability of the modifications was evaluated. After storage of the DBS cards at 4 °C or room temperature up to 7 weeks, we isolated globin from a quarter of the spot every week. The extents of 11 sites and types of post-translational modifications (PTMs), including nitration and nitrosylation of tyrosine and oxidation of cysteine and methionine residues, in human hemoglobin were measured in the trypsin digest by nanoflow liquid chromatography-nanospray ionization tandem mass spectrometry (nanoLC-NSI/MS/MS) using selected reaction monitoring. The extents of all these PTMs are stable within 14 days when stored on DBS at room temperature and at 4 °C, while those from direct extraction of fresh blood are stable for at least 8 weeks when stored as an aqueous solution at -20 °C. Extraction of globin from a DBS card is of particular importance for hemolytic blood samples. To our knowledge, this is the first report on the stability of oxidative modifications of hemoglobin on DBSs, which are stable for 14 days under ambient conditions (room temperature, in air). Therefore, it is feasible and convenient to analyze these hemoglobin modifications from DBSs in studies

  7. Hemoglobin, hematocrit, and changes in cerebral blood flow : The Second Manifestations of ARTerial disease-Magnetic Resonance study

    NARCIS (Netherlands)

    van der Veen, Pieternella H.; Muller, Majon; Vincken, Koen L.; Westerink, Jan; Mali, Willem P. T. M.; van der Graaf, Yolanda; Geerlings, Mirjam I.; Doevendans, PAFM

    Hemoglobin and hematocrit are important determinants of blood viscosity and arterial oxygen content and may therefore influence cerebral blood flow (CBF). We examined cross-sectional and prospective associations of hemoglobin and hematocrit with CBF in 569 patients with manifest arterial disease

  8. Simultaneous Monitoring of Vascular Oxygenation and Tissue Oxygen Tension of Breast Tumors Under Hyperbaric Oxygen Exposure

    National Research Council Canada - National Science Library

    Xia, Mengna

    2005-01-01

    The goals of the study in the first stage are 1) to develop a mathematic model by which we can derive tumor blood flow and metabolic rate of oxygen from hemoglobin concentration during interventions, 2...

  9. Hemoglobin-Based Oxygen Carrier (HBOC) Development in Trauma: Previous Regulatory Challenges, Lessons Learned, and a Path Forward.

    Science.gov (United States)

    Keipert, Peter E

    2017-01-01

    Historically, hemoglobin-based oxygen carriers (HBOCs) were being developed as "blood substitutes," despite their transient circulatory half-life (~ 24 h) vs. transfused red blood cells (RBCs). More recently, HBOC commercial development focused on "oxygen therapeutic" indications to provide a temporary oxygenation bridge until medical or surgical interventions (including RBC transfusion, if required) can be initiated. This included the early trauma trials with HemAssist ® (BAXTER), Hemopure ® (BIOPURE) and PolyHeme ® (NORTHFIELD) for resuscitating hypotensive shock. These trials all failed due to safety concerns (e.g., cardiac events, mortality) and certain protocol design limitations. In 2008 the Food and Drug Administration (FDA) put all HBOC trials in the US on clinical hold due to the unfavorable benefit:risk profile demonstrated by various HBOCs in different clinical studies in a meta-analysis published by Natanson et al. (2008). During standard resuscitation in trauma, organ dysfunction and failure can occur due to ischemia in critical tissues, which can be detected by the degree of lactic acidosis. SANGART'S Phase 2 trauma program with MP4OX therefore added lactate >5 mmol/L as an inclusion criterion to enroll patients who had lost sufficient blood to cause a tissue oxygen debt. This was key to the successful conduct of their Phase 2 program (ex-US, from 2009 to 2012) to evaluate MP4OX as an adjunct to standard fluid resuscitation and transfusion of RBCs. In 2013, SANGART shared their Phase 2b results with the FDA, and succeeded in getting the FDA to agree that a planned Phase 2c higher dose comparison study of MP4OX in trauma could include clinical sites in the US. Unfortunately, SANGART failed to secure new funding and was forced to terminate development and operations in Dec 2013, even though a regulatory path forward with FDA approval to proceed in trauma had been achieved.

  10. Characterization of hemodynamics and oxygenation in the renal cortex of rats

    Science.gov (United States)

    Grosenick, Dirk; Wabnitz, Heidrun; Macdonald, Rainer; Niendorf, Thoralf; Cantow, Kathleen; Flemming, Bert; Arakelyan, Karen; Seeliger, Erdmann

    2015-03-01

    We have performed a pre-clinical study on 13 rats to investigate the potential of near-infrared spectroscopy for quantification of hemoglobin concentration and oxygen saturation of hemoglobin in the renal cortex of small animals. These measurements were combined with laser-Doppler fluxmetry and a fluorescence quenching technique for quantification of tissue oxygen tension. Hemoglobin concentration and oxygen saturation were determined from experimental data by a Monte Carlo model. The methods were applied to investigate and compare temporal changes during several types of interventions such as arterial and venous occlusions, as well as hyperoxia, hypoxia and hypercapnia induced by different mixtures of the inspired gas.

  11. [Hemoglobin variants in Colombian patients referred to discard hemoglobinopathies].

    Science.gov (United States)

    Romero-Sánchez, Consuelo; Gómez Gutiérrez, Alberto; Duarte, Yurani; Amazo, Constanza; Manosalva, Clara; Chila M, Lorena; Casas-Gómez, María Consuelo; Briceño Balcázar, Ignacio

    2015-10-01

    Oxygen transport is altered in hemoglobinopathies. To study the distribution of hemoglobinopathies in Andean subjects without African ancestry. We analyzed blood samples of 1,407 subjects aged 18 to 59 years (58% females), living in the central Andean region of Colombia, referred to discard hemoglobinopathies. The frequency and type of hemoglobinopathy was established by capillary and agarose gel electrophoresis. The frequency of hemoglobinopathies was 34.5% and higher among females. The structural variants found were: AS-heterozygous hemoglobin (8.1%), homozygous SS (3.7%), heterozygous SC (2.2%), AC heterozygotes (0.5%) and heterozygous AE (0.3%). Quantitative variants found were Hb A-Beta thalassemia (13.91%) and Hb H (0.06%), Beta-thalassemia heterozygotes C (0.88%), S-Beta thalassemia heterozygotes (6.07%) and compound heterozygous SC/Beta thalassemia (0.25%), with a persistence of fetal hemoglobin 0. Composite thalassemia was also found in 31%. All techniques showed good correlation and capillary electrophoresis demonstrated a greater detection of hemoglobin variants. The frequency of hemoglobin variants in the analyzed population was high, which is an important public health indicator. The most common hemoglobin variant was HbA/Increased structural Hb A2 and the mos frequent structural hemoglobinopathy was sickle cell trait. Capillary electrophoresis can discern any Hb variants present in the population.

  12. Effect of ethanol of the radiation sensitivity of human hemoglobin

    International Nuclear Information System (INIS)

    Szweda-Lewandowska, Z.; Puchala, M.

    1981-01-01

    Radiation sensitivity of oxy-, deoxy-, and methemoglobin (HbOs, Hbbj, and MetHb) in water solutions containing 0.2 M ethanol and in ethanol-free solutions was compared. Radiation sensitivity was estimated on the basis of changes in absorbance at the Soret band (a = 430 nm for deoxyhemoglobin), changes in the absorbance ration Avqv/Avwt determined after conversion of irradiated preparations to methemoglobin, and changes in the value of parameters describing the reaction of hemoglobin oxygenation. The protection coefficient p of hemoglobin by ethanol (ratio of a change in the absence of ethanol to that in its presence) calculated from changes in absorbance at the Soret band equaled about 1.5 at a 4-Mrad dose in all bases except MetHb irradiated in air for which p was much higher (about 3.2). The protection coefficient p' calculated from Dtx values for changes in Avchemically bondv/Avwt equaled 2.2 for HbOs, and 2.8 for MetHb for preparations irradiated in air; p' = 1.7 for Hbbj and 1.8 for MetHb for preparations irradiated under argon. On the basis of these results, the role of /sup ./OH radicals and oxygen in the radiation damage of hemoglobin is discussed

  13. Repeated elevational transitions in hemoglobin function during the evolution of Andean hummingbirds.

    Science.gov (United States)

    Projecto-Garcia, Joana; Natarajan, Chandrasekhar; Moriyama, Hideaki; Weber, Roy E; Fago, Angela; Cheviron, Zachary A; Dudley, Robert; McGuire, Jimmy A; Witt, Christopher C; Storz, Jay F

    2013-12-17

    Animals that sustain high levels of aerobic activity under hypoxic conditions (e.g., birds that fly at high altitude) face the physiological challenge of jointly optimizing blood-O2 affinity for O2 loading in the pulmonary circulation and O2 unloading in the systemic circulation. At high altitude, this challenge is especially acute for small endotherms like hummingbirds that have exceedingly high mass-specific metabolic rates. Here we report an experimental analysis of hemoglobin (Hb) function in South American hummingbirds that revealed a positive correlation between Hb-O2 affinity and native elevation. Protein engineering experiments and ancestral-state reconstructions revealed that this correlation is attributable to derived increases in Hb-O2 affinity in highland lineages, as well as derived reductions in Hb-O2 affinity in lowland lineages. Site-directed mutagenesis experiments demonstrated that repeated evolutionary transitions in biochemical phenotype are mainly attributable to repeated amino acid replacements at two epistatically interacting sites that alter the allosteric regulation of Hb-O2 affinity. These results demonstrate that repeated changes in biochemical phenotype involve parallelism at the molecular level, and that mutations with indirect, second-order effects on Hb allostery play key roles in biochemical adaptation.

  14. The Reaction of Oxy Hemoglobin with Nitrite

    DEFF Research Database (Denmark)

    Hathazi, Denisa; Scurtu, Florina; Bischin, Cristina

    2018-01-01

    The autocatalytic reaction between nitrite and the oxy form of globins involves free radicals. For myoglobin (Mb), an initial binding of nitrite to the iron-coordinated oxygen molecule was proposed; the resulting ferrous-peroxynitrate species was not detected, but its decay product, the high...... to a simple kinetic model involving a transient met-aqua form, in contrast to the ferryl detected in the case of Mb in a similar reaction sequence. These data are in line with a previous observation of a transient accumulation of ferryl Hb under auto-catalytic conditions at much lower concentrations......-peroxynitrate. Density functional theory (DFT) calculations support this latter assignment. The reaction allows for differentiating between the reactivities of various chemically modified hemoglobins, including candidates for blood substitutes. Polymerization of hemoglobin slows the nitrite-induced oxidation, in sharp...

  15. Hemoglobin promotes somatic embryogenesis in peanut cultures.

    Science.gov (United States)

    Jayabalan, N; Anthony, P; Davey, M R; Power, J B; Lowe, K C

    2004-02-01

    Critical parameters influencing somatic embryogenesis include growth regulators and oxygen supply. Consequently, the present investigation has focused on optimization of a somatic embryogenic system for peanut (Arachis hypogaea L.) through media supplementation with the auxin, picloram. The latter at 30 mg L(-1) was optimal for inducing regeneration of somatic embryos from cultured explants of zygotic embryos. In contrast, somatic embryogenesis did not occur in the absence of this growth regulator. An assessment has also been made of the beneficial effect on somatic embryogenesis and plant regeneration of the commercial hemoglobin (Hb) solution, Erythrogen. Hemoglobin at 1:50 and 1:100 (v:v) stimulated increases in mean fresh weight (up to a maximum of 57% over control), mean number of explants producing somatic embryos (15%) and mean number of somatic embryos per explant (29%).

  16. Automatic labeling method for injectable {sup 15}O-oxygen using hemoglobin-containing liposome vesicles and its application for measurement of brain oxygen consumption by PET

    Energy Technology Data Exchange (ETDEWEB)

    Tiwari, Vijay Narayan [Biomedical Imaging Research Center, University of Fukui, Fukui (Japan)], E-mail: tiwaridr@u-fukui.ac.jp; Kiyono, Yasushi; Kobayashi, Masato; Mori, Tetsuya; Kudo, Takashi [Biomedical Imaging Research Center, University of Fukui, Fukui (Japan); Okazawa, Hidehiko [Biomedical Imaging Research Center, University of Fukui, Fukui (Japan); Research and Education Program for Life Science, University of Fukui, Fukui (Japan); Fujibayashi, Yasuhisa [Biomedical Imaging Research Center, University of Fukui, Fukui (Japan); Research and Education Program for Life Science, University of Fukui, Fukui (Japan)], E-mail: yfuji@u-fukui.ac.jp

    2010-01-15

    Introduction: The aim of this study was to develop an injectable {sup 15}O-O{sub 2} system using hemoglobin-containing vesicles (HbV), a type of artificial red blood cell, and to investigate the feasibility of {sup 15}O{sub 2}-labeled HbV ({sup 15}O{sub 2}-HbV) to measure cerebral metabolic rate of oxygen (CMRO{sub 2}) in rats. Methods: The direct bubbling method was combined with vortexing to enhance labeling efficiency of HbV with {sup 15}O-O{sub 2} gas. L-Cysteine was added as a reductant to protect hemoglobin molecules in HbV from oxidation at different concentrations, and labeling efficiencies were also compared. Measurement of cerebral blood flow (CBF) and CMRO{sub 2} in five normal rats was performed using a small animal PET scanner after the injection of H{sub 2}{sup 15}O and {sup 15}O{sub 2}-HbV to evaluate the precision of hemodynamic parameters quantitatively. Results: The labeling efficiency of HbV was significantly increased when vortexing and bubbling were combined compared with the simple bubbling method (P<.05). The most efficient method for labeling was bubbling of {sup 15}O-O{sub 2} combined with vortexing and the addition of 2.8 mM L-cysteine in HbV solution. The mean radioactivity of 214.4{+-}7.8 MBq/mL HbV was obtained using this method. PET scans using {sup 15}O{sub 2}-HbV and H{sub 2}{sup 15}O yielded a mean CMRO{sub 2} value of 6.8{+-}1.4 (mL/min per 100 g) in rats with normal CBF of 51.4{+-}7.9 (mL/min per 100 g). Conclusion: Addition of L-cysteine to HbV and simple direct bubbling of {sup 15}O-O{sub 2} gas combined with vortexing was the most efficient method for preparation of {sup 15}O{sub 2}-HbV. The present injectable system using {sup 15}O{sub 2}-HbV was successfully utilized to measure CMRO{sub 2} in rats, indicating that this new method could be useful for animal models to measure oxygen metabolism in the brain.

  17. Biochemistry Applied to Everyday Life: Chemical Equilibrium and the Transporting Function of the Hemoglobin

    Directory of Open Access Journals (Sweden)

    Carlos Mario Echeverría Palacio

    2006-12-01

    Full Text Available The hemoglobin is a blood protein which cantransport oxygen, a gas insoluble in water, todifferent organs where it is required for the properfunction; this protein also transports themetabolic products, CO2 and H+ for theirexcretion. This process depends on pH, the BPGconcentration, pO2 and pCO2. The cooperativebinding between hemoglobin and those compoundsand the conformational changes necessaryfor oxygen and CO2 uptake and release inthe specific place where they are required. Abruptchanges of atmospheric pressure associatedwith height and the exposure to other gases suchas CO present in vehicles and closed roomscould compromise the normal functioning of theorganism because their presence affects thetransport function of the hemoglobin. In thispaper, we will explain everyday phenomenarelated to the transport of gases through hemoglobinas a demonstration that a knowledge ofbiochemistry begins to be useful from now on to understand everyday situations and give usan expectation of their value to comprehendmany health problems that would be faced inthe future

  18. Misconceptions in Reporting Oxygen Saturation

    NARCIS (Netherlands)

    Toffaletti, John; Zijlstra, Willem G.

    2007-01-01

    BACKGROUND: We describe some misconceptions that have become common practice in reporting blood gas and cooximetry results. In 1980, oxygen saturation was incorrectly redefined in a report of a new instrument for analysis of hemoglobin (Hb) derivatives. Oxygen saturation (sO(2)) was redefined as the

  19. Reaction of oxygen with the respiratory chain in cells and tissues.

    Science.gov (United States)

    Chance, B

    1965-09-01

    This paper considers the way in which the oxygen reaction described by Dr. Nicholls and the ADP control reactions described by Dr. Racker could cooperate to establish a purposeful metabolic control phenomenon in vivo. This has required an examination of the kinetic properties of the respiratory chain with particular reference to methods for determinations of oxygen affinity (K(m)). The constant parameter for tissue respiration is k(1), the velocity constant for the reaction of oxygen with cytochrome oxidase. Not only is this quantity a constant for a particular tissue or mitochondria; it appears to vary little over a wide range of biological material, and for practical purposes a value of 5 x 10(7) at 25 degrees close to our original value (20) is found to apply with adequate accuracy for calculation of K(m) for mammalia. The quantity which will depend upon the tissue and its metabolic state is the value of K(m) itself, and K(m) may be as large as 0.5 microM and may fall to 0.05 microM or less in resting, controlled, or inhibited states. The control characteristic for ADP may depend upon the electron flux due to the cytochrome chain (40); less ADP is required to activate the slower electron transport at lower temperatures than at higher temperatures. The affinity constants for ADP control appear to be less dependent upon substrate supplied to the system. The balance of ADP and oxygen control in vivo is amply demonstrated experimentally and is dependent on the oxygen concentration as follows. In the presence of excess oxygen, control may be due to the ADP or phosphate (or substrate), and the kinetics of oxygen utilization will be independent of the oxygen concentration. As the oxygen concentration is diminished, hemoglobin becomes disoxygenated, deep gradients of oxygen concentration develop in the tissue, and eventually cytochrome oxidase becomes partially and then completely reduced. DPN at this point will become reduced and the electron flow diminished. The rate

  20. Purification, crystallization and x-ray diffraction data analysis of oxy hemoglobin-I from the catfish-Liposarcus anisitsi (Pisces)

    International Nuclear Information System (INIS)

    Smarra, A.L.S.; Arni, R.K.; Azevedo Junior, W.F. de; Colombo, M.F.; Bonilla-Rodriguez, G.O.

    1997-01-01

    Full text. Hemoglobin remains, despite the enormous amount of research involving this molecule, as a prototype of allosteric models and new conformations. The present work describes the purification crystallization and X-ray diffraction data analysis of the first hemoglobin (LHb-I) from the four components which constitutes Lopisarcus anisitsi's hemolysate. The functional behaviour of this hemoglobin has shown that proton and chloride effects are dependent on the presence of phosphates. Under these conditions emerges an alkaline Bohr effect, whereas chloride increases Hb oxygen-affinity. The usual interpretation for those findings involves pKa changes induced by phosphate binding and Cl competition for the phosphate binding site respectively. Alternatively we hypothesize that conformational changes can account for those observations. Accordingly, we have chose to perform Hb crystallization under different conditions to check for alternative conformations induced by these anions. The LHb-I has an isoelectric point of 8.1 being purified by ion-exchange chromatography on DEAE-Sephadex using a pH gradient, subsequent de ionization on amberlite M B 1 resin, concentrated and stored in liquid nitrogen until use. The protein solution was crystallized using the Sparce - matrix method, being obtained two monocrystal forms. First form: space group C 2, and cell parameters: a=185.42 A b=63.04 A c=57.59 A, α=γ= 90 deg β=92.79 deg. Crystallographic data was collected to 2.8 A. Second form: hexagonal system, a=b=63.9 A, c=327.96 A, α=β90 deg, γ=120 deg. Crystallographic data was collected to 2.7 A. The structure determination of first form has been initiated by molecular replacement methods. (author)

  1. Gene duplication and the evolution of hemoglobin isoform differentiation in birds.

    Science.gov (United States)

    Grispo, Michael T; Natarajan, Chandrasekhar; Projecto-Garcia, Joana; Moriyama, Hideaki; Weber, Roy E; Storz, Jay F

    2012-11-02

    The majority of bird species co-express two functionally distinct hemoglobin (Hb) isoforms in definitive erythrocytes as follows: HbA (the major adult Hb isoform, with α-chain subunits encoded by the α(A)-globin gene) and HbD (the minor adult Hb isoform, with α-chain subunits encoded by the α(D)-globin gene). The α(D)-globin gene originated via tandem duplication of an embryonic α-like globin gene in the stem lineage of tetrapod vertebrates, which suggests the possibility that functional differentiation between the HbA and HbD isoforms may be attributable to a retained ancestral character state in HbD that harkens back to a primordial, embryonic function. To investigate this possibility, we conducted a combined analysis of protein biochemistry and sequence evolution to characterize the structural and functional basis of Hb isoform differentiation in birds. Functional experiments involving purified HbA and HbD isoforms from 11 different bird species revealed that HbD is characterized by a consistently higher O(2) affinity in the presence of allosteric effectors such as organic phosphates and Cl(-) ions. In the case of both HbA and HbD, analyses of oxygenation properties under the two-state Monod-Wyman-Changeux allosteric model revealed that the pH dependence of Hb-O(2) affinity stems primarily from changes in the O(2) association constant of deoxy (T-state)-Hb. Ancestral sequence reconstructions revealed that the amino acid substitutions that distinguish the adult-expressed Hb isoforms are not attributable to the retention of an ancestral (pre-duplication) character state in the α(D)-globin gene that is shared with the embryonic α-like globin gene.

  2. Gene Duplication and the Evolution of Hemoglobin Isoform Differentiation in Birds*

    Science.gov (United States)

    Grispo, Michael T.; Natarajan, Chandrasekhar; Projecto-Garcia, Joana; Moriyama, Hideaki; Weber, Roy E.; Storz, Jay F.

    2012-01-01

    The majority of bird species co-express two functionally distinct hemoglobin (Hb) isoforms in definitive erythrocytes as follows: HbA (the major adult Hb isoform, with α-chain subunits encoded by the αA-globin gene) and HbD (the minor adult Hb isoform, with α-chain subunits encoded by the αD-globin gene). The αD-globin gene originated via tandem duplication of an embryonic α-like globin gene in the stem lineage of tetrapod vertebrates, which suggests the possibility that functional differentiation between the HbA and HbD isoforms may be attributable to a retained ancestral character state in HbD that harkens back to a primordial, embryonic function. To investigate this possibility, we conducted a combined analysis of protein biochemistry and sequence evolution to characterize the structural and functional basis of Hb isoform differentiation in birds. Functional experiments involving purified HbA and HbD isoforms from 11 different bird species revealed that HbD is characterized by a consistently higher O2 affinity in the presence of allosteric effectors such as organic phosphates and Cl− ions. In the case of both HbA and HbD, analyses of oxygenation properties under the two-state Monod-Wyman-Changeux allosteric model revealed that the pH dependence of Hb-O2 affinity stems primarily from changes in the O2 association constant of deoxy (T-state)-Hb. Ancestral sequence reconstructions revealed that the amino acid substitutions that distinguish the adult-expressed Hb isoforms are not attributable to the retention of an ancestral (pre-duplication) character state in the αD-globin gene that is shared with the embryonic α-like globin gene. PMID:22962007

  3. The refractive index of human hemoglobin in the visible range

    International Nuclear Information System (INIS)

    Zhernovaya, O; Tuchin, V; Sydoruk, O; Douplik, A

    2011-01-01

    Because the refractive index of hemoglobin in the visible range is sensitive to the hemoglobin concentration, optical investigations of hemoglobin are important for medical diagnostics and treatment. Direct measurements of the refractive index are, however, challenging; few such measurements have previously been reported, especially in a wide wavelength range. We directly measured the refractive index of human deoxygenated and oxygenated hemoglobin for nine wavelengths between 400 and 700 nm for the hemoglobin concentrations up to 140 g l -1 . This paper analyzes the results and suggests a set of model functions to calculate the refractive index depending on the concentration. At all wavelengths, the measured values of the refractive index depended on the concentration linearly. Analyzing the slope of the lines, we determined the specific refraction increments, derived a set of model functions for the refractive index depending on the concentration, and compared our results with those available in the literature. Based on the model functions, we further calculated the refractive index at the physiological concentration within the erythrocytes of 320 g l -1 . The results can be used to calculate the refractive index in the visible range for arbitrary concentrations provided that the refractive indices depend on the concentration linearly.

  4. Structure of the Zymomonas mobilis respiratory chain: oxygen affinity of electron transport and the role of cytochrome c peroxidase.

    Science.gov (United States)

    Balodite, Elina; Strazdina, Inese; Galinina, Nina; McLean, Samantha; Rutkis, Reinis; Poole, Robert K; Kalnenieks, Uldis

    2014-09-01

    The genome of the ethanol-producing bacterium Zymomonas mobilis encodes a bd-type terminal oxidase, cytochrome bc1 complex and several c-type cytochromes, yet lacks sequences homologous to any of the known bacterial cytochrome c oxidase genes. Recently, it was suggested that a putative respiratory cytochrome c peroxidase, receiving electrons from the cytochrome bc1 complex via cytochrome c552, might function as a peroxidase and/or an alternative oxidase. The present study was designed to test this hypothesis, by construction of a cytochrome c peroxidase mutant (Zm6-perC), and comparison of its properties with those of a mutant defective in the cytochrome b subunit of the bc1 complex (Zm6-cytB). Disruption of the cytochrome c peroxidase gene (ZZ60192) caused a decrease of the membrane NADH peroxidase activity, impaired the resistance of growing culture to exogenous hydrogen peroxide and hampered aerobic growth. However, this mutation did not affect the activity or oxygen affinity of the respiratory chain, or the kinetics of cytochrome d reduction. Furthermore, the peroxide resistance and membrane NADH peroxidase activity of strain Zm6-cytB had not decreased, but both the oxygen affinity of electron transport and the kinetics of cytochrome d reduction were affected. It is therefore concluded that the cytochrome c peroxidase does not terminate the cytochrome bc1 branch of Z. mobilis, and that it is functioning as a quinol peroxidase. © 2014 The Authors.

  5. Clinical, hematological and genetic data of a cohort of children with hemoglobin SD

    Directory of Open Access Journals (Sweden)

    Paulo do Val Rezende

    Full Text Available ABSTRACT INTRODUCTION: The hemoglobin FSD is very uncommon in newborn screening programs for sickle cell disease. In the program of Minas Gerais, Brazil, the clinical course of children with hemoglobin SD was observed to be heterogeneous. The objective of this study was to estimate the incidence (1999-2012 and to describe the natural history of a cohort of newborns with hemoglobin SD. METHODS: Isoelectric focusing was the primary method used in newborn screening. Polymerase chain reaction-restriction fragment length polymorphism and gene sequencing were used to identify mutant alleles and for haplotyping. Gap-polymerase chain reaction was used to detect alpha-thalassemia. RESULTS: Eleven cases of hemoglobin S/D-Punjab and eight of Hb S-Korle Bu were detected. Other variants with hemoglobin D mobility were not identified. All hemoglobin D-Punjab and hemoglobin Korle Bu alleles were associated with haplotype I. Among the children with hemoglobin S/D-Punjab, there were four with the ßS CAR haplotype, six with the Benin haplotype, and one atypical. Results of laboratory tests for hemoglobin S/D-Punjab and hemoglobin S-Korle Bu were: hemoglobin 8.0 and 12.3 g/dL (p-value <0.001, leukocyte count 13.9 × 109/L and 10.5 × 109/L (p-value = 0.003, reticulocytes 7.5% and 1.0% (p-value <0.001, hemoglobin F concentration 16.1% and 6.9% (p-value = 0.001 and oxygen saturation 91.9% and 97% (p-value = 0.002, respectively. Only hemoglobin S/D-Punjab children had acute pain crises and needed blood transfusions or hydroxyurea. Those with the Benin ßS haplotype had higher total hemoglobin and hemoglobin F concentrations compared to the CAR haplotype. Transcranial Doppler was normal in all children. CONCLUSION: The clinical course and blood cell counts of children with hemoglobin S/D-Punjab were very similar to those of hemoglobin SS children. In contrast, children with hemoglobin S-Korle Bu had clinical course and blood cell counts like children with the sickle

  6. Quantification of extra-cerebral and cerebral hemoglobin concentrations during physical exercise using time-domain near infrared spectroscopy.

    Science.gov (United States)

    Auger, Héloïse; Bherer, Louis; Boucher, Étienne; Hoge, Richard; Lesage, Frédéric; Dehaes, Mathieu

    2016-10-01

    Fitness is known to have beneficial effects on brain anatomy and function. However, the understanding of mechanisms underlying immediate and long-term neurophysiological changes due to exercise is currently incomplete due to the lack of tools to investigate brain function during physical activity. In this study, we used time-domain near infrared spectroscopy (TD-NIRS) to quantify and discriminate extra-cerebral and cerebral hemoglobin concentrations and oxygen saturation ( SO 2 ) in young adults at rest and during incremental intensity exercise. In extra-cerebral tissue, an increase in deoxy-hemoglobin ( HbR ) and a decrease in SO 2 were observed while only cerebral HbR increased at high intensity exercise. Results in extra-cerebral tissue are consistent with thermoregulatory mechanisms to dissipate excess heat through skin blood flow, while cerebral changes are in agreement with cerebral blood flow ( CBF ) redistribution mechanisms to meet oxygen demand in activated regions during exercise. No significant difference was observed in oxy- ( HbO 2 ) and total hemoglobin ( HbT ). In addition HbO 2 , HbR and HbT increased with subject's peak power output (equivalent to the maximum oxygen volume consumption; VO 2 peak) supporting previous observations of increased total mass of red blood cells in trained individuals. Our results also revealed known gender differences with higher hemoglobin in men. Our approach in quantifying both extra-cerebral and cerebral absolute hemoglobin during exercise may help to better interpret past and future continuous-wave NIRS studies that are prone to extra-cerebral contamination and allow a better understanding of acute cerebral changes due to physical exercise.

  7. Neoplasms radiosensitivity: how to increase the efficiency of radiotherapy

    International Nuclear Information System (INIS)

    Calais, G.

    1991-01-01

    The hypoxia in the neoplasms is a radioresistance factor. This article is about the methods able to reduce the hypoxia in tumors: use of hyperbaric oxygen, radiosensitizers (as metronidazole), hyperthermia and modification of oxygen release in the tissues in modifying the blood flow and in reducing the hemoglobin affinity for oxygen [fr

  8. Coupling of tertiary and quaternary changes in human hemoglobin: A 1D and 2D NMR study of hemoglobin Saint Mande (βN102Y)

    International Nuclear Information System (INIS)

    Craescu, C.T.; Blouquit, Y.; Mispelter, J.

    1990-01-01

    Hemoglobin Saint Mande (βN102Y) is a low-affinity mutant with the substitution site situated in the quaternary-sensitive α 1 β 2 interface. In adult hemoglobin the Asn102β contributes to the stability of the liganded (R) state, forming a hydrogen bond with Asp94α. The quaternary and tertiary perturbations subsequent to the Tyr for Asn substitution in monocarboxylated hemoglobin Saint Mande have been investigated by one-and two-dimensional nuclear magnetic resonance (NMR) spectroscopy. Analysis of the one-dinensional NMR spectra of the liganded and unliganded samples in 1 H 2 O provides evidence that both R and T quaternary structures of Hb Saint Mande are different from the corresponding ones in HbA. In the monocarboxylated form of the mutant hemoglobin, at acid pH, the authors have observed the disappearance of an R-type hydrogen bond and the appearance of a new one whose proton resonates like a deoxy T marker. Using two-dimensional NMR methods and on the basis of previous results on the monocarboxylated HbA, they have obtained a significant number of resonance assignments in the spectra of monocarboxylated Hb Saint Mande at pH 5.6 in the presence or absence of a strong allosteric effector, inositol hexaphosphate. This enabled us to characterize the tertiary conformational changes triggered by the quaternary-state modification. The observed structural variations are confined within the heme pocket regions but concern both the α and β subunits

  9. [Hemoglobin and testosterone: importance on high altitude acclimatization and adaptation].

    Science.gov (United States)

    Gonzales, Gustavo F

    2011-03-01

    The different types of response mechanisms that the organism uses when exposed to hypoxia include accommodation, acclimatization and adaptation. Accommodation is the initial response to acute exposure to high altitude hypoxia and is characterized by an increase in ventilation and heart rate. Acclimatization is observed in individuals temporarily exposed to high altitude, and to some extent, it enables them to tolerate the high altitudes. In this phase, erythropoiesis is increased, resulting in higher hemoglobin and hematocrit levels to improve oxygen delivery capacity. Adaptation is the process of natural acclimatization where genetical variations and acclimatization play a role in allowing subjects to live without any difficulties at high altitudes. Testosterone is a hormone that regulates erythropoiesis and ventilation and could be associated to the processes of acclimatization and adaptation to high altitude. Excessive erythrocytosis, which leads to chronic mountain sickness, is caused by low arterial oxygen saturation, ventilatory inefficiency and reduced ventilatory response to hypoxia. Testosterone increases during acute exposure to high altitude and also in natives at high altitude with excessive erythrocytosis. Results of current research allow us to conclude that increase in serum testosterone and hemoglobin is adequate for acclimatization, as they improve oxygen transport, but not for high altitude adaptation, since high serum testosterone levels are associated to excessive erythrocytosis.

  10. Возможности медикаментозной коррекции напряжения кислорода в крови у пациентов с хронической сердечной недостаточностью

    OpenAIRE

    Кукес, В.; Прокофьев, А.; Горошко, О.; Чеча, О.

    2014-01-01

    Under hypoxic conditions of different genesis decreases the affinity of hemoglobin for oxygen by increasing the synthesis of 2,3-diphosphoglycerate. Course administration ethylmethylhydroxypyridine malate promotes restoration of activity of 2,3-DPG and the normalization of blood oxygen tension in patients with CHF for 5 days.

  11. The quaternary state of polymerized human hemoglobin regulates oxygenation of breast cancer solid tumors: A theoretical and experimental study

    Science.gov (United States)

    Ju, Julia A.; Baek, Jin Hyen; Yalamanoglu, Ayla; Buehler, Paul W.; Gilkes, Daniele M.; Palmer, Andre F.

    2018-01-01

    A major constraint in the treatment of cancer is inadequate oxygenation of the tumor mass, which can reduce chemotherapeutic efficacy. We hypothesize that polymerized human hemoglobin (PolyhHb) can be transfused into the systemic circulation to increase solid tumor oxygenation, and improve chemotherapeutic outcomes. By locking PolyhHb in the relaxed (R) quaternary state, oxygen (O2) offloading at low O2 tensions (20 mm Hg) is facilitated with tense (T) state PolyhHb. Therefore, R-state PolyhHb may deliver significantly more O2 to hypoxic tissues. Biophysical parameters of T and R-state PolyhHb were used to populate a modified Krogh tissue cylinder model to assess O2 transport in a tumor. In general, we found that increasing the volume of transfused PolyhHb decreased the apparent viscosity of blood in the arteriole. In addition, we found that PolyhHb transfusion decreased the wall shear stress at large arteriole diameters (>20 μm), but increased wall shear stress for small arteriole diameters (state PolyhHb may be more effective than T-state PolyhHb for O2 delivery at similar transfusion volumes. Reduction in the apparent viscosity resulting from PolyhHb transfusion may result in significant changes in flow distributions throughout the tumor microcirculatory network. The difference in wall shear stress implies that PolyhHb may have a more significant effect in capillary beds through mechano-transduction. Periodic top-load transfusions of PolyhHb into mice bearing breast tumors confirmed the oxygenation potential of both PolyhHbs via reduced hypoxic volume, vascular density, tumor growth, and increased expression of hypoxia inducible genes. Tissue section analysis demonstrated primary PolyhHb clearance occurred in the liver and spleen indicating a minimal risk for renal damage. PMID:29414985

  12. Effect of Locomotor Respiratory Coupling Induced by Cortical Oxygenated Hemoglobin Levels During Cycle Ergometer Exercise of Light Intensity.

    Science.gov (United States)

    Oyanagi, Keiichi; Tsubaki, Atsuhiro; Yasufuku, Yuichi; Takai, Haruna; Kera, Takeshi; Tamaki, Akira; Iwata, Kentaro; Onishi, Hideaki

    This study aimed to clarify the effects of locomotor-respiratory coupling (LRC) induced by light load cycle ergometer exercise on oxygenated hemoglobin (O2Hb) in the dorsolateral prefrontal cortex (DLPFC), supplementary motor area (SMA), and sensorimotor cortex (SMC). The participants were 15 young healthy adults (9 men and 6 women, mean age: 23.1 ± 1.8 (SEM) years). We conducted a task in both LRC-inducing and LRC-non-inducing conditions for all participants. O2Hb was measured using near-infrared spectroscopy. The LRC frequency ratio during induction was 2:1; pedaling rate, 50 rpm; and intensity of load, 30 % peak volume of oxygen uptake. The test protocol included a 3-min rest prior to exercise, steady loading motion for 10 min, and 10-min rest post exercise (a total of 23 min). In the measurement of O2Hb, we focused on the DLPFC, SMA, and SMC. The LRC frequency was significantly higher in the LRC-inducing condition (p < 0.05). O2Hb during exercise was significantly lower in the DLPFC and SMA, under the LRC-inducing condition (p < 0.05). The study revealed that even light load could induce LRC and that O2Hb in the DLPFC and SMA decreases during exercise via LRC induction.

  13. Determination of the PO2 temperature blood factor from oxygen dissociation curves.

    Science.gov (United States)

    Hérigault, R A; Soulard, C D; Teisseire, B P; Laurent, D N

    1983-01-01

    The variation with saturation of the temperature coefficient of PO2 in human blood (delta log PO2/delta T) was determined by continuous recording of the oxygen dissociation curve (ODC), at 37 degrees C and 25 degrees C, on the same blood samples. PCO2 and pH were held constant through an ODC run, and PCO2 was reduced at 25 degrees C to the value measured by anaerobic cooling of the same sample. delta log PO2/delta T was calculated from isosaturation points on the 37 and 25 degrees C curves. The temperature coefficient was also computed as an independent check on this method by determination of the effects of temperature (25, 30, 37 and 40 degrees C) on hemoglobin ligand interaction: fixed acid Bohr effect (delta log PO2/delta pH), carbamino-formation (delta log PO2/delta log PCO2) and hemoglobin oxygen affinity. The values of delta log PO2/delta T ratio obtained from the two different approaches were found to be in good agreement. The coefficient decreased when [H+] concentration was increased. A linear relationship between the Bohr factor and the temperature was found: delta log PO2/delta pH = 0.00267 T-0.520 (r = 0.85; n = 40) At 25 degrees C, the carbamino-formation was one order of magnitude lower than at 37 degrees C. Acid-base state and saturation value appeared to be major determinant factors for the temperature correction coefficient to be applied to blood PO2 values measured at standard (37 degrees C) temperature.

  14. Blood hemoglobin level and treatment outcome of early breast cancer

    International Nuclear Information System (INIS)

    Henke, M.; Sindlinger, F.; Ikenberg, H.; Gerds, T.; Schumacher, M.

    2004-01-01

    Background and purpose: to determine whether the blood hemoglobin concentration correlates with the prognosis of patients with early breast cancer and, if so, whether this is restricted to treatment modality. Patients and methods: data were collected retrospectively from patients with early breast cancer (T1,2 NO-2 MO) who underwent either breast-conserving surgery followed by adjuvant radiotherapy (BCS-RT; n = 96) or a modified radical mastectomy (MRM; n = 194). The effect of preoperative blood hemoglobin level, nodal status, histological grading and hormone receptor status on disease-free survival was determined for both treatment modalities using a cox regression model and visualized by kaplan-meier plots. Results: the blood hemoglobin concentration significantly correlated with disease-free survival of patients receiving BCS-RT (relative risk [RR]: 0.67 per g/dl; p = 0.007). This was independent of other known risk factors for breast cancer patients, as determined by multivariate analysis. By contrast, the blood hemoglobin level had no prognostic significance when patients were treated with MRM. Conclusion: blood hemoglobin concentration seems to affect the prognosis of patients with early breast cancer when a treatment schedule that includes radiotherapy is applied. Reduced radiosensitivity due to diminished tumor oxygenation may be the underlying cause. Confirmative trials and studies intended to elucidate the underlying mechanism are warranted. (orig.)

  15. NITRITE REDUCTASE ACTIVITY OF NON-SYMBIOTIC HEMOGLOBINS FROM ARABIDOPSIS THALIANA†

    Science.gov (United States)

    Tiso, Mauro; Tejero, Jesús; Kenney, Claire; Frizzell, Sheila; Gladwin, Mark T.

    2013-01-01

    Plant non-symbiotic hemoglobins possess hexa-coordinate heme geometry similar to the heme protein neuroglobin. We recently discovered that deoxygenated neuroglobin converts nitrite to nitric oxide (NO), an important signaling molecule involved in many processes in plants. We sought to determine whether Arabidopsis thaliana non-symbiotic hemoglobins class 1 and 2 (AHb1 and AHb2) might function as nitrite reductases. We found that the reaction of nitrite with deoxygenated AHb1 and AHb2 generates NO gas and iron-nitrosyl-hemoglobin species. The bimolecular rate constants for nitrite reduction to NO are 19.8 ± 3.2 and 4.9 ± 0.2 M−1s−1, at pH = 7.4 and 25°C, respectively. We determined the pH dependence of these bimolecular rate constants and found a linear correlation with the concentration of protons, indicating the requirement for one proton in the reaction. Release of free NO gas during reaction in anoxic and hypoxic (2% oxygen) conditions was confirmed by chemiluminescence detection. These results demonstrate that deoxygenated AHb1 and AHb2 reduce nitrite to form NO via a mechanism analogous to that observed for hemoglobin, myoglobin and neuroglobin. Our findings suggest that during severe hypoxia and in the anaerobic plant roots, especially in water submerged species, non-symbiotic hemoglobins provide a viable pathway for NO generation via nitrite reduction. PMID:22620259

  16. Haemoglobin Pierre-Benite--a high affinity variant associated with relative polycythaemia.

    Science.gov (United States)

    Beard, M E; Potter, H C; Spearing, R L; Brennan, S O

    2001-12-01

    This is the second reported example of Hb Pierre--Benite (beta90 Glu-->Asp). This mutation is associated with increased oxygen affinity and polycythaemia. No instability was found and there was no charge shift detected by cellulose acetate electrophoresis at pH 8.3. The mutation was however, clearly indicated by electrospray ionization mass spectrometry (ESI MS), which showed an abnormal beta chain with a 14 Da decrease in mass. Blood volume studies documented a relative rather than a true polycythaemia and this finding has been reported in at least two other high affinity haemoglobin variants--Hb Heathrow and Hb Rahere. This finding led to delay in diagnosis because high oxygen affinity variants are conventionally considered to cause a true polycythaemia.

  17. Structural characterization of hemoglobins from Monilifera and Frenulata tubeworms (Siboglinids): first discovery of giant hexagonal-bilayer hemoglobin in the former "Pogonophora" group.

    Science.gov (United States)

    Meunier, Cédric; Andersen, Ann C; Bruneaux, Matthieu; Le Guen, Dominique; Terrier, Peran; Leize-Wagner, Emmanuelle; Zal, Franck

    2010-01-01

    Siboglinids are symbiotic polychete annelids having hemoglobins as essential oxygen- and sulfide-carriers for their endosymbiotic bacteria. We analyzed the structure of the hemoglobins from two species of siboglinids: the monilifera Sclerolinum contortum and the frenulata Oligobrachia webbi (i.e. haakonmosbiensis) from Norwegian cold seeps. Measured by Multi-Angle Laser Light Scattering (MALLS), Sclerolinum shows a 3190+/-50 kDa hexagonal bilayer hemoglobin (HBL-Hb) and a 461+/-46 kDa ring-Hb, just as vestimentifera, whereas Oligobrachia has a 409+/-3.7 kDa ring-Hb only. Electrospray Ionization-Mass Spectrometry (ESI-MS) showed Sclerolinum HBL-Hb composed of seven monomeric globins (15-16 kDa), three disulfide-bonded globin heterodimers and three linkers. The heterodimers always contain globin-b (15814.4+/-1.5 Da). Sclerolinum ring-Hb is composed of globins and dimers with identical masses as its HBL-Hb, but lacks linkers. Oligobrachia ring-Hb has three globin monomers (14-15 kDa) only, with no disulfide-bonded dimers. Comparison of Sclerolinum hemoglobins between Storegga and Haakon Mosby Mud Volcano, using the normalized height of deconvoluted ESI-MS peaks, shows differences in globin monomers abundances that could reflect genetic differences or differential gene expression between distinct seep populations. The discovery of HBL-Hb in Sclerolinum is a new element supporting the hypothesis of monilifera being phylogenetically more closely related to vestimentifera, than to frenulata.

  18. Purification and physical characteristics of a hemoglobin solution modified by coupling to 2-nor-2-formylpyridoxal 5‘-phosphate (NFPLP)

    NARCIS (Netherlands)

    van der Plas, J; de Vries-van Rossen, A; Koorevaar, JJ; Buursma, Anneke; Zijlstra, Willem; Bakker, JC

    1988-01-01

    Human stroma-free hemoglobin (Hb) was crosslinked with 2-nor-2- formylpyridoxal 5′-phosphate (NFPLP), purified over crosslinked dextran, and eluted with a linear salt gradient. The oxygen dissociation curve of this crosslinked hemoglobin appeared to be shifted to the right with a standard P50 of 49

  19. Spin Label Studies of the Hemoglobin-Membrane Interaction During Sickle Hemoglobin Polymerization

    International Nuclear Information System (INIS)

    Falcon Dieguez, Jose E.; Rodi, Pablo; Lores Guevara, Manuel A.; Gennaro, Ana Maria

    2009-12-01

    An enhanced hemoglobin-membrane association has been previously documented in Sickle Cell Anemia. However, it is not known how this interaction is modified during the hemoglobin S polymerization process. In this work, we use a model of reconstituted erythrocytes from ghost membranes whose cytoskeleton proteins had been previously labeled with the 4-maleimido Tempo spin label, and that were subsequently resealed with hemoglobin S or A solutions. Using EPR spectroscopy, we studied the time dependence of the spectral W/S parameter, indicative of the conformational state of cytoskeleton proteins (mainly spectrin) under spontaneous deoxygenation, with the aim of detecting the eventual effects due to hemoglobin S polymerization. The differences observed in the temporal behaviour of W/S in erythrocytes reconstituted with both hemoglobins were considered as experimental evidence of an increment in hemoglobin S-membrane interaction, as a result of the polymerization process of hemoglobin S under spontaneous deoxygenation. (author)

  20. Convergent Evolution of Hemoglobin Function in High-Altitude Andean Waterfowl Involves Limited Parallelism at the Molecular Sequence Level.

    Directory of Open Access Journals (Sweden)

    Chandrasekhar Natarajan

    2015-12-01

    Full Text Available A fundamental question in evolutionary genetics concerns the extent to which adaptive phenotypic convergence is attributable to convergent or parallel changes at the molecular sequence level. Here we report a comparative analysis of hemoglobin (Hb function in eight phylogenetically replicated pairs of high- and low-altitude waterfowl taxa to test for convergence in the oxygenation properties of Hb, and to assess the extent to which convergence in biochemical phenotype is attributable to repeated amino acid replacements. Functional experiments on native Hb variants and protein engineering experiments based on site-directed mutagenesis revealed the phenotypic effects of specific amino acid replacements that were responsible for convergent increases in Hb-O2 affinity in multiple high-altitude taxa. In six of the eight taxon pairs, high-altitude taxa evolved derived increases in Hb-O2 affinity that were caused by a combination of unique replacements, parallel replacements (involving identical-by-state variants with independent mutational origins in different lineages, and collateral replacements (involving shared, identical-by-descent variants derived via introgressive hybridization. In genome scans of nucleotide differentiation involving high- and low-altitude populations of three separate species, function-altering amino acid polymorphisms in the globin genes emerged as highly significant outliers, providing independent evidence for adaptive divergence in Hb function. The experimental results demonstrate that convergent changes in protein function can occur through multiple historical paths, and can involve multiple possible mutations. Most cases of convergence in Hb function did not involve parallel substitutions and most parallel substitutions did not affect Hb-O2 affinity, indicating that the repeatability of phenotypic evolution does not require parallelism at the molecular level.

  1. Hemoglobin (image)

    Science.gov (United States)

    Hemoglobin is the most important component of red blood cells. It is composed of a protein called ... exchanged for carbon dioxide. Abnormalities of an individual's hemoglobin value can indicate defects in the normal balance ...

  2. Fasting serum glucose and glycosylated hemoglobin level in obesity.

    Science.gov (United States)

    Das, R K; Nessa, A; Hossain, M A; Siddiqui, N I; Hussain, M A

    2014-04-01

    Obesity is a condition in which the body fat stores are increased to an extent which impairs health and leads to serious health consequences. The amount of body fat is difficult to measure directly, and is usually determined from an indirect measure - the body mass index (BMI). Increased BMI in obese persons is directly associated with an increase in metabolic disease, such as type 2 diabetes mellitus. This Analytical cross sectional study was undertaken to assess the relation between obesity and glycemic control of body by measuring fasting serum glucose and glycosylated hemoglobin. This study was carried out in the Department of Physiology, Mymensingh Medical College, Mymensingh from 1st July 2011 to 30th June 2012 on 120 equally divided male and female persons within the age range of 25 to 55 years. Age more than 55 years and less than 25 years and diagnosed case of Hypothyroidism, Cushing's syndrome, polycystic ovary, Antipsychotic drug user and regular steroid users were excluded. Non probability purposive type of sampling technique was used for selecting the study subjects. Measurement of body mass index was done as per procedure. Fasting serum glucose was estimated by glucose oxidase method and Glycosylated hemoglobin by Boronate Affinity method. Statistical analysis was done by SPSS (version 17.0). Data were expressed as Mean±SE and statistical significance of difference among the groups were calculated by unpaired student's 't' test and Pearson's correlation coefficient tests were done as applicable. The Mean±SE of fasting serum glucose was significant at 1% level (P value obese group of BMI. There was no significant difference of glycosylated hemoglobin level between control and study groups. But there was positive correlation within each group. Fasting serum glucose also showed a bit stronger positive correlation with BMI. Both obese male and female persons showed higher levels of fasting serum glucose and glycosylated hemoglobin. The observed positive

  3. Clinical effectiveness of hemoglobin spray (Granulox® as adjunctive therapy in the treatment of chronic diabetic foot ulcers

    Directory of Open Access Journals (Sweden)

    Sharon D. Hunt

    2016-11-01

    Full Text Available Introduction: Hemoglobin spray (Granulox® comprises purified hemoglobin and is a novel approach for increasing oxygen availability in the wound bed in diabetic foot ulcer patients. Its mode of action is to bind oxygen from the atmosphere and diffuse it into the wound bed to accelerate wound healing in slow-healing wounds. Patients and methods: Wound healing outcomes, that is, wound size, pain, percentage of slough, and exudate levels, were compared retrospectively to a similar cohort of patients treated over the same period the previous year. The same inclusion and exclusion criteria applied to both groups. Results: All 20 (100% hemoglobin spray-treated patients and 15 (75% control patients experienced some wound healing by week 4, with 5 (25% and 1 (5%, respectively, achieving complete wound closure. At week 4, mean wound size reduction was 63% in the hemoglobin spray group versus 26% for controls, increasing to 95% reduction at week 28 in the hemoglobin spray group versus 63% for controls (p<0.05 at all timepoints. Hemoglobin spray was associated with substantially lower pain scores using a 10-cm visual analogue scale, with 19/19 patients (100% being pain-free from week 12 onwards, compared to 6/18 patients (33% in the control group. At week 28, 2/18 patients (11% in the control group still had pain. Both groups had similar baseline slough levels, but hemoglobin spray-treated wounds had slough completely eliminated after 4 weeks versus 10% mean reduction in the control group (p<0.001. Hemoglobin spray was associated with markedly reduced exudate levels; within 4 weeks, no patients had high exudate levels in the hemoglobin spray group versus 5 in the control group. Conclusion: Standard wound care plus hemoglobin spray results in improvements in wound closure, wound size reduction, pain, slough, and exudate levels compared to control patients for chronic diabetic foot ulcer treatment.

  4. Seasonal changes in blood oxygen transport and acid-base status in the tegu lizard, Tupinambis merianae.

    Science.gov (United States)

    Andrade, Denis V; Brito, Simone P; Toledo, Luís Felipe; Abe, Augusto S

    2004-05-20

    Oxygen-binding properties, blood gases, and acid-base parameters were studied in tegu lizards, Tupinambis merianae, at different seasons and temperatures. Independent of temperature and pH, blood oxygen affinity was higher in dormant lizards than in those active during the summer. Haematocrit (Hct) and hemoglobin content ([Hb]) were greater in active lizards resulting in a higher oxygen-carrying capacity. Nucleoside triphosphate content ([NTP]) was reduced during dormancy, but the ratio between [NTP] and [Hb] remained unchanged. Dormancy was accompanied by an increase in plasma bicarbonate ([HCO-(3)]pl) and an elevation of arterial CO2 partial pressure (PaCO2) and CO2 content in the plasma (CplCO2). These changes in acid-base parameters persist over a broad range of body temperatures. In vivo, arterial O2 partial pressure (PaO2) and O2 content (CaO2) were not affected by season and tended to increase with temperature. Arterial pH (pHa) of dormant animals is reduced compared to active lizards at body temperatures below 15 degrees C, while no significant difference was noticed at higher temperatures. Copyright 2003 Elsevier B.V.

  5. Haptoglobin preferentially binds β but not α subunits cross-linked hemoglobin tetramers with minimal effects on ligand and redox reactions.

    Science.gov (United States)

    Jia, Yiping; Wood, Francine; Buehler, Paul W; Alayash, Abdu I

    2013-01-01

    Human hemoglobin (Hb) and haptoglobin (Hp) exhibit an extremely high affinity for each other, and the dissociation of Hb tetramers into dimers is generally believed to be a prerequisite for complex formation. We have investigated Hp interactions with native Hb, αα, and ββ cross-linked Hb (ααXLHb and ββXLHb, respectively), and rapid kinetics of Hb ligand binding as well as the redox reactivity in the presence of and absence of Hp. The quaternary conformation of ββ subunit cross-linking results in a higher binding affinity than that of αα subunit cross-linked Hb. However, ββ cross-linked Hb exhibits a four fold slower association rate constant than the reaction rate of unmodified Hb with Hp. The Hp contact regions in the Hb dimer interfaces appear to be more readily exposed in ββXLHb than ααXLHb. In addition, apart from the functional changes caused by chemical modifications, Hp binding does not induce appreciable effects on the ligand binding and redox reactions of ββXLHb. Our findings may therefore be relevant to the design of safer Hb-based oxygen therapeutics by utilizing this preferential binding of ββXLHb to Hp. This may ultimately provide a safe oxidative inactivation and clearance pathway for chemically modified Hbs in circulation.

  6. Recombinant hemoglobin II from Lucina pectinata: a large-scale method for hemeprotein expression in E. coli.

    Science.gov (United States)

    Ramos, Cacimar; Pietri, Ruth; Lorenzo, Wilmarie; Roman, Elddie; Granell, Laura B; Cadilla, Carmen L; López-Garriga, Juan

    2010-02-01

    Hemoglobin II from the clam L. pectinata is an O(2) reactive protein that remains oxygenated in the presence of other molecules. To determine the mechanism of ligand selection in this hemoglobin, rHbII was expressed in large quantities using an improved fermentation process. The highest protein yield was obtained by: transforming HbII into the BLi5 cells, inducing and supplementing the culture during the mid-log phase with 1 mM IPTG, 30 microg/mL hemin chloride and 1% glucose, and decreasing the temperature to 30 degrees C after induction. In addition, cell culture density was greatly enhanced by using glycerol, adding MgSO(4), supplementing the media with glucose after the glycerol was consumed and maintaining the dissolved oxygen at 35%. Under these conditions the maximum protein yield obtained was approximately 2,300 mg/L. The results indicate that rHbII is similar to the native protein. The protocol was validated with other hemoglobins, indicating that it can be extended to other hemeproteins.

  7. Cerebral oxygen transport failure?: decreasing hemoglobin and hematocrit levels after ischemic stroke predict poor outcome and mortality: STroke: RelevAnt Impact of hemoGlobin, Hematocrit and Transfusion (STRAIGHT)--an observational study.

    Science.gov (United States)

    Kellert, Lars; Martin, Evgenia; Sykora, Marek; Bauer, Harald; Gussmann, Philipp; Diedler, Jennifer; Herweh, Christian; Ringleb, Peter A; Hacke, Werner; Steiner, Thorsten; Bösel, Julian

    2011-10-01

    Although conceivably relevant for penumbra oxygenation, the optimal levels of hemoglobin (Hb) and hematocrit (Hct) in patients with acute ischemic stroke are unknown. We identified patients from our prospective local stroke database who received intravenous thrombolysis based on multimodal magnet resonance imaging during the years 1998 to 2009. A favorable outcome at 3 months was defined as a modified Rankin Scale score≤2 and a poor outcome as a modified Rankin Scale score≥3. The dynamics of Hemoglobin (Hb), Hematocrit (Hct), and other relevant laboratory parameters as well as cardiovascular risk factors were retrospectively assessed and analyzed between these 2 groups. Of 217 patients, 114 had a favorable and 103 a poor outcome. In a multivariable regression model, anemia until day 5 after admission (odds ratio [OR]=2.61; 95% CI, 1.33 to 5.11; P=0.005), Hb nadir (OR=0.81; 95% CI, 0.67 to 0.99; P=0.038), and Hct nadir (OR=0.93; 95% CI, 0.87 to 0.99; P=0.038) remained independent predictors for poor outcome at 3 months. Mortality after 3 months was independently associated with Hb nadir (OR=0.80; 95% CI, 0.65 to 0.98; P=0.028) and Hb decrease (OR=1.34; 95% CI, 1.01 to 1.76; P=0.04) as well as Hct decrease (OR=1.12; 95% CI, 1.01 to 1.23; P=0.027). Poor outcome and mortality after ischemic stroke are strongly associated with low and further decreasing Hb and Hct levels. This decrease of Hb and Hct levels after admission might be more relevant and accessible to treatment than are baseline levels.

  8. Erythrocyte 2,3-diphosphoglycerate depletion associated with hypophosphatemia detected by routine arterial blood gas analysis.

    Science.gov (United States)

    Larsen, V H; Waldau, T; Gravesen, H; Siggaard-Andersen, O

    1996-01-01

    To describe a clinical case where an extremely low erythrocyte 2,3-diphosphoglycerate concentration (2,3-DPG) was discovered by routine blood gas analysis supplemented by computer calculation of derived quantities. The finding of a low 2,3-DPG revealed a severe hypophosphatemia. Open uncontrolled study of a patient case. Intensive care observation during 41 days. A 44 year old woman with an abdominal abscess. Surgical drainage, antibiotics and parenteral nutrition. daily routine blood gas analyses with computer calculation of the hemoglobin oxygen affinity and estimation of the 2,3-DPG. An abrupt decline of 2,3-DPG was observed late in the course coincident with a pronounced hypophosphatemia. The fall in 2,3-DPG was verified by enzymatic analysis. 2,3-DPG may be estimated by computer calculation of routine blood gas data. A low 2,3-DPG which may be associated with hypophosphatemia causes an unfavorable increase in hemoglobin oxygen affinity which reduces the oxygen release to the tissues.

  9. Radioimmunochemical characterization of hemoglobins Lepore and Kenya: unique antigenic determinants located on hybrid hemoglobins

    International Nuclear Information System (INIS)

    Garver, F.A.; Altay, G.; Baker, M.M.; Gravely, M.; Huisman, T.H.J.

    1978-01-01

    Antisera were produced in rabbits to the three known types of Lepore hemoglobins, which contain hybrid delta-β non-α-chains, and to hemoglobin Kenya, which has a hybrid γ-β non-α-chain. By using a sensitive radioimmunoassay technique, the absorbed antisera were shown to contain an antibody population that was specific for the hybrid hemoglobin and did not cross-react with normal hemoglobins. However, with the absorbed Lepore-specific antisera, the three known types of Lepore hemoglobins were antigenically indistinguishable from each other, suggesting that antibodies are not produced to the primary structural differences which define the three non-α-chains of the Lepore hemoglobins. These studies demonstrate that the non-α-subunits of hemoglobins Lepore and Kenya possess unique antigenic determinant sites, evidently resulting from an altered polypeptide conformation

  10. A haptoglobin-hemoglobin receptor conveys innate immunity to Trypanosoma brucei in humans

    DEFF Research Database (Denmark)

    Vanhollebeke, Benoit; De Muylder, Géraldine; Nielsen, Marianne J

    2008-01-01

    The protozoan parasite Trypanosoma brucei is lysed by apolipoprotein L-I, a component of human high-density lipoprotein (HDL) particles that are also characterized by the presence of haptoglobin-related protein. We report that this process is mediated by a parasite glycoprotein receptor, which...... binds the haptoglobin-hemoglobin complex with high affinity for the uptake and incorporation of heme into intracellular hemoproteins. In mice, this receptor was required for optimal parasite growth and the resistance of parasites to the oxidative burst by host macrophages. In humans, the trypanosome...... immunity against the parasite....

  11. Hemoglobin levels and blood transfusion in patients with sepsis in Internal Medicine Departments.

    Science.gov (United States)

    Muady, Gassan Fuad; Bitterman, Haim; Laor, Arie; Vardi, Moshe; Urin, Vitally; Ghanem-Zoubi, Nesrin

    2016-10-13

    Acute reduction in hemoglobin levels is frequently seen during sepsis. Previous studies have focused on the management of anemia in patients with septic shock admitted to intensive care units (ICU's), including aggressive blood transfusion aiming to enhance tissue oxygenation. To study the changes in hemoglobin concentrations during the first week of sepsis in the setting of Internal Medicine (IM) units, and their correlation to survival. Observational prospective study. We recorded hemoglobin values upon admission and throughout the first week of hospital stay in a consecutive cohort of septic patients admitted to IM units at a community hospital, the patients were enrolled into a prospective registry. Data on blood transfusions was also collected, we examined the correlation between hemoglobin concentrations during the first week of sepsis and survival, the effect of blood transfusion was also assessed. Eight hundred and fifteen patients (815) with sepsis were enrolled between February 2008 to January 2009. More than 20 % of them had hemoglobin levels less than 10g/dL on admission, a rate that was doubled during the first week of sepsis. Overall, 68 (8.3 %) received blood transfusions, 14 of them (20.6 %) due to bleeding. Typically, blood transfusion was given to older patients with a higher rate of malignancy and lower hemoglobin levels. While hemoglobin concentration on admission had strong correlation with in-hospital mortality (O.R-0.83 [95 % C.I. 0.74-0.92], blood transfusion was not found to be an independent predicting factor for mortality. Anemia is very common in sepsis. While hemoglobin level on admission exhibit independent correlation with survival, blood transfusion do not.

  12. [Influence of mastication on the amount of hemoglobin in human brain tissue].

    Science.gov (United States)

    Sasaki, A

    2001-03-01

    The purpose of this study was to investigate the influence of mastication on the amount of hemoglobin in human brain tissue. Nine healthy volunteers (6 males and 3 females) participated in this study. They underwent two tasks: 1) at rest, 2) gum-chewing. In seven of the nine (4 males and 3 females), experimental occlusal interference was applied to the first molar of the mandibule on the habitual masticatory side. They underwent the gum-chewing task. To evaluate the amount of hemoglobin, both the hemoglobin oxygenation state and blood volume during gum-chewing were measured in the frontal region, using near-infrared spectroscopy. The amount of total-hemoglobin (blood volume) and oxyhemoglobin of subjects significantly increased during gum-chewing (p experimental occlusal interference was imposed on the subject, the amount of them significantly decreased compared with subjects without experimental occlusal interference (p < 0.05). The results suggested that increases of cerebral blood flow in the frontal region were not due to the mandibular movement, and that human brain activity caused by mastication was not only in the cortical masticatory area but also in the frontal region.

  13. Study on the relationship between blood levels of glycated hemoglobin (HbA1c) and micro-vascular nephropathy in patients with type 2 diabetes

    International Nuclear Information System (INIS)

    Luo Rong; Li Zhuocheng; Yan Dewen

    2004-01-01

    Objective: To evaluate the relationship between blood levels of glycated hemoglobin and microvascular nephropathy in patients with type diabetes. Methods: Blood Glycosylated hemoglobin levels were determined with affinity chromatography and 24 hour urinary microalbumin (m-Alb), β 2 microglobin (β 2 -m) quantified with RIA in 76 patients and 30 controls. Results: With glycated hemoglobin within normal range, there were no differences between the amounts of patients' urinary protein contents and those in controls (P>0.05). With higher blood glycated hemoglobin levels, significant differences could be observed (P 2 microglobin. Differences among the 24 hour urinary quantities of mAlb and β 2 -m in the three groups of patients (divided according to the HbA1c levels, namely 9.0%) were also significant (P 2 microglobin is very important for early detection of diabetic nephropathy

  14. Electronic structure of human hemoglobin: ultrasoft X-ray emission study

    International Nuclear Information System (INIS)

    Soldatov, A.V.; Kravtsova, A.N.; Fedorovich, E.N.; Kurmaev, E.Z.; Moewes, A.

    2004-01-01

    Full text: The iron L 2,3 and carbon, nitrogen and oxygen Kα X-ray emission spectra (XES) of human hemoglobin have been recorded at the soft X-ray spectroscopy endstation on Undulator Beam line 8.0 at Advanced Light Source (ALS) located at the Lawrence Berkeley National Laboratory. The theoretical calculations of Fe L 3 -XES have been performed using ab initio code FEFF8.2. The calculations have been carried out for the structure of hemoglobin presented in PDB (entry 3HHB) as well as for the molecule with symmetrical heme plane. It was found that the Fe L 3 emission spectrum calculated for the ideal molecule agrees slightly better with the experiment as compared with those calculated for the real molecule. Thus, one can use the structure of the ideal molecule for theoretical Fe L 3 -XES simulations. The theoretical analysis has shown that the fist peak of experimental Fe L 3 - emission spectrum is enhanced by the nearest nitrogen atoms lying in heme plane around the central iron atom. The theoretical C K- and N K-XES spectra of hemoglobin have been calculated. A good agreement between theoretical and experimental spectra has been obtained. The distribution of the partial electronic densities of states in the valence and conduction bands of hemoglobin has been determined

  15. Autologous blood sequestration using a double venous reservoir bypass circuit and polymerized hemoglobin prime.

    Science.gov (United States)

    Neragi-Miandoab, Siyamek; Guerrero, J Luis; Vlahakes, Gus J

    2002-01-01

    Cardiac surgery often necessitates transfusion of homologous blood. Hemoglobin based oxygen carrying solutions (HBOCs) transport oxygen, suggesting use in cardiopulmonary bypass. HBOC was used in a novel oxygenator double-reservoir circuit that permits acute sequestration of a portion of the autologous blood volume during bypass. Two groups of seven mongrel dogs each were studied in an experimental bypass model using global myocardial ischemia and cardioplegia protection: HBOC group, initial venous return drained to a separate reservoir and hypothermic bypass was conducted with HBOC containing perfusate in a second bypass reservoir; Control group, crystalloid prime in a conventional circuit. Hemodynamics and metabolic and hematologic parameters were measured before and 60 min after aortic clamp removal and reinfusion of sequestered autologous blood. Blood gases, base excess, hematocrit, total hemoglobin, and platelet counts were measured. In the HBOC group, metabolic acidosis did not occur, and ventricular function was preserved. Net conservation of platelets was noted at study conclusion: control 33+/-13 x 10(3) per mm3 versus HBOC 48+/-13 x 10(3), p conservation of the platelet mass occurs, a portion of which is not exposed to the deleterious effects of hypothermia and cardiopulmonary bypass.

  16. Influence of peripheral blood hemoglobin concentration on the result of radiotherapy for nasopharyngeal carcinoma

    International Nuclear Information System (INIS)

    He Beiwa; Zhang Guofen; Zhao Yutian; Wang Zhenwu; Xu Min; Hu Yulin

    2002-01-01

    Objective: To determine the influence of peripheral blood hemoglobin concentration on the radiotherapy result of nasopharyngeal carcinoma (NPC). Methods: From January 1989 to December 1998, 304 patients with pathologically confirmed NPC received radical radiation. There were 209 males and 95 females. The ages ranged from 16 to 77 years with a median of 42. All patients were irradiated by 60 Co or 6 MV external beam with a total dose of 64 - 76 Gy for the primary tumor and 46 - 77 Gy for the cervical lymph nodes. The peripheral blood hemoglobin concentration for all patients was measured before, during and after radiotherapy. These patients were divided into three groups according to the peripheral blood hemoglobin concentration before radiotherapy: anemia ( 160 g/L), and into two groups according to the change in the peripheral blood hemoglobin concentration during radiotherapy as increased and decreased groups. Results: All patients were followed with a follow-up rate of 90.5%. The peripheral blood hemoglobin concentration had a significant effect on the survival of NPC patients. Its decrease or increase during radiotherapy affected the survival and local control rates of NPC patients. Conclusions: The change of peripheral hemoglobin concentration affecting the oxygen content in the blood, can influence the local control and survival rates of NPC patients. Increase results in higher survival

  17. Raman Tweezers as a Diagnostic Tool of Hemoglobin-Related Blood Disorders

    Directory of Open Access Journals (Sweden)

    Giulia Rusciano

    2008-12-01

    Full Text Available This review presents the development of a Raman Tweezers system for detecting hemoglobin-related blood disorders at a single cell level. The study demonstrates that the molecular fingerprint insight provided by Raman analysis holds great promise for distinguishing between healthy and diseased cells in the field of biomedicine. Herein a Raman Tweezers system has been applied to investigate the effects of thalassemia, a blood disease quite diffuse in the Mediterranean Sea region. By resonant excitation of hemoglobin Raman bands, we examined the oxygenation capability of normal, alpha- and beta-thalassemic erythrocytes. A reduction of this fundamental red blood cell function, particularly severe for beta-thalassemia, has been found. Raman spectroscopy was also used to draw hemoglobin distribution inside single erythrocytes; the results confirmed the characteristic anomaly (target shape, occurring in thalassemia and some other blood disorders. The success of resonance Raman spectroscopy for thalassemia detection reported in this review provide an interesting starting point to explore the application of a Raman Tweezers system in the analysis of several blood disorders.

  18. A novel base change leading to Hb Vanderbilt [β89(F5)Ser→Arg, AGT>AGA].

    Science.gov (United States)

    Goodyer, Matthew J; Elhassadi, Ezzat I; Percy, Melanie J; McMullin, Mary F

    2011-01-01

    We describe a high oxygen affinity hemoglobin (Hb) variant (Hb Vanderbilt) as a result of a heterozygous novel base change from T to A at codon 89 (AGT>AGA) leading to an amino acid change from serine to arginine.

  19. Alpha chain hemoglobins with electrophoretic mobility similar to that of hemoglobin S in a newborn screening program.

    Science.gov (United States)

    Silva, Marcilene Rezende; Sendin, Shimene Mascarenhas; Araujo, Isabela Couto de Oliveira; Pimentel, Fernanda Silva; Viana, Marcos Borato

    2013-01-01

    To characterize alpha-chain variant hemoglobins with electric mobility similar to that of hemoglobin S in a newborn screening program. β(S) allele and alpha-thalassemia deletions were investigated in 14 children who had undefined hemoglobin at birth and an electrophoretic profile similar to that of hemoglobin S when they were six months old. Gene sequencing and restriction enzymes (DdeI, BsaJI, NlaIV, Bsu36I and TaqI) were used to identify hemoglobins. Clinical and hematological data were obtained from children who attended scheduled medical visits. THE FOLLOWING ALPHA CHAIN VARIANTS WERE FOUND: seven children with hemoglobin Hasharon [alpha2 47(CE5) Asp>His, HbA2:c.142G>C], all associated with alpha-thalassemia, five with hemoglobin Ottawa [alpha1 15(A13) Gly>Arg, HBA1:c.46G>C], one with hemoglobin St Luke's [alpha1 95(G2) Pro>Arg, HBA1:c.287C>G] and another one with hemoglobin Etobicoke [alpha212 84(F5) Ser>Arg, HBA212:c.255C>G]. Two associations with hemoglobin S were found: one with hemoglobin Ottawa and one with hemoglobin St Luke's. The mutation underlying hemoglobin Etobicoke was located in a hybrid α212 allele in one child. There was no evidence of clinically relevant hemoglobins detected in this study. Apparently these are the first cases of hemoglobin Ottawa, St Luke's, Etobicoke and the α212 gene described in Brazil. The hemoglobins detected in this study may lead to false diagnosis of sickle cell trait or sickle cell disease when only isoelectric focusing is used in neonatal screening. Additional tests are necessary for the correct identification of hemoglobin variants.

  20. Detection of Sickle Cell Hemoglobin in Haiti by Genotyping and Hemoglobin Solubility Tests

    Science.gov (United States)

    Carter, Tamar E.; von Fricken, Michael; Romain, Jean R.; Memnon, Gladys; St. Victor, Yves; Schick, Laura; Okech, Bernard A.; Mulligan, Connie J.

    2014-01-01

    Sickle cell disease is a growing global health concern because infants born with the disorder in developing countries are now surviving longer with little access to diagnostic and management options. In Haiti, the current state of sickle cell disease/trait in the population is unclear. To inform future screening efforts in Haiti, we assayed sickle hemoglobin mutations using traditional hemoglobin solubility tests (HST) and add-on techniques, which incorporated spectrophotometry and insoluble hemoglobin separation. We also generated genotype data as a metric for HST performance. We found 19 of 202 individuals screened with HST were positive for sickle hemoglobin, five of whom did not carry the HbS allele. We show that spectrophotometry and insoluble hemoglobin separation add-on techniques could resolve false positives associated with the traditional HST approach, with some limitations. We also discuss the incorporation of insoluble hemoglobin separation observation with HST in suboptimal screening settings like Haiti. PMID:24957539

  1. In vivo distribution and elimination of hemoglobin modified by intramolecular cross-linking with 2-nor-2-formylpyridoxal 5'-phosphate

    International Nuclear Information System (INIS)

    Bleeker, W.K.; van der Plas, J.; Feitsma, R.I.; Agterberg, J.; Rigter, G.; de Vries-van Rossen, A.; Pauwels, E.K.; Bakker, J.C.

    1989-01-01

    Modified hemoglobin solutions have potential application as plasma expanders with oxygen-transporting capacity. In a previous study it was found that modification of hemoglobin by intramolecular cross-linking with 2-nor-2-formylpyridoxal 5'-phosphate (NFPLP) improves the vascular retention time by a factor of three, and it also improves the oxygen-transporting properties. In the present study we investigated in rats how, after exchange transfusion of a clinically relevant dose, the modified hemoglobin (HbNFPLP) was distributed in the body compared with how the unmodified hemoglobin was distributed. By using a new technetium 99m labeling technique, we found in a scintigraphic study that accumulation of hemoglobin in the kidneys was greatly diminished by the intramolecular cross-linking with NFPLP. These findings were confirmed by light-microscopic observations after diaminobenzidine staining. It was concluded that the impairment of kidney function caused by blockade of the tubuli is not to be expected from HbNFPLP. In the liver and spleen, where the free HbNFPLP is possibly eliminated, some accumulation of 99mTc label was observed, but the major part of the extravascular label was diffusely spread throughout the body. This led to the conclusion that important accumulation of undegraded HbNFPLP does not occur in the liver and spleen. Rapid appearance of both hemoglobin and HbNFPLP in the lymph showed that cross-linking with NFPLP does not prevent the distribution of hemoglobin over the interstitial space in the first hours after administration. However, pharmacokinetic analysis demonstrated that transcapillary transfer contributes only to a limited extent to the disappearance from the circulation. During 24-hour infusions of HbNFPLP, a steady state with a constant plasma concentration was easily reached

  2. An Origin of Cooperative Oxygen Binding of Human Adult Hemoglobin: Different Roles of the α and β Subunits in the α2β2 Tetramer.

    Directory of Open Access Journals (Sweden)

    Shigenori Nagatomo

    Full Text Available Human hemoglobin (Hb, which is an α2β2 tetramer and binds four O2 molecules, changes its O2-affinity from low to high as an increase of bound O2, that is characterized by 'cooperativity'. This property is indispensable for its function of O2 transfer from a lung to tissues and is accounted for in terms of T/R quaternary structure change, assuming the presence of a strain on the Fe-histidine (His bond in the T state caused by the formation of hydrogen bonds at the subunit interfaces. However, the difference between the α and β subunits has been neglected. To investigate the different roles of the Fe-His(F8 bonds in the α and β subunits, we investigated cavity mutant Hbs in which the Fe-His(F8 in either α or β subunits was replaced by Fe-imidazole and F8-glycine. Thus, in cavity mutant Hbs, the movement of Fe upon O2-binding is detached from the movement of the F-helix, which is supposed to play a role of communication. Recombinant Hb (rHb(αH87G, in which only the Fe-His in the α subunits is replaced by Fe-imidazole, showed a biphasic O2-binding with no cooperativity, indicating the coexistence of two independent hemes with different O2-affinities. In contrast, rHb(βH92G, in which only the Fe-His in the β subunits is replaced by Fe-imidazole, gave a simple high-affinity O2-binding curve with no cooperativity. Resonance Raman, 1H NMR, and near-UV circular dichroism measurements revealed that the quaternary structure change did not occur upon O2-binding to rHb(αH87G, but it did partially occur with O2-binding to rHb(βH92G. The quaternary structure of rHb(αH87G appears to be frozen in T while its tertiary structure is changeable. Thus, the absence of the Fe-His bond in the α subunit inhibits the T to R quaternary structure change upon O2-binding, but its absence in the β subunit simply enhances the O2-affinity of α subunit.

  3. An Origin of Cooperative Oxygen Binding of Human Adult Hemoglobin: Different Roles of the α and β Subunits in the α2β2 Tetramer

    Science.gov (United States)

    Sakurai, Hiroshi; Imai, Kiyohiro; Mizusawa, Naoki; Ogura, Takashi

    2015-01-01

    Human hemoglobin (Hb), which is an α2β2 tetramer and binds four O2 molecules, changes its O2-affinity from low to high as an increase of bound O2, that is characterized by ‘cooperativity’. This property is indispensable for its function of O2 transfer from a lung to tissues and is accounted for in terms of T/R quaternary structure change, assuming the presence of a strain on the Fe-histidine (His) bond in the T state caused by the formation of hydrogen bonds at the subunit interfaces. However, the difference between the α and β subunits has been neglected. To investigate the different roles of the Fe-His(F8) bonds in the α and β subunits, we investigated cavity mutant Hbs in which the Fe-His(F8) in either α or β subunits was replaced by Fe-imidazole and F8-glycine. Thus, in cavity mutant Hbs, the movement of Fe upon O2-binding is detached from the movement of the F-helix, which is supposed to play a role of communication. Recombinant Hb (rHb)(αH87G), in which only the Fe-His in the α subunits is replaced by Fe-imidazole, showed a biphasic O2-binding with no cooperativity, indicating the coexistence of two independent hemes with different O2-affinities. In contrast, rHb(βH92G), in which only the Fe-His in the β subunits is replaced by Fe-imidazole, gave a simple high-affinity O2-binding curve with no cooperativity. Resonance Raman, 1H NMR, and near-UV circular dichroism measurements revealed that the quaternary structure change did not occur upon O2-binding to rHb(αH87G), but it did partially occur with O2-binding to rHb(βH92G). The quaternary structure of rHb(αH87G) appears to be frozen in T while its tertiary structure is changeable. Thus, the absence of the Fe-His bond in the α subunit inhibits the T to R quaternary structure change upon O2-binding, but its absence in the β subunit simply enhances the O2-affinity of α subunit. PMID:26244770

  4. Alpha chain hemoglobins with electrophoretic mobility similar to that of hemoglobin S in a newborn screening program

    Directory of Open Access Journals (Sweden)

    Marcilene Rezende Silva

    2013-01-01

    Full Text Available OBJECTIVE: To characterize alpha-chain variant hemoglobins with electric mobility similar to that of hemoglobin S in a newborn screening program. METHODS: βS allele and alpha-thalassemia deletions were investigated in 14 children who had undefined hemoglobin at birth and an electrophoretic profile similar to that of hemoglobin S when they were six months old. Gene sequencing and restriction enzymes (DdeI, BsaJI, NlaIV, Bsu36I and TaqI were used to identify hemoglobins. Clinical and hematological data were obtained from children who attended scheduled medical visits. RESULTS: The following alpha chain variants were found: seven children with hemoglobin Hasharon [alpha2 47(CE5 Asp>His, HbA2:c.142G>C], all associated with alpha-thalassemia, five with hemoglobin Ottawa [alpha1 15(A13 Gly>Arg, HBA1:c.46G>C], one with hemoglobin St Luke's [alpha1 95(G2 Pro>Arg, HBA1:c.287C>G] and another one with hemoglobin Etobicoke [alpha212 84(F5 Ser>Arg, HBA212:c.255C>G]. Two associations with hemoglobin S were found: one with hemoglobin Ottawa and one with hemoglobin St Luke's. The mutation underlying hemoglobin Etobicoke was located in a hybrid α212 allele in one child. There was no evidence of clinically relevant hemoglobins detected in this study. CONCLUSION: Apparently these are the first cases of hemoglobin Ottawa, St Luke's, Etobicoke and the α212 gene described in Brazil. The hemoglobins detected in this study may lead to false diagnosis of sickle cell trait or sickle cell disease when only isoelectric focusing is used in neonatal screening. Additional tests are necessary for the correct identification of hemoglobin variants.

  5. To Classify Spontaneous Motion Intention of Step Size by Using Cerebral Hemoglobin Information

    Directory of Open Access Journals (Sweden)

    Zhu Kai

    2017-01-01

    Full Text Available To improve the effect of walking-assistive devices, there is a need for it to develop devices controlled by spontaneous intention of patients. In recent study, we identified spontaneous motion intention of walking step based on cerebral hemoglobin information. Twenty healthy subjects performed walking tasks in three levels of step size (small, normal and large. According to distribution features of signals’ power spectral-density, six frequency bands (0-0.18Hz with an interval of 0.03Hz for each band width divided by applying wavelet packets decomposition were mainly analyzed. Feature vectors were extracted from the difference between oxygenated hemoglobin (oxyHb and deoxygenated hemoglobin (dexoyHb in different measuring channels in the six frequency bands. Support vector machine (SVM method was utilized to classify the three levels of step sizes. Mean recognition accuracy achieved up to 83.3%. The result indicated that it is possible to identify spontaneous walking by using cerebral hemoglobin information. This is helpful for enhancing the intelligence of walking-assistive devices and motivating the active control of patients, which further is profitable for enhancing self-confidence of patients.

  6. Hemoglobin Wayne Trait with Incidental Polycythemia.

    Science.gov (United States)

    Ambelil, Manju; Nguyen, Nghia; Dasgupta, Amitava; Risin, Semyon; Wahed, Amer

    2017-01-01

    Hemoglobinopathies, caused by mutations in the globin genes, are one of the most common inherited disorders. Many of the hemoglobin variants can be identified by hemoglobin analysis using conventional electrophoresis and high performance liquid chromatography; however hemoglobin DNA analysis may be necessary in other cases for confirmation. Here, we report a case of a rare alpha chain hemoglobin variant, hemoglobin Wayne, in a 47-year-old man who presented with secondary polycythemia. Capillary zone electrophoresis and high performance liquid chromatography revealed a significant amount of a hemoglobin variant, which was further confirmed by hemoglobin DNA sequencing as hemoglobin Wayne. Since the patient was not homozygous for hemoglobin Wayne, which is associated with secondary polycythemia, the laboratory diagnosis in this case was critical in ruling out hemoglobinopathy as the etiology of his polycythemia. © 2017 by the Association of Clinical Scientists, Inc.

  7. The Hemoglobin E Thalassemias

    Science.gov (United States)

    Fucharoen, Suthat; Weatherall, David J.

    2012-01-01

    Hemoglobin E (HbE) is an extremely common structural hemoglobin variant that occurs at high frequencies throughout many Asian countries. It is a β-hemoglobin variant, which is produced at a slightly reduced rate and hence has the phenotype of a mild form of β thalassemia. Its interactions with different forms of α thalassemia result in a wide variety of clinical disorders, whereas its coinheritance with β thalassemia, a condition called hemoglobin E β thalassemia, is by far the most common severe form of β thalassemia in Asia and, globally, comprises approximately 50% of the clinically severe β-thalassemia disorders. PMID:22908199

  8. Mechanism of the Enhancement of the Bohr Effect in Mammalian Hemoglobins by Diphosphoglycerate

    Science.gov (United States)

    Riggs, Austen

    1971-01-01

    The number of protons released from several mammalian hemoglobins as a consequence of oxygenation is greater in the presence of low concentrations of 2,3-diphosphoglycerate than in its absence. A mechanism for this enhancement of proton release is proposed. The basis of this mechanism is that 2,3-diphosphoglycerate binds primarily between the protonated α-NH2 terminal groups of the two β chains in deoxyhemoglobin. This binding will shift the ionization equilibria in favor of the protonation of the deoxyhemoglobin. Partial release of 2,3-diphosphoglycerate upon oxygenation of the hemoglobin is then accompanied by a release of protons. The apparent enthalpy of diphosphoglycerate binding appears to be close to zero. The previously reported temperature dependence appears to be due entirely to the associated protonation reaction. If only a single diphosphoglycerate binding site is assumed, the intrinsic association constant is estimated to be 3.9 × 105 M-1 for deoxyhemoglobin and 1.05 × 104 M-1 for oxyhemoglobin at 20°C in 0.1 M NaCl. PMID:5289365

  9. Mechanism of the enhancement of the Bohr effect in mammalian hemoglobins by diphosphoglycerate.

    Science.gov (United States)

    Riggs, A

    1971-09-01

    The number of protons released from several mammalian hemoglobins as a consequence of oxygenation is greater in the presence of low concentrations of 2,3-diphosphoglycerate than in its absence. A mechanism for this enhancement of proton release is proposed. The basis of this mechanism is that 2,3-diphosphoglycerate binds primarily between the protonated alpha-NH(2) terminal groups of the two beta chains in deoxyhemoglobin. This binding will shift the ionization equilibria in favor of the protonation of the deoxyhemoglobin. Partial release of 2,3-diphosphoglycerate upon oxygenation of the hemoglobin is then accompanied by a release of protons. The apparent enthalpy of diphosphoglycerate binding appears to be close to zero. The previously reported temperature dependence appears to be due entirely to the associated protonation reaction. If only a single diphosphoglycerate binding site is assumed, the intrinsic association constant is estimated to be 3.9 x 10(5) M(-1) for deoxyhemoglobin and 1.05 x 10(4) M(-1) for oxyhemoglobin at 20 degrees C in 0.1 M NaCl.

  10. Muscle Oxygen Supply Impairment during Exercise in Poorly Controlled Type 1 Diabetes

    Science.gov (United States)

    TAGOUGUI, SEMAH; LECLAIR, ERWAN; FONTAINE, PIERRE; MATRAN, RÉGIS; MARAIS, GAELLE; AUCOUTURIER, JULIEN; DESCATOIRE, AURÉLIEN; VAMBERGUE, ANNE; OUSSAIDENE, KAHINA; BAQUET, GEORGES; HEYMAN, ELSA

    2015-01-01

    ABSTRACT Purpose Aerobic fitness, as reflected by maximal oxygen (O2) uptake (V˙O2max), is impaired in poorly controlled patients with type 1 diabetes. The mechanisms underlying this impairment remain to be explored. This study sought to investigate whether type 1 diabetes and high levels of glycated hemoglobin (HbA1c) influence O2 supply including O2 delivery and release to active muscles during maximal exercise. Methods Two groups of patients with uncomplicated type 1 diabetes (T1D-A, n = 11, with adequate glycemic control, HbA1c 8%) were compared with healthy controls (CON-A, n = 11; CON-I, n = 12, respectively) matched for physical activity and body composition. Subjects performed exhaustive incremental exercise to determine V˙O2max. Throughout the exercise, near-infrared spectroscopy allowed investigation of changes in oxyhemoglobin, deoxyhemoglobin, and total hemoglobin in the vastus lateralis. Venous and arterialized capillary blood was sampled during exercise to assess arterial O2 transport and factors able to shift the oxyhemoglobin dissociation curve. Results Arterial O2 content was comparable between groups. However, changes in total hemoglobin (i.e., muscle blood volume) was significantly lower in T1D-I compared with that in CON-I. T1D-I also had impaired changes in deoxyhemoglobin levels and increase during high-intensity exercise despite normal erythrocyte 2,3-diphosphoglycerate levels. Finally, V˙O2max was lower in T1D-I compared with that in CON-I. No differences were observed between T1D-A and CON-A. Conclusions Poorly controlled patients displayed lower V˙O2max and blunted muscle deoxyhemoglobin increase. The latter supports the hypotheses of increase in O2 affinity induced by hemoglobin glycation and/or of a disturbed balance between nutritive and nonnutritive muscle blood flow. Furthermore, reduced exercise muscle blood volume in poorly controlled patients may warn clinicians of microvascular dysfunction occurring even before overt

  11. Development of Selective Excitation Methods in Nuclear Magnetic Resonance: Investigation of Hemoglobin Oxygenation in Erythrocytes Using Proton and Phosphorus -31 Nuclear Magnetic Resonance

    Science.gov (United States)

    Fetler, Bayard Keith

    1993-01-01

    Nuclear magnetic resonance (NMR) offers a potential method for making measurements of the percent oxygenation of hemoglobin (Hb) in living tissue non-invasively. As a demonstration of the feasibility of such measurements, we measured the percent oxygenation of Hb in red blood cells (erythrocytes) using resonances in the proton-NMR (^1H-NMR) spectrum which are characteristic of oxyhemoglobin (oxy-Hb) and deoxyhemoglobin (deoxy-Hb), and are due to the unique magnetic properties of these molecules. To perform these measurements, we developed a new NMR method of selectively exciting signals in a region of interest with uniform phase and amplitude, while suppressing the signal of the water resonance. With this method, we are able to make exact calculations distinguishing between uniform phase excitation produced at large flip-angles using the non-linear properties of the Bloch equations, and uniform phase excitation produced at small flip-angles using asymmetric pulse excitation functions. We measured the percent oxygenation of three characteristic ^1H-NMR resonances of Hb: two from deoxy-Hb, originating from the N_delta H protons of histidine residue F8, which occur at different frequencies for the alpha and beta chains of Hb; and one from oxy-Hb, originating from the gamma_2 -CH_3 protons of valine residue E11. We performed experiments both on fresh erythrocytes and on erythrocytes depleted of 2,3-diphosphoglycerate (2,3-DPG), and found that oxygen is more tightly bound to Hb in the former case. In both fresh and 2,3-DPG-depleted samples, we found that: (i) from the deoxy-Hb marker resonances, there is a small but significant difference in the oxygen saturation between the alpha and beta chains; (ii) the decrease in the areas of the deoxy-Hb marker resonances correlates well with the increase in the percent oxygenation of Hb as measured optically; (iii) the area of the oxy-Hb marker resonance may be up to ~15% less than the optically measured Hb saturation. We are

  12. Haemoglobin Rahere (beta Lys-Thr): A new high affinity haemoglobin associated with decreased 2, 3-diphosphoglycerate binding and relative polycythaemia.

    Science.gov (United States)

    Lorkin, P A; Stephens, A D; Beard, M E; Wrigley, P F; Adams, L; Lehmann, H

    1975-01-01

    A new haemoglobin with increased oxygen affinity, beta82 (EF6) lysine leads to threonine (Hb Rahere), was found during the investigation of a patient who was found to have a raised haemoglobin concentration after a routine blood count. The substitution affects one of the 2, 3-diphosphoglycerate binding sites, resulting in an increased affinity for oxygen, but both the haem-haem interaction and the alkaline Bohr effect are normal in the haemolysate. This variant had the same mobility as haemoglobin A on electrophoresis at alkaline pH but was detected by measuring the whole blood oxygen affinity; it could be separated from haemoglobin A, however, by electrophoresis in agar at acid pH. The raised haemoglobin concentration was mainly due to a reduction in plasma volume (a relative polycythaemia) and was associated with a persistently raised white blood count. This case emphasises the need to measure the oxygen affinity of haemoglobin in all patients with absolute or relative polycythaemia when some obvious cause is not evident. PMID:124

  13. Kinetics of photodissociated oxygen recombination to human oxyhemoglobin

    International Nuclear Information System (INIS)

    Bokut', S.B.; Syakhovich, V.E.; Parul', D.A.; Lepeshkevich, S.V.; Dzhagarov, B.M.

    2001-01-01

    Oxygen binding to the tetrameric hemoglobin (Hb) is a basic reaction for study of a cooperativity and allosteric homotropic and heterotropic interactions in proteins. In tetrameric hemoglobin the certain sites in the α 1 β 2 -interface have the precise geometry and chemical reactivity to bind 2,3-diphosphoglycerate, protons, chloride and hence shift the equilibrium away from the oxyconformation, thereby favoring O 2 release. Post-translational modifications of the major hemoglobin fraction Hb A 1 with sugar moiety in the Hb central cavity leads to differences in geometry of the effectors binding region providing a useful experimental tool to study the long range relationship in the tetramer molecule. Here we present the results of the nongeminate biomolecular association of Hb and O 2 obtained by nanosecond laser flash-photolysis. All measurements were carried out in 50 mM potassium-phosphate buffer pH 7.4 with the following samples Hb A 1 , HbA 1c , HbA 1b , and HbA 1 in the presence of the tenfold excess of inositol hexaphosphate (IHP). Our results show that oxygen recombination kinetics are characterized by two processes with different decay times and Hb-form-dependent contributions. This process can be described by the following expression: A(t)=A 1 exp(-t/τ 1 )+A 2 exp(-t/τ 2 ), where A(t) is a normalized number of the deoxy-Hb molecules. The short-live component has a lifetime τ 1 , which is Hb-type dependent and changes in the intervals 30-60 μs, the second component has a lifetime τ 2 around 100 μs, and also is sample-dependent value. A(t=0) is proportional to apparent quantum yields of the photodissociation and determines by geminate stages of oxygen binding to Fe from the protein matrix areas. These results show that post-translational modifications of the major hemoglobin component HbA 1 have influence on hemoglobin transport function via the long range relationship in the tetramer molecule

  14. BLOOD SUBSTITUTES: EVOLUTION FROM NON-CARRYING TO OXYGEN AND GAS CARRYING FLUIDS

    Science.gov (United States)

    Cabrales, Pedro; Intaglietta, Marcos

    2013-01-01

    The development of oxygen (O2) carrying blood substitutes has evolved from the goal of replicating blood O2 transports properties to that of preserving microvascular and organ function, reducing the inherent or potential toxicity of the material used to carry O2, and treating pathologies initiated by anemia and hypoxia. Furthermore, the emphasis has shifted from blood replacement fluid to “O2 therapeutics” that restore tissue oxygenation to specific tissues regions. This review covers the different alternatives, potential and limitations of hemoglobin based O2 carriers (HBOCs) and perfluorocarbon based O2 carriers (PFCOCs), with emphasis on the physiological conditions disturbed in the situation that they will be used. It describes how concepts learned from plasma expanders without O2 carrying capacity can be applied to maintain O2 delivery and summarizes the microvascular responses due to HBOCs and PFCOCs. This review also presents alternative applications of HBOCs and PFCOCs namely: 1) How HBOC O2 affinity can be engineered to target O2 delivery to hypoxic tissues; and 2) How the high gas solubility of PFCOCs provides new opportunities for carrying, dissolving and delivering gases with biological activity. It is concluded that current blood substitutes development has amplified their applications horizon by devising therapeutic functions for oxygen carriers requiring limited O2 delivery capacity restoration. Conversely, full, blood-like O2 carrying capacity re-establishment awaits control of O2 carrier toxicity. PMID:23820271

  15. Hemoglobin C, S-C, and E Diseases

    Science.gov (United States)

    ... quickly than others, resulting in chronic anemia. Hemoglobin C disease Hemoglobin C disease occurs mostly in blacks. ... a common complication of hemoglobin C disease. Hemoglobin S-C disease Hemoglobin S-C disease occurs in people who ...

  16. Direct sGC activation bypasses no scavenging reactions of intravascular free oxy-hemoglobin and limits vasoconstriction

    NARCIS (Netherlands)

    N.J.H. Raat (Nicolaas); D.M. Tabima (D. Marcela); P. Specht (Patricia); J. Tejero (Jesús); M.P. Champion (Michael); D.B. Kim-Shapiro (Daniel); J.G. Baust (John ); E.G. Mik (Egbert); M. Hildesheim (Mariana); J.-P. Stasch (Johannes-Peter); E.-M. Becker (Eva-Maria); H. Truebel (Hubert); M.T. Gladwin (Mark)

    2013-01-01

    textabstractAims: Hemoglobin-based oxygen carriers (HBOC) provide a potential alternative to red blood cell (RBC) transfusion. Their clinical application has been limited by adverse effects, in large part thought to be mediated by the intravascular scavenging of the vasodilator nitric oxide (NO) by

  17. Development of Liposome Encapsulated Hemoglobin (LEH) and Studies of Hemorrhagic Shock by Use of Imaging Studies with Oxygen-15 and Other Radiotracers

    National Research Council Canada - National Science Library

    Phillips, William T; Goins, Beth; Awasthi, Vibhudutta

    2004-01-01

    .... Encapsulating hemoglobin inside a protective lipid membrane, which mimics a red blood cell, has the advantages of decreasing the toxicity of the free hemoglobin, increasing its circulation time...

  18. Crystallization and preliminary X-ray structural studies of hemoglobin A2 and hemoglobin E, isolated from the blood samples of β-thalassemic patients

    International Nuclear Information System (INIS)

    Dasgupta, Jhimli; Sen, Udayaditya; Choudhury, Debi; Datta, Poppy; Chakrabarti, Abhijit; Chakrabarty, Sudipa Basu; Chakrabarty, Amit; Dattagupta, J.K.

    2003-01-01

    Hemoglobin A 2 (α 2 δ 2 ), a minor (2-3%) component of circulating red blood cells, acts as an anti-sickling agent and its elevated concentration in β-thalassemia is a useful clinical diagnostic. In β-thalassemia major, where there is a failure of β-chain production, HbA 2 acts as the predominant oxygen deliverer. Hemoglobin E, is another common abnormal hemoglobin, caused by splice site mutation in exon 1 of β globin gene, when combines with β-thalassemia, causes severe microcytic anemia. The purification, crystallization, and preliminary structural studies of HbA 2 and HbE are reported here. HbA 2 and HbE are purified by cation exchange column chromatography in presence of KCN from the blood samples of individuals suffering from β-thalassemia minor and Eβ-thalassemia. X-ray diffraction data of HbA 2 and HbE were collected upto 2.1 and 1.73 A, respectively. HbA 2 crystallized in space group P2 1 with unit cell parameters a=54.33 A, b=83.73 A, c=62.87 A, and β=99.80 degree sign whereas HbE crystallized in space group P2 1 2 1 2 1 with unit cell parameters a=60.89 A, b=95.81 A, and c=99.08 A. Asymmetric unit in each case contains one Hb tetramer in R 2 state

  19. (Pyridoxylated hemoglobin)-(polyoxyethylene) conjugate solution as blood substitute for normothermic whole body rinse-out.

    Science.gov (United States)

    Agishi, T; Funakoshi, Y; Honda, H; Yamagata, K; Kobayashi, M; Takahashi, M

    1988-01-01

    In order to investigate a new possibility for artificial blood with oxygen-carrying capability to be applied to other than mere supplementation, normothermic whole body rinse-out in which artificial blood deriving from perfluorochemical emulsion, Fluosol-DA 20% (Green Cross Co., Ltd., Osaka, Japan) or stabilized hemoglobin solution, (pyridoxylated hemoglobin)-(polyoxyethylene) conjugate solution (Ajinomoto Co., Ltd., Tokyo, Japan) were used as rinsing fluid for a blood purification experiment. Replacement either with approximately 150 ml/kg of Fluosol-DA or stabilized hemoglobin solution showed effective removal of digoxin at a reduction rate of 96.3% or 92.2%, respectively. However, when Fluosol-DA was used, a certain amount of perfluorochemical should be retrieved by centrifugation to avoid a possible toxic effect on the reticulo-endothelial system. Even though 3 out of 6, and 3 out of 8 dogs, respectively, survived for a long period after the procedure, the experimental dogs were very susceptible to infection.

  20. Imaging the effect of hemoglobin on properties of RBCs using common-path digital holographic microscope

    Science.gov (United States)

    Joglekar, M.; Shah, H.; Trivedi, V.; Mahajan, S.; Chhaniwal, V.; Leitgeb, R.; Javidi, B.; Anand, A.

    2017-07-01

    Adequate supply of oxygen to the body is the most essential requirement. In vertebrate species this function is performed by Hemoglobin contained in red blood cells. The mass concentration of the Hb determines the oxygen carrying capacity of the blood. Thus it becomes necessary to determine its concentration in the blood, which helps in monitoring the health of a person. If the amount of Hb crosses certain range, then it is considered critical. As the Hb constitutes upto 96% of red blood cells dry content, it would be interesting to examine various physical and mechanical parameters of RBCs which depends upon its concentration. Various diseases bring about significant variation in the amount of hemoglobin which may alter certain parameters of the RBC such as surface area, volume, membrane fluctuation etc. The study of the variations of these parameters may be helpful in determining Hb content which will reflect the state of health of a human body leading to disease diagnosis. Any increase or decrease in the amount of Hb will change the density and hence the optical thickness of the RBCs, which affects the cell membrane and thereby changing its mechanical and physical properties. Here we describe the use of lateral shearing digital holographic microscope for quantifying the cell parameters for studying the change in biophysical properties of cells due to variation in hemoglobin concentration.

  1. Oxygen dependence of respiration in rat spinotrapezius muscle in situ

    OpenAIRE

    Golub, Aleksander S.; Pittman, Roland N.

    2012-01-01

    The oxygen dependence of respiration in striated muscle in situ was studied by measuring the rate of decrease of interstitial Po2 [oxygen disappearance curve (ODC)] following rapid arrest of blood flow by pneumatic tissue compression, which ejected red blood cells from the muscle vessels and made the ODC independent from oxygen bound to hemoglobin. After the contribution of photo-consumption of oxygen by the method was evaluated and accounted for, the corrected ODCs were converted into the Po...

  2. Cationic composition and acid-base state of the extracellular fluid, and specific buffer value of hemoglobin from the branchiopod crustacean Triops cancriformis.

    Science.gov (United States)

    Pirow, Ralph; Buchen, Ina; Richter, Marc; Allmer, Carsten; Nunes, Frank; Günsel, Andreas; Heikens, Wiebke; Lamkemeyer, Tobias; von Reumont, Björn M; Hetz, Stefan K

    2009-04-01

    Recent insights into the allosteric control of oxygen binding in the extracellular hemoglobin (Hb) of the tadpole shrimp Triops cancriformis raised the question about the physico-chemical properties of the protein's native environment. This study determined the cationic composition and acid-base state of the animal's extracellular fluid. The physiological concentrations of potential cationic effectors (calcium, magnesium) were more than one order of magnitude below the level effective to increase Hb oxygen affinity. The extracellular fluid in the pericardial space had a typical bicarbonate concentration of 7.6 mM but a remarkably high CO(2) partial pressure of 1.36 kPa at pH 7.52 and 20 degrees C. The discrepancy between this high CO(2) partial pressure and the comparably low values for water-breathing decapods could not solely be explained by the hemolymph-sampling procedure but may additionally arise from differences in cardiovascular complexity and efficiency. T. cancriformis hemolymph had a non-bicarbonate buffer value of 2.1 meq L(-1) pH(-1). Hb covered 40-60% of the non-bicarbonate buffering power. The specific buffer value of Hb of 1.1 meq (mmol heme)(-1) pH(-1) suggested a minimum requirement of two titratable histidines per heme-binding domain, which is supported by available information from N-terminal sequencing and expressed sequence tags.

  3. Polar bear hemoglobin and human Hb A0: same 2,3-diphosphoglycerate binding site but asymmetry of the binding?

    Science.gov (United States)

    Pomponi, Massimo; Bertonati, Claudia; Patamia, Maria; Marta, Maurizio; Derocher, Andrew E; Lydersen, Christian; Kovacs, Kit M; Wiig, Oystein; Bårdgard, Astrid J

    2002-11-01

    Polar bear (Ursus maritimus) hemoglobin (Hb) shows a low response to 2,3-diphosphoglycerate (2,3-DPG), compared to human Hb A0, even though these proteins have the same 2,3-DPG-binding site. In addition, polar bear Hb shows a high response to chloride and an alkaline Bohr effect (deltalog P50/deltapH) that is significantly greater than that of human Hb A0. The difference in sequence Pro (Hb A0)-->Gly (polar bear Hb) at position A2 in the A helix seems to be critical for reduced binding of 2,3-DPG. Our results also show that the A2 position may influence not only the flexibility of the A helix, but that differences in flexibility of the first turn of the A helix may affect the unloading of oxygen for the intrinsic ligand affinities of the alpha and beta chains. However, preferential binding to either chain can only take place if there is appreciable asymmetric binding of the phosphoric effector. Regarding this point, 31P NMR data suggest a loss of symmetry of the 2,3-DPG-binding site in the deoxyHb-2,3-DPG complex.

  4. Estimation of Melanin and Hemoglobin Using Spectral Reflectance Images Reconstructed from a Digital RGB Image by the Wiener Estimation Method

    Directory of Open Access Journals (Sweden)

    Yoshihisa Aizu

    2013-06-01

    Full Text Available A multi-spectral diffuse reflectance imaging method based on a single snap shot of Red-Green-Blue images acquired with the exposure time of 65 ms (15 fps was investigated for estimating melanin concentration, blood concentration, and oxygen saturation in human skin tissue. The technique utilizes the Wiener estimation method to deduce spectral reflectance images instantaneously from an RGB image. Using the resultant absorbance spectrum as a response variable and the extinction coefficients of melanin, oxygenated hemoglobin and deoxygenated hemoglobin as predictor variables, multiple regression analysis provides regression coefficients. Concentrations of melanin and total blood are then determined from the regression coefficients using conversion vectors that are numerically deduced in advance by the Monte Carlo simulations for light transport in skin. Oxygen saturation is obtained directly from the regression coefficients. Experiments with a tissue-like agar gel phantom validated the method. In vivo experiments on fingers during upper limb occlusion demonstrated the ability of the method to evaluate physiological reactions of human skin.

  5. Hemoglobin-carbon nanotube derived noble-metal-free Fe5C2-based catalyst for highly efficient oxygen reduction reaction

    Science.gov (United States)

    Vij, Varun; Tiwari, Jitendra N.; Lee, Wang-Geun; Yoon, Taeseung; Kim, Kwang S.

    2016-02-01

    High performance non-precious cathodic catalysts for oxygen reduction reaction (ORR) are vital for the development of energy materials and devices. Here, we report an noble metal free, Fe5C2 nanoparticles-studded sp2 carbon supported mesoporous material (CNTHb-700) as cathodic catalyst for ORR, which was prepared by pyrolizing the hybrid adduct of single walled carbon nanotubes (CNT) and lyophilized hemoglobin (Hb) at 700 °C. The catalyst shows onset potentials of 0.92 V in 0.1 M HClO4 and in 0.1 M KOH which are as good as commercial Pt/C catalyst, giving very high current density of 6.34 and 6.69 mA cm-2 at 0.55 V vs. reversible hydrogen electrode (RHE), respectively. This catalyst has been confirmed to follow 4-electron mechanism for ORR and shows high electrochemical stability in both acidic and basic media. Catalyst CNTHb-700 possesses much higher tolerance towards methanol than the commercial Pt/C catalyst. Highly efficient catalytic properties of CNTHb-700 could lead to fundamental understanding of utilization of biomolecules in ORR and materialization of proton exchange membrane fuel cells for clean energy production.

  6. Optical determination of the hemoglobin oxygenation state of breast biopsies and human breast cancer xenografts in nude mice

    Science.gov (United States)

    Marks, Fay A.

    1992-05-01

    Differences in the oxygenation state of benign and malignant breast biopsies, and human breast cancer xenografts in immune-deficient mice were monitored using a spectrophotometer with integrating sphere. The breast biopsies were maintained below -50 degree(s)C and the mouse model tumors maintained in growth medium at 0 degree(s)C. Tissue sections 500 (mu) thick were allowed to come up to room temperature for mounting between quartz slides and were evaluated over the wavelength region 240 - 2500 nm. Data collection was done within 10 minutes of the removal of the biopsies from storage and, within 5 minutes for the xenografts. That this preparation protocol allowed us to study the samples very close to the in- vivo state was evident from the lack of deoxyhemoglobin in the benign samples. Component analysis performed in the 300 - 800 nm region showed that the malignant samples contained predominantly deoxygenated blood while the benign samples exhibited oxyhemoglobin signature. Absorption peaks due to fat and traces of bilirubin were also resolved in some of the samples. Assuming that the samples are very nearly representative of the in-vivo condition, these hemoglobin differences may well serve as a basis for imaging tumors or, for tissue characterization in a minimally invasive environment.

  7. Oxygen affinity and Bohr effect responses to 2,3-diphosphoglycerate in equine and human blood.

    Science.gov (United States)

    diBella, G; Scandariato, G; Suriano, O; Rizzo, A

    1996-05-01

    The dependence of blood oxygen affinity and the Bohr effect on the concentration of 2,3-diphosphoglycerate (DPG) in erythrocytes was investigated in 24 trotter horses and 24 healthy men. The oxygen tension at half saturation and standard conditions (P50st at pH 7.4, PCO2(40) mmHg and 37 degrees C) and the carbon dioxide or fixed-acid-induced Bohr effect (dlogP50/dpH) were determined. Samples of fresh blood and blood depleted of or enriched with DPG were studied. In the absence of measurable DPG, the equine and human blood had similar mean (SD) values of P50st (16.6 [0.6] and 16.2 [0.7] mmHg, respectively). In both species these values increased with increasing DPG, but the response of equine blood was significantly lower, at least up to physiological values (P50st = 24.6 [0.6] and 26.2 [0.7]) mmHg; DPG = 14([1.8] and 12.8 [1.2] mumol gHb-1, respectively, in fresh blood). For concentrations above 20 to 25 mumol gHb-1 of DPG the difference between the values of P50st in the two species tended to decrease because the response in human blood reached a plateau. The interactions between the Bohr effect and the concentration of DPG showed that in the horses, as in the men, the level of DPG played an important role in governing the relative magnitude of carbon dioxide and fixed acid factors. The difference between them, which is associated with the oxylabile carbamino binding, was greatest in DPG-depleted blood, but whereas in the men the difference was suppressed by an above normal DPG concentration, in the horses it was still measurable.

  8. White Matter Damage Relates to Oxygen Saturation in Children With Sickle Cell Anemia Without Silent Cerebral Infarcts.

    Science.gov (United States)

    Kawadler, Jamie M; Kirkham, Fenella J; Clayden, Jonathan D; Hollocks, Matthew J; Seymour, Emma L; Edey, Rosanna; Telfer, Paul; Robins, Andrew; Wilkey, Olu; Barker, Simon; Cox, Tim C S; Clark, Chris A

    2015-07-01

    Sickle cell anemia is associated with compromised oxygen-carrying capability of hemoglobin and a high incidence of overt and silent stroke. However, in children with no evidence of cerebral infarction, there are changes in brain morphometry relative to healthy controls, which may be related to chronic anemia and oxygen desaturation. A whole-brain tract-based spatial statistics analysis was carried out in 25 children with sickle cell anemia with no evidence of abnormality on T2-weighted magnetic resonance imaging (13 male, age range: 8-18 years) and 14 age- and race-matched controls (7 male, age range: 10-19 years) to determine the extent of white matter injury. The hypotheses that white matter damage is related to daytime peripheral oxygen saturation and steady-state hemoglobin were tested. Fractional anisotropy was found to be significantly lower in patients in the subcortical white matter (corticospinal tract and cerebellum), whereas mean diffusivity and radial diffusivity were higher in patients in widespread areas. There was a significant negative relationship between radial diffusivity and oxygen saturation (Plevel negative relationship between radial diffusivity and hemoglobin (Pcell anemia, and provides for the first time direct evidence of a relationship between brain microstructure and markers of disease severity (eg, peripheral oxygen saturation and steady-state hemoglobin). This study suggests that diffusion tensor imaging metrics may serve as a biomarker for future trials of reducing hypoxic exposure. © 2015 American Heart Association, Inc.

  9. Acclimatory responses of the Daphnia pulex proteome to environmental changes. I. Chronic exposure to hypoxia affects the oxygen transport system and carbohydrate metabolism

    Directory of Open Access Journals (Sweden)

    Madlung Johannes

    2009-04-01

    Full Text Available Abstract Background Freshwater planktonic crustaceans of the genus Daphnia show a remarkable plasticity to cope with environmental changes in oxygen concentration and temperature. One of the key proteins of adaptive gene control in Daphnia pulex under hypoxia is hemoglobin (Hb, which increases in hemolymph concentration by an order of magnitude and shows an enhanced oxygen affinity due to changes in subunit composition. To explore the full spectrum of adaptive protein expression in response to low-oxygen conditions, two-dimensional gel electrophoresis and mass spectrometry were used to analyze the proteome composition of animals acclimated to normoxia (oxygen partial pressure [Po2]: 20 kPa and hypoxia (Po2: 3 kPa, respectively. Results The comparative proteome analysis showed an up-regulation of more than 50 protein spots under hypoxia. Identification of a major share of these spots revealed acclimatory changes for Hb, glycolytic enzymes (enolase, and enzymes involved in the degradation of storage and structural carbohydrates (e.g. cellubiohydrolase. Proteolytic enzymes remained constitutively expressed on a high level. Conclusion Acclimatory adjustments of the D. pulex proteome to hypoxia included a strong induction of Hb and carbohydrate-degrading enzymes. The scenario of adaptive protein expression under environmental hypoxia can be interpreted as a process to improve oxygen transport and carbohydrate provision for the maintenance of ATP production, even during short episodes of tissue hypoxia requiring support from anaerobic metabolism.

  10. Hemoglobin Test: MedlinePlus Lab Test Information

    Science.gov (United States)

    ... page: https://medlineplus.gov/labtests/hemoglobintest.html Hemoglobin Test To use the sharing features on this page, please enable JavaScript. What is a Hemoglobin Test? A hemoglobin test measures the levels of hemoglobin ...

  11. Interplay of tumor vascular oxygenation and tumor pO2 observed using near-infrared spectroscopy, an oxygen needle electrode, and 19F MR pO2 mapping.

    Science.gov (United States)

    Kim, Jae G; Zhao, Dawen; Song, Yulin; Constantinescu, Anca; Mason, Ralph P; Liu, Hanli

    2003-01-01

    This study investigates the correlation of tumor blood oxygenation and tumor pO(2) with respect to carbogen inhalation. After having refined and validated the algorithms for calculating hemoglobin concentrations, we used near-infrared spectroscopy (NIRS) to measure changes of oxygenated hemoglobin concentration (delta[HbO(2)]) and used an oxygen needle electrode and (19)F MRI for pO(2) measurements in tumors. The measurements were taken from Dunning prostate R3327 tumors implanted in rats, while the anesthetized rats breathed air or carbogen. The NIRS results from tumor measurements showed significant changes in tumor vascular oxygenation in response to carbogen inhalation, while the pO(2) electrode results showed an apparent heterogeneity for tumor pO(2) response to carbogen inhalation, which was also confirmed by (19)F MR pO(2) mapping. Furthermore, we developed algorithms to estimate hemoglobin oxygen saturation, sO(2), during gas intervention based on the measured values of delta[HbO(2)] and pO(2). The algorithms have been validated through a tissue-simulating phantom and used to estimate the values of sO(2) in the animal tumor measurement based on the NIRS and global mean pO(2) values. This study demonstrates that the NIRS technology can provide an efficient, real-time, noninvasive approach to monitoring tumor physiology and is complementary to other techniques, while it also demonstrates the need for an NIR imaging technique to study spatial heterogeneity of tumor vasculature under therapeutic interventions. Copyright 2003 Society of Photo-Optical Instrumentation Engineers

  12. Factors associated with blood oxygen partial pressure and carbon dioxide partial pressure regulation during respiratory extracorporeal membrane oxygenation support: data from a swine model.

    Science.gov (United States)

    Park, Marcelo; Mendes, Pedro Vitale; Costa, Eduardo Leite Vieira; Barbosa, Edzangela Vasconcelos Santos; Hirota, Adriana Sayuri; Azevedo, Luciano Cesar Pontes

    2016-01-01

    The aim of this study was to explore the factors associated with blood oxygen partial pressure and carbon dioxide partial pressure. The factors associated with oxygen - and carbon dioxide regulation were investigated in an apneic pig model under veno-venous extracorporeal membrane oxygenation support. A predefined sequence of blood and sweep flows was tested. Oxygenation was mainly associated with extracorporeal membrane oxygenation blood flow (beta coefficient = 0.036mmHg/mL/min), cardiac output (beta coefficient = -11.970mmHg/L/min) and pulmonary shunting (beta coefficient = -0.232mmHg/%). Furthermore, the initial oxygen partial pressure and carbon dioxide partial pressure measurements were also associated with oxygenation, with beta coefficients of 0.160 and 0.442mmHg/mmHg, respectively. Carbon dioxide partial pressure was associated with cardiac output (beta coefficient = 3.578mmHg/L/min), sweep gas flow (beta coefficient = -2.635mmHg/L/min), temperature (beta coefficient = 4.514mmHg/ºC), initial pH (beta coefficient = -66.065mmHg/0.01 unit) and hemoglobin (beta coefficient = 6.635mmHg/g/dL). In conclusion, elevations in blood and sweep gas flows in an apneic veno-venous extracorporeal membrane oxygenation model resulted in an increase in oxygen partial pressure and a reduction in carbon dioxide partial pressure 2, respectively. Furthermore, without the possibility of causal inference, oxygen partial pressure was negatively associated with pulmonary shunting and cardiac output, and carbon dioxide partial pressure was positively associated with cardiac output, core temperature and initial hemoglobin.

  13. Fetal hemoglobin is much less prone to DNA cleavage compared to the adult protein

    Directory of Open Access Journals (Sweden)

    Sandeep Chakane

    2017-08-01

    Full Text Available Hemoglobin (Hb is well protected inside the red blood cells (RBCs. Upon hemolysis and when free in circulation, Hb can be involved in a range of radical generating reactions and may thereby attack several different biomolecules. In this study, we have examined the potential damaging effects of cell-free Hb on plasmid DNA (pDNA. Hb induced cleavage of supercoiled pDNA (sc pDNA which was proportional to the concentration of Hb applied. Almost 70% of sc pDNA was converted to open circular or linear DNA using 10 µM of Hb in 12 h. Hb can be present in several different forms. The oxy (HbO2 and met forms are most reactive, while the carboxy-protein shows only low hydrolytic activity. Hemoglobin A (HbA could easily induce complete pDNA cleavage while fetal hemoglobin (HbF was three-fold less reactive. By inserting, a redox active cysteine residue on the surface of the alpha chain of HbF by site-directed mutagenesis, the DNA cleavage reaction was enhanced by 82%. Reactive oxygen species were not directly involved in the reaction since addition of superoxide dismutase and catalase did not prevent pDNA cleavage. The reactivity of Hb with pDNA can rather be associated with the formation of protein based radicals. Keywords: Adult hemoglobin, Fetal hemoglobin, Supercoiled plasmid DNA, DNA cleavage, Cysteine, Protein radicals

  14. Processing of pulse oximeter signals using adaptive filtering and autocorrelation to isolate perfusion and oxygenation components

    Science.gov (United States)

    Ibey, Bennett; Subramanian, Hariharan; Ericson, Nance; Xu, Weijian; Wilson, Mark; Cote, Gerard L.

    2005-03-01

    A blood perfusion and oxygenation sensor has been developed for in situ monitoring of transplanted organs. In processing in situ data, motion artifacts due to increased perfusion can create invalid oxygenation saturation values. In order to remove the unwanted artifacts from the pulsatile signal, adaptive filtering was employed using a third wavelength source centered at 810nm as a reference signal. The 810 nm source resides approximately at the isosbestic point in the hemoglobin absorption curve where the absorbance of light is nearly equal for oxygenated and deoxygenated hemoglobin. Using an autocorrelation based algorithm oxygenation saturation values can be obtained without the need for large sampling data sets allowing for near real-time processing. This technique has been shown to be more reliable than traditional techniques and proven to adequately improve the measurement of oxygenation values in varying perfusion states.

  15. A new hemoglobin gene from soybean: a role for hemoglobin in all plants

    DEFF Research Database (Denmark)

    Anderson, C R; Jensen, E O; LLewellyn, D J

    1996-01-01

    We have isolated a new hemoglobin gene from soybean. It is expressed in cotyledons, stems of seedlings, roots, young leaves, and in some cells in the nodules that are associated with the nitrogen-fixing Bradyrhizobium symbiont. This contrasts with the expression of the leghemoglobins, which...... are active only in the infected cells of the nodules. The deduced protein sequence of the new gene shows only 58% similarity to one of the soybean leghemoglobins, but 85-87% similarity to hemoglobins from the nonlegumes Parasponia, Casuarina, and barley. The pattern of expression and the gene sequence...... indicate that this new gene is a nonsymbiotic legume hemoglobin. The finding of this gene in legumes and similar genes in other species strengthens our previous suggestion that genomes of all plants contain hemoglobin genes. The specialized leghemoglobin gene family may have arisen from a preexisting...

  16. A technique for measuring oxygen saturation in biological tissues based on diffuse optical spectroscopy

    Science.gov (United States)

    Kleshnin, Mikhail; Orlova, Anna; Kirillin, Mikhail; Golubiatnikov, German; Turchin, Ilya

    2017-07-01

    A new approach to optical measuring blood oxygen saturation was developed and implemented. This technique is based on an original three-stage algorithm for reconstructing the relative concentration of biological chromophores (hemoglobin, water, lipids) from the measured spectra of diffusely scattered light at different distances from the probing radiation source. The numerical experiments and approbation of the proposed technique on a biological phantom have shown the high reconstruction accuracy and the possibility of correct calculation of hemoglobin oxygenation in the presence of additive noise and calibration errors. The obtained results of animal studies have agreed with the previously published results of other research groups and demonstrated the possibility to apply the developed technique to monitor oxygen saturation in tumor tissue.

  17. A study of membrane protein defects and alpha hemoglobin chains of red blood cells in human beta thalassemia

    International Nuclear Information System (INIS)

    Rouyer-Fessard, P.; Garel, M.C.; Domenget, C.; Guetarni, D.; Bachir, D.; Colonna, P.; Beuzard, Y.

    1989-01-01

    The soluble pool of alpha hemoglobin chains present in blood or bone marrow cells was measured with a new affinity method using a specific probe, beta A hemoglobin chain labeled with [ 3 H]N-ethylmaleimide. This pool of soluble alpha chains was 0.067 ± 0.017% of hemoglobin in blood of normal adult, 0.11 ± 0.03% in heterozygous beta thalassemia and ranged from 0.26 to 1.30% in homozygous beta thalassemia intermedia. This elevated pool of soluble alpha chains observed in human beta thalassemia intermedia decreased 33-fold from a value of 10% of total hemoglobin in bone marrow cells to 0.3% in the most dense red blood cells. The amount of insoluble alpha chains was measured by using the polyacrylamide gel electrophoresis in urea and Triton X-100. In beta thalassemia intermedia the amount of insoluble alpha chains was correlated with the decreased spectrin content of red cell membrane and was associated with a decrease in ankyrin and with other abnormalities of the electrophoretic pattern of membrane proteins. The loss and topology of the reactive thiol groups of membrane proteins was determined by using [ 3 H]N-ethylmaleimide added to membrane ghosts prior to urea and Triton X-100 electrophoresis. Spectrin and ankyrin were the major proteins with the most important decrease of thiol groups

  18. Aerobic growth at nanomolar oxygen concentrations

    DEFF Research Database (Denmark)

    Stolper, Daniel Aaron; Revsbech, Niels Peter; Canfield, Donald Eugene

    2010-01-01

    that Escherichia coli K-12, chosen for its well-understood biochemistry, rapid growth rate, and low-oxygen-affinity terminal oxidase, grows at oxygen levels of ≤ 3 nM, two to three orders of magnitude lower than previously observed for aerobes. Our study expands both the environmental range and temporal history...... of aerobic organisms....

  19. Non-invasive hemoglobin monitoring.

    Science.gov (United States)

    Joseph, Bellal; Haider, Ansab; Rhee, Peter

    2016-09-01

    Technology has transformed the practice of medicine and surgery in particular over the last several decades. This change in practice has allowed diagnostic and therapeutic tests to be performed less invasively. Hemoglobin monitoring remains one of the most commonly performed diagnostic tests in the United States. Recently, non-invasive hemoglobin monitoring technology has gained popularity. The aim of this article is to review the principles of how this technology works, pros and cons, and the implications of non-invasive hemoglobin technology particularly in trauma surgery. Copyright © 2015 IJS Publishing Group Ltd. Published by Elsevier Ltd. All rights reserved.

  20. Blood Test: Hemoglobin A1C

    Science.gov (United States)

    ... Why Are Hemoglobin A1c Tests Done? When a child has diabetes, hemoglobin A1c levels are followed to see how well medicines are working. If a child with diabetes has a high hemoglobin A1c level, it may ...

  1. Hemoglobin estimation by the HemoCue® portable hemoglobin photometer in a resource poor setting

    Directory of Open Access Journals (Sweden)

    Idriss Ali

    2011-04-01

    Full Text Available Abstract Background In resource poor settings where automated hematology analyzers are not available, the Cyanmethemoglobin method is often used. This method though cheaper, takes more time. In blood donations, the semi-quantitative gravimetric copper sulfate method which is very easy and inexpensive may be used but does not provide an acceptable degree of accuracy. The HemoCue® hemoglobin photometer has been used for these purposes. This study was conducted to generate data to support or refute its use as a point-of-care device for hemoglobin estimation in mobile blood donations and critical care areas in health facilities. Method EDTA blood was collected from study participants drawn from five groups: pre-school children, school children, pregnant women, non-pregnant women and men. Blood collected was immediately processed to estimate the hemoglobin concentration using three different methods (HemoCue®, Sysmex KX21N and Cyanmethemoglobin. Agreement between the test methods was assessed by the method of Bland and Altman. The Intraclass correlation coefficient (ICC was used to determine the within subject variability of measured hemoglobin. Results Of 398 subjects, 42% were males with the overall mean age being 19.4 years. The overall mean hemoglobin as estimated by each method was 10.4 g/dl for HemoCue, 10.3 g/dl for Sysmex KX21N and 10.3 g/dl for Cyanmethemoglobin. Pairwise analysis revealed that the hemoglobin determined by the HemoCue method was higher than that measured by the KX21N and Cyanmethemoglobin. Comparing the hemoglobin determined by the HemoCue to Cyanmethemoglobin, the concordance correlation coefficient was 0.995 (95% CI: 0.994-0.996, p Conclusion Hemoglobin determined by the HemoCue method is comparable to that determined by the other methods. The HemoCue photometer is therefore recommended for use as on-the-spot device for determining hemoglobin in resource poor setting.

  2. Aerobic growth at nanomolar oxygen concentrations

    DEFF Research Database (Denmark)

    Stolper, Daniel; Revsbech, Niels Peter; Canfield, Donald Eugene

    2010-01-01

    that Escherichia coli K-12, chosen for its well-understood biochemistry, rapid growth rate, and low-oxygen-affinity terminal oxidase, grows at oxygen levels of ≤ 3 nM, two to three orders of magnitude lower than previously observed for aerobes. Our study expands both the environmental range and temporal history...... of aerobic organisms....

  3. Cell-free oxygen carriers: scientific foundations, clinical development, and new directions.

    Science.gov (United States)

    Winslow, Robert M

    2008-10-01

    The most significant hurdle to the development of a safe and effective hemoglobin-based oxygen carrier ("blood substitute") is generally thought to be its propensity to cause vasoconstriction in the microcirculation and hypertension. Two theories for this effect are currently being studied: in one, scavenging NO by hemoglobin reduces vasorelaxation; in the other, cell-free hemoglobin oversupplies O2 (a known vasoconstrictor) to vascular walls by facilitated diffusion. While both mechanisms might lead to reduction of local NO concentration, the important distinction between the two is that if the NO scavenging theory is correct, it greatly diminishes the prospects to develop any solution based on free hemoglobin. However, if the O2-oversupply theory is correct, modifications to the hemoglobin molecule can be envisioned that can prevent oversupply and reduce toxicity. This review summarizes the development of Hemospan, a novel modification of human hemoglobin whose design is based on the O2-oversupply theory. Because of its low P50 and increased molecular size, the release of O2 in resistance vessels (arterioles) by Hemospan is restricted, and vasoconstriction is greatly reduced.

  4. Determination Of Ph Including Hemoglobin Correction

    Science.gov (United States)

    Maynard, John D.; Hendee, Shonn P.; Rohrscheib, Mark R.; Nunez, David; Alam, M. Kathleen; Franke, James E.; Kemeny, Gabor J.

    2005-09-13

    Methods and apparatuses of determining the pH of a sample. A method can comprise determining an infrared spectrum of the sample, and determining the hemoglobin concentration of the sample. The hemoglobin concentration and the infrared spectrum can then be used to determine the pH of the sample. In some embodiments, the hemoglobin concentration can be used to select an model relating infrared spectra to pH that is applicable at the determined hemoglobin concentration. In other embodiments, a model relating hemoglobin concentration and infrared spectra to pH can be used. An apparatus according to the present invention can comprise an illumination system, adapted to supply radiation to a sample; a collection system, adapted to collect radiation expressed from the sample responsive to the incident radiation; and an analysis system, adapted to relate information about the incident radiation, the expressed radiation, and the hemoglobin concentration of the sample to pH.

  5. Oxygen-Binding Characteristics of Hemoglobins from Hypoxia and Hypercapnia Tolerant African Mole Rats

    DEFF Research Database (Denmark)

    Weber, Roy E.; Jarvis, Jennifer U. M; Fago, Angela

    2016-01-01

    ) originating from a range of different biomes and soil types. The study shows no evidence for distinguishing interspecific differences in hematological characters (e.g. DPG and Hb levels and isoHb differentiation). Additionally small differences observed in Hb’s intrinsic O2 affinity and in the effects of p...

  6. Agreement between arterial partial pressure of carbon dioxide and saturation of hemoglobin with oxygen values obtained by direct arterial blood measurements versus noninvasive methods in conscious healthy and ill foals.

    Science.gov (United States)

    Wong, David M; Alcott, Cody J; Wang, Chong; Bornkamp, Jennifer L; Young, Jessica L; Sponseller, Brett A

    2011-11-15

    To determine agreement between indirect measurements of end-tidal partial pressure of carbon dioxide (PetCO(2)) and saturation of hemoglobin with oxygen as measured by pulse oximetry (SpO(2)) with direct measurements of PaCO(2) and calculated saturation of hemoglobin with oxygen in arterial blood (SaO(2)) in conscious healthy and ill foals. Validation study. 10 healthy and 21 ill neonatal foals. Arterial blood gas analysis was performed on healthy and ill foals examined at a veterinary teaching hospital to determine direct measurements of PaCO(2) and PaO(2) along with SaO(2). Concurrently, PetCO(2) was measured with a capnograph inserted into a naris, and SpO(2) was measured with a reflectance probe placed at the base of the tail. Paired values were compared by use of Pearson correlation coefficients, and level of agreement was assessed with the Bland-Altman method. Mean ± SD difference between PaCO(2) and PetCO(2) was 0.1 ± 5.0 mm Hg. There was significant strong correlation (r = 0.779) and good agreement between PaCO(2) and PetCO(2). Mean ± SD difference between SaO(2) and SpO(2) was 2.5 ± 3.5%. There was significant moderate correlation (r = 0.499) and acceptable agreement between SaO(2) and SpO(2). Both PetCO(2) obtained by use of nasal capnography and SpO(2) obtained with a reflectance probe are clinically applicable and accurate indirect methods of estimating and monitoring PaCO(2) and SaO(2) in neonatal foals. Indirect methods should not replace periodic direct measurement of corresponding parameters.

  7. Hemoglobin estimation by the HemoCue® portable hemoglobin photometer in a resource poor setting.

    Science.gov (United States)

    Nkrumah, Bernard; Nguah, Samuel Blay; Sarpong, Nimako; Dekker, Denise; Idriss, Ali; May, Juergen; Adu-Sarkodie, Yaw

    2011-04-21

    In resource poor settings where automated hematology analyzers are not available, the Cyanmethemoglobin method is often used. This method though cheaper, takes more time. In blood donations, the semi-quantitative gravimetric copper sulfate method which is very easy and inexpensive may be used but does not provide an acceptable degree of accuracy. The HemoCue® hemoglobin photometer has been used for these purposes. This study was conducted to generate data to support or refute its use as a point-of-care device for hemoglobin estimation in mobile blood donations and critical care areas in health facilities. EDTA blood was collected from study participants drawn from five groups: pre-school children, school children, pregnant women, non-pregnant women and men. Blood collected was immediately processed to estimate the hemoglobin concentration using three different methods (HemoCue®, Sysmex KX21N and Cyanmethemoglobin). Agreement between the test methods was assessed by the method of Bland and Altman. The Intraclass correlation coefficient (ICC) was used to determine the within subject variability of measured hemoglobin. Of 398 subjects, 42% were males with the overall mean age being 19.4 years. The overall mean hemoglobin as estimated by each method was 10.4 g/dl for HemoCue, 10.3 g/dl for Sysmex KX21N and 10.3 g/dl for Cyanmethemoglobin. Pairwise analysis revealed that the hemoglobin determined by the HemoCue method was higher than that measured by the KX21N and Cyanmethemoglobin. Comparing the hemoglobin determined by the HemoCue to Cyanmethemoglobin, the concordance correlation coefficient was 0.995 (95% CI: 0.994-0.996, p < 0.001). The Bland and Altman's limit of agreement was -0.389 - 0.644 g/dl with the mean difference being 0.127 (95% CI: 0.102-0.153) and a non-significant difference in variability between the two measurements (p = 0.843). After adjusting to assess the effect of other possible confounders such as sex, age and category of person, there was no

  8. Multilayer affinity adsorption of albumin on polymer brushes modified membranes in a continuous-flow system.

    Science.gov (United States)

    Hu, Meng-Xin; Li, Xiang; Li, Ji-Nian; Huang, Jing-Jing; Ren, Ge-Rui

    2018-02-23

    Polymer brushes modified surfaces have been widely used for protein immobilization and isolation. Modification of membranes with polymer brushes increases the surface concentration of affinity ligands used for protein binding. Albumin is one of the transporting proteins and shows a high affinity to bile acids. In this work, the modified membranes with cholic acid-containing polymer brushes can be facilely prepared by the immobilization of cholic acid on the poly(2-hydroxyethyl methacrylate) grafted microporous polypropylene membranes (MPPMs) for affinity adsorption of albumin. ATR/FT-IR and X-ray photoelectron spectroscopy were used to characterize the chemical composition of the modified membranes. Water contact angle measurements were used to analyze the hydrophilic/hydrophobic properties of the membrane surface. The modified MPPMs show a high affinity to albumin and have little non-specific adsorption of hemoglobin. The dynamic binding capacity of albumin in the continous-flow system increases with the cycle number and feed rate as the binding degree of cholic acid is moderate. The highest binding capacity of affinity membranes is about 52.49 g/m 2 membrane, which is about 24 times more than the monolayer binding capacity. These results reveal proteins could be captured in multilayers by the polymer brushes containing affinity ligands similar to the polymer brushes containing ion-exchange groups, which open up the potential of the polymer brushes containing affinity ligands in protein or another components separation. And the cholic acid containing polymer brushes modified membranes has the promising potential for albumin separation and purification rapidly from serum or fermented solution in medical diagnosis and bioseparation. Copyright © 2018 Elsevier B.V. All rights reserved.

  9. Effects of diaspirin cross-linked hemoglobin (DCLHb) during and post-CPR in swine.

    Science.gov (United States)

    Chow, M S; Fan, C; Tran, H; Zhao, H; Zhou, L

    2001-04-01

    The purpose of the study was to test the hypothesis that diaspirin cross-linked hemoglobin (DCLHb) can produce improved resuscitation during cardiac arrest. DCLHb, a derivative of human hemoglobin, has previously been demonstrated to produce a vasopressor response that is associated with increased blood flow to vital organs. In addition, it is an oxygen carrier. These effects may be beneficial to extreme low flow states, such as that during cardiac arrest and cardiopulmonary resuscitation (CPR). Experimental cardiac arrest and CPR were carried out in 32 anesthetized immature pigs. In each animal, ventricular fibrillation was induced for 5 min, followed by 10 min of standard CPR with a pneumatic device and room air ventilation. High (15 ml/kg) and low (5 ml/kg) doses of DCLHb or equivalent volume of normal saline were infused at the beginning of CPR in a random and blind manner. Cardiac output, organ blood flow, aortic pressure, coronary perfusion pressure, blood gases, and lactate concentrations were obtained before and during CPR. Following the 10-min CPR, the animals were defibrillated and the return of spontaneous circulation (ROSC) determined. DCLHb treatment achieved 75% ROSC compared with 25% in the saline group (p CPR significantly improves ROSC. This is most likely related to its improvement in coronary perfusion and myocardial oxygen delivery.

  10. Blood oxygen saturation determined by transmission spectrophotometry of hemolyzed blood samples

    Science.gov (United States)

    Malik, W. M.

    1967-01-01

    Use of the Lambert-Beer Transmission Law determines blood oxygen saturation of hemolyzed blood samples. This simplified method is based on the difference in optical absorption properties of hemoglobin and oxyhemoglobin.

  11. Affine and quasi-affine frames for rational dilations

    DEFF Research Database (Denmark)

    Bownik, Marcin; Lemvig, Jakob

    2011-01-01

    In this paper we extend the investigation of quasi-affine systems, which were originally introduced by Ron and Shen [J. Funct. Anal. 148 (1997), 408-447] for integer, expansive dilations, to the class of rational, expansive dilations. We show that an affine system is a frame if, and only if......, the corresponding family of quasi-affine systems are frames with uniform frame bounds. We also prove a similar equivalence result between pairs of dual affine frames and dual quasi-affine frames. Finally, we uncover some fundamental differences between the integer and rational settings by exhibiting an example...

  12. Ligand exchange reactions of the heme group in hemoglobin and myoglobin as studied by pulse radiolysis

    International Nuclear Information System (INIS)

    Raap, I.A.

    1978-01-01

    In this thesis, the kinetic aspects of the ligand exchange reactions of hemoglobin are studied using the pulse radiolysis technique, in particular, the reactions of hydrated electrons with methemoglobin. A hitherto unobserved transient state of the heme group is observed which appears immediately after the rapid reduction process. The absorption spectrum of this new species has the characteristics of a ferrous low-spin state and can therefore be ascribed to the formation of a hemochrome non-equilibrium state. The subsequent relaxation of this intermediate structure into a deoxy-conformation is dependent on the amount of proton activity in the solution and on the presence of organic and inorganic phosphate anions. The final absorption spectrum of the heme group is shown to correspond to a ferrous high-spin state in the relaxed quaternary conformation. This is in agreement with the kinetics observen the binding of carbon monoxide and oxygen to partially reduced methemoglobin. At reduction degrees of methemoglobin as well as of valncy 8ybrids where there is an important contribution from species with two reduced subunits, the binding of carbon monoxide to hemoglobin occurs with on-rate constants characteristic for the tensed quaternary conformation. It is argued that this conformational change of hemoglobin (the R-to-T transition) takes place very rapidly, which suggests the participation of an activated relaxed conformation. In addition, it is found that there is a distinct heterogeneity in the binding of oxygen to partially reduced methemoglobin even at low degrees of reduction

  13. Effect of Repeated Whole Blood Donations on Aerobic Capacity and Hemoglobin Mass in Moderately Trained Male Subjects: A Randomized Controlled Trial.

    Science.gov (United States)

    Meurrens, Julie; Steiner, Thomas; Ponette, Jonathan; Janssen, Hans Antonius; Ramaekers, Monique; Wehrlin, Jon Peter; Vandekerckhove, Philippe; Deldicque, Louise

    2016-12-01

    The aims of the present study were to investigate the impact of three whole blood donations on endurance capacity and hematological parameters and to determine the duration to fully recover initial endurance capacity and hematological parameters after each donation. Twenty-four moderately trained subjects were randomly divided in a donation (n = 16) and a placebo (n = 8) group. Each of the three donations was interspersed by 3 months, and the recovery of endurance capacity and hematological parameters was monitored up to 1 month after donation. Maximal power output, peak oxygen consumption, and hemoglobin mass decreased (p donation with a maximal decrease of 4, 10, and 7%, respectively. Hematocrit, hemoglobin concentration, ferritin, and red blood cell count (RBC), all key hematological parameters for oxygen transport, were lowered by a single donation (p donations (p donation was 11% for hematocrit, 10% for hemoglobin concentration, 50% for ferritin, and 12% for RBC (p donation group. Maximal, but not submaximal, endurance capacity was altered after blood donation in moderately trained people and the expected increase in capacity after multiple maximal exercise tests was not present when repeating whole blood donations.

  14. Hemoglobin Variants: Biochemical Properties and Clinical Correlates

    Science.gov (United States)

    Thom, Christopher S.; Dickson, Claire F.; Gell, David A.; Weiss, Mitchell J.

    2013-01-01

    Diseases affecting hemoglobin synthesis and function are extremely common worldwide. More than 1000 naturally occurring human hemoglobin variants with single amino acid substitutions throughout the molecule have been discovered, mainly through their clinical and/or laboratory manifestations. These variants alter hemoglobin structure and biochemical properties with physiological effects ranging from insignificant to severe. Studies of these mutations in patients and in the laboratory have produced a wealth of information on hemoglobin biochemistry and biology with significant implications for hematology practice. More generally, landmark studies of hemoglobin performed over the past 60 years have established important paradigms for the disciplines of structural biology, genetics, biochemistry, and medicine. Here we review the major classes of hemoglobin variants, emphasizing general concepts and illustrative examples. PMID:23388674

  15. Characteristic emission in glutaraldehyde polymerized hemoglobin

    International Nuclear Information System (INIS)

    Ma Li; Wang Xiaojun

    2011-01-01

    Hemoglobin with different modifications has been investigated using spectroscopic techniques. A new emission at around 371 nm has been observed under excitation of 305 nm from glutaraldehyde polymerized human hemoglobin. Intensity and peak position of the emission are dependent on both oxidation state and ligand environment and the emission has been identified from the hemoglobin oligomer.

  16. Effect of Red Light-Emitting Diodes Irradiation on Hemoglobin for Potential Hypertension Treatment Based on Confocal Micro-Raman Spectroscopy

    Directory of Open Access Journals (Sweden)

    Xuejun Qiu

    2017-01-01

    Full Text Available Red light-emitting diodes (LED were used to irradiate the isolated hypertension hemoglobin (Hb and Raman spectra difference was recorded using confocal micro-Raman spectroscopy. Differences were observed between the controlled and irradiated Hb by comparing the spectra records. The Raman spectrum at the 1399 cm−1 band decreased following prolonged LED irradiation. The intensity of the 1639 cm−1 band decreased dramatically in the first five minutes and then gradually increased in a time-dependent manner. This observation indicated that LED irradiation increased the ability of oxygen binding in Hb. The appearance of the heme aggregation band at 1399 cm−1, in addition to the oxygen marker band at 1639 cm−1, indicated that, in our study, 30 min of irradiation with 15.0 mW was suitable for inhibiting heme aggregation and enhancing the oxygen-carrying capacity of Hb. Principal component analysis showed a one-to-one relationship between irradiated Hb at different time points and the corresponding Raman spectra. Our approach could be used to analyze the hemoglobin from patients with confocal micro-Raman spectroscopy and is helpful for developing new nondrug hypertension therapy.

  17. Replacing the Transfusion of 1–2 Units of Blood with Plasma Expanders that Increase Oxygen Delivery Capacity: Evidence from Experimental Studies

    Directory of Open Access Journals (Sweden)

    Amy G. Tsai

    2014-10-01

    Full Text Available At least a third of the blood supply in the world is used to transfuse 1–2 units of packed red blood cells for each intervention and most clinical trials of blood substitutes have been carried out at this level of oxygen carrying capacity (OCC restoration. However, the increase of oxygenation achieved is marginal or none at all for molecular hemoglobin (Hb products, due to their lingering vasoactivity. This has provided the impetus for the development of “oxygen therapeutics” using Hb-based molecules that have high oxygen affinity and target delivery of oxygen to anoxic areas. However it is still unclear how these oxygen carriers counteract or mitigate the functional effects of anemia due to obstruction, vasoconstriction and under-perfusion. Indeed, they are administered as a low dosage/low volume therapeutic Hb (subsequently further diluted in the circulatory pool and hence induce extremely small OCC changes. Hyperviscous plasma expanders provide an alternative to oxygen therapeutics by increasing the oxygen delivery capacity (ODC; in anemia they induce supra-perfusion and increase tissue perfusion (flow by as much as 50%. Polyethylene glycol conjugate albumin (PEG-Alb accomplishes this by enhancing the shear thinning behavior of diluted blood, which increases microvascular endothelial shear stress, causes vasodilation and lowering peripheral vascular resistance thus facilitating cardiac function. Induction of supra-perfusion takes advantage of the fact that ODC is the product of OCC and blood flow and hence can be maintained by increasing either or both. Animal studies suggest that this approach may save a considerable fraction of the blood supply. It has an additional benefit of enhancing tissue clearance of toxic metabolites.

  18. Effects of a radiation-induced α-thalassemia on the production of multiple forms of hemoglobins in fetal mice

    International Nuclear Information System (INIS)

    Popp, R.A.; Bradshaw, B.S.; Hirsch, G.P.

    1978-01-01

    Embryonic hemoglobins in α-thalassemic heterozygotes and normal fetuses were compared to study the effects of the deficient α chain on the synthesis of hemoglobins in the nucleated embryonic erythrocytes derived from the fetal yolk sac. Acrylamide gel electrophoresis showed that less hemoglobin Ell (α 2 y 2 ) was formed in α-thalassemic heterozygotes between 12 1 / 2 and 14 1 / 2 days of gestation. Quantitation of in vitro synthesis between 11 1 / 2 and 13 1 / 2 days of gestation also showed that Ell was synthesized less rapidly in α-thalassemic fetuses. In contrast, the synthesis of Elll (α 2 z 2 ) was higher in α-thalassemic than in normal fetuses at 12 1 / 2 and 13 1 / 2 days of gestation. Measurements of the synthesis of individual chains in El (x 2 y 2 ) and Ell showed that x chain synthesis was normal and that α chain synthesis was deficient in α-thalassemic fetuses at 11 1 / 2 and 12 1 / 2 days of gestation. Thus, there is still no proof for close linkage of x- and α-chain genes in chromosome 11. Differences in the electrophoretic patterns of embryonic hemoglobins of α-thalassemic and normal fetuses can be explained by normal synthesis of x chains, deficient synthesis of α chains, and a higher affinity of z than y for the reduced amount of α chain present in the nucleated embryonic erythrocytes of α-thalassemic mice

  19. Radio-ligand immunoassay for human hemoglobin variants

    International Nuclear Information System (INIS)

    Javid, J.; Pettis, P.K.; Miller, J.E.

    1981-01-01

    A quantitative method is described for the individual assay of human hemoglobin variants occurring singly or in mixture. The hemoglobin to be assayed is bound to specific antibody; the immune complex is attached to protein A-containing S. aureus and removed from the mixture. The hemoglobin thus isolated is quantified by its ability to bind radiolabeled haptoglobin. The technique is accurate and distinguishes among the 4 hemoglobins tested, namely Hb A, S, C and F. It has the advantage over conventional radioimmunoassay that a single probe, radiolabeled haptoglobin, is needed for the specific assay of any hemoglobin. (Auth.)

  20. Further studies on Hb Canebière [β12(G4)Asn→His], a low affinity hemoglobin variant

    DEFF Research Database (Denmark)

    Froelund, Ulf; Sandbakken, Erik; Szecsi, Pal Bela

    2010-01-01

    A case of Hb Canebière [ß102(G4)Asn¿His] was diagnosed in an otherwise healthy 21-year-old Danish woman. The clinical consequences were minor, since her only symptom consisted of transient cyanosis in lips and fingers when exposed to cold environments. Whole blood p50 was 59.9 mmHg. The Hb Canebi...... Canebière variant could not be separated from Hb A by high performance liquid chromatography (HPLC) and isoelectric focusing (IEF), and it was thus missed by routine hemoglobin (Hb) fractionation techniques....

  1. Further studies on Hb Canebière [β12(G4)Asn→His], a low affinity hemoglobin variant

    DEFF Research Database (Denmark)

    Froelund, Ulf; Sandbakken, Erik; Szecsi, Pal Bela

    2010-01-01

    A case of Hb Canebière [β102(G4)Asn→His] was diagnosed in an otherwise healthy 21-year-old Danish woman. The clinical consequences were minor, since her only symptom consisted of transient cyanosis in lips and fingers when exposed to cold environments. Whole blood p50 was 59.9 mmHg. The Hb...... Canebière variant could not be separated from Hb A by high performance liquid chromatography (HPLC) and isoelectric focusing (IEF), and it was thus missed by routine hemoglobin (Hb) fractionation techniques....

  2. Central venous oxygenation: when physiology explains apparent discrepancies.

    Science.gov (United States)

    Squara, Pierre

    2014-11-10

    Central venous oxygen saturation (ScvO2) >70% or mixed venous oxygen saturation (SvO2) >65% is recommended for both septic and non-septic patients. Although it is the task of experts to suggest clear and simple guidelines, there is a risk of reducing critical care to these simple recommendations. This article reviews the basic physiological and pathological features as well as the metrological issues that provide clear evidence that SvO2 and ScvO2 are adaptative variables with large inter-patient variability. This variability is exemplified in a modeled population of 1,000 standard ICU patients and in a real population of 100 patients including 15,860 measurements. In these populations, it can be seen how optimizing one to three of the four S(c)vO2 components homogenized the patients and yields a clear dependency with the fourth one. This explains the discordant results observed in large studies where cardiac output was increased up to predetermined S(c)vO2 thresholds following arterial oxygen hemoglobin saturation, total body oxygen consumption needs and hemoglobin optimization. Although a systematic S(c)vO2 goal-oriented protocol can be statistically profitable before ICU admission, appropriate intensive care mandates determination of the best compromise between S(c)vO2 and its four components, taking into account the specific constraints of each individual patient.

  3. Lower Hemoglobin Concentration Is Associated with Retinal Ischemia and the Severity of Diabetic Retinopathy in Type 2 Diabetes.

    Science.gov (United States)

    Traveset, Alicia; Rubinat, Esther; Ortega, Emilio; Alcubierre, Nuria; Vazquez, Beatriz; Hernández, Marta; Jurjo, Carmen; Espinet, Ramon; Ezpeleta, Juan Antonio; Mauricio, Didac

    2016-01-01

    Aims. To assess the association of blood oxygen-transport capacity variables with the prevalence of diabetic retinopathy (DR), retinal ischemia, and macular oedema in patients with type 2 diabetes mellitus (T2DM). Methods. Cross-sectional, case-control study (N = 312) with T2DM: 153 individuals with DR and 159 individuals with no DR. Participants were classified according to the severity of DR and the presence of retinal ischemia or macular oedema. Hematological variables were collected by standardized methods. Three logistic models were adjusted to ascertain the association between hematologic variables with the severity of DR and the presence of retinal ischemia or macular oedema. Results. Individuals with severe DR showed significantly lower hemoglobin, hematocrit, and erythrocyte levels compared with those with mild disease and in individuals with retinal ischemia and macular oedema compared with those without these disorders. Hemoglobin was the only factor that showed a significant inverse association with the severity of DR [beta-coefficient = -0.52, P value = 0.003] and retinal ischemia [beta-coefficient = -0.49, P value = 0.001]. Lower erythrocyte level showed a marginally significant association with macular oedema [beta-coefficient = -0.86, P value = 0.055]. Conclusions. In patients with DR, low blood oxygen-transport capacity was associated with more severe DR and the presence of retinal ischemia. Low hemoglobin levels may have a key role in the development and progression of DR.

  4. Hemoglobin, hematocrit, and changes in cerebral blood flow: the Second Manifestations of ARTerial disease-Magnetic Resonance study.

    Science.gov (United States)

    van der Veen, Pieternella H; Muller, Majon; Vincken, Koen L; Westerink, Jan; Mali, Willem P T M; van der Graaf, Yolanda; Geerlings, Mirjam I

    2015-03-01

    Hemoglobin and hematocrit are important determinants of blood viscosity and arterial oxygen content and may therefore influence cerebral blood flow (CBF). We examined cross-sectional and prospective associations of hemoglobin and hematocrit with CBF in 569 patients with manifest arterial disease (mean age 57 ± 10 years) with available data on magnetic resonance angiography to measure parenchymal CBF. Mean (SD) parenchymal CBF at baseline was 52.3 (9.8) mL/min/100 mL and decreased with 1.5 (11.0) mL/min/100 mL after on average 3.9 years of follow-up. Linear regression analyses showed that greater hemoglobin and hematocrit values were associated with lower baseline parenchymal CBF and more decline in parenchymal CBF over time, independent of cardiovascular risk factors, use of antiplatelet drugs, anticoagulants, or diuretics, and brain measures: adjusted mean differences (95% confidence interval [CI]) in decline in parenchymal CBF between patients in the lower and upper quartiles of hemoglobin and hematocrit were -2.48 (95% CI -3.70 to -1.25) and -3.69 (95% CI -5.45 to -1.94) mL/min/100 mL. Higher hemoglobin and hematocrit were associated with lower baseline parenchymal CBF and a greater decline in parenchymal CBF over time, possibly as a result of physiological compensating mechanisms. Copyright © 2015 Elsevier Inc. All rights reserved.

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

    Directory of Open Access Journals (Sweden)

    Seyed Ali Mousavi

    2015-01-01

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

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

    Science.gov (United States)

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

    2015-01-01

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

  7. [2,3 diphosphoglycerate in preterm newborns].

    Science.gov (United States)

    Scopesi, F; Canini, S; Mazzella, M; Arioni, C; Lantieri, P; Serra, G

    2000-01-01

    It has been largely shown that during the first month of life, in the preterm neonate Hb levels and Hct percentages rapidly decrease, high HbF concentration persists and a high oxygen affinity occurs. Data are needed to establish the level at which 2,3 dyphosphoglycerate (2,3 DPG) interacts with the regulation of oxygen affinity. 24 samples, from eight uncomplicated preterm newborns (34.1 +/- 1.83 GW, 1869 +/- +/- 291 BW) obtained at the same time as those required for the clinical management of the infants, were collected on the 2nd, 7th and 14th day of life. Blood gases, total hemoglobin and hematocrit were obtained from 0.3 ml arterialised capillary blood. Assays of 2,3 DPG were made separately on 0.4 ml venous blood. As expected tHb concentration and Hct percentages significantly decreased from day 2 to day 14 in all eight cases. On the contrary 2,3 DPG and p50 values remained stable. Subsequently throughout the study period all neonates had an increased 2,3 DPG/Hb ratio that was significantly related with p50 at standard conditions (p < 0.05). Stable 2,3 DPG concentrations during all study period have been detected. The subsequent significant increased 2.3 DPG/Hb, ratio related to increased p50 values, could have a key role in a physiological mechanism aimed to ensure adequate oxygen delivery to the tissues and to counteract the higher oxygen affinity of fetal hemoglobin. A wider sample is needed to validate this hypothesis.

  8. Hemoglobin mRNA Changes in the Frontal Cortex of Patients with Neurodegenerative Diseases

    Directory of Open Access Journals (Sweden)

    Silvia Vanni

    2018-01-01

    Full Text Available Background: Hemoglobin is the major protein found in erythrocytes, where it acts as an oxygen carrier molecule. In recent years, its expression has been reported also in neurons and glial cells, although its role in brain tissue remains still unknown. Altered hemoglobin expression has been associated with various neurodegenerative disorders. Here, we investigated hemoglobin mRNA levels in brains of patients affected by variant, iatrogenic, and sporadic forms of Creutzfeldt-Jakob disease (vCJD, iCJD, sCJD, respectively and in different genetic forms of prion diseases (gPrD in comparison to Alzheimer's disease (AD subjects and age-matched controls.Methods: Total RNA was obtained from the frontal cortex of vCJD (n = 20, iCJD (n = 11, sCJD (n = 23, gPrD (n = 30, and AD (n = 14 patients and age-matched controls (n = 30. RT-qPCR was performed for hemoglobin transcripts HBB and HBA1/2 using four reference genes for normalization. In addition, expression analysis of the specific erythrocyte marker ALAS2 was performed in order to account for blood contamination of the tissue samples. Hba1/2 and Hbb protein expression was then investigated with immunofluorescence and confocal microscope analysis.Results: We observed a significant up-regulation of HBA1/2 in vCJD brains together with a significant down-regulation of HBB in iCJD. In addition, while in sporadic and genetic forms of prion disease hemoglobin transcripts did not shown any alterations, both chains display a strong down-regulation in AD brains. These results were confirmed also at a protein level.Conclusions: These data indicate distinct hemoglobin transcriptional responses depending on the specific alterations occurring in different neurodegenerative diseases. In particular, the initial site of misfolding event (central nervous system vs. peripheral tissue—together with specific molecular and conformational features of the pathological agent of the disease—seem to dictate the peculiar

  9. Hemoglobin mRNA Changes in the Frontal Cortex of Patients with Neurodegenerative Diseases.

    Science.gov (United States)

    Vanni, Silvia; Zattoni, Marco; Moda, Fabio; Giaccone, Giorgio; Tagliavini, Fabrizio; Haïk, Stéphane; Deslys, Jean-Philippe; Zanusso, Gianluigi; Ironside, James W; Carmona, Margarita; Ferrer, Isidre; Kovacs, Gabor G; Legname, Giuseppe

    2018-01-01

    Background: Hemoglobin is the major protein found in erythrocytes, where it acts as an oxygen carrier molecule. In recent years, its expression has been reported also in neurons and glial cells, although its role in brain tissue remains still unknown. Altered hemoglobin expression has been associated with various neurodegenerative disorders. Here, we investigated hemoglobin mRNA levels in brains of patients affected by variant, iatrogenic, and sporadic forms of Creutzfeldt-Jakob disease (vCJD, iCJD, sCJD, respectively) and in different genetic forms of prion diseases (gPrD) in comparison to Alzheimer's disease (AD) subjects and age-matched controls. Methods: Total RNA was obtained from the frontal cortex of vCJD ( n = 20), iCJD ( n = 11), sCJD ( n = 23), gPrD ( n = 30), and AD ( n = 14) patients and age-matched controls ( n = 30). RT-qPCR was performed for hemoglobin transcripts HBB and HBA1/2 using four reference genes for normalization. In addition, expression analysis of the specific erythrocyte marker ALAS2 was performed in order to account for blood contamination of the tissue samples. Hba1/2 and Hbb protein expression was then investigated with immunofluorescence and confocal microscope analysis. Results: We observed a significant up-regulation of HBA1/2 in vCJD brains together with a significant down-regulation of HBB in iCJD. In addition, while in sporadic and genetic forms of prion disease hemoglobin transcripts did not shown any alterations, both chains display a strong down-regulation in AD brains. These results were confirmed also at a protein level. Conclusions: These data indicate distinct hemoglobin transcriptional responses depending on the specific alterations occurring in different neurodegenerative diseases. In particular, the initial site of misfolding event (central nervous system vs. peripheral tissue)-together with specific molecular and conformational features of the pathological agent of the disease-seem to dictate the peculiar hemoglobin

  10. Dependence of nitrite oxidation on nitrite and oxygen in low-oxygen seawater

    Science.gov (United States)

    Sun, Xin; Ji, Qixing; Jayakumar, Amal; Ward, Bess B.

    2017-08-01

    Nitrite oxidation is an essential step in transformations of fixed nitrogen. The physiology of nitrite oxidizing bacteria (NOB) implies that the rates of nitrite oxidation should be controlled by concentration of their substrate, nitrite, and the terminal electron acceptor, oxygen. The sensitivities of nitrite oxidation to oxygen and nitrite concentrations were investigated using 15N tracer incubations in the Eastern Tropical North Pacific. Nitrite stimulated nitrite oxidation under low in situ nitrite conditions, following Michaelis-Menten kinetics, indicating that nitrite was the limiting substrate. The nitrite half-saturation constant (Ks = 0.254 ± 0.161 μM) was 1-3 orders of magnitude lower than in cultivated NOB, indicating higher affinity of marine NOB for nitrite. The highest rates of nitrite oxidation were measured in the oxygen depleted zone (ODZ), and were partially inhibited by additions of oxygen. This oxygen sensitivity suggests that ODZ specialist NOB, adapted to low-oxygen conditions, are responsible for apparently anaerobic nitrite oxidation.

  11. Temperature effects on hemocyanin oxygen binding in an antarctic cephalopod.

    Science.gov (United States)

    Zielinski, S; Sartoris, F J; Pörtner, H O

    2001-02-01

    The functional relevance of oxygen transport by hemocyanin of the Antarctic octopod Megaleledone senoi and of the eurythermal cuttlefish Sepia officinalis was analyzed by continuous and simultaneous recordings of changes in pH and hemocyanin oxygen saturation in whole blood at various temperatures. These data were compared to literature data on other temperate and cold-water cephalopods (octopods and giant squid). In S. officinalis, the oxygen affinity of hemocyanin changed at deltaP50/degrees C = 0.12 kPa (pH 7.4) with increasing temperatures; this is similar to observations in temperate octopods. In M. senoi, thermal sensitivity was much smaller (delta log P50/delta pH) increased with increasing temperature in both the cuttlefish and the Antarctic octopod. At low PO2 (1.0 kPa) and pH (7.2), the presence of a large venous oxygen reserve (43% saturation) insensitive to pH reflects reduced pH sensitivity and high oxygen affinity in M. senoi hemocyanin at 0 degrees C. In S. officinalis, this reserve was 19% at pH 7.4, 20 degrees C, and 1.7 kPa O2, a level still higher than in squid. These findings suggest that the lower metabolic rate of octopods and cuttlefish compared to squid is reflected in less pH-dependent oxygen transport. Results of the hemocyanin analysis for the Antarctic octopod were similar to those reported for Vampyroteuthis--an extremely high oxygen affinity supporting a very low metabolic rate. In contrast to findings in cold-adapted giant squid, the minimized thermal sensitivity of oxygen transport in Antarctic octopods will reduce metabolic scope and thereby contribute to their stenothermality.

  12. Evolution of factors affecting placental oxygen transfer

    DEFF Research Database (Denmark)

    Carter, A M

    2009-01-01

    A review is given of the factors determining placental oxygen transfer and the oxygen supply to the fetus. In the case of continuous variables, such as the rate of placental blood flow, it is not possible to trace evolutionary trends. Discontinuous variables, for which we can define character sta......, where fetal and adult haemoglobin are not different, developmental regulation of 2, 3-diphosphoglycerate ensures the high oxygen affinity of fetal blood. Oxygen diffusing capacity is dependent on diffusion distance, which may vary with the type of interhaemal barrier. It has been shown...

  13. Characterization of hemoglobin-benzo[a]pyrene adducts

    International Nuclear Information System (INIS)

    Haugen, D.A.; Myers, S.R.

    1987-01-01

    Cultures of Syrian hamster embryo (SHE) cells were supplemented with human Hb (0.2 mM heme) and [ 3 H]BP (1 μM). After a 24-h incubation, the medium was removed and subjected to cation-exchange liquid chromatography (CM-Sepharose) to resolve hemoglobins from serum proteins in the medium. The BP-treated Hb was subjected to analysis in each of three column chromatographic systems established for isolation and characterization of human hemoglobin and its genetic and post-translationally modified variants. Results demonstrate that hemoglobin-carcinogen adducts can be resolved from native hemoglobin by established conventional and high-performance liquid chromatographic procedures, suggesting the basis for development of general approaches for isolating and characterizing hemoglobin-carcinogen adducts. The results also suggest the basis for a model system in which adducts between carcinogens and human hemoglobin are formed in cultures of mammalian cells or tissues

  14. A relay network of extracellular heme-binding proteins drives C. albicans iron acquisition from hemoglobin.

    Science.gov (United States)

    Kuznets, Galit; Vigonsky, Elena; Weissman, Ziva; Lalli, Daniela; Gildor, Tsvia; Kauffman, Sarah J; Turano, Paola; Becker, Jeffrey; Lewinson, Oded; Kornitzer, Daniel

    2014-10-01

    Iron scavenging constitutes a crucial challenge for survival of pathogenic microorganisms in the iron-poor host environment. Candida albicans, like many microbial pathogens, is able to utilize iron from hemoglobin, the largest iron pool in the host's body. Rbt5 is an extracellular glycosylphosphatidylinositol (GPI)-anchored heme-binding protein of the CFEM family that facilitates heme-iron uptake by an unknown mechanism. Here, we characterize an additional C. albicans CFEM protein gene, PGA7, deletion of which elicits a more severe heme-iron utilization phenotype than deletion of RBT5. The virulence of the pga7-/- mutant is reduced in a mouse model of systemic infection, consistent with a requirement for heme-iron utilization for C. albicans pathogenicity. The Pga7 and Rbt5 proteins exhibit distinct cell wall attachment, and discrete localization within the cell envelope, with Rbt5 being more exposed than Pga7. Both proteins are shown here to efficiently extract heme from hemoglobin. Surprisingly, while Pga7 has a higher affinity for heme in vitro, we find that heme transfer can occur bi-directionally between Pga7 and Rbt5, supporting a model in which they cooperate in a heme-acquisition relay. Together, our data delineate the roles of Pga7 and Rbt5 in a cell surface protein network that transfers heme from extracellular hemoglobin to the endocytic pathway, and provide a paradigm for how receptors embedded in the cell wall matrix can mediate nutrient uptake across the fungal cell envelope.

  15. A probe to study the toxic interaction of tartrazine with bovine hemoglobin at the molecular level.

    Science.gov (United States)

    Li, Yating; Wei, Haoran; Liu, Rutao

    2014-03-01

    Tartrazine is an artificial azo dye commonly used in food products, but tartrazine in the environment is potentially harmful. The toxic interaction between tartrazine and bovine hemoglobin (BHb) was investigated using fluorescence, synchronous fluorescence, UV-vis absorption, circular dichroism (CD) and molecular modeling techniques under simulated physiological conditions. The fluorescence data showed that tartrazine can bind with BHb to form a complex. The binding process was a spontaneous molecular interaction, in which van der Waals' forces and hydrogen bonds played major roles. Molecular docking results showed that the hydrogen bonds exist between the oxygen atoms at position 31 of tartrazine and the nitrogen atom NZ7 on Lys99, and also between the oxygen atoms at position 15 of tartrazine and the nitrogen atom NZ7 on Lys104, Lys105. The results of UV-vis and CD spectra revealed that tartrazine led to conformational changes in BHb, including loosening of the skeleton structure and decreasing α helix in the secondary structure. The synchronous fluorescence experiment revealed that tartrazine binds into the hemoglobin central cavity, and this was verified using a molecular modeling study. Copyright © 2013 John Wiley & Sons, Ltd.

  16. Hemoglobin of mice with radiation-induced mutations at the hemoglobin loci

    Energy Technology Data Exchange (ETDEWEB)

    Popp, R A; Stratton, L P; Hawley, D K; Effron, K [Oak Ridge National Lab., TN (USA)

    1979-01-15

    Chemical analyses were done on the abnormal hemoglobins of the five (101 x SEC)F/sub 1/ offspring of X- irradiated adult SEC mice to determine which hemoglobin genes were expressed in each hemoglobin variant. Three offspring of irradiated SEC males did not express either of the two kinds of ..cap alpha..-chains normally found in all SEC mice. The deficient ..cap alpha..-chain synthesis caused these mice to exhibit an ..cap alpha..-thalassemia similar to human ..cap alpha..-thalassemia. Scanning electron microscopy was used to show that many erythrocytes of mice with ..cap alpha..-thalassemia have bizarre shapes; e.g. many erythrocytes appeared flattened or had thorny projections (acanthocytes). One mutant with a tandem duplication of a segment of chromosome 7 (site of locus determining ..beta..-chain structure) produced twice as much SEC as 101 ..beta..-chain polypeptides. One mutant that probably arose by non-disjunction of chromosome 7's in its unirradiated 101 mother and loss of chromosome 7 from the gamete of its irradiated SEC father did not express the SEC ..beta..-chain gene.

  17. Hemoglobin of mice with radiation-induced mutations at the hemoglobin loci

    International Nuclear Information System (INIS)

    Popp, R.A.; Stratton, L.P.; Hawley, D.K.; Effron, K.

    1979-01-01

    Chemical analyses were done on the abnormal hemoglobins of the five (101 x SEC)F 1 offspring of X- irradiated adult SEC mice to determine which hemoglobin genes were expressed in each hemoglobin variant. Three offspring of irradiated SEC males did not express either of the two kinds of α-chains normally found in all SEC mice. The deficient α-chain synthesis caused these mice to exhibit an α-thalassemia similar to human α-thalassemia. Scanning electron microscopy was used to show that many erythrocytes of mice with α-thalassemia have bizarre shapes; e.g. many erythrocytes appeared flattened or had thorny projections (acanthocytes). One mutant with a tandem duplication of a segment of chromosome 7 (site of locus determining β-chain structure) produced twice as much SEC as 101 β-chain polypeptides. One mutant that probably arose by non-disjunction of chromosome 7's in its unirradiated 101 mother and loss of chromosome 7 from the gamete of its irradiated SEC father did not express the SEC β-chain gene. (author)

  18. Quinones: reactions with hemoglobin, effects within erythrocytes and potential for antimalarial development

    International Nuclear Information System (INIS)

    Denny, B.J.

    1986-01-01

    The focus of this research was to characterize the interactions of some simple quinone like compounds with purified hemoglobin and to study the effects of these compounds within erythrocytes. It is proposed that these sorts of agents can have an antimalarial effect. The simplest compounds chosen for study were benzoquinone, methylquinone (toluquinone) and hydroquinone. When 14 C-quinone was reacted with purified hemoglobin (Hb) there was rapid binding of the first two moles of substrate per Hb molecule. An unusual property of the modified Hb's is that in the presence of a redox sensitive agent such as cytochrome c they are capable of generating superoxide anions. Within erythrocytes, quinone and toluquinone which differ only by a single methyl group have completely different effects. Toluquinone causes the cells to hemolyse and the effect was enhanced when the erythrocyte superoxide dismutase was inhibited; the effect was diminished when scavengers of activated oxygen such as histidine, mannitol and vital E were present. Benzoquinone on the other hand did not cause the cells to hemolyse and instead appeared to protect the cells from certain hemolytic stresses. Growth of malaria parasites in erythrocytes has been shown to be inhibited by activated forms of oxygen, also some quinone like agents in the past have been shown to inhibit the parasite's metabolism. An initial experiment with erythrocytes infected with malaria parasites showed that quinone and toluquinone could both inhibit the growth rate of parasites

  19. A proton nuclear magnetic resonance investigation of proximal histidyl residues in human normal and abnormal hemoglobins: a probe for the heme pocket

    International Nuclear Information System (INIS)

    Takahashi, S.; Lin, A.K.L.; Ho, C.

    1982-01-01

    Proton nuclear magnetic resonance spectroscopy at 250 MHz has been used to investigate the conformations of proximal histidyl residues of human normal adult hemoglobin, hemoglobin Kempsey [K145(HC2) Tyr #betta# Asp], and hemoglobin McKees Rocks [K145(HC2) Tyr #betta# Term] around neutral pH in H 2 O at 27 0 C, all in the deoxy form. Two resonances that occur between 58 and 76 ppm downfield from the water proton signal have been assigned to the hyperfine shifted proximal histidyl NH-exchangeable protons of the J and K-chains of deoxyhemoglobin. These two resonances are sensitive to the quaternary state of hemoglobin, amino acid substitutions in the J 1 K 2 -subunit interface and in the carboxy-terminal region of the K-chain, and the addition of organic phosphates. The experimental results show that there are differences in the heme pockets among these four hemoglobins studied. The structural and dynamic information derived from the hyperfine shifted proximal histidyl NH-exchangeable proton resonances complement that obtained from the ferrous hyperfine shifted and exchangeable proton resonances of deoxyhemoglobin over the spectral region from 5 to 20 ppm downfield from H 2 O. The relationship between these findings and Perutz's stereochemical mechanism for the cooperative oxygenation of hemoglobin is discussed

  20. Moessbauer study of hemoglobin of diabetes

    International Nuclear Information System (INIS)

    Li Aiguo; Ni Xinbo; Cai Yingwen; Zhang Guilin; Zhang Hongde; Ge Yongxin

    2000-01-01

    The hemoglobins from normal adults (Gly-Hb 5%), people infected with diabetes (Gly-Hb 10%) and serious diabetics (Gly-Hb 15%) were investigated by Moessbauer spectroscopy at liquid nitrogen temperature. All the experimental spectra of hemoglobin are composed of three doublets corresponding to oxy-hemoglobin (Oxy-Hb), deoxy-hemoglobin (Deoxy-Hb) and low-spin hemo-chrome (Ls-Hemo) respectively. It is found that Oxy-Hb is decreasing but Deoxy-hb increasing for diabetes. Experimental results also indicate that the line-width of Moessbauer spectra of Oxy-Hb for diabetics is narrower than that for normal adults, showing that while Fe on Oxy-Hb exists in pile-up of some similar states for normal adults, but it becomes in single state for serious diabetes

  1. Strategies for Small Volume Resuscitation: Hyperosmotic-Hyperoncotic Solutions, Hemoglobin Based Oxygen Carriers and Closed-Loop Resuscitation

    Science.gov (United States)

    Kramer, George C.; Wade, Charles E.; Dubick, Michael A.; Atkins, James L.

    2004-01-01

    Introduction: Logistic constraints on combat casualty care preclude traditional resuscitation strategies which can require volumes and weights 3 fold or greater than hemorrhaged volume. We present a review of quantitative analyses of clinical and animal data on small volume strategies using 1) hypertonic-hyperosmotic solutions (HHS); 2) hemoglobin based oxygen carriers (HBOCs) and 3) closed-loop infusion regimens.Methods and Results: Literature searches and recent queries to industry and academic researchers have allowed us to evaluate the record of 81 human HHS studies (12 trauma trials), 19 human HBOCs studies (3trauma trials) and two clinical studies of closed-loop resuscitation.There are several hundreds animal studies and at least 82 clinical trials and reports evaluating small volume7.2%-7.5% hypertonic saline (HS) most often combined with colloids, e.g., dextran (HSD) or hetastarch(HSS). HSD and HSS data has been published for 1,108 and 392 patients, respectively. Human studies have documented volume sparing and hemodynamic improvements. Meta-analyses suggest improved survival for hypotensive trauma patients treated with HSD with significant reductions in mortality found for patients with blood pressure blood use and lower mortality compared to historic controls of patients refusing blood. Transfusion reductions with HBOC use have been modest. Two HBOCs (Hemopure and Polyheme) are now in new or planned large-scale multicenter prehospital trials of trauma treatment. A new implementation of small volume resuscitation is closed-loop resuscitation (CLR), which employs microprocessors to titrate just enough fluid to reach a physiologic target . Animal studies suggest less risk of rebleeding in uncontrolled hemorrhage and a reduction in fluid needs with CLR. The first clinical application of CLR was treatment of burn shock and the US Army. Conclusions: Independently sponsored civilian trauma trials and clinical evaluations in operational combat conditions of

  2. Lower Hemoglobin Concentration Is Associated with Retinal Ischemia and the Severity of Diabetic Retinopathy in Type 2 Diabetes

    Science.gov (United States)

    Traveset, Alicia; Rubinat, Esther; Ortega, Emilio; Alcubierre, Nuria; Vazquez, Beatriz; Hernández, Marta; Jurjo, Carmen; Espinet, Ramon; Ezpeleta, Juan Antonio; Mauricio, Didac

    2016-01-01

    Aims. To assess the association of blood oxygen-transport capacity variables with the prevalence of diabetic retinopathy (DR), retinal ischemia, and macular oedema in patients with type 2 diabetes mellitus (T2DM). Methods. Cross-sectional, case-control study (N = 312) with T2DM: 153 individuals with DR and 159 individuals with no DR. Participants were classified according to the severity of DR and the presence of retinal ischemia or macular oedema. Hematological variables were collected by standardized methods. Three logistic models were adjusted to ascertain the association between hematologic variables with the severity of DR and the presence of retinal ischemia or macular oedema. Results. Individuals with severe DR showed significantly lower hemoglobin, hematocrit, and erythrocyte levels compared with those with mild disease and in individuals with retinal ischemia and macular oedema compared with those without these disorders. Hemoglobin was the only factor that showed a significant inverse association with the severity of DR [beta-coefficient = −0.52, P value = 0.003] and retinal ischemia [beta-coefficient = −0.49, P value = 0.001]. Lower erythrocyte level showed a marginally significant association with macular oedema [beta-coefficient = −0.86, P value = 0.055]. Conclusions. In patients with DR, low blood oxygen-transport capacity was associated with more severe DR and the presence of retinal ischemia. Low hemoglobin levels may have a key role in the development and progression of DR. PMID:27200379

  3. Synthesis and characterization of aba-type copolymers for encapsulation of bovine hemoglobin

    International Nuclear Information System (INIS)

    Lima, Felipe F.; Andrade, Cristina T.

    2012-01-01

    The use of biopolymers for the development of oxygen carriers has been extensively investigated. In this work, three different ABA triblock copolymers were synthesized and used to encapsulate purified bovine hemoglobin, using a double emulsion technique. The effect of polymer composition, homogenization velocity, and addition of a surfactant, on the protein entrapment was evaluated. These copolymers, which have a hydrophilic block, achieved higher values of encapsulation efficiency than the corresponding homopolymers. The increase in homogenization strength also promoted an increase in encapsulation efficiency. Capsules formation occurred even in the absence of PVA. (author)

  4. Electron transfer reactions, cyanide and O2 binding of truncated hemoglobin from Bacillus subtilis

    International Nuclear Information System (INIS)

    Fernandez, Esther; Larsson, Jonas T.; McLean, Kirsty J.; Munro, Andrew W.; Gorton, Lo; Wachenfeldt, Claes von; Ferapontova, Elena E.

    2013-01-01

    The truncated hemoglobin from Bacillus subtilis (trHb-Bs) possesses a surprisingly high affinity for oxygen and resistance to (auto)oxidation; its physiological role in the bacterium is not understood and may be connected with its very special redox and ligand binding reactions. Electron transfer reactions of trHb-Bs were electrochemically studied in solution and at graphite electrodes. Spectrophotometrical potentiometric titration and direct electrochemical measurements gave a heme iron redox potential of −103 ± 4 mV and −108 ± 2 mV vs. NHE, at pH 7, respectively. The redox potential of the heme in trHb-Bs shifted −59 mV per pH unit at pH higher than 7, consistently with a 1e − /1 H + – transfer reaction. The heterogeneous rate constant k s for a quasi-reversible 1e − – 1H + – transfer reaction between graphite and trHb-Bs was 10.1 ± 2.3 s −1 . Upon reversible cyanide binding the k s doubled, while the redox potential of heme shifted 21 mV negatively, presumably reflecting changes in redox activity and in vivo signaling functions of trHb-Bs associated with ligand binding. Bioelectrocatalytic reduction of O 2 catalyzed by trHb-Bs was one of the most efficient hitherto reported for Hbs, with an apparent catalytic rate constant, k cat , of 56 ± 6 s −1 . The results obtained are of particular interest for applications of trHb in environmental biosensing and toxicity screening

  5. Red blood cell transfusions and tissue oxygenation in anemic hematology outpatients

    NARCIS (Netherlands)

    Yuruk, Koray; Bartels, Sebastiaan A.; Milstein, Dan M. J.; Bezemer, Rick; Biemond, Bart J.; Ince, Can

    2012-01-01

    BACKGROUND: There is little clinical evidence that red blood cell (RBC) transfusions improve oxygen availability at the microcirculatory level. We tested the hypotheses that anemia in chronically anemic patients with relatively healthy microcirculation would be associated with low tissue hemoglobin

  6. Molecular electron affinities

    International Nuclear Information System (INIS)

    Fukuda, E.K.

    1983-01-01

    Molecular electron affinities have historically been difficult quantities to measure accurately. These difficulties arise from differences in structure between the ion and neutral as well as the existence of excited negative ion states. To circumvent these problems, relative electron affinities were determined in this dissertation by studying equilibrium electron transfer reactions using a pulsed ion cyclotron resonance (ICR) spectrometer. Direct measurement of ion and neutral concentrations for reactions of the general type, A - + B = B - + A, allow calculation of the equilibrium constant and, therefore, the free energy change. The free energy difference is related to the difference in electron affinities between A and B. A relative electron affinity scale covering a range of about 45 kcal/mol was constructed with various substituted p-benzoquinones, nitrobenzenes, anhydrides, and benzophenones. To assign absolute electron affinities, various species with accurately known electron affinities are tied to the scale via ion-cyclotron double resonance bracketing techniques. After the relative scale is anchored to these species with well-known electron affinities, the scale is then used as a check on other electron affinity values as well as generating new electron affinity values. Many discrepancies were found between the electron affinities measured using the ICR technique and previous literature determinations

  7. Monitoring hemodynamics and oxygenation of the kidney in rats by a combined near-infrared spectroscopy and invasive probe approach

    Science.gov (United States)

    Grosenick, Dirk; Cantow, Kathleen; Arakelyan, Karen; Wabnitz, Heidrun; Flemming, Bert; Skalweit, Angela; Ladwig, Mechthild; Macdonald, Rainer; Niendorf, Thoralf; Seeliger, Erdmann

    2015-07-01

    We have developed a hybrid approach to investigate the dynamics of perfusion and oxygenation in the kidney of rats under pathophysiologically relevant conditions. Our approach combines near-infrared spectroscopy to quantify hemoglobin concentration and oxygen saturation in the renal cortex, and an invasive probe method for measuring total renal blood flow by an ultrasonic probe, perfusion by laser-Doppler fluxmetry, and tissue oxygen tension via fluorescence quenching. Hemoglobin concentration and oxygen saturation were determined from experimental data by a Monte Carlo model. The hybrid approach was applied to investigate and compare temporal changes during several types of interventions such as arterial and venous occlusions, as well as hyperoxia, hypoxia and hypercapnia induced by different mixtures of the inspired gas. The approach was also applied to study the effects of the x-ray contrast medium iodixanol on the kidney.

  8. HYPERBARIC OXYGENATION AND AEROBIC PERFORMANCE

    Directory of Open Access Journals (Sweden)

    Irvine D. Prather

    2004-03-01

    Full Text Available The continuing desire to improve performance, particularly at the national and international levels, has led to the use of ergogenic aids. Ergogenic aids are defined as 'a procedure or agent that provides the athlete with a competitive edge beyond that obtained via normal training methods'. Random drug testing has been implemented in an effort to minimize an athlete's ability to gain an unfair advantage. However, other means of improving performance have been tried. Blood doping has been used to enhance endurance performance by improving oxygen delivery to working muscles. As oxygen is carried in combination with the hemoglobin, it seems logical that increasing the number of red blood cells (RBC's in the body would increase the oxygen carrying capacity to the tissues and result in improved performance. The first experiments of removing and then reinfusing blood showed a significant improvement in performance time

  9. Comparison of changes in oxygenated hemoglobin during the tree-drawing task between patients with schizophrenia and healthy controls.

    Science.gov (United States)

    Nakano, Shinya; Shoji, Yoshihisa; Morita, Kiichiro; Igimi, Hiroyasu; Sato, Mamoru; Ishii, Youhei; Kondo, Akihiko; Uchimura, Naohisa

    2018-01-01

    Tree-drawing test is used as a projective psychological test that expresses the abnormal internal experience in patients with schizophrenia (SZ). Despite the widely accepted view that the cognitive function is involved in characteristic tree-drawing in patients with SZ, no study has psychophysiologically examined it. The present study aimed to investigate the involvement of cognitive function during tree-drawing in patients with SZ. For that purpose, we evaluated the brain function in patients with SZ during a tree-drawing task by using near-infrared spectroscopy (NIRS) and compared them with those in healthy controls. The subjects were 28 healthy controls and 28 patients with SZ. Changes in the oxygenated hemoglobin ([oxy-Hb]) concentration in both the groups during the task of drawing a tree imagined freely (free-drawing task) and the task of copying an illustration of a tree (copying task) were measured by using NIRS. Because of the difference between the task conditions, [oxy-Hb] levels in controls during the free-drawing task were higher than that during the copying task at the bilateral frontal pole regions and left inferior frontal region. Because of the difference between the groups, [oxy-Hb] levels at the left middle frontal region, bilateral inferior frontal regions, bilateral inferior parietal regions, and left superior temporal region during the free-drawing task in patients were lower than that in controls. [oxy-Hb] during the tree-drawing task in patients with SZ was lower than that in healthy controls. Our results suggest that brain dysfunction in patients with SZ might be associated with their tree-drawing.

  10. The dual roles of red blood cells in tissue oxygen delivery

    DEFF Research Database (Denmark)

    Jensen, Frank Bo

    2009-01-01

    Vertebrate red blood cells (RBCs) seem to serve tissue oxygen delivery in two distinct ways. Firstly, RBCs enable the adequate transport of O2 between respiratory surfaces and metabolizing tissues by means of their high intracellular concentration of hemoglobin (Hb), appropriate allosteric...

  11. Generation of a haptoglobin-hemoglobin complex-specific Fab antibody blocking the binding of the complex to CD163

    DEFF Research Database (Denmark)

    Horn, Ivo R; Nielsen, Marianne Jensby; Madsen, Mette

    2003-01-01

    During intravascular hemolysis hemoglobin (Hb) binds to haptoglobin (Hp) leading to endocytosis of the complex by the macrophage receptor, CD163. In the present study, we used a phage-display Fab antibody strategy to explore if the complex formation between Hp and Hb leads to exposure of antigenic...... epitopes specific for the complex. By Hp-Hb-affinity screening of a phage-Fab library, we isolated a phage clone against the ligand complex. Surface plasmon resonance analyses of the Fab part expressed as a recombinant protein revealed a high affinity binding (KD = 3.9 nm) to Hp-Hb, whereas no binding...... was measured for non-complexed Hp or Hb. The Fab antibody completely inhibited the binding of 125I-labeled Hp-Hb complexes to CD163 and blocked their uptake in CD163-transfected cells. In conclusion, we have raised a receptor-blocking antibody specifically recognizing the Hp-Hb complex. In addition to provide...

  12. The utility of affine variables and affine coherent states

    International Nuclear Information System (INIS)

    Klauder, John R

    2012-01-01

    Affine coherent states are generated by affine kinematical variables much like canonical coherent states are generated by canonical kinematical variables. Although all classical and quantum formalisms normally entail canonical variables, it is shown that affine variables can serve equally well for many classical and quantum studies. This general purpose analysis provides tools to discuss two major applications: (1) the completely successful quantization of a nonrenormalizable scalar quantum field theory by affine techniques, in complete contrast to canonical techniques which only offer triviality; and (2) a formulation of the kinematical portion of quantum gravity that favors affine kinematical variables over canonical kinematical variables, and which generates a framework in which a favorable analysis of the constrained dynamical issues can take place. All this is possible because of the close connection between the affine and the canonical stories, while the few distinctions can be used to advantage when appropriate. This article is part of a special issue of Journal of Physics A: Mathematical and Theoretical devoted to ‘Coherent states: mathematical and physical aspects’. (review)

  13. Small angle X-ray scattering on concentrated hemoglobin solutions

    International Nuclear Information System (INIS)

    Zinke, M.; Damaschun, G.; Mueller, J.J.; Ruckpaul, K.

    1978-01-01

    The small-angle X-ray scattering technique was used to determine the intermolecular structure and interaction potentials in oxi-and deoxi-hemoglobin solutions. The pair correlation function obtained by the ZERNICKE-PRINS equation characterizes the intermolecular structure of the hemoglobin molecules. The intermolecular structure is concentration dependent. The hemoglobin molecules have a 'short range order structure' with a range of about 4 molecule diameters at 324 g/l. The potential functions of the hemoglobin-hemoglobin interaction have been determined on the basis of fluid theories. Except for the deoxi-hemoglobin solution having the concentration 370 g/l, the pair interaction consists in a short repulsion and a weak short-range attraction against kT. The potential minimum is between 1.2 - 1.5 nm above the greatest hemoglobin diameter. (author)

  14. Spectroscopic study of gamma irradiated bovine hemoglobin

    International Nuclear Information System (INIS)

    Maghraby, Ahmed Mohamed; Ali, Maha Anwar

    2007-01-01

    In the present study, the effects of ionizing radiation of Cs-137 and Co-60 from 4.95 to 743.14 Gy and from 40 Gy to 300 kGy, respectively, on some bovine hemoglobin characteristics were studied. Such an effect was evaluated using electron paramagnetic resonance (EPR) spectroscopy, and infra-red (IR) spectroscopy. Bovine hemoglobin EPR spectra were recorded and analyzed before and after irradiation and changes were explained in detail. IR spectra of unirradiated and irradiated Bovine hemoglobin were recorded and analyzed also. It was found that ionizing radiation may lead to the increase of free radicals production, the decrease in α-helices contents, which reflects the degradation of hemoglobin molecular structure, or at least its incomplete performance. Results also show that the combined application of EPR and FTIR spectroscopy is a powerful tool for determining structural modification of bovine hemoglobin samples exposed to gamma irradiation

  15. Erythrocyte 2,3-DPG, PO2 50% and available O2 during the early post-natal fall in hemoglobin in rabbits.

    Science.gov (United States)

    Holter, P H; Halvorsen, S; Refsum, H E

    1982-09-01

    Erythrocyte 2,3-DPG, PO2 50%, whole blood hemoglobin and available O2, and fixed acid Bohr effect were studied during the first 10 days after birth in rapidly growing suckling rabbits. The post-natal fall in hemoglobin concentration was accompanied by a marked rise in erythrocyte 2,3-DPG and a gradual increase in PO2 50%. The rise in PO2 50% was sufficient to keep the available O2 of the blood unchanged throughout the observation period. The observations show that a 2,3-DPG mediated rise in PO2 50% very effectively contributes to maintenance of adequate tissue oxygenation during the post-natal fall in hemoglobin. The rise in 2,3-DPG and and PO2 50% may be due to the ordinary hypoxia-induced shift to the right of the hemoglobin O2 dissociation curve, as observed under other circumstances when blood hemoglobin is rapidly reduced, but the very marked rise in 2,3-DPG and the very low delta PO2 50%/delta 2,3-DPG ratio suggest that the rise may as well be due to hypoxia independent, pre-programmed processes. The fixed acid Bohr effect was essentially the same in newborn and adult rabbits, and was uninfluenced by large variations in 2,3-DPG.

  16. Genetic hemoglobin disorders rather than iron deficiency are a major predictor of hemoglobin concentration in women of reproductive age in rural prey Veng, Cambodia.

    Science.gov (United States)

    Karakochuk, Crystal D; Whitfield, Kyly C; Barr, Susan I; Lamers, Yvonne; Devlin, Angela M; Vercauteren, Suzanne M; Kroeun, Hou; Talukder, Aminuzzaman; McLean, Judy; Green, Timothy J

    2015-01-01

    Anemia is common in Cambodian women. Potential causes include micronutrient deficiencies, genetic hemoglobin disorders, inflammation, and disease. We aimed to investigate factors associated with anemia (low hemoglobin concentration) in rural Cambodian women (18-45 y) and to investigate the relations between hemoglobin disorders and other iron biomarkers. Blood samples were obtained from 450 women. A complete blood count was conducted, and serum and plasma were analyzed for ferritin, soluble transferrin receptor (sTfR), folate, vitamin B-12, retinol binding protein (RBP), C-reactive protein (CRP), and α1 acid glycoprotein (AGP). Hemoglobin electrophoresis and multiplex polymerase chain reaction were used to determine the prevalence and type of genetic hemoglobin disorders. Overall, 54% of women had a genetic hemoglobin disorder, which included 25 different genotypes (most commonly, hemoglobin E variants and α(3.7)-thalassemia). Of the 420 nonpregnant women, 29.5% had anemia (hemoglobin 8.3 mg/L), hemoglobin disorders, respectively. There was no biochemical evidence of vitamin A deficiency (RBP 5 mg/L) and 26% (AGP >1 g/L) of nonpregnant women, respectively. By using an adjusted linear regression model, the strongest predictors of hemoglobin concentration were hemoglobin E homozygous disorder and pregnancy status. Other predictors were 2 other heterozygous traits (hemoglobin E and Constant Spring), parity, RBP, log ferritin, and vitamin B-12. Multiple biomarkers for anemia and iron deficiency were significantly influenced by the presence of hemoglobin disorders, hence reducing their diagnostic sensitivity. Further investigation of the unexpectedly low prevalence of IDA in Cambodian women is warranted. © 2015 American Society for Nutrition.

  17. Lyophilized bovine hemoglobin as a possible reference material for the determination of hemoglobin derivatives in human blood

    NARCIS (Netherlands)

    Maas, BHA; Buursma, A; Ernst, RAJ; Maas, AHJ; Zijlstra, WG

    We investigated the suitability of a lyophilized bovine hemoglobin (LBH) preparation containing various fractions of oxyhemoglobin (O(2)Hb), carboxyhemoglobin (COHb), and methemoglobin (MetHb) for quality assessment in multicomponent analysis (MCA) of hemoglobin derivatives. It was demonstrated that

  18. Lyophilized bovine hemoglobin as a possible reference material for the determination of hemoglobin derivatives in human blood

    NARCIS (Netherlands)

    Maas, BHA; Buursma, A; Ernst, RAJ; Maas, AHJ; Zijlstra, WG

    1998-01-01

    We investigated the suitability of a lyophilized bovine hemoglobin (LBH) preparation containing various fractions of oxyhemoglobin (O(2)Hb), carboxyhemoglobin (COHb), and methemoglobin (MetHb) for quality assessment in multicomponent analysis (MCA) of hemoglobin derivatives. It was demonstrated that

  19. The effect of 2,3-diphosphoglycerate on the oxygen dissociation curve of human haemoglobin.

    Science.gov (United States)

    Goodford, P J; Norrington, F E; Paterson, R A; Wootton, R

    1977-01-01

    1. Oxygen dissociation curves for concentrated human haemoglobin solutions (1.6 mmol dm-3 in haem) have been measured by mixing known quantities of oxy- and deoxyhaemoglobin solutions and measuring the resulting partial pressure of oxygen with an oxygen electrode. 2. Observations in the presence of 2,3-diphosphoglycerate support previous conclusions derived from experiments at low haemoglobin concentrations, the validity of which has been questioned. 3. The two affinity state model of Monod, Wyman & Changeux (1965) does not fully describe the actions of 2,3-diphosphoglycerate and a model in which this allosteric effector not only binds preferentially to the T state but also lowers the oxygen affinity of this state gives an improved fit to the data. PMID:604451

  20. Comparison of crystal and solution hemoglobin binding of selected antigelling agents and allosteric modifiers

    International Nuclear Information System (INIS)

    Mehanna, A.S.; Abraham, D.J.

    1990-01-01

    This paper details comprehensive binding studies (solution and X-ray) of human hemoglobin A with a group of halogenated carboxylic acids that were investigated as potential antisickling agents. It is, to our knowledge, the first study to compare solution and crystal binding for a series of compounds under similar high-salt conditions used for cocrystallization. The compounds include [(3,4-dichlorobenzyl)oxy]acetic acid, [(p-bromobenzyl)oxy]acetic acid, clofibric acid, and bezafibrate. The location and stereochemistry of binding sites have been established by X-ray crystallography, while the number of binding sites and affinity constants were measured by using equilibrium dialysis. The observed crystal structures are consistent with the binding observed in solution and that the number of binding sites is independent of salt concentration, while the binding constant increases with increasing salt concentration. The studies also reveal that relatively small changes in the chemical structure of a drug molecule can result in entirely different binding sites on the protein. Moreover, the X-ray studies provide a possible explanation for the multiplicity in function exhibited by these compounds as allosteric modulators and/or antisickling agents. Finally, the studies indicate that these compounds bind differently to the R and T states of hemoglobin, and observation of special significance to the original design of these agents

  1. Hemoglobin analyses in the Netherlands reveal more than 80 different variants including six novel ones.

    Science.gov (United States)

    van Zwieten, Rob; Veldthuis, Martijn; Delzenne, Barend; Berghuis, Jeffrey; Groen, Joke; Ait Ichou, Fatima; Clifford, Els; Harteveld, Cornelis L; Stroobants, An K

    2014-01-01

    More than 20,000 blood samples of individuals living in The Netherlands and suspected of hemolytic anemia or diabetes were analyzed by high resolution cation exchange high performance liquid chromatography (HPLC). Besides common disease-related hemoglobins (Hbs), rare variants were also detected. The variant Hbs were retrospectively analyzed by capillary zone electrophoresis (CZE) and by isoelectric focusing (IEF). For unambiguous identification, the globin genes were sequenced. Most of the 80 Hb variants detected by initial screening on HPLC were also separated by capillary electrophoresis (CE), but a few variants were only detectable with one of these methods. Some variants were unstable, had thalassemic properties or increased oxygen affinity, and some interfered with Hb A2 measurement, detection of sickle cell Hb or Hb A1c quantification. Two of the six novel variants, Hb Enschede (HBA2: c.308G  > A, p.Ser103Asn) and Hb Weesp (HBA1: c.301C > T, p.Leu101Phe), had no clinical consequences. In contrast, two others appeared clinically significant: Hb Ede (HBB: c.53A > T, p.Lys18Met) caused thalassemia and Hb Waterland (HBB: c.428C > T, pAla143Val) was related to mild polycytemia. Hb A2-Venlo (HBD: c.193G > A, p.Gly65Ser) and Hb A2-Rotterdam (HBD: c.38A > C, p.Asn13Thr) interfered with Hb A2 quantification. This survey shows that HPLC analysis followed by globin gene sequencing of rare variants is an effective method to reveal Hb variants.

  2. Report: Affinity Chromatography.

    Science.gov (United States)

    Walters, Rodney R.

    1985-01-01

    Supports, affinity ligands, immobilization, elution methods, and a number of applications are among the topics considered in this discussion of affinity chromatography. An outline of the basic principles of affinity chromatography is included. (JN)

  3. Oxygen dissociation curves of whole blood from the Egyptian free ...

    African Journals Online (AJOL)

    Tadarida aegyptiaca (mean body mass 13.5 g) is a fast flying insectivorous bat that hunts in open areas for extended periods, covering extensive distances during its foraging bouts. Whole blood samples taken from the wing arteries were analysed for 2,3-diphosphoglyceric acid, oxygen affinity and pH. The mean oxygen ...

  4. Postoperative hemoglobin level in patients with femoral neck fracture.

    Science.gov (United States)

    Nagra, Navraj S; Van Popta, Dmitri; Whiteside, Sigrid; Holt, Edward M

    2016-01-01

    The aim of this study was to analyze the changes of hemoglobin levels in patients undergoing fixation for femoral neck fracture. Peroperative hemoglobin levels of patients who underwent either dynamic hip screw (DHS) fixation (n=74; mean age: 80 years) or hip hemiarthroplasty (n=104; mean age: 84 years) for femoral neck fracture was monitored. There was a statistically and clinically significant mean drop of 31.1 g/L between the preoperative (D0) and postoperative Day 5 Hb levels (pmeasurement, DHS patients had lower hemoglobin values over hemiarthroplasty patients (p=0.046). The decrease in hemoglobin in the first 24-hour postoperative period (D0 to Day 1) is an underestimation of the ultimate lowest value in hemoglobin found at Day 2. Relying on the Day 1 hemoglobin level could be detrimental to patient care. We propose a method of predicting patients likely to be transfused and recommend a protocol for patients undergoing femoral neck fracture surgery to standardize postoperative hemoglobin monitoring.

  5. [Evaluation of heart impact in the 100 m extreme intensity sport using near-infrared non-invasive muscle oxygen detecting device and sports heart rate detection technology].

    Science.gov (United States)

    Wang, Pei-Yong; Long, Fei-Xiao; Fu, Lan-Ying; Li, Yue; Ding, Hai-Shu; Qu, An-Lian; Zhou, Xiao-Ping

    2010-02-01

    Using continuous two wavelength near-infrared technology to detect the variation in the consistency of oxygen hemoglobin in the muscle and the sports heart rate wireless real time collection technology, we devised the real time muscle tissue oxygenation and instantaneous heart rate experiment scheme and implemented it for the process of the 100 m run with two parameters given simultaneously. The experiment shows that the concentration of the oxygen hemoglobin in the muscle tissue continues decreasing after the end of the 100 m run, and the time interval between the moment when the concentration of the oxygen hemoglobin attains the minimum value and the moment when the athletes finish the 100 m run is (6.65 +/- 1.10) sec; while the heart rate continues increasing after the end of the 100 m run, and the time interval between the moment when the heart rate attains the maximum value and the moment when the athletes finish the 100 m run is (8.00 +/- 1.57) sec. The results show that the two wavelength near-infrared tissue oxygenation detection technology and the sports heart rate real time collection equipment can accurately measure the sports tissue oxygenation and the heart rate in the extreme intensity sport, and reveal the process of muscle oxygen transportation and consumption and its dynamic character with the heart rate in the extreme intensity sport.

  6. Transverse water relaxation in whole blood and erythrocytes at 3T, 7T, 9.4T, 11.7T and 16.4T; determination of intracellular hemoglobin and extracellular albumin relaxivities.

    Science.gov (United States)

    Grgac, Ksenija; Li, Wenbo; Huang, Alan; Qin, Qin; van Zijl, Peter C M

    2017-05-01

    Blood is a physiological substance with multiple water compartments, which contain water-binding proteins such as hemoglobin in erythrocytes and albumin in plasma. Knowing the water transverse (R 2 ) relaxation rates from these different blood compartments is a prerequisite for quantifying the blood oxygenation level-dependent (BOLD) effect. Here, we report the Carr-Purcell-Meiboom-Gill (CPMG) based transverse (R 2CPMG ) relaxation rates of water in bovine blood samples circulated in a perfusion system at physiological temperature in order to mimic blood perfusion in humans. R 2CPMG values of blood plasma, lysed packed erythrocytes, lysed plasma/erythrocyte mixtures, and whole blood at 3 T, 7 T, 9.4 T, 11.7 T and 16.4 T were measured as a function of hematocrit or hemoglobin concentration, oxygenation, and CPMG inter-echo spacing (τ cp ). R 2CPMG in lysed cells showed a small τ cp dependence, attributed to the water exchange rate between free and hemoglobin-bound water to be much faster than τ cp . This was contrary to the tangential dependence in whole blood, where a much slower exchange between cells and blood plasma applies. Whole blood data were fitted as a function of τ cp using a general tangential correlation time model applicable for exchange as well as diffusion contributions to R 2CPMG , and the intercept R 20blood at infinitely short τ cp was determined. The R 20blood values at different hematocrit and the R 2CPMG values of lysed erythrocyte/plasma mixtures at different hemoglobin concentration were used to determine the relaxivity of hemoglobin inside the erythrocyte (r 2Hb ) and albumin (r 2Alb ) in plasma. The r 2Hb values obtained from lysed erythrocytes and whole blood were comparable at full oxygenation. However, while r 2Hb determined from lysed cells showed a linear dependence on oxygenation, this dependence became quadratic in whole blood. This possibly suggests an additional relaxation effect inside intact cells, perhaps due to hemoglobin

  7. Hemoglobin levels in normal Filipino pregnant women.

    Science.gov (United States)

    Kuizon, M D; Natera, M G; Ancheta, L P; Platon, T P; Reyes, G D; Macapinlac, M P

    1981-09-01

    The hemoglobin concentrations during pregnancy in Filipinos belonging to the upper income group, who were prescribed 105 mg elemental iron daily, and who had acceptable levels of transferrin saturation, were examined in an attempt to define normal levels. The hemoglobin concentrations for each trimester followed a Gaussian distribution. The hemoglobin values equal to the mean minus one standard deviation were 11.4 gm/dl for the first trimester and 10.4 gm/dl for the second and third trimesters. Using these values as the lower limits of normal, in one group of pregnant women the prevalence of anemia during the last two trimesters was found lower than that obtained when WHO levels for normal were used. Groups of women with hemoglobin of 10.4 to 10.9 gm/dl (classified anemic by WHO criteria but normal in the present study) and those with 11.0 gm/dl and above could not be distinguished on the basis of their serum ferritin levels nor on the degree of decrease in their hemoglobin concentration during pregnancy. Many subjects in both groups, however, had serum ferritin levels less than 12 ng/ml which indicate poor iron stores. It might be desirable in future studies to determine the hemoglobin cut-off point that will delineate subjects who are both non-anemic and adequate in iron stores using serum ferritin levels as criterion for the latter.

  8. Hepatically-metabolized and -excreted artificial oxygen carrier, hemoglobin vesicles, can be safely used under conditions of hepatic impairment

    International Nuclear Information System (INIS)

    Taguchi, Kazuaki; Miyasato, Mayumi; Ujihira, Hayato; Watanabe, Hiroshi; Kadowaki, Daisuke; Sakai, Hiromi; Tsuchida, Eishun; Horinouchi, Hirohisa; Kobayashi, Koichi; Maruyama, Toru; Otagiri, Masaki

    2010-01-01

    The hemoglobin vesicle (HbV) is an artificial oxygen carrier in which a concentrated Hb solution is encapsulated in lipid vesicles. Our previous studies demonstrated that HbV is metabolized by the mononuclear phagocyte system, and the lipid components are excreted from the liver. It is well-known that many hepatically-metabolized and -excreted drugs show altered pharmaceutics under conditions of liver impairment, which results in adverse effects. The aim of this study was to determine whether the administration of HbV causes toxicity in rats with carbon tetrachloride induced liver cirrhosis. Changes in plasma biochemical parameters, histological staining and the pharmacokinetic distribution of HbV were evaluated after an HbV injection of the above model rats at a putative clinical dose (1400 mgHb/kg). Plasma biochemical parameters were not significantly affected, except for a transient elevation of lipase, lipid components and bilirubin, which recovered within 14 days after an HbV infusion. Negligible morphological changes were observed in the kidney, liver, spleen, lung and heart. Hemosiderin, a marker of iron accumulation in organs, was observed in the liver and spleen up to 14 days after HbV treatment, but no evidence of oxidative stress in the plasma and liver were observed. HbV is mainly distributed in the liver and spleen, and the lipid components are excreted into feces within 7 days. In conclusion, even under conditions of hepatic cirrhosis, HbV and its components exhibit the favorable metabolic and excretion profile at the putative clinical dose. These findings provide further support for the safety and effectiveness of HbV in clinical settings.

  9. The influence of systemic hemodynamics and oxygen transport on cerebral oxygen saturation in neonates after the Norwood procedure.

    Science.gov (United States)

    Li, Jia; Zhang, Gencheng; Holtby, Helen; Guerguerian, Anne-Marie; Cai, Sally; Humpl, Tilman; Caldarone, Christopher A; Redington, Andrew N; Van Arsdell, Glen S

    2008-01-01

    Ischemic brain injury is an important morbidity in neonates after the Norwood procedure. Its relationship to systemic hemodynamic oxygen transport is poorly understood. Sixteen neonates undergoing the Norwood procedure were studied. Continuous cerebral oxygen saturation was measured by near-infrared spectroscopy. Continuous oxygen consumption was measured by respiratory mass spectrometry. Pulmonary and systemic blood flow, systemic vascular resistance, oxygen delivery, and oxygen extraction ratio were derived with measurements of arterial, and superior vena cava and pulmonary venous gases and pressures at 2- to 4-hour intervals during the first 72 hours in the intensive care unit. Mean cerebral oxygen saturation was 66% +/- 12% before the operation, reduced to 51% +/- 13% on arrival in the intensive care unit, and remained low during the first 8 hours; it increased to 56% +/- 9% at 72 hours, still significantly lower than the preoperative level (P blood flow and oxygen delivery (P blood flow (P = .001) and hemoglobin (P = .02) and negatively correlated with systemic vascular resistance (P = .003). It was not correlated with oxygen consumption (P > .05). Cerebral oxygen saturation decreased significantly in neonates during the early postoperative period after the Norwood procedure and was significantly influenced by systemic hemodynamic and metabolic events. As such, hemodynamic interventions to modify systemic oxygen transport may provide further opportunities to reduce the risk of cerebral ischemia and improve neurodevelopmental outcomes.

  10. Etude de la relation entre la consommation maximale d'oxygene et ...

    African Journals Online (AJOL)

    Thus the limiting factors are variously attributed to the cardiac output, to muscle movement, hemoglobin, metabolism and muscle activity. ... Three protocols measurements of maximum oxygen consumption were made, two different protocols for the year with a member less than 50 revolutions per minute (1P50) and 100 ...

  11. Spatio-temporal imaging of the hemoglobin in the compressed breast with diffuse optical tomography

    Science.gov (United States)

    Boverman, Gregory; Fang, Qianqian; Carp, Stefan A.; Miller, Eric L.; Brooks, Dana H.; Selb, Juliette; Moore, Richard H.; Kopans, Daniel B.; Boas, David A.

    2007-07-01

    We develop algorithms for imaging the time-varying optical absorption within the breast given diffuse optical tomographic data collected over a time span that is long compared to the dynamics of the medium. Multispectral measurements allow for the determination of the time-varying total hemoglobin concentration and of oxygen saturation. To facilitate the image reconstruction, we decompose the hemodynamics in time into a linear combination of spatio-temporal basis functions, the coefficients of which are estimated using all of the data simultaneously, making use of a Newton-based nonlinear optimization algorithm. The solution of the extremely large least-squares problem which arises in computing the Newton update is obtained iteratively using the LSQR algorithm. A Laplacian spatial regularization operator is applied, and, in addition, we make use of temporal regularization which tends to encourage similarity between the images of the spatio-temporal coefficients. Results are shown for an extensive simulation, in which we are able to image and quantify localized changes in both total hemoglobin concentration and oxygen saturation. Finally, a breast compression study has been performed for a normal breast cancer screening subject, using an instrument which allows for highly accurate co-registration of multispectral diffuse optical measurements with an x-ray tomosynthesis image of the breast. We are able to quantify the global return of blood to the breast following compression, and, in addition, localized changes are observed which correspond to the glandular region of the breast.

  12. Determining total hemoglobin mass by means of {sup 13}CO breath analysis

    Energy Technology Data Exchange (ETDEWEB)

    Sowa, Marcus; Hering, Peter [Institut fuer Lasermedizin, Universitaetsklinikum Duesseldorf (Germany)

    2010-07-01

    The aim of our investigations is the development of a non-invasive method for the determination of the total hemoglobin mass in the human body by means of Cavity Leak-Out Spectroscopy (CALOS). The mentioned CALOS system utilizes a CO gas laser in the mid infrared region around 5{mu}m. This system allows isotopologue selective online measurements of {sup 13}CO with a sensitivity of 7 ppb.Hz{sup -1/2}. {sup 13}CO is a non radioactive isotopologue occurring in a ratio of about 1.1 % of the natural CO composition. CO is commonly known as a highly toxic gas but it is also endogenously produced during heme degradation. About 80 % of this CO is exhaled yielding to CO concentrations between 1 ppm to 4 ppm in healthy humans. Transportation of CO through the body is established by hemoglobin which has a high affinity towards CO. Because of this fact inhaled CO is taken up by the blood until equilibrium between the alveolar air and the blood is reached. By determining the exhaled CO concentrations before and after the inhalation of a certain amount of CO a measure for the t-Hb mass can be calculated. The enormous advantage of the isotopologue measurement is the very small amount of {sup 13}CO which can be used for harmless CO inhalation. All data necessary for calculating the t-Hb mass are obtained from breath measurements making this method non invasive.

  13. Heterozygote Hemoglobin G-Coushatta as the Cause of a Falsely Decreased Hemoglobin A1C in an Ion-Exchange HPLC Method

    Directory of Open Access Journals (Sweden)

    Kurtoğlu Ayşegül Uğur

    2017-09-01

    Full Text Available Glycated hemoglobin (HbA1c is used for the assessment of glycemic control in patients with diabetes. The presence of genetic variants of hemoglobin can profoundly affect the accuracy of HbA1c measurement. Here, we report two cases of Hemoglobin G-Coushatta (HBB:c.68A>C variant that interferes in the measurement of HbA1c by a cation-exchange HPLC (CE-HPLC method. HbA1c was measured by a CE-HPLC method in a Tosoh HLC-723 G7 instrument. The HbA1c levels were 2.9% and 4%. These results alerted us to a possible presence of hemoglobinopathy. In the hemoglobin variant analysis, HbA2 levels were detected as 78.3% and 40.7% by HPLC using the short program for the Biorad Variant II. HbA1c levels were measured by an immunoturbidimetric assay in a Siemens Dimension instrument. HbA1c levels were reported as 5.5% and 5.3%. DNA mutation analysis was performed to detect the abnormal hemoglobin variant. Presence of Hemoglobin G-Coushatta variant was detected in the patients. The Hb G-Coushatta variants have an impact on the determination of glycated hemoglobin levels using CEHPLC resulting in a false low value. Therefore, it is necessary to use another measurement method.

  14. Preparation and in vivo evaluation of two bovine hemoglobin-based plasma expanders

    International Nuclear Information System (INIS)

    Sheffield, C.L.; DeLoach, J.R.

    1990-01-01

    A hemoglobin (Hb)-based oxygen carrier was successfully transfused into rats. An ultrapure lipid-free bovine Hb was prepared by hypotonic dialysis and ultrafiltration. The Hb was polymerized with glutaraldehyde and the P50 was 24.3 mm Hg. On the basis of immunological analysis, immuno blot, the Hb preparations were not antigenic. A second transfusion produced no adverse immunological side effects. A right shift in P50 was obtained by further treatment of polymerized Hb with inositol hexaphosphate; however, this Hb preparation was unsuitable for transfusion as all animals died within a few minutes. A 30% exchange transfusion in rats with the polymerized bovine Hb resulted in a 100% survival of all animals. P50 values of treated animals were reduced by about 2 mm Hg for 14 days. The Hb product circulated for 14 days as determined by 51 Cr labeling. Ultrapure bovine Hb has the potential to circulate and carry oxygen in rats and causes no immunological side effects

  15. Monitoring of blood oxygenation in brain by resonance Raman spectroscopy

    DEFF Research Database (Denmark)

    Brazhe, Nadezda A; Thomsen, Kirsten; Lønstrup, Micael

    2018-01-01

    Blood oxygenation in cerebral vessels is an essential parameter to evaluate brain function and to investigate the coupling between local blood flow and neuronal activity. We apply resonance Raman spectroscopy in vivo to study hemoglobin oxygenation in cortex vessels of anesthetized ventilated mice....... We demonstrate that the pairs of Raman peaks at 1355 and1375 cm-1(symmetric vibrations of pyrrol half-rings in the heme molecule), 1552 and 1585 cm-1and 1602 and 1638 cm-1(vibrations of methine bridges in heme molecule) are reliable markers for quantitative estimation of the relative amount...

  16. Quantification of extra-cerebral and cerebral hemoglobin concentrations during physical exercise using time-domain near infrared spectroscopy

    OpenAIRE

    Auger, Héloïse; Bherer, Louis; Boucher, Étienne; Hoge, Richard; Lesage, Frédéric; Dehaes, Mathieu

    2016-01-01

    Fitness is known to have beneficial effects on brain anatomy and function. However, the understanding of mechanisms underlying immediate and long-term neurophysiological changes due to exercise is currently incomplete due to the lack of tools to investigate brain function during physical activity. In this study, we used time-domain near infrared spectroscopy (TD-NIRS) to quantify and discriminate extra-cerebral and cerebral hemoglobin concentrations and oxygen saturation (SO2) in young adults...

  17. Individualized anemia management reduces hemoglobin variability in hemodialysis patients.

    Science.gov (United States)

    Gaweda, Adam E; Aronoff, George R; Jacobs, Alfred A; Rai, Shesh N; Brier, Michael E

    2014-01-01

    One-size-fits-all protocol-based approaches to anemia management with erythropoiesis-stimulating agents (ESAs) may result in undesired patterns of hemoglobin variability. In this single-center, double-blind, randomized controlled trial, we tested the hypothesis that individualized dosing of ESA improves hemoglobin variability over a standard population-based approach. We enrolled 62 hemodialysis patients and followed them over a 12-month period. Patients were randomly assigned to receive ESA doses guided by the Smart Anemia Manager algorithm (treatment) or by a standard protocol (control). Dose recommendations, performed on a monthly basis, were validated by an expert physician anemia manager. The primary outcome was the percentage of hemoglobin concentrations between 10 and 12 g/dl over the follow-up period. A total of 258 of 356 (72.5%) hemoglobin concentrations were between 10 and 12 g/dl in the treatment group, compared with 208 of 336 (61.9%) in the control group; 42 (11.8%) hemoglobin concentrations were hemoglobin concentrations were >12 g/dl in the treatment group compared with 46 (13.4%) in the control group. The median ESA dosage per patient was 2000 IU/wk in both groups. Five participants received 6 transfusions (21 U) in the treatment group, compared with 8 participants and 13 transfusions (31 U) in the control group. These results suggest that individualized ESA dosing decreases total hemoglobin variability compared with a population protocol-based approach. As hemoglobin levels are declining in hemodialysis patients, decreasing hemoglobin variability may help reduce the risk of transfusions in this population.

  18. Proton nuclear magnetic resonance study of the ferrous derivatives of the dimeric and tetrameric hemoglobin from the mollusc Scapharca inaequivalvis

    International Nuclear Information System (INIS)

    Inubushi, Toshiero; Yonetani, Takahashi; Chiancone, E.; Univ. 'La Sapienza', Rome

    1988-01-01

    Proton NMR spectra have been measured for the two hemoglobins from the mollusc Scapharca inaequivalvis: HbI, a homodimer, and HbII, a heterotetramer. These hemoglobins are endowed with a unique subunit assembly, since the heme carrying E and F helices are involved in the major intersubunit contact. In the far-downfield region of hyperfine-shifted resonances the spectra of HbI and HbII in the deoxy state show respectively one (66.7 ppm) and two (67.8 and 63.6 ppm) exchangeable signals of the proximal histidine N/sub delta/H groups, the resonance position being indicative of a significant strain in the iron-imidazole interaction. In the hydrogen-bonded proton region, inter-and intrasubunit hydrogen-bonded proton signals have been detected for both hemoglobins. Deoxy-HbI shows two unique downfied resonances at 11.83 and 11.51 ppm which disappear in the oxygenated state, suggesting that the corresponding hydrogen bonds are iinvolved in the stabilization of the tertiary and/or quaternary structure of the deoxy form. HbII shows even smaller changes in this region upon changes in ligation state. These results therefore provide further proof that, at variance with the vertebrate hemoglobin tetramer, the unique subunit assembly of these proteins is stabilized mainly by hydrophobic interactions

  19. RSR13 e modificação alostérica da afinidade hemoglobina-oxigênio: abuso entre atletas RSR13 and allosteric change in the hemoglobin-oxygen afinity: abuse among athletes

    Directory of Open Access Journals (Sweden)

    Antonio Claudio Lucas da Nóbrega

    2002-02-01

    Full Text Available O ácido metilpropiônico (RSR13 é um modificador alostérico da hemoglobina, com a qual se liga de forma não-covalente, diminuindo sua afinidade pelo oxigênio de modo dose-dependente e, conseqüentemente, aumentando a oxigenação periférica. O objetivo deste artigo é apresentar brevemente as evidências científicas acerca das características farmacológicas e funcionais, indicações médicas e efeitos adversos do uso do RSR13 por atletas, a mais recente alternativa de aumento artificial do desempenho. Estudos experimentais preliminares verificaram algum efeito positivo do RSR13 sobre a recuperação do miocárdio isquêmico e sobre a extensão da isquemia cerebral, mas as principais indicações estudadas atualmente são a cirurgia com hipotermia e cardioplegia durante circulação extracorpórea e o uso como agente coadjuvante potenciador da radioterapia para certos tumores sólidos. Somente um estudo em modelo canino mostrou aumento do consumo máximo de oxigênio em músculo isolado, não existindo evidências de que o RSR13 possa efetivamente melhorar o desempenho em humanos. Em realidade, já foram descritos efeitos adversos, como diminuição da perfusão sanguínea, elevação da pressão arterial e diminuição da função renal. Antecipando o potencial aumento da utilização do RSR13 por atletas, métodos já foram desenvolvidos para sua detecção em amostras de urina humana.Methylpropionic acid (RSR13 is an allosteric hemoglobin modifier to which it binds in a non-covalent manner, reducing its affinity to oxygen in a dose-dependent fashion, and consequently, increasing peripheral oxygenation. The purpose of this article is to briefly present scientific evidence concerning pharmacological and functional characteristics, medical indications, and adverse effects of RSR13 use by athletes, the most recent alternative to enhance performance artificially. Preliminary experimental studies have verified some positive effect of RSR13

  20. Dynamic Factors Affecting Gaseous Ligand Binding in an Artificial Oxygen Transport Protein‡

    Science.gov (United States)

    Zhang, Lei; Andersen, Eskil M.E.; Khajo, Abdelahad; Magliozzo, Richard S.; Koder, Ronald L.

    2013-01-01

    We report the functional analysis of an artificial hexacoordinate oxygen transport protein, HP7, which operates via a mechanism similar to that of human neuroglobin and cytoglobin: the destabilization of one of two heme-ligating histidine residues. In the case of HP7 this is the result of the coupling of histidine side chain ligation with the burial of three charged glutamate residues on the same helix. Here we compare gaseous ligand binding, including rates, affinities and oxyferrous state lifetimes, of both heme binding sites in HP7. We find that despite the identical sequence of helices in both binding sites, there are differences in oxygen affinity and oxyferrous state lifetime which may be the result of differences in the freedom of motion imposed by the candelabra fold on the two sites of the protein. We further examine the effect of mutational removal of the buried glutamates on function. Heme iron in the ferrous state of this mutant is rapidly oxidized when when exposed to oxygen. Compared to HP7, distal histidine affinity is increased by a 22-fold decrease in the histidine ligand off-rate. EPR comparison of these ferric hemoproteins demonstrates that the mutation increases disorder at the heme binding site. NMR-detected deuterium exchange demonstrates that the mutation greatly increases water penetration into the protein core. The inability of the mutant protein to bind oxygen may be due to increased water penetration, the large decrease in binding rate caused by the increase in distal histidine affinity, or a combination of the two factors. Together these data underline the importance of the control of protein dynamics in the design of functional artificial proteins. PMID:23249163

  1. RAPID MULTICOMPONENT ANALYSIS OF HEMOGLOBIN DERIVATIVES FOR CONTROLLED ANTIDOTAL USE OF METHEMOGLOBIN-FORMING AGENTS IN CYANIDE POISONING

    NARCIS (Netherlands)

    ZIJLSTRA, WG

    When cyanide poisoning is treated with a methemoglobin-forming agent, oxidative metabolism is protected at the expense of the oxygen capacity of the blood.The affinity of methemoglobin for CN- is high enough to compete with cytochrome oxidase, which protects the latter from becoming blocked, but all

  2. Porphyromonas endodontalis binds, reduces and grows on human hemoglobin.

    Science.gov (United States)

    Zerr, M; Drake, D; Johnson, W; Cox, C D

    2001-08-01

    Porphyromonas endodontalis is a black-pigmented, obligate anaerobic rod-shaped bacterium implicated as playing a major role in endodontic infections. We have previously shown that P. endodontalis requires the porphyrin nucleus, preferably supplied as hemoglobin, as a growth supplement. The bacteria also actively transport free iron, although this activity does not support growth in the absence of a porphyrin source. The purpose of this study was to further investigate the binding and subsequent utilization of human hemoglobin by P. endodontalis. P. endodontalis binds hemoglobin and reduces the Fe(III) porphyrin, resulting in a steady accumulation of ferrous hemoglobin. Reduction of methemoglobin was similar to the extracellular reduction of nitrobluetetrazolium in the presence of oxidizable substrate. Turbidimetric and viable cell determinations showed that P. endodontalis grew when supplied only hemoglobin. Therefore, we conclude that hemoglobin appears to serve as a sole carbon and nitrogen source, and that these bacteria reduce extracellular compounds at the expense of oxidized substrates.

  3. Post-transfusion hemoglobin values and patient blood management

    DEFF Research Database (Denmark)

    Moerman, Jan; Vermeulen, Edith; Van Mullem, Mia

    2018-01-01

    Objectives: The objective of this retrospective study was to evaluate the added value of communicating post-transfusion hemoglobin values to clinicians as a strategy to improve RBC utilization in a 500-bed hospital. Methods: The total number of RBC transfusions, the mean number of RBC units...... transfused per patient, the mean pre- and post-transfusion hemoglobin values, the ratio of patients transfused and the ratio of patients with a post-transfusion hemoglobin > 10.5 g/dL were calculated per service and per department for six months. The data were reported to each service and compared...... with the data of the department as peer group. The impact of this communication strategy was evaluated in the following six months. Results: In the six months pre-intervention, the mean post-transfusion hemoglobin value was 9.2 g/dL. Post-transfusion hemoglobin was > 10.5 g/dL in 13.4% of patients (112...

  4. Hirota's solitons in the affine and the conformal affine Toda models

    International Nuclear Information System (INIS)

    Aratyn, H.; Constantinidis, C.P.; Ferreira, L.A.; Gomes, J.F.; Zimerman, A.H.

    1993-01-01

    We use Hirota's method formulated as a recursive scheme to construct a complete set of soliton solutions for the affine Toda field theory based on an arbitrary Lie algebra. Our solutions include a new class of solitons connected with two different types of degeneracies encountered in Hirota's perturbation approach. We also derive an universal mass formula for all Hirota's solutions to the affine Toda model valid for all underlying Lie groups. Embedding of the affine Toda model in the conformal affine Toda model plays a crucial role in this analysis. (orig.)

  5. Cation modulation of hemoglobin interaction with sodium n-dodecyl sulphate (SDS iv: magnesium modulation at pH 7.20

    Directory of Open Access Journals (Sweden)

    Ali Akbar Moosavi-Movahedi

    2016-03-01

    Full Text Available We investigate the interaction of Mg2+ (0–2.30 mM and sodium n-dodecyl sulfate (SDS with hemoglobins (Hbs A and S at pH 7.20. SDS was used to model both membranes (0.60 mM SDS and proteases (5.0 mM SDS. Via UV-visible spectroscopy, second derivative and difference second derivative spectroscopy, we interrogated for difference(s in the interaction of these ligands with the proteins that can account for the HbS resistance to malaria parasite while been prone to sickling. Our results show that Mg2+ interaction with the proteins lowered the HbS oxygen affinity in comparison with the HbA. Additionally, [SDS]-protein interactions resulted in oxoferryl heme species formation that was prominent for the HbA and highly diminished for the HbS. [Mg2+] introduction to the [SDS]-protein mixture, however decreased the concentration of denatured protein species. The [Mg2+]-[SDS]-protein interactions suggest that while ionic or coulomb interactions for the HbA, in the presence of the surfactants, are [Mg2+] dependent, those of the HbS are not. Furthermore, hydrophobicity is a crucial force for the HbS interaction at neutral pH and is little-masked by ionic, electrostatic or coulombic interactions. In conclusion, at physiological pH, the Mg-SDS interaction decreased the HbS denaturation in comparison to the HbA.

  6. The solutions of affine and conformal affine Toda field theory

    International Nuclear Information System (INIS)

    Papadopoulos, G.; Spence, B.

    1994-02-01

    We give new formulations of the solutions of the field equations of the affine Toda and conformal affine Toda theories on a cylinder and two-dimensional Minkowski space-time. These solutions are parameterised in terms of initial data and the resulting covariant phase spaces are diffeomorphic to the Hamiltonian ones. We derive the fundamental Poisson brackets of the parameters of the solutions and give the general static solutions for the affine theory. (authors). 10 refs

  7. Retinopathy of prematurity and induced changes in arterial oxygen saturation with near infrared spectrophotometry: a retrospective cohort study

    Science.gov (United States)

    von Siebenthal, K.; Keel, M.; Dietz, V.; Fauchere, J. C.; Martin, X.; Wolf, Martin; Duc, G.; Bucher, H. U.

    1996-10-01

    Near-infrared spectrophotometry (NIRS) is a noninvasive method for measuring oxygenated and deoxygenated hemoglobin in the neonatal brain. Using oxygen as a tracer, it is possible to calculate cerebral blood flow (cbf) and hemoglobin concentration (cHbc), which corresponds to cerebral blood volume, by inducing small changes in arterial oxygen saturation. Variability of tcpO2 is considered to be associated with severe retinopathy of prematurity (ROP). A preliminary analysis without control found a 51 percent incidence of ROP in infants subjected to NIRS measurements whereas among infants who were not exposed to oxygen changes, only 29 percent developed ROP. A controlled study with matched pairs was performed. Thirty-nine premature newborns who had received NIRS recordings were matched with 39 out of 172 infants who had not received NIRS. Using this controlled study design there was no difference in the incidence and severity of ROP between the two groups. The conclusions are that: 1) small changes in oxygen saturation of 3 to 10 percent to measure cbf and cHbc did not increase the incidence or the degree of severity of ROP. 2) A controlled study design is important. Analyses of uncontrolled data would have led to the conclusion that oxygen changes as used with NIRS increase the risk of ROP.

  8. Biphasic oxidation of oxy-hemoglobin in bloodstains

    NARCIS (Netherlands)

    Bremmer, Rolf H.; de Bruin, Daniel M.; de Joode, Maarten; Buma, Wybren Jan; van Leeuwen, Ton G.; Aalders, Maurice C. G.

    2011-01-01

    In forensic science, age determination of bloodstains can be crucial in reconstructing crimes. Upon exiting the body, bloodstains transit from bright red to dark brown, which is attributed to oxidation of oxy-hemoglobin (HbO(2)) to met-hemoglobin (met-Hb) and hemichrome (HC). The fractions of

  9. Biphasic Oxidation of Oxy-Hemoglobin in Bloodstains

    NARCIS (Netherlands)

    Bremmer, R.H.; de Bruin, D.M.; de Joode, M.; Buma, W.J.; van Leeuwen, T.G.; Aalders, M.C.G.

    2011-01-01

    Background In forensic science, age determination of bloodstains can be crucial in reconstructing crimes. Upon exiting the body, bloodstains transit from bright red to dark brown, which is attributed to oxidation of oxy-hemoglobin (HbO2) to met-hemoglobin (met-Hb) and hemichrome (HC). The fractions

  10. Lectin affinity electrophoresis.

    Science.gov (United States)

    Kobayashi, Yuka

    2014-01-01

    An interaction or a binding event typically changes the electrophoretic properties of a molecule. Affinity electrophoresis methods detect changes in the electrophoretic pattern of molecules (mainly macromolecules) that occur as a result of biospecific interactions or complex formation. Lectin affinity electrophoresis is a very effective method for the detection and analysis of trace amounts of glycobiological substances. It is particularly useful for isolating and separating the glycoisomers of target molecules. Here, we describe a sensitive technique for the detection of glycoproteins separated by agarose gel-lectin affinity electrophoresis that uses antibody-affinity blotting. The technique is tested using α-fetoprotein with lectin (Lens culinaris agglutinin and Phaseolus vulgaris agglutinin)-agarose gels.

  11. Kadar Hemoglobin dan Kecerdasan Intelektual Anak

    Directory of Open Access Journals (Sweden)

    Yuni Kusmiyati

    2013-10-01

    Full Text Available Kualitas sumber daya manusia dipengaruhi oleh inteligensi anak. Skor kecerdasan intelektual yang tidak menetap pada usia tertentu dapat berubah karena faktor genetik, gizi, dan lingkungan. Tujuan penelitian ini adalah mengetahui hubungan kadar hemoglobin dengan kecerdasan intelektual anak. Penelitian observasional dengan desain potong lintang ini dilakukan pada populasi siswa kelas VI Sekolah Dasar Negeri Giwangan Yogyakarta, tahun 2013. Penarikan sampel dilakukan dengan metode simple random sampling terhadap 37 sampel siswa. Instrumen untuk mengukur kecerdasan intelektual dengan Cultural Fair Intelligence Quotient Test yang dirancang untuk meminimalkan pengaruh kultural dengan memperhatikan prosedur evaluasi, instruksi, konten isi, dan respons peserta. Tes dilakukan oleh Biro Psikologi Universitas Ahmad Dahlan Yogyakarta, kadar hemoglobin diukur menggunakan Portable Hemoglobin Digital Analyzer Easy Touch secara digital.Variabel luar indeks massa tubuh diukur langsung menggunakan parameter tinggi badan dan berat badan. Analisis menggunakan uji regresi linier. Hasil penelitian menunjukkan indeks massa tubuh tidak berhubungan dengan kecerdasan intelektual (nilai p = 0,052. Anemia berhubungan cukup dengan kecerdasan anak (r = 0,491 dan berpola positif, semakin tinggi kadar hemoglobin semakin tinggi kecerdasan intelektual anak. Nilai koefisien determinasi 0,241 menerangkan bahwa 24,1% variasi anemia cukup baik untuk menjelaskan variabel kecerdasan intelektual. Ada hubungan antara kadar hemoglobin dengan kecerdasan intelektual (nilai p = 0,002. Quality of human resources is influenced by the child’s intelligent. Intelligence Quotient (IQ score will not settle at a certain age and can change due to genetic factors, nutrition, and the environment. The objective is known relationship of anemia with IQ to child. Method of observational study with cross sectional design. Population are students of class VI elementary school of Giwangan Yogyakarta in

  12. Receptor targeting of hemoglobin mediated by the haptoglobins

    DEFF Research Database (Denmark)

    Nielsen, Marianne Jensby; Moestrup, Søren Kragh

    2009-01-01

    Haptoglobin, the haptoglobin-hemoglobin receptor CD163, and the heme oxygenase-1 are proteins with a well-established function in the clearance and metabolism of "free" hemoglobin released during intravascular hemolysis. This scavenging system counteracts the potentially harmful oxidative and NO......-scavenging effects associated with "free" hemoglobin, and, furthermore, elicits an anti-inflammatory response. In the late primate evolution, haptoglobin variants with distinct functions have arisen, including haptoglobin polymers and the haptoglobin-related protein. The latter associates with a subspecies of high......-density lipoprotein (HDL) particles playing a crucial role in the innate immunity against certain trypanosome parasites. Recent studies have elucidated this fairly sophisticated immune defense mechanism that takes advantage of a trypanosomal haptoglobin-hemoglobin receptor evolved to supply the parasite with heme...

  13. Evaluation of arterial oxygen saturation using RGB camera-based remote photoplethysmography

    Science.gov (United States)

    Nishidate, Izumi; Nakano, Kazuya; McDuff, Daniel; Niizeki, Kyuichi; Aizu, Yoshihisa; Haneishi, Hideaki

    2018-02-01

    Plethysmogram is the periodic variation in blood volume due to the cardiac pulse traveling through the body. Photo-plethysmograph (PPG) has been widely used to assess the cardiovascular system such as heart rate, blood pressure, cardiac output, vascular compliance. We have previously proposed a non-contact PPG imaging method using a digital red-green-blue camera. In the method, the Monte Carlo simulation for light transport is used to specify a relationship among the RGB-values and the concentrations of oxygenated hemoglobin (CHbO) and deoxygenated hemoglobin (CHbR). The total hemoglobin concentration (CHbT) can be calculated as a sum of CHbO and CHbR. Applying the fast Fourier transform (FFT) band pass filters to each pixel of the sequential images for CHbT along the time line, two-dimentional plethysmogram can be reconstructed. In this study, we further extend the method to imaging the arterial oxygen saturation (SaO2). The PPG signals for both CHbO and CHbR are extracted by the FFT band pass filter and the pulse wave amplitudes (PWAs) of CHbO and CHbR are calculated. We assume that the PWA for CHbO and that for CHbR are decreased and increased as SaO2 is decreased. The ratio of PWA for CHbO and that for CHbR are associated to the reference value of SaO2 measured by a commercially available pulse oximeter, which provide an empirical formula to estimate SaO2 from the PPG signal at each pixel of RGB image. In vivo animal experiments with rats during varying the fraction of inspired oxygen (FiO2) demonstrated the feasibility of the proposed method.

  14. Cell volume regulation in hemoglobin CC and AA erythrocytes

    International Nuclear Information System (INIS)

    Berkowitz, L.R.; Orringer, E.P.

    1987-01-01

    Swelling hemoglobin CC erythrocytes stimulates a ouabain-insensitive K flux that restores original cell volume. Studies were performed with the K analog, 86 Rb. This volume regulatory pathway was characterized for its anion dependence, sensitivity to loop diuretics, and requirement for Na. The swelling-induced K flux was eliminated if intracellular chloride was replaced by nitrate and both swelling-activated K influx and efflux were partially inhibited by 1 mM furosemide or bumetanide. K influx in swollen hemoglobin CC cells was not diminished when Na in the incubation medium was replaced with choline, indicating Na independence of the swelling-induced flux. Identical experiments with hemoglobin AA cells also demonstrated a swelling-induced increase in K flux, but the magnitude and duration of this increase were considerably less than that seen with hemoglobin CC cells. The increased K flux in hemoglobin AA cells was likewise sensitive to anion replacement and to loop diuretics and did not require the presence of Na. These data indicate that a volume-activated K pathway with similar transport characteristics exists in both hemoglobin CC and AA red cells

  15. Hemoglobin and heme scavenger receptors

    DEFF Research Database (Denmark)

    Nielsen, Marianne Jensby; Møller, Holger Jon; Moestrup, Søren Kragh

    2010-01-01

    Heme, the functional group of hemoglobin, myoglobin, and other hemoproteins, is a highly toxic substance when it appears in the extracellular milieu. To circumvent potential harmful effects of heme from hemoproteins released during physiological or pathological cell damage (such as hemolysis...... and rhabdomyolysis), specific high capacity scavenging systems have evolved in the mammalian organism. Two major systems, which essentially function in a similar way by means of a circulating latent plasma carrier protein that upon ligand binding is recognized by a receptor, are represented by a) the hemoglobin...

  16. Hyperbaric oxygen and radiotherapy

    International Nuclear Information System (INIS)

    Mayer, R.; Hamilton-Farrell, M.R.; Kleij, A.J. van der

    2005-01-01

    Background: Hyperbaric oxygen (HBO) therapy is the inhalation of 100% oxygen at a pressure of at least 1.5 atmospheres absolute (150 kPa). It uses oxygen as a drug by dissolving it in the plasma and delivering it to the tissues independent of hemoglobin. For a variety of organ systems, HBO is known to promote new vessel growth into areas with reduced oxygen tension due to poor vascularity, and therewith promotes wound healing and recovery of radiation-injured tissue. Furthermore, tumors may be sensitized to irradiation by raising intratumoral oxygen tensions. Methods: A network of hyperbaric facilities exists in Europe, and a number of clinical studies are ongoing. The intergovernmental framework COST B14 action 'Hyperbaric Oxygen Therapy' started in 1999. The main goal of the Working Group Oncology is preparation and actual implementation of prospective study protocols in the field of HBO and radiation oncology in Europe. Results: In this paper a short overview on HBO is given and the following randomized clinical studies are presented: (a) reirradiation of recurrent squamous cell carcinoma of the head and neck after HBO sensitization; (b) role of HBO in enhancing radiosensitivity on glioblastoma multiforme; (c) osseointegration in irradiated patients; adjunctive HBO to prevent implant failures; (d) the role of HBO in the treatment of late irradiation sequelae in the pelvic region. The two radiosensitization protocols (a, b) allow a time interval between HBO and subsequent irradiation of 10-20 min. Conclusion: Recruitment of centers and patients is being strongly encouraged, detailed information is given on www.oxynet.org. (orig.)

  17. 21 CFR 864.7455 - Fetal hemoglobin assay.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Fetal hemoglobin assay. 864.7455 Section 864.7455 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES HEMATOLOGY AND PATHOLOGY DEVICES Hematology Kits and Packages § 864.7455 Fetal hemoglobin...

  18. Molecularly imprinted photo-sensitive polyglutamic acid nanoparticles for electrochemical sensing of hemoglobin

    International Nuclear Information System (INIS)

    Zhang, Rongli; Xu, Sheng; Luo, Jing; Liu, Xiaoya

    2015-01-01

    A voltammetric sensor for hemoglobin (Hb) was prepared from molecularly imprinted polymer nanoparticles (MINPs) via electrophoretic deposition. A photo-sensitive copolymer composed of poly-γ-glutamic grafted with the fluorophore 7-amino-4-methylcoumarin was converted into nanoparticles that were imprinted with Hb. The resultant MINPs were then placed on a glassy carbon electrode (GCE) via electrophoretic deposition. Subsequent photo-crosslinking locks the recognition sites. The template was removed by extraction with a mixture of acetic acid and methanol at a ratio of 1:9 (v:v) to obtain a voltammetric sensor for Hb. The current response of the sensor at a working voltage of −260 mV is linearly related to the concentration of Hb in the range from 5 to 100 μg mL −1 , and recoveries range from 98.7 to 102.3 %. Compared to the respective non-imprinted nanoparticles, the sensor displays high recognition capability and affinity for Hb. (author)

  19. Dynamic factors affecting gaseous ligand binding in an artificial oxygen transport protein.

    Science.gov (United States)

    Zhang, Lei; Andersen, Eskil M E; Khajo, Abdelahad; Magliozzo, Richard S; Koder, Ronald L

    2013-01-22

    We report the functional analysis of an artificial hexacoordinate oxygen transport protein, HP7, which operates via a mechanism similar to that of human neuroglobin and cytoglobin: the destabilization of one of two heme-ligating histidine residues. In the case of HP7, this is the result of the coupling of histidine side chain ligation with the burial of three charged glutamate residues on the same helix. Here we compare gaseous ligand binding, including rates, affinities, and oxyferrous state lifetimes, of both heme binding sites in HP7. We find that despite the identical sequence of helices in both binding sites, there are differences in oxygen affinity and oxyferrous state lifetime that may be the result of differences in the freedom of motion imposed by the candelabra fold on the two sites of the protein. We further examine the effect of mutational removal of the buried glutamates on function. Heme iron in the ferrous state of this mutant is rapidly oxidized when exposed to oxygen. Compared to that of HP7, the distal histidine affinity is increased by a 22-fold decrease in the histidine ligand off rate. Electron paramagnetic resonance comparison of these ferric hemoproteins demonstrates that the mutation increases the level of disorder at the heme binding site. Nuclear magnetic resonance-detected deuterium exchange demonstrates that the mutation greatly increases the degree of penetration of water into the protein core. The inability of the mutant protein to bind oxygen may be due to an increased level of water penetration, the large decrease in binding rate caused by the increase in distal histidine affinity, or a combination of the two factors. Together, these data underline the importance of the control of protein dynamics in the design of functional artificial proteins.

  20. High-Dose Polymerized Hemoglobin Fails to Alleviate Cardiac Ischemia/Reperfusion Injury due to Induction of Oxidative Damage in Coronary Artery.

    Science.gov (United States)

    Yang, Qian; Wu, Wei; Li, Qian; Chen, Chan; Zhou, Ronghua; Qiu, Yanhua; Luo, Ming; Tan, Zhaoxia; Li, Shen; Chen, Gang; Zhou, Wentao; Liu, Jiaxin; Yang, Chengmin; Liu, Jin; Li, Tao

    2015-01-01

    Objective. Ischemia/reperfusion (I/R) injury is an unavoidable event for patients in cardiac surgery under cardiopulmonary bypass (CPB). This study was designed to investigate whether glutaraldehyde-polymerized human placenta hemoglobin (PolyPHb), a hemoglobin-based oxygen carrier (HBOC), can protect heart against CPB-induced I/R injury or not and to elucidate the underlying mechanism. Methods and Results. A standard dog CPB model with 2-hour cardiac arrest and 2-hour reperfusion was established. The results demonstrated that a low-dose PolyPHb (0.1%, w/v) provided a significant protection on the I/R heart, whereas the high-dose PolyPHb (3%, w/v) did not exhibit cardioprotective effect, as evidenced by the impaired cardiac function, decreased myocardial oxygen utilization, and elevated enzymes release and pathological changes. Further study indicated that exposure of isolated coronary arteries or human umbilical vein endothelial cells (HUVECs) to a high-dose PolyPHb caused impaired endothelium-dependent relaxation, which was companied with increased reactive oxygen species (ROS) production, reduced superoxide dismutase (SOD) activity, and elevated malonaldehyde (MDA) formation. Consistent with the increased oxidative stress, the NAD(P)H oxidase activity and subunits expression, including gp91(phox), p47(phox), p67(phox), and Nox1, were greatly upregulated. Conclusion. The high-dose PolyPHb fails to protect heart from CPB-induced I/R injury, which was due to overproduction of NAD(P)H oxidase-induced ROS and resultant endothelial dysfunction.

  1. High-Dose Polymerized Hemoglobin Fails to Alleviate Cardiac Ischemia/Reperfusion Injury due to Induction of Oxidative Damage in Coronary Artery

    Directory of Open Access Journals (Sweden)

    Qian Yang

    2015-01-01

    Full Text Available Objective. Ischemia/reperfusion (I/R injury is an unavoidable event for patients in cardiac surgery under cardiopulmonary bypass (CPB. This study was designed to investigate whether glutaraldehyde-polymerized human placenta hemoglobin (PolyPHb, a hemoglobin-based oxygen carrier (HBOC, can protect heart against CPB-induced I/R injury or not and to elucidate the underlying mechanism. Methods and Results. A standard dog CPB model with 2-hour cardiac arrest and 2-hour reperfusion was established. The results demonstrated that a low-dose PolyPHb (0.1%, w/v provided a significant protection on the I/R heart, whereas the high-dose PolyPHb (3%, w/v did not exhibit cardioprotective effect, as evidenced by the impaired cardiac function, decreased myocardial oxygen utilization, and elevated enzymes release and pathological changes. Further study indicated that exposure of isolated coronary arteries or human umbilical vein endothelial cells (HUVECs to a high-dose PolyPHb caused impaired endothelium-dependent relaxation, which was companied with increased reactive oxygen species (ROS production, reduced superoxide dismutase (SOD activity, and elevated malonaldehyde (MDA formation. Consistent with the increased oxidative stress, the NAD(PH oxidase activity and subunits expression, including gp91phox, p47phox, p67phox, and Nox1, were greatly upregulated. Conclusion. The high-dose PolyPHb fails to protect heart from CPB-induced I/R injury, which was due to overproduction of NAD(PH oxidase-induced ROS and resultant endothelial dysfunction.

  2. Lp-dual affine surface area

    Science.gov (United States)

    Wei, Wang; Binwu, He

    2008-12-01

    According to the notion of Lp-affine surface area by Lutwak, in this paper, we introduce the concept of Lp-dual affine surface area. Further, we establish the affine isoperimetric inequality and the Blaschke-Santaló inequality for Lp-dual affine surface area. Besides, the dual Brunn-Minkowski inequality for Lp-dual affine surface area is presented.

  3. Genomic organization and evolution of the Atlantic salmon hemoglobin repertoire

    Directory of Open Access Journals (Sweden)

    Phillips Ruth B

    2010-10-01

    Full Text Available Abstract Background The genomes of salmonids are considered pseudo-tetraploid undergoing reversion to a stable diploid state. Given the genome duplication and extensive biological data available for salmonids, they are excellent model organisms for studying comparative genomics, evolutionary processes, fates of duplicated genes and the genetic and physiological processes associated with complex behavioral phenotypes. The evolution of the tetrapod hemoglobin genes is well studied; however, little is known about the genomic organization and evolution of teleost hemoglobin genes, particularly those of salmonids. The Atlantic salmon serves as a representative salmonid species for genomics studies. Given the well documented role of hemoglobin in adaptation to varied environmental conditions as well as its use as a model protein for evolutionary analyses, an understanding of the genomic structure and organization of the Atlantic salmon α and β hemoglobin genes is of great interest. Results We identified four bacterial artificial chromosomes (BACs comprising two hemoglobin gene clusters spanning the entire α and β hemoglobin gene repertoire of the Atlantic salmon genome. Their chromosomal locations were established using fluorescence in situ hybridization (FISH analysis and linkage mapping, demonstrating that the two clusters are located on separate chromosomes. The BACs were sequenced and assembled into scaffolds, which were annotated for putatively functional and pseudogenized hemoglobin-like genes. This revealed that the tail-to-tail organization and alternating pattern of the α and β hemoglobin genes are well conserved in both clusters, as well as that the Atlantic salmon genome houses substantially more hemoglobin genes, including non-Bohr β globin genes, than the genomes of other teleosts that have been sequenced. Conclusions We suggest that the most parsimonious evolutionary path leading to the present organization of the Atlantic salmon

  4. Genomic organization and evolution of the Atlantic salmon hemoglobin repertoire

    Science.gov (United States)

    2010-01-01

    Background The genomes of salmonids are considered pseudo-tetraploid undergoing reversion to a stable diploid state. Given the genome duplication and extensive biological data available for salmonids, they are excellent model organisms for studying comparative genomics, evolutionary processes, fates of duplicated genes and the genetic and physiological processes associated with complex behavioral phenotypes. The evolution of the tetrapod hemoglobin genes is well studied; however, little is known about the genomic organization and evolution of teleost hemoglobin genes, particularly those of salmonids. The Atlantic salmon serves as a representative salmonid species for genomics studies. Given the well documented role of hemoglobin in adaptation to varied environmental conditions as well as its use as a model protein for evolutionary analyses, an understanding of the genomic structure and organization of the Atlantic salmon α and β hemoglobin genes is of great interest. Results We identified four bacterial artificial chromosomes (BACs) comprising two hemoglobin gene clusters spanning the entire α and β hemoglobin gene repertoire of the Atlantic salmon genome. Their chromosomal locations were established using fluorescence in situ hybridization (FISH) analysis and linkage mapping, demonstrating that the two clusters are located on separate chromosomes. The BACs were sequenced and assembled into scaffolds, which were annotated for putatively functional and pseudogenized hemoglobin-like genes. This revealed that the tail-to-tail organization and alternating pattern of the α and β hemoglobin genes are well conserved in both clusters, as well as that the Atlantic salmon genome houses substantially more hemoglobin genes, including non-Bohr β globin genes, than the genomes of other teleosts that have been sequenced. Conclusions We suggest that the most parsimonious evolutionary path leading to the present organization of the Atlantic salmon hemoglobin genes involves

  5. Absolute measurement of cerebral optical coefficients, hemoglobin concentration and oxygen saturation in old and young adults with near-infrared spectroscopy

    Science.gov (United States)

    We present near-infrared spectroscopy measurement of absolute cerebral hemoglobin concentration and saturation in a large sample of 36 healthy elderly (mean age, 85 ± 6 years) and 19 young adults (mean age, 28 ± 4 years). Non-invasive measurements were obtained on the forehead using a commercially a...

  6. Symbiotic and nonsymbiotic hemoglobin genes of Casuarina glauca

    DEFF Research Database (Denmark)

    Jacobsen-Lyon, K; Jensen, Erik Østergaard; Jørgensen, Jan-Elo

    1995-01-01

    Casuarina glauca has a gene encoding hemoglobin (cashb-nonsym). This gene is expressed in a number of plant tissues. Casuarina also has a second family of hemoglobin genes (cashb-sym) expressed at a high level in the nodules that Casuarina forms in a nitrogen-fixing symbiosis with the actinomycete...... of the Casuarina gene. The finding that the nonsymbiotic Casuarina gene is also correctly expressed in L. corniculatus suggests to us that a comparable non-symbiotic hemoglobin gene will be found in legume species. Udgivelsesdato: 1995-Feb...

  7. Identification of a haptoglobin-hemoglobin complex in the Alaskan Least Cisco (Coregonus sardinella).

    Science.gov (United States)

    Wahl, S M; Boger, J K; Michael, V; Duffy, L K

    1992-01-01

    The hemoglobin and a hemoglobin binding protein have been characterized in the Arctic fish (Coregonus sardinella). The evolutionary significance of the hemoglobin and plasma protein differences between fish and mammals is still unresolved. Blood samples from the Alaskan Least Cisco were separated into plasma and hemoglobin fractions and the proteins in these fractions were analyzed both by alkaline agarose gel electrophoresis, by isolelectric focusing, and by capillary electrophoresis. Staining the plasma proteins gels with o-dianisidine revealed hemoglobin containing protein complexes. A hemoglobin-containing band was observed in hemolyzed plasma which did not migrate with free hemoglobin, and is believed to be hemoglobin-haptoglobin complex. Size exclusion chromatography further characterized the hemoglobin as disassociating freely into dimers, and hemoglobin-haptoglobin complex having a molecular weight greater then 200,000 daltons.

  8. The effect of glycerol on regional cerebral blood flow, blood volume and oxygen metabolism

    International Nuclear Information System (INIS)

    Ishikawa, Masatsune; Kikuchi, Haruhiko; Nagata, Izumi; Yamagata, Sen; Taki, Waro; Kobayashi, Akira; Yonekura, Yoshiharu; Nishizawa, Sadahiko.

    1989-01-01

    Using positron emission tomography with 15 O-labelled CO 2 , O 2 and CO gases, the effects of glycerol on regional cerebral blood flow (CBF), blood volume (CBV) and oxygen metabolism (CMRO 2 ) were investigated in 6 patients with meningioma accompanying peritumoral brain edema. The same study was done in 5 normal volunteers. The changes of blood gases, hematocrit and hemoglobin were also examined. After a drip infusion of glycerol, the regional CBF increased not only in the peritumoral cortex and white matter but also in the intact cortex and white matter on the contralateral side. The increase of CBF was extensive and substantially there were no regional differences. In contrast, the changes of CMRO 2 were not significant. This was derived from the increase in oxygen extraction fraction throughout extensive areas including the peritumoral area. There were no changes in CBV. Hematocrit and hemoglobin decreased to a small degree. In the normal volunteers, the same findings were noted. Thus, glycerol increases the functional reserve for cerebral oxygen metabolism, not only in the peritumoral regions but also in the intact regions. The effects of glycerol on hemodynamics and metabolism were discussed with reference to some differences from mannitol. (author)

  9. Radiation - induced changes in the optical properties of hemoglobin molecule

    International Nuclear Information System (INIS)

    Selim, N.S; El-Marakby, S.M.

    2009-01-01

    Adult male albino rats were exposed to different doses of gamma radiation from Cs-137 source. Hemoglobin samples were analyzed 24 hrs after irradiation. The UV-visible spectrum of hemoglobin molecule was measured in the range 200 to 700 nm. The overall spectrum of the hemoglobin molecule showed hypochromicity that increased with dose increase. To investigate the effect of radiation on the hemoglobin molecule, different parameters of the spectrum were calculated: molar absorption coefficient, absorption cross section, transition dipole moment , dipole length, the optical energy gap and activation energy for each characteristic peak. The obtained results revealed that the radiation effect can induce rearrangement of the transition dipole moments and change molecular energy levels of the hemoglobin molecule

  10. Hemoglobin levels in persons with depressive and/or anxiety disorders

    NARCIS (Netherlands)

    Lever-van Milligen, Bianca A.; Vogelzangs, Nicole; Smit, Johannes H.; Penninx, Brenda W. J. H.

    Objective: Both low and high hemoglobin levels lead to more physical diseases, and both are linked to mortality. Low hemoglobin, often classified as anemia, has also been linked to more depressive symptoms, but whether both hemoglobin extremes are associated with depressive disorder and potentially

  11. Interactions of human hemoglobin with charged ligand-functionalized iron oxide nanoparticles and effect of counterions

    Energy Technology Data Exchange (ETDEWEB)

    Ghosh, Goutam, E-mail: ghoshg@yahoo.com [UGC-DAE Consortium for Scientific Research, Mumbai Centre (India); Panicker, Lata [Bhabha Atomic Research Centre, Solid State Physics Division (India)

    2014-12-15

    Human hemoglobin is an important metalloprotein. It has tetrameric structure with each subunit containing a ‘heme’ group which carries oxygen and carbon dioxide in blood. In this work, we have investigated the interactions of human hemoglobin (Hb) with charged ligand-functionalized iron oxide nanoparticles and the effect of counterions, in aqueous medium. Several techniques like DLS and ζ-potential measurements, UV–vis, fluorescence, and CD spectroscopy have been used to characterize the interaction. The nanoparticle size was measured to be in the range of 20–30 nm. Our results indicated the binding of Hb with both positively as well as negatively charged ligand-functionalized iron oxide nanoparticles in neutral aqueous medium which was driven by the electrostatic and the hydrophobic interactions. The electrostatic binding interaction was not seen in phosphate buffer at pH 7.4. We have also observed that the ‘heme’ groups of Hb remained unaffected on binding with charged nanoparticles, suggesting the utility of the charged ligand-functionalized nanoparticles in biomedical applications.

  12. Manipulation of hemoglobin expression affects Arabidopsis shoot organogenesis

    DEFF Research Database (Denmark)

    Wang, Yaping; Elhiti, Mohamed; Hebelstrup, Kim

    2011-01-01

    Over the past few years non-symbiotic plant hemoglobins have been described in a variety of plant species where they fulfill several functions ranging from detoxification processes to basic aspects of plant growth and post-embryonic development. To date no information is available on the role...... of hemoglobins during invitro morphogenesis. Shoot organogenesis was induced in Arabidopsis lines constitutively expressing class 1, 2 and 3 hemoglobins (GLB1, 2 and 3) and lines in which the respective genes were either downregulated by RNAi (GLB1) or knocked out (GLB2 and GLB3). The process was executed......, 15, and 16), feed-back repressors of the cytokinin pathway, was repressed in both hemoglobin over-expressors whereas that of several Type-B ARRs (ARR2, 12, and 13), transcription activators of cytokinin-responsive genes, was induced. Such changes enhanced the sensitivity of the root explants...

  13. [Importance of binding of 2,3-diphosphoglycerate and ATP to hemoglobin for erythrocyte glycolysis: activation by 2,3-diphosphoglycerate of hexokinase at intracellular conditions].

    Science.gov (United States)

    Geier, T; Glende, M; Reich, J G

    1978-01-01

    In a theoretical study the influence of hemoglobin and Mg-ions as binding partners of red cell 2,3-diphosphoglycerate and ATP was investigated. Free hemoglobin may be an efficient competitor of Mg2+ for the ligand ATP. At conditions which favour hemoglobin as binding partner (i.e. desoxygenation, low medium pH and incubation temperature, as in blood preservation) up to 95% of the whole cellular ATP (ca. 2mM in cell water) may be bound to hemoglobin (ca. 7 mM). This binding is largely prevented in the presence of physiological amounts of diphosphoglycerate (ca. 7 mM) which is in excess and has a higher binding affinity to hemoglobin. Therefore, diphosphoglycerate keeps ATP (MgATP) in cell water solution at conditions in which Hb would trop it in the presence of Mg2+ (ca. 3mM). It can be calculated that, by lack of free MgATP, the activity of hexokinase within the cell drops by a factor of greater than 10 when diphosphoglycerate is metabolized. This indirect activation by diphosphoglycerate of hexokinase is operative at free concentrations of DPG far below those which exert the well known excess inhibitory effect on hexokinase and phosphofructokinase. In a model study, the activation by diphosphoglycerate of the initial two-kinase stage was introduced into a simplified kinetic model of glycolysis. A pronounced hysteresis loop of the stationary concentrations of ATP and diphosphoglycerate was produced indicating the existence of several stationary states, one with high ATP and high diphosphoglycerate, the other one with low values. It is demonstrated that diphosphoglycerate, being a protector of glycolysis at physiological concentrations, triggers an autocatalytic breakdown of the energy state when permitted to drop to low values.

  14. Hemoglobin Values During Pregnancy | Leffler | Nigerian Medical ...

    African Journals Online (AJOL)

    It is known that the iron turnover in expectant mothers is up to three times that of an average adult. This is reflected in lower hemoglobin levels. The study showed that hemoglobin levels can be maintained by taking Bio-Strath®, provided that the patients' diet contains adequate fresh fruits and vegetables, whole grains, lean ...

  15. The repeated-bout effect: influence on biceps brachii oxygenation and myoelectrical activity.

    Science.gov (United States)

    Muthalib, Makii; Lee, Hoseong; Millet, Guillaume Y; Ferrari, Marco; Nosaka, Kazunori

    2011-05-01

    This study investigated biceps brachii oxygenation and myoelectrical activity during and following maximal eccentric exercise to better understand the repeated-bout effect. Ten men performed two bouts of eccentric exercise (ECC1, ECC2), consisting of 10 sets of 6 maximal lengthening contractions of the elbow flexors separated by 4 wk. Tissue oxygenation index minimum amplitude (TOI(min)), mean and maximum total hemoglobin volume by near-infrared spectroscopy, torque, and surface electromyography root mean square (EMG(RMS)) during exercise were compared between ECC1 and ECC2. Changes in maximal voluntary isometric contraction (MVC) torque, range of motion, plasma creatine kinase activity, muscle soreness, TOI(min), and EMG(RMS) during sustained (10-s) and 30-repeated isometric contraction tasks at 30% (same absolute force) and 100% MVC (same relative force) for 4 days postexercise were compared between ECC1 and ECC2. No significant differences between ECC1 and ECC2 were evident for changes in torque, TOI(min), mean total hemoglobin volume, maximum total hemoglobin volume, and EMG(RMS) during exercise. Smaller (P < 0.05) changes and faster recovery of muscle damage markers were evident following ECC2 than ECC1. During 30% MVC tasks, TOI(min) did not change, but EMG(RMS) increased 1-4 days following ECC1 and ECC2. During 100% MVC tasks, EMG(RMS) did not change, but torque and TOI(min) decreased 1-4 days following ECC1 and ECC2. TOI(min) during 100% MVC tasks and EMG(RMS) during 30% MVC tasks recovered faster (P < 0.05) following ECC2 than ECC1. We conclude that the repeated-bout effect cannot be explained by altered muscle activation or metabolic/hemodynamic changes, and the faster recovery in muscle oxygenation and activation was mainly due to faster recovery of force.

  16. On Atomistic Models for Molecular Oxygen

    DEFF Research Database (Denmark)

    Javanainen, Matti; Vattulainen, Ilpo; Monticelli, Luca

    2017-01-01

    Molecular oxygen (O2) is key to all life on earth, as it is constantly cycled via photosynthesis and cellular respiration. Substantial scientific effort has been devoted to understanding every part of this cycle. Classical molecular dynamics (MD) simulations have been used to study some of the key...... processes involved in cellular respiration: O2 permeation through alveolar monolayers and cellular membranes, its binding to hemoglobin during transport in the bloodstream, as well as its transport along optimal pathways toward its reduction sites in proteins. Moreover, MD simulations can help interpret...

  17. The treatment of tumors by the induction of anemia and irradiation in hyperbaric oxygen

    International Nuclear Information System (INIS)

    Sealy, R.; Jacobs, P.; Wood, L.; Levin, W.; Barry, L.; Boniaszczuk, J.; Blekkenhorst, G.

    1989-01-01

    Because increased effects have been achieved when murine tumors are irradiated after a period of hypoxia and because of anecdotal clinical experiences of an improved result after irradiation of previously anemic patients in hyperbaric oxygen, the relationship between irradiation and increased survival was investigated in seventy-two patients with advanced head and neck or cervical cancer. Anemia was achieved by means of a two-stage isovolemic venesection maintained for seventy-two hours, hemoglobin was returned to a normal level, and treatment in hyperbaric oxygen was started. Marked tumor shrinkage after the induction of anemia and before radiotherapy was seen and was probably disease, site, and hemoglobin level related. As a result, a possible new approach to cancer therapy is suggested. After completion of therapy, the 1-year disease-free survival for patients with head and neck and cervical cancer was not improved, but the 21-month survival for cervical cancer was improved. Further studies are strongly urged

  18. Artificial oxygen carriers as a possible alternative to red cells in clinical practice

    Directory of Open Access Journals (Sweden)

    Fabiano Timbó Barbosa

    Full Text Available Fluid resuscitation is intended to eliminate microcirculatory disorders and restore adequate tissue oxygenation. The safety limits for a restrictive transfusion policy are given by patients' individual tolerance of acute normovolemic anemia. Artificial oxygen carriers based on perfluorocarbon or hemoglobin are attractive alternatives to allogenic red blood cells. There are many risks involved in allogenic blood transfusions and they include transmission of infections, delayed postoperative wound healing, transfusion reactions, immunomodulation and cancer recurrence. Regardless of whether artificial oxygen carriers are available for routine clinical use, further studies are needed in order to show the safety and efficacy of these substances for clinical practice.

  19. Conformational changes in hemoglobin triggered by changing the iron charge

    International Nuclear Information System (INIS)

    Croci, S.; Achterhold, K.; Ortalli, I.; Parak, F. G.

    2008-01-01

    In this work the hemoglobin conformational changes induced by changing the iron charge have been studied and compared with Myoglobin. Moessbauer spectroscopy was used to follow the change of the iron conformation. In order to compare the conformational relaxation of hemoglobin and myoglobin, and to study a possible influence of the quaternary structure, an intermediate metastable state of hemoglobin has been created by low temperature X-ray irradiation of methemoglobin. The irradiation reduces the Fe(III) of the heme groups to Fe(II) Low Spin, where the water is still bound on the sixth coordination. Heating cycles performed at temperatures from 140 K to 200 K allow the molecules to overcome an activation energy barrier and to relax into a stable conformation such as deoxy-hemoglobin or carboxy-hemoglobin, if CO is present. Slightly different structures (conformational substates) reveal themselves as a distribution of energy barriers (ΔG). The distribution of the activation energy, for the decay of the Fe(II) Low Spin intermediate, has been fitted with a Gaussian. For comparison, published myoglobin data were re-analysed in the same way. The average energy value at characteristic temperature is very similar in case of myoglobin and hemoglobin. The larger Gaussian energy distribution for myoglobin with respect to hemoglobin shows that more conformational substates are available. This may be caused by a larger area exposed to water. In hemoglobin, part of the surface of the chains is not water accessible due to the quaternary structure.

  20. A thermodynamical measure of cooperativity: application to hemoglobin

    International Nuclear Information System (INIS)

    Jacchieri, S.G.; Ferreira, R.C.

    1984-01-01

    A comparative analysis of the heat requirements for dioxygen exchange is made for hemoglobin and myoglobin, the latter taken as the prototype of the vertebrate hemoglobin's ancestor. it is shown that cooperativity manifests itself also in terms of energy utilization. (Author) [pt

  1. Molecular recognition of malachite green by hemoglobin and their specific interactions: insights from in silico docking and molecular spectroscopy.

    Science.gov (United States)

    Peng, Wei; Ding, Fei; Peng, Yu-Kui; Sun, Ying

    2014-01-01

    Malachite green is an organic compound that can be widely used as a dyestuff for various materials; it has also emerged as a controversial agent in aquaculture. Since malachite green is proven to be carcinogenic and mutagenic, it may become a hazard to public health. For this reason, it is urgently required to analyze this controversial dye in more detail. In our current research, the interaction between malachite green and hemoglobin under physiological conditions was investigated by the methods of molecular modeling, fluorescence spectroscopy, circular dichroism (CD) as well as hydrophobic ANS displacement experiments. From the molecular docking, the central cavity of hemoglobin was assigned to possess high-affinity for malachite green, this result was corroborated by time-resolved fluorescence and hydrophobic ANS probe results. The recognition mechanism was found to be of static type, or rather the hemoglobin-malachite green complex formation occurred via noncovalent interactions such as π-π interactions, hydrogen bonds and hydrophobic interactions with an association constant of 10(4) M(-1). Moreover, the results also show that the spatial structure of the biopolymer was changed in the presence of malachite green with a decrease of the α-helix and increase of the β-sheet, turn and random coil suggesting protein damage, as derived from far-UV CD and three-dimensional fluorescence. Results of this work will help to further comprehend the molecular recognition of malachite green by the receptor protein and the possible toxicological profiles of other compounds, which are the metabolites and ramifications of malachite green.

  2. HEMOGLOBIN AND HEMATOCRITE CHANGES DURING UNCOMPLICATED ANESTHESIA: GENERAL ANESTHESIA AND LOCAL ANESTHESIA

    Directory of Open Access Journals (Sweden)

    KH NAGHIBI

    2002-12-01

    Full Text Available Introduction. Despite of vital role of blood and it"s components as an only curable treatment, it"s transfusion is accompanied by many complications. In the other way, the most important adverse effects of anemia is decrease in oxygen supply to the tissues. Therefore, it is essential to determine those patients need to blood transfusion and exact hemoglobine and hematocrite level which transfusion become necessary. Recent studies show that during general anesthesia due to vasodilation in the level of microcirculation and passage of many red blood cells from microcirculation there is a decreasing in hemoglobine level measured in peripheral veins which named plasma skimming. So, during sampling of hemoglobine and hematocrite from peripheral veins, there is a pseudodecrease in Hb and HCT levels. In this study we want to determine this decrease in Hb and HeT. Methods. Study was done in 182 patients with ASA 1 and 2 undergoing general or local anesthesia for cataract surgery. Duration of nill per os (NPO, preoperotive and intraoperative intravenous fluid administration were simillar in two groups. A sample of blood for preoperative evaluation and another one immediately after operation achevied and compared with each other. Results. There was not significant differences between mean Hb and HCT in two groups preoperotive. But postoperative, there was a significant differences between mean Hb and HCT in general anesthesia vs local anesthesia (P < 0.01. This decrease in Hb and HCT was orderly 0.91 ± 1.14 gr/dl for Hb and 2.862±3.6 percent for Hct. Discussion. In determining of Hb and HCT immediately after general anesthesia, there is some pseudo decrease due to plasma skimming that must be appreciated.

  3. Mechanisms of the adjuvant effect of hemoglobin in experimental peritonitis. VII. Hemoglobin does not inhibit clearance of Escherichia coli from the peritoneal cavity

    International Nuclear Information System (INIS)

    Dunn, D.L.; Barke, R.A.; Lee, J.T. Jr.; Condie, R.M.; Humphrey, E.W.; Simmons, R.L.

    1983-01-01

    Hemoglobin has been shown to be a potent adjuvant in experimental Escherichia coli peritonitis, although a satisfactory mechanistic rationale is still obscure. Hemoglobin has been thought to impair intraperitoneal neutrophil function, delay clearance of bacteria from the peritoneal cavity by the normal absorptive mechanisms, or directly enhance bacterial growth. Using highly purified stroma-free hemoglobin (SFHgb), we have largely discounted any direct effect of hemoglobin on peritoneal white blood cell function. In the present study, we confirmed that uncontrolled proliferation of bacteria takes place in the presence of hemoglobin in the peritoneal cavity. Nonviable 5-iododeoxyuridine 125 I-labelled bacteria were then used to directly study peritoneal clearance kinetics, eliminating the problem of bacterial growth. SFHgb had no influence on the removal of intraperitoneal bacteria. The rate of bloodstream appearance of radiolabel was similar with or without intraperitoneal SFHgb. Thus, SFHgb does not prevent clearance of bacteria from the peritoneal cavity by interfering with normal host clearance mechanisms. SFHgb may act as a bacterial growth adjuvant, either by serving as a bacterial nutrient or by suitably modifying the environment so that extensive bacterial proliferation can occur. The latter hypothesis appears to be an area in which investigation concerning the adjuvant effect of hemoglobin may prove most fruitful

  4. Hemoglobins: models of physiological adaptation, with special reference to O2 availability and temperature

    DEFF Research Database (Denmark)

    Weber, Roy E.

    In transporting O2 from the respiratory surfaces to the respiring tissues of animals, hemoglobin (Hb) directly links aerobic metabolism with O2 availability and is a paradigm for studying mechanisms of molecular adaptations. Hb-O2 binding is cooperative (described by sigmoid O2 binding curves......) and decreased by allosteric effectors (protons, CO2, lactate, organic phosphates and chloride ions) that modulate O2 binding in response to changes in environmental and metabolic dictates. Hb-O2 affinity moreover decreases with rising temperature. This increases O2 unloading in warm tissues that consume more O2......, but may be maladaptive – and thus is reduced - in regional heterothermic animals where it may hamper O2 unloading (in cold extremities of Artic mammals) or cause excessive O2 release (in warm organs of fast-swimming fish). Illustrated with case studies (estivating lungfish, high altitude frogs, birds...

  5. The relationship between tumor oxygenation and cell proliferation in human soft tissue sarcomas

    International Nuclear Information System (INIS)

    Nordsmark, Marianne; Hoeyer, Morten; Keller, Johnny; Nielsen, Ole Steen; Jensen, Oluf Myhre; Overgaard, Jens

    1996-01-01

    Purpose: In malignant tumors the oxygenation status and tumor cell proliferation are known to influence local tumor control after radiotherapy. However, the relationship between oxygenation status and tumor cell kinetics in human tumors has not yet been described. Newly developed clinically applicable techniques such as oxygen electrode measurements and assessment of tumor cell proliferation rates have been suggested as promising predictive assays. The purpose of the present study was to characterize tumor oxygenation status in soft tissue sarcomas and to compare this with tumor cell kinetics and clinical parameters. Methods and Materials: Pretreatment tumor oxygenation status was measured by polarographic oxygen needle electrodes and evaluated as the median pO 2 and the percentage of pO 2 values ≤ 5 mmHg and ≤ 2.5 mmHg in 22 patients with primary soft tissue sarcomas. All tumors were characterized by histology, grade of malignancy, the level of microscopic necrosis, the level of effective hemoglobin, and magnetic resonance imaging estimation of tumor volume. The tumor cell potential doubling time and labeling index were measured by flow cytometric and immunohistochemical analysis of tumor biopsy specimens after in vivo incorporation of iododeoxyuridine. Results: There was a significant correlation between the median pO 2 and the tumor cell potential doubling time (p = 0.041), whereas no correlation was found between the level of hypoxia expressed by the percentage of pO 2 values ≤ 2.5 and ≤ 5 mmHg, respectively, and tumor cell potential doubling time. Furthermore, no correlation was found between either of the three tumor oxygenation parameters and labeling index. The material represented large intertumor heterogeneity in oxygenation status, cell kinetics, and tumor volume, and no correlation was found between oxygenation status and either volume, histopathology, grade of malignancy, or effective hemoglobin. Conclusion: This report is the first to suggest

  6. The effect of biofiltration on red blood cells 2.3-diphosphoglycerate and pH.

    Science.gov (United States)

    Umimoto, K; Hirai, Y; Hayashi, T; Tanaka, H

    2000-12-01

    To investigate the effect of biofiltration (BF) on the ability of blood to supply oxygen to the peripheral tissues, a 2 week crossover study was conducted with bicarbonate hemodialysis (BcHD) and BF using 5 male patients with diabetic renal failure as subjects. BcHD and BF were performed for 4 h and 3.5 h per session, respectively. Blood gases, the pH of red blood cells (RBC-pH), and 2. 3-diphosphoglycerate in RBC (RBC-2.3DPG) were measured during each treatment. After a 2 week BF treatment, the plasma HCO3- at the beginning of BF was significantly higher than that of BcHD (p level (p levels. The RBC-2.3DPG during BcHD remained unchanged, but during BF significantly increased (p level. The improved metabolic acidosis might occur as a result of the increase in RBC-2.3DPG during BF. This increase in RBC-2.3DPG has the effect of reducing the affinity of oxygen for hemoglobin and allows more oxygen to be delivered to the peripheral tissues although the increase in RBC-pH by dialysis restricts the dissociation of oxygen from hemoglobin.

  7. Surface Modification of Multi-Walled Carbon Nanotubes via Hemoglobin-Derived Iron and Nitrogen-Rich Carbon Nanolayers for the Electrocatalysis of Oxygen Reduction

    Directory of Open Access Journals (Sweden)

    Wensheng Li

    2017-05-01

    Full Text Available The great challenge of boosting the oxygen reduction reaction (ORR activity of non-noble-metal electrocatalysts is how to achieve effective exposure and full utilization of nitrogen-rich active sites. To realize the goals of high utilization of active sites and fast electron transport, here we report a new strategy for synthesis of an iron and nitrogen co-doped carbon nanolayers-wrapped multi-walled carbon nanotubes as ORR electrocatalyst (N-C@CNT-Fe via using partially carbonized hemoglobin as a single-source precursor. The onset and half-wave potentials for ORR of N-C@CNT-Fe are only 45 and 54 mV lower than those on a commercial Pt/C (20 wt.% Pt catalyst, respectively. Besides, this catalyst prepared in this work has been confirmed to follow a four-electron reaction mechanism in ORR process, and also displays ultra-high electrochemical cycling stability in both acidic and alkaline electrolytes. The enhancement of ORR activity can be not only attributed to full exposure and utilization of active site structures, but also can be resulted from the improvement of electrical conductivity owing to the introduction of CNT support. The analysis of X-ray photoelectric spectroscopy shows that both Fe–N and graphitic-N species may be the ORR active site structures of the prepared catalyst. Our study can provide a valuable idea for effective improvement of the electrocatalytic activity of non-noble-metal ORR catalysts.

  8. Biophysical Monitoring and dose response characteristics of irradiated hemoglobin

    International Nuclear Information System (INIS)

    Elshemey, W.M; Selim, N.S.; Desouky, O.

    2003-01-01

    The present work aims to move a step forward towards a deeper understanding of the scattering of x-ray, from lyophilized biological samples. Comparative study has been performed using LAXS and UV-visible spectrophotometry for monitoring the dose response characteristics of the hemoglobin molecule of irradiated blood. Blood samples were irradiated at doses ranging from 5 up to 100 Gy. Diluted hemoglobin solution was scanned in the UV- visible range (200-700 nm), and lyophilized hemoglobin was prepared for LAXS measurement. The radiation-induced changes in the hemoglobin structure have been evaluated. The LAXS profile of hemoglobin molecule is characterized by the presence of two peaks in the forward direction of scattering. These peaks were found to be sensitive to the variations in the molecular structure of a given sample. The obtained results suggest that the 1 s t peak, recorded at 4.65 o , is sensitive to the tertiary and quaternary structure of the globin part, while the major peak, recorded at 10.5 o , appeared to be related to its primary and secondary structure

  9. Hepatoprotective effects of Poly-[hemoglobin-superoxide dismutase-catalase-carbonic anhydrase] on alcohol-damaged primary rat hepatocyte culture in vitro.

    Science.gov (United States)

    Jiang, Wenhua; Bian, Yuzhu; Wang, Zhenghui; Chang, Thomas Ming Swi

    2017-02-01

    We have prepared a novel nanobiotherapeutic, Poly-[hemoglobin-superoxide dismutase-catalase-carbonic anhydrase], which not only transports both oxygen and carbon dioxide but also a therapeutic antioxidant. Our previous study in a severe sustained 90 min hemorrhagic shock rat model shows that it has a hepatoprotective effect. We investigate its hepatoprotective effect further in this present report using an alcohol-damaged primary hepatocyte culture model. Results show that it significantly reduced ethanol-induced AST release, lipid peroxidation, and ROS production in rat primary hepatocytes culture. It also significantly enhanced the viability of ethanol-treated hepatocytes. Thus, the result shows that Poly-[hemoglobin-superoxide dismutase-catalase-carbonic anhydrase] also has some hepatoprotective effects against alcohol-induced injury in in vitro rat primary hepatocytes cell culture. This collaborate our previous observation of its hepatoprotective effect in a severe sustained 90-min hemorrhagic shock rat model.

  10. Hypoxia and anoxia effects on alcohol dehydrogenase activity and hemoglobin content in Chironomus riparius Meigen, 1804

    Directory of Open Access Journals (Sweden)

    Valentina Grazioli

    2016-02-01

    Full Text Available The metabolic effects of low oxygen content on alcohol-dehydrogenase (ADH activity and hemoglobin (Hb concentration were investigated in IV-instar larvae of Chironomus riparius (Diptera: Chironomidae from an Italian stream. Two series of short-term (48 h experiments were carried out: exposure to (1 progressive hypoxia (95 to 5% of oxygen saturation and (2 anoxia (at <5% of oxygen saturation. In (1, Hb amount increased with increasing oxygen depletion up to a critical value of oxygenation (about 70% of oxygen saturation. Below this percentage, the Hb amount declined to values comparable with those present in the control. The respiration rate (R remained almost constant at oxygen saturation >50% and decreased significantly only after 48 h of treatment (= <5% of oxygen saturation reaching values <100 mmolO2 gAFDW-1 h-1. ADH activity showed two phases of growth, within the first 14 h and over 18 h of exposure. Overall, we inferred that i Hb might function as short-term oxygen storage, enabling animals to delay the on-set of anaerobiosis; and ii alcoholic fermentation co-occurs for a short time with aerobic respiration, becoming the prevalent metabolic pathway below 5% of oxygen saturation (<1 mg L-1. These considerations were supported also by results from anoxia exposure (2. In such condition, larvae were visibly stressed, becoming immobile after few minutes of incubation, and ADH reached higher values than in the hypoxia treatment (2.03±0.15 UADH mg prot-1. Overall, this study showed a shift from aerobic to anaerobic activity in C. riparius larvae exposed to poorly oxygenated water with an associated alteration of ADH activity and the Hb amount. Such metabolites might be valid candidate biomarkers for the environmental monitoring of running waters.

  11. Photoacoustic microscopy of cerebral hemodynamic and oxygen-metabolic responses to anesthetics

    Science.gov (United States)

    Cao, Rui; Li, Jun; Ning, Bo; Sun, Naidi; Wang, Tianxiong; Zuo, Zhiyi; Hu, Song

    2017-02-01

    General anesthetics are known to have profound effects on cerebral hemodynamics and neuronal activities. However, it remains a challenge to directly assess anesthetics-induced hemodynamic and oxygen-metabolic changes from the true baseline under wakefulness at the microscopic level, due to the lack of an enabling technology for high-resolution functional imaging of the awake mouse brain. To address this challenge, we have developed head-restrained photoacoustic microscopy (PAM), which enables simultaneous imaging of the cerebrovascular anatomy, total concentration and oxygen saturation of hemoglobin (CHb and sO2), and blood flow in awake mice. From these hemodynamic measurements, two important metabolic parameters, oxygen extraction fraction (OEF) and the cerebral metabolic rate of oxygen (CMRO2), can be derived. Side-by-side comparison of the mouse brain under wakefulness and anesthesia revealed multifaceted cerebral responses to isoflurane, a volatile anesthetic widely used in preclinical research and clinical practice. Key observations include elevated cerebral blood flow (CBF) and reduced oxygen extraction and metabolism.

  12. Extracellular hemoglobin: the case of a friend turned foe

    Science.gov (United States)

    Quaye, Isaac K.

    2015-01-01

    Hemoglobin (Hb) is a highly conserved molecule present in all life forms and functionally tied to the complexity of aerobic organisms on earth in utilizing oxygen from the atmosphere and delivering to cells and tissues. This primary function sustains the energy requirements of cells and maintains cellular homeostasis. Decades of intensive research has presented a paradigm shift that shows how the molecule also functions to facilitate smooth oxygen delivery through the cardiovascular system for cellular bioenergetic homeostasis and signaling for cell function and defense. These roles are particularly highlighted in the binding of Hb to gaseous molecules carbon dioxide (CO2), nitric oxide (NO) and carbon monoxide (CO), while also serving indirectly or directly as sources of these signaling molecules. The functional activities impacted by Hb outside of bioenergetics homeostasis, include fertilization, signaling functions, modulation of inflammatory responses for defense and cell viability. These activities are efficiently executed while Hb is sequestered safely within the confines of the red blood cell (rbc). Outside of rbc confines, Hb disaggregates and becomes a danger molecule to cell survival. In these perpectives, Hb function is broadly dichotomous, either a friend in its natural environment providing and facilitating the means for cell function or foe when dislocated from its habitat under stress or pathological condition disrupting cell function. The review presents insights into how this dichotomy in function manifests. PMID:25941490

  13. Role of α-globin H helix in the building of tetrameric human hemoglobin: interaction with α-hemoglobin stabilizing protein (AHSP) and heme molecule.

    Science.gov (United States)

    Domingues-Hamdi, Elisa; Vasseur, Corinne; Fournier, Jean-Baptiste; Marden, Michael C; Wajcman, Henri; Baudin-Creuza, Véronique

    2014-01-01

    Alpha-Hemoglobin Stabilizing Protein (AHSP) binds to α-hemoglobin (α-Hb) or α-globin and maintains it in a soluble state until its association with the β-Hb chain partner to form Hb tetramers. AHSP specifically recognizes the G and H helices of α-Hb. To investigate the degree of interaction of the various regions of the α-globin H helix with AHSP, this interface was studied by stepwise elimination of regions of the α-globin H helix: five truncated α-Hbs α-Hb1-138, α-Hb1-134, α-Hb1-126, α-Hb1-123, α-Hb1-117 were co-expressed with AHSP as two glutathione-S-transferase (GST) fusion proteins. SDS-PAGE and Western Blot analysis revealed that the level of expression of each truncated α-Hb was similar to that of the wild type α-Hb except the shortest protein α-Hb1-117 which displayed a decreased expression. While truncated GST-α-Hb1-138 and GST-α-Hb1-134 were normally soluble; the shorter globins GST-α-Hb1-126 and GST-α-Hb1-117 were obtained in very low quantities, and the truncated GST-α-Hb1-123 provided the least material. Absorbance and fluorescence studies of complexes showed that the truncated α-Hb1-134 and shorter forms led to modified absorption spectra together with an increased fluorescence emission. This attests that shortening the H helix leads to a lower affinity of the α-globin for the heme. Upon addition of β-Hb, the increase in fluorescence indicates the replacement of AHSP by β-Hb. The CO binding kinetics of different truncated AHSPWT/α-Hb complexes showed that these Hbs were not functionally normal in terms of the allosteric transition. The N-terminal part of the H helix is primordial for interaction with AHSP and C-terminal part for interaction with heme, both features being required for stability of α-globin chain.

  14. 21 CFR 522.1125 - Hemoglobin glutamer-200 (bovine).

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Hemoglobin glutamer-200 (bovine). 522.1125 Section... (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS IMPLANTATION OR INJECTABLE DOSAGE FORM NEW ANIMAL DRUGS § 522.1125 Hemoglobin glutamer-200 (bovine). (a) Specifications. Each 125 milliliter bag contains 13...

  15. Propanil-induced methemoglobinemia and hemoglobin binding in the rat

    Energy Technology Data Exchange (ETDEWEB)

    McMillan, D.C.; McRae, T.A.; Hinson, J.A. (National Center for Toxicological Research, Jefferson, AR (USA))

    1990-09-15

    Administration of (ring-U-14C)propanil (3,4-dichloropropionanilide) to male Sprague-Dawley rats (30, 100, and 300 mg/kg, ip) increased the formation of methemoglobin at the two highest doses. Following a propanil dose of 100 mg/kg, methemoglobin formation attained a maximum level of 5% by 1.5 hr and declined to normal levels (approximately 2.5%) by 12 hr. Hemoglobin binding attained a maximum level of 50 pmol/mg protein by 12 hr, and remained constant for 24 hr. Following a propanil dose of 300 mg/kg, methemoglobin formation attained a maximum level of 24% by 4.5 hr, and declined to a level of 5% by 24 hr. Hemoglobin binding attained a maximum level of 425 pmol/mg protein by 12 hr, and remained constant for 24 hr. Hemoglobin binding was also detected at the lowest propanil dose (10 pmol/mg protein) even though methemoglobin formation was not observed. HPLC analysis of alkaline-treated hemoglobin from propanil-treated rats indicated the presence of one radiolabeled compound with the same HPLC retention time as 3,4-dichloraniline. These data are consistent with the concept that propanil is converted to N-hydroxy-3,4-dichloroaniline in the liver. Subsequently, this metabolite enters the erythrocyte and is oxidized by hemoglobin to 3,4-dichloronitrosobenzene with concomitant conversion of oxyhemoglobin to methemoglobin. The 3,4-dichloronitrosobenzene binds to cysteine residues on hemoglobin as the corresponding sulfinic acid amide adduct. These data suggest that human exposure to propanil may be monitored in the absence of observable toxicity by the analysis of propanil metabolites bound to hemoglobin.

  16. Pilot study assessment of dynamic vascular changes in breast cancer with near-infrared tomography from prospectively targeted manipulations of inspired end-tidal partial pressure of oxygen and carbon dioxide.

    Science.gov (United States)

    Jiang, Shudong; Pogue, Brian W; Michaelsen, Kelly E; Jermyn, Michael; Mastanduno, Michael A; Frazee, Tracy E; Kaufman, Peter A; Paulsen, Keith D

    2013-07-01

    The dynamic vascular changes in the breast resulting from manipulation of both inspired end-tidal partial pressure of oxygen and carbon dioxide were imaged using a 30 s per frame frequency-domain near-infrared spectral (NIRS) tomography system. By analyzing the images from five subjects with asymptomatic mammography under different inspired gas stimulation sequences, the mixture that maximized tissue vascular and oxygenation changes was established. These results indicate maximum changes in deoxy-hemoglobin, oxygen saturation, and total hemoglobin of 21, 9, and 3%, respectively. Using this inspired gas manipulation sequence, an individual case study of a subject with locally advanced breast cancer undergoing neoadjuvant chemotherapy (NAC) was analyzed. Dynamic NIRS imaging was performed at different time points during treatment. The maximum tumor dynamic changes in deoxy-hemoglobin increased from less than 7% at cycle 1, day 5 (C1, D5) to 17% at (C1, D28), which indicated a complete response to NAC early during treatment and was subsequently confirmed pathologically at the time of surgery.

  17. Rice (Oryza) hemoglobins

    Science.gov (United States)

    Hemoglobins (Hbs) corresponding to non-symbiotic (nsHb) and truncated (tHb) Hbs have been identified in rice (Oryza). This review discusses the major findings from the current studies on rice Hbs. At the molecular level, a family of the nshb genes, consisting of hb1, hb2, hb3, hb4 and hb5, and a sin...

  18. Continuous affine processes

    DEFF Research Database (Denmark)

    Buchardt, Kristian

    2016-01-01

    Affine processes possess the property that expectations of exponential affine transformations are given by a set of Riccati differential equations, which is the main feature of this popular class of processes. In this paper we generalise these results for expectations of more general transformati...

  19. Affinity in electrophoresis.

    Science.gov (United States)

    Heegaard, Niels H H

    2009-06-01

    The journal Electrophoresis has greatly influenced my approaches to biomolecular affinity studies. The methods that I have chosen as my main tools to study interacting biomolecules--native gel and later capillary zone electrophoresis--have been the topic of numerous articles in Electrophoresis. Below, the role of the journal in the development and dissemination of these techniques and applications reviewed. Many exhaustive reviews on affinity electrophoresis and affinity CE have been published in the last few years and are not in any way replaced by the present deliberations that are focused on papers published by the journal.

  20. Evans Syndrome Complicated by Intratubular Hemoglobin Cast Nephropathy

    Directory of Open Access Journals (Sweden)

    Iván González

    2017-01-01

    Full Text Available Evans syndrome (ES is a rare autoimmune disorder whose exact pathophysiology is unknown. It is characterized by the simultaneous or subsequent development of autoimmune hemolytic anemia (AIHA and immune thrombocytopenia (ITP. Intravascular hemolysis, with hemoglobinemia, is known to produce acute kidney injury; however, the development of intratubular hemoglobin casts (hemoglobin cast nephropathy in the setting of acute hemolysis is uncommon. Likewise, the association of ES and acute renal failure is equally uncommon. We present a case of a 7-year-old girl with ES who developed acute kidney injury in the setting of intravascular hemolysis and had widespread intratubular hemoglobin casts.

  1. 21 CFR 864.7400 - Hemoglobin A2 assay.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Hemoglobin A2 assay. 864.7400 Section 864.7400 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES HEMATOLOGY AND PATHOLOGY DEVICES Hematology Kits and Packages § 864.7400 Hemoglobin A2...

  2. Nitrosyl hemoglobins: EPR above 80 K

    Energy Technology Data Exchange (ETDEWEB)

    Wajnberg, E.; Bemski, G.; El-Jaick, L.J.; Alves, O.C.

    1995-03-01

    The EPR spectra of nitrosyl hemoglobin and myoglobin in different conditions (native, denatured and lyophilized), as well as of hematin-NO were obtained in the temperature range of 80 K-280 K. There is a substantial and reversible.decrease of the areas of the EPR spectra of all the hemoglobin samples above 150 K. The interpretation of the results implies the existence of two conformational states in thermal equilibrium only one of which is EPR detectable. Thermodynamical parameters are determined for the hexa and penta-coordinated cases. (author). 25 refs, 3 figs.

  3. Nitrosyl hemoglobins: EPR above 80 K

    International Nuclear Information System (INIS)

    Wajnberg, E.; Bemski, G.; El-Jaick, L.J.; Alves, O.C.

    1995-03-01

    The EPR spectra of nitrosyl hemoglobin and myoglobin in different conditions (native, denatured and lyophilized), as well as of hematin-NO were obtained in the temperature range of 80 K-280 K. There is a substantial and reversible.decrease of the areas of the EPR spectra of all the hemoglobin samples above 150 K. The interpretation of the results implies the existence of two conformational states in thermal equilibrium only one of which is EPR detectable. Thermodynamical parameters are determined for the hexa and penta-coordinated cases. (author). 25 refs, 3 figs

  4. Evaluation of light scattering properties and chromophore concentrations in skin tissue based on diffuse reflectance signals at isosbestic wavelengths of hemoglobin

    Science.gov (United States)

    Yokokawa, Takumi; Nishidate, Izumi

    2016-04-01

    We investigate a method to evaluate light-scattering properties and chromophore concentrations in human skin tissue through diffuse reflectance spectroscopy using the reflectance signals acquired at isosbestic wavelengths of hemoglobin (420, 450, 500, and 585 nm). In the proposed method, Monte Carlo simulation-based empirical formulas are used to specify the scattering parameters of skin tissue, such as the scattering amplitude a and the scattering power b, as well as the concentration of melanin C m and the total blood concentration C tb. The use of isosbestic wavelengths of hemoglobin enables the values of C m, C tb, a, and b to be estimated independently of the oxygenation of hemoglobin. The spectrum of the reduced scattering coefficient is reconstructed from the scattering parameters. Experiments using in vivo human skin tissues were performed to confirm the feasibility of the proposed method for evaluating the changes in scattering properties and chromophore concentrations in skin tissue. The experimental results revealed that light scattering is significantly reduced by the application of a glycerol solution, which indicates an optical clearing effect due to osmotic dehydration and the matching of the refractive indices of scatterers in the epidermis.

  5. The metric-affine gravitational theory as the gauge theory of the affine group

    International Nuclear Information System (INIS)

    Lord, E.A.

    1978-01-01

    The metric-affine gravitational theory is shown to be the gauge theory of the affine group, or equivalently, the gauge theory of the group GL(4,R) of tetrad deformations in a space-time with a locally Minkowskian metric. The identities of the metric-affine theory, and the relationship between them and those of general relativity and Sciama-Kibble theory, are derived. (Auth.)

  6. A spectroscopic study on the interaction between gold nanoparticles and hemoglobin

    International Nuclear Information System (INIS)

    Garabagiu, Sorina

    2011-01-01

    Highlights: ► The interaction was studied using UV–vis and fluorescence spectroscopy. ► Gold nanoparticles quench the fluorescence emission of hemoglobin solution. ► The binding and thermodynamic constants were calculated. ► Major impact: electrochemical applications of the complex onto a substrate. -- Abstract: The interaction between horse hemoglobin and gold nanoparticles was studied using optical spectroscopy. UV–vis and fluorescence spectra show that a spontaneous binding process occurred between hemoglobin and gold nanoparticles. The Soret band of hemoglobin in the presence of gold nanoparticles does not show significant changes, which proves that the protein retained its biological function. A shift to longer wavelengths appears in the plasmonic band of gold nanoparticles upon the attachment of hemoglobin molecules. Gold nanoparticles quench the fluorescence emission of tryptophan residues in the structure of hemoglobin. The Stern–Volmer quenching constant, the binding constant and the number of binding sites were also calculated. Thermodynamic parameters indicate that the binding was mainly due to hydrophobic interactions.

  7. Human macrophage hemoglobin-iron metabolism in vitro

    International Nuclear Information System (INIS)

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

    1982-01-01

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

  8. The impact of hemoglobin on the efficacy of phototherapy in hyperbilirubinemic infants

    DEFF Research Database (Denmark)

    Donneborg, Mette L; Vandborg, Pernille K; Hansen, Bo M

    2017-01-01

    BackgroundPhototherapy is the routine treatment for neonatal hyperbilirubinemia. Absorption of light in the skin transforms the native Z,Z-bilirubin to photobilirubins. This study investigates whether the hemoglobin concentration has an impact on efficacy of phototherapy, expressed by the decline...... decrease in TsB after 24 h was 121 (57-199) μmol/l; the median hemoglobin was 12.0 (7.0-14.7) mmol/l. There was a significant effect of hemoglobin concentration on the decrease in TsB of -3.61 μmol/mmol hemoglobin (P=0.022), after adjusting for initial TsB and postnatal age. That is, assuming the same...... initial TsB and postnatal age, for each mmol/l increase in hemoglobin, the decrease in TsB was 3.61 μmol/l smaller. In our hemoglobin range, the decrease in TsB is reduced by 28 μmol/l (23%).ConclusionIncreasing hemoglobin levels led to a decrease in the efficacy of phototherapy. Our data provide...

  9. Comparative study of bedside and laboratory measurements of hemoglobin.

    Science.gov (United States)

    Krenzischek, D A; Tanseco, F V

    1996-11-01

    The purpose of this study was to examine the effects of variations in technique on measurements of hemoglobin level done at the bedside and to compare these results with laboratory measurements of hemoglobin. In accordance with hospital policy, procedure, and protocol, various techniques were used to obtain samples of capillary and venous blood and of blood from arterial and central venous catheters. Levels of hemoglobin were measured at the bedside and in the laboratory, and the results were compared. The Johns Hopkins Hospital adult postanesthesia care unit. A total of 187 blood samples were obtained from 62 adults who had undergone general surgery. Group I comprised 20 subjects with capillary and venous blood samples. Group II comprised 21 subjects with arterial blood samples. Group III comprised 21 subjects with central venous blood samples. The results showed that the amount of blood to be discarded before obtaining samples of arterial and central venous blood need not be any larger than double the dead space of the catheter, and that shaking the blood sample for 10 seconds was sufficient to mix the sample before measurement of hemoglobin levels. Results of bedside and laboratory measurements of hemoglobin level were comparable. Bedside measurement of hemoglobin increases efficiency in patient care, decreases risk of blood-transmitted infection for staff, and decreases cost to the patient. However, the persons who perform the assay must be responsible in adhering to the standard of practice to minimize errors in the measurements.

  10. Prognostic value of hemoglobin concentration in radiotherapy for cancer of supraglottic larynx

    International Nuclear Information System (INIS)

    Tarnawski, Rafal; Skladowski, Krzysztof; Maciejewski, Boguslaw

    1997-01-01

    Purpose: The aim of this work is the estimation of correlations between hemoglobin concentration either before or after radiotherapy and local tumor control probability for laryngeal cancer. Methods and Materials: Retrospective analysis of 847 cases of laryngeal supraglottic squamous cell carcinoma treated with radiation alone was performed using maximum likelihood estimations, and step-wise logistic regression. All patients were in good initial performance status (Karnofsky index >70). The minimum follow-up time was 3 years. Results: Logistic regression showed that the hemoglobin concentration after radiotherapy is an important prognostic factor. There was a very strong correlation between hemoglobin concentration and tumor local control probability. Hemoglobin concentration at the beginning of radiotherapy does not correlate with treatment outcome, but any decrease of hemoglobin during therapy is a strong prognostic factor for treatment failure. Conclusions: Although regression models with many variables may be instable, the present results suggest that hemoglobin concentration after treatment is at least as important as overall treatment time. It was not possible to find out whether the low concentration of hemoglobin is an independent cause of low TCP or whether it reflects other mechanisms that may influence both hemoglobin level and the TCP

  11. A nanocluster-based fluorescent sensor for sensitive hemoglobin detection.

    Science.gov (United States)

    Yang, Dongqin; Meng, Huijie; Tu, Yifeng; Yan, Jilin

    2017-08-01

    In this report, a fluorescence sensor for sensitive detection of hemoglobin was developed. Gold nanoclusters were first synthesized with bovine serum albumin. It was found that both hydrogen peroxide and hemoglobin could weakly quench the fluorescence from the gold nanoclusters, but when these two were applied onto the nanolcusters simultaneously, a much improved quenching was resulted. This enhancing effect was proved to come from the catalytic generation of hydroxyl radical by hemoglobin. Under an optimized condition, the quenching linearly related to the concentration of hemoglobin in the range of 1-250nM, and a limit of detection as low as 0.36nM could be obtained. This provided a sensitive means for the quantification of Hb. The sensor was then successfully applied for blood analyses with simple sample pretreatment. Copyright © 2017 Elsevier B.V. All rights reserved.

  12. Hemoglobin Concentration and Risk of Incident Stroke in Community-Living Adults.

    Science.gov (United States)

    Panwar, Bhupesh; Judd, Suzanne E; Warnock, David G; McClellan, William M; Booth, John N; Muntner, Paul; Gutiérrez, Orlando M

    2016-08-01

    In previous observational studies, hemoglobin concentrations have been associated with an increased risk of stroke. However, these studies were limited by a relatively low number of stroke events, making it difficult to determine whether the association of hemoglobin and stroke differed by demographic or clinical factors. Using Cox proportional hazards analysis and Kaplan-Meier plots, we examined the association of baseline hemoglobin concentrations with incident stroke in the Reasons for Geographic and Racial Differences in Stroke (REGARDS) study, a cohort of black and white adults aged ≥45 years. A total of 518 participants developed stroke over a mean 7±2 years of follow-up. There was a statistically significant interaction between hemoglobin and sex (P=0.05) on the risk of incident stroke. In Cox regression models adjusted for demographic and clinical variables, there was no association of baseline hemoglobin concentration with incident stroke in men, whereas in women, the lowest (14.0 g/dL) quartiles of hemoglobin were associated with higher risk of stroke when compared with the second quartile (12.4-13.2 g/dL; quartile 1: hazard ratio, 1.59; 95% confidence interval, 1.09-2.31; quartile 2: referent; quartile 3: hazard ratio, 0.91; 95% confidence interval, 0.59-1.38; quartile 4: hazard ratio, 1.59; 95% confidence interval, 1.08-2.35). Similar results were observed in models stratified by hemoglobin and sex and when hemoglobin was modeled as a continuous variable using restricted quadratic spline regression. Lower and higher hemoglobin concentrations were associated with a higher risk of incident stroke in women. No such associations were found in men. © 2016 American Heart Association, Inc.

  13. Nonenzymatic glycosylation of human hemoglobin at multiple sites

    International Nuclear Information System (INIS)

    Shapiro, R.; McManus, M.; Garrick, L.; McDonald, M.J.; Bunn, H.F.

    1979-01-01

    The most abundant minor hemoglobin component of human hemolysate is Hb A1c, which has glucose bound to the N-terminus of the beta chain by a ketoamine linkage. Hb A1c is formed slowly and continuously throughout the 120 day lifespan of the red cell. It can be synthesized in vitro by incubating purified hemoglobin with 14C-glucose. Other minor components, Hb A1a1 and Hb A1a2 are adducts of sugar phosphates at the N-terminus of the beta chain. Hb A1b contains an unidentified nonphosphorylated sugar at the beta N-terminus. In addition, a significant portion of the major hemoglobin component (Hb Ao) is also glycosylated by a glucose ketoamine linkage at other sites on the molecule, including the N-terminus of the alpha chain and the epsilon-amino group of several lysine residues on both the alpha and the beta chains. The results indicate that the interaction of glucose and hemoglobin is rather nonspecific and suggests that other proteins are modified in a similar fashion

  14. Detection of Hb Rothschild HBB: c.[112T>A or 112T>C], Through High Index of Suspicion on Abnormal Pulse Oximetry.

    Science.gov (United States)

    Alli, Nazeer A; Wessels, Piet; Rampersad, Narisha; Clark, Barnaby E; Thein, Swee Lay

    2017-03-01

    We describe a case with a low oxygen affinity hemoglobin (Hb) variant who presented with cyanosis in the absence of cardiopulmonary disease. The patient, a 27-year-old pregnant female (P1G2), complained of a productive cough and bluish discoloration of the lips that started 3 days prior to seeking attention. She had no previous episodes and has generally been in good health. A positive family history of cyanosis was obtained in one sibling. Systematic examination, notably the cardiorespiratory system, revealed no abnormalities. The arterial Hb oxygen saturation (SpO 2 ) on pulse oximetry was 81.0% and Hb separation studies revealed an Hb variant identified as Hb Rothschild [β37(C3)Trp→Arg] (HBB: c.[112 T>A or 112 T>C]) by gene sequencing. The amino acid substitution (Trp→Arg) is an important contact point at the α1β2 interface and favors a T-quaternary state of the Hb tetramer. This leads to a low oxygen affinity state, which results in premature release of oxygen and drop in oxygen saturation. In the absence of cardiopulmonary disease, a decreased oxygen saturation reading, with or without cyanosis, should arouse suspicion for a possible dysHb.

  15. Guinea Pig Oxygen-Sensing and Carotid Body Functional Properties

    Science.gov (United States)

    Gonzalez-Obeso, Elvira; Docio, Inmaculada; Olea, Elena; Cogolludo, Angel; Obeso, Ana; Rocher, Asuncion; Gomez-Niño, Angela

    2017-01-01

    Mammals have developed different mechanisms to maintain oxygen supply to cells in response to hypoxia. One of those mechanisms, the carotid body (CB) chemoreceptors, is able to detect physiological hypoxia and generate homeostatic reflex responses, mainly ventilatory and cardiovascular. It has been reported that guinea pigs, originally from the Andes, have a reduced ventilatory response to hypoxia compared to other mammals, implying that CB are not completely functional, which has been related to genetically/epigenetically determined poor hypoxia-driven CB reflex. This study was performed to check the guinea pig CB response to hypoxia compared to the well-known rat hypoxic response. These experiments have explored ventilatory parameters breathing different gases mixtures, cardiovascular responses to acute hypoxia, in vitro CB response to hypoxia and other stimuli and isolated guinea pig chemoreceptor cells properties. Our findings show that guinea pigs are hypotensive and have lower arterial pO2 than rats, probably related to a low sympathetic tone and high hemoglobin affinity. Those characteristics could represent a higher tolerance to hypoxic environment than other rodents. We also find that although CB are hypo-functional not showing chronic hypoxia sensitization, a small percentage of isolated carotid body chemoreceptor cells contain tyrosine hydroxylase enzyme and voltage-dependent K+ currents and therefore can be depolarized. However hypoxia does not modify intracellular Ca2+ levels or catecholamine secretion. Guinea pigs are able to hyperventilate only in response to intense acute hypoxic stimulus, but hypercapnic response is similar to rats. Whether other brain areas are also activated by hypoxia in guinea pigs remains to be studied. PMID:28533756

  16. Guinea Pig Oxygen-Sensing and Carotid Body Functional Properties.

    Science.gov (United States)

    Gonzalez-Obeso, Elvira; Docio, Inmaculada; Olea, Elena; Cogolludo, Angel; Obeso, Ana; Rocher, Asuncion; Gomez-Niño, Angela

    2017-01-01

    Mammals have developed different mechanisms to maintain oxygen supply to cells in response to hypoxia. One of those mechanisms, the carotid body (CB) chemoreceptors, is able to detect physiological hypoxia and generate homeostatic reflex responses, mainly ventilatory and cardiovascular. It has been reported that guinea pigs, originally from the Andes, have a reduced ventilatory response to hypoxia compared to other mammals, implying that CB are not completely functional, which has been related to genetically/epigenetically determined poor hypoxia-driven CB reflex. This study was performed to check the guinea pig CB response to hypoxia compared to the well-known rat hypoxic response. These experiments have explored ventilatory parameters breathing different gases mixtures, cardiovascular responses to acute hypoxia, in vitro CB response to hypoxia and other stimuli and isolated guinea pig chemoreceptor cells properties. Our findings show that guinea pigs are hypotensive and have lower arterial pO 2 than rats, probably related to a low sympathetic tone and high hemoglobin affinity. Those characteristics could represent a higher tolerance to hypoxic environment than other rodents. We also find that although CB are hypo-functional not showing chronic hypoxia sensitization, a small percentage of isolated carotid body chemoreceptor cells contain tyrosine hydroxylase enzyme and voltage-dependent K + currents and therefore can be depolarized. However hypoxia does not modify intracellular Ca 2+ levels or catecholamine secretion. Guinea pigs are able to hyperventilate only in response to intense acute hypoxic stimulus, but hypercapnic response is similar to rats. Whether other brain areas are also activated by hypoxia in guinea pigs remains to be studied.

  17. Histopathologic Study Following Administration of Liposome-Encapsulated Hemoglobin in the Normovolemic Rat

    National Research Council Canada - National Science Library

    Rudolph, Alan

    1995-01-01

    ... bovine hemoglobin in the normovolemic rat. We have also examined the administration of the liposome vehicle, tetrameric bovine hemoglobin, and liposome encapsulated bovine hemoglobin that had been lyophilized with 300 mM trehalose...

  18. A Generalized Affine Isoperimetric Inequality

    OpenAIRE

    Chen, Wenxiong; Howard, Ralph; Lutwak, Erwin; Yang, Deane; Zhang, Gaoyong

    2004-01-01

    A purely analytic proof is given for an inequality that has as a direct consequence the two most important affine isoperimetric inequalities of plane convex geometry: The Blaschke-Santalo inequality and the affine isoperimetric inequality of affine differential geometry.

  19. The Use of Hemoglobin Vesicles for Delivering Medicinal Gas for the Treatment of Intractable Disorders.

    Science.gov (United States)

    Taguchi, Kazuaki; Yamasaki, Keishi; Sakai, Hiromi; Maruyama, Toru; Otagiri, Masaki

    2017-09-01

    Bioactive gaseous molecules, such as oxygen (O 2 ) and carbon monoxide (CO), are essential elements for most living organisms to maintain their homeostasis and biological activities. An accumulating body of evidence suggests that such molecules can be used in clinics as a medical gas in the treatment of various intractable disorders. Recent developments in hemoglobin-encapsulated liposomes, namely hemoglobin vesicles (HbV), possess great potential for retaining O 2 and CO and could lead to strategies for the development of novel pharmacological agents as medical gas donors. HbV with either O 2 or CO bound to it has been demonstrated to have therapeutic potential for treating certain intractable disorders and has the possibility to serve as diagnostic and augmenting product by virtue of unique physicochemical characteristics of HbV. The present review provides an overview of the present status of the use of O 2 - or CO-binding HbV in experimental animal models of intractable disorders and discusses prospective clinical applications of HbV as a medical gas donor. Copyright © 2017 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

  20. Fatty acid and drug binding to a low-affinity component of human serum albumin, purified by affinity chromatography

    DEFF Research Database (Denmark)

    Vorum, H; Pedersen, A O; Honoré, B

    1992-01-01

    Binding equilibria for decanoate to a defatted, commercially available human serum albumin preparation were investigated by dialysis exchange rate determinations. The binding isotherm could not be fitted by the general binding equation. It was necessary to assume that the preparation was a mixture...... of two albumin components about 40% of the albumin having high affinity and about 60% having low affinity. By affinity chromatography we succeeded in purifying the low-affinity component from the mixture. The high-affinity component, however, could not be isolated. We further analyzed the fatty acid...... and drug binding abilities of the low-affinity component. The fatty acids decanoate, laurate, myristate and palmitate were bound with higher affinity to the mixture than to the low-affinity component. Diazepam was bound with nearly the same affinity to the low-affinity component as to the albumin mixture...

  1. Influence of heme environment structure on dioxygen affinity for the dual function Amphitrite ornata hemoglobin/dehaloperoxidase. Insights into the evolutional structure-function adaptations

    Energy Technology Data Exchange (ETDEWEB)

    Sun, Shengfang; Sono, Masanori; Wang, Chunxue; Du, Jing; Lebioda, Lukasz; Dawson, John H. [SC

    2014-05-15

    Sea worm, Amphitrite ornata, has evolved its globin (an O2 carrier) also to serves as a dehaloperoxidase (DHP) to detoxify haloaromatic pollutants generated by competing species. A previous mutagenesis study by our groups on both DHP and sperm whale myoglobin (SW Mb) revealed some structural factors that influence the dehaloperoxidase activities (significantly lower for Mb) of both proteins. Using an isocyanide/O2 partition constant measurement method in this study, we have examined the effects of these structural factors on the O2 equilibrium constants (KO2) of DHP, SW Mb, and their mutants. A clear trend of decreasing O2 affinity and increasing catalytic activity along with the increase in the distal His Nε–heme iron distance is observed. An H93K/T95H Mb double mutant mimicking the DHP proximal His positioning exhibited markedly enhanced O2 affinity, confirming the essential effect of proximal His rotation on the globin function of DHP. For DHP, the L100F, T56G and M86E variants showed the effects of distal volume, distal His flexibility and proximal electronic push, respectively, on the O2 affinity. This study provides insights into how DHP has evolved its heme environment to gain significantly enhanced peroxidase capability without compromising its primary function as an O2 carrier.

  2. [Hemoglobins, XXXII. Analysis of the primary structure of the monomeric hemoglobin CTT VIIA (erythrocruorin) or Chironomus thummi thummi, Diptera (author's transl)].

    Science.gov (United States)

    Kleinschmidt, T; Braunitzer, G

    1980-01-01

    The dimeric hemoglobin CTT VIIA (erythrocruorin) was isolated from the hemolymph of the larva from Chironomus thummi thummi and purified by preparative polyacrylamide gel electrophoresis. Peptides obtained by limited tryptical digestion were sequenced by automatic Edman degradation. For the elucidation of the sequence in the C-terminal region of the chain, additional cleavages with proteinase of Staphylococcus aureus and chymotrypsin were necessary. CTT VIIA is compared with human beta-chains and other hemoglobins of Chironomus. The amino acid residues in the pocket are especially discussed. Most of them are invariant in all Chironomus hemoglobins, independent of the size of the heme pocket, which is normal in some components and enlarged in others.

  3. Metal-loaded SBA-16-like silica – Correlation between basicity and affinity towards hydrogen

    International Nuclear Information System (INIS)

    Ouargli-Saker, R.; Bouazizi, N.; Boukoussa, B.; Barrimo, Diana; Paola-Nunes-Beltrao, Ana; Azzouz, A.

    2017-01-01

    Highlights: • Metal dispersion in longitudinal channels confers adsorption properties to SBA-16. • Both Fe"0-NPs and Cu"0-NPs seem to be responsible of this effect. • Effect of the repetitive adsorption-desorption cycles on CO_2 and water sorption. • Hydrogen storage on the functionalized materials. - Abstract: Nanoparticles of Cu"o (CuNPs) and Fe"o (FeNPs) were dispersed in SBA-16-like silica, resulting metal-loaded materials (Cu-SBA-16 and Fe-SBA-16) with improved affinity towards hydrogen. Electron microscopy and X-ray diffraction showed that MNP dispersion occurs mainly inside SBA-16 channels. MNP incorporation was found to confer affinity to the silica surface, since higher CO_2 retention capacity (CRC) was registered Cu/SBA-16 and Fe/SBA-16. This was accompanied by a significant improvement of the affinity towards hydrogen, as supported by hydrogen adsorption tests. This was explained in terms of strong hydrogen interaction with MNP and lattice oxygen atoms. The results reported herein open new prospects for SBA-16 as potential adsorbents for hydrogen storage.

  4. Metal-loaded SBA-16-like silica – Correlation between basicity and affinity towards hydrogen

    Energy Technology Data Exchange (ETDEWEB)

    Ouargli-Saker, R. [Department of Materials Engineering, University of Science and Technology, El M’naouer, BP 1505, Oran (Algeria); Nanoqam, Department of Chemistry, University of Quebec at Montreal, H3C3P8 (Canada); Bouazizi, N. [Nanoqam, Department of Chemistry, University of Quebec at Montreal, H3C3P8 (Canada); Unité de recherche, Electrochimie, Matériaux et Environnement, Faculté des Sciences de Gabès, Université de Gabès, Cité Erriadh, 6072 Gabès (Tunisia); Boukoussa, B. [Department of Materials Engineering, University of Science and Technology, El M’naouer, BP 1505, Oran (Algeria); Lqamb, Laboratório de Química Analítica Ambiental, Faculdade de Química, Pontifícia Universidade Católica do Rio Grande do Sul (Brazil); Barrimo, Diana [Nanoqam, Department of Chemistry, University of Quebec at Montreal, H3C3P8 (Canada); Paola-Nunes-Beltrao, Ana [Nanoqam, Department of Chemistry, University of Quebec at Montreal, H3C3P8 (Canada); Laboratory of Materials Chemistry L.C.M, University of Oran1 Ahmed Ben Bella, BP 1524, El-Mnaouer, 31000 Oran (Algeria); Azzouz, A., E-mail: azzouz.a@uqam.ca [Nanoqam, Department of Chemistry, University of Quebec at Montreal, H3C3P8 (Canada)

    2017-07-31

    Highlights: • Metal dispersion in longitudinal channels confers adsorption properties to SBA-16. • Both Fe{sup 0}-NPs and Cu{sup 0}-NPs seem to be responsible of this effect. • Effect of the repetitive adsorption-desorption cycles on CO{sub 2} and water sorption. • Hydrogen storage on the functionalized materials. - Abstract: Nanoparticles of Cu{sup o} (CuNPs) and Fe{sup o} (FeNPs) were dispersed in SBA-16-like silica, resulting metal-loaded materials (Cu-SBA-16 and Fe-SBA-16) with improved affinity towards hydrogen. Electron microscopy and X-ray diffraction showed that MNP dispersion occurs mainly inside SBA-16 channels. MNP incorporation was found to confer affinity to the silica surface, since higher CO{sub 2} retention capacity (CRC) was registered Cu/SBA-16 and Fe/SBA-16. This was accompanied by a significant improvement of the affinity towards hydrogen, as supported by hydrogen adsorption tests. This was explained in terms of strong hydrogen interaction with MNP and lattice oxygen atoms. The results reported herein open new prospects for SBA-16 as potential adsorbents for hydrogen storage.

  5. Severe anemia is associated with poor tumor oxygenation in head and neck squamous cell carcinomas

    International Nuclear Information System (INIS)

    Becker, Axel; Stadler, Peter; Lavey, Robert S.; Haensgen, Gabriele; Kuhnt, Thomas; Lautenschlaeger, Christine; Feldmann, Horst Juergen; Molls, Michael; Dunst, Juergen

    2000-01-01

    Purpose: To investigate the relationship between tumor oxygenation and the blood hemoglobin (Hb) concentration in patients with squamous cell carcinoma of the head and neck (SCCHN). Methods and Materials: A total of 133 patients with SCCHN underwent pretreatment polarographic pO 2 measurements of their tumors. In 66 patients measurements were also made in sternocleidomastoid muscles. The patients were divided into three groups according to their Hb concentration--severe anemia (Hb 2 . Conclusion: Our data suggest that a low Hb concentration and cigarette smoking contribute to inadequate oxygenation of SCCHN and thus for increased radioresistance. Consequently, Hb correction and abstinence from smoking may significantly improve tumor oxygenation

  6. FRET imaging of hemoglobin concentration in Plasmodium falciparum-infected red cells.

    Directory of Open Access Journals (Sweden)

    Alessandro Esposito

    Full Text Available During its intraerythrocytic asexual reproduction cycle Plasmodium falciparum consumes up to 80% of the host cell hemoglobin, in large excess over its metabolic needs. A model of the homeostasis of falciparum-infected red blood cells suggested an explanation based on the need to reduce the colloid-osmotic pressure within the host cell to prevent its premature lysis. Critical for this hypothesis was that the hemoglobin concentration within the host cell be progressively reduced from the trophozoite stage onwards.The experiments reported here were designed to test this hypothesis by direct measurements of the hemoglobin concentration in live, infected red cells. We developed a novel, non-invasive method to quantify the hemoglobin concentration in single cells, based on Förster resonance energy transfer between hemoglobin molecules and the fluorophore calcein. Fluorescence lifetime imaging allowed the quantitative mapping of the hemoglobin concentration within the cells. The average fluorescence lifetimes of uninfected cohorts was 270+/-30 ps (mean+/-SD; N = 45. In the cytoplasm of infected cells the fluorescence lifetime of calcein ranged from 290+/-20 ps for cells with ring stage parasites to 590+/-13 ps and 1050+/-60 ps for cells with young trophozoites and late stage trophozoite/early schizonts, respectively. This was equivalent to reductions in hemoglobin concentration spanning the range from 7.3 to 2.3 mM, in line with the model predictions. An unexpected ancillary finding was the existence of a microdomain under the host cell membrane with reduced calcein quenching by hemoglobin in cells with mature trophozoite stage parasites.The results support the predictions of the colloid-osmotic hypothesis and provide a better understanding of the homeostasis of malaria-infected red cells. In addition, they revealed the existence of a distinct peripheral microdomain in the host cell with limited access to hemoglobin molecules indicating the

  7. Quantifying risk of penile prosthesis infection with elevated glycosylated hemoglobin.

    Science.gov (United States)

    Wilson, S K; Carson, C C; Cleves, M A; Delk, J R

    1998-05-01

    Elevation of glycosylated hemoglobin above levels of 11.5 mg.% has been considered a contraindication to penile prosthesis implantation in diabetic patients. We determine the predictive value of glycosylated hemoglobin A1C in penile prosthesis infections in diabetic and nondiabetic patients to confirm or deny this prevalent opinion. We conducted a 2-year prospective study of 389 patients, including 114 diabetics, who underwent 3-piece penile prosthesis implantation. All patients had similar preoperative preparation without regard to diabetic status, control or glycosylated hemoglobin A1C level. Risk of infection was statistically analyzed for diabetics versus nondiabetics, glycosylated hemoglobin A1C values above and below 11.5 mg.%, insulin dependent versus oral medication diabetics, and fasting blood sugars above and below 180 mg.%. Prosthesis infections developed in 10 diabetics (8.7%) and 11 nondiabetics (4.0%). No increased infection rate was observed in diabetics with high fasting sugars or diabetics on insulin. There was no statistically significant increased infection risk with increased levels of glycosylated hemoglobin A1C among all patients or among only the diabetics. In fact, there was no meaningful difference in the median or mean level of glycosylated hemoglobin A1C in the infected and noninfected patients regardless of diabetes. Use of glycosylated hemoglobin A1C values to identify and exclude surgical candidates with increased risk of infections is not proved by this study. Elevation of fasting sugar or insulin dependence also does not increase risk of infection in diabetics undergoing prosthesis implantation.

  8. Determinants of oxygen and carbon dioxide transfer during extracorporeal membrane oxygenation in an experimental model of multiple organ dysfunction syndrome.

    Science.gov (United States)

    Park, Marcelo; Costa, Eduardo Leite Vieira; Maciel, Alexandre Toledo; Silva, Débora Prudêncio E; Friedrich, Natalia; Barbosa, Edzangela Vasconcelos Santos; Hirota, Adriana Sayuri; Schettino, Guilherme; Azevedo, Luciano Cesar Pontes

    2013-01-01

    Extracorporeal membrane oxygenation (ECMO) has gained renewed interest in the treatment of respiratory failure since the advent of the modern polymethylpentene membranes. Limited information exists, however, on the performance of these membranes in terms of gas transfers during multiple organ failure (MOF). We investigated determinants of oxygen and carbon dioxide transfer as well as biochemical alterations after the circulation of blood through the circuit in a pig model under ECMO support before and after induction of MOF. A predefined sequence of blood and sweep flows was tested before and after the induction of MOF with fecal peritonitis and saline lavage lung injury. In the multivariate analysis, oxygen transfer had a positive association with blood flow (slope = 66, Pmembrane PaCO(2) (slope = -0.96, P = 0.001) and SatO(2) (slope = -1.7, Ptransfer had a positive association with blood flow (slope = 17, Pmembrane PaCO(2) (slope = 1.2, Ptransfers were significantly determined by blood flow. Oxygen transfer was modulated by the pre-membrane SatO(2) and CO(2), while carbon dioxide transfer was affected by the gas flow, pre-membrane CO(2) and hemoglobin.

  9. Oxygen and Perfusion Kinetics in Response to Fractionated Radiation Therapy in FaDu Head and Neck Cancer Xenografts Are Related to Treatment Outcome

    Energy Technology Data Exchange (ETDEWEB)

    Hu, Fangyao [Department of Biomedical Engineering, Duke University, Durham, North Carolina (United States); Vishwanath, Karthik [Department of Physics, Miami University, Oxford, Ohio (United States); Salama, Joseph K. [Department of Radiation Oncology, Duke University, Durham, North Carolina (United States); Division of Radiation Oncology, Veterans Administration Medical Center, Durham, North Carolina (United States); Erkanli, Alaattin; Peterson, Bercedis [Department of Biostatistics and Bioinformatics, Duke University Medical Center, Durham, North Carolina (United States); Oleson, James R. [Department of Radiation Oncology, Duke University, Durham, North Carolina (United States); Division of Radiation Oncology, Veterans Administration Medical Center, Durham, North Carolina (United States); Lee, Walter T. [Department of Radiation Oncology, Duke University, Durham, North Carolina (United States); Division of Head and Neck Surgery and Communicative Sciences, Duke University Medical Center, Durham, North Carolina (United States); Section of Otolaryngology Head and Neck Surgery, Veterans Administration Medical Center, Durham, North Carolina (United States); Brizel, David M. [Department of Radiation Oncology, Duke University, Durham, North Carolina (United States); Division of Head and Neck Surgery and Communicative Sciences, Duke University Medical Center, Durham, North Carolina (United States); Ramanujam, Nimmi [Department of Biomedical Engineering, Duke University, Durham, North Carolina (United States); Dewhirst, Mark W., E-mail: mark.dewhirst@duke.edu [Department of Radiation Oncology, Duke University, Durham, North Carolina (United States)

    2016-10-01

    Purpose: To test whether oxygenation kinetics correlate with the likelihood for local tumor control after fractionated radiation therapy. Methods and Materials: We used diffuse reflectance spectroscopy to noninvasively measure tumor vascular oxygenation and total hemoglobin concentration associated with radiation therapy of 5 daily fractions (7.5, 9, or 13.5 Gy/d) in FaDu xenografts. Spectroscopy measurements were obtained immediately before each daily radiation fraction and during the week after radiation therapy. Oxygen saturation and total hemoglobin concentration were computed using an inverse Monte Carlo model. Results: First, oxygenation kinetics during and after radiation therapy, but before tumor volumes changed, were associated with local tumor control. Locally controlled tumors exhibited significantly faster increases in oxygenation after radiation therapy (days 12-15) compared with tumors that recurred locally. Second, within the group of tumors that recurred, faster increases in oxygenation during radiation therapy (day 3-5 interval) were correlated with earlier recurrence times. An area of 0.74 under the receiver operating characteristic curve was achieved when classifying the local control tumors from all irradiated tumors using the oxygen kinetics with a logistic regression model. Third, the rate of increase in oxygenation was radiation dose dependent. Radiation doses ≤9.5 Gy/d did not initiate an increase in oxygenation, whereas 13.5 Gy/d triggered significant increases in oxygenation during and after radiation therapy. Conclusions: Additional confirmation is required in other tumor models, but these results suggest that monitoring tumor oxygenation kinetics could aid in the prediction of local tumor control after radiation therapy.

  10. Oxygen and Perfusion Kinetics in Response to Fractionated Radiation Therapy in FaDu Head and Neck Cancer Xenografts Are Related to Treatment Outcome

    International Nuclear Information System (INIS)

    Hu, Fangyao; Vishwanath, Karthik; Salama, Joseph K.; Erkanli, Alaattin; Peterson, Bercedis; Oleson, James R.; Lee, Walter T.; Brizel, David M.; Ramanujam, Nimmi; Dewhirst, Mark W.

    2016-01-01

    Purpose: To test whether oxygenation kinetics correlate with the likelihood for local tumor control after fractionated radiation therapy. Methods and Materials: We used diffuse reflectance spectroscopy to noninvasively measure tumor vascular oxygenation and total hemoglobin concentration associated with radiation therapy of 5 daily fractions (7.5, 9, or 13.5 Gy/d) in FaDu xenografts. Spectroscopy measurements were obtained immediately before each daily radiation fraction and during the week after radiation therapy. Oxygen saturation and total hemoglobin concentration were computed using an inverse Monte Carlo model. Results: First, oxygenation kinetics during and after radiation therapy, but before tumor volumes changed, were associated with local tumor control. Locally controlled tumors exhibited significantly faster increases in oxygenation after radiation therapy (days 12-15) compared with tumors that recurred locally. Second, within the group of tumors that recurred, faster increases in oxygenation during radiation therapy (day 3-5 interval) were correlated with earlier recurrence times. An area of 0.74 under the receiver operating characteristic curve was achieved when classifying the local control tumors from all irradiated tumors using the oxygen kinetics with a logistic regression model. Third, the rate of increase in oxygenation was radiation dose dependent. Radiation doses ≤9.5 Gy/d did not initiate an increase in oxygenation, whereas 13.5 Gy/d triggered significant increases in oxygenation during and after radiation therapy. Conclusions: Additional confirmation is required in other tumor models, but these results suggest that monitoring tumor oxygenation kinetics could aid in the prediction of local tumor control after radiation therapy.

  11. Lp-mixed affine surface area

    Science.gov (United States)

    Wang, Weidong; Leng, Gangsong

    2007-11-01

    According to the three notions of mixed affine surface area, Lp-affine surface area and Lp-mixed affine surface area proposed by Lutwak, in this article, we give the concept of ith Lp-mixed affine surface area such that the first and second notions of Lutwak are its special cases. Further, some Lutwak's results are extended associated with this concept. Besides, applying this concept, we establish an inequality for the volumes and dual quermassintegrals of a class of star bodies.

  12. Amphiphilic Bio-molecules/ZnO Interface: Enhancement of Bio-affinity and Dispersibility

    International Nuclear Information System (INIS)

    Meng Xiu-Qing; Fang Yun-Zhang; Wu Feng-Min

    2012-01-01

    The dispersibility of bio-molecules such as lecithins on the surface of ZnO nanowires are investigated for biosensor applications. Lecithins can be absorbed on an as-synthesized ZnO nanowire surface in the form of sub-micro sized clusters, while scattering well on those annealed under oxygen atmosphere. Wettability analysis reveals that the as-synthesized ZnO nanowires bear a super-hydrophobic surface, which convents to superhydrophilic after oxygen annealing. First-principles calculations indicate that the adsorption energy of ZnO with water is about 0.2 eV at a distance of 2 Å when it is superhydrophilic, suggesting that lecithin can be absorbed on the hydrophilic surface stably at this distance and the bio-affinity can be enhanced under this condition. (condensed matter: structure, mechanical and thermal properties)

  13. Oxygen binding properties, capillary densities and heart weights in high altitude camelids.

    Science.gov (United States)

    Jürgens, K D; Pietschmann, M; Yamaguchi, K; Kleinschmidt, T

    1988-01-01

    The oxygen binding properties of the blood of the camelid species vicuna, llama, alpaca and dromedary camel were measured and evaluated with respect to interspecific differences. The highest blood oxygen affinity, not only among camelids but of all mammals investigated so far, was found in the vicuna (P50 = 17.6 Torr compared to 20.3-21.6 Torr in the other species). Low hematocrits (23-34%) and small red blood cells (21-30 microns 3) are common features of all camelids, but the lowest values are found in the Lama species. Capillary densities were determined in heart and soleus muscle of vicuna and llama. Again, the vicuna shows exceptional values (3720 cap/mm2 on average in the heart) for a mammal of this body size. Finally, heart weight as percent of body weight is higher in the vicuna (0.7-0.9%) than in the other camelids studied (0.5-0.7%). The possibility that these parameters, measured in New World tylopodes at sea level, are not likely to change considerably with transfer to high altitude, is discussed. In the vicuna, a unique combination of the following features seems to be responsible for an outstanding physical capability at high altitude: saturation of blood with oxygen in the lung is favored by a high blood oxygen affinity, oxygen supply being facilitated by low diffusion distances in the muscle tissue. Loading, as well as unloading, of oxygen is improved by a relatively high oxygen transfer conductance of the red blood cells, which is due to their small size and which compensates the negative effect of a low hematocrit on the oxygen conductance of blood.(ABSTRACT TRUNCATED AT 250 WORDS)

  14. Ammonium and nitrite oxidation at nanomolar oxygen concentrations in oxygen minimum zone waters.

    Science.gov (United States)

    Bristow, Laura A; Dalsgaard, Tage; Tiano, Laura; Mills, Daniel B; Bertagnolli, Anthony D; Wright, Jody J; Hallam, Steven J; Ulloa, Osvaldo; Canfield, Donald E; Revsbech, Niels Peter; Thamdrup, Bo

    2016-09-20

    A major percentage of fixed nitrogen (N) loss in the oceans occurs within nitrite-rich oxygen minimum zones (OMZs) via denitrification and anammox. It remains unclear to what extent ammonium and nitrite oxidation co-occur, either supplying or competing for substrates involved in nitrogen loss in the OMZ core. Assessment of the oxygen (O2) sensitivity of these processes down to the O2 concentrations present in the OMZ core (Chile at manipulated O2 levels between 5 nmol⋅L(-1) and 20 μmol⋅L(-1) Rates of both processes were detectable in the low nanomolar range (5-33 nmol⋅L(-1) O2), but demonstrated a strong dependence on O2 concentrations with apparent half-saturation constants (Kms) of 333 ± 130 nmol⋅L(-1) O2 for ammonium oxidation and 778 ± 168 nmol⋅L(-1) O2 for nitrite oxidation assuming one-component Michaelis-Menten kinetics. Nitrite oxidation rates, however, were better described with a two-component Michaelis-Menten model, indicating a high-affinity component with a Km of just a few nanomolar. As the communities of ammonium and nitrite oxidizers were similar to other OMZs, these kinetics should apply across OMZ systems. The high O2 affinities imply that ammonium and nitrite oxidation can occur within the OMZ core whenever O2 is supplied, for example, by episodic intrusions. These processes therefore compete with anammox and denitrification for ammonium and nitrite, thereby exerting an important control over nitrogen loss.

  15. Comparison of pulseoximetry oxygen saturation and arterial oxygen saturation in open heart intensive care unit

    Directory of Open Access Journals (Sweden)

    Alireza Mahoori

    2013-08-01

    Full Text Available Background: Pulseoximetry is widely used in the critical care setting, currently used to guide therapeutic interventions. Few studies have evaluated the accuracy of SPO2 (puls-eoximetry oxygen saturation in intensive care unit after cardiac surgery. Our objective was to compare pulseoximetry with arterial oxygen saturation (SaO2 during clinical routine in such patients, and to examine the effect of mild acidosis on this relationship.Methods: In an observational prospective study 80 patients were evaluated in intensive care unit after cardiac surgery. SPO2 was recorded and compared with SaO2 obtained by blood gas analysis. One or serial arterial blood gas analyses (ABGs were performed via a radial artery line while a reliable pulseoximeter signal was present. One hundred thirty seven samples were collected and for each blood gas analyses, SaO2 and SPO2 we recorded.Results: O2 saturation as a marker of peripheral perfusion was measured by Pulseoxim-etry (SPO2. The mean difference between arterial oxygen saturation and pulseoximetry oxygen saturation was 0.12%±1.6%. A total of 137 paired readings demonstrated good correlation (r=0.754; P<0.0001 between changes in SPO2 and those in SaO2 in samples with normal hemoglobin. Also in forty seven samples with mild acidosis, paired readings demonstrated good correlation (r=0.799; P<0.0001 and the mean difference between SaO2 and SPO2 was 0.05%±1.5%.Conclusion: Data showed that in patients with stable hemodynamic and good signal quality, changes in pulseoximetry oxygen saturation reliably predict equivalent changes in arterial oxygen saturation. Mild acidosis doesn’t alter the relation between SPO2 and SaO2 to any clinically important extent. In conclusion, the pulse oximeter is useful to monitor oxygen saturation in patients with stable hemodynamic.

  16. Hb Heathrow [β103(G5)Phe→Leu], a First Report in an Asian Patient with Erythrocytosis.

    Science.gov (United States)

    Shin, Sang Yong; Kim, Hyun Young; Kim, Hee Jin; Kim, Hoon Gu

    2017-05-01

    Congenital erythrocytosis (CE) is a rare and heterogeneous disease. The high oxygen affinity hemoglobin (Hb) variants are the most common cause of CE. Herein, we report a Korean patient with isolated erythrocytosis. A 25-year-old man was referred to our hospital for evaluation of high Hb level (Hb 20.4 g/dL, hematocrit 58%, reticulocyte count 2.90%, white blood cell count 6.83×10⁹/L, and platelet count 195×10⁹/L). Bone marrow biopsy revealed normocellular marrow without myeloproliferative features. JAK2 (V617F, exon 12), CALR (exon 9), and MPL W515K/L mutations were not detected. P₅₀ (partial pressure at which Hb is half saturated with oxygen), which is an indicator of left-shift of oxygen dissociation curve (high oxygen affinity state), was 14.3 mm Hg (reference value 22.6-29.4 mm Hg). He was suspected to have CE. Mutation analysis of the HBB gene revealed the known Hb variant, Hb Heathrow [β103(G5)Phe→Leu]. This is the first report of Hb Heathrow in Asian. © Copyright: Yonsei University College of Medicine 2017.

  17. PERBEDAAN KADAR HEMOGLOBIN METODE SIANMETHEMOGLOBIN DENGAN DAN TANPA SENTRIFUGASI PADA SAMPEL LEUKOSITOSIS

    Directory of Open Access Journals (Sweden)

    wahdah norsiah

    2015-12-01

    Full Text Available Abstract: Examination of hemoglobin levels influenced leukocytosis sianmethemoglobin method that causes increased absorbance measurements of hemoglobin levels increased significantly and the false blood sample that has been diluted with a solution Drabkins in centrifugation at 3000 rpm for 10 minutes and then the absorbance of the supernatant was measured with a photometer at λ 546 nm. This study aimed to analyze the differences in hemoglobin level examination siamethemoglobin method with and without centrifugation at sample leukocytosis. This type of research is observational research laboratory. The study design was cross-sectional study. Samples were taken from the remaining blood samples of patients who have been examined leukositnya number more than 20,000 / uL with Hematology Analyzer (CEL-DYN Ruby February-April 2014, and were divided into 4 groups based on criteria that group 1. leukocyte count of 20,000 / uL-29 999 / mL, group II. 30,000 / uL-39 999 / uL, the group III. 40,000 / uL-49,999 / uL, the group IV. More than 50,000 / uL. The number of samples taken were 20 samples of each group, a total sample of 80 samples. The analysis showed no significant difference in hemoglobin levels siamethemoglobin method with and without centrifugation at sample leukocytosis with a value of p = 0.000 less than 0.05 α. Leukocytosis Turbidity affects the difference in hemoglobin levels with and without centrifugation, the higher the number the greater the difference in leukocyte levels of hemoglobin, hemoglobin level examination results of the study based on the criteria of the number of leukocytes obtained by the difference in hemoglobin levels with and without centrifugation in group I. 0.22 ± 0.07 g / dL, group II 0.40 ± 0.22 g / dL, a group III. 0.44 ± 0.14 g / dL, Group IV. 0.85 ± 0.41 g / dL. The level of hemoglobin in the sample sianmethemoglobin method leukocytosis with more than 20,000 / uL need a centrifuge so that appropriate

  18. Study of LAXS Profile of Hemoglobin from Irradiated Blood

    International Nuclear Information System (INIS)

    Selim, N.S.; Desouky, O.S.; Elshemey, W.M.

    2006-01-01

    The present work aims to move a step forward towards a deeper understanding of the scattering of x-ray, from lyophilized biological samples. Comparative study has been performed using low angle x-ray scattering (LAXS) and UV-visible spectrophotometry for monitoring the dose response characteristics of the hemoglobin molecule of irradiated blood. Blood samples were exposed to gamma rays, at doses ranging from 5 up to 100 Gy. Diluted hemoglobin solution was scanned in the UV-visible range (200-700 nm), and lyophilized hemoglobin was prepared for LAXS measurement. The radiation-induced changes in the hemoglobin structure have been evaluated. The LAXS profile of hemoglobin molecule is characterized by the presence of 2 peaks in the forward direction of scattering. These peaks were found to be sensitive to the variations in the molecular structure of a given sample. The obtained results suggest that the 1st peak, recorded at 4.65O (equivalent to momentum transfer, x= 0.526 nm-1), is sensitive to the tertiary and quaternary structure of the globin part, while the major peak, recorded at 10.5O (equivalent to momentum transfer, x= 1.189 nm-1), appeared to be related to its primary and secondary structure

  19. Is a blood sample for hemoglobins in the transfusional range reliable?

    Science.gov (United States)

    López, A; Gómez, L; Petinal, G; Adán, N; Alvarado, S; Carballo, N

    2018-02-27

    To evaluate the correlation and agreement in our unit and population of hemoglobin in gasometry versus hematology analyzer, to evaluate errors in transfusion or lack thereof. strong association between Point-of-care (POC) and hematimetry, with P<.001, with a coefficient of determination r 2 of 0.56, an intraclass correlation coefficient of 0.63 and a Lin's concordance correlation coefficient of 0.65. For hemoglobins less than 7g/dL, a success rate of 29.41% was obtained. Low-moderate agreement of POC hemoglobin with standard haemothymetry. High probability of errors in the indication of transfusion based on gasometer hemoglobins, especially in low hemoglobins. Copyright © 2018 Sociedad Española de Anestesiología, Reanimación y Terapéutica del Dolor. Publicado por Elsevier España, S.L.U. All rights reserved.

  20. Hemoglobin Levels Across the Pediatric Critical Care Spectrum: A Point Prevalence Study.

    Science.gov (United States)

    Hassan, Nabil E; Reischman, Diann E; Fitzgerald, Robert K; Faustino, Edward Vincent S

    2018-05-01

    To determine the prevailing hemoglobin levels in PICU patients, and any potential correlates. Post hoc analysis of prospective multicenter observational data. Fifty-nine PICUs in seven countries. PICU patients on four specific days in 2012. None. Patients' hemoglobin and other clinical and institutional data. Two thousand three hundred eighty-nine patients with median age of 1.9 years (interquartile range, 0.3-9.8 yr), weight 11.5 kg (interquartile range, 5.4-29.6 kg), and preceding PICU stay of 4.0 days (interquartile range, 1.0-13.0 d). Their median hemoglobin was 11.0 g/dL (interquartile range, 9.6-12.5 g/dL). The prevalence of transfusion in the 24 hours preceding data collection was 14.2%. Neonates had the highest hemoglobin at 13.1 g/dL (interquartile range, 11.2-15.0 g/dL) compared with other age groups (p < 0.001). The percentage of 31.3 of the patients had hemoglobin of greater than or equal to 12 g/dL, and 1.1% had hemoglobin of less than 7 g/dL. Blacks had lower median hemoglobin (10.5; interquartile range, 9.3-12.1 g/dL) compared with whites (median, 11.1; interquartile range, 9.0-12.6; p < 0.001). Patients in Spain and Portugal had the highest median hemoglobin (11.4; interquartile range, 10.0-12.6) compared with other regions outside of the United States (p < 0.001), and the highest proportion (31.3%) of transfused patients compared with all regions (p < 0.001). Patients in cardiac PICUs had higher median hemoglobin than those in mixed PICUs or noncardiac PICUs (12.3, 11.0, and 10.6 g/dL, respectively; p < 0.001). Cyanotic heart disease patients had the highest median hemoglobin (12.6 g/dL; interquartile range, 11.1-14.5). Multivariable regression analysis within diagnosis groups revealed that hemoglobin levels were significantly associated with the geographic location and history of complex cardiac disease in most of the models. In children with cancer, none of the variables tested correlated with patients' hemoglobin levels

  1. Point-of-care hemoglobin testing for postmortem diagnosis of anemia.

    Science.gov (United States)

    Na, Joo-Young; Park, Ji Hye; Choi, Byung Ha; Kim, Hyung-Seok; Park, Jong-Tae

    2018-03-01

    An autopsy involves examination of a body using invasive methods such as dissection, and includes various tests using samples procured during dissection. During medicolegal autopsies, the blood carboxyhemoglobin concentration is commonly measured using the AVOXimeter® 4000 as a point-of-care test. When evaluating the body following hypovolemic shock, characteristics such as reduced livor mortis or an anemic appearance of the viscera can be identified, but these observations arequite subjective. Thus, a more objective test is required for the postmortem diagnosis of anemia. In the present study, the AVOXimeter® 4000 was used to investigate the utility of point-of-care hemoglobin testing. Hemoglobin tests were performed in 93 autopsy cases. The AVOXimeter® 4000 and the BC-2800 Auto Hematology Analyzer were used to test identical samples in 29 of these cases. The results of hemoglobin tests performed with these two devices were statistically similar (r = 0.969). The results of hemoglobin tests using postmortem blood were compared with antemortem test results from medical records from 31 cases, and these results were similar. In 13 of 17 cases of death from internal hemorrhage, hemoglobin levels were lower in the cardiac blood than in blood from the affected body cavity, likely due to compensatory changes induced by antemortem hemorrhage. It is concluded that blood hemoglobin testing may be useful as a point-of-care test for diagnosing postmortem anemia.

  2. Enhancement of Salinity Tolerance during Rice Seed Germination by Presoaking with Hemoglobin

    Directory of Open Access Journals (Sweden)

    Sheng Xu

    2011-04-01

    Full Text Available Salinity stress is an important environmental constraint limiting the productivity of many crops worldwide. In this report, experiments were conducted to investigate the effects of seed presoaking by bovine hemoglobin, an inducer of heme oxygenase-1 (HO-1, on salinity tolerance in rice (Oryza sativa plants. The results showed that different concentrations of the hemoglobin (0.01, 0.05, 0.2, 1.0, and 5.0 g/L differentially alleviated the inhibition of rice seed germination and thereafter seedling shoot growth caused by 100 mM NaCl stress, and the responses of 1.0 g/L hemoglobin was the most obvious. Further analyses showed that application of hemoglobin not only increased the HO-1 gene expression, but also differentially induced catalase (CAT, ascorbate peroxidase (APX, and superoxide dismutase (SOD activities or transcripts, thus decreasing the lipid peroxidation in germinating rice seeds subjected to salt stress. Compared with non-hemoglobin treatment, hemoglobin presoaking also increased the potassium (K to sodium (Na ratio both in the root and shoot parts after salinity stress. The effect is specific for HO-1 since the potent HO-1 inhibitor zinc protoporphyrin IX (ZnPPIX blocked the positive actions of hemoglobin on seed germination and seedling shoot growth. Overall, these results suggested that hemoglobin performs an advantageous role in enhancement of salinity tolerance during rice seed germination.

  3. Mapping Affinities in Academic Organizations

    Directory of Open Access Journals (Sweden)

    Dario Rodighiero

    2018-02-01

    Full Text Available Scholarly affinities are one of the most fundamental hidden dynamics that drive scientific development. Some affinities are actual, and consequently can be measured through classical academic metrics such as co-authoring. Other affinities are potential, and therefore do not leave visible traces in information systems; for instance, some peers may share interests without actually knowing it. This article illustrates the development of a map of affinities for academic collectives, designed to be relevant to three audiences: the management, the scholars themselves, and the external public. Our case study involves the School of Architecture, Civil and Environmental Engineering of EPFL, hereinafter ENAC. The school consists of around 1,000 scholars, 70 laboratories, and 3 institutes. The actual affinities are modeled using the data available from the information systems reporting publications, teaching, and advising scholars, whereas the potential affinities are addressed through text mining of the publications. The major challenge for designing such a map is to represent the multi-dimensionality and multi-scale nature of the information. The affinities are not limited to the computation of heterogeneous sources of information; they also apply at different scales. The map, thus, shows local affinities inside a given laboratory, as well as global affinities among laboratories. This article presents a graphical grammar to represent affinities. Its effectiveness is illustrated by two actualizations of the design proposal: an interactive online system in which the map can be parameterized, and a large-scale carpet of 250 square meters. In both cases, we discuss how the materiality influences the representation of data, in particular the way key questions could be appropriately addressed considering the three target audiences: the insights gained by the management and their consequences in terms of governance, the understanding of the scholars’ own

  4. Novel subunit structure observed for noncooperative hemoglobin from Urechis caupo.

    Science.gov (United States)

    Kolatkar, P R; Meador, W E; Stanfield, R L; Hackert, M L

    1988-03-05

    Tetrameric hemoglobin from the "fat innkeeper" worm Urechis caupo possesses a novel subunit arrangement having an "inside out" quaternary structure in that the G/H helices are located on the outer surface of the tetramer. A 5-A resolution crystal structure reveals that although the individual subunits are beta-like, having a distinct D helix and the general myoglobin fold, the subunit contacts are very different from those previously observed for hemoglobins. Furthermore, the hemoglobin from U. caupo is also quite different from the unusual hemoglobin tetramer from clam which also has its G/H helices on the outer surface but with the hemes in close proximity through E-F helical contacts (Royer, W. E., Jr., Love, W. E., and Fenderson, F. F. (1985) Nature 316, 277-280).

  5. Effect of smoking on oxygen delivery and outcome in patients treated with radiotherapy for head and neck squamous cell carcinoma – A prospective study

    International Nuclear Information System (INIS)

    Molich Hoff, Camilla; Grau, Cai; Overgaard, Jens

    2012-01-01

    Background: Head and neck cancer patients with high hemoglobin respond better to irradiation compared to patients with low hemoglobin possibly due to hypoxia induced radioresistance. The hemoglobin level is, however, a crude indicator of the amount of oxygen available to the tissue and may be influenced by a number of factors, smoking being of potential importance. The aim of the present study was to examine the effect of smoking on available oxygen to tumors and the effect on outcome in head and neck cancer patients treated with radiotherapy in a prospective study. Materials and methods: A total of 232 consecutive patients with squamous cell carcinoma of the larynx, pharynx and oral cavity completed questionnaires on smoking habits prior to treatment. Venous blood samples were collected before and/or during treatment to determine the hemoglobin and carboxyhemoglobin level. Patients were treated with primary curative radiotherapy 62–68 Gy, 2 Gy/fx, 5 fx/week. Results: All but 12 patients had a history of smoking, 35 were long term quitters, 23 recent quitters, 54 moderate smokers and 108 heavy smokers (>1 pack/day). There was no relationship between total hemoglobin and carboxyhemoglobin, but effective hemoglobin and carboxyhemoglobin were linearly correlated. The amount of carboxyhemoglobin increased with increasing smoking status. Actuarial 5-year univariate analysis showed that heavy smokers had a significantly reduced probability of loco-regional control (44% vs. 65%, p = 0.001), disease-specific (56% vs. 77%, p = 0.003) and overall survival (39% vs. 66%, p = 0.0004) compared to non-smoking patients. Multivariate analyses showed that patients characterized as non-smokers, with low T and N classifications and high hemoglobin level had the best outcome measurements. A rise in carboxyhemoglobin significantly decreased the probability of loco-regional control and each additional pack year increased the risk of death. Smokers and former smokers develop secondary

  6. A Novel β-Globin Chain Hemoglobin Variant, Hb Allentown [β137(H15)Val→Trp (GTG>TGG) HBB: c.412_413delinsTG, p.Val138Trp], Associated with Low Oxygen Saturation, Intermittent Aplastic Crises and Splenomegaly.

    Science.gov (United States)

    Collier, Anderson B; Coon, Lea M; Monteleone, Philip; Umaru, Samuel; Swanson, Kenneth C; Hoyer, James D; Oliveira, Jennifer L

    2016-01-01

    Hemoglobin (Hb) variants may be associated with low oxygen saturation and exacerbated episodes of anemia from common stressors such as viral infections. These attributes frequently cause increased clinical concern and unnecessary and expensive testing if not considered early in the evaluation of the patient. Some clinically significant Hb variants result in a normal Hb electrophoresis result, which can be method-dependent. Herein we describe a patient with low oxygen saturation and a history of hemolytic anemia who was subsequently found to carry a novel, unstable β-globin variant that we have named Hb Allentown [β137(H15)Val→Trp (GTG>TGG) HBB: c.412_413delinsTG, p.Val138Trp] for the place of identification of the variant. Hb Allentown is formed by a rare double nucleotide substitution within the same codon. Additionally, positive identification of rare Hb variants characterized by a single method is discouraged, as the Hb variant was misclassified as Hb S-South End or β6(A3)Glu→Val;β132(H10)Lys→Asn (HBB: c.[20A > T;399A > C]) by the initial laboratory.

  7. Fundamentals of affinity cell separations.

    Science.gov (United States)

    Zhang, Ye; Lyons, Veronica; Pappas, Dimitri

    2018-03-01

    Cell separations using affinity methods continue to be an enabling science for a wide variety of applications. In this review, we discuss the fundamental aspects of affinity separation, including the competing forces for cell capture and elution, cell-surface interactions, and models for cell adhesion. Factors affecting separation performance such as bond affinity, contact area, and temperature are presented. We also discuss and demonstrate the effects of nonspecific binding on separation performance. Metrics for evaluating cell separations are presented, along with methods of comparing separation techniques for cell isolation using affinity capture. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  8. Improvements in or relating to antibodies active against human hemoglobin Asub(1C)

    International Nuclear Information System (INIS)

    Javid, J.; Cerami, A.; Koenig, R.J.; Pettis, P.K.

    1980-01-01

    A method is described for preparing an antibody against human hemoglobin Asub(1c) which is substantially free of cross-reactivity against the human hemoglobins A 0 , Asub(1a) and Asub(1b). The antibodies are collected from cats, goats or sheep following injections of purified hemoglobin Asub(1c) antigen since these animals do not naturally produce hemoglobin Asub(1c). A radioimmunoassay method is also described whereby these antibodies are used to determine the quantity of hemoglobin Asub(1c) in blood samples. This is a useful technique in the diagnosis of diabetes mellitus. (U.K.)

  9. Noninvasive optical quantification of absolute blood flow, blood oxygenation, and oxygen consumption rate in exercising skeletal muscle

    Science.gov (United States)

    Gurley, Katelyn; Shang, Yu; Yu, Guoqiang

    2012-07-01

    This study investigates a method using novel hybrid diffuse optical spectroscopies [near-infrared spectroscopy (NIRS) and diffuse correlation spectroscopy (DCS)] to obtain continuous, noninvasive measurement of absolute blood flow (BF), blood oxygenation, and oxygen consumption rate (\\Vdot O2) in exercising skeletal muscle. Healthy subjects (n=9) performed a handgrip exercise to increase BF and \\Vdot O2 in forearm flexor muscles, while a hybrid optical probe on the skin surface directly monitored oxy-, deoxy-, and total hemoglobin concentrations ([HbO2], [Hb], and THC), tissue oxygen saturation (StO2), relative BF (rBF), and relative oxygen consumption rate (r\\Vdot O2). The rBF and r\\Vdot O2 signals were calibrated with absolute baseline BF and \\Vdot O2 obtained through venous and arterial occlusions, respectively. Known problems with muscle-fiber motion artifacts in optical measurements during exercise were mitigated using a novel gating algorithm that determined muscle contraction status based on control signals from a dynamometer. Results were consistent with previous findings in the literature. This study supports the application of NIRS/DCS technology to quantitatively evaluate hemodynamic and metabolic parameters in exercising skeletal muscle and holds promise for improving diagnosis and treatment evaluation for patients suffering from diseases affecting skeletal muscle and advancing fundamental understanding of muscle and exercise physiology.

  10. Physical and Chemical Processes and the Morphofunctional Characteristics of Human Erythrocytes in Hyperglycaemia

    Directory of Open Access Journals (Sweden)

    Victor V. Revin

    2017-08-01

    Full Text Available Background: This study examines the effect of graduated hyperglycaemia on the state and oxygen-binding ability of hemoglobin, the correlation of phospholipid fractions and their metabolites in the membrane, the activity of proteolytic enzymes and the morphofunctional state of erythrocytes.Methods: Conformational changes in the molecule of hemoglobin were determined by Raman spectroscopy. The structure of the erythrocytes was analyzed using laser interference microscopy (LIM. To determine the activity of NADN-methemoglobinreductase, we used the P.G. Board method. The degree of glycosylation of the erythrocyte membranes was determined using a method previously described by Felkoren et al. Lipid extraction was performed using the Bligh and Dyer method. Detection of the phospholipids was performed using V. E. Vaskovsky method.Results: Conditions of hyperglycaemia are characterized by a low affinity of hemoglobin to oxygen, which is manifested as a parallel decrease in the content of hemoglobin oxyform and the growth of deoxyform, methemoglobin and membrane-bound hemoglobin. The degree of glycosylation of membrane proteins and hemoglobin is high. For example, in the case of hyperglycaemia, erythrocytic membranes reduce the content of all phospholipid fractions with a simultaneous increase in lysoforms, free fatty acids and the diacylglycerol (DAG. Step wise hyperglycaemia in incubation medium and human erythrocytes results in an increased content of peptide components and general trypsin-like activity in the cytosol, with a simultaneous decreased activity of μ-calpain and caspase 3.Conclusions: Metabolic disorders and damage of cell membranes during hyperglycaemia cause an increase in the population of echinocytes and spherocytes. The resulting disorders are accompanied with a high probability of intravascular haemolysis.

  11. Lower versus Higher Hemoglobin Threshold for Transfusion in Septic Shock

    DEFF Research Database (Denmark)

    Holst, Lars B; Haase, Nicolai; Wetterslev, Jørn

    2014-01-01

    BACKGROUND: Blood transfusions are frequently given to patients with septic shock. However, the benefits and harms of different hemoglobin thresholds for transfusion have not been established. METHODS: In this multicenter, parallel-group trial, we randomly assigned patients in the intensive care...... unit (ICU) who had septic shock and a hemoglobin concentration of 9 g per deciliter or less to receive 1 unit of leukoreduced red cells when the hemoglobin level was 7 g per deciliter or less (lower threshold) or when the level was 9 g per deciliter or less (higher threshold) during the ICU stay...... were similar in the two intervention groups. CONCLUSIONS: Among patients with septic shock, mortality at 90 days and rates of ischemic events and use of life support were similar among those assigned to blood transfusion at a higher hemoglobin threshold and those assigned to blood transfusion...

  12. Comparison of changes in oxygenated hemoglobin during the tree-drawing task between patients with schizophrenia and healthy controls

    Directory of Open Access Journals (Sweden)

    Nakano S

    2018-04-01

    Full Text Available Shinya Nakano,1,2 Yoshihisa Shoji,1,3 Kiichiro Morita,1,3 Hiroyasu Igimi,1,4 Mamoru Sato,1,3 Youhei Ishii,1 Akihiko Kondo,1 Naohisa Uchimura1,3 1Cognitive and Molecular Research Institute of Brain Diseases, Kurume University, Kurume, Japan; 2Department of Clinical Laboratory Medicine, Kurume University Hospital, Kurume, Japan; 3Department of Neuropsychiatry, Kurume University School of Medicine, Kurume, Japan; 4Department of Neuropsychiatry, Horikawa Hospital, Medical Corporation Association Horikawakai, Kurume, Japan Background: Tree-drawing test is used as a projective psychological test that expresses the abnormal internal experience in patients with schizophrenia (SZ. Despite the widely accepted view that the cognitive function is involved in characteristic tree-drawing in patients with SZ, no study has psychophysiologically examined it. The present study aimed to investigate the involvement of cognitive function during tree-drawing in patients with SZ. For that purpose, we evaluated the brain function in patients with SZ during a tree-drawing task by using near-infrared spectroscopy (NIRS and compared them with those in healthy controls. Patients and methods: The subjects were 28 healthy controls and 28 patients with SZ. Changes in the oxygenated hemoglobin ([oxy-Hb] concentration in both the groups during the task of drawing a tree imagined freely (free-drawing task and the task of copying an illustration of a tree (copying task were measured by using NIRS. Results: Because of the difference between the task conditions, [oxy-Hb] levels in controls during the free-drawing task were higher than that during the copying task at the bilateral frontal pole regions and left inferior frontal region. Because of the difference between the groups, [oxy-Hb] levels at the left middle frontal region, bilateral inferior frontal regions, bilateral inferior parietal regions, and left superior temporal region during the free-drawing task in patients were

  13. Influence of hemoglobin on non-invasive optical bilirubin sensing

    Science.gov (United States)

    Jiang, Jingying; Gong, Qiliang; Zou, Da; Xu, Kexin

    2012-03-01

    Since the abnormal metabolism of bilirubin could lead to diseases in the human body, especially the jaundice which is harmful to neonates. Traditional invasive measurements are difficult to be accepted by people because of pain and infection. Therefore, the real-time and non-invasive measurement of bilirubin is of great significance. However, the accuracy of currently transcutaneous bilirubinometry(TcB) is generally not high enough, and affected by many factors in the human skin, mostly by hemoglobin. In this talk, absorption spectra of hemoglobin and bilirubin have been collected and analyzed, then the Partial Least Squares (PLS) models have been built. By analyzing and comparing the Correlation and Root Mean Square Error of Prediction(RMSEP), the results show that the Correlation of bilirubin solution model is larger than that of the mixture solution added with hemoglobin, and its RMSEP value is smaller than that of mixture solution. Therefore, hemoglobin has influences on the non-invasive optical bilirubin sensing. In next step, it is necessary to investigate how to eliminate the influence.

  14. Hemoglobin levels and new-onset heart failure in the community

    NARCIS (Netherlands)

    Klip, IJsbrand T.; Postmus, Douwe; Voors, Adriaan A.; Brouwers, Frank P. J.; Gansevoort, Ron T.; Bakker, Stephan J. L.; Hillege, Hans L.; de Boer, Rudolf A.; van der Harst, Pim; van Gilst, Wiek H.; van Veldhuisen, Dirk J.; van der Meer, Peter

    Background In established cardiovascular disease and heart failure (HF), low hemoglobin levels are associated with unfavorable outcome. Whether hemoglobin levels are associated with the development of new-onset HF in the population is unclear. This study sought to investigate the relationship

  15. Affine field theories

    International Nuclear Information System (INIS)

    Cadavid, A.C.

    1989-01-01

    The author constructs a non-Abelian field theory by gauging a Kac-Moody algebra, obtaining an infinite tower of interacting vector fields and associated ghosts, that obey slightly modified Feynman rules. She discusses the spontaneous symmetry breaking of such theory via the Higgs mechanism. If the Higgs particle lies in the Cartan subalgebra of the Kac-Moody algebra, the previously massless vectors acquire a mass spectrum that is linear in the Kac-Moody index and has additional fine structure depending on the associated Lie algebra. She proceeds to show that there is no obstacle in implementing the affine extension of supersymmetric Yang-Mills theories. The result is valid in four, six and ten space-time dimensions. Then the affine extension of supergravity is investigated. She discusses only the loop algebra since the affine extension of the super-Poincare algebra appears inconsistent. The construction of the affine supergravity theory is carried out by the group manifold method and leads to an action describing infinite towers of spin 2 and spin 3/2 fields that interact subject to the symmetries of the loop algebra. The equations of motion satisfy the usual consistency check. Finally, she postulates a theory in which both the vector and scalar fields lie in the loop algebra of SO(3). This theory has an expanded soliton sector, and corresponding to the original 't Hooft-Polyakov solitonic solutions she now finds an infinite family of exact, special solutions of the new equations. She also proposes a perturbation method for obtaining an arbitrary solution of those equations for each level of the affine index

  16. Modeling hemoglobin at optical frequency using the unconditionally stable fundamental ADI-FDTD method.

    Science.gov (United States)

    Heh, Ding Yu; Tan, Eng Leong

    2011-04-12

    This paper presents the modeling of hemoglobin at optical frequency (250 nm - 1000 nm) using the unconditionally stable fundamental alternating-direction-implicit finite-difference time-domain (FADI-FDTD) method. An accurate model based on complex conjugate pole-residue pairs is proposed to model the complex permittivity of hemoglobin at optical frequency. Two hemoglobin concentrations at 15 g/dL and 33 g/dL are considered. The model is then incorporated into the FADI-FDTD method for solving electromagnetic problems involving interaction of light with hemoglobin. The computation of transmission and reflection coefficients of a half space hemoglobin medium using the FADI-FDTD validates the accuracy of our model and method. The specific absorption rate (SAR) distribution of human capillary at optical frequency is also shown. While maintaining accuracy, the unconditionally stable FADI-FDTD method exhibits high efficiency in modeling hemoglobin.

  17. Optical wavelength selection for portable hemoglobin determination by near-infrared spectroscopy method

    Science.gov (United States)

    Tian, Han; Li, Ming; Wang, Yue; Sheng, Dinggao; Liu, Jun; Zhang, Linna

    2017-11-01

    Hemoglobin concentration is commonly used in clinical medicine to diagnose anemia, identify bleeding, and manage red blood cell transfusions. The golden standard method for determining hemoglobin concentration in blood requires reagent. Spectral methods were advantageous at fast and non-reagent measurement. However, model calibration with full spectrum is time-consuming. Moreover, it is necessary to use a few variables considering size and cost of instrumentation, especially for a portable biomedical instrument. This study presents different wavelength selection methods for optical wavelengths for total hemoglobin concentration determination in whole blood. The results showed that modelling using only two wavelengths combination (1143 nm, 1298 nm) can keep on the fine predictability with full spectrum. It appears that the proper selection of optical wavelengths can be more effective than using the whole spectra for determination hemoglobin in whole blood. We also discussed the influence of water absorptivity on the wavelength selection. This research provides valuable references for designing portable NIR instruments determining hemoglobin concentration, and may provide some experience for noninvasive hemoglobin measurement by NIR methods.

  18. Crystallization and preliminary x-ray crystallography data of the dimer of tetramer s (abcd)2 of extracellular hemoglobin from Glossoscolex paulistus in cyano met form

    International Nuclear Information System (INIS)

    Ferreira, Frederico M.; Oliveira, Paulo S.L. de; Oliva, Glaucius

    1996-01-01

    Full text. The extracellular hemoglobin from Glossoscolex paulistus has a molecular weight near to 3.1 x 10 6 Da and a structure organized in a double-layered hexagonal oligomer. The tertiary complex of dimer of tetramers (abcd) 2 was obtained by chromography in Sephadex G-200, in pH 9.0, as a result of alkaline dissociation. Aiming to obtain a better understanding of the oligomeric structure and specially for the inter subunit interactions the extracellular hemoglobins, we have obtained crystals of dimer of tetramers (abcd) 2 of hemoglobin from Glossoscolex and we are studying the in behavior in different conditions of precipitants and pH's. Our goal is to solve the crystal structure in order to characterize, at atomic level, the subunits contacts, heme environment and differences in residues involved in oxygenation in order to understand in this hemoglobin. The crystallization experiments the protein concentration in the cyanomet form was about 10 mg/ml and the experiments were carried out at 18 0 C. The optimal crystallization condition achieved from factorial assays was 10% (w/v). Polyethylene glycol (PEG) 8,000 and 8%(v/v) ethylene glycol in 100 mM HEPES pH 7.5. The optimization of this condition was carried out with the variation of PEG concentrations from 6% up to 10% (by 1% step) and pH between 7.0 and 8.0. A quite critical p-H-dependence has been observed on crystal nucleation, decreasing from pH 7.0, in which the number of microcrystals in higher, up to pH 8.0, in which crystals did not appear even at higher PEG 8,000 (10% w/v). As several structures of hemoglobin from different sources (vertebrate and invertebrates) are available, we hope to solve their structure of hemoglobin from Glossoscolex paulistus by Molecular Replacement, even though the tetramer organization may be different in the earthworm as compared related to other known tetrameric hemoglobin structures. (author)

  19. A new multi-wavelength optical-plethysmograph for quantitative determination of pulpal hemoglobin content and oxygen level using green and near-infrared LEDs

    Science.gov (United States)

    Kakino, S.; Miwa, Z.; Kirimoto, A.; Ohuchi, K.; Takatani, S.; Takagi, Y.

    2007-02-01

    A new multi-wavelength optical-plethysmograph has been designed to study the relation between the transmitted optical density (OD) of the tooth vs. hemoglobin (Hb) content and oxygen saturation (SO II) of the pulpal blood using the 467, 506, 522 and 810 nm light emitting diodes (LEDs). The experimental model utilized the extracted human upper incisor where the pulp cavity was filled with the blood having various values of Hb and SO II. A resin cap was made to fit the tooth crown and optical fibers for transmission measurement. The LEDs were pulsed sequentially at 520 Hz with the pulse duration of 240 μs. The OD as a function of Hb for the isosbestic wavelengths of 506 and 522 nm increased almost linearly from 8.0 to 11.0 for Hb changing from 0.0 (saline control) to 2.5 g/dL, but beyond 2.5 g/dL no change was observed. At 810 nm, the OD increased linearly till Hb of 13.4 g/dL, but its change was much smaller with 1.0 OD per 13.4 g/dL. As for SO II, the OD at 467 nm with Hb of 1.0 g/dL that simulated the mean pulpal Hb content in vivo varied by about 1.0 for SO II changing from 100 to 40%. The OD change with respect to Hb change at 506 and 522 nm showed better sensitivity than that at 810 nm. The combination of 467 and 506 or 522 nm wavelengths can provide a noninvasive measurement of both pulpal Hb content and SO II to diagnose pulp vitality of teeth in vivo.

  20. Trends in brain oxygenation during mental and physical exercise measured using near-infrared spectroscopy (NIRS): potential for early detection of Alzheimer's disease

    Science.gov (United States)

    Allen, Monica S.; Allen, Jeffery W.; Mikkilineni, Shweta; Liu, Hanli

    2005-04-01

    Motivation: Early diagnosis of Alzheimer's disease (AD) is crucial because symptoms respond best to available treatments in the initial stages of the disease. Recent studies have shown that marked changes in brain oxygenation during mental and physical tasks can be used for noninvasive functional brain imaging to detect Alzheimer"s disease. The goal of our study is to explore the possibility of using near infrared spectroscopy (NIRS) and mapping (NIRM) as a diagnostic tool for AD before the onset of significant morphological changes in the brain. Methods: A 16-channel NIRS brain imager was used to noninvasively measure spatial and temporal changes in cerebral hemodynamics induced during verbal fluency task and physical activity. The experiments involved healthy subjects (n = 10) in the age range of 25+/-5 years. The NIRS signals were taken from the subjects' prefrontal cortex during the activities. Results and Conclusion: Trends of oxygenated and deoxygenated hemoglobin in the prefrontal cortex of the brain were observed. During the mental stimulation, the subjects showed significant increase in oxygenated hemoglobin [HbO2] with a simultaneous decrease in deoxygenated hemoglobin [Hb]. However, physical exercise caused a rise in levels of HbO2 with small variations in Hb. This study basically demonstrates that NIRM taken from the prefrontal cortex of the human brain is sensitive to both mental and physical tasks and holds potential to serve as a diagnostic means for early detection of Alzheimer's disease.